ARTHRITIS

1. What are both osteo and rheumatoid arthritis?

2. They are both chronic conditions developed not born with, characterised by
inflammatory component, last for months/years, cause irreversible damage to joints
and surrounding tissues and get remission/relapse periods. [chronic because damage
done to body parts cannot be repaired]
3. What is the difference between OA and RA in terms of causation?
OA is from overworking joints whereas RA is an AUTOIMMUNE disorder
4. What is the key difference between arthritic joints and normal ones?
Arthritic joints have bone erosion, thinning of cartilage, cartilage remnants and
destruction of cartilage
5. What damage does RA have more of?
More membrane damage, more cartilage damage and also more inflammation in this
one

6. Which areas does OA affect?

Limbs, Hands -- fingers/thumbs, Spine - neck/lower back, knees and hips, Pelvic joints
7. Name some financial and lifestyle effects of OA?
Financial cost of treatment, wages lost due to time off work;
Lifestyle depression, anxiety, limitations of daily activities as decreased mobility
8. What is the pathogenesis of OA?
Tissue destruction the tissue is infiltrated by macrophages, plasma cells and
lymphocytes granulation tissue forms - fibroblasts and new blood vessels but
eventually turns into a scar tissue fibrosis occurs = the thickening and scarring of
connective tissue, usually as a result of injury.)
9. How do the fingers appear in OA?
Fingers are still able to move and are somewhat ALIGNED, opposite to RA

10. Which factors make RA classed as a chronic inflammation condition?

Repeated bouts of acute inflammation
Persistence of agents that caused injury
If the materials formed in acute inflammatory response not removed
11. What are the 2 classifications of chronic inflammation?
Non-specific or Granulomatous
12. What do the fingers look like in RA?
Fingers not aligned, seen ANGLING called swan legs the tendons and CT does not
work at all and damage to cartilage entirely by immune system
13. What treatments are given for OA (3)?
Pain control [pain in RA more severe]
Local topical treatments
NSAIDS [more used in OA than RA]
14. Why are NSAIDS problematic?
Inhibit PG which take out some of the protective factors
They also cause more emergency admissions to hospital than any other drug
15. What old age treatment did people used to do?
Local topical treatment using hot chilli i.e. capsaicin related to the heat

16. What types/ additional drugs given for rheumatoid arthritis?

Disease modifying drugs (DMARDs) aka systemic treatment! Target the cells that
damaged joints so two approaches:
drugs to suppress local disease process or drugs that affect the immune response
17. Which drugs for RA suppress the local disease/process (4)?
(a) Gold (sodium aurothiomalate) first one, gold in colloidal suspension, injected,
shuts macrophages as hate heavy metals, some people respond well whilst others not,
a little TOXIC as can damage liver and kidney; ONLY DRUG THAT REVERSED
CONDITION
(b) Penicillamine copper colloid, found by accident and dont know what it does,
limited to how long it can be given for!
(c) Antimalarials did do something in RA but unsure what, also limited for length
(d) Sulphasalazine better than others when modified and still used
18. Which drugs given for RA affect the immune response?
Azathioprine, Methotrexate and Cytokine modulators
19. What are Aza and Metho considered as?
Not clean drugs as they damage other parts of body as well e.g. GI and oral cavity
20. Which drugs are cytokine modulators and how do they work?
(a) Adalimumab/etanercept moderate to severe RA inhibits the action of tumour
necrosis factor so it is very specific
(b) Abatacept stops full activation of T cells; working at molecular level
21. Why are NSAIDS/corticosteroids not used often?
Peoples perceptions have changed has brain effects, damped things down so it has
never been a long term solution!

ASTHMA IMPORANT Q

1. What is the 2014 statistics on asthma prevalence?

5.4 million UK currently receiving treatment for it; of which 1.1 million are children and rest adults i.e.
1 in 11 children and 1 in 12 adults. Steady state prevalence since 1990s -- UK has highest rate in
Europe. 2014 deaths were 1216 most at young age
2. What is FEV1 and how is it in asthmatics?
Forced expiratory volume per second decline is part of normal ageing process, peak occurs
at around 20 before decline begins - - asthmatics have ageing loss AND loss of air exchange
that decreases FEV1 each time there is an attack
3. What kind of disease is asthma?
A REVERSIBLE airway disease; progressive loss over time
Reversibility if attack is not severe then recovery can occur e.g. reduce activity
4. What 3 key features does it have?
Inflammation Bronchoconstriction Hyperreactivity
Chronic inflammation cos of immune system, bronco as airways are narrowed, and hyper as
for some reason asthmatics more reactive to some things, attack
5. How does the epithelial tube look like in asthma?
There are more cells and muscle as the bottom to thicker tube in some parts
When muscle constricts, they twist and spiral down and a small change in radius creates bigger
impact thus in asthmatics theres an even bigger reduction in radius
6. What is produced more in asthmatics from epithelial cells?
More mucus is produced as airflow decreases
7. What are the characteristic symptoms (4)?
Wheezing, Breathlessness, Cough, Chest tightness
8. Why does these symptoms occur?
-- Because of restriction of flow from narrowed artery [Wheeze]
-- Cough to get rid of mucus
-- Chest tightness from inflammatory materials released
9. Why is asthma statistics paradoxical?
Despite better diagnoses, treatment and recognition deaths still occur!
10. Who gets asthma?
YOUNG 12 to 15% of children, and approx. 2.5% in adults
MALES more than females
11. How can it be allergic response?
More than 90% of asthmatic children are allergic on testing could be a reaction to house
dust mites, cat fur, pollen etc. UK has worst dust mite problem!
12. How can dust mites be allergenic?
The excretor it puts out, pellets, are small and airborne and when pellets get in the airstream
we breathe them in a protein inside it is what we create antibodies against
13. List all the precipitating factors
Viral infections, exercise, emotional disturbances, non specific irritants and dusts, fumes,
changes in humidity and temperature
[means more likely to get an attack]
14. What are the theories for why asthma occurs
Some say all to do with activity of the airways
Could be the control of the airway calibre that is abnormal
15. How do leukotrienes compare with histamine release in sensitivity?
Abnormal reactivity of airways smooth muscle to LT, and LT are found to be MORE SENSITIVE
to histamine [magnitude of 10,000]
16. What one factor is known for certain?
ROLE OF MAST CELLS histamine is released from mast cell. When antibody develops against
pollen e.g. sticks to membrane of mast cell and next time the antigen comes along get Ag-Ab
reaction on mast surface cell triggers calcium channels so inside contents are all released
[leukotrienes and bradykinins!!]
Antibodies that bind are IgE only!!
17. Explain extent of it being immune system
It is an INFLAMMATORY DISEASE! Airways are grossly inflamed
Airway wall is oedematous and infiltrated by inflammatory cells [eosino and lymphocytes]
macrophages are activated and also T cells there
18. What is the mucus like in asthma?
Airway lumen is OCCLUDED by tenacious mucus plugs that come from plasma proteins plus the
mucus glycoproteins from surface epithelial wall
Like thick wallpaper and coughing it up is difficult
19. What do people with asthma die of usually?
HYPOXIA
20. How can sensitivity of airway all be detected?
Histamine challenge or methacholine challenge
21. Difference between acute and chronic inflammation?
In acute inflammation REVERSIBLE changes
Chronic inflammation leads to STRUCTURAL changes, as seen on FEV1 graph
22. What is treatment governed by?
Guidelines from BTS!
23. What are the principal aims behind treatment (3)?
(a) Control the symptoms [including nocturnal, exercise induced]
(b) Prevent exacerbations
(c) Achieve best possible pulmonary function with minimal side effects
24. Why is the night-time dangerous for asthmatics?
Circadian rhythm changes, so for e.g. 2am in morning airflow and respiration rate drops, and
bronchospasm coupled with reduction is dangerous!
25. What was first injected into asthmatics?
Adrenal extracts! These contained adrenaline, corticosteroids but this was not known
26. What thus followed on from this?
Ephedrine, Adrenaline [dangerous] and Theophylline
27. When were beta agonists developed and explain?
1960s inhaled but non-selective e.g. isoprenaline was first one. Then got selective beta
agonists such as salbutamol [REVOLUTIONARY]
28. What developed in the 1970s?
Corticosteroids that were less potent and most given by aerosol not mouth
29. What other drug also developed during that time?
ANTI MAST CELL the first one called sodium cromoglycate
30. What were then developed/used?
BECLOMETHASONE inhalant potent corticosteroids
31. In 1990s came..
Long acting beta 2 agonists called SALMETEROL
32. In 2000s..
LEUKOTRIENE ANTAGONISTS
33. What developed in late 2000s?
AMALIZUMAB monoclonal Ab that targets IgE stops it getting bound to mast cell so dont
get the symptoms but the problem is it has to be given FREQUENTLY to mop them up and is
expensive
34. So what is the strategy summary?
Relieve bronchospasm bronchodilators get the airway better
Stop inflammatory response corticosteroids
Somehow block MAST cell response now the MAb

GI DISORDERS: INFLAMMATORY BOWEL DISEASE 1

1. What are the two areas where there are major limitations in knowledge for gastrointestinal
disorders?
Inflammatory bowel diseases and functional gastrointestinal diseases
2. What does functional GI diseases mean?
Functional refers to there being a wrong function but the cause cannot be pinpointed or seen
where it is
3. What is the most common functional GI disease?
Irritable bowel syndrome tends to come and go, can have a stressful component
4. Why is the gastrointestinal system complex?
Itself is complex but also because it is a functional organ, it is always doing things secretion,
motility, altering blood flow etc.
5. What are some functions of the GI system?
(a) Process ingested food i.e. ABSORPTION and digestion
(b) Deal with antigenic material that GI tract brings in, so GI is the first port of call for the
IMMUNE system for those items that come in orally
(c) Communicate with the CNS for food intake and satiety by nerves and its own nervous
system
(d) Secrete HORMONES into blood stream that control functions of accessory organs and GI
tract
6. What are the layers of the digestive tract wall?
(a) Mucosa = innermost
(b) Submucosa = connective tissue and blood vessels, and immune cells
(c) Muscle layers = circular and longitudinal oriented
(d) Serosa = continuous with the mesentery
7. What does the mucosa have?
Epithelial cells (or absorptive cells in the small intestine), the secretory cells, supporting cells
and hormone secreting cells
8. What are the two nerve plexuses and where are they found?
(a) Submucosal plexus found between the submucosa and circular layer
(b) Myenteric plexus between the two layers of the muscular sheath
9. What do the plexuses do?
Have cell bodies that send processes into tissues of the GI tract and into smooth muscle layers
alter motility in these areas. Submucosal can alter functionality in those tissues
10. Do the autonomic nerves connect with these plexuses?
YES autonomic nerves come in and make synapses, with the myenteric plexus nerves allowing
communication with the rest of the body
11. What could inflammatory bowel disease look like in an endoscopic photograph?
Sections of ulceration, inflammation and sore looking. May also see granulomatous lumps and
some pus. Bleeding is possible but not always seen. So basically looks SORE AND INFLAMED
12. What is inflammatory bowel disease?
Abnormal inflammatory and immune response to intestinal microflora or to something that is
there but not usually harmful
13. What kind of inflammatory state is the bowel usually in?
Bowel is always in a state of chronic subclinical inflammation which is usually controlled i.e. it is
always on alert to evade pathogenic species, so constantly vigilant.
14. What happens to the vigilant bowel in IBD?
In most people the vigilance will be maintained at low level vigilance but in IBD the control
level escalates and hence get the abnormal response to anything
15. What is the pattern of the condition?
That it is ALWAYS THERE! It will not completely go away hence it is chronic. Can get periods of
relapse and remission but there will always be some level of abnormality in the gut
16. Is there any genetic involvement?
YES there does some to be some genetics involved in why some people get it. Specific genes
associated with some inflammatory bowel diseases
17. What does IBD have a risk for in the long term?
CANCER in long term people are prone to developing malignancies from the chronic
inflammation in the colon so at risk for colon cancer
18. What extra intestinal symptoms can patients with IBD also present (7)?
(a) Mouth ulcers indicative of GI disease unless chronic unexplained
(b) Joint pains arthritis, osteopenia are fairly common
(c) Eye inflammation scleritis and episcleritis, inflamed blood vessels show
(d) Skin lesions two types of them
(e) Hepatobiliary complications liver and biliary system, blockages & inflamm
(f) Anaemia
(g) Ankylosing Spondylitis
19. What are the two types of skin lesions seen?
(a) Erythema Nodosum defined area of inflammation, see blotches, mostly around just above
elbow or legs
(b) Pyoderma Gangrenosum severe skin eruption
20. What is the immune system doing in IBD?
It is wrongly responding or extra strongly responding to a stimulus that is normal such as food
and launches a response against the material, but this then includes cells of the intestines too
breakdown of ability to distinguish SELF AND NON SELF CELLS
21. How do the immune cells contribute?
Leukocytes are continually released and invade lining of the intestines to produce chronic
inflammation
22. What is the main management problem with IBD?
The symptoms get worse over time or the number of relapses will increase which drastically
effects the QoL of the patient, and the problem is made worse by the patient not being able
to be kept in remission other than by surgical means
23. What are the two theories to explain the dysregulation of immune response in IBD?
(a) Dysregulation of response could be to luminal bacteria or material generated by the
bacteria
(b) Intrinsic alterations in mucosal barrier function to organisms that usually do not induce a
response
24. What are the two main groups of inflammatory bowel disease?
Ulcerative colitis and Crohns disease
25. What do all diseases have in common?
Follow the same pathway of inflammatory responses, relapses and remissions
26. What other conditions can present such symptoms?
A proportion of people can exhibit colitis like symptoms as a result of DRUG side effects such
as from NSAIDS, PPI and antibiotics antibiotics are a common cause because they change the
balance of normal levels of bacteria [[however these conditions are self limiting!!!]
27. What does UC affect mainly?
Only affects the colon [large intestine] which could be a small part of it or a large part of it
but it DOES NOT EXTEND TO SMALL INTESTINE, so it is confined to large intestine
28. What parts of the colon are most likely to be affected in UC?
The latter parts i.e. rectal and sigmoid
29. What does Crohns disease affect?
Can be ANYWHERE in the GI tract i.e. large intestine or oesophagus but it is largely the small
and large intestine
30. What are the parts of intestine most affected in Crohns?
Major inflammation found in terminal ileum, inflammation of colon and anorectal area
patient could have just once, two or all three or others.
31. What are the symptoms/signs that are present in both diseases?
Diarrhoea, Tachycardia, Fever, Trigger foods aggravating condition
32. Is abdominal pain a good marker in the two conditions?
NO it is not always a clear marker; but generally more present in Crohns and rather
variable in UC
33. In which one is rectal bleeding more common?
UC
34. In which one is mucus produced more?
UC mucus found in stools more because the mucus cells in Crohns have been damaged so
hardly any produced whereas in UC the damage is not so extensive into the skin
35. Why does malnutrition/anaemia occur more in Crohns?
If the terminal ileum is inflamed, it affects BILE reabsorption and absorption of some vitamins
especially B12 so malnutrition occurs and anaemia is related to the bleeding and lack of iron
reabsorption
36. Why is dehydration present and in which condition does it occur more?
Dehydration occurs because the gut is not able to absorb fluid as normal and a lot is lost at
the same time because of diarrhoea. It affects UC more
37. Is any abdominal mass felt in UC/Crohns?
Palpatable mass is felt in Crohns
38. What is the location of presentation for Crohns?
Can occur anywhere from top-bottom of GI, about half occurs between ileum and caecum
39. What is the location of presentation for UC?
ONLY COLON very common in the rectal area (40%), then left colon (40%) and pancolitis
i.e. whole colon is in 20%.
40. Why is distribution not enough to distinguish the two conditions?
Can have Crohns that is only affecting the large intestine so this would be similar to UC
41. How is the inflammation seen in Crohns?
Common to see patches of NORMAL mucosa interspersed with inflamed patches skip lesions
so have normal, abnormal, normal
42. How far is the inflammation in the wall for Crohns?
Inflammation is much more deeper into the wall of the intestine going right through the
submucosa and muscle layers [leads to complications] DEEP ULCERATION
43. What is the overall appearance of inflamed tissue in Crohns?
Wall is thickened because of inflammatory tissues and mediators giving it a ROCKY
appearance and also because of GRANULOMATOUS sections [hard pockets of granulomas]
44. How is the inflammation in UC?
Inflammation is CONTINIOUS with no healthy tissues in between; only the mucosa is inflamed
here
45. How far is the inflammation in the wall for UC?
It only affects the mucosal area i.e. superficial and have FINE ULCERATIONS
46. What is the overall appearance of inflamed tissue in UC?
Thinner wall with ulcers and inflammation not extending beyond the mucosa and no
granulomas present
47. What can happen in the ulcers in Crohns as a result of being deep?
Some complications perforate, leakage of materials into peritoneum
48. In which condition are fissures, fistulas and strictures more commonly seen in?
Crohns is more common, in UC they are absent
49. What are fissures?
Lesions that open up [in Crohns fissures in anal area a problem]
50. What are fistulas?
Links between different areas of the GI tract through ulcerated areas fusing, can occur at the
anal orifice
51. What are strictures?
Intense narrowings of the GI tract so whole thing is some type of spasm and can only be seen
on imaging
52. In which condition is bleeding more common?
In UC
53. Where can pain be present in both conditions?
In Crohns often in right iliac fossa and terminal ileum
In UC pain often in left iliac fossa
54. What functionality problems does stricture string sign cause?
Wont be able to move material into that segment or get water/fluid absorbed thus see worse
dehydration
55. Which condition is more likely to have smokers?
Crohns more likely to be smokers than non, whereas in UC less likely but there is a period of
ex-smokers being prone to UC [smoking may decrease symptoms of UC though?]
56. What are the age demographics?
Peak age 10-40 years, but 15% are over 60 at diagnosis
57. How common is it globally?
Not that common but it is increasing, globally seen more in Western countries, incidence in UK
is about 150/100,000 people
58. Does ethnicity seem to have an affect?
Seems to have a significant effect, so it could be related to the genetics
59. Is there any relationship to gender?
If looking across the spectrum there seems to be an equal distribution of males and females
60. What are the genetics findings?
UC seems to have a lot more involved polygenetic and HLA
Crohns couple of genes have been associated
Overall in both, if first degree relative has it, more chances that an individual has it as well
61. What factor confers a protective response?
BREASTFEEDING! Seems to reduce the risk in both types
62. What is unknown about the intestinal bacteria at the moment?
Dont know much about the demographics of the intestinal bacteria biotome i.e. the
microbiological population, and evidence is emerging that there could be differences in
bacterial populations between people with IBD and not
63. Explain the pathophysiology involving the inflammatory mediators?
There seems to be a imbalance between the PRO inflammatory and ANTI inflammatory
cytokines. Pro IL12, TNF-a, IFN-y, IL-8 etc, whilst anti IL4,13,10 and TGF
64. How does chronic activation of mucosal immune response occur?
* Combination of environmental factors and genetic response *
-- Imagine assaulted or challenged by an environmental factor, the response will be
inflammation, by T cells but this would be limited by APOPTOSIS of the T cells so that would
then restore normal gut function and has dealt with environmental factor.
-- With a GENETIC PREDISPOSITION as well T cells do not undergo apoptosis, which means
there is a chronic state of inflammation producing TNF and IL-12 disproportionately
[proinflammatory]
* So key thing is the apoptotic step of T cells *
65. What is therefore the main direction of newer therapies?
Aimed at pro-inflammatory mediators such as TNF-a and IL-12 in relieveing the symptoms
associated from them or block their actions.
66. Which other inflammatory mediator is involved, especially in Crohns?
MACROPHAGE! secretes cytokines and also released TNF-a
67. What is the likelihood of remission, for Crohns?
People going into remission falls with time initially some occurs but becomes less as condition
goes on, with more periods of aggressiveness
 68. What is the trend for surgical remission?
Proportion of patients in surgical remission increases over time this is because with drugs
patients can become refractory however surgery controls over longer period of time

GI DISORDERS: INFLAMMATORY BOWEL DISEASE 2

1. What is the dietary treatment for UC (3)?

(a) Sufficient amount of IRON & VIT B12 from medications/food if not able to get it normally
[because of larger involvement of terminal ileum]
(b) LOW ROUGHAGE diet move away from complex carbohydrates
(c) MILK exclusion recommended usually
2. What are the surgical options for UC?
* Depends on extent of inflammation! *
If pancolitis total removal of colon is expected and formation of STOMA between ileum and
external environment but this would not be done as first point of call [pharmaco, minor
surgeries then major]
3. What is the dietary treatment for Crohns (2)?
(a) LOW ROUGHAGE diet restricted fiber diet with no raw fruit, veg, nuts or whole grains
as well
(b) LOW FAT DIET -- helps as less fat amount moving into the large intestine which reduces
motility symptoms
4. What are the surgical options for Crohns?
May require removal of sections however consideration needs to be made about
interference with absorption [i.e. consider nutritional support]]
5. What are the 4 traditional pharmacological approaches for IBD?
(a) Corticosteroids
(b) Aminosalicylates
(c) Immunomodulators e.g. azathioprine, 6-mercaptopurine, MTX
(d) Antibiotics
* Think in same line as rheumatoid disorders *
** Get some benefit in a proportion of patients but cannot guaranatee that sustained response
hence ultimately leads to surgery **
6. When are corticosteroids used?
For treatment of ACTIVE IBD i.e. when inflammation is active or severe relapse ** basically
used to drive down inflammation and get patient back into a steady condition **
7. How would corticosteroids be given if a relapse?
Given IV rather than orally
8. Which corticosteroid would be given emergency?
HYDROCORTISONE would be given in an emergency flare up, IV usually for 5 days but can
also be given intramuscularly
9. What other forms of hydrocortisone therapy are available?
Suppository if need to get it in the rectum, foams to get it further in rectum and enemas would
go even further into rectum these forms are used for control as well getting into remission
periods.
10. After hydrocortisone, what corticosteroid would be used?
PREDNISOLONE would be used next either orally or local routes to give continued benefit
11. How do corticosteroids exert their effect?
They work because of anti-inflammatory response and actions which are relatively quick and
not subtle either
12. Why are they only used for active treatment and not maintenance?
Severe drawback is that they have serious long term side effects with chronic use
 osteoporosis, suppression of normal steroid balance, adrenal suppression and withdrawal
symptoms
13. When are aminosalicylates used?
When trying to induce and maintain remission
14. What are some examples of these drugs?
Sulphalazine, Mesalazine, Olsalazine and Balsalazine Mesalazine is most commonly used
and available in lots of dosage forms, Balsalazine is newer with supposedly fewer side effects
15. How do aminosalicylates work?
Have a local effect on epithelial cells by helping to block mediator release, cytokine and
reactive oxygen species release and therefore reduce damage
16. Which condition is aminosalicylates really good for?
UC as there is less penetration of mucosa. Not so useful for CD with there being deeper
damage
17. How can the different formulations be used?
Common to see different formulations e.g. delayed release of mensalazine and
supplementation by rectal dosage as they may be needed together
18. When are immunosuppresants used?
When trying to induce and maintain remission just like aminosalicylates and are used side by
side with the aminosalicylates!
19. What are some examples of these drugs?
Azathioprine, 6-mercaptopurine, Methotrexate and Ciclosporin
20. How do immunosuppressants work (3)?
(a) Dampen T cell function by inhibiting PURINE SYNTHESIS
(b) Reduce mediator release by INHIBITING cytokine/eicosanoid synthesis by modifying
adenosine levels [some evidence, especially MTX]
(c) CALCINEURIN inhibitor so stops release of inflammatory cytokines such as Il-12 and others
21. When are immunosuppressants particularly used?
In patients unresponsive to steroid therapy and aminosalicylates, or in patients who relapse
when steroids are withdrawn
22. When are antibiotics used?
To control bacterial infection in Crohns disease as part of complications
23. Which drugs are used?
Metronidazole is usually used always
24. What kind of infections does it treat?
Complications arising from fistulae forming or lots of infections, or bacteria growth into the
small intestine or if perforation has taken place
25. What other ability does metronidazole offer?
Has ability to also reduce the inflammatory response by reducing PHOSPHOLIPASE A levels
reduces damage caused by leukocytes
26. What other pharmacological therapies may patients have?
(a) Anti-diarrhoeal loperamide or codeine, but risk so be vigilant
(b) Thalidomide in Crohns when NOTHING ELSE WORKS! Inhibit TNF-a
(c) Fish oils some evidence for benefical use
(d) Probiotics change microbial content of the gut, small studies benefit
(e) Others such as FAECAL TRANSPLANTS get a sample of faeces from healthy donor, insert
long endoscopy tube in and put faecal sample as far down intestine as possible **idea is to
change microbial profile and maybe allow good bacteria to colonise in preference to the
aggravating bacteria**
27. Why must there be caution if using anti diarrhoeal?
Could mask other processes that have infection or could promote conditions where an
obstruction could occur as the guts normal motility is being stopped so if there is faecal
contents in there blockage would occur and becomes emergency
28. What is a newer pharmacological approach?
MONOCLONAL ANTIBODIES! usually used when other treatments are not working anymore
or not tolerated
29. Why are they not used straight away?
They are very expensive and this is the main reason for why they are not used immediately in
patients even though there is some evidence for better prognosis
30. What are some disadvantages of their use (2)?
(a) Have to reviewed for efficacy each year as become ineffective often around 2 years
(b) Patients often can react immunologically to the monoclonal Ab
31. How do MAb function?
Stop/prevent cytokines from binding with cellular receptors which then stops intracellular
signalling resulting from cytokines especially TNF-a and Il-12
32. What are the structural differences among Mabs?
Can have murine, chimeric, humanised or completely human Mabs. Immune response varies in
all these but would expect less from human type than murine, humanised can still get a
response
33. Give the three main approaches of Mab therapies?
(a) Anti TNF-a -- inhibit binding of TNF-a to receptor by sitting on it
(b) T-cell proliferation inhibitors interfere with proliferation, AB to A chain of IL-2 receptor of
T cells
(c) Anti-leukocyte adhesion stops cell adhesion and stop sticking so reduces immune response
so leukocyte cant pass through cells
34. What are the two anti TNF-a Mab?
ADALIMUNAB fully humanised
INFLIXIMAB chimeric human/murine
35. What is the Mab for T cell proliferation inhibitors?
BASILIXIMAB chimeric human/murine
36. What are the anti leukocyte adhesion Mabs?
NATALIZUMAB fully humanised and more for Crohns
VEDOLIZUMAB newly approved for Crohns and CD, more GI selective
37. What future therapies hold promise?
ADENOSINE (A2B) RECEPTOR ANTAGONIST the receptor is involved in inflammatory
response and in animal models has shown that antagonism is beneficial reduces production of
pro inflammatory mediators
38. What key considerations have to be made post surgery (4)?
(a) Stoma care how to manage output
(b) Short bowel syndrome especially Crohns
(c) Parenteral nutrition at home especially Crohns
(d) Malnutrition, dehydration and social issues
39. What is short bowel syndrome?
A patient that has had a lot of bowel removed are technically discharged as having SBS
although 200cm is the critical amount needed for SI that can be left for nutrients, if a lot has
been removed leaving a couple of meters then there is this trouble
40. What has to be considered in these patients regarding food?
We still want them to use their bowel so ENCOURAGE THEM TO EAT FOOD!
41. How is nutritional support provided to people with insufficient SI?
Via IV or parenteral nutrition people can be released home and hook themselves to a driver
overnight (3-4 times a week) for nutrition and hydration
** Can lead to social issues **
42. What does a stoma do and what will the stoma be like in SBS patients?
Stoma collecting material from the small intestine; longer intestine means less substance
remaining as more will be absorbed, stoma appears on surface looking like an outie belly
button
There will be a large stoma a high throughput one which may well show food in the bag
right away
43. What medications can be given to help the stoma?
Medications can be given to help slow down gut transit e.g. Loperamide but even with this
pharmacological help, there will still be a high throughput stoma
 HEART FAILURE

1. What is the difference between heart failure and attack?

In heart attack the blood stops pumping
In heart failure, efficiency is decreased, below the oxygen requirement of body
[muscles cannot pump blood out, more retained in LV, ejection fraction goes down]
2. What exactly is heart failure?
Condition in which CARDIAC OUTPUT is inadequate to provide metabolic needs of body
3. What are the mechanical properties of the heart?
(a) Preload
(b) Contractility
(c) Afterload
4. What is preload?
The degree of stretch of ventricles before contracting
5. What is the Frank-Starling Law?
6. What is contractility?
Strength of the contraction
7. What is afterload?
Pressure that has to be overcome by the LV so that blood can be pushed into aorta hence depends
on ARTERIAL PRESSURE if it is higher, heart will have to work harder
8. Describe chronic heart failure
Progressive disorder with a gradual decline in CO punctuated by acute decompensations
9. Describe acute heart failure
Rapid onset if symptoms with reduced CO and pulmonary or systemic congestion
Rapid onset mainly because of myocardial infarction as portion of heart gets damaged so muscle
not as efficient anymore
10. What does congestive mean?
Means stage of which fluid builds up around the heart causing it to pump inefficiently
11. What are the two types of heart failures?
Left sided and right sided heart failure
12. What happens in left-sided heart failure?
The left ventricle loses the ability to contract normally so heart cannot pump with enough force.
This leads to SYSTOLIC FAILURE as L.ventricle cannot push enough blood into circulation
This leads to DIASTOLIC FAILURE/dysfunction as L.ventricle loses ability to relax normally; the heart
cant properly fill with blood during the resting period between each beat
13. What is the key associated feature of left-sided heart failure?
PULMONARY OEDEMA ventricle can only accommodate so much so accumulation occurs and
pressure backs into pulmonary veins and into lungs [fluid moves out from blood into lungs as
pressure is increased so fluid accumulates in the lung!]
14. What happens in right-sided heart failure?
More pressure in the right ventricle thus leading to more in the right atrium. Mostly as a result of left
sided heart failure! As when L.ventricle failes, increase fluid pressure is in effect transferred back
through the lungs ultimately damaging right side
15. What is the key associated feature of right-sided heart failure?
SYSTEMIC OEDEMA pressure backs up into vena cava and blood then backs up into the bodys
veins causing swelling there, mostly in legs and ankles etc.
16. What does cardiac modelling lead to?
Hypertrophy and dilation of the heart
17. What is hypertrophy?
When the thickness of the wall increases but the cells dont increase
18. What is one of the main reasons for heart failure?
HYPERTENSION prolonged or chronic hypertension results in making the heart work harder and
thus it then undergoes remodelling
19. What are the two types of remodelling?
Concentric and eccentric
20. What happens in concentric remodelling with sarcomeres?
They are added parallel only so wall thickness increases greatly without really changing ventricular
chamber radius
21. What happens in eccentric remodelling with sarcomeres?
They are added parallel as well as in series so that thickness of wall increases as well as chamber
dilation because the sarcomeres are added in series to existing sarcomeres [so ventricular chamber
radius and thickness are increased!]
22. What other features present in concentric remodelling?
Ventricles become stiff i.e. compliance decreases; they dont relax fully and dont allow ventricle to
fill properly thus termed DIASTOLIC FAILURE
[seen in cases of chronic HPT, chronic pressure overload]
23. What other features present in eccentric remodelling?
Dilated ventricle has high stress from wall with elevated oxygen demand and lower mechanical
efficiency so fails to contract properly it is associated with symptoms of heart failure and
REDUCED EJECTION FRACTION SYSTOLIC FAILURE
24. What is the ejection fraction?
Percentage of total volume of blood in the ventricle that is pumped out during each contraction
measure of pump performance [measures EDV that pumps out]
25. What is the normal ejection fraction?
Varies between 55-70%
26. What happens to the ejection fraction in heart failure?
This fraction falls BELOW 50% -- however in some patients there is not always a significant change
in EF, yet the oxygen requirement is still not being met [e.g. anemia]
27. What are the 2 main category causes of heart failure and describe them?
(a) Diseases of the MYOCARDIUM such as ischaemic heart disease; blood supply to heart
decreases can lead to damage of the myocardium and result in HF
(b) CIRCULATORY factors can be either volume overload or pressure overload [leaky
valves/arteriovenous shunts or stenosed narrow values/arterial hypertension]
28. How can heart failure be prevented (7)?
Quit smoking, keep BP at healthy level, keep cholesterol levels under control, maintain healthy
weight and eat food healthy [less salt], ensure iron in diet, exercise regularly and limit alcohol
consumption!
29. What are the symptoms of heart failure (4)?
SOB body not getting enough oxygen so of course have to breathe more often
Fatigue
Oedema
Kidney problems sodium and fluid retention
30. How is diagnosis made?
Blood tests, ECG, echo or X-ray
31. What is the theory of compensatory mechanisms?
When there is heart failure, the body tries to compensate for it however the mechanisms can
actually AGGRAVATE the failure one idea is that the body confuses it with haemorrhage
[bleeding decrease blood vol and CO] since the oxygen is reduced so the compensatory
mechanisms always INCREASE CARDIAC OUTPUT
32. Describe the RAS system?
Renin is released by kidneys when it detects decreased renal blood flow. It increases force and
rate of contraction and preload. It also helps increase levels of angiotensin I.
33. What is the stroke volume and pressure difference in failing hearts versus non failing hearts?
In non-failing hearts, the stroke volume varies from 20-100 in a small range of pressure difference
around 10mmHg.
In failing hearts, the SV is decreased a lot whilst the pressure difference is between 10-30mmHg
34. How many stages is heart failure classified into?
Four stages
35. What is stage A?
A high risk but no signs and symptoms
36. What is stage B?
Evidence of structural heart disease but still no symptoms
37. What is stage C?
Structural heart disease with symptoms, respond to ordinary therapy
38. What is stage D?
Heart failure that is refractive to ordinary therapy
39. What treatment is involved in A and B?
LIFESTYLE changes level of activity, diet, intake
Focus is on control of underlying pathologies such as HPT, hyperlipidaemia, diabetes
40. When does pharmacotherapy begin?
Stage C onwards
41. Drug treatment is common with hypertension
Only thing that is different is how it is STARTED
42. How is treatment started in heart failure?
Begins with TWO DRUGS -- Ace inhibitor and beta blocker for ALL cases
[BB has to be added in slowly in a drug titrated manner]
43. If ACE inhibitor doesnt work, then go for?
Angiotensin II receptor blocker
44. If patient doesnt improve with those two then?
Add aldosterone receptor antagonist
45. If there is fluid overload?
Add a diuretic to remove the excess fluid
46. Ace Inhibitors examples
Captopril, Enalapril
47. Beta blockers examples
Bisoprolol, Cardevilol, Nebvulol
48. Angiotensin II receptor antagonist examples
Losartan, Canderstan, Valsartan
49. Aldosterone antagonists
Spironolactone, Epleronone
50. Diuretics examples
Thiazides or Loop diuretics such as Furosemide
Pts should receive diuretic + dietary fluid + salt restriction
51. Which vasodilators can be used?
Venous ones Isosorbide nitrate
Arteriolar ones Hydralazine
52. When would vasodilators be used?
Used in addition to ACE inhibitors and BB in particular for patients from African/Caribb origin with
mod-severe HPT
53. When would digoxin be used?
Reserved for patients symptomatic despite on all above treatments
54. What is the function of digoxin?
Blocks sodium-potassium transporter channel in heart tissues thus calcium is retained in higher levels
increases FORCE OF CONTRACTION
55. What are calcium channel blockers used for?
Treatment of comorbidities of hypertension and/or angina in patients with HF too
Choose the DIHYDROPIRIDINE ones i.e. Amlodipine
-- short acting ones are not recommended, also exclude verapamil, diltiazem
56. What is the most common cause for acute heart failure occurring?
An ACUTE MI
57. What else can cause acute heart failure (5)?
(a) People suffering from chronic heart failure can also suddenly develop MI, called
decomposition
(b) Cardiopulmonary bypass surgery
(c) Actute infection
(d) Valve dysfunctions
(e) Severe arrhythmias
58. How should all treatments be for acute?
ALL SHOULD BE IV
59. What 5 categories of drugs are given:
(a) Diuretic Furosemide
(b) Positive ionotropic drugs
(c) Levosimendan
(d) Vasodilators
(e) Conivaptan
60. Give examples of positive ionotropic drugs
Dopamine, Dobutamine have prompt onset and short duration action
61. What is the function of Levosimendan?
CALCIUM SENSITISER binds with troponin C on cardiac cells so increases sensitivity of muscle to
calcium
-- Thus with same amount of calcium, the force of contraction increases
62. What other effects does Levosimendan have?
Has vasodilatory effects too as it can open ATP-SENSITIVE POTASSIUM channels
63. Give examples of vasodilators
Nitroprusside, Nitroglycerine
64. Conivaptan use and function
ADH RECEPTOR ANTAGONIST it increases flow of fluid and this decreases severity of symptoms,
especially beneficial in patients with hyponatremia

HIV 1

1. What virus is HIV caused by?

Retrovirus
2. What cells does it primarily affect?
CD4 T cells, dendritic cells and macrophages
3. Why is HIV no longer a death sentence?
Condition is much more effectively controlled now; as a chronic condition
4. What did one mathematical model suggest?
Person infected with HIV at 25 years and given effective treatment should expect to live another 35 years
5. What kind of life expectancy do they have?
Similar to if developed type 1 diabetes!
6. What are they still at risk for however?
The adverse effects of ART therapy [hepatotoxicity, impaired glucose metabolism, pancreatitis, lactic
acidosis]
7. What comorbidities do they present?
Cardiovascular disease, cerebrovascular disease, renal disease, bone disease and diabetes
8. Which virus type is the leading cause of HIV?
HIV-1
9. Describe the structure of HIV virus
Everything is packaged into virion
Then have the envelope with MHC proteins on them and gp
Nucleocapsid encloses the RNA genome, reverse transcriptase, integrase and protease enzymes
10. Why are there so many strains of HIV?
HIV is a highly variable virus which mutates readily
11. What is the difference between HIV-1 and 2?
HIV-2 seems to be less EASILY TRANSMITTED
Period between initial infection and illness LONGER
Uncommon and is concentrated in West Africa
12. How is HIV transmitted, for both types HIV 1 and 2?
By sexual contact, through blood and from mother-child
13. What is the meaning of cellular tropism?
The ability of the HIV to enter particular cell type i.e. T cells and dendritic
14. What are the initial stages in life cycle of HIV related to dendritic cells?
Dendritic cells initiate infection by transporting HIV from mucosal surfaces to lymphoid tissue
Camping base for HIV infection to increase before transport
Because as viral load increases, HIV begins to favour T-cells
15. How does HIV enter cells?
By means of two surface GLYCOPROTEINS: gp120 and gp41 in the viral envelope that bind to hosts
surface protein gp120 binds with CD4 but at same time needs gp120 to bind to co-receptors which are
chemokine such as CCR5 and CXCR4 [these are expressed on activated T cells]
16. What does the binding of gp120 to CD4 cause?
It releases gp41 which causes fusion of the viral envelope with the cell membrane and release of the viral
core into the cytoplasm
17. What happens to the virus once it is released into cytoplasm?
The viral core releases the RNA genome which is reverse-transcribed into DOUBLE STRANDED cDNA using
the viral reverse transcriptase
18. What then happens to the viral cDNA?
It migrates to the nucleus and together with viral integrase and the Vpr protein it is integrated into host
cell DNA, become a provirus
19. What does activation of CD4 T cells result in?
Initiate transcription of provirus at a low level
20. How are the first viral transcripts produced?
Produced using spliced mRNAs encoding several regulatory proteins including Tat and Rev
21. What does Tat then do?
It amplifies transcription of the provirus and binds to the RNA transcripts to stabilise them
22. What does Rev do?
Rev binds to the RNA transcript and transports them to the cytosol, and as Rev levels increase, more
transport out of nucleus of spliced and unspliced viral transcripts occurs
23. What occurs in the late stages?
The late proteins Gag, Pol and Env are translated and assembled into virus particles which bud from
the cell
24. What are the WHO recognised stages of all of the above?
(a) Binding HIV binds to receptors on surface of CD4
(b) Fusion HIV envelope and CD4 cell membrane fuse which allows HIV entry
(c) Reverse Transcription Once inside HIV releases and uses reverse transcriptase to convert genetic
material of RNA to DNA to allow nucleus entry
(d) Integration Inside the CD4 nucleus, HIV releases integrase which isused to insert i.e. integrate its viral
DNA into DNA of CD4 cell
(e) Replication Once integrated, HIV begins to use machinery of CD4 cell to make long chains of HIV
proteins that are building blocks for more HIV
(f) Assembly New HIV proteins and HIV RNA move to cell surface
(7) Budding Newly formed immature HIV pushes itself out of CD4 cell and then releases protease which
breaks up the long protein chains that form immature virus and thus the mature infectious HIV forms
25. Describe the typical course of untreated infection with HIV?
(i) First few weeks typically acute influenza like viral illness aka SEROCONVERSION disease
(ii) Adaptive immune response follows which controls the illness acutely, restoring levels of CD4 T cells but
dont eradicate virus ASYMPTOMATIC phase
(iii) Opportunistic infections and other symptoms become more frequent as CD4 T cell count falls, from
500microlitre cells SYMPTOMATIC PHASE
(iv) When cell count falls below 200microlitre the patient said to have AIDS
26. Describe the immune response to HIV?
(i) Initially have high response in seroconversion, i.e. first 4-8 weeks
(ii) During prolonged asymptomatic phase, virus is relatively low level in peripheral blood whilst it is
replicated persistently in lymphoid tissues, so CD4 T cells gradually decline with antibodies and CD8 T cells
against HIV are high
(iii) Eventually levels of antibody and cytotoxic T cells also decline with a progressive increase in infectious
HIV in peripheral blood [after 12 years ish]
27. AIDS related conditions in GI tract?
Kaposis sarcoma, malignant lymphoma, infections such as cryptosporidiosis, salmonella, candidiasis,
gingivitis, cytomegalovirus
28. AIDS related conditions in respiratory tract?
Kaposis sarcoma, pneumonia infections from PCP and PJP, TB, cytomegalovirus.
-- Co-trimoxazole treats PCP
29. AIDS related conditions in CNS?
Meningitis, encephalititis, AIDS complex dementia, Multifocal leucoencephalopathy, malignant lymphoma,
infections such as toxoplasma gondii, herpex simplex and zoster, cytomegalovirus
30. AIDS related conditions in skin?
Kaposis sarcoma and infections such as herpes simplex and zoster
31. AIDS related conditions in eye?
Cytomegalovirus retinitis give oral valganciclovir maintenance therapy or IV ganciclovir, foscarnet or
cidofovir
32. What are the key difference in AIDS presentation in children and adults?
Children symptomatic, rapid progress, Kaposis rare, bacterial sepsis major problem
Adults asymptomatic periods, variable progression, Kaposi common
33. What is the aim of combination therapy HAART?
To reduce the plasma viral load to below 50 copies/ml within 6 months of initiation
34. Rationale for ART?
Preserve anti-HIV immune response, reduce morbidity associated with viraemia and low CD4 count and
reduce risk of onward transmission
35. What are the 6 drug categories?
NRTIs, NNRTI, PI, Fusion inhibitor, integrase inhibitor, CCR5 antagonist
36. What are NRTIs? Non-nucleoside analogue reverse transcriptase inhibitors
Abacavir, Lamivudine, Tenofovir & Emtricitabine
False substrate! Similar to working as anti-cancer drugs-get incorporated into DNA transcript and cause viral
stasis as its a malformed transcript now
37. What are side effects of NRTIs?
Myelosuppression, peripheral neuropathy, pancreatitis, raised hepatic enzymes and CNS disturbances.
RESISTANCE
38. What are non nucleoside reverse transcriptase inhibitors NNRTIs?
Efavirenz, Nevirapine, Etravirine
Bind to reverse transcriptase enzyme to inhibit replication thus are direct acting, RESISTAN
39. What are protease inhibitors?
Amprenavir, Atazanavir, Fosamprenavir, Ritonavir, Saquinavir, Tipranavir
Attacks protease enzyme which is required for viral maturation after leaving host cell, produces functional
viral core all are metabolised by CYP450! **
40. What are side effects of protease inhibitors?
Most commonly get GI disturbances and LIPODYSTROPY
41. What is boosted PI?
Using a PI with another drug as boost mainly RITonavir and COBICIstat as they are inhibitors of P450 at
low dose so can add to another PI above
42. What are fusion inhibitors?
Enfuvirtide
Attacks the earliest stage and prevents fusion of HIV glycoproteins with CD4 cell surface
43. What are side effects of fusion inhibitors?
Injection site reactions, insomnia, peripheral neuropathy and pancreatitis
44. What are integrase inhibitors?
Raltegravir, Dolutegravir, Elvitegravir
Inhibit the integrase enzyme which the complement DNA requires to use host DNA machinery
45. What are CCR-5 antagonists?
Maraviroc
Attacks specifically where CCR-5 is the coreceptor
Licensed for patients exclusively infected with CCR5-tropic HIV
46. What are some clinical features of HIV associated drug hypersensitivity?
Maculopapular rash, fever, myalgias/fatigue, mucosal ulceration
47. Why is combination therapy used, HAART or CART?
Overcome resistance mainly and side effects!
48. When should therapy be initiated?
When the individual becomes SYMPTOMATIC or CD4 count is below 350cells [normal is 500-1200], or in
 patients with rapidly falling CD4 count/rapidly increasing viral load
DO NOT initiate in asymptomatic as drugs have side effects and may worsen condition
--ALSO if AIDS, Hep B/C, CVD

HYPERTENSION

1. What is hypertension?
Blood pressure that stays elevated more than 140/90
2. What is the level of hypertension if there is diabetes/kidney disease?
Hypertension of 130/80 it is slightly lower if have these comorbidities
3. What is the pressure in 1 atmosphere?
760 mmHg this goes down as you climb up mountain level
4. What is diastolic pressure?
Pressure when the heart is RELAXING
5. What is systolic pressure?
Pressure when the heart is CONTRACTING
6. How prevalent is hypertension?
Most prevalence cardiovascular disease, can only be CONTROLLED not cured
7. What is it usually called or known as?
Silent killer usually does not present any major symptoms
8. What is the rule of halves?
Half of those who have it are undiagnosed
9. How many people does it affect over the age of 65?
Affects around 45% of over 65
10. What is the equation for blood pressure control?
BP = cardiac output x total peripheral resistance
11. What 3 factors are controlled to maintain BP?
(a) Blood volume
(b) Cardiac output
(c) Total peripheral resistance
12. What is cardiac output?
Stroke volume x heart rate
The amount of blood formed by the heart per minute; it takes 1 minute to send it all through body once
13. What is total peripheral resistance?
Resistance that occurs when blood flows through enclosed space i.e. vessels
14. How would blood volume be targeted?
Diuretics would cause people to pee more which would reduce the blood volume and then decrease blood pressure
15. How would cardiac output be targeted?
Can reduce the heart rate or reduce the force of the contraction
16. How would peripheral resistance be targeted?
By dilating the vessels to decrease resistance using direct dilators or chemicals
17. What are the two types of hypertension?
(a) Idiopathic or Essential HPT
(b) Type 2 or Secondary HPT
18. What is idiopathic/essential HPT?
Without identifiable cause but mostly indirect and constitutes around 90% of all cases
19. What can secondary HPT be caused by?
(a) Medical treatment e.g. from being on steroids
(b) Renal vascular disease urine volume changes blood volume, as more volume means more pressure exerted on
arteries walls
(c) Parenchymal disease
(d) Gestational HPT
 (e) Phaeocytochroma adrenal medulla responsible for NA & A and A will stimulate heart to beat faster
(f) Cushings syndrome
(g) Aortic coarctation
20. How many stages are there for HPT classification?
3 stages
21. What is the BP in stage 1?
Clinic blood pressure is 140/90 AND subsequent ambulatory daytime average or home BP is 135/85
22. What is the BP in stage 2?
Clinic BP is 160/100 AND subsequent ABPM is 150/95
23. What is the BP in stage 3 severe HPT?
Clinic systolic is 180+ OR diastolic is 110+ i.e. exceeds 180/110
24. What environmental factors can increase BP (6)?
(a) High SODIUM diet more sodium, more H20 retention, increased blood vol
(b) OBESITY related to angiogenesis, increased perfusion demands of body
(c) SEDENTARY lifestyle
(d) KIDNEY disease e.g. stenosis of renal artery
(e) STRESS and type A personality increased sympathetic activity, get release of cortisol & adrenaline
which stimulate heart, increase rate and force
(f) SMOKING via atherosclerosis as arteries become brittle, less elastic
25. What are the symptoms?
Usually NO SYMPTOMS or signs present silent killer detection of high BP only made through
measurements
26. What is the exception to the symptoms?
If MALIGNANT HPT can cause headache, congestive heart failure, stroke, seizure, papilledema, renal
failure and anuria
27. What is papilledema?
Optic disk affected
28. Why does malignant HPT lead to congestive heart failure?
If pressure too high in vessels the heart has to pump more forcefully to get the blood out so has to overcome
higher pressures and work harder
29. What are the consequences of HPT (6)?
(a) Accelerated atherosclerosis in turn could lead to stroke, CAD, MI, aneurysms or occlusive aortic disease
(b) Remodelling of heart as compensatory mechanisms but could lead to diastolic dysfunction
(c) Dilation of heart lead to systolic congestive heart failure
(d) Kidney damage renal failure
(e) Stroke risk
(f) Eyes affected loss of vision
30. What are the mechanisms for HPT (4)?
(a) Volume ejected from the left ventricle is too high
(b) There is high intravascular volume
(c) An elevated venous tone
(d) High arterial elastance
31. How does volume ejected too high contribute?
Cardiac output is basically high and one reason could be excessive contraction during systole high end
systolic pressure-volume relationship i.e. ESP-VR
32. How does a high intravascular volume contribute?
If kidney is damaged/dysfunctional, it could result in intravascular volume higher as there is subsequent fluid
retention or even due to exogenous administration
33. How does elevated venous tone contribute?
Veins are contracting more than normal will lead to a rise in LVEDV [LV-end diastolic volume] which can be
due to normal or low actual blood volume; LVEDV is the volume of blood in LV at end of diastole [heart
relaxed]
34. What is the normal volume of LV and LVEDV?
It can accommodate 120ml of blood, of which 70ml is pumped out leaving 50ml in each LVEDV
35. High arterial elastance
Can arise due to high arterial resistance or low arterial compliance
36. What is the rationale behind pharmacotherapy?
(a) Reduce the left ventricle systolic performance i.e. reduce ESP-RV negative ionotropes, beta
 blockers, calcium channel blockers
(b) Reduce blood volume i.e. drop LVEDV diuretics
(c) Reduce venous tone and venous return sympatholyticcs [drugs that reduce overall sympathetic
return]
(d) Reduce arterial tone and thus reduce elastance ACE inhibitors, Angiotensin blockers, calcium
channel blockers, nitric oxide donors, alpha-1 blockers
37. What are negative ionotropes?
Any drug that REDUCES FORCE of contraction such as B-blockers B1 receptors I heart which bind
adrenaline to increase contraction force as opposed to B2 in lungs which relaxes smooth muscle!
38. Properties of an ideal antihypertensive drug (5)?
(a) Good BP control over 24 hours
(b) Reduction in incidence of stroke & MI etc.
(c) No adverse affects or contraindications from use
(d) Once daily dosage
(e) Cost effectiveness
39. Guidelines for step 1 for patients below 55 and not AA/C
Start on an ACE INHIBITOR
If not tolerant then offer an ANGIOTENSIN RECEPTOR BLOCKER
40. If both above drugs are contraindicated then use?
BETA BLOCKERS
41. Guidelines for step 2
If target BP not met, add a CALCIUM CHANNEL BLOCKER to ACEI/ARB
42. What if calcium channel blocker is not tolerated in step 2?
Give a thiazide related diuretic instead
43. Guidelines for step 3
Either ACEI + calcium channel blocker + thiazide diuretic or ARB + calcium channel blocker + thiazide
diuretic
44. Guidelines for step 4
Consider SPECIALIST ADVICE! Also can add LOW DOSE SPIRONOLACTONE [aldosterone receptor
antagonist] or a high dose thiazide diuretic
If this is contraindicated or ineffective etc. then consider an ALPHA BLOCKER
45. What are the different guidelines for over 55 and AA/C origin?
Step 1 start on CALCIUM CHANNEL BLOCKER
Step 2 calcium channel blocker/thiazide diuretic in combination with ACE INHIBITOR or
ANGIOTENSIN RECEPTOR ANTAGONIST [this one is preferred]
46. An example of angiotensin converting enzyme inhibitors ACE-I
Captopril [all end in prils]
47. What is ACE-I function?
Inhibit the conversion of ANGIOTENSIN 1 to ANGIOTENSIN 2 by blocking enzyme ACE
48. What other effects on the heart can it have aside from BP decrease?
Decrease ventricular HYPERTROPHY, appear to improve mortality/morbidity and can also offer extra
cardioprotection
49. What other conditions are they also indicated for?
Diabetes and after an MI appears to improve glucose tolerance
50. When are they contraindicated?
In renal vascular disease, aortic stenosis and pregnancy [foetal renal damage?]
51. What is the normal function of angiotensin etc.?
Angiotensin 2 is a potent VASOCONSTRICTOR and also stimulates adrenal gland to produce aldosterone
[retains water thus increases blood volume]
52. What is a side effect as a result of bradykinin breakdown?
Persistent cough possibly due to the increased levels of bradykinin as ACE is responsible for bradykinin
breakdown
53. What other side effects are there (3)?
(a) Severe 1st dosage HYPOTENSION can occur
(b) RENAL impairment
(c) TASTE changes or loss of taste completely
54. Examples of angiotensin receptor antagonist?
Losartan [ends in sartans]
55. What is their function?
Blocks effects of angiotensin II at their receptors in the vascular muscle thus similar to ACEI without the
cough!
56. What are some adverse effects?
Few and mild but very expensive
57. Examples of calcium channel blockers
Amlodipine, Nifedipine, Ditiazem and Verapamil
58. What do the dipines affect more?
The smooth muscle hence blood vessels
59. What is their function generally?
To reduce calcium entry into muscles during excitation which decreases contraction of vascular muscle and
thus decreases TPR
60. Why should verapamil be avoided in heart failure?
Verapamil has an increased effect on the heart depresses the muscle so must avoid
61. What are adverse effects (4)?
(a) Headache
(b) Flushing
(c) Oedema
(d) Fatigue
62. Examples of aldosterone receptor antagonist
Spironolactone and Eplerenone [end in one]
63. What is the action (2)?
(a) Increases EXCRETION of sodium and water
(b) Decreases excretion of POTASSIUM
64. What are adverse effects (2)?
(a) Hyperkalaemia
(b) Gynaecomastia enlargement of mens breast because of hormonal imbalance
65. Example of diuretics
Bendroflumethiazide ends in thiazide
66. What is its function?
Initially increases sodium and water excretion thus reducing blood volume, CO and BP. Later however,
CO returns to normal while BP remains low -- ?? Suggests an action on just the vascular wall??
67. Why is it not given with a beta blocker anymore?
Both beta blockers and thiazide diuretics can push up glucose levels and cause or worsen diabetes so
combination not used anymore
68. What are adverse effects (5)?
(a) HYPOKALAEMIA not very frequent but can cause dysrhythmias in failing hearts or ischaemic hearts
(b) Dizziness
(c) Nausea
(d) HYPERGLYCAEMIA in about 10%, those with impaired glucose tolerance
(e) HYPERURICAEMIA in about 30%, aggravates diabetes and gout
(f) Increase levels of TRIGYLCERIDES, LDL and total cholesterol
69. Examples of beta-blockers?
Propranolol
70. What is its main action?
Decrease effects of sympathetic nervous system on the heart and reduce renin
71. What is its main problem mostly?
Unselective! In asthma, can block B2 action of relaxation so contraindicated
72. What else are beta-blockers very good at?
Anti-dysrhythmias
73. What are its possible mechanisms for lowering BP (4)?
(a) Decrease CO, HR and SV
(b) Reduce RENIN output via B1 receptors in kidney
(c) CENTRAL effect on CNS may decrease sympathetic flow?
(d) Decrease TOTAL PERIPHERAL RESISTANCE maybe they limit noradrenaline release at sympathetic
nerve terminals
74. In whom are they more effective?
Younger patients rather than elderly
75. What are some adverse effects (6)?
(a) BRONCHOCONSTRICTION major adverse effect
(b) COLD hands and feet
(c) Fatigue and sometimes depression
(d) Sleep disturbance vivid dreams, nightmares
(e) Decreased libido, impotence
(f) ADVERSE affect on LIPIDS
76. What are cardioselective beta-blockers?
Act on just a specific receptor ATENOLOL affects B1 more, no cross BBB
77. Examples of alpha blockers
Prazosin
78. What are alpha-1 receptors responsible for?
Vasoconstriction
79. How does it have action in HPT?
Decreases peripheral resistance and improve LIPID profile by increasing HDL
80. What are adverse effects (4)?
(a) POSTURAL hypotension
(b) Dizziness
(c) Weakness
(d) Headache
81. Example of a/b blockers?
Labetalol
82. What do they do?
Decrease CO and TPR by blocking a1, B1 and B2 receptors
83. Why are they not used often?
Little evidence of being more advantageous over simple B-blockers
84. Examples of centrally acting drugs of alpha 2 agonists?
a-methyldopa and Clonidine
85. What does alpha 2 usually do?
Inhibits noradrenaline so it decreases sympathetic neurotransmitter
86. When are they used?
As 2nd/3rd line treatents in patients not responding to other agents or those with contraindications
87. What is special about methyldopa use in people?
Safe in PREGNANCY, ASTHMATICS and heart failure!
88. What is a serious disadvantage of clonidine?
If suddenly stopped or withdrawn, lead to rebound hypertensive crises
89. What are some side effects?
(a) SEDATION
(b) POSTURAL hypotension
(c) Rebound hypertension
90. What are the drugs used in hypertensive crises (6)?
(1) IV sodium nitroprusside
(2) Labetalol
(3) Glyceryl trinitrate
(4) Phentolamine
(5) Hydralazine
(6) Esmolol

MALARIA 1
1. What kind of disease is malaria?
A protozoal disease
2. What is a protozoa?
A single cell animal, can be simple or complex organisms
3. What are some examples of other diseases caused by protozoans?
Amoebiasis, Giardiasis and Cryptosporidiosis
4. What do these three conditions of A, G and C have in common?
They all affect the gut and cause diarrhoea
5. Give three further examples of diseases that are more global as well?
Trichomoniasis, Leishomoniasis and Tyrpanosomiasis
6. What is trichomoniasis?
It is an STI which affects mainly women more than men
7. What is Leishamaniasis?
A complex of diseases that affect the skin, symptoms include getting sores and ulcers
8. What is trypanosomiasis?
Also a complex of diseases, with two main types of African sleeping sickness and Chagas
disease which is more common in South America. Exposed to a fly called tsetse.
9. Why is it called sleeping sickness?
There is disturbance of the sleep cycle in the disease which is a key feature
10. Who is affected the most by malaria?
The greatest burden is in Africa and most children under 5 years old die. It is greatly associated
with poverty.
11. How has malaria become global?
With travel patterns increasing, now malaria is a problem all over the world
12. How do deaths from malaria occur in the UK?
Generally people die because malaria is not recognised quickly enough. There are about 10-20
people dying in approximately 10-20,000 cases each year. It is assumed to just be a fever for
example.
13. Why is malaria and/or malaria treatment such a problem?
Parasites have become resistant to antimalarials.
14. Which was the first drug to develop for malaria?
Chloroquine was the first effective drug to be developed, it was widely used and deaths
dropped considerably.
15. Why did chloroquine become less successful?
The parasite started becoming resistant to chloroquine, this started occurring shortly after
around 1965. The situation since 1987 when resistance had spread a lot only became worse.
16. What is the trend for the deaths since 1950 then?
Deaths initially went down in the 1950s, but then came up slowly. Between 1980-2010
mortality from malaria was high and this was due to the resistance developed to chloroquine.
The number of deaths are now coming down slowly because of better treatments
17. How is the disease caused in humans?
The parasite is carried in the Anopheles mosquito. It is only carried in female mosquitoes! Only
the female bite; assumed to be because the female needs blood to intubate her eggs and
help develop them as blood contains proteins that are needed by her.
18. How does the blood sucking process occur?
The bite occurs on human skin (or other animals) as the female has specific mouth anatomy that
allows it to occur. The blood then goes straight to the stomach of the female mosquito. Red
blood cells are filtered out which leaves the plasma behind to be eliminated from the other
end of the mosquito as droplets. Thus the RBCs are retained in the stomach.
19. Which are the two most important parasitic species that affect humans?
Plasmodium falciparum and Plasmodium Vivax.
20. How many deaths are caused by each species?
P.Falciparum has around 1 million deaths annually however in the last few years it has gone
below 1 million. This is largely due to cerebral malaria occurring and the resistance to
chloroquine amongst other drugs.
P.vivax has lower mortality and the key feature is that relapse occurs later (months/years) and
chloroquine resistance is rare
21. What is the clinical assumption made if someone presents with P falciparum malaria?
Someone presenting with P.falci is assumed to be resistant to chloroquine and thus not treated
with it unless it can be known for sure.
22. What are three other strains that can cause malaria in humans?
(a) P.malariae; it is less common and main feature is that it can cause kidney disease. (b)
P.ovale; is even rarer and occurs in certain parts of Africa. (c) P.knowles; is very rare and has
only been known in humans for the past few years, it usually infects primates (monkeys) but
now seems to have jumped from monkeys to humans
23. In which part of the body does the mosquito carry the parasite?
The saliva -- the parasite travels in to the salivary gland and huge numbers are found there.
This is how it is injected into humans whilst feeding occurs, it inoculates parasite into humans
blood
24. What is the first stage of the cycle called?
The first stage parasites are known as sporozoites, these are the ones that have been
inoculated into the bloodstream
25. Where do the sporozoites travel to?
In a short period of time, they can be found travelling to the liver and infecting hepatocytes. It
is here where the multiplication of the parasite begins
26. What is the next stage called and what happens?
Once the multiplication occurs, the parasites break out of the cell after maturation in thousands
and go into the blood stream, these are known as morozoites
27. What do morozoites do?
They infect the red blood cells, each merozoite binds to 1 RBC and then begins to grow. This
growing stage is termed trophozoites whilst it is growing, and it also further multiples
28. What is the result of the growing and multiplying?
A schizont is formed, it means splitting, through asexual reproduction. The parasite has
divided into about 15 new parasites and these break away again.
29. What are the final stage parasites called?
They are then known as morozoites which go on to infect more RBCs and so forth.
30. When can the immune system get involved?
The immune system can only attack the parasites when it breaks out of RBCs because whilst
attached to them the parasite is protected. This is when the symptoms then appear of chills and
fevers and why it can be intermittent in some people.
31. What else can parasites do apart from infecting RBCs?
They can form metosoites which is the process by which parasites induce the cycle back in the
mosquito. If a mosquito feeds on infected blood from human, it can get metosoites into its body
as it is taken up in the stomach. These combine by male and female sexual production to
complete the cycle and the parasite travels to the salivary gland.
32. How is this process different in P vivax compared with P falci?
The above process only occurs with P.falci really, in P.vivax there is a complication. This is
because there is a relaxing form of the parasite, it forms hyponzoites which means dormant
or sleeping stage, and these parasites can stay in the liver (hepatocytes) for months or years.
Then something causes them to break out of their cells but it is not known what. [This also occurs
with P.malariae]
33. What do parasites look like under the microscope?
See greyish cells that are the RBCs and the parasites show up as a BLUE colour from G
staining. Some of the cells can also have rings in them, which show the early growing stages.
These would grow and eventually form schizonts.
34. What material does the schizont contain that can be seen in microscope?
A browny material can be seen in the schizont which is called the malarial pigment or
haemazoin.
35. What is the malarial pigment?
Haemozoin/malarial pigment is derived from iron in Hb. Parasites feed on the haemoglobin in
the red blood cells but in the centre of the haemoglobin is the haem ring containing iron. The
parasites cannot take this and leave this behind which is what is seen in the cultures
36. Are all the presenting symptoms of malaria the same in people?
NO the most important aspect is this fact; presenting symptoms are often variable and non
specific
37. Why are the symptoms difficult to pinpoint malaria?
The presenting symptoms are things that not in themselves suggest a serious condition for
example, diarrhoea, flu-like illness, fever, chills, pain and nausea are all broad symptoms
38. Why is malaria so dangerous?
It can kill within 24 hours! The flu is not taken seriously but the timespan can be very short for
death.
39. What considerations should be made for people travelling from malarious countries?
Malaria should be considered in people who visited malarious countries for up to a year after
returning. This is because people may have been taking antimalarials that suppressed the
malaria for a while but does not exclude the malaria being there.
40. List 6 symptoms of malaria
Liver/spleen enlargement, anaemia, hypoglycaemia, convulsions due to fever or cerebral
malaria, renal failure and septicaemia.
41. Why is hypoglycaemia so important?
Hypoglycamemia is a common complication of P.falci and could lead the patient into a coma.
If this happens, the coma could be mistaken for cerebral malaria and this mistake is just as
dangerous
42. Why does cerebral malaria occur?
Red blood cells infected with parasites are can bind or stick to brain capillary walls,
sequestration which occurs because the parasite induces changes in the RBC membrane
forming nobs on the membrane and its these changes that bind to receptors on the capillary
wall. The capillary wall then gets clogged up with these infected parasites, leading to a loss of
oxygen and release of chemokines (TNF). It is this combination of hypoxia and cytokine
activation that causes coma.
43. Why are children under 5 most at risk or die?
Children have very little immunity against malaria at this young age, however what generally
happens is that the average African child could get several infections with malaria and if lucky
will develop immunity and survive. But in most this does not happen
44. Why are pregnant women susceptible to malaria?
The immune system is modified and suppressed in the pregnant mother to ensure that rejection
of the foetus does not occur, thus there is an increased risk of malaria in pregnancy. Death can
occur in a similar way to cerebral malaria as the infected RBCs can be sequestered into
placenta and bound by receptors.
45. What is the relationship between malaria and genetic disease?
Malaria is considered to be a major cause of genetic disease and this is seen through sickle
cell disease especially. It is for those with abnormal haemoglobin SCD and thalassaemias. It
is thought that the resulting abnormal Hb is a response by the body to provide resistance to
malaria.

MALARIA 2

1. What are the two questions that must be asked when patients present with malaria?
Which type of malaria is it, vivax or falciparum?
Are the parasites drug resistant?
This is because all over the world it is common for people to take antimalarials when there is
fever but this is the problem of overuse.
2. What is the first choice drug for P. vivax?
Chloroquine is the first choice drug still for this strain as it is rarely resistant to it.
3. How can P.vivax become a fatal condition?
It can kill people when the spleen grows enormous and could burst. Also need to remember
than they stay dormant in liver and break out to reinfect at any time.
4. What is the problem with treating P.falciparum?
This strain is often drug resistant, even if there is no guarantee that the patient will be resistant,
just have to assume that they are
5. In what conditions can P.falci be fatal?
It is often fatal if cerebral malaria occurs (leading cause of death), if it occurs in children or
pregnant women. Also, if we go to Africa we will be at great risk, as we do not have immunity
and the people who have moved away from Africa and then go back as they have decreased
their immunity.
6. What two categories of antimalarial drugs exist?
Blood schizontocides kill the parasites in blood, but are not effective against parasites in the
liver hence they are known by blood schizont, they are also known for the stage they attack,
schizont.
Tissue schizontocides kill parasites in liver for example in vivax we need this one to get rid of
dormant parasites. There is only 1 of this in clinical use!!
7. List all the treatments
Quinine, Chloroquine, Mefloquine, Artemisinin, Lumefantrine, Atovaquone + Proguanil,
Pyrimethamine + Sulphadoxine, Doxycycline and Primaquine.
8. Historically what was the main anti-malarial?
Cinchona bark was used for malaria in Europe from about 1630, it was originally from South
America but in that time Europe had a big malaria problem and this bark was used to treat
fevers in SA so it was found it was effective against malaria
9. What was in the cinchona bark?
Quinine was later extracted from this bark, in 1820, and was found to be the main agent
effective.
10. Why did the use of quinine decline and when?
Quinine use declined in the 1950s when chloroquine came into use, however now that malaria
is resistant to chloroquine, quinine is increasing again.
11. What are the two main problems with quinine?
It is a slow acting drug and it has significant side effects.
12. What is cinchonism?
Almost all patients will suffer from this set of symptoms that come about from excessive use of
quinine, as a lot has to be given to treat malaria. This includes tinnitus, problems with balance,
nausea, vertigo and abdominal pain.
13. What other symptoms are present (4)?
Hypoglycaemia can also occur to due insulin release, the patient may already have
hypoglycaemia from malaria and so this can precipitate coma.
Hypotension
Cardiac arrhythmias
Convulsions
Blindness
These latter ones are heart toxicities. If it is injected too quickly or given as a strong solution it
can cause death as it has strong effects on the heart.
14. How must quinine be administrated then?
It has to be given as a dilated solution infusion and slowly, NEVER AS IV BOLUS
15. What kind of compound is chloroquine?
It is similar to quinine, related to it. Chemically it is known as a 4-aminoquinoline.
16. How is chloroquine administrated?
It is used mostly by mouth (orally) or given as injection (parenteral) for chloroquine sensitive
patients.
17. What are the adverse effects associated with chloroquine?
Most effects are milder, compared to quinine. But severe ones are neurotixicity and
cardiovascular toxicity, again if it is injected too quickly
18. What singular strange phenomenon is observed in Africans?
It can cause intense itching (pruritis) in Africans especially in the soles of their feet, unknown
why.
19. What is mefloquine?
Another quinolone derivative; a 4-quinoline methanol. It was developed in order to combat
chloroquine resistance and it was pretty effective. [used as treatment and prevention for
chloroquine resistant malaria]
20. How is mefloquine administrated?
It is usually given orally. IT CANNOT BE INJECTED, as it is an irritant. Hence it cannot be given
to the severely ill patient.
21. What is the most serious adverse effect?
Main problem is that it can cause psychiatric side effects that can be severe, especially when It
is used as prophylactic treatment rather than when given as a short course treatment, so if
person was given regular doses then more prone to get this problem than if it was a short
course treatment
22. What other symptoms can there be (5)?
Anxiety
Hallucinations
Mania
Suicidal thoughts
Chronic Fatigue Syndrome after treatment people complain about this a lot.
Effects are said to be rare but are not really, so should not rush to prescribe this drug!!
23. When and in whom can mefloquine never be given?
Airline pilots are not allowed to be using this drug and it is not allowed to be administered in
depression (WHO).
24. How do quinolines work?
All the quinolones interfere with haemozoin. In the RBC, the parasite feeds on Hb, digesting it
and using the globin as protein for its own growth. It leaves the haem as it is toxic, converting
the haem into haemozoin which is the brown pigment found in the middle, this is non toxic and
happens spontaneously, do not fully understand how and may not necessarily require an
enzyme. The quinolones block this process of haem to haemozoin occurring, by binding to haem
and preventing the conversion to non toxic material. This drug-haem complex kills the parasite.
25. How was artemisinin discovered?
Following the revolution in China, the Chinese people investigated their own herbal medicines
and especially those that were used herbally for malaria. One of these was Qing Hao, used
for centuries against malaria. The plant name is Artemisia annua. From this, the material
artemisinin was isolated and shown to exhibit potent antimalarial activity. [discovery saved
millions of deaths from malaria, it was effective against all forms of malaria!]
26. What is the problem with the discovered artemisinin?
The substance was not very soluble so derivatives had to be made in order to improve
bioavailability.
27. What alternative forms were developed?
Arthemeter: dissolved in oil so could be given intramuscularly or orally
Artesunate: water soluble so could be given IV
28. What are the key advantages of artemisinin (6)?
Rapid action most rapidly active antimalarial drug
Highly effective against cerebral malaria those with coma would wake up very quickly
Effective against drug resistant parasites however because it has been used a lot there are
resistant strains emerging in some places, particularly Vietnam & Thailand
It has very low toxicity in contrast to quinine [unsure about toxicity in the first trimester of
pregnancy]
May help prevent malaria transmission as it kills male and female forms of parasite so not
likely to suffer sexual reproduction stages
29. What is the important part of the artemisinin structure?
The most important part of this unusual structure is the O-O molecule; it is a PEROXIDE. This
means it is very reactive. The antimalarial effect depends entirely on this peroxide, if removed
it does not work at all
30. How does artemisinin work?
It is based on the same pathway as the quinolones i.e. the Hb being digested to leave iron.
However, the iron in the haem activates the peroxide group in artemisinin. The iron triggers
breakdown of the peroxide group, causing production of FREE RADICALS [molecule with a
single unpaired electron thus highly reactive]. These free radicals react with the parasite and
cause death. So the mechanism of action is different but artemisinin also relies on the Hb. [if
you add iron to hydrogen peroxide, it would decompose and release all the oxygen which is
similar in this case]
 31. What are the limitations of artemisinin (2)?
One of the main problems is RECRUDESCENCE the drug has a very short half life, a couple
of hours, which means that even though it is effective, some parasites will escape, so this
recrudescence happens because not all the parasites are killed and thus can grow again. It is
not like a relapse and not like when parasites stay dormant, it is just because it does not kill in
one go. Thats why WHO says it must be given with another drug and this also decreases the
chances of resistance occurring.
Secondly it may not be safe in the first trimester of pregnancy it is not established however
if a pregnant women gets malaria, the risks are so great compared to drug toxicity that
artemisinin would still be used.
32. Give examples of other blood schizontocides (4)
(a) Lumefantrine given with arthemeter as the combination therapy to prevent recrudescence
(b) Atovaquone with proguanil known as MALARONE, also a combination therapy, popular
treatment and prevention
(c) Pyrimethamine and sulphadoxine has some resistance
(d) Doxycycline often used as a preventative but not in children, as it affects bones being a
tetracycline drug
33. What is the only tissue schizontocides in clinical use?
Primaquine
34. How does primaquine work?
It kills the dormant cells in the liver so active against the liver stages of P.vivax. If patient has
vivax, first given chloroquine to kill the blood parasites and then given primaquine to kill those
dormant in the liver to prevent relapse.
35. When is primaquine toxic?
Primaquine and chloroquine together are toxic so they cannot be given together only
before/after
36. What are the disadvantages of primaquine?
It is quite toxic. It causes adverse effects especially in patients with G6PD deficiency as their
red blood cells are easily broken down? It has to be given as a small dose over a longer
period of time
37. What treatment should be initiated for severely ill patients?
Use PARENTERAL therapy with the drugs arthemeter and quinine. Quinine is the first choice in
BNF, but most would choose artemisinin, as it is a safer option.
38. What drugs should be used for oral therapy in P.falci?
Arthemeter + Lumefantrine
Atovaquone + Proguanil
Mefloquine
39. What treatment is initiated for P vivax?
Chloroquine is used (as rarely resistant) followed by primaquine to prevent relapse

OBESITY 1

1. What is the global trend of obesity currently?

It is increasing globally, WHO calls it globesity. It is a pandemic now
2. Describe the classical example of obesity in the US trends
In 1990, it was below 10% in any state. Within a year more darker parts came for between
15-19%. By 1993, almost 1/3 of states had <10%. By 1995, half of US was covered in 15-
19%. In 1997, another group had to be added for above 20%. In 1999, half of US was more
than 20%, and by 2001, another 1 colour had to be added for more than 25%.
3. What is obesity?
BMI over 30
4. What are the epidemic statistics for the UK for 2004 and then 2010?
20% of adults and 10% of 6 year olds were classed as obese, though overweight people
were not considered. By 2010, 26% of adults were obese and 30% of children were
overweight or obese
5. What is the leading cause of death worldwide currently?
MALNUTRITION premature death in Africa and underdeveloped countries
6. What is the malnutrition of?
Protein energy malnutrition
7. What is estimated to be become the leading number one cause of death?
OBESITY premature death worldwide
8. Why would obesity be the leading cause of death in developed countries?
Eating indiscriminately so people are suffering from MICRONUTRIENT malnutrition
9. Why does weight gain occur?
Energy intake exceeds expenditure. Genetics may play a small role
10. What is obesity considered to be risk factor for?
Cardiovascular disease independent risk factor for CV events
Type II diabetes BMI, waist circumference, waist-hip ratio all predict diabetes
Cancers hormone dependent, weight-hip ratio positively associated with premenopausal
breast cancer, but strength differs in ethnicities
11. Why else can cancer risk increase?
Pollutants in the air are fat soluble so get stored in fat
12. What is the meaning of metabolic syndrome?
Umbrella term for all the disorders that can develop as a result of obesity; such as Type II
diabetes, dyslipidaemia, hypertension, mechanical stress
13. What can mechanical stress caused by obesity lead to?
Osteoarthritis
Low back pain
Shortness of breath
Sleep apnea because of increased fat mass which pressurises muscles so during sleep have
apnea
14. What is the economic cost to the NHS?
Around 4.2billion in NHS
15. What is the cause of obesity?
When there is excessive energy intake, there is no energy balance anymore [balance between
intake and outtake]
16. What is the energy intake?
Energy that is utilised and energy that is stored
17. What does the first law of thermodynamics say about energy and weight?
Energy can only be transformed, never created or destroyed. Thus, if there is more food intake
than needed, our body will change shape as a result
18. How does weight loss occur?
Through decreased food intake and/or increased energy expenditure
19. What does a positive energy balance of just 1% equal in weight?
An extra 10kg of fat per decade [for a 100kg person]
20. What are the units of energy measured in?
Calories the big C is used for food whilst kcal used for other things
21. What is a calorie defined as?
The heat required to raise the temperature of 1g of water by 1 degrees Celsius [chemical
energy is predominantly given out as heat]
22. What is a bomb calorimeter?
A steel container used to determine the energy contained in a substance by measuring the heat
generated during its combustion
23. What does 1 Calorie equal in Jules?
4.18
24. How much does 1g of starch and lipid weight in kJ?
17.6 kJ and 39.6kJ, so lipid has double the amount of Calories
25. What are the 3 main factors that influence energy expenditure?
(a) Basal metabolic rate, BMR 60-75%
(b) Voluntary physical activity 15-30%
(c) Diet induced thermogenesis around 10%
26. What additional factors influence energy expenditure?
(a) Cold induced thermogenesis white vs. brown fat, need brown fat for moving to a colder
climate as brown fat is involved in thermogenesis, if person from tropics then dont have brown
fat. A decrease in room temp from 28-22 results in 7% increase in heat production
(b) Psychologically induced thermogenesis situation where someone has to fight or flight,
would be an adrenaline rush
(c) Drug induced thermogenesis such as amphetamines
(d) Special needs e.g. if pregnant, lactating, convalescence
27. What is the basal metabolic rate?
Energy required to sustain the functioning of the vital organs. This is basal but when exercising
it changes so then it is not BMR anymore. So it is when sat down and not spending much
energy!
28. When can BMR be measured?
In temperate environments post digestion and post absorptive period e.g. a few hours after
breakfast
29. What is BMR determined by?
Body weight mostly free fat mass
30. How does the BMR differ with age?
Children have the highest BMR, versus the older population so BMR DECREASES with age; slows
down
31. What type of person has the highest energy requirement?
Taller and more muscular people have highest basic energy requirement. This is because it all
depends on body surface and mass so larger person typically requires more energy to do
the same task
32. What does voluntary physical activity describe?
The energy needed relates to the intensity of the work and the time spent doing it, so it
related to how stressful a job is because if work is stressful or demanding it is reflected in the
BMR, will be higher
33. How is exercise related to thermogenesis?
Exercise uses energy to power mechanical work, it produces a lot of heat which is called EAT
[exercise associated thermo]
34. Is it just physical activity that contributes to energy?
NO mental activities can also result in energy expenditure but the contribution varies e.g.
those who play chess have body weight decreases.
35. How can activity related energy be expressed?
As a ratio physical activity ratios describes the energy cost per hour as a multiple of the
BMR, this average differs in males and females e.g. walking slowly there is a bigger PAR in
females than males
36. What is diet-induced thermogenesis?
It is the thermic effect of food; whatever we eat needs to be digested and absorbed and thus
requires energy which diet induced describes.
37. What does the energy depend on?
The type of molecule proteins needs the highest amount of energy for digestion [hence feel
lethargic after consuming lots of energy food] the least energy is for carbohydrates and fats
38. Can dietary components stimulate thermogenesis?
YES some can, such as caffeine; a cup of coffee can increase BMR by up to 10% for 2 hours
39. What is the BMI scale?
A world-recognised scale of adiposity, measures lean and fat mass. It is the ratio of weight to
height. Normale range is 20-25, obese is 30-35
40. What is a limitation of BMI?
It cannot be used to measure fit muscular people, so should have different scales for lean
mass and fat mass?
41. What is the adjusted scales used for children?
The UK90 BMI reference the scales are adjusted in centiles of a reference population, so
 whoever is under the 2 percentile is underweight, it is normal until 85 percentile and over that
is overweight
42. What other scales exist for children?
Internationally there is the IOTF scale but it is not applicable to the UK, more like the BMI
43. How is body mass percentage measured?
The skinfold thickness calipers are used to measure a pinch of subcutaneous fat in various
areas of the body and these are summed together
Another way is using MRI can give idea on lean and fat mass
44. What is another machine way to calculate total % body fat?
A bioelectrical impedance can be used to calculate lean and fat mass however there is no
consensus on PBF cut off points
45. How much essential fat do men and women have roughly?
Women have 10-13%, whilst men have 2-5%, and female athletes have even more than
normal women
46. Where does fat get stored?
SUBCUTANEOUS just under the skin is the main site
47. What is the typical male and female body fat deposition like?
In males when obesity develops, central obesity happens first and this is shaped as a pear
the visceral fat is stored in the abdominal cavity [omentum]
In females it is similar but also more prone to apple shape, rounded
48. How is waist circumference useful?
It has good correlation with BMI and indicates VISCERAL fat there is if the circumference is
more than 94cm there is increased risk of metabolic disorders [measured between lower rib
and iliac crest
49. What is the waist to hip ratio WHR useful for?
More indicative of the ratio of visceral to subcutaneous fat, rather than just total fat. It has
more correlation with CVD risk factors and Type II diabetes a ratio exceeding 0.9 in men
means significantly higher risk of developing metabolic complications
50. What would obese people have in WHR?
Obese people have higher waist number and smaller hip
51. What is a new scale being developed?
A waist to height ratio, with a healthy boundary proposed at 0.5 for men and women
52. What are the key reasons for energy imbalance and obesity?
(a) Decreased energy expenditure
(b) Increased intake of energy dense foods
(c)
53. What are some reasons for decreased energy expenditure?
In the olden days people used to work more collectively and harder, now have office jobs.
Car ownership trends have also changed, people not owning cars has decreased over the
years, so about 77-80% own cars now
54. How have energy dense foods in diet contributed to obesity?
People have evolved an inbuilt appetite for energy dense foods such as chocolate, burgers, all
which are highly refined and energy dense [225-275 kcal per 100g]
Prepared convenience and takeaway food are also heavily consumed
People not thinking consciously about their food/calorie intake!
55. What does research for dietary fat intake show in the US?
Between 1955-90 people did decrease fat intake but still the number of overweight people
increased, though less fat was being eaten research shows a difference between saturated
and unsaturated fat? Could be that people started eating more of the bad, saturated, which
would increase insulin sensitivity and storage into fat
56. What happened to sugar consumption levels?
Pver the years refined sugar intake decreased however high fructose corn syrup intake
increased very dangerous [[corn starch that has been hydrolysed then isomerised to fructose
and glucose]]
Why is high fructose corn syrup dangerous?
It is eventually converted into fat metabolised predominantly in the liver so increased potential for
fatty liver?
OBESITY 2

1. What one other factor can influence process of gaining positive energy?
Complications with the hunger-satiety cycle, when appetite exceeds hunger [hormones],
psychological stress and genetics.
2. What is the hunger-satiety cycle?
A complex interplay of biological and behavioural functions combining to maintain energy
balance mostly it is the relation to the behaviour [as it is difficult to have a stimulus that will
distract someone from eating nice energy dense foods]
3. What is the difference between appetite and hunger?
HUNGER = ready to eat. Have a demand for energy/need, for any food
APPETITE = demand for a particular food so it is selective for food that a person likes and
specific
4. How can the brain be involved with hunger-satiety?
One of the brain systems that has evolved is the reward system, so even when someone is not
hunger it can suppress that feeling and push you to eat something for e.g. pizza, so it can
override impulse
5. What is satiety?
The state of hunger/appetite being met i.e. feeling of fullness. As soon as you start eating this
feeling kicks on so that it can give rise to eventually stop eating
6. What are the biological drivers of hunger?
(a) MECHANORECEPTORS in stomach when empty it delivers hunger pangs, if asleep it
wakes you up
(b) GHRELIN released by stomach major hormone that makes you feel hungry, It is high in the
blood when hungry
(c) LOW SUGAR/fatty acids/amino acids/peptides also make you eat
7. What are the biological drivers of satiety?
(a) MECHANORECEPTORS in stomach when it is full stomach expands so mechanoreceptors
expand, this sends signal via vagus nerve to brain centre
(b) LEPTIN release [stimulated from insulin] increases hormone from fat cells which are low in
blood and high when hunger decreases
(c) DECREASED GHRELIN levels will eventually decrease as satiety factors increase, stomach
decreases secretion
(d) HIGH SUGAR/fatty acids, amino acid levels
8. What is the short-term control of feeding?
ST controls are due to the stretch receptor activation/inactivation in liver and GI tract which tell
whether hungry or not by sending signals to brainstem via vagus nerve [stretch receptors,
chemoreceptors, peptide hormone receptors]
9. What is the long term control of feeding?
LT is control by the brain itself and involvement of insulin and leptin these are known as
adiposity signal
Peptide hormone YY which is secreted by the GI and ghrelin also maintain LT control
10. What exactlty is ghrelin and how is it released?
It is a feeding stimulant i.e. OREXIGENIC. The parietal cells have HCl and they are responsible
for ghrelin synthesis
11. What are the normal levels for ghrelin in the day?
Usually, ghrelin slowly increases overnight with a peak in the morning which avtivates feeling
of hunger and drives people to have breakfast for e.g. At lunchtime increases again.
12. What are ghrelin levels like in obese people?
Ghrelin does not follow same pattern as lean something is wrong after dinner as the levels
stay up and thats when they could go and eat other things thus this hormone is higher in
obese people!!
13. What is ghrelins relationship with body weight?
it is secreted inverse to body weight! So losing weight results in hunger
14. How is leptin produced/released?
Produced in fat cells (adipocytes) and leptin receptors are present in many different tissues. It
is secreted as a proportion of body fat, so more fat cells means more leptin
15. What does leptin then do?
As a satiety signal it tells the brain how much adipose tissue it has in the body, acting through
its own receptor
16. What are the variety of roles leptin has in different tissues?
Hypothalamus and brain stem decreases APPETITE
Fat cells increased lipase activity, decreased Acetyl CoA expression and increased
mitochondrial uncoupling proteins
17. How does leptin help maintain body weight?
It causes increased burning or oxidation of fat
18. What is the man centre of appetite regulation?
HYPOTHALAMUS! Base of skull there are also other centres in brain stem that receive
signals and have good connections etc.
19. What is the function of adipose tissue?
Storage site but not just a storage site!! Fat cells have evolved as an endocrine cell, it is an
organ in itself as it secretes several cytokines and chemokines involved in homeostatic function.
The inner fat tissue is considered an endocrine gland now [[release leptin & adiponectin,
cytokines, neurotrophins, chemokines, angiotensinogen, acute phase protiens]]
20. What is important about adiponectin molecule?
About 90% of T2 diabetic people are obese. But not all obese people develop T2 diabetes
WHY? Because adiponectin prevents obese people developing T2.
21. What happens with leptin in obese people?
Leptin is satiety factor so if there is more fact, more leptin would be secreted, in obese people
leptin levels are high so why does appetite not decrease?
The SIGNALLING mechanism is disrupted! Leptin does not function properly and leptin
receptors in obesity are damaged [hence why treatment never worked]
22. How does leptin decrease appetite?
When it is released into circulation from fat cells, it binds with neurons in the hypothalamus and
does two things:
(a) stimulates alpha melanocyte stimulating hormone, a-MSH
(b) decreases activity of neuropeptide Y
23. What is the function of alpha-melanocyte stimulating hormone?
It stimulates production of melanin and in the brain it acts as an appetite suppressor i.e. it is
ANOREXIGENIC
24. What is the function of neuropeptide Y?
It is a highly appetite stimulating peptide, but is also involved in cognition, sexual function,
anxiety, vascular resistance, circadian rhythms etc., so it is OREXIGENIC
25. How might leptin-signalling stop working properly in obesity (3)?
(a) Could be a mutation in the leptin molecule which would result in protein folding mutation
(b) Mutation in the receptor on neurones that express a-MSH, and that is important because a-
MSH is an important neuropeptide as a major appetite suppressant.
(c) Down regulation of leptin receptor on neurones expressing neuropeptide Y -- The receptor
on NPY molecule is said to be deformed, so if leptin is not working properly anymore then
NPY will stay increased and make you eat all the time.
26. Is a mutation in leptin likely?
This occurs in a very small number of people, and of those who overate and became obese,
leptin injections corrected it, and only a few people found mutation
27. Does the second theory of receptor dysfunction on neurones with a-MSH apply to obesity?
This is found to occur in 5% of morbidly obese people; sufferers are constantly hungry and the
obesity level being related to the degree of receptor mutations
28. Does the third theory of receptor dysfunction on neurones with NPY apply?
The vast majority of obese people have extremely high levels of circulating leptin and it could
be that sensitivity is reduced over a long period of time, i.e. receptors become used to a high
level of background noise [similar to insulin resistance in T2 diabetes]
29. What are incretin hormones?
Intestinal secretions
30. How does insulin work with appetite?
After meal insulin is secreted as glucose levels are up. It directs glucose into muscle, liver and
fat for storage. Higher levels of insulin suppress appetite, lower levels of insulin increase
appetite
31. What is Peptide YY, PYY?
New molecule released in ILEUM and COLON following a meal.
32. What is the function of PYY (3)?
(a) Involved in decreasing gastric motility and emptying. So stomach stays full if there is higher
levels of PYY
(b) Decrease ghrelin levels
(c) Increase energy expenditure and fat oxidation rates
It is therefore ANOREXIGENIC
33. How is PYY in obese people?
Lower levels found in obese people so it could be a possible treatment option!
34. What is POMC?
It is the precursor to a-MSH
35. Describe the relationship of appetite hormones to POMC and NPY
Insulin and Ghrelin stimulate POMC (decrease appetite) and suppress NPY (decrease
appetite)
Ghrelin activates NPY (increase appetite)
PYY inhibits NPY (decrease appetite)
36. What is happening when appetite exceeds hunger?
You may not be hungry but have appetite and these sensations come from centres in the brain
apart from the hypothalamus
37. What is sensory specific satiety?
When people/animals are offered a range of foods, they continue to eat for longer
38. What is palatability?
Pleasure provided by foods dopamine is the major reward transmitter which can be involved
39. How can dopamine relate to appetite and feeding?
Feeding stimulates dopamine release, so dopamine is secreted whenever person has appetite
for food, also the smell of food can trigger the release too in other parts of the brain.
The release can depend on VOLUME i.e. bigger meals release more dopamine and
COMPOSITION i.e. foods high in fat/carbo release more dopamine
40. Obesity and a food addiction?
Dopamine is strongly related to behaviour, learning and cognition. People prone to addictive
behaviour often have fewer dopamine receptors in the brain and in obesity people are
addicted to food that they like, so obesity could be a food addiction through dopamine
41. What has research found for dopamine receptors in obesity?
Overstimulation of dopamine receptors by palatable foods can cause a DOWNREGULATION
of dopamine receptors in animals [[DA receptors are down regulated after stimulation, so the
secretion of DA can play a big role]]
42. What affects do cocaine have?
Cocaine and related compounds can inhibit dopamine reuptake which decreases appetite; so
DA itself can suppress appetite which happens in cocaine addicts
43. What affects does olanzapine have?
Olanzapine and other agents with affinity for DA receptors can result in WEIGHT GAIN
44. What is another neurotransmitter involved in reward system?
SEROTONIN makes you feel good. Also involved in appetite, mood and sleep regulation
45. How is serotonin involved in appetite?
It is ANOREXIGENIC thus appetite suppressant [agonists will therefore also reduce appetite
but antagonists can increase it such as antipsychotics]
46. How can drugs therefore contribute to obesity/weight gain?
Antipyschotics have side effects of weight gain up to 5kg or more e.g. with clozapine and
olanzapine. Several other drugs have lesser effects on weight with smaller increases between
1-3kg e.g. haloperidol, and some have negligible e.g. ziprasidone
Weight change does NOT PLATEAU hence does not stop anywhere
47. How should weight gain be managed in antipsychotic treatment?
Warn patients beforehand, eat less move more ask them to stop using drugs that may
 further contribute to gain, consider stop switch, consider supplementary therapy e.g. orlistat
[[prevent fat absorption in body]]
48. How can psychological stress contribute to weight gain?
The flight and fight response has effects on the body such as increasing heart rate, blood flow
and levels of glucose etc. In the acute response, appetite is suppressed and eat
indiscriminately [think of war] especially by noradrenaline. In chronic response, get slow
release of CORTISOL an appetite stimulant. It also increases levels of neuropeptide Y
49. Can stress have a negative impact on food intake however?
YES it can increase energy requirements through trembling and lack of sleep, and at same
time decrease food intake through irritations to the GI tract
50. What evidence is there for obesity and genetics?
One study found that if you adopt children from lean parents, they do not become obese no
matter what the lifestyle, thus children are more like biological parents, two obese parents
would more likely have obese children
51. What are thrifty genes?
Evolving difference in fat storage potential in different populations genes that have helped
us to survive in the older periods when there were drought but in this period they are
constantly stimulated
52. What example is given for thrifty genes?
Southern Pacific Islanders may have been slightly overweight as they ate fish all the time but
when they migrated, sedentary lifestyle and chemicals caused them to develop obesity and T2
diabetes
53. What are thrifty phenotypes?
Prenatal nutrition conditions foetus to survive in prevalent environment e.g. if pregnant
women suffering from a lack of nutrition and babies born with low birth weight, child in future
exposed to nutrients may become obese
54. What is the first stage for management?
LIFESTLE CHANGES! Obese individuals undergo guided weight loss but the weekly weight
loss should not exceed 0.5-1kg. This therapy is aimed at changing the behaviour leading to
obesity [[yoyo diets, malnutrition, gallstones]]
55. What is the second stage of management -- drugs?
ORLISTAT can be prescribed if BMI above 30, or BMI above 28 with comorbidities such as T2
diabetes/hypertension. *The patient must continue a low fat diet!!*
56. What is the regiment for orlistat dosing?
Initial 3 month prescription, followed by a review. It can be continued up to 12 months if
significant weight loss occurs [more than 5% of initial body weight]
Typical dose 3 x 120mg a day before meals
57. How does Orlistat function?
It is a pancreatic lipase inhibitor so it prevents absorption on lipids in the gut. Fewer
triglycerides broken down and absorbed and hence increased fat content in faeces
58. What other affects can Orlistat have?
It can act as a fat aversion therapy
59. What are the side effects of Orlistat (4)?
(a) Fatty/oily stools and oily rectal discharge
(b) Increased defecation frequency
(c) Flatulence and general abdominal discomfort
(d) MALABSORPTION OF FAT SOLUBLE VITAMINDS AND MEDICATIONS [[Vit A, D, E and K,
adek*]
60. In whom should Orlistat not be used?
Children, pregnant/breastfeeding women, people taking blood thinners, people with
malabsorption, kidney disease patients
61. What is the other drug used for obesity but not in the UK, just the USA?
Phentermine USA and Australia [phenyl tertiary butylamine]
62. How does it function?
Similar action to amphetamines stimulates production of noradrenaline and adrenaline (to
reduce appetite and burn fat)
63. What are some side effects of Phentermine?
Mood swings, insomnia, tremors, gastric problems and CV effects (high bp, heart rate,
palpitations)
64. What is the third stage of management - surgery?
(a) Bariatric surgery cut part of GI tract to prevent absorption -- BMI above 40 OR BMI
above 35 with comorbidities
(b) Gastric band surgery partly occlude stomach [restrictive approach]
(c) Gastric bypass bypass lower section of stomach and upper part of small intestine
[malabsorptive approach]

RISKS = mortality is 50% no matter what you do!!!!

OCULAR 1

1. What is the structure of the eyelid?

It is skin on the outside and conjunctiva on the inside; the conjunctiva double backs on itself
2. What are the protective functions of the eyelids?
(a) Physical screening
(b) Reflex blinking such as for when there is an object approaching or bright light so it is a
response to a stimulus
(c) Spontaneous blinking such as right now we are all doing it, partly to top up the tear film
so acts as optical lubrication
(d) Secretions from the Zeis and Meibomian glands. These prevent overflow of tears, reduce
the evaporation of tears and lubricate lid margin. The glands produce the outermost, i.e.
anterior, layer of the tear film [see later]
3. What are the three parts to tears?
Tear film, tear chamber and tear drainage
4. What are the functions of the tear film (5)?
(a) Maintain optically uniform corneal surface
(b) Flush cellular debris and foreign material from the cornea and conjuctivial sac
(c) Lubricate the corneal and conjuctivial sac
(d) Provide oxygen to the cornea as the cornea is avascular so tearfilm provides oxygen
and nutrients
(e) Antibacterial protection
5. What are the three structural parts to the tearfilm?
Anterior LIPID
Middle AQUEOUS
Epithelial MUCOID
[going from location wise]
6. Describe the anterior lipid part of tearfilm and function:
It is 0.1 micrometre in thickness, secreted by the Zeis and Meibomian gland
Function reduce evaporation and prevent overflow of tears from lid margin
7. Describe the middle aqueous part and function:
It is 6.5-7.5 micrometre in thickness [so thickest of all], secreted by Lacrimal glands
Function provide nutrients and uptake of oxygen for the cornea
8. Describe the epithelial mucoid part and function:
It is 0.02-0.05 micrometres, from the goblet cells in conjunctiva
Function allow tear film to spread evenly on a hydrophobic surface
9. How much space does the tear chamber have?
It has room for about 30 microliters in a non-blinking eye and about 10microliters in a blinking
eye
10. How much space do tears take up?
Approx. 7 microliters is taken up by tears, average drop size is 25-50 microliters. [THEY ARE
CONTINIOUSLY REPLACED]
11. Where dos drainage of tears occur?
The lacrimal duct it has the lacrimal passages, lacrimal sac and nasolacrimal duct
12. Describe the drainage process
It begins with drainage via the superior and inferior PUNCTA, travelling to the lacrimal
CANALICULI, at the inner corner of eyelids, then into the lacrimal sac and down the
nasolacrimal duct
13. How are tears taken to the lacrimal sac?
Capillary attraction plays a role in pulling tears into the lacrimal sac
14. How is reflux of tears prevented?
By an internal valve system
15. What can happen to the drainage?
It can cause obstruction dry or watery eyes
Can also be used to get drugs absorbed through here, the nasolacrimal duct
16. What is the conjunctiva?
It is a thin transparent mucous membrane
17. What are the three parts that make up conjunctiva?
(a) Bulbar conjunctiva lining the globe, covers the eyeball
(b) Palpebral conjunctiva lining the posterior eye lids
(c) Fornix corners/edges of the eye, where the two parts of conjunctiva come together
18. What cells does the conjunctiva contain?
GOBLET cells produce mucus that act as a lubricant
19. What gland is found in the conjunctiva?
The lachrymal gland produce aqueous tears
20. Is the conjunctiva vascular?
Yes it is quite vascular but vessels are usually constricted and not apparent. They rapidly
dilate with irritation or inflammation
21. What is the sclera?
The white of the eye Found beneath the conjunctiva, it is a thick opaque layer and blends
with the cornea at the limbus. Composed of COLLAGEN
22. Is the sclera vascular?
NO it is relatively avascular. Repair therefore depends on blood vessels from tissues on
either side of it such as the choroid internally and conjunctiva externally
23. What are the functions of the sclera (2)?
(a) Protect the eye
(b) Ensure rigidity of eye dimensions by focusing light on to the retina
24. What is the episclera?
It is a thin membrane that covers the sclera, lying between the conjunctiva and sclera.
25. What is the cornea?
It is the curved and transparent window of the eye, allowing light rays to enter the eye and
become focused as an image on the retina.
26. Is the cornea vascular?
NO avascular. Supply comes from limbal blood vessels next to the sclera
27. What is unique about the cornea in terms of structure?
It is multi-layered yet transparent
28. What are the parts of the cornea (3 main ones, divided in total in to 5)?
(a) Multi-layered epithelium consists of epithelium, layer and Bowmans membrane
(b) Middle stroma made of collage and extracellular matrix
(c) Inner monolayer of endothelial cells Descemets membrane
29. What is the cornea vital for?
Adequate vision it provides a coarse non-variable focus of light onto the retina thus the
cornea must be maintained healthily.
30. Is the cornea easily damaged?
No it is the main barrier to interior eye structures so it is tough and resistant to damage; so
do not usually get infection here. Unless there is severe damage or trauma, which would lead
to scarring of the cornea and thus eyesight damage.
31. What is the anterior chamber composed of?
Aqueous humour, iris, ciliary body and lens make up the anterior chamber
32. Where is the anterior chamber located?
Immediately behind the cornea
33. What is the function of the aqueous humour (2)?
(a) Maintain appropriate intraocular pressure so that cornea retains optical shape
(b) Nourish the lens and cornea by supplying oxygen and nutrients and carrying away
wastes
34. How is the aqueous humour formed?
It is continually being made by an active process in the CILIARY BODY. It is then filtered into
the posterior chamber, past the iris and into the anterior chamber, where it mixes with fluid
that is already there
35. What are the two drainage pathways for aqueous humour?
(a) Canal of Schlemm continual drainage from the eye at the ANTERIOR CHAMBER ANGLE,
which is where the iris meets the cornea. Through the trabecular meshwork. 70-90% drains this
way
(b) Uveoscleral pathway termed non-trabecular, and is pressure independent. Across the
ciliary body into the supra-choroidal space and into the venous circulation of the sclera. 10-
30% drains this way.
36. What can a blockage of this aqueous outflow cause?
Increased intraocular pressure which can lead to glaucoma
37. What does the uvea consist of?
Iris, posterior choroid and ciliary body
38. What is the iris?
The coloured part of the eye it is like a diaphragm separating the anterior and posterior
chambers of the eye. So it is an incomplete circle with an aperture in the centre, called the
pupil. [diaphragm that opens and closes in a circular movement]
39. What is the iris made of?
Consists largely of connective tissue that contains muscle fibers, blood vessels and pigment cells
40. What is the function of the iris?
It expands and contracts! Causing the pupil to expand and contract too.
(a) Constricts called MIOSIS, occurs through constrictor muscles
(b) Dilates called MYDRIASIS, occurs through dilator muscles
It therefore controls the light entry into retina
41. What happens to the pupil in light and dark?
In the light the pupil CONSTRICTS constriction of ring of smooth muscle around pupil by the
parasympathetic system
In the dark the pupil DILATES contraction of radial smooth muscle fibers by the sympathetic
system
42. What is the ciliary body made of (2)?
(a) Ciliary PROCESS
(b) Ciliary MUSCLE
43. What is the function of the ciliary process?
Formation of the aqueous humour
44. What is the function of the ciliary muscle (2)?
(a) It controls the refractive capacity of the lens, changes its shape to vary distance of vision
i.e. ACCOMODATION
(b) It also anchors the lens in place
45. What does accommodate mean?
It is the function of changing shape of the lens for near or far vision by the ciliary muscles
changing it
46. How does contraction of the ciliary muscles change lens shape?
The contraction reduces the tension on the ZONULES that hold the lens in place, so that the lens
becomes more convex to focus. Oppositely, relaxation increases the tension
47. What is the lens?
The transparent refractive area of the eye responsible for fine focusing of light on to the
retina
48. What is the lens composed of?
It is made of approx. 34% proteins and 65% water, the protein is mostly soluble and a bit of
insoluble (12%).
49. What can happen with age and these proteins?
With age, the amount of insoluble proteins can increase, to about 34-40% of insoluble
proteins
50. What else can aging cause?
CATARACTS an opaque lens
51. What is the vitreous humour?
A thick clear gel made up of collagen, hyaluronic acid and majority water. 80& of the eye is
made of VH.
52. What is the function of the vitreous humour?
It gives the eye its shape and structure
53. What is the retina?
Light senstitive layer that contains the photoreceptor cells; rods and cones (night vs.
day/colour)

OCULAR 2

1. What is conjunctivitis?
Inflammation of the conjunctiva. It is the most common red eye condition
2. What are the types of conjunctivitis?
(a) Bacterial (b) Viral (c) Allergic (d) Irritation [from e.g. smoke, chlorine]
Bacterial is highly infective!
3. What is another type of conjunctivitis that is less common but serious?
Chlamydia originated can lead to blindness. It is called trachoma after the infectious agent
[chlamydia trachomatis]
4. Is it self-limiting?
YES it gets better by itself mostly, but may require treatment sometimes. Usually gone within
a week but viral may last longer
5. What do all types have in common in terms of symptoms?
All present variations of three symptoms: (a) redness (b) discharge and (c) pain

6. What is the most common bacterial infection causing BC?

Staphylococcus infection is common; others may be haemophilus and strep.
7. Are both eyes affected?
YES usually it is bilateral; one eye typically becoming infected before the other. It is difficult
to stop the transfer from one eye to the other. Also common for one eye to appear worse than
the other
8. What do patients experience the most?
Discomfort smarting, burning or grittiness experiences but not true pain, it is really more of a
discomfort
9. What kind of discharge is present?
Watery at first and then it is PURULENT can cause lids to become stuck together or crusted
upon awakening
10. Does the vision change?
NO vision not affected but the discharge may distort vision slightly however blinking will
clear it up
11. Is the pupil any different?
NO pupil not affected; it looks normal and reacts normally to light
12. What is the redness like?
Generalised and diffused. There is more redness in the peripheral and inner aspects of the
eyelids, in fornices and angles. Limbal areas and sclera/cornea are less red.
13. What is the first line treatment of BC?
NO TREATMENT! Reassure the patients and say that treatment wont make it better quicker.
However, if a drug is to be used, it will be CHLORAMPHENICOL eye-drops. However, 10% of
people who would use it are allergic to the preservative in the drop so could get allergic
conjunctivitis then
14. What other treatment options are available?
Fusidic acid may be prescribed if chloramphenicol is not suitable e.g. in children, elderly and
pregnancy

15. What is the most common virus causing VC?

Usually from adenovirus or herpes simplex, adenovirus may be linked to common cold, VC is
commonly associated with upper respiratory tract infections
16. Are both eyes affected?
YES bilateral, patient usually complains of it being in both eyes
17. Do patients experience discomfort?
YES patients complain of discomfort and grittiness. There may also be cough and cold
18. What is the main difference with bacterial?
The discharge is different! The discharge is usually WATERY and may take longer to clear up
19. What is the redness like?
General and diffused. The peripheral areas are typically more affected. [Similar to
bacterial!!]
20. What else can patients present with (2)?
(a) Can get FOLLICLE FORMATION minute clear like jelly blobs, particularly on insides of
eyelid, the lower lid. Doesnt usually affect the conjunctiva over the sclera. Look like grains of
rice
(b) Can have PRE-AURICULAR SWELLINGS by the ear
21. Is there anything dangerous with the previous symptoms?
Occasionally can get severe eyelid swelling from the follicles, which would be sufficient enough
to close lids together.
22. In whom is allergic conjunctivitis usually seen?
Children and young adults and there may be a history of atopy with eczema or asthma
23. What is the most common troublesome symptom?
PRURITIS! Can have intense eye itching that can make the other symptoms (redness) worse. It is
localised to the inner corner of the eye
24. Are both eyes affected?
YES it is bilateral. As you cant really get pollen in just one eye
25. What is the discharge like?
Usually watery leads to nasal symptoms as well as the extra discharge just travels to the
nose
26. What is the redness like?
The conjunctivae are DIFFUSELY RED, mostly as a result of rubbing and may be oedematous
(called chemosis)
27. What other symptom could be present or seen?
Round swellings, called PAPILLAE, may be seen on the conjunctiva covering the eyelids i.e. the
palpebral
28. What is the treatment for allergic C?
Use SODIUM CROMOGLYCATE or BETHAMETHASONE.
Sodium cromo is a mast cell stabiliser; it is more of a preventative thing so if someone starts
getting symptoms they would use these drops but takes a few days for the effects. Betha is a
strong anti-inflammatory steroid (cortico?)
29. What other treatments options are there?
Antihistamine eye-drops such as Azelastine, Emedastine
Other mast cell stabilisers such as Lodoxamide
30. What is keratitis?
inflammation of the cornea, another common cause of red eye"
31. How can this occur to a robust structure such as the cornea?
Cornea is exposed a lot during waking hours and although normal corneal epithelium resists
 infection well, some sort of weakening or damage to epithelium precedes keratitis usually, such
as injury or overuse of steroid eye-drops. Much more painful condition!!
32. What are the key symptoms?
Red eye
Watery discharge
Possible photophobia
33. What is the redness like?
Redness is the greatest around the IRIS thus it is often called ciliary flush/injection, and the
redness is often a deeper red than conjunctivitis
34. What is photophobia?
Dislike of bright light
35. What can the infection cause?
Infection can enter the superficial layers of the cornea to produce a corneal layer and this is
how an ulcer develops
36. What does the ulcer result in?
It distorts the smooth mirror surface of the cornea and therefore can impair vision!
37. Does vision become impaired?
YES if it is a centrally located ulcer then vision is often impaired
38. What is a hypopyon?
If there is penetration of the whole cornea, it opens sup to infection and this is what results
39. How can you find out if there is damage to the cornea?
Look under light using a blue light source and a special dye, if there is damage it would
appear in a green colour
40. If the keratitis is caused by herpes simplex, what is it called?
Epithelial dendritic keratitis!
41. What are the features of dendritic keratitis?
Branches are seen in eye caused by the HS virus and the formation of a dendritic ulcer which
is how the branching pattern occurs
42. How can dendritic keratitis develop?
It can be primary or secondary primary is when it is subclinical in childhood. A latent stage in
the TRIGEMINAL GANGLION can be reactivated allowing the virus to travel to the eye
43. How can dendritic keratitis be treated?
By giving acyclovir, an antiviral medicine
44. What is another type of keratitis called that is rare but serious?
Acanthamoeba keratitis
45. What is this keratitis associated with?
CONTACT LENS use
46. How does it occur?
Acanthamoeba is a protozoa that is water-borne and can be found in tap water as well, so it
can occur by swimming in dirty water or washing lens with water
47. How is keratitis treatment approached?
Depends on how the keratitis originated, i.e. bacterial, viral, fungal, and then treatment can
commence

48. What is anterior uveitis?

Inflammation of the uveal tract [iris, ciliary body and choroid]
49. Why is it called uveitis?
Because iritis does not usually occur without cyclitis so together referred to as uveitis
50. What is the most common reason for it occurring?
Most likely due to ANTIGEN-ANTIBODY reactions rather than infections
51. What is the most common symptom first presented?
PHOTOPHOBIA
52. Are both eyes affected?
NO it is usually unilateral i.e. just one eye
53. What other key symptom is present?
PAIN pain is moderate to severe and described as a deep pain from within the eye. The
pain does not cease when eyes are closed
54. What can happen to the muscles because of the iris?
The muscles can go into SPASMS because of the iris can get smaller pupils, constricted and
irregularly shaped
55. What is the redness like?
Redness around the iris get ciliary flush where the cornea meets the sclera
56. Does the vision change?
Varies it could in some
57. How long does this condition last?
Lasts for weeks and months, relapses are common
58. What can anterior uveitis be part of?
A multisystem disease called Bechets syndrome it is an autoimmune disease
59. What is the treatment for AV?
BETHAMETHASONE DROPS -- corticosteroid used to reduce inflammation
60. What other possible treatments can be used?
Can also give a MYDRIATIC drug to dilate the pupil as it is constricted these would be
cycloplegics such as atropine and homatropine
61. What is subconjunctival haemorrhage?

SKIN
1. Skin diseases depend upon which factors (5)?
(a) Age related structural changes? Children not born with condition! As get older,
skin gets thinner with less collagen and fat. Also element of pigmentation
(b) Socio-economic factors vitamins play a role?
(c) Degree of industrial activity skin not made for certain environments such as acids
and alkalis, e.g. occupational dermatitis which can occur from cement handling
(d) Pill for every ill problem of expectations! Not every skin condition has cure
(e) Psychogenic skin disorders dermatitis artefacta is where pick at own skin,
typically deny it
2. What is the most common skin disease and describe it?
ECZEMA means to boil over, not born with this, mainly starts on cheeks, it is
problematic for skin development. Also can be generic term for acute/chronic
inflammatory condition
3. What are the key hallmarks of eczema and skin conditions (7)?
(a) Erythematous redness from inflammation
(b) Oedematous
(c) Papular
(d) Vesicular fluid filled blisters
(e) Crusting vesicular bursts
(f) and (g) Lichenification & Scaling this is the bodys response mechanism to repair
damage caused by persistent vesicular and crusting
4. Give the figures of skin diseases per 100 of population?
Eczema = 90; Acne = 86; Infections = 46; Viral warts = 34; Psoriasis = 16
5. What are the statistics of skin diseases seen in GPs?
Eczema = 30%; B&V infection = 16%; Miscellaneous = 14%; Fungal = 10%; Acne =
9%, Urticaria = 7%, Psoriasis = 6%; Viral warts = 6%; Tumour = 2%
6. What are the statistics of skin diseases seen in hospital dermatological clinics?
Benign tumours = 30%; Miscellaneous = 17%; Malignant tumours = 15%;
Eczema/dermatitis = 14%: Acne/rosacea = 8%; Viral warts = 7%; Psoriasis = 6%;
Infections = 3%
7. How much damage occurs in eczema?
Have only EPIDERMAL damage with hairs becoming damaged as well
8. How much damage occurs in acne?
Damage is epidermal & DERMIS can never go back to original tissue as scarred
9. Which skin diseases have male dominance (8)?
Seborrheic dermatitis; Dermatitis herpetiformis; Porphyria cutanea tarda; Polyarteritis
nodosa; Pruritus ani; Tinea pedis and cruris; Mycosis fungoides; Squamous cell
carcinoma
10. What is seborrheic dermatitis?
A type of eczema that affects the scalp the most, could be abnormal response to yeast
11. What is dermatitis herpetiformis?
Blisters filled with water, looks like herpes hence name
12. What is porphyria cutanea tarda?
Problem with Hb, precursor of it builds up, cant tolerate light, blisters, inherited?
13. Which skin diseases have female dominance (9)?
Palmoplantar pustulosis; Lichen sclerosus; Lupus erythematous; Morphoea; Rosacea;
Dermatitis artefacta; Venous ulceration; Intraepidermal carcinoma; Malignant
melanoma
14. What is palmoplantar pustulosis?
Affects palms and soles, get pustules, thickened scary red and cracks
15. What is lichen schlerosus?
Affects skin of genitals, itchy and white patches, menopausal women more, immune?
16. What is morphoea?
Localised scleroderma, excessive collagen, thickened dermis and hard skin
17. Which skin disorders develop at childhood (8)?
Port-wine stain and strawberry naevi; Ichthyosis; Epidermolysis bullosa; Atopic eczema;
Infantile seborrhoeic dermatitis; Viral warts; Molluscum contagiosum; Impetigo
18. What is port-wine stain?
Capillary vascular malformation red/purple colour and well defined borders
19. What is strawberry naevi?
Strange protrusions that look like a strawberry
20. What is ichytosis?
Means fish scale skin, so looks scaly and skin development becomes difficult
21. Which skin disorders develop at adolescence (4)?
Acne; Psoriasis esp. guttate; Seborrhoeic dermatitis; Vitiligo
22. Which skin disorders develop at early adulthood (5)?
Psoriasis; Seborrhoeic dermatitis; Dermatitis hepetiformis; Vitilgo; Tinea versicolor)
23. Which skin disorders develop at middle age (7)?
Lichen planus; Rosacea; Pemphigus vulgaris; Venous ulceration; Malignant melanoma;
Basal cell carcinoma; Mycosis fungoides)
24. Which skin disorders develop at old age (8)?
Senile pruritis; Venous and arterial ulcers; Seborrheic keratosis senile keratosis;
 Solar keratosis; Solar elastosis; Basal cell carcinoma; Squamous cell carcinoma; Herpes
zoster
25. _______ eczema These conditions arise in what are known as __________
________ _________. These conditions are called different types at different ages
because they change their ______ __ ______with age. Perhaps the commonest is a
_____ eczema. (endogenous, continually predisposed individuals, patterns of
distribution, atopic)
26. What does Intertriginous areas mean?
Behind knees and arms
27. What are the 7 types of eczema?
Atopic; Seborrheic; Varicose; Discoid; Pompholyx; Lichen; Asteatotic
28. What are the susceptible ages for atopic eczema?
Infancy and childhood
29. What are the susceptible ages for seborrhoeic eczema?
Infancy, adults [cradle cap]
30. What are the susceptible ages for varicose eczema?
Middle age to told age
31. Which eczema types affect adults?
Discoid eczema, Pompholyx eczema, Lichen simplex
32. Which eczema type affects elderly?
Asteototic eczema
33. Who is affected by eczema?
Both sexes affected and all races. More common in urban environments. 20-30% UK
population potentially atopic have genetic predisposition.
34. What else can be present with the atopic eczema?
Asthma due to allergens, rhinitis and/or conjunctivitis
35. How many of the population develop it and by age?
Around 5% population will develop some form of atopic eczema. 50% sufferers
acquired atopic eczema by age 1. VERY RARE before age of 1 MONTH.
36. When are all cases usually occurred?
90% cases before age of 5 6. Remaining 10% present later but very rare for
condition present after age 30 years. Unfortunately, 75% children show the skin
problems will show signs of asthma/hay fever
37. Where on body is atopic eczema found in babies?
Face and trunk
38. Where on body is atopic eczema found in childhood?
Flexural surfaces face cheeks and forehead. Flexural surfaces involved include
neck, antecubital fossae, popliteal fossae, gluteal folds, ankles and wrists. Anogenital,
hands especially backs but palms can be affected.
39. Treatments?
Natural history, Aetiology, Differential diagnosis, Diagnosis and investigations,
Treatments - Physical/drug

 TUBERCULOSIS

1. What other names are given to Tuberculosis and why?

The white plague because patients would become very pale and emaciated and also
consumption as it would literally consume people
2. What is the current global statistics?
9 million cases each year so a major global issue
A quarter are associated with AIDS (25% cases) as they are susceptible
3. How many UK cases annually?
It is now around 9000 cases annually 1880s was a massive problem then with
antibiotics it declined to 8 but now has come up again
4. What is the main reason for such a massive increase of TB globally?
Drug resistant organisms! The bacteria have become widely resistant
5. What are the two classes of resistance?
Multidrug resistance MDR and Extremely drug resistant XDR
6. What is extremely drug resistant?
Dont respond to ANY of the tuberculosis drugs so people are untreatable
Although theres only a small amount of people, worry is that it can spread
7. Where is tuberculosis most common?
South Africa is seen to have the most, possibly because it is a bad area for AIDS/HIV too,
next highest is Asia
8. What other places have high TB incidence?
Former soviet union countries, Mongolia area, Greenland
9. What is the distribution of TB like in England?
UNEVEN! London has very high incidence, compared to other places
10. Where has MDR TB occurred the most?
Most MDR TB areas are in South Asia, i.e. China and India BUT the most TB is seen is
South Africa hence higher incidence rates do not mean higher MDR resistant strain
incidence
11. What is the most common causative agent of TB called?
Mycobacterium tuberculosis [[however now TB can be caused by a number of bacteria]]
12. What is the TB agent now called?
Mycobacterium tuberculosis complex it includes two other strains
13. What other strains are found in the mycobacterium complex?
(a) M. bovis usually affects cattle
(b) M. Africanum usually humans fairly resistant to this strain but now seeing it more
because of AIDS patients whom get this strain
14. How is TB spread?
Spread by inhalation of droplets via coughing from infected people so it is highly
CONTAGIOUS infectious patients are taken very seriously and sent for CXR immediately
15. What other diseases are caused by mycobacteriums?
(a) Leprosy by Mycobacterium leprae difficult to treat and quite common too, if not
treated more than often patient becomes disabled as leprosy bacteria destroys nerves so
affects movement and get deformities
(b) Buruli ulcer by M.ulcerans get ulcers on the skin that are very difficult to treat
16. What do all diseases from Mycobacteria have in common?
The bacteria are SLOW GROWING and difficult to treat so not ameanable to
antibiotics as those are only good at killing rapidly growing bacteria
17. What is the most common type of TB?
PULMONARY TB is the most common site of infection, 50% of UK cases [[but can get other
places too!!]]
18. What are the initial symptoms?
Persistent cough for weeks which starts of dry and then begins to produce sputum i.e.
PURULENT and as disease progressed can get blood in cough
19. What other common symptoms can there be (3)?
Malaise, significant weight loss and fever
20. What is an associated characteristic symptom of TB?
NIGHT SWEATS!
21. What symptoms occur in later stages of TB (2)?
(a) CHEST PAIN and especially pleuritic chest pain pleural fluid around lungs get
infected with bacteria
(b) BREATHLESSNESS due to lung damage
22. How is diagnosis made?
Usual to take a sample of SPUTUM and look for bacteria in there. Also a CHEST X RAY
will give good idea of extent of disease. Sometimes may want to take sample of pleural
fluid
23. What is another common site of TB infection?
LYMPH NODES particularly the neck i.e. cervical, 30% of non-PTB
24. What complication can occur because of cervical lymph node infected?
SCROFULA lymph node may break down and discharges out of skin if it is not treated
[so see pus draining out of neck along with debris etc.]
25. What other sites of infection are there (4)?
(a) Bones and joints common sites particularly along the spine; find a lot of people with
pain in spine with TB as it destroys the bone
(b) CNS/brain meningitis TB, mortality is high
(c) Pericardium
(d) Disseminated or MILIARY in whole body as it spread through blood
26. When the bacteria is inhaled, what is the response of the body?
Immune system response stimulated as bacteria are ingested by macrophages and this
sets off the inflammatory response via cytokines such as interferon-gamma and TNF
27. What do the inflammatory cells produce?
GRANULOMAS or TUBERCULES body is trying to seal the bacteria by isolating them
28. Can the tubercules be seen?
YES on a CXR
29. What happens to the tubercules?
In about 80% of people, the isolated bacteria are then killed, however in some people
this does not happen so the bacteria are isolated but still alive dont get out of the
tubercule though
30. When can the tubercules suddenly become activated?
If the immune system fails, such as in AIDS, then the bacteria can get reactivated again.
Another reason for reappearance is because of age; elderly immune system declines
31. What are the risk factors for TB (6)?
(a) Close contact with a person having active TB
(b) People born in a country with higher TB incidence
(c) Immunosuppression e.g. AIDS
(d) Very young or elderly
(e) Chronic poor health a lot of the TB patients in England because of this as they are
generally not well, particularly if have drug/alcohol problems and TB among homeless is
high
(f) If had previous TB that was not treated properly the bacteria then that would emerge
are likely to be resistant to the treatment given then
32. Is there anything positive about being born in a country with high TB rates?
MAYBE people in such areas can develop immunity to TB so could be good?
33. What does treatment depend on?
Whether bacteria is resistant to treatment or not
34. Why is TB so difficult to treat (2)?
(a) SLOW GROWING so makes it difficult to treat by antibiotics
(b) Bacteria have a THICK WALL called a waxy coating that makes it difficult for
drugs to penetrate as they were usually water soluble so cannot get inside bacteria easily
35. What is the treatment regiment for drug sensitive TB?
Patients undergo initial phase of treatment lasting 6 MONTHS as it is a slow disease
36. What are the first line drugs?
Isoniazid and Rifampicin
37. What two additional drugs are used in the initial phase as first line?
Ethambutol and Pyrazinamide FIRST 2 MONTHS ONLY
38. What other regiments have been tried?
Shorter length ones have been tried but did not work
39. What is multi drug resistance MDR?
When TB fails to respond to FIRST LINE therapy drugs!
40. How are patients treated if found to be MDR?
First line drugs are replaced with 2ND LINE DRUGS but dont need to necessarily replace
them all, just the ones that are resistant
41. What are the second line drugs (4)?
(a) Fluoroquinolines e.g. moxifloxacin
(b) Aminoglycosides e.g. amikacin
(c) Older anti-TB drugs such as ethionamide and thiacetazone not used much these days
because of toxicity
42. Why are aminoglycosides not very helpful?
They have to be given by injection
43. What happens if second line treatment also fails?
Drugs are considered to then be EXTREMELY DRUG RESISTANT TB and this is the
worrying one because it is almost impossible to cure!!
44. What is one of the major problems with TB treatments for patients?
ADHERENCE/COMPLIANCE! Difficult to get patients to take the medications properly
especially in the developing world start treatment, then feel better and stop taking it
[maybe because they cannot afford it, tempted to sell medicine at bazaar, poverty]
Also drugs have side effects!
45. What is the problem with non-adherence then?
It encourages development of resistant bacteria
46. How can non-adherence be targeted (2)?
(a) Give a fixed dose combination that contains all the drugs they need in one tablet
rather than separate ones i.e. take 1 tablet 3 times a day e.g.
(b) DOTS directly observed therapy which is idea that patient goes to a health provider
and they are observed taking their treatment every day but this requires a lot of
organisation and personnel [harder in poor countries??]
47. What does isoniazid do to the bacteria?
KILLS them doesnt just stop them from growing
48. What are the key advantages of isoniazid (3)?
(a) Tolerated quite well
(b) Doesnt often cause serious adverse effects
(c) It is cheap so not a problem for developing countries
49. What are two serious effects that can occur?
(a) Peripheral neuritis
(b) Liver toxicity
50. How can nerve damage i.e. peripheral neuritis occur?
The nerve damage usually shows in pins and needles but it can be minimised by giving
PYRIDOXINE so this effect is manageable
51. How does liver toxicity come about?
Drug itself has a toxic metabolite which is damaging to the liver so treatment with isoniazid
would immediately have to be stopped
52. How is isoniazid normally metabolised?
By Phase II metabolism drug is usually acetylated to make it more water soluble and
excreted in urine
53. Why can some people have toxic metabolites then?
Some people are deficient in the enzyme, N-acetyltransferase, that does the acetylation
and are called slow acetylators this is a genetic condition and thus they are at risk of
liver toxicity because they get production of a toxic metabolite as well
 54. How is the toxic metabolite of isoniazid produced?
Isoniazid can undergo Phase I metabolism which has a change in functional group it can
undergo metabolism via hydrolase enzyme to release HYDRAZINE
55. What is hydrazine?
The hydrazine group is in isoniazid but it is removed and this is a very reactive compound,
H2N=NH2
56. What is rifampicin?
An antibiotic that is very effective against TB and tolerated well usually
57. What does rifampicin look like?
It is a red compound so when excreted in urine it may look orange! Can also be excreted
in sweat and tears
58. What is a serious adverse effect of rifampicin?
RESPIRATORY AND SHOCK SYNDROME occurs in people who do not take the drugs
properly e.g. take for a week, stop and then start again later
59. What else can rifampicin do in people?
INDUCE METABOLISM of other drugs! Can cause liver enzymes to increase so that other
drugs are metabolised more than usual such as oral contraceptives
60. What is the main problem with pyrazinamide?
Can cause LIVER TOXICITY so people should be monitored and also arthralgia [joint
pain]
61. What is the problem with ethambutol?
Can be toxic to OPTIC NERVE initially patient may experience red-green colour
blindness but if the treatment is not stopped it can lead to blindness so regular eye tests
needed!
** shows that a lot of monitoring is needed with TB drugs!! **
62. What is a relatively new anti tuberculosis drug?
Bedaquiline
63. What is bedaquiline?
It is a DIARYLQUINOLONE related to fluoroquinolones but differs in mode of action and
structure
64. How does it function against TB?
It inhibits ATP SYNTHASE so prevents ATP production in the mycobacteria selective
65. What are the advantages of using bedaquiline?
(a) Active against most mycobacterium strains including resistant ones
(b) Effective against active and dormant bacteria!
(c) Appears to be safe (??)
66. What are some disadvantages of bedaquiline?
Only a few studies so far but results are encouraging
Although safe, there were some unexplained deaths hence liver function should be
monitored
Only licensed for respiratory TB for now