Metabolism

Diabetes
pathology of disorder - disorder of carbohydrate metabolism, symptoms come from
a lack of insulin or
resistance to insulin s actions.
Type 1 pancreatic beta cells are destroyed by an autoimmune response and no long
er produce insulin;
referred to as insulin dependent. Tx goals include prevention of complications v
ia glycemic control together with
dietary measures and exercise.
Type 2 receptors on cells are resistant to insulin, especially liver, skeletal m
uscle, and adipose tissue; often
coupled with impaired (reduced) insulin secretion. Tx goals include prevention o
f complications via glycemic
control together with dietary measures and exercise, BP, cholesterol, etc.
Pathology behind insulin resistance - autoimmune process, development of antibod
ies against the patient s
own beta cells; trigger unknown.
Importance of education, self monitoring, and glucose control education about th
e disease, proper
monitoring, and glucose control tactics can significantly reduce complications.
Signs and symptoms of Hypoglycemia tachycardia, palpitations, sweating; SNS acti
vation

Insulin
Where synthesized endogenous: beta cells within the islets of Langerhans of panc
reas; exogenous:
bovine/porcine in the past, now made by genetically engineered E. coli
Importance of proinsulin as a precursor consists of insulin plus a peptide loop
that runs from the A chain to
the B chain, this loop is the connecting peptide. In the final step of insulin p
roduction, the peptide is clipped; this
is therapeutically important because levels of the peptide can be tested in peop
le with Type 2 diabetes to
indicate if the pancreas is still producing some insulin of its own.

Stimulus for insulin release

GLUCOSE! Also amino acids, fatty acids, ketone bodies.

Function of insulin
primary targets of insulin liver, skeletal muscle, adipose tissue + brain, kidne
y, intestines.
effect on metabolism anabolic; promotes conservation of energy and buildup of en
ergy stores.
anabolic actions stimulates cellular uptake of glucose, amino acids, nucleotides
, and K+ and promotes
synthesis of complex organic molecules (glycogen, proteins, triglycerides)

Clinical implications related to insulin (endogenous & Regular insulin only)

onset of action 30 min to 1 hour
peak action 1 to 5 hours
duration of action 6 to10 hours

Implications of the various types of insulin

Short: rapid acting administered with meals to control rise in BG. (Lispro, Aspa
rt, Glulisine) onset within
15 minutes (rapid)
slower acting Regular insulin unmodified human insulin.
Intermediate: Neutral Protamine Hagedorn (NPH) action is delayed, duration is ex
tended cannot be used at
mealtimes, injected BID, suitable to mix with short-acting insulins. CLOUDY SUSP
ENSION.
Detemir analog to human insulin, not used with meals, can last 12 24 h depending
on dose,
Long: Glargine action at least 24 hours. Modified human insulin. Once daily admi
nistration by subcut
injection. Helps make blood levels relatively steady over 24 hours.
Why they may be used in combination administration: using these in combination h
elps maintain blood
glucose levels within normal limits throughout the day, including mealtimes and
exercise regimens.

Insulins
Type
Onset
Peak
Duration
Regular
30 min 1 hour
1-5 hours
6-10 hours
Lispro
15 30 min
30 min 2.5 hours
3-6.5 hours
NPH
1-2 hours
6-14 hours
16-24 hours
Glargine
1 + hours
None
24 hours
Administration
Sources: bovine & porcine pancreas/ genetically engineered E. coli (recombinant
DNA technology)
Routes: subcutaneous injection (most common) or subcut infusion (with pump), inh
aled (Exubera regular), IV
(Regular insulin only in case of emergencies only), IM (rarely used).
Insulin orders: must be written clearly, contain the brand name of insulin, the
action time, the number of units
to be administered, the route (usu. subcut), the time it should be given (eg 30
minutes before meals), and the
strength (U-100 is typical; U-500 is possible).
Preparing for injection: use an insulin syringe! Read the order carefully & get
the correct insulin, Remember
the 5 Rights: right drug, right dose, right patient, right time, right route (ri
ght documentation) Don t shake cloudy
insulin suspension (NPH); instead, roll it gently between your palms to evenly d
isperse the solute. Swab the
bottle cap with alcohol before loading the syringe. Eliminate air bubbles from t
he syringe & needle after loading.
Clean the skin with alcohol (or soap & water) prior to injection.
Sites of injection: Upper arm, thigh, abdomen. Fastest absorption from thigh. Be
st to choose one site
(abdomen or thigh) and rotate around that region (in one inch increments) to red
uce the incidence of
lipohypertrophy. Use each site only once per month.
Syringes to be used: ONLY USE AN INSULIN SYRINGE! U-100 syringes in 30 units (1/
3 mL), 50 units (1/2
mL) or 100 units (1 mL) sizes. Important to use needle length to deliver insulin
into the subcutaneous fat. Pen
injectors & jet injectors available.
Concentrations of insulin available: U-100 & U-500
mixing insulins: it is common to mix insulins; only mix NPH with short acting in
sulins (Lehne p. 655). Draw up
the short acting insulin first in order to prevent contamination of the short ac
ting insulin with the NPH. Procedure:
1. Use alcohol swab to clean vials. 2. Inject air equal to amt being withdrawn i
nto vial of cloudy insulin (NPH)
first. 3. Remove needle from NPH vial. 4. Inject air into short acting insulin,
then invert the bottle and draw out
the desired amount. 5. Remove the syringe from short acting insulin and tap to r
emove any air bubbles. 6.
Withdraw the desired dosage from the NPH vial. 7. Total number of units in the s
yringe will be the sum of the
two insulin orders.

Usefulness of combination therapy with various types of insulin and how this aff
ects the timing of
administration
Using a combination of therapy allows for tighter control of glucose levels sinc
e you can use a long acting
(glargine) with a short acting (regular or lispro) to overlap and allow for cons
istent effects.

Glargine Insulin (Lantus)

This type of insulin is unique because it can be given once before bedtime, & la
st for 24 hours;It has no peak,
but remains a steady level in the blood.

Situations that increase or decrease the need for insulin

Increase: stress, infection, pregnancy (beyond 12 weeks), obesity, adolescent gr
owth spurt, and inflammation;
Decrease: exercise, pregnancy (first 12 weeks)

Adverse effects of insulin

Hypoglycemia (occurs when insulin levels exceed insulin needs)

Patient teaching regarding hypoglycemia & hyperglycemia

Be sure that patients & families are aware of the s/s of hypoglycemia (see above
). Rapid tx of hypoglycemia is
critical to preventing brain damage or death, give simple sugars if patient is c
onscious (honey, OJ, sugar cube,
nondiet soda, etc). If po method is not possible, give IV glucose. Diabetic pati
ents should always carry around
simple sugars (hard candy, sugar packets) and wear identification (medic alert b
racelet).

Use of oral hypoglycemics

Generally only used in patients with Type 2 diabetes.
Sulfonylureas work by promoting insulin release Tolbutamide (Orinase)
Meglitinides work by stimulating the pancreas to release insulin.
Biguanides decreases gluconeogenisis by the liver & enhances uptake. Metformin (
Glucophage)
Thiazolidnediones decreases insulin resistance by activating a specific receptor
in the cell that increases
cellular responses to insulin.
Alpha-glucosidase inhibitors delays absorption of carbohydrates, thus keeping gl
ucose out of the blood.
Side effects include diarrhea, cramping, flatulence, abdominal distension, etc.
Diabetic ketoacidosis in general, know pathology & treatment
If hyperglycemia is allowed to persist, the liver breaks down fat and proteins i
n response to a perceived need for
substrates. Cascade: hyperglycemia, production of ketoacids, Hemoconcentration,
acidosis, coma. Brought on
by altered fat and glucose metabolism. Symptoms include dehydration, hyperventil
ation, loss of glucose, Na+ &
K+, polyuria; vomiting. Treatment includes insulin replacement, water, Na+ & K+
replacement, normalization of
glucose levels, bicarbonate.

Hormones secreted by thyroid gland

T3 (Triiodothyronine) - liothyronine = generic name of synthetic T3
T4 (Thyroxine) - levothyroxine = generic name of synthetic T4

Principal actions of these hormones

Stimulation of energy use - elevates basal metabolic rate, leading to increased
oxygen consumption and heat
production
Stimulation of heart - increased rate and force of contraction (increased CO and
oxygen demand)
Promotion of growth and development - essential for normal development of brain
and other nervous system
component

Role of iodine in thyroid hormones

Deficient iodine decreases production of thyroid hormones - a drop in thyroid ho
rmone levels leads to promotion
of TSH (thyroid-stimulating hormone) release ==> acts on thyroid to grow (causin
g goiter)

Hypothyroidism
Severe deficiency of thyroid hormone; Myxedema (adults), Cretinism (infancy). Ca
use: malfunction of thyroid,
insufficient iodine in diet, surgical removal of thyroid, and radiation SE. Sign
s/Symptoms: fatigue, hair loss,
brittle hair, HR, low Tb, face is pale, puffy, expressionless. Tx: Replacement t
herapy with thyroid hormones
using levothyroxine (T4) --> more common use and body can convert T4 to T3 (acti
ve form) Levothyroxine
(Synthroid)
Hyperthyroidism
Excess of thyroid hormone; Graves disease (most common cause) or Plummer s disease.
Cause: Thyroid-
stimulating immunoglobulins (TSIs) (antibodies produced by an autoimmune process
) TSI mimics the effects of
TSH. Signs/Symptoms: increased HR, dysrhythmias, and angina, CNS stimulated (ner
vousness, insomnia), wt
loss, bulging eyes (only in Grave s, cause unknown). Tx: (1) surgical removal of t
hyroid tissue (2) destruction of
thyroid tissue -Radioactive Iodine-131 (3) suppression of thyroid hormone synthe
sis
Propylthiouracil (PTU)

Steroid hormones produced by the adrenal cortex & their principal actions
Glucocorticoids - increase availability of glucose Hydrocortisone
Mineralocorticoids - modulate salt and water balance Fludrocortisone (Florinef)
Androgens - contribute to expression of sexual characteristics (stimulate effect
s of testosterone produced by
testes; precursor for estrogen)
Two most familiar forms of adrenocortical dysfunction: Adrenal hormone excess (C
ushing s syndrome) &
Adrenal hormone deficiency (Addison s disease)

Glucocorticoids
Physiological effects - Carbohydrate Metabolism - promotes glucose availability;
Protein Metabolism -
promotes protein breakdown, providing amino acids for glucose synthesis; Fat Met
abolism - promotes lipolysis;
high levels for extended time periods cause fat redistribution (Cushing s).
Cardiovascular System - low levels of glucocorticoids increase capillary permeab
ility, decrease ability of vessels
to constrict, and BP falls. Skeletal Muscle - maintains circulatory competence.
Central Nervous System mood
and CNS excitability. Stress - works together with adrenal cortex (Epinephrine i
s released upon stress) to
maintain BP and blood glucose.
Exogenous glucocorticoids: physiologic vs pharmacologic effects - Physiologic ef
fects occur at low levels
of glucocorticoids; Pharmacologic effects occur at high levels of glucocorticoid
s.
Changing glucocorticoid needs in response to stress
In response to stress, glucocorticoids and epinephrine are released to maintain
BP and blood glucose content; if
stress is extreme (trauma, surgery, infection), glucocorticoid deficiency can re
sult in circulatory collapse and
death, provide glucocorticoid supplements if pt has adrenal insufficiency.
Mineralocorticoids
Aldosterone is the most important; influences renal processing of Na, K, and H.

Overlap of glucocorticoid and mineralocorticoid properties in drugs used for cor

ticosteroid replacement
Used in the treatment of sepsis-induced hypotension or shock; helps to re-stabil
ize the body after a massivly
stressful event. Also used as replacement therapy for adrenocortical insufficiency
.

Use of glucocorticoids in nonendocrine diseases

Therapeutic uses - rheumatoid arthritis, systemic lupus erythematosus, inflammat
ory bowel disease,
inflammatory disorders, allergies, asthma, dermatologic disorders, neoplasms, su
ppression of allograft rejection
prevention of respiratory distress syndrome.
Adverse effects - adrenal insufficiency, osteoporosis (long term use can have se
vere effects), infection,
glucose intolerance, myopathy, fluid and electrolyte disturbance, growth retarda
tion, psych disturbances,
cataracts and glaucoma, PUD, iatrogenic Cushing s syndrome.

Guidelines for withdrawing glucocorticoid therapy and WHY this needs to be

When exogenous glucocorticoids are administered, the endogenous production shuts
down, creating adreanal
insufficiency. Exogenous therapy needs to be tapered to allow the body to begin
producing glucocorticoid
endogoneously.

GI Drugs

Defensive vs aggressive factors and the relationship to the development of pepti

c ulcer disease (PUD)
Defensive factors Mucus, bicarbonate, blood flow, prostaglandins
Aggressive factors H. pylori, NSAIDs, gastric acid, pepsin, smoking
*Peptic ulcers develop when there is an imbalance between defensive and aggressi
ve factors. When aggressive
factors outweigh mucosal defenses, gastritis and peptic ulcers result.

Role of Helicobacter pylori in PUD most cases of PUD caused by infection with H.
pylori (gram neg
bacillus), eradication of this bacteria not only promotes healing, but greatly r
educes the chance of recurrence.
Colonizes space between epithelial cells and mucus barrier that protects them, e
scaping destruction by acid and
pepsin. Possible mechanisms used to promote ulcers include enzymatic degradation
of the protective mucus
layer, elaboration of a cytotoxin that injures mucosal cells, and infiltration o
f neutrophils and other inflammatory
cells in response to bacteria, produces urease. Promotes gastric cancer and decl
ared a type 1 carcinogen.

Goal of drug therapy in PUD

Alleviate symptoms
Promote healing
Prevent complications (hemorrhage, perforation, obstruction)
Prevent recurrence

Various classes of antiulcer drugs used to treat PUD

- Antibiotics
- Antisecretory agents (histamine2-receptor antagonists, proton pump inhibitors,
muscarinic antagonists)
- Mucosal protectants
- Antisecretory agents that enhance mucosal defenses
- Antacids
Receptors and compounds involved in
gastric acid secretion in the parietal cell

Production of gastric acid stimulated by 3

endogenous compounds:
ACH acting at muscarinic receptors
Histamine acting at H2-receptors
Gastrin acting at gastrin receptors
All 3 act thru intracellular messengers to
increase the activity of H,K-ATPase (the ethat actually produces gastric acid)
*Prostaglandins DECREASE acid production

Know the M of A of histamine2 receptor blockers and proton pump inhibitors AND w
here in the parietal
cell these actions occur
Histamine2-receptor Antagonists:
Mechanism of Action promote ulcer healing by suppressing secretion of gastric ac
id. By blocking H2
receptors, they reduce the volume of gastric juice and its hydrogen ion concentr
ation. Suppresses basal acid
secretion and secretion stimulated by gastrin and ACH.
Where? H2 receptor on capillary side of parietal cell
Cimetidine (Tagamet) cheapest, most side effects (inhibits hepatic enzyme activi
ty!)

Proton Pump Inhibitors:

Mechanism of Action most effective drugs for suppressing secretion of gastric ac
id! Causes irreversible
inhibition of H,K-ATPase (the enzyme that generates gastric acid). Because it bl
ocks the final common pathway
of gastric acid production, it can inhibit basal and stimulated acid release. Ef
fects persist until new enzyme is
synthesized.
Where? works on LUMINAL side
Omeprazole (Prilosec) binds to receptor IRREVERSIBLY!

Ulcer binding / protective barrier drugs

Sucralfate (Carafate) binds to ulcer bed and inhibits further damage by forming
a protective surface to
prevent irritation. Treats acute ulcers (short term treatment). Not absorbed, ad
vantage for patients with liver
disease. Drug interactions - can bind to other medications.

Role of anticholinergic drugs in PUD

VERY LIMITED ROLE in PUD. Original anti-ulcer drug, but high doses are required
to block acid secretion,
which causes muscarinic blockade throughout the body, causing MANY anticholinerg
ic side effects (dry mouth,
constipation, urinary retention, visual disturbances).

Role of prostaglandins in PUD

Play an important role in maintaining defenses. They stimulate secretion of mucu
s and bicarbonate, and they
promote vasodilation which helps maintain submucosal blood flow. They provide ad
ditional protection by
suppressing secretion of gastric acid.

Drugs involved in treating PUD vs GERD

similar to those used in PUD except antibiotics are not used

Step-up versus step-down approach to treating GERD

Step-up start with antacid ..H2RA ..PPI
Step-down start with PPI ..H2RA .. antacids
M of A of antacids; implications of magnesium & aluminum compounds in antacids
Alkaline compounds that neutralize stomach acid. React with gastric acid to prod
uce neutral salts or salts of low
acidity, thereby decreasing destruction of the gut wall. Enhances mucosal protec
tion by stimulating production of
prostaglandins. If treatment raises pH above 5, they will reduce pepsin activity
as well.
Magnesium promotes diarrhea, aluminum compounds promote constipation.

Patient teaching implications of antacid administration

Patients should be encouraged to take med as prescribed, even after symptoms are
gone. Inconvenient and
unpleasant to ingest, making adherence difficult to achieve, especially in the a
bsence of pain. Effects on bowel
can be minimized by combining aluminum and magnesium compound antacids. Patients
should be taught to
adjust the dosage of one agent or the other to normalize bowel function.

Overall reasons for using laxatives to ease or stimulate defecation

Indications for using the particular classes of laxatives

Diagnosis: colonoscopy, Treatment/procedure preparation, Constipation, or Poison
ing

Compare the various categories of laxatives in terms of M of A, indications for

use, patient teaching, and
nursing implications
- Bulk forming laxatives: treatment of choice. Psyllium (Metamucil). Combines w
ith water in GI contents to
form emollient gel/solutions that promotes peristalsis. Must be taken with liqui
d. Do not take at night. Lower
cholesterol. Side effect: flatulence.
- Surfactant laxatives: Docusate sodium (Colace). Increase secretion of water. R
eserved for pts. who
should avoid straining (post MI, increased Intracranial Pressure).
- Lubricants: Mineral oil, potential nutritional problems.

Know the alternatives to laxative use! Exercise, fluid intake, massage.

General principles regarding antidiarrheals:

Decrease GI Motility, Opiod Related, Absorbents.

Role of opioids in antidiarrheal therapy: Can be used to decrease GI motility. C

odeine, Diphenoxylate
(lomotiol), Loperaminde (Imodium).

In general, know the M of A, AND when clinically we would use prokinetic drugs a
nd antiemetic drugs:
Prokinetic drugs: Blocks dompamine receptors in chemoreceptor trigger zone of th
e CNS. Stimulates motility of
the upper GI tract and accelerates gastric emptying. Metoclopramide (Reglan), Er
thromycin. Indications:
prevention of chemotherapy-induced emesis. Facilitation of small bowel intubatio
n in radiographic procedures.
Management of esophageal reful.
Antiemtic drugs: Suppresses vomiting. Postop and chemotherapy patients.

Pain Drugs
Definition: opioid
Opioid- any drug, natural or synthetic that has actions similar to Morphine.

Endogenous opioid peptides

There are three families of endogenous opiod peptides
1. Enkephalins
2. Endorphins
3. Dynorphins

These endogenous opioid peptides function as

Neurotransmitters
neurohormones
neuromodulators.
Opioid receptors mu, kappa, delta receptors; response to stimulation
Mu receptors- responses to activation of mu receptors include: analgesia, respir
atory depression, euphoria and
sedation. Mu activation is also related to physical dependence.
Kappa receptors- activation of Kappa receptors results in analgesia and sedation
. May be responsible for
psychotomimetic effects (psychosis, bizarre behavior, etc.)
Delta receptors- Not really understood. These receptors are not usually involved
with opioids analgesics.
*Drugs will stimulate Mu receptors or Kappa receptors or BOTH.

Classification of opioid analgesics

Pure opioid agonists: Activate mu and kappa receptors. Can be broken down into t
wo groups: strong opioid
agonists (ex. Morphine) and moderate-strong opioids (ex. Codeine)
Agonist-Antagonist opioids- When administered alone they produce analgesia. If g
iven to a patient who is
taking a pure opiod agonist, the drugs can antagonize analgesia caused by the ag
onist.
Pure opioid antagonist- Act as antagonists at mu and kappa receptors. Do not pro
duce analgesia or any of the
side effects caused by opioid agonists. Their principal use is to reverse CNS an
d respiratory depression caused
by overdose with opioid agonists.

Morphine (strong opioid analgesics) source, uses, therapeutic effects, side effe
cts
Morphine: Prototype drug of the strong opioid analgesics.
Source: seed pod of the poppy plant.
Uses: relief of moderate to severe pain, decreases sensation of pain, decreases
the emotional reaction to pain.
The principal use is relief of moderate to severe pain. Relives pain without los
of consciousness or affecting
other senses. Most effective against constant, dull rather than sharp intermitte
nt pain. The drug can relieve
postoperative pain, chronic pain of cancer, and pain associated with labor and d
elivery. Sometimes used to
relieve pain associated with MI and dyspnea associated with left ventricular fai
lure and pulmonary edema.
Causes mental clouding, sedation, euphoria and a decrease in anxiety which all c
ontribute to the relief of pain. *
Relieves pain without affecting other senses (sight, touch, smell, hearing) and
without causing a loss of
consciousness.
Side Effects- Good and bad: Pain relief, Respiratory depression, urinary retenti
on, cough suppression, miosis,
emesis, mental clouding, drowsiness, constipation, euphoria/dysphoria, sense of
well-being, orthostatic
hypotension and reduction of anxiety.

Know mechanism of action & ways to decrease the impact of the primary SE of the
opioid analgesics
MOA; morphine and other opioid agonists relieve pain by mimicking the actions of
endogenous opioid peptides,
especially at the mu receptors.

Side effects
Respiratory Depression: most serious side effect. To minimize side effect monito
r respiratory rate before
administration of drug. If RR is 12 bpm or less the opioid should be withheld an
d the physician should be
notifies. Monitoring the very young, the very old and patient s with respiratory d
isease. Do not combine with
alcohol or other CNS depressants.
Constipation: Caused by a decrease in propulsive intestinal contraction, increas
e in non-propulsive contractions
(cramp-like muscle contractions), increase in tone of anal sphincter and decreas
e of secretion of fluids into the
intestinal lumen. Side effect can be reduced with the use of pharmacological mea
sures (stimulant laxatives,
stood softeners, osmotic laxatives) and/or non-pharmacological measures (increas
ed water intake, fiber).
*Morphine was first used for relief of diarrhea!
Orthostatic Hypotension: BP is decreased by blunting baroreceptor reflex and dil
ating peripheral arterioles and
veins. Peripheral vasodilation results from morphine induced release of histamin
e. Patients should be
educated on the symptoms of hypotension and understand that moving slowly when c
hanging from a supine or
seated position to a standing position can help minimize hypotension. If hypoten
sion is significant, patients
should avoid walking.
Urinary Retention: cause urinary hesitance and urinary retention by increasing t
he tone in the sphincter of the
bladder and increasing the tone of the detrussor muscle. Can also cause an incre
ase of pressure within the
bladder. Can cause a decrease in awareness of bladder stimuli. Don t know when you
have to use the
bathroom. May also decrease urine production by decreasing renal blood flow and
by promoting release of
ADH. Urinary retention should be monitored by monitoring intake and output and b
y palpating the lower
abdomen every 4-6 hours to check for bladder distention. Catheterization may be
needed.
Cough Suppression- act at opioid receptors in the medulla to suppress cough. Cod
eine and hydrocodone are
used as cough remedies. Suppression of cough may lead to build up of secretions
in the airways. Patients
should try to actively cough at certain intervals. Lung sounds should be assesse
d.
Emesis- promotes nausea and vomiting by direct stimulation of the chemoreceptor
trigger zone of the medulla.
Nausea is greatest with the initial dose. Uncommon with recumbent patients, but
occurs in 15-40% of walking
patients, this suggests a vestibular component. Can be reduces by using an antie
metic drug and by having the
patient stay still.
Other Factors: Increase intracranial pressure can occur due to decreased respira
tory rate (compounding
factory), sedation, euphoria (reason for addictive behavior), dysphoria and mios
is.

Pharmacokinetics of Morphine
Can be administered by many different routes: oral, IM, IV, SubQ, epidural, and
intrathecal. Onset is slowest
with oral administration. Must know where to find table of equianalgesia effects
for different routes of
administration. Oral doses are subject to the first pass effect and therefore must
be given in much larger
doses. In order to relieve pain morphine must cross the BBB. Morphine is not ver
y lipid soluble, so it does not
easily cross the BBB. Therefore, only a small amount of drug actually reaches si
tes of analgesic relief in the
brain.

Know definitions and impact of the following on pain relief and medication admin
istration
Tolerance- a state in which a larger dose is required to produce the same respon
se that could formerly be
elicited by a smaller dose. A condition in which a particular dose now produces
a smaller response than it did
when treatment began. Because of tolerance, dosage must be increased to produce
same desired effects.
Develops with analgesia, euphoria, sedation, and respiratory depression. Does NO
T develop with constipation
and miosis- these remain a chronic problem in addicts. Cross-tolerance with othe
r opioid agonists may also
occur.
Physical dependence- a state in which an abstinence syndrome will occur if drug
use is abruptly discontinues.
Results from adaptive cellular changes that occur in response to the continuous
presence of opioid drugs.
Abstinence syndrome- withdrawal symptoms. Usually occurs after 3 weeks (20 days)
 of drug use. Not dose
dependant, time dependant. The intensity and duration of opioid abstinence syndr
ome depends on two factors:
the half-life of the drug (if half life is short, withdrawal is short and intens
e, if half-life is long, withdrawal is longer
and less intense), and the degree of physical dependence. The intensity of withd
rawal parallels the degree of
dependence. Symptoms: Initial- yawning, rhinorrhea, sweating. Second- anorexia,
irritability, tremor. Finally-
nausea, vomiting, abdominal cramps, muscle spasm, bone and muscle pain, weakness
, kicking movements.
Usually lasts 7-10 days.
Abuse- Wrong or improper drug use. Drug use that is inconsistent with medical or
social norms. Opioids
subject to abuse because of pleasurable sensations (euphoria). Abuse is race whe
n opioids are used to treat
pain.
Addiction- behavior patterns characterized by continued use of a substance despi
te physical, psychological or
social harm Physical dependence no required for addiction to occur, but it can c
ontribute to addictive behavior.
*To minimize addiction use the lowest effective dose for the shortest time neede
d!

Meaning and clinical relevance of equianalgesic equal pain reduction effects of

different meds; morphine
20 mg is equianalgesic to 100 mg of tilidine (another opioid agonist). See equal
analgesic chart in med rooms

Controlled substance act

Schedules I-V. Schedule I has the highest potential for abuse, Schedule V has th
e lowest potential for abuse
Schedule I drugs (ex. Heroin) There is no clinical use for these in the US. Sche
dule II are strong opioid
agonists. Schedule IV are agonist antagonists.

Patients requiring precautions re: opioid therapy

Extra precautions needed for people with decreased respiratory reserves, during
pregnancy, during labor and
delivery, head injuries (due to decrease respiratory rate leading to increased i
ntracranial pressure), infants and
the elderly, inflammatory bowel disease, liver impairment, hypotension or reduce
d blood volume and prostatic
hypertrophy.

Opioid overdose; symptoms and treatment

Symptoms: Classic triad = coma, respiratory depression, pinpoint pupils
Teatment: ventilatory support, opioid antagonist (ex. Naloxone (Narcan))
Consideration for dosing with opioids
Doses are extremely individualized. High doses are needed for people with low to
lerance to pain or with
extremely painful disorders. Patients with sharp, stabbing pain need higher dose
s than patients with dull pain.
Elderly adults need lower doses than young adults. Infants need lower doses beca
use the BBB is not fully
developed. Doses need to be decreased as pain decreases.

Other strong opioid analgesics: Fentanyl, Demerol (Meripidine), Methadone

Mod-strong opioid analgesics Fentanyl (Duragesic), Methadone (Methadose)

Codeine- used for mild to moderate pain. Degree of pain relief is less than that
of morphine. Dispensed in
combination with non-opioid analgesic (ex Tylenol). Effective as a cough suppres
sant.
Oxycodone (oxycontin)- increased risk of abuse- people can crush and snort or in
ject drug. Often combined
with a non-opioid analgesic (ex. ASA or Tylenol).

Agonist-antagonists Pentazocine (Talwin)

Act as antagonists at mu receptors and agonists at kappa receptors. They are con
sidered partial agonists due
to chemical structure.
Low potential for abuse, decreased potential for respiratory depression, less po
werful analgesia. If given to
someone who is physically dependent on a pure opioid it will precipitate withdra
wal syndrome.

Opioid antagonists Naloxone (Narcan)

Drugs that block the effects of opiod agonists- act as a competitive antagonist
at opioid receptors. Principal
uses are treatment of opioid overdose, reversal of postoperative opioid effects
and management of opioid
addiction. short half life. Has no effect in the absense of opioids.

Factors to consider in the clinical use of opioids

Must assess pain correctly and be aware of patients over and under reporting of
pain. Ask good questions and
individualize doses. Do not administer PRN, opioids should be administered on a
fixed schedule. Use a PCA
as needed to maintain constant durg blood plasma levels and maintain continuous
pain control.

Barriers to opioid therapy (think about this one)

Addiction and abuse in association to opiods, physicians often prescribe less pa
in medication, nurses
sometimes administer less pain medication, inadequate assessment.

Non opioid analgesics classification, uses, side effects

NSAIDS- Ibuprofen (Motrin, Advil, etc.) initial drugs from mild to moderate pain
, suppresses inflammation
reduces fever.
Side effects: gastric ulceration, acute renal failure, bleeding.
DOES NOT CAUSE tolerance or physical and psychological dependence.
Aspirin- Acetylsalicylic acid (aspirin, Bayer) also an NSAID. Effective analgesi
c, can be dangerous
because it causes irreversible inhibition of platelet aggregation. Effects last
for the life of the platelet (7-8 days).
Acetaminophen (Tylenol, Panadol) - relieves mild to moderate pain. Inhibits COS
in CNS but not in the
periphery. Lacks anti-inflammatory actions. NO gastric ulceration, NO inhibition
of platelet aggregation.
Often combined with an opioid to produce greater analgesia. Do not combine with
alcohol or Coumadin.
NSAIDs stop cyclooxygenase enzymes (COX enzymes) from working. COX enzymes speed
up production of
prostaglandins. Prostaglandins cause the feeling of pain by irritating your nerv
e endings and cause fever. By
reducing the level of prostaglandins, NSAIDs help relieve pain from conditions l
ike arthritis. They also help
reduce inflammation (swelling), lower fevers and prevent blood from clotting.
Cox 1 versus Cox 2 (stimulation vs inhibition)
COX 1: found in the stomach, kidneys, platelets and for the most part all tissue
s.
Stomach: protects gastric mucosa from self-digestion. Platelets: promotes aggreg
ation. Kidney: promotes
vasodilation to maintain renal blood flow.
COX 2: found at sites of tissue injury and in the brain.
Tissues: Promotes inflammation, sensitizes receptors to painful stimuli. Brain:
Modulates perception of pain and
promotes fever.
What's the main difference between traditional NSAIDs and COX-2 inhibitors?
You have 2 types of COX enzymes in your body: COX-1 and COX-2. Researchers belie
ve that one of the jobs
of COX-1 enzymes is to help protect your stomach lining. The COX-2 enzyme doesn'
t play a role in protecting
your stomach.
Traditional NSAIDs stop both COX-1 and COX- 2 enzymes from doing their jobs. Whe
n COX-1 enzymes are
blocked, pain and inflammation is reduced, but the protective lining of your sto
mach is also reduced. This can
cause problems such as upset stomach, ulcers and bleeding in your stomach and in
testines.
COX-2 inhibitors only stop COX-2 enzymes from working. Since the COX-2 enzyme do
esn't help to protect your
stomach, COX-2 inhibitors may be less likely to irritate your stomach or intesti
nes.

Pain definition (in general)

Pain: An unpleasant sensory and emotional experience associated with actual or po
tential tissue damage, or
described in terms of such damage
Note: includes patient s emotional and cognitive responses to both sensation and c
ause of pain
* Patient s pain description is the cornerstone of pain assessment

Factors affecting the pain experience

Very individualized. There is no objective measurement for pain. Affected by a p
atient s emotional and
cognitive responses to both the sensation and the cause of the pain.

Nociceptive versus neuropathic pain; descriptions, response to analgesics / adju

vant therapy
Nociceptive pain: results from injury to tissues. Somatic pain: bones, joints an
d muscles. Pain is localized and
sharp in quality. Visceral pain: visceral organs (kidney, small intestine, etc.)
Pain is vaguely localized and diffuse
and aching in quality. Nociceptive pain responds well to opioid analgesics and m
ay respond to non-opioids.
Neuropathic pain- Results from injury to peripheral nerves and can happen in man
y disorders. Different
sensations such as burning, shooting, jabbing, tearing, numb, dead and cold.
***Responds poorly to opioids. Does respond to adjuvant therapy, because of the
combination of effects.
Adjuvant analgesics; in general know examples of the classes of drugs used for a
djuvant therapy
Drugs used to complement the effects of opioids. Used in combination with opioid
s. These drugs can enhance
analgesia from opioids, manage symptoms that increase pain, treat side effects c
aused by opioids.
Examples: tricyclic antidpressants (TCA), anticonvulsants, local anesthetic/anti
disrhymthics, CNS stimulants,
antihisamines, and glucocorticoids.

Factors involved in pain assessment

When assessing pain ask about: Onset and temporal pattern, location, quality, in
tensity (0-10), modulating
factors, previous treatment, and impact.

WHO analgesic ladder for pain management

Step 1; Mild to moderate pain > Use: nonopiod analgesic- NSAIDS and acetaminophe
n.
Step 2: More severe pain > Use: Add opiod analgesic, oxycodone, hydrocodone
Step 3: Severe pain > Use: substitute opioid- morphine, fentanyl

In general, know nondrug interventions for pain relief

Application of heat and cold, massage, exercise, acupunture, realaxation, imager
y, peer group support,
neurolytic nerve block (frees nerve from inflammation) , radiation therapy, neur
osurgery, tumor surgery, TENS,
cognitive distraction.

Management of pain in special populations

The elderly have heightened drug sensitivity, and an increased risk of side effe
cts and adverse reactions. Are
often undertreated for pain.
Young children are hard to assess for pain. They also have a less developed BBB
and developing kidneys and
livers.
Codeine (Paveral)
Class: OPIOID with mild-moderate analgesia, dispensed with non-opioids, cough su
ppressant, opioid agonist.
Usual & common uses: management of mild to moderate pain. Antitussive. (Manageme
nt of diarrhea)
Mechanism: Binds to opiate receptors in CNS.
Expected responses: decreased severity of pain. Suppression of cough reflex. Rel
ief of diarrhea.
Side effects: confusion, sedation, hypotension, constipation, nausea, vomiting,
Nursing implications: assess type, location, and intensity of pain prior to and
1-2 hours after administration.
Assess BP, HR, RR, bowel function before and routinely during administration. Pr
olonged use may lead to
physical and psychological dependence. Assess cough & lung sounds.

Diuretics

Proximal Convoluted Tubule about 65% of filtered sodium and chloride is reabsorb
ed at the PCT. Almost all
K+ and HCO3- is reabsorbed here. H20 follows passively. Pumps for active secreti
on are located here. These
pumps transport compounds from the plasma into the lumen of the nephron.

Loop of Henle: upper portion is in the cortex and lower portion in medulla. Two
loops: descending and
ascending. As loop passes into hypertonic renal medulla, water is drawn into int
erstitial space. Tonicity goes
from 300 mOsm/L at the upper regions of the cortex to 1200 mOsm/L at the lowest
part of the loop of henle.
The loop diuretics (Furosemide/Lasix) work here to block reabsoption of Na+ and
Cl- which prevents passive
reabsorption of water
Descending Limb freely permeable to water. Water is drawn from the loop into the
interstitial space, causing
urine to become concentrated
Ascending Limb 20% of filtered sodium and chloride is reabsorbed, impermeable to
water, it remains in loop

Distal Convoluted Tubule (early segment) about 10% of filtered sodium and chlori
de is reabsorbed, water
follows passively.
Late Distal Convoluted Tubule and Collecting Duct (distal nephron) 2 processes:
1 At tubule: aldosterone
stimulates reabsorption of Na from the distal nephron (Na retention). At the sam
e time, aldosterone causes K to
be secreted (K excretion). 2 At collecting duct - ADH regulates final concentrat
ion of urine. ADH acts on
collecting duct to make it permeable to H2O.
Distribution of water in the body; how diuretics affect this distribution
Total body water=45-60% of body weight
Intracellular fluid (ICF)=66% of total body water
Extracellular fluid (ECF)=33%
Interstitial fluid 75% of ECF
Plasma 25% of ECF
Diuretics affect the ECF volume (specifically plasma) by interfering with reabso
rption of Na and Cl at the
nephron. Trapping solutes and the water that would passively follow them back in
to the plasma, diuretics cause
them to both be excreted.

Hydrostatic and oncotic pressure

- Hydrostatic pressure pushes fluid from blood vessels into the interstitium -
at the beginning of an arteriole
bed, blood pressure is higher than oncotic pressure (proteins-albumins), pushing
water outward into interstitium
- Oncotic pressure keeps fluid inside blood vessels - this can be illustrated a
t the venule end of the capillary
bed where the hydrostatic pressure has petered out, and with the loss of fluid t
o the interstitium, a higher ratio of
albumins-proteins (which cannot traverse the capillary vessel wall) remain in th
e venule. These proteins are the
main force that pull water back in from the interstitium. One factor leading to
edema is when hydrostatic
pressure is higher than oncotic pressure at the venule end and the protein conce
ntration isn't able to passively
draw water back into the venule.

Potassium and sodium in relation to intracellular and extracellular fluid; norma

l movement of these
electrolytes in the loop of henle, early distal convoluted tubule, and late dist
al convoluted tubule
ICF (inside cell) higher concentrations of K and phosphate
ECF (inside vascular space) higher concentrations of Na and Cl
-Proximal convoluted tubule Na and Cl reabsorbed into vascular space (65%)
-Loop of Henle Na and CL reabsorbed (20%)
-Early Distal Conv. Tubule Na and Cl reabsorbed (10%)
-Late Distal Conv. Tubule Na reabsorbed (1-5%), K into lumen
Three basic renal processes filtration, reabsorption, active secretion
VERY IMPORTANT!! - Where in the nephron each of these processes occurs AND the a
mount of solutes
exchanged at each of the functional sites within the nephron.
- Filtration occurs at the GLOMERULUS and is the first step of urine formation.
Virtually all small
molecules present in plasma undergo filtration.
- Reabsorption this conserves valuable constituents of the filtrate while allowi
ng wastes to undergo
excretion. Takes place by way of active transport. Water then follows passively
along the osmotic gradient
created by solute reuptake.
-Proximal convoluted tubule Na and Cl reabsorbed into plasma (65%)
-Loop of Henle Na and CL reabsorbed (20%)
-Early Distal Conv. Tubule Na and Cl reabsorbed (10%)
-Late Distal Conv. Tubule Na reabsorbed (1-5%), K into lumen
- Active Tubular Secretion Two major pumps for active secretion which transport co
mpounds from
the plasma into the lumen of the nephron. Each selective for organic acids or or
ganic bases. Together, these
pumps can promote the excretion of metabolic wastes, drugs, and toxins. The pump
s for active secretion are
located in the PROXIMAL CONVOLUTED TUBULE.

Know overall way in which diuretics work and the mechanism of action
Diuretics block sodium and chloride reabsorption. By blocking the reabsorption o
f these solutes, diuretics create
osmotic pressure within the nephron that prevents the passive reabsorption of wa
ter. Hence, diuretics cause
water and solutes to be retained within the nephron, and thereby promote the exc
retion of both. The increase in
urine flow that a diuretic produces is directly related to the amount of sodium
and chloride reabsorption that it
blocks. Drugs whose site of action is early in the nephron have the opportunity
to block the greatest amount of
solute reabsorption - producing the greatest diuresis.

The significance of the Cockroff-Gault Equation in assessing renal function

How to calculate estimated Creatinine Clearance, is the volume of blood plasma t
hat is cleared of creatinine per
unit time and is a useful measure for approximating the GFR [(140-age)/SCr*72]*I
BW (*0.85 for women)
Know normal Creatinine Clearance and normal serum creatinine
Normal Serum Creatinine Male= 0.6-1.5 mg/dL, Female=0.6-1.1 mg/dL (in book 0.6-1
.2 mg/dL)
Creatinine Clearance
Normal Range males: 70 mL/min/m2 (plus or minus 10 mL/min/m2);
females: 60 mL/min/m2 (plus or minus 10 mL/min/m2 )
<60 indicates mild renal insufficiency
<30 indicates moderate renal insufficiency
<15 indicates severe renal insufficiency
If at 0, patient is on dialysis

Therapeutic uses of diuretics and how they work in HTN & heart failure
Therapeutic uses for hypertension, heart failure, liver failure, volume overload
states (nephritic syndrome, renal
insufficiency, iatrogenic causes)
Hypertension diuretics are first line therapy for mild to moderate hypertension.
They reduce blood volume and
reduce arterial resistance (vasodilation). Thiazides mostly used.
Heart failure by reducing blood volume, diuretics decrease venous pressure, arte
rial pressure (afterload),
pulmonary edema, peripheral edema, and cardiac dilation.
***Spironolactone (K-sparing diuretic) decreases mortality in cardiac patients,
primarily by blocking the
receptors for aldosterone (aldosterone makes us retain Na and water in exchange
for K)

Specific monitoring parameters to determine therapeutic outcomes

Urine Output
Weight want to see a drop of 1-2kg per day
Lab Results Na normalize and go up, Hct go up
Symptoms! lung sounds, oxygenation, edema, BP, etc.
Adverse Effects:
Electrolytes hypo/hyperkalemia
Hemodynamics if you dehydrate too much, may see low cardiac output, orthostatic
hypotension, tachycardia
Electrolytes that are important to monitor in diuretic therapy K, Na

Monitoring parameters to assess side effects of diuretic therapy

Thiazide Diuretics hypokalemia, hypercalcemia, dehydration, glucose interance, p
recipitate gout, drug
interactions
Loop Diuretics hypokalemia, dehydration, OTOTOXICITY!!, hypersensitivity, drug i
nteractions
Potassium Sparing Diuretics hyperkalemia, dehydration, impotence, gynecomastia
Osmotic Diuretics headache, volume overload

Patient education regarding diuretic therapy including duration, timing, expecte

d symptoms resulting
from diuretic therapy, and education re: dietary implications
Duration needs to know how long they need to be on med (ie. different for tx of
hypertension and when given
post-op)
Timing don t take before bed or before long trips, etc.
Symptoms you will get better on this drug , know both therapeutic and adverse effec
ts (cardiac disarrythmias,
muscle cramping with hypokalemia, etc.)
Dietary limitations
Na limit Na intake
K don t take salt substitutes, regular intake of K, foods high in K
Fluids 2 L per day fluid restriction

Role of aldosterone in the nephron

aldosterone makes us retain Na and water in exchange for K

Foods that will increase K+ in the diet bananas, raisins, apricots, avocados, be
ll pepper, eggplant, broccoli,
spinach, cantaloupe, tuna, halibut, etc.
Mechanism / site of action in nephron, clinical uses, and side effects for the f
ollowing 4 categories of
diuretics:
Thiazides - Hydrochlorothiazide (Hydrodiuril) - increases renal excretion of Na,
Cl, K, and H2O.
Blocks reabsorption of Na and Cl in distal conv. tubule. since only 10% of Na an
d Cl are normally reabsorbed at
this site, maximum diuresis produced is considerably lower than that produced by
loop diuretics. Also, thiazides
cannot be used to promote fluid loss in patients with severe renal impairment. P
harmocokinetics - good
absorption, renal elimation, onset 1-2 hrs. Side effects - hypokalemia, hypercal
cemia, dehydration, glucose
interance, precipitate gout, drug interactions
Loop diuretics - Furosemide (Lasix) called high ceiling diuretics. MOA - inhibit
Na and Cl
reaborption in the ascending limb of the Loop of Henle. Pharmacokinetics - rapid
absorption, GI edema may
impair, highly protein bound, renal elimination, usually needed in high doses. S
ide effects - hypokalemia,
dehydration, OTOTOXICITY!!, hypersensitivity, drug interactions. oral, IV, IM
Potassium-sparing diuretics - Spironolactone (Aldactone) - Aldosterone antagonis
t; decreases
Na absorption in distal convoluted tubule. Pharmacokinetics - oral agents good a
bsorption, metabolized
(amiloride has poor absorption and renal elimation), most often used in combo wi
th thiazides. Produce a
modest increase in urine production, substantial decrease in potassium excretion
. Side Effects - hyperkalemia,
dehydration, impotence, gynecomastia (spironolactone decreases testosterone leve
ls).
Osmotic diuretics - Mannitol (Osmitrol) - Promotes diuresis by creating an osmot
ic force in lumen
of nephron (mannitol undergoes minimal reabsorption, so it remains in the lumen,
inhibiting passive
reabsorption of water into plasma). The more mannitol present, the greater the d
iuresis. Has no significant
effect on K excretion. Used mainly in acute settings to reduce cerebral or intra
ocular pressure.
Pharmacokinetics - onset 1-3 hrs, half-life 1-2 hrs. Side Effects - headache, vo
lume overload. must be given
parenterally

Respiratory
Asthma
Symptoms- cough, including at night (airway nadir/smallest around 4am), wheezing
, chest tightness, SOB,
mucus plugging
pathophysiology - allergens bind to IgE antibodies on mast cells --> mast cells
release inflammatory mediators
(histamines,, leukotrienes, prostaglandins) --> mediators cause inflammatory cel
ls (eosinophils, leukocytes) to
infiltrate airway wall, releasing more inflammatory mediators --> END result: ai
rway inflammation and edema,
increased mucus, smooth muscle hypertrophy, bronchospasm,"ramped up" airway hype
reactivity

Classes of drugs used to treat asthma

Bronchodilators - beta2 agonists, methylxanthines, anticholinergics
Anti-inflammatory - glucocorticoids (steroids), cromolyn, leukotriene modifiers,
IgE blockers

Various methods of delivery of inhaled medications & efficacy

Factors affecting efficacy include particle size, specific equipment use, and de
livery technique.
Metered-dose Inhalers (MDIs) - small, handheld, pressurized devices that deliver
a measured dose of drug
with each activation. Only about 10% absorbed in lungs, can be difficult to used
correctly due to hand eye
coordination. use of a spacer - increases delivery of drugs to lungs, no coordin
ation needed
Dry-Powder Inhalers (DPIs) - Used to deliver drugs in the form of a dry, microni
zed powder directly to lungs.
No propellant is employed. Breath activated. 20% of drug delivered to lungs.
Nebulizers - small machine used to convert a drug solution into a mist. Droplets
are much finer than those
produced by inhalers. Takes several minutes to deliver the same amt of drug in 1
puff of an inhaler. However,
may be more effective for some patients than an inhaler.

Inhaled versus systemic routes of administration

Inhaled medication - enhanced local effects, fast acting, (hoping for) not very
much systemic effects.
Oral administration - Not as fast effects, we'll get systemic effects
Mechanism of action, major SE & role in treatment (acute vs long term control) f
or the following:
Bronchodilators
Beta2 adrenergic agonists (inhaled short acting, inhaled long acting, and oral l
ong acting)
Sympathomimetic drugs: activate beta2-adrenergic receptors in smooth muscle of a
irways causing
bronchodilation. Inhaled and oral. Can be used as "rescue meds" or for preventio
n/control. Never used as
monotherapies. May get beta-1 side effects due to cross over effects

Inhaled Short-Acting - Albuterol (Proventil) - standard therapy for asthma sympt

oms. Used PRN for ongoing
attack or before exercise induced asthma.
- Adverse Effects: usually well tolerated. Tachycardia, angina, and tremor could
occur.
Inhaled Long-Acting - for long-term control, dosing on fixed schedule, not PRN.
Should not be used alone but
rather added to a regimen of a long-term control drug, and only if that med has
been inadequate by itself.
- Adverse Effects: may increase risk of severe asthma and asthma related death B
UT only when used
incorrectly as a monotherapy. Should never be used as first line therapy and nev
er used alone.
Oral Long-Acting - Only used for long term control. Onset is too slow to abort a
n ongoing attack. Should not be
used alone.
- Adverse effects: likely to activate beta-1 receptors in the heart, causing ang
ina pectoris and
tachydysrhythmias (patients should report chest pain or change in HR or rhythm).
Can cause tremor by
activating beta-2 receptors in skeletal muscle.

Anticholinergics
Promotes bronchodilation by blocking muscarinic receptors in airway (blocks bron
choconstriction!), which leads
to smooth muscle relaxation. Additive effects when used with beta-2 agonists. MD
I or nebulizer. Indications:
COPD, asthma

Methylxanthines
Don't see as much, on its way out. Very narrow therapeutic range. Toxicity can b
e fatal. Multiple drug
interactions. Plasma levels must be monitored.

Anti-inflammatory Drugs
Glucocorticoids inhaled; systemic; effect on beta2 receptors
Inhaled, IV, and oral. Decreases mediators, activity of inflammatory cells, airw
ay edema, mucus production.
Increases responsiveness to beta-2 agonists so often given alongside these drugs
. First line therapy for chronic
moderate to severe asthma (to maintain control, NOT abort acute attacks!)
Inhaled Glucocorticoids - Beclomethasone dipropionate (Beclovent) MDI or DPI. 1-
2 puffs 2-4 times a
day. Should rinse mouth after use.
- Adverse Effects: not much, but can cause adrenal suppression and bone loss in
prolonged therapy.
Should get IV during times of stress.
Systemic Glucocorticoids - short term therapy for acute exacerbations, chronic u
se if unable to control
symptoms otherwise. IV for acute attack needing emergency care (Epi pen for bron
chodilation). Used in high-
dose, short-term "pulses" to control acute exacerbations.
- Adverse Effects: bone loss, adrenal suppression, hyperglycemia, very grim if u
sed long term.

Mast cell stabilizers

Cromolyn - Cromolyn (Intal) stabilizes mast cells --> reduced release of mediato
rs, inhibits proliferation of
inflammatory cells, used for prophylaxis of asthma. 2nd tier - first line drug f
or control of asthma (not for acute
attacks), probably one of the safest drugs

Leukotriene modifiers
Montelukast (Singulair) Decreases eosinophil infiltration, mucus production, air
way edema,
bronchoconstriction. Oral administration. Prophylaxis/maintenance.
- Adverse Effects: can get changes in liver enzyme metabolism so need to watch d
rug interactions.
May induce liver toxicity.

IgE blockers
Binds circulating IgE, inhibits binding of IgE to mast cells preventing release
of inflammatory mediators, down-
regulates mast cell receptors for IgE. Drawbacks are they can only be administer
ed subQ and are very
expensive!
Chemotherapeutic Agents

Characteristics of neoplastic (cancer) cells:

persistent proliferation
invasive growth
formation of metastases
o immortality

Etiology/pathophysiology of cancer
Altered DNA in cancer cells results from activation of oncogenes (cancer causing
genes) and inactivation of
tumor suppressor genes (genes that prevent replication of cells that have become
cancerous).

Grading and differentiation; staging

Malignant transformation of the cancer cells DNA has 3 stages: 1) initiation 2)
promotion 3) progression (Lehne)
or Pauline:
T - Tumor: local involvement/invasion
N - Nodes: lymph node involvement
M - Metastasis: Distant Locations

Cell cycle
http://www.biologycorner.com/resources/cell_cycle.jpg

Cancer therapy

Goals
cure- prolonged absence of disease
control - extension of life when cure is unrealistic, preventing growth of cance
r without complete
elimination of disease
 palliation - comfort (reduction of side effects and symptoms) when cure or contr
ol is not possible

Roles definitions of use

induction/primary: given as primary therapy; main treatment for advanced/metasta
tic disease
neoadjuvant: given before surgery for localized cancers to reduce tumor burden &
improve efficacy of
surgery
adjuvant: given after local therapy (surgery or radiation) to decrease incidence
of local and systemic
recurrance
consolidation: given after complete response is achieved to "mop-up" micrometast
atic disease
palliative: to decrease symptoms/pain
chemoprevention: use of selected pharmaceuticals to prevent cancer in high-risk
individuals (e.g.
tamoxifen)

Text Box: G1: Cycle begins here! Cell prepares to make DNA by synthesizing neces
sary components.
S: DNA synthesis takes place
G2: Prepares for mitosis
M: Mitosis
2 options for daughter cells of mitosis:
o enter G1 and repeat cycle
o enter G0 (between M and G1) and be dormant "resting
Obstacles to Cancer Treatment
- absence of truly early detection
- cure requires 100% cell kill
- limited drug access to tumor cells
- heterogenity of tumor cells
- toxicity to normal tissues
- dose reduction or delay
- response of solid tumors
- development of drug resistance
- tumor burden
- rate of tumor growth

Growth fraction and how it relates types of cancers and responsiveness to chemot
herapy
The growth fraction of a tissue is defined as the ratio of proliferating cells t
o cells in G0. Tissues with a large
percentage of proliferating cells and few cells in G0 have a high growth fractio
n. Conversely, tissues composed
mostly of G0 cells have a low growth fraction. Cytotoxic anticancer drugs are mo
re toxic to cancers that have a
high growth fraction than to cancers that have a low growth fraction because cyt
otoxic anticancer drugs are
more active against proliferating cells than against cells in G0.
solid tumors - low growth fraction > respond poorly to drugs
disseminated cancers - high growth fraction > respond well to drugs
Serious toxicity occurs to normal tissues that have a high growth fraction (bone
marrow, GI epithelium,
hair follicles, sperm forming cells)

Types of Resistance
1. induced drug efflux,
2. reduced drug activation,
3. reduced target molecule sensitivity
4. increased repair of drug-induced damage to DNA

*P-glycoprotein is a large molecule that spans the cytoplasmic membrane and pump
s drugs out of the cell. If
this molecule is induced following exposure to a single anti-cancer drug can pro
duce cross-resistance.
More Types of Resistance
1. kinetic resistance: resistance by virtue of a cell's position in the cell cyc
le
2. pharmacologic resistance: due to insufficient drug concentration
3. cellular resistance: mutations
4. multiple drug resistance: P-glycoproten, a drug transport molecule that is wi
thin the membrane of cancer
cells.

Strategies for achieving maximum benefit from chemotherapy

optimizing dosing schedules
dose dense regimens
intermittent chemotherapy
combination chemotherapy
regional drug delivery
maintaining prescribed schedule

Describe the potential benefits of

Dose Dense Regimes does not allow for resistance to develop, allows more delive
ry in shorter time.

Intermittent chemotherapy allows normal cells to repopulate between rounds of tr

eatment.

Combination chemotherapy including guidelines for drug selection More effective

than single-drug
therapy because they can suppress drug resistance, increase cell kill and reduce
injury to normal cells.
They should have:
different MOA's
minimally overlapping toxicities
good efficacy when used alone

Regional drug delivery

Intra-arterial delivery allows for treatment of localized, solid tumors (routes
include ceratoid
artery for brain tumors, hepatic artery for liver metastases)
Intrathecal delivery is done by injection into subarachnoid space, it bypasses t
he BBB and is
used to treat CNS tumors
Other specialized routes include directly into the bladder, intraperitoneal, ple
ural space
Implications of maintaining a prescribed schedule on survival and patient educat
ion
Dose reduction or delay may reduce survival, hence it is important to educate pa
tient about the importance of
maintaining a schedule

Differences between cell cycle non-specific and cell cycle-specific agents

Non-specific
Specific
Active in all phases
-most toxic to proliferating cells
Active in specific cell cycle phases
Not schedule dependent
Schedule dependent
Can treat tumors with few dividing cells

Administration: bolus injection

Administration: continuous infusion or multiple
repeated dose

Major toxicities of chemotherapeutic drugs

Cytotoxic drugs lack selective toxicity. Serious toxicity occurs to normal tissu
es with high growth fraction
bone marrow
GI epithelium
hair follicles
sperm-forming cells

Major side effects of cancer treatments and preventention & intervention strateg
ies
Nausea and vomiting - drugs stimulate chemoreceptor trigger zone
 to reduce - premedicate with antiemetics (combo of aprepitant, dexamethasone, &
ondansetron)

Diarrhea and constipation -damage to epithelial lining of GI tract cause stomati

tis and diarrhea leading to
impaired absorption of fluids and nutrients. Recommendations: diet high in fiber
, constipating foods (cheeses),
and medications depending on the cause. Constipation can occur from certain drug
s and this can be managed
by: stool softeners, laxatives, fluids, exercise, diet in high fiber
Bone marrow suppression causes thrombocytopenia, neutropenia, and anemia
thrombocytopenia - loss of thrombocytes resulting in risk of bleeding
neutropenia- loss of neutrophils resulting in increased risk of infection, may b
e minimized by treatment
with colony-stimulating factor or granulocyte-macrophage colony-stimulating fact
or, both act on bone
marrow to increase neutrophil production. Must count neutrophils regularly and p
ostpone future chemo
until counts reach 500/mm3. Lowest neutrophil count, nadir, occurs between days
10-14.
anemia- due to loss of erythrocytes

Fatigue fatigue may be a side effect of the other side effects; anemia, poor nut
rition, and sleep disturbance
may cause fatigue. (#1 reported SE) Drugs are available to combat the precipitat
ing factors
Alopecia - damage to hair follicles resulting in hair loss. Warn patient and dis
cuss their options of wearing
a hairpiece. If they choose this, they should get it before hair loss occurs. Yo
u can also suggest they cut their
hair to avoid the pain associated with hair loss.
Mucositis/stomatitis the painful inflammation and ulceration of the mucous membr
anes lining the oral and
digestive tract. Tx is good oral hygiene, mouth jelly for lubrication, salt mout
hwash, avoid irritating food and
drink, or medications to preserve and promote cell growth and healing.
Extravasation of vesicants infiltration of a chemo drug into the tissues surroun
ding the infusion access;
causes necrosis, pain, inflammation, and tissue damage. Do not flush, no compres
ses, call the physician & and
other docs immediately, may require graft.

Tumor lysis syndrome definition, in general signs and symptoms, strategies for p
revention
Tumor Lysis syndrome is a collection of metabolic disorders associated with lysi
s of cancer cells
S/Sx: hyperkalemia, hyperphosphatemia, hypocalcemia, hyperuricemia, acute renal
failure
Prevention is KEY!!! Identify patients at risk (high grade lymphoproliferative m
alignancies, larger tumor burden,
high LDL levels, extensive bone marrow involvement, high tumor sensitivity to ch
emotherapy, pre-existing renal
failure or insufficiency), Hydration (start before chemo and 2-3 days after), Al
kalinization of urine (maintenance
of pH>7.0, NaHCO3 added to IV fluids), Allopurinol (blocks formation of uric aci
d), Treat electrolyte imbalances
Chemo precautions
Personal protective equipment used (gown, thick extra long gloves, face mask wit
h shield), Chemotherapy spill
kit, biologic safety cabinet *chemo can be excreted in stool, urine, emesis, pre
gnant women should not be giving
chemotherapy without special precautions*

Understand how the NCCN guidelines for emetogenicity are used

-See handout Emetogenic Potential of Antineoplastic Agents
-Agents rated for Low to High Emetic Risk (Combination Regimens increase risk)
-Individual Patient Risk increases risk

Use of hormonal therapy in cancer importance of ER+, PR+, HER2+

ER+ (Estrogen Receptor) Tumors are required to be ER+ in order to respond to hor
monal therapies such
as aromatase inhibitors and antiestrogens
PR + (Progesterone Receptor) some tumors are ER-, 10% of those are PR+ and will
respond to PR tx
HER2+ (Human Epideral Growth Factor Receptor) 25-30% of metastatic breast cancer
produces
excessive HER2, If positive, candidate for Trastuzumab (Herceptin) because it bi
nds to HER2 and therby
inhibits cell proliferation and promotes antibody-dependent cell death

Definition of biotherapy
the use of agents derived from biologic sources or agents that affect biologic r
esponses

Methods of biotherapeutic action

-enhancing immune response
-altering body s responses that allow cancer cells to grow
-increasing vulnerability of cancer cells
-preventing metastasis
-altering pathway of transformation of normal cells into malignant cells
-enhancing repair of normal cells
-changing behavior of cancer cells
In general, know why the following are beneficial in cancer treatment
cytokines a broad class of protein cell regulators produced by the immune system
, includes:
-interferons- antiviral, antiproliferative, immunomodulatory
-interleukins stimulate activation of immune cells (T & B cells, NK cells, LAK
cells, tumor-infiltrating
lymphocytes
-hematopoietic growth factors

monoclonal unconjugated antibodies highly specific proteins derived from a singl

e clone of antibody-
producing cells that recognize and bind to only one tumor associated antigen, un
conjugated
Actions of unconjugated monoclonal antibodies: direct effects in producing apop
tosis or programmed
cell death, indirect effects by activating host defense mechanisms to mediate an
titumor activity

angiogenesis inhibitors target the neovasculature of tumors to halt their growth

, prevent tumor invasion,
and preclude metastatic spread (angiogenesis is the growth of new blood vessels
within a tumor)

VEGF inhibitor (VEGF are circulating growth factors known to induce angiogenesis
), VEGF inhibitors
decreases angiogenesis and the growth of new blood vessels

Drugs to Know

Cyclophosphamide (Cytoxan) SE: GI: anorexia, nausea, voimiting; GU: hematuria; D

erm: alopecia; Hemat:
thrombocytopenia

Cisplatin (Platinol-AQ) SE: EENT: ototoxicity, tinnitus; GI: severe nausea, vomi
ting; Fand E: hypocalcemia,
hypokalemia, hypomagnesemia; Hemat: anemia
Doxorubicin (Adriamycin) SE: GI: diarrhea, esophagitis, nausea, stomatitis, vomi
ting; GU: red urine; Derm:
alopecia; Hemat: anemia, leucopenia, thrombocytopenia; Local: phlebitis
Paclitaxel (Taxol) SE: CV: ECG changes, hypotension; GI: abnormal liver function
tests, diarrhea, mucositis,
nausea, vomiting; Derm: alopecia; Hemat: anemia, neutropenia, thrombocytopenia;
MS: arthralgia, myalgia;
Neuro: peripheral neuropathy; Misc. life threatening and frequent: anaphylaxis a
nd Stevens-Johnson syndrome

Methotrexate (MTX) SE: CNS: arachnoiditis (IT use only); GI: anorexia, hepatotox
icity, nausea, stomatitis,
vomiting; Hemat: anemia, leucopenia, thrombocytopenia; Misc: nephropathy

Bevacizumab (Avastin) Davis drug guide doesn t have any of the SE listed as frequen
t

Depression/Anxiety

Depression - Clinical symptoms

Persistent and recurrent symptoms of sadness, inability to experience pleasure,
loss of interest, sleep
disturbance, GI disturbance, and changes in eating habits, suicidal ideation, an
d helplessness everyday for at
least two weeks.

Pathogenesis of depression - Monoamine hypothesis of depression

Depression is caused by a functional insufficiency of monoamine neurotransmitter
s; based on two factors a
monoamine depleter can cause depression and drugs that effectively treat depress
ion intensify monoamine
mediated neurotransmission

Know M of A and major SE for the following categories of antidepressants:

Tricyclic antidepressants
- M of A = blockade of neuronal reuptake of NE and 5-HT
- SE = orthostatic hypotension, sedation, anticholenergic, and cardiotoxicity
- Inexpensive, effective, relatively safe, easy to administer; drug of 1st choic
e for some pts

MAO inhibitors (including med interactions, food, significance of tyramine in di

et etc.)
- M of A = blockade of the enzyme that breaks down excess monoamine
- SE = CNS stim, orthostatic hypotension, hypertensive crisis from dietary thymi
ne (strict dietary
restrictions)
- Generally reserved for pts who have not responded to TCAs or SSRIs; drug of ch
oice for pts with
atypical depression

SSRIs - Fluoxetine (Prozac)

- M of A = selective inhibition of 5-HT reuptake
- SE = sexual dysfunction, weight gain, serotonin syndrome, withdrawal syndrome
- Just as effective & better tolerated, high cost, has become most widely prescr
ibed antidepressants

Serotonin-norepinephrine reuptake inhibitors

- M of A = selective inhibition of NE and 5-HT reuptake (w/o blockade of choline
rgic, histamine, or alpha
receptors)
- SE = nausea, headache, anorexia, nervousness, sweating, and insomnia

Atypical antidepressants - Bupropion (Wellbutrin)

- M of A = stimulant properties similar to amphetamine; blocks the reuptake of d
opamine
- SE = seizure, agitation, headache, dry mouth, constipation, tachycardia, and t
remor

Overall compliance issues with antidepressants

Treatment takes weeks to effect symptoms, side effects, cost, and stigma

Implications for patient teaching

- Monitor for increased suicidal bx
- Expected time to see results in mood
- Side effects and expectations
- Potential food and drug interactions

Time needed to see effects (biochemical vs clinical effects)

Biochemical effects occur within hours of the first dose whereas clinical effect
s (relief of symptoms) begins
in approximately 1-2 weeks and maximal effect can take as long as 1-2 months
Suicide risk with antidepressant drugs and ways to decrease chance of suicide
Suicide risk may increase due to increased energy to carry out a plan or length
of symptom relief; patients
need to be made aware of this potential and family and friends should be educate
d on the signs of
impending action.

Definition of Anxiety
Uncomfortable state with both psychological and physical components
.. psychological fear apprehension, dread, uneasiness
.. physical tachycardia, palpitations, trembling, dry mouth, sweating, weakness
, fatigue,
shortness of breath

Overall treatment goals and classes of drugs used in treatment

Relief of symptoms. Treatment with Benzodiazepines or SSRIs.

Significance of distinguishing between situationally-appropriate anxiety and dis

abling anxiety
.. if mod and situationally appropriate, therapy not needed
.. if persistent and disabling, intervention clearly indicated

Benzodiazepines - Alprazolam (Xanax)

- M of A = potentiation of the actions of gamma-aminobutyric acid (GABA), an inh
ibitory neurotransmitter
found throughout the CNS
- SE = CNS depression, anterograde amnesia, paradoxical effects, respiratory dep
ression, and abuse

Differences of benzodiazepines to barbiturates related to abuse potential and re

spiratory depression
Benzodiazepines have a lower risk for abuse and respiratory depression than barb
iturates
Anticoagulants

Physiology & Pathophysiology of coagulation (in general just to understand coagu

lation cascade)
Hemostasis; Stage 1 - platelet aggregation and plug formation > Stage 2 - coagul
ation begins with fibrin
network formation
Definitions
Arterial thrombosis adhesion of platelets to the arterial wall, initiating plate
let aggregation and
coagulation cascade; results in LOCAL tissue injury.
Venous thrombosis stagnation of blood flow initiates the coagulation cascade; re
sults in potential emboli
and DISTANT site injury.
Anticoagulants drugs that suppress production of fibrin, interrupting the clotti
ng cascade
Antiplatelet drugs drugs that inhibit platelet aggregation, blocking the clottin
g cascade
Thrombolytic drugs drugs that promote lysis of fibrin, destroying existing clots
(thrombi)

Anticoagulants Heparin & Warfarin (Coumadin)

- Prophylaxis of VENOUS thrombosis
- M of A = Activation of antithrombin, a protein that inactivates 2 major clotti
ng factors; thrombin and Xa,
production of fibrin is reduced and clotting is suppressed
- SE = risk of hemorrhage, thrombocytopenia, hypersensitivity
- Antidotes = Protamine sulfate (Heparin) / Vitamin K (Warfarin)
- Monitoring = activated partial thromboplastin time aPTT (Heparin) / internatio
nal normalized ratio INR
(Warfarin)

HIT (Heparin-induced thrombocytopenia)

A potentially fatal immune-mediated disorder characterized by reduced platelet c
ounts (thrombocytopenia)
and a seemingly paradoxical increase in thrombotic events; inducing thrombosis.
Low-molecular weight Heparin
Fractionated Heparin molecules; preparations of molecules shorter than those found
in unfractionated
Heparin. Advantages include fixed-dose schedule, no aPTT monitoring, and reduced
likelihood of HIT.
First choice for DVT treatment and prophylaxis because of ease of use and reduce
d adverse effects.

Comparison of Heparin and Coumadin

Both used to prevent thrombosis; Heparin is immediate, whereas warfarin has dela
yed onset of action,
making it ideal for long-term prophylaxis of thrombosis.

Cardiovascular
Physiology of the CV system
2 primary functions
1. delivery of oxygen, nutrients, hormones, electrolytes, and other essentials t
o cells
2. removal of CO2, metabolic wastes, and other detritus from cells
> Veins > R Atrium > R Ventricle > Lungs > L Atrium > L Ventricle > Arteries > C
apillary Beds >

Starling s Law and relationship to preload

The degree of stretch of the muscle fibers during preload is the prime determina
nt of stroke volume; OR the
more in, the more out!

Regulation of arterial pressure

BP=SVR x CO. SVR is regulated primarily through constriction and dilation of ar
terioles and CO=HR x SV.
Regulation of arterial pressure controlled by three systems: the ANS (through b
aroreceptor reflexes),
renin-angiotensin-aldosterone system, and the kidneys.

Determinants of cardiac output

CO=HR x SV

Determinants of stroke volume

Preload degree of ventricular filling (increase in preload=increase in SV)
Contractility force of contraction to eject blood (increase in contractility=inc
rease in SV)
Afterload tension or pressure the ventricle to eject blood (increase in afterloa
d=decrease in SV)

Factors that contribute to preload, afterload, contractility

Preload: blood volume, distribution of blood volume, and altered size of the va
sculature.
Afterload: Vasodialation or Vasoconstriction, SVR, aortic pressure and complian
ce, and aortic stenosis
Contractility: Ventricular muscle mass, MI, cardiomyopathy, Ischemia, Hypoxia.
Inotropic drugs (+ Increase, - Decrease).

Ejection fraction compared to SV

Ejection fraction is the percentage of blood from the L ventricle that is ejecte
d; whereas the SV is the volume
that is ejected.

Implications of pulmonary resistance & peripheral resistance on CO and blood flo

w
An increase in peripheral Resistance (SVR) leads to a decrease in SV, which lea
ds to a decrease in CO. An
increase in pulmonary resistance would lower the amount of blood pumped out by t
he right side of the heart and
since the amount of blood pumped by the two sides is always equal (according to
Starlings law) this would lead
to a decrease in overall SV and thus a decrease in overall CO.
Inotropic - impacting the force of muscle contraction via muscle fibers
- positive inotropic agents increase myocardial contractile force, leading to in
crease CO
- negative inotropic agents decrease myocardial contractile force, leading to de
crease CO
Chronotropic impacting heart rate via nerve fibers
- positive chronotropic =increase heart rate
- negative chronotropic = decrease heart rate
 Classes of drugs that decrease and increase preload, afterload, and contractili
ty
Decrease Preload: Diuretics, venous dilators (ARBs, ACEs--which block vasoconst
riction effect of Renin-
angiotensin pathway), and SARAs (Selective Aldosterone Receptor Antagonists
Decrease Afterload: Calcium channel blockers, ACE inhibitors, ARBs (Angiotensin
Receptor Blockers), any
kind of drug that is an arterial dilator
Decrease Contractility: Beta Blockers and Calcium channel blockers
Increase blood flow through coronary arteries: Nitroglycerins and other nitrate
s, calcuim channel blockers
(increase myocardial blood flow because they dilate coronary blood vessels). Asp
irin, platelet inhibitors, and
anticoagulants prevent thrombus formation.

The relationship of O2 demand and supply to the determinants of CO

Demand decreased preload, afterload, and contractility leads to decreased deman
d
Supply- the supply of O2 to the heart depends upon blood flow and vasculature.

Renin-angiotensin system (RAS) actions of angiotensin II, effects of aldosterone

release
Angiotensin II causes peripheral vasoconstriction, elevating blood pressure lea
ding to an increase in organ
perfusion, so - kidney gets more blood flow. Angiotensin II causes the adrenal c
ortex to release aldosterone -
causing sodium and water retention in the renal tubules, increasing blood volume
leading to an increase in
preload, increasing cardiac output, blood pressure and organ perfusion.

Specifically where in the RAS beta blockers, ACE inhibitors, ARBs, and SARAs wor
k
- Beta blockers inhibit the release of Renin. This blocks Angio I from becoming
Angio II
- ACE inhibitors also block the converting enzyme ACE from transforming angiote
nsin I into angiotensin II
- ARBs (angiotensin II receptor blockers) block angiotensin II receptors and dec
rease the effect
- SARAs (selective Aldosterone Receptor Antagonists) blocks aldosterone recepto
rs.

For the following classes of drugs, know mechanism of action, primary indication
s for use, primary side
effects, & patient teaching implications:
ACE inhibitors - Captopril
MoA: blocks conversion of Angio I to Angiotensin II leading to vasodilation and
diuresis (blocks production)
Indications for use: MI, CHF, Hypertension, Diabetic Nephropathy
SE: cough, hypotension, hyperkalemia, renal failure, angioedema, rash, neutrope
nia, & agranulocytosis
Pt teaching: report swelling, light-headedness, infection-sore throat, fever; r
eport jaundice; avoid salt sub
ARBs (Angiotensin Receptor Blockers) - Losartan
MoA: Blocks the action of Angiotensin II by occupying receptor sites (antagonist
) (blocks action)
Indications for use: patients who cannot tolerate ACEIs; & heart failure, strok
e prevention
SE: hypotension, renal failure, angioedema (less than ACEIs), rash, neutropenia
, & agranulocytosis
Pt teaching: report swelling, orthostatic hypotension precautions, infection si
gns, avoid salt sub
Aldosterone blockers / SARAs
MoA: Blocks receptors for aldosterone (antagonist) blocking reabsorbtion of Na+
and H2O
Indications for use: Hypertension & Heart Failure
SE: hyperkalemia, secondary sex characteristics (Spironolactone only)
Pt teaching: Drug interactions, no salt subs, monitor BP
* SARA = Selective Aldosterone Receptor Antagonist. Blocks receptors for mineral
ocorticoids,
therefore it does not allow Na+ and water retention. Reduces Pre-load. Same acti
on as Spironolactone
with minimal side effects.
Beta Blockers Propranolol (non-selective) & Metprolol (selective)
MoA: Blockade of Beta-adrenergic receptors, blocking the sympathetic response (&
AV block)
Indications for use: angina, hypertension, MI (acute & F/U), arrhythmias, obstr
uctive cardiomyopathy
SE: Bradycardia, CHF, hypotension, bronchoconstriction, pulmonary edema, depres
sion, hypoglycemia
Pt teaching: do not abruptly stop, orthostatic hypotension warning, check BP, o
ther med interactions
 Calcium Channel blockers Verapamil (vessels & heart) & Nifedipine (vessels only
)
MoA: Prevents calcium ions from entering cells, regulating contractions of muscl
e
Indications for use: Angina pectoris, chronic hypertension, cardiac dysrythmia
SE: constipation, dizziness, flushing, headache, edema of the LE, compromised c
ardiac function
Pt teaching: void large quantities of grapefruit juice, orthostatic hypotension
warning, gum enlargement
Meaning of prodrugs
A substance given in an inactive form that is then activated through metabolism.
Sympathetic nervous system effect of stimulating alpha and beta receptors on the
heart and vessels
Alpha 1 receptor- stimulation causes constriction of the arterioles in the skin
, viscera and mucous
membranes, and constriction of the veins. Dilates pupils.
Beta 1 receptor- stimulation causes increase in HR, force of contraction, and A
V conduction velocity.
Beta 2 receptor- stimulation causes dilation of arterioles in heart, lungs, and
skeletal muscle. Causes
bronchodilation.

Mechanism of action of ADP inhibitors, Aspirin, & GP IIb / IIIa inhibitors

Antiplatelet drugs; ADP inhibitors and Aspirin block one pathway, GP IIb/IIIa b
lock all.
- Aspirin irreversibly inhibits cyclooxygenase, blocking the ability to synthesi
ze thromboxane, a promoter of
platelet aggregation.
- ADP inhibitors block ADP on platelets, preventing ADP mediated aggregation. Pl
avix
- GP IIb/IIIa inhibitors ( super aspirin ) reversible of inhibition of GP IIb/IIIa (
the platelet glue ) stopping the
final step in platelet aggregation.

Understand the reasons why a low HR can be beneficial

Low HR can allow for more filling time (increased preload=increase CO=increased
supply of blood to the
myocardium) and also increases time spent in diastole during which the heart rec
eives its blood supply.

Understand the relationship of BP to CO and SVR (BP = CO x SVR)

Nonselective versus selective beta blockers

Cardio-selective beta blockers affect only beta receptors in the heart (Beta 1)
and do not affect Beta 2
receptors in the lungs. Non selective beta blockers act on both beta 1 and beta
2 receptors and may cause
unwanted side effects such as bronchoconstriction.

Beta blockers with combined alpha and beta blocking capabilities; benefits of us
e
Used primarily for hypertensive crisis, non-selective drugs block beta 1 and be
ta 2 and alpha 1 receptors.
This limits vasoconstriction throughout the body.
Effect of calcium & the role of calcium channel blockers on the heart and vascul
ar smooth muscle
Calcium depolarizes the sinus and AV nodes; it also binds to actin and myosin i
n cardiac and smooth
muscle to assist in heart muscle contraction and contraction of the smooth muscl
e layer around peripheral blood
vessels. Calcium blockers decrease contraction potential and vasodialate.

Different sites of action between dihydropyridines and other calcium channel blo
ckers
Dihydropyridines (suffix pine) acts on arterioles. Verapamil/Diltiazem - site of
action is the heart/arterioles

Various classes of drugs and why they are used to treat hypertension
Diuretics reduces blood volume
Sympatholytics suppression of the sympathetic nervous system; slower HR & vasod
ilation
Direct-Acting Vasodialators dilation of arterioles
Calcium Channel Blockers dilation of arterioles and some suppress the heart
ACE Inhibitors blocks Angio II production from Angio I; prevents vasoconstricti
on & volume increase
Angio II Receptor Blockers blocks the action of Angio II; prevents vasoconstric
tion & volume increase
Aldosterone Antagonists promotes renal excretion of sodium and water

Various classes of drugs and why they are used to treat heart failure
Diuretics decreases venous pressure, arterial pressure (afterload), pulmonary &
peripheral edema
ACE Inhibitors blocks Angio II production from Angio I; arteriolar dilation, ve
nous dilation, volume stability
Angio II Receptor Blockers blocks the action of Angio II; improvement of LV eje
ction fraction
Aldosterone Antagonists promotes renal excretion of sodium and water; reduces c
ardiac remodeling
Beta-Blockers Antagonize beta receptors; improve LV ejection fraction, slow pro
gression of HF
Cardiac Glycosides - Digoxin - + inotropic action; increases contractile force,
increasing cardiac output