Basic Lab Tests:

1. Define each of the components of a CMP

CMP complete metabolic profile. Set of labs run on one machine to save amount of
blood needed and cost/time.
Components:
Glucose, Sodium, Potassium, Calcium, Chloride, Carbon Dioxide (CO
2
), Creatinine, Blood
Urea Nitrogen (BUN)
Albumin, Total Protein, Total Bilirubin, Alkaline Phosphatase (ALP), Aspartate
Aminotransferase, (AST), Alanine Aminotransferase (ALT)

2. Explain the function of each component of a CMP
Glucose:
Measuring glucose in the blood determines if a patient is hyperglycemic or
hypoglycemic.
Fasting hyperglycemia is associated with Type 1 or Type 2 diabetes mellitus.
Normal fasting plasma glucose (FPG) is 70 to 99 mg/dL
Clinical symptom of hyperglycemia polyuria, polydipsia, and weight loss
Clinical symptoms of hypoglycemia tremor, palpitations, anxiety, cognitive
impairment, behavioral changes
Sodium:
Regulation of plasma volume
Generation of nerve impulses
Generation of muscle contractions
Facilitation of glucose absorption in the small intestine
Normal plasma sodium is 136-146 mEq/L
HYPERNATREMIA & HYPONATREMIA represent sodium imbalances (usually
more about water balance)
Clinical symptoms of Hypernatremia lethargy, weakness, irritability, seizure
Clinical symptoms of Hyponatremia nausea, malaise, headache, lethargy, seizures


Potassium:
Generation of nerve impulses
Generation of muscle contractions
Acid Base Balance
Normal plasma potassium is 3.5-5.1 mEq/L
Clinical symptoms of Hyperkalemia muscle weakness, cardiac conduction
abnormalities, cardiac arrhythmias
Clinical symptoms of Hypokalemia muscle weakness, rhabdomyolysis, cardiac
arrhythmias
Calcium:
Muscle contraction
Cardiac function
Enzyme activation
Exocytosis of neurotransmitters
Blood clotting
Normal bone and tooth architecture
Normal plasma calcium is 8.6-10.2 mg/dL
Clinical symptoms of Hypercalcemia nephrolithiasis, Kidney stones, nausea, vomiting,
bone pain, confusion
Clinical symptoms of Hypocalcemia muscle twitching, tetany, cardiac arrhythmias,
papilledema
Chloride:
Acid base balance
Facilitates actions of certain neurotransmitters (GABA, glycine)
Normal plasma chloride is
95-105 mEq/L
Creatinine:
Creatinine is a waste product made in skeletal muscle and filtered by the kidneys. When
the kidneys fail to filter creatinine, the level of creatinine in the blood increases.
Normal serum creatinine is
0.9-1.3 mg/dL in males and
0.6-1.1 mg/dL in females
Elevated BUN and creatinine in the blood can suggest kidney dysfunction (lack of
filtration)

Blood Urea Nitrogen (BUN):
Blood urea nitrogen is a measure of the amount of urea in the blood. Urea is a waste
product made in the liver from amino acid metabolism and ammonia. Similar to
creatinine, it is filtered by the kidneys.
Normal BUN is
6-20 mg/dL (adult)
Elevated BUN and creatinine in the blood can suggest kidney dysfunction (lack of
filtration)
Albumin / Total Protein:
Albumin is a protein synthesized by the liver. It is used to determine nutritional status or
to screen for certain liver and kidney disorders as well as other diseases.
Maintenance of oncotic pressure
Transportation of thyroid hormones, fat-soluble hormones, "free" fatty acids,
unconjugated bilirubin, many drugs
Competitively binds calcium ions (Ca
+2
) (Buffers pH)
Total Bilirubin:
Bilirubin is a hydrophobic waste product from the metabolism of hemoglobin inside of
red blood cells. RBCs generally live for 90-120 days, after which they begin to
structurally deteriorate as they circulate in the bloodstream. The 3 tissues responsible for
removing these deteriorating RBCs from the circulation are the liver, spleen and bone
marrow. These tissues degrade the hemoglobin inside the RBCs and make bilirubin.
Eventually, all bilirubin gets sent to and processed by the liver. Increased bilirubin is
usually a liver problem.
Hyperbilirubinemia Jaundice
ALT, AST and ALP:
SERUM AMINOTRANSFERASES (TRANSAMINASES)
Alanine aminotransferase (ALT) an enzyme mainly found in the liver; involved in
amino acid catabolism
Aspartate aminotransferase (AST) an enzyme found in the liver and a few other places,
particularly the heart and skeletal muscles; also involved in amino acid catabolism
Both found in liver, but also found in other places, like skeletal muscles.
Alkaline phosphatase (ALP) an enzyme related to the bile ducts; often increased when
they are blocked or inflamed; when this occurs, the ALP can overflow (or regurgitate)
like a backed up sewer and seep out of the liver and into the bloodstream; also found in
bone and placenta.

3. Understand the clinical significance of measuring each component of a CMP
4. List all of the components of a basic lipid panel
Lipid Screening:
Exam for risk of coronary artery disease
Include:
Total cholesterol
High density lipoprotein cholesterol (HDL-C, good)
Low density lipoprotein cholesterol (LDL-C, bad)
Triglycerides
May include non-HDL, VLDL or Cholesterol/HDL ratio
Need to fast for this, because fatty acids take a while to get rid of.

5. Discuss the role of dyslipidemia when calculating CV risk
Doctor uses online calculator
6. Interpret the laboratory values of a basic lipid panel
Not on test.
7. List the components of a urinalysis (UA)
In-office dipstick or lab
pH, Specific gravity, Leukocytes (Leukocytes Esterace), Nitrites, Protein, Bilirubin,
Ketones, Blood, Glucose and Microscopic examination of the urine sediment

8. Understand the clinical significance of measuring the components of a UA
White blood cells Infection/Inflammation
Red blood cells Kidney/Bladder disease, Blood disease
Epithelial cells often a sign of contamination
Bacteria Infection
Casts tube-shaped proteins (kidney disorders)
Crystals possible nephroliathisis (kidney stones)
High specific gravity dehydration
Positive WBC (Leukocyte esterace) infection/inflammation
Positive Nitrites presence of bacteria
Positive Protein chronic kidney disease
Positive Glucose hyperglycemia or diabetes
Positive Ketones diabetes or starvation
Positive Bilirubin liver disease
Positive Blood (many things) kidney or bladder damage
Into to Hematology and the CBC: normals will be given on test
Anemia - in a persons hemoglobin level below his or her baseline value.
1. Review a complete blood count lab report and differentiate between macrocytic,
normocytic, and microcytic anemia.

Mean Corpuscular Volume (MCV) - "mean cell volume", is a measure of the average volume of a
red blood cell.

2. Interpret a CBC report to identify a patient with leukocytosis or leukopenia.
Leukocytosis: WBC higher than normal
Leukopenia: WBC lower than normal

3. Interpret a CBC report to identify a patient with thrombocytosis or thrombocytopenia.
Platelets:
Primary function is to stop bleeding.
Thrombocytosis too many platelets. It can be a reaction to an infection (reactive
thrombocytosis), or it can be due to a blood and bone marrow disease.
Thrombocytopenia too few platelets. (increased bleeding risk)

4. Why is the gentleman on the first slide eating dirt?
Paika Iron deficiency.

Pharmacokinetics pt. 2:
1. If given a drugs elimination half-life, determine the time required to achieve steady-state
serum levels on a dosage regimen (slides 9, 13)
Steady State - point in a consistent dosing regimen where serum levels are no longer
changing
Time to steady state is a function of the drugs elimination half-life
After 4 half-lives, the serum levels are about 94% of steady state
Loading doses can decrease the time needed to achieve steady state
Loading Dose - If maintenance doses will take some time to reach the therapeutic range,
to quickly achieve therapeutic drug levels, start therapy with a LOADING DOSE
Examples:
Give 600 mg IV now then start IV infusion of 30 mg/hr
Give 1000 mg first dose orally, then 500 mg orally every 12 hours

2. Describe what is meant by prodrug (slide 24)
Prodrug - a medication that is administered in an inactive or less than fully active form,
and is then converted to its active form through a normal metabolic process. precursor
chemical compound of a drug.

3. List the 4 possible outcomes of liver drug metabolism (slide 24)
Termination of drug
Active metabolite formed
Bio-activation of prodrug
Toxification - toxic metabolite formed from parent drug

4. Explain the differences between Phase I and Phase II drug liver metabolism (slides 25-
27)
PHASE I: involves cytochrome p 450 (CYP) liver enzyme system (activation of
metabolites)
Inducer and Inhibitor; Can cause Drug Interactions
Inducer: speeds up the metabolism of other drugs

PHASE II: conjugation step (with glucuronic acid, sulfate etc.)
Phase 2 metabolism involves conjugation - that is, the attachment of an ionised group to
the drug. This attachment of ionized group makes it more water soluble and more readily
excreted.

5. Define what is meant by enzyme induction or inducer (slide 29)
Drugs which induce hepatic enzymes may have the following effects:
may decrease the bioavailability of other drugs which are metabolised by those enzymes
may increase the bioavailability of drugs which require metabolism for their activation

6. Describe enterohepatic recycling (slide 31)
Enterohepatic Drug Recycling: can prolong drug duration of action

Circulation of drugs, or other substances from the liver to the bile,
followed by entry into the small intestine, absorption by the
enterocyte and transport back to the liver


7. Outline the role of the kidney in drug elimination (slide 32)
Drug Out: Parent drug & metabolites -
Filtered out at glomerulus
Secreted by renal tube
Drug In: Renal tubular reabsorption
pH effect and ion trapping = therapeutically change urine pH to alter drug ionization
and lipid solubility
Example: Increase urine pH to increase secretion of aspirin in an overdose situation



Antihistamine Objectives:

1. Explain the mechanism of action of the antihistamines diphenhydramine, loratadine and
fexofenadine (slide 36, 37, 39)
Histamine initiates its effects by stimulating cell membrane
G-protein coupled receptors
Four different histamine receptors have been identified (H1-4)
Antihistamines block H1 receptors
Dry Mouth
Constipation
Urinary
Retention (males
w/ enlarged
prostate)
Blurred
Vision
Confusion;
memory loss
(elderly)
-Diphenhydramine (benedryll)
-Lordatine (claratin)
-Fexofenadine (allegra)
Antihistamines do not affect the allergic reaction that is causing the release of histamine,
just affects number of histamines binding to H1 receptor

H2 receptor blockers block H2

2. State the initial drug of choice for emergency treatment of severe allergic reactions (slide
43)
Epinephrine
-then benadryll
3. Explain two clinical advantages that loratadine and fexofenadine have over
diphenhydramine
Benadryll (diphenhydramine): highest incidence of causing sedation and anticholinergic
effects.
Loratadine and Fexofenadine are 2
nd
generation drugs and are basically non-drowsy
and have a low incidence of anticholinergic effects. These drugs have a decreased ability
to cross into the CNS (this explains the non-drowsy).
Loratadine has an active metabolite, desloratadine. After oral administration, loratadine is
rapidly and well absorbed and undergoes extensive first pass metabolism, mainly by
CYP3A4 and CYP2D6. The major metabolite-desloratadine-is therefore responsible for a
large part of the clinical effect.


4. Describe the anticholinergic effects from diphenhydramine (Benadryll) (slide 48-50)




Anticholinergic Side Effects



Antimicrobials:
1. Define the term selective toxicity (slide 7)
Selective Toxicity - antimicrobial selective toxicity refers to the ability of these drugs
to kill or inhibit the growth of microbes, leaving the human host unharmed. Use markers
or processes specific to non human cells.
Bacteriostatic vs. Bactericidal
Bacteriostatic stops microbial growth and lets the immune system kill them.

MIC = minimal inhibitory concentration
MBC = minimal bactericidal concentration
A Microscan Panel: determines antimicrobial MICs

2. Describe pharmacodynamic bactericidal principles (slides 14, 15)
Used for antibacterial dosage regimen design
Concentration dependent killer: Peak/MIC
(best activity when the peak drug level exceeds the MIC by a certain magnitude)
Time dependent killer: Time>MIC
(best activity when the drug level stays above the MIC)
Both can also include post-antibiotic effect
Combining Antimicrobials:
Synergism more effective than the two independent effects put together.
Antagonism drugs negate each others effects

3. Explain the post-antibiotic effect and how it can affect antibacterial dosing (slide 15)
Time and Concentration dependent killing can both also include post-antibiotic effect
where bacterial growth is inhibited for a time after the drug levels drop below the MIC of
the organism; can allow for a longer interval between drug doses
4. List the mechanisms of bacterial resistance to antibacterial agents (slide 16-17)
Antibiotic Effectiveness:
Must reach its target in an active form
Bind to the target
Interfere with its function.

Antibiotic Resistance:
The drug does not reach its target (permeability, porin channel mutation, efflux pumps)
The drug is inactivated (enzymes, for example beta-lactamases)
The target or biochemical pathway is altered so drug cannot bind and/or act
5. Discuss the concerns with microbial resistance and list strategies used to improve
antibiotic utilization (slides 19-26)
Strategies:
Formulary restriction and preauthorization
Prospective audit with intervention and feedback
Standardized order sets and clinical pathways (foster evidence-based prescribing)
Antimicrobial order forms
De-escalation of therapy (Review culture and sensitivity (C&S) results; on-going review
of therapy)
Dose optimization (right dose for site of infection; renal dose adjustment)
Intravenous (IV) to oral dose conversion

6. Explain de-escalation of antimicrobial therapy (slides 26, 30)
De-escalation of therapy (Review culture and sensitivity (C&S) results; on-going review
of therapy)
Discontinue antimicrobials
Switch to more focused therapy based on culture/sensitivity (C&S) results
Change to oral antimicrobials


7. Describe the use of antibiogram and culture/sensitivity reports (slides 12, 32-33, 42-43)
antibiogram is a local summary of selected antibiotic activity versus common bacterial
isolates; it is used for drug formulary decisions and to guide empiric treatment
Ex:

If treating a UTI due to E. Coli, start by using Maropenum. The higher the number, the
better choice to use. Number under each antibiotic is percent of bacteria sensitive to the
antibiotic.