Principles of Drug Disposition

Question 1

Pharmacokinoetic principles in:
Absorption?
Distribution?
Elimination?

Answer 1

A - Bioavailability
D - V(d) and Protein Binding
E - Clearance and half-life

Question 2

4 primary systems affecting first pass effect

Answer 2

GI lumen, Gut wall enzymes, Bacterial Enzymes and Hepatic Enzymes

Question 3

3 processes that Solids undergo before absorption

Answer 3

Disintegration: solid –> granules
Disaggregation: granules –> smaller particles
Dissolution: solid –> solution

Question 4

Easily absorbed: Protonated or deprotonated?

Answer 4

Deprotonated

Question 5

What will you do during a poisoning:
w/ acidic drug?
w/ basic drug?

Answer 5

alkalinize the urine to convert it to ionic form

acidify urine to convert it to ionic form

Question 6

Other factors affecting absorption:
Concentration?
Area of Absorption?
Gastric Emptying?

Answer 6

Higher concentration injected, higher concentration absorbed

Small intestine absorbs more than stomach, higher SA and more blood flow

Lower Gastric emptying time, higher absorption rate, immediately goes to intestine

Question 7

Increase in GET: Atropine vs Domperidone?

Answer 7

Atropine; Domperidone decreases

Question 8

Billroth Syndrome

Answer 8

Gastric dumping syndrome - faster GET, results into diarrhea since undigested food in the intestinal lumen attracts ions and water

Question 9

Fundamental Relationships to repeated administration:
Steady state?
Fluctuation?

Answer 9

SS is achieved after 4 half lives
independent of dosage

Fluctuation proportional to dosage interval/half-times

Question 10

PK Principle Bioavailability:
standard universal benchmark?
Vs Bioequivalence?

Answer 10

60% for innovator product;

Ratio of bioavailability of 2 drugs

Question 11

Factors affecting Distribution

Answer 11

Cardiac output
Vascular perfusion
Tissue permeability to drug
Drug partitioning between tissues and blood

Question 12

PK Principle: Protein Binding:
Weakly acidic drug bind to?
Weakly basic drug bind to?
Example of highly bound drug?
When is binding significant?

Answer 12

Albumin;
Alpha-glycoprotein;
Anticoagulants;
If binding is more than 80% and for drugs with a very narrow margin of safety;

Question 13

PK Principle: V(d):
Pharmacologic or physiologic concept? homogenous or heterogenous w/ blood?
Binding to tissues result in?
Binding to plasma proteins result in?
Formula?

Answer 13

Pharmacologic; Homogenous w/ blood;

Inc V(d) and dec in plasma conc;
Dec V(d) and inc in plasma conc;

V(d) = Drug amt in body/Conc     or
V(d) = (Dose x F)/Conc

Question 14

If higher V(d), more drug found in ____

If less V(d), more drug found in ____

Answer 14

Extravascular tissue (not homogenously distributed);
Vascular compartment;

Question 15

2 Phases of Metabolism?

Answer 15

Phase I (Non-Synthetic) and Phase II (Synthetic)

Question 16

Processes involved in Phase I

Answer 16

CHORD
Cyclization, Hydrolysis, Oxidation, Reduction, Decyclization

Just a simple reaction

Question 17

Processes involved in Phase II

Answer 17

CAMS

Conjugation (glucoronide, glutathione, glycine, sulfate), Acetylation, Methylation, Synthesis (RNA/DNA)

Question 18

Give the prodrug:
Ampicillin, Alpha-methylnorepinephrine, Enalaprat, Fluorudine Monophosphate, Dopamine, Prednisolone, Methyl-
mercaptopurineribonucleotide

Answer 18

BACampicillin, PIVampicillin || Alpha-methyldopa || Enalapril || Fluorouracil || Levodopa || Prednisone || Methylmercaptopurine

Question 19

Why do prodrugs need to be ingested orally?

Answer 19

So that they will pass the liver and be metabolized into active metabolites

Question 20

Most important drug metabolizing reaction?

What enzyme used?

Answer 20

Oxidation

Hepatic oxygenases - CYP450

Question 21

Most abundant CYP? Least abundant?

CYP is responsible for degradation of ___ and ___.

Answer 21

CYP3A; CYP1A2;
Astemizole (antihistamine, causes arrhythmia)
Chloramphenicol (for typhoid)

Question 22

Microsomal Drug Metab. Enzyme
Location? Inducible or not?
# 1 inducer?

Answer 22

sER of liver cells;

Inducible; Phenobarbital induce enzyme maturation

Question 23

Non-microsomal DME

Location? Inducible or not? #1 inducer?

Answer 23

plasma, cytoplasm and mitochondria of liver cells;

Not inducible;

Question 24

Meaning in Plasma Concentration graph:
Rapid decline
slow decline

Answer 24

Distribution of drug

Elimination of drug

Question 25

Clearance:
Formula?
Best clearance time? Slow clearance?

Answer 25

CL = Dose / AUC;

from 1 y.o. until puberty; neonates and elderly;