Pharmacokinetics

Question 1

Pharmacokinetics

Answer 1

What organism does to drug.

Conc as function of time.

Question 2

ADME

Answer 2

(fate of drug)
Absorption
Distribution
Metabolism
Excretion

Sometimes also: liberation (from medication) and toxic effects

Question 3

parameters of absorption, distribution, metabolism/excretion

Answer 3

A: bioavailability F
D: volume of distribution Vd
M/E: clearance CL

Question 4

Therapeutic index

Answer 4

(max non-toxic dose) / (min effective dose)

Question 5

AUC (drug kinetics)

Answer 5

Area under curve. Total amount of drug absorbed (conc vs time).

Question 6

Bioavailability

Answer 6

Extent to which drug reaches systemic circulation.

AUC) / (AUCiv
iv= intravenous

Question 7

Routes of drug administration determined by..

Answer 7

Physiochemical properties of drug
Therapeutic objectives
Stability of drug

Question 8

Routes of administration

Answer 8

Enteral: oral, sublingual/buccal, rectally
Parenteral: intravenous, intramuscular/subcutaneous
Other: inhalation, topical, transdermal

Question 9

Oral

Answer 9

Safe, convenient, high compliance, antidotes possible.

But: slow onset, limited bioavailability, first-pass effect.

Question 10

Sublingual, buccal

Answer 10

Under tongue / between gums and cheek.

Safe, convenient, high compliance, rapid absorption, avoids first-pass metbolism.

Question 11

Rectal

Answer 11

Partially avoids first-pass. Avoids drug damage in GI. Suitable for vomiting/unconscious patients, babies.
But: low compliance, may cause irritation, difficult to control.

Question 12

parenteral - suitable for?

Answer 12

Drugs with low enteral bioavailability / that are unstable in GI. For unconscious patients. Rapid onset.

Question 13

Intravenous

Answer 13

Directly into systemic circulation, immediate effect > emergencies. Highest bioavailability. Suitable for peptides. Easily controlled, predictable.
But: low ocmpliance, local tissue damage/infection, irreversible, not for highly lipophilic drugs.

Question 14

Intramuscular, subcutaneous

Answer 14

Sustained, slow release (depot). For poorly soluble suspension / larger drug molecules. High bioavailability. Avoids first-pass.
But: low compliance, ltissue damage/ infection, pain,local adverse effects

Question 15

Inhalation

Answer 15

Rapid delivery, local application, lower systemic side-effects.
But: some systemic absorption.

Question 16

Topical

Answer 16

Local application > lower side-effects.

Some systemic absorption may occur, low delivery to target tissue

Question 17

Transdermal

Answer 17

Slow, sustained. Safe, convenient. Lipophilic drugs.

But: only highly lipophilic drug, allergic reaction from patches,.

Question 18

Mechanisms of drug passage across biological membranes

Answer 18

1. Passive diffusion
2. Facilitated diffusion (carriers)
3. Activated transport (transport proteins, ATP!)
4. Endocytosis (large drugs)

Question 19

Distribution depends on:

Answer 19

1. Local blood flow (> perfusion rate)
2. Capillary permeability
3. Protein binding in plasma and tissue
4. Lipophilicity and size of drug, substrate specificity for transporters

Question 20

Volume of distribution

Answer 20

Vd = Dose of drug / C0

C0 = conc at time point 0

Question 21

Routes of drug elimination

Answer 21

Excretion through kidneys (hydrophilic drugs)
Hepatic metabolism (lipophilic drugs)
Biliary elimination
Intestinal metaboism
Secretion into gut lumen after absorption
Elimination via faeces/lung/breast milk/sweat/saliva/skin

Question 22

Drug clearance

Answer 22

Amount of drug eliminated over time.

CL = [ln(2)xVd] / [t1/2]

Question 23

Enzymatic reactions in the liver to increase hydrophilicity of lipophilic drugs

Answer 23

Phase 1: additional of polar functional groups via oxidation/reduction/hydrolysis
Phase 2: conjugation with hydrophilc molecules eg glutathion/sulfate/aa

Then: excretion via kidneys/bile

Question 24

CYP enzymes

Answer 24

Phase I enzymes. Cytochrome P450.
Cofactor haem. Liver and GI. Metabolise 50% of all drugs by oxidation.
Important: CYP3A4, CYP2D6

Question 25

Prodrug, advantages?

Answer 25

Inactive/lower activity precursor. Converted to active drug by enzymes in organ.

Higher absorption, lower first-pass, higher CNS-permability, less undesired effects.

Question 26

Pharmacokinetics vs - dynamics

Answer 26

Dynamics: What drug does to organism (effect/log conc)
Where/how/why is there effect?

Kinetics: What organism does to durg (conc/time.
Where/how is drug absorbed/distributed/excreted?

Question 27

CYP3A4 drug interactions

Answer 27

Inhibitors: eg grapefruit juice (bergamottin) > increase conc of drugs metabolised by CYP3A3 (eg felodipine, used to lower bp)

Inducers: eg Rifampicin, St. Johns wort > lower conc of felodipine

Question 28

Interaction of MAO-inhibitors with dietary substances

Answer 28

MAO-inhibitors block monoamine oxidase (enzyme that breaks down tyramine).
Patient eats tyramine-high foods > increase in blood pressure