pharmacokinetics / pharmacodynamics

Question 1

absorption

Answer 1

Movement of a drug from its site of administration into the blood

Question 2

Variables that influence absorption

Answer 2

Nature of the cell membrane (lipid layer or aqueous channel)
Blood flow to the site of administration (higher blood flow = better absorption)
Solubility of the drug (depends also on the delivery system)
pH ( weak acids are absorbed well in acidic environments of the stomach)
Drug concentration ( diffusion from a high concentration to low concentration)
Dosage form (delivery mode/ package)

Question 3

Enteral

Answer 3

Oral - passive or active transport affected by pH and bacterial enzymatic excretion
Sublingual - absorbed into the veins, not subject to the first pass effect
Buccal - mucous membrane of the mouth which are very vascular
Rectal- erratic absorption, not always consistent blood flow

Question 4

Parenteral

Answer 4

Inhalation - absorption across lung surface, not subject to first pass effect (unless some gets swallowed)
Injection- IV -gold standard of bioavailability, most rapid route; SQ: max 2-3 mls; IM very vascular but might be affected in obese people

Question 5

Topical

Answer 5

Local effect, ointments more occlusive, better than creams or gels
Hydration increases absorption
Transdermal delivery, minimizes peak and trough fluctuations

Question 6

First pass effect

Answer 6

Drug metabolism that occurs when it is absorbed from the gut and travels to the portal circulation and undergoes metabolism→ the greater the first pass effect, the less drug that is available in circulation (mainly when taken by mouth obvi)

Question 7

bioavalabilty

Answer 7

IM: 75- 100
SQ: 75 -100. 
PO: 5-100, 
PR: 30-100, 
inhalation: 5-100, 
transdermal: 80-100

Question 8

Distribution

Answer 8

Movement of absorbed drug in bodily fluids throughout the body to the target tissues

Question 9

initial vs second phase of distribution

Answer 9

Distribution requires adequate blood supply
Initial phase:
Drugs distributed to high flow ares (heart, liver, kidneys, brain)
Second phase:
Areas of lower blood flow (bone, fat, skin)
Affected by body composition, cardiac output, regional blood flow, binding protein, lipid and water solubility, varies from person to person

Question 10

distribution ; fat

Answer 10

Lipid soluble drugs have a high affinity for adipose tissue

Adipose tissue has a low blood flow, can be mitigated by lipid soluble drugs

Question 11

distribution ; bone

Answer 11

some drugs have affinity for bone ( tetracyclines deposits in bone and teeth)

Question 12

distribution ; BBB

Answer 12

relatively impenetrable

- usually protective
- only lipid soluble drugs cross barrier *

Question 13

distribution ; placental barrier

Answer 13

• many drugs pass this barrier

- low molecular weight drugs pass easier (ETOH, opiates)

Question 14

protein binding

Answer 14

Plasma protein binding → drug bound to albumin
Affinity for aqueous or lipid tissue and the degree of binding to protein determines where the drug goes and whether it reaches a therapeutic level
Drug molecules that attach to plasma proteins cannot leave the vascular space and do not have therapeutic effect
Only unbound drugs have a therapeutic effect
Undernourished → less albumin → more likely for toxicity

Question 15

metabolism

Answer 15

Chemical inactivation of a drug through conversion into a more water soluble compound that can be excreted by the body (kidneys and liver)

Question 16

Phase 1.

Biotransformation

Answer 16

Oxidation → makes the drug more hydrophilic (mixable with water)
40 different cytochrome P450 enzymes in the liver may participate as a catalyst in the oxidation process
P450 (CYP) enzymes are very sensitive, and can be inhibited or induced by drugs

Question 17

Phase 2.

Conjugation

Answer 17

For metabolites that are still too lipophilic

Increases the ability to be eliminated from the body

Question 18

Cytochrome P450 system (CYP)

Answer 18

Is the power that fuels the metabolic process
Highly affected by the individuals health and genetic status (hard to predict)
CYP is a superfamily of enzymes that can be divides into families, subfamilies, and single enzymes (single enzymes are not functional)
Major catalyst for drug oxidation***
CYP3A is the enzyme family that is responsible for hepatic metabolism of 60% of currently available drugs
CYP enzymes are mostly in the lipid layer of the endoplasmic reticulum of hepatocytes (liver cells)
Very disease (cirrhosis) and/ or health status (smoking) sensitive → how does that effect them?
CYP metabolism also occurs to a lesser extent in the small intestine, kidney, lung and brain
Catalyze the interaction between many drugs

Question 19

Substrate:

Answer 19

a compound (drug) that is metabolized by a given enzyme; in most cases a drug can be metabolized by more than one enzyme

Question 20

Inhibitor:

Answer 20

a compound (drug) that slows down the metabolism of a substrate by a given enzyme; generally leads to a higher level of the drug (ie. prozac slows down the metabolism of norpramine, resulting in higher levels of norpramine) inverse relationship

Question 21

inducer

Answer 21

a compound that speeds up the metabolism of a substrate by a given enzyme
-generally leads to a lower amount of the drug due to the increased speed of metabolism / clearing from the system

Question 22

common inhibitors

Answer 22

(GPACMAN)

		- grapefruit
		- protease inhibitors (for HIV)
		- azole antifungals
		- cimetidine
		- macrolides ( except azithromycin)
		- amiodarone
		- non DHP CCBs ( diltiazem, verapamil)

Question 23

common inducers

Answer 23

Common inhibitors: (PCRABS)
Phenytoin
Carbamazepine
Rifampin
Alcohol (chronic)
Barbiturates
St johns wort

Question 24

Elimination:

Answer 24

Most drugs excreted by the kidney, can can be excreted by the lungs, skin, breast milk and sweat

Question 25

Onset of action:

Answer 25

time between administration and the first sign of drug effect

Question 26

Peak of action

Answer 26

maximum concentration of drug → point at which the amount of the drug being absorbed and distributed is equal to the amount that is being metabolized and excreted.

Question 27

Duration of action

Answer 27

continued entry of a drug into the body with levels above minimum effective concentration (how long the drug is working)

Question 28

Agonist receptors

Answer 28

stimulates physiologic activity at receptors (histamine, nori, morphine, albuterol)

Question 29

Antagonist:

Answer 29

inhibits the effect that is produced by drugs or eliminates undesired physiologic effects caused by illness (naloxone, ipratropium, beta blockers)
Reduced the effect of the agonist at the receptor site