Pharmacokinetics & Pharmacodynamics

Question 1

Pharmacokinetics

Answer 1

What the body does to the drug; what happens to the drug as it moves through the body

(ADME: absorption, distribution, metabolism, excretion)

Question 2

Absorption

Answer 2

Movement of a drug from the site of administration to the blood

Question 3

Distribution

Answer 3

Movement of the drug from the blood to the interstitial spaces and cells

Question 4

Metabolism

Answer 4

Biochemical reactions that alter the drug (usually inactivates but NOT always)

Question 5

Excretion

Answer 5

Exit of the drug from the body

Question 6

Acid

Answer 6

H+ (proton) donor

• in neutral or basic environments, the substance ionizes

Question 7

Base

Answer 7

H+ (proton) acceptor

• in neutral or acidic environment, the substance ionizes

Question 8

Ion Trapping

Answer 8

Accumulation of drug on one side of a membrane due to ionization

(Drug diffuses along concentration gradient, and then ionizes and cannot get back across. Further drug then diffuses, ionizes.)

Question 9

pKa

Answer 9

The pH at which a drug is 50% ionized and 50% unionized

(lower pKa = stronger acid)

Question 10

approx pH of:
- plasma
- stomach
- placenta
- urine

Why does this matter?

Answer 10

• plasma = 7.4
• stomach = 1-3
• fetus = 7.3
• urine = 6.0

Ionized drug can accumulate on one side of a membrane. (Fetal overdose, increased urinary excretion, decreased absorption from GI tract)

Question 11

Factors that affects drugs’ absorption

Answer 11

• rate of dissociation
• surface area for absorption
• blood flow (including cardiac output)
• lipid solubility
• administration route

Question 12

First pass effect

Answer 12

Metabolism by the liver prior to entering the systemic circulation

(PO drugs since they are absorbed to the portal vein which goes straight to liver)

Question 13

Enterohepatic cycling

Answer 13

Drug passage from GI tract to portal vein to liver, which excretes drug or metabolites into bile.

The drug is then retaken up into the portal vein and the cycle continues

(Only some drugs)

Question 14

Volume of distribution (Vd)

Answer 14

How widespread the drug distributes throughout the body
(Small Vd- drug is mostly in the vasculature
Large Vd- drug is in various body compartments, interstitial spaces, and cells)

Question 15

Where is the drug if it has a small Vd?

Answer 15

Vasculature

Question 16

What affects Vd?

Answer 16

• blood flow (including cardiac output)
• tissue perfusion
• type of capillary system (especially BBB)
• drug polarity
• protein binding

Question 17

Blood brain barrier

Answer 17

Specialized capillaries surrounding the CNS
- tight junctions
- p-glycoprotein (PGP)

Question 18

What is the main site of metabolism?
List a couple other sites as well.

Answer 18

Liver

Others:
- kidneys
- GI tract
- lungs
- skin
- plasma
- placenta

Question 19

Phase I metabolism

Answer 19

Oxidation/reduction/hydrolysis
(CYP450 reactions are phase I)

Prepares drug for phase II reactions or direct renal elimination

Question 20

Phase II metabolism

Answer 20

Conjugation reactions
May (or may not) be preceded by phase I reactions.

Prepares drug for excretion (usually kidneys or bile)

Question 21

Cytochrome P450 Enzyme system

Answer 21

12 enzyme families
- CYP1-3 metabolize drugs
- CYP4-12 metabolize endogenous substances

Designed to biochemically convert substances into polar molecules

Question 22

CYP450 induction

Answer 22

Increase in enzyme concentration

Leads to faster metabolism of drugs that are metabolized through that pathway (inadequate drug levels)

Question 23

CYP450 Inhibition

Answer 23

Decrease in enzyme concentration

Leads to a decrease in metabolism of drugs that are metabolized through that pathway (drug accumulation)

Question 24

What is the main site of drug excretion?
List a couple other sites of drug excretion.

Answer 24

Urine

Others:
- feces
- sweat
- saliva
- breast milk
- expired air

Question 25

Minimum effective concentration

Answer 25

Lowest plasma concentration of a drug that elicits a therapeutic response

Question 26

Therapeutic range

Answer 26

The range of plasma drug concentrations between the minimum effective concentration and toxic concentration. I.e. the range we aim for with pharmacotherapy

Question 27

Half life

Answer 27

Time required for the amount of drug in the body to be decreased by 50%

Question 28

What number of half lives is required to reach drug plateau?

Answer 28

Approx 4

Question 29

Zero order kinetics

Answer 29

The same amount of drug is metabolized per hour regardless of total drug concentration

Question 30

First order kinetics

Answer 30

The same percentage of drug is metabolized per hour regardless of total drug concentration *most drugs

Question 31

Pharmacodynamics

Answer 31

What the drug does to the body How the drug elicits it’s response

Question 32

4 types of receptors

Answer 32

- cell membrane embedded enzymes - ligand gated ion channels - G protein coupled receptors (GPCRs) - transcription factors (in nucleus)

Question 33

Potency

Answer 33

How much drug must be administered to elicit response Related to the affinity of the drug for its receptor

Question 34

Efficacy

Answer 34

Intensity of the effect the drug produces The intrinsic activity of the drug

Question 35

Agonist

Answer 35

Mimics the action of the endogenous ligand

Question 36

Partial agonist

Answer 36

Mimics the action of the endogenous ligand, but to a lesser intensity The drug will have a lower maximal effect

Question 37

Antagonist

Answer 37

Blocks the action of the endogenous ligand

Question 38

Draw the dose response curve

Answer 38

https://www.merckmanuals.com/professional/clinical-pharmacology/pharmacodynamics/dose-response-relationships

Question 39

Upregulation

Answer 39

Increase in number of receptors due to continuous antagonist usage

Question 40

Downregulation

Answer 40

Decrease in number of receptors due to continuous agonist usage

Question 41

Effective dose 50 (ED50)

Answer 41

The dose required to produce a therapeutic effect in 50% of the population

Question 42

Lethal dose 50 (LD50)

Answer 42

The dose that would produce death in 50% of the population

Question 43

Therapeutic index (TI)

Answer 43

The range between ED50 and LD50. Determination of the drug’s safety

Question 44

Black boxed warning

Answer 44

FDA-implemented safety warning

Question 45

Quaternary ammonium

Answer 45

Drug that contains a Nitrogen with four Hydrogens - makes it a positively charged drug Thus, the drug cannot cross membranes freely. Cannot be absorbed through GI tract and or respiratory membranes

Question 46

P- glycoprotein

Answer 46

ATP-dependent pump that pumps substances OUT of cells

Question 47

Protein Binding

Answer 47

Binding of drugs to proteins in the plasma and tissues Usually, only UNBOUND drug is pharmacologically active, so high protein binding % results in lower drug activity