module 2 pharmacokinetics pharmacodynamics

Question 1

what is pharmacokinteics

Answer 1

it is what the body does to the drug, administration, distribution, metabolism, excretion ADME

Question 2

what is pharmacodynamics

Answer 2

what the drug does to the body, drug concentration as related to magnitude of effect

Question 3

Why Study clinical PK?

Answer 3

individualize patient drug therapy
maximize efficacy, mnimize toxicity and adv reactions
monitor drugs with narrow therapeutic index
monitor drug PK/PD as a diagnostic tool for some underlying diseases

Question 4

define Absorption and factors affecting it

Answer 4

Movement of the drug from the site of administration into the general circulation

Affected by factors such as: Route of Administration, pH, Blood flow to the absorption site, Total surface area available for absorption & Contact time at the absorption surface

Question 5

define Bioavailability (F)

Answer 5

The proportion of administered drug that reaches the systemic circulation in unchanged form

Question 6

define Bioequivalence

Answer 6

a desirable feature of a generic drug dosage form (after patency is expired for a brand drug) is that it produces the same serum concentration / time profile as its brand name counterpart.

When generic drug product meets this requirement, it is said to be Bioequivalent to the brand drug.

Question 7

define distribution and the factors affecting it

Answer 7

The transfer of drug from the general circulation into different organs of the body

Affected by factors such as: Blood flow, Capillary permeability (Esp. BBB), Binding of drugs to plasma proteins

Question 8

why is drug distribution different in elderly and pediatrics than adults?

Answer 8

due to difference in body composition and protein binding

Question 9

define volume of distribution

Answer 9

Vd is a hypothetical volume that relates drug serum concentrations to the amount of drug in the body.

Question 10

Vd can be very small. eg?

Answer 10

warfarin 5-7L

drug primarily contained in the blood

Question 11

Vd can be large. eg?

Answer 11

digoxin 500L

drug distributes widely and is mostly bound to body tissues

Question 12

give the formula for Loading Dose

Answer 12

LD = Vd (L) x Desired Plasma Concentration

Question 13

define metabolism and the factors affecting the drug

Answer 13

Process of converting drugs to another form by the action of enzymes
Affected by factors such: Age, Disease, Genetics, Enzyme inducers & Enzyme inhibitors

Question 14

define excretion/clearance and the factors affecting the drug

Answer 14

The volume of blood completely cleared of the drug per unit time. Expressed as volume per unit time (e.g. L/h or mL/min.)
Affected by factors such: Age, Disease and pH

Question 15

What are the organs responsible for excretion?

Answer 15

Glomerular filtration matures in relation to age, adult values reached by 3 yrs of age

Question 16

the half life of a drug depends on the size of the administered dose. t/f

Answer 16

false. does not depend on the size of the dose.

Question 17

how is the dosage interval of a drug determined?

Answer 17

The dosage interval for a drug is determined by its half-life.

Question 18

give the formula for Maintenance Dose

Answer 18

Maintenance Dose = Average Css x Cl

Question 19

define half life elimination rate constant and give its formula

Answer 19

K is Fraction of drug in the body removed per unit time (hr)
k = Cl / Vd

Question 20

give the formula for t1/2

Answer 20

t1/2 = 0.693/k

Question 21

what happens at Css?

Answer 21

Serum drug concentrations increase until the rate of drug administration equals the rate of drug metabolism & excretion

Question 22

what happens in linear kinetics?

Answer 22

the rate of elimination is proportional to the amount of drug present

Question 23

what happens if dosage is increased in linear kinetics

Answer 23

there is a proportional increase in plasma drug levels

Question 24

what happens in non linear pharmacokinetics

Answer 24

rate of elimination is constant regardless of amount of drug present

Question 25

When steady-state concentrations is different than expected after dosage change, there are two typical explanations. what are they?

Answer 25

Saturated plasma protein binding sites e.g. Valproic acid Autoinduction of drug metabolism: e.g. Carbamazepine

Question 26

drugs that exhibit non linear pharmacokinetics are easy to dose correctly. t/f

Answer 26

false. Drugs that exhibit non-linear pharmacokinetics are often very difficult to dose correctly.

Question 27

what happens in Michaelis-Menten Kinetics

Answer 27

Follows linear kinetics until enzymes become saturated

Question 28

what happens when ezymes become saturated in michaelis menten kinetics

Answer 28

Enzymes responsible for metabolism become saturated resulting in non-proportional increase in drug levels

Question 29

the michaelis menten kinetics is known by another name. what is it?

Answer 29

This phenomenon is also known as “Saturable pharmacokinetics”.

Question 30

give examples of drugs that follow michaelis menten kinetics

Answer 30

Phenytoin and salicylic acid.

Question 31

how long does it take for Css to be achieved

Answer 31

4-5 half lives

Question 32

give 4 examples of Pharmacokinetics Drug-Drug Interaction

Answer 32

Absorption e.g. Ketoconazole and gastric acid suppressants Distribution e.g. drugs with difference in protein binding affinity Metabolism: e.g. enzyme induction & enzyme inhibition Excretion e.g. drugs competing to same excretion mechanism

Question 33

why is creatinine clearance used to asses renal function in patients.

Answer 33

It is renally excreted entirely unchanged and offers a clinically convenient measure of the renal function

Question 34

The most commonly used equation for calculation is ___________.

Answer 34

Crockcroft-Gault.

Question 35

what is useful to identify therapeutic failures and unanticipated toxicity

Answer 35

pharmacogenetics

Question 36

define therapeutic index. give its formula.

Answer 36

TI = toxic dose / effective dose TI is a measure of a drug’s safety A large number = a wide margin of safety A small number = a small margin of safety

Question 37

Why Measure Drug Concentrations?

Answer 37

To individualize therapy To diagnose toxicity (including addiction) To guide withdrawal of therapy To assess adherence to therapy To determine whether a patient is already taking a drug before starting therapy (e.g. theophylline in an unconscious patient with asthma) In research (e.g. to monitor for drug interactions in post-marketing surveillance Using population pharmacokinetics).

Question 38

Potential for Error When Using TDM

Answer 38

Assuming patient is at steady-state Assuming patient is actually taking the drug as prescribed Assuming patient is receiving drug as prescribed Not knowing when the drug concentration was measured in
relation to dose administration Assuming the patient is static and that changes in condition don’t affect clearance Not considering drug interactions

Question 39

``` what is used to measure the drug concentration for the following drugs Aminoglycoside antibiotics Cyclosporin Digoxin and digitoxin Lithium Phenytoin Theophylline Paracetamol and salicylate (overdose) ```

Answer 39

Aminoglycoside antibiotics (plasma or serum) Cyclosporin (whole blood) Digoxin and digitoxin (plasma or serum) Lithium (serum) Phenytoin (plasma or serum) Theophylline (plasma or serum) Paracetamol and salicylate (overdose) (plasma or serum).

Question 40

Other drugs are sometimes measured. give examples Anticonvulsants other than phenytoin Tricyclic antidepressants Anti-arrhythmic drugs

Answer 40

Anticonvulsants other than phenytoin (e.g. carbamazepine, valproate) Tricyclic antidepressants (especially nortriptyline) Anti-arrhythmic drugs (e.g. amiodarone).