Pharmacokinetics

Question 1

agonist

Answer 1

binds to a receptor and activates it

Question 2

antagonist

Answer 2

binds to a receptos and inhibits it

Question 3

Presence of a competitive antagonist does what to the dose-response curve of the agonist?

Answer 3

shifts it to the right but does not affect Emax because it takes higher concentrations of agonist to overcome a competitive antagonist, but it can still bind to all of the necessary sites once it has out-competed the antagonist

Question 4

inert binding sites

Answer 4

bind to drug molecule with no effect - buffer drug concentrations

Question 5

Two important plasma drug-binding proteins?

Answer 5

albumin and orosomucoid

Question 6

aqueous diffusion

Answer 6

diffusion of small drug molecules through water-filled pores of capillaries from blood to extravascular space - governed by Fick’s Law.

Question 7

Which tissues lack aqueous pores in their capillaries?

Answer 7

brain, testes

Question 8

Lipid diffusion

Answer 8

passive movement of molecules through membranes and other lipid barriers - governed by Fick’s Law

Question 9

transport via special carriers

Answer 9

transporter molecules move a substance across the membrane that cannot passively move through

transporters exist for ions, neurotransmitters, metabolites like glucose/amino acids, and foreign molecules like anticancer drugs

Question 10

Clinical significance of transporters used for endocytosis of amine neurotransmitters (dopamine, norepinephrine, and serotonin) back into the pre-synaptic membrane?

Answer 10

many antidepressants inhibit these transporters, not allowing amine neurotransmitters back into the nerve endings they came from.

Question 11

endocytosis of drugs

Answer 11

drug binds to receptor on cell membrane and the area of the membrane folds and internalizes the drug

Question 12

Why is endocytosis so selective?

Answer 12

drug/molecule must bind with a specific receptor on the cell membrane

Question 13

What does Fick’s Law tell us?

Answer 13

rate of movement of molecules across a barrier

Question 14

What is the EQ for Fick’s Law and what does it indicate about drug absorption in different tissues?

Answer 14

rate: (concentration gradient) C1-C2 x (permeability coefficient/thickness) x area.

Tells us that tissues with more surface area will absorb drugs faster, and tissues with thin membrane barriers - (not very thick.)

Question 15

What is the aqueous solubility of a drug related to?

Answer 15

its degree of ionization - this changes based on the pH of the environment

Question 16

How can you find the fraction of drug molecules in ionized state?

Answer 16

Henderson-Hasselbalch:

log (protonated/unprotonted) = pKa - pH.

Question 17

What is the importance of determining the pH and pKa of drug molecules?

Answer 17

the ionization of the drug depends on the pH of the tissue, such that the pH can determine how much of a drug is soluble in that tissue

Question 18

In what pH is a weak base drug molecule more soluble?

Answer 18

low pH - acidic, donates a proton to the weak base, making it a charged molecule

Question 19

bioavailability

Answer 19

amount of drug absorbed into systemic circulation/amount of drug administered = bioavailability by that route

Question 20

What influences absorption from intramuscular and subcutaneous administration of a drug? why?

Answer 20

blood flow - maintains concentration gradient between tissue and blood vessel

Question 21

How does size of an organ influence distribution into particular tissues?

Answer 21

larger organs are better at maintaining drug blood-tissue concentration gradient. Smaller tissues dissipate the concentration gradient - no where for the tissue drug concentration to go

Question 22

What does high blood flow do to the rate of drug uptake?

Answer 22

increases rate of uptake in well-profused tissues

Question 23

How does solubility of a drug in a particular tissue influence uptake?

Answer 23

If a drug is more soluble in a tissue, then the concentration in the area adjacent to the blood vessel will be lower, maintaining a more favorable concentration gradient.

Question 24

How does binding of a drug to macromolecules in a tissue/compartment affect concentration of drug in different tissues? examples?

Answer 24

If a drug has high affinity for a macromolecules that is primarily present in a certain tissue or compartment, more of the drug will remain in that space. examples: warfarin binds to albumin and remains in the bloodstream, chloroquine binds to extravascular proteins so is not concentrated in the blood

Question 25

What is Vd?

Answer 25

related amount of drug in the body to the amount in the blood

Question 26

Where does drug metabolism occur primarily?

Answer 26

in the liver

Question 27

elimination

Answer 27

conversion of a drug into a biologically inactive derivative/metabolite

Question 28

prodrugs

Answer 28

inactive when administered and active when metabolized by the body - ex: levodopa, minoxidil

Question 29

drugs that have active metabolites?

Answer 29

morphine, some benzodiazepines

Question 30

What is the difference between first-order and zero-order elimination?

Answer 30

Drugs with first-order kinetics are eliminated at a slower rate as their plasma concentration decreases.

Drugs with zero-order kinetics are eliminated at a constant rate regardless of concentration.

Question 31

Examples od drugs with zero-order elimination

Answer 31

ethanol, phenytoin (anticonvulsant), and aspirin at therapeutic or toxic concentrations

Question 32

Loading dose

Answer 32

dose required to achieve a specific plasma concentration with a single dose of the drug.

Loading dose(in mg) = Cp(target plasma concentration) x Vd (volume of distribution)

Question 33

Maintenance dose

Answer 33

dose required for regular administration to maintain a target plasma level - requires restoring the amount of drug that is lost to elimination (clearance, CL)

Maintenance dose (in mg/time) = Cp (target concentration) x CL (clearance)

Question 34

therapeutic window

Answer 34

range between the minimum effective concentration and the minimum toxic concentration.

Question 35

clearance

Answer 35

ratio of elimination of drug to concentration of drug in plasma. units of volume/time

Question 36

Half-life

Answer 36

time required for amount of drug to fall by 50%

Question 37

First-pass effect

Answer 37

elimination of a drug prior to it getting to the bloodstream

Question 38

Steady state

Answer 38

rate of elimination = rate of administration

average total amount of drug in the body does not change over multiple dosing cycles