Lecture 1 part 2

Question 1

Pharmacodynamic properties determines….

Answer 1

the group in which the drug is classified. plays the major role in deciding whether that group is appropriate therapy for the disease

Question 2

pharmacokinetic properties determine…..

Answer 2

the ADME of drugs

great importance in the choice and administration of a particular drug for a particular patient
(a pt with impaired renal function)

Question 3

explain what agonists are.

do they have affinity, efficacy, or both?

Answer 3

drugs that bind to and activate the receptor which directly or indirectly brings about the effect

HAS BOTH AFFINITY AND EFFICACY

Question 4

explain antagonist drugs

do they have affinity, efficacy, or both?

Answer 4

they bind to a receptor and PREVENT binding by other molecules

has only affinity and no efficacy

Question 5

explain how an agonist drug can either directly or indirectly bring about an effect

Answer 5

direct – some receptors have effector machinery in their own molecule (opening of an ion channel or activation of enzyme activity)

indirect – other receptors are linked through 1 or more coupling molecules to a SEPARATE effector molecule

Question 6

give an example and explain an antagonist drug

Answer 6

atropine is an ACh receptor blocker. prevents the access of acetylcholine (and similar agonist drugs) to the ach receptor.

therefore, reduces the effects of acetylcholine

Question 7

what combination produces the MOST effective drug

Answer 7

agonist + allosteric activator

Question 8

what combination produces the least efficacious drug? what about the least potent?

Answer 8

least efficacious = agonist + allosteric inhibitor

least potent = agonist + competitive inhibitor

Question 9

true or false

the allosteric activator could be another drug

Answer 9

TRUE

Question 10

“decreases the action of the agonist and requires a larger dose to get the same effect”

Answer 10

competitive inhibitor

Question 11

“binds at a different site than the agonist and enhances its effect”

Answer 11

allosteric activator

Question 12

explain what a partial agonist is

Answer 12

drug that binds and activates a receptor but has only PARTIAL EFFICACY

Question 13

true or false

a partial agonist binds to fewer receptors than its agonist

Answer 13

FALSE

binds the same amount of receptors but produces a partial effect

Question 14

explain acetylcholinesterase inhibitors

Answer 14

they slow down the destruction of acetylcholine and thus cause cholinomimetic effects that resemble that actions of a cholinoceptor agonist, EVEN THOUGH IT DOES NOT BIND TO CHOLINOCEPTORS

Question 15

give an example of a drug that binds to receptors and activates them, but does not evoke as great of a repsonse as a fyll agonist

Answer 15

pindolol is a beta adrenoceptor partial agonist that can act as an agonist (if no full agonist is present) OR as an antagonist (if a full agonist is present)

Question 16

explain what determines how long the effect of a drug will last

Answer 16

in some cases, the effect only lasts as long as the drug occupies the receptor - therefore, the dissociation of the drug from its receptor automatically stops the effect

in many cases the action may persist AFTER the drug has dissociated (some coupling molecules are still active)

in the case of drugs that COVALENTLY bind, the effect may persist until the drug-receptor complex is destroyed and new receptors are synthesized (phenoxybenzamine(

Question 17

what do many receptor-effector systems incorporate to prevent excessive activation when drug molecules are present for a long period of time??

what is this associated with?

Answer 17

desensitization mechanisms

leads to drug addiction.

take more drug before the drug detaches from its receptor – only 80% of the receptors are available so you will want to keep increasing the dose in order to experience the effect you had at the beginning. leads to withdrawal symptoms if you suddenly stop

Question 18

to function as a receptor, an endogenous molecule must first do ___ and second ____

Answer 18

must 1st be selective in choosing which drug molecules to bind

second, its function must change upon binding so that the function of the biologic system is altered

Question 19

true or false

all molecules in the body that are capable of binding drugs are receptors

Answer 19

FALSE

the drug can bind to a NONregulatory molecule like labumin which results in no detectable change of the biologic system so this is called an INERT BINDING SITE

it has significance bc it affects the distribution of the drug and determines amt of free drug in circulation

Question 20

is it ever possible to directly apply a drug to its target tissue?

Answer 20

YES

a few situations. ex: topical application of an anti inflammatory agent to inflamed skin or mucous membrane

drug can also be given IV and circulate in blood directly to target blood vessels

Question 21

drug is absorbed into where? distributed where?

Answer 21

absorbed into the blood and distributed to the site of action

Question 22

basic drug will be excreted in which urine?

Answer 22

acidic urine

Question 23

drug permeation proceeds by which mechanisms?

Answer 23

4 mechanisms:

-aqueous diffusion
-lipid diffusion
-special carriers
-endocytosis and exocytosis

Question 24

explain aqueous diffusion

Answer 24

occurs across epithelial membrane tight junctions and across endothelial lining of bloof vessels through AQOUS PORES that permit molecules as large as 20,000-30,000 MW

usually driven by concentration gradient – FICKS LAW

Question 25

true or false drugs bound to large plasma proteins will NOT permeate through aqueous pores

Answer 25

TRUE

Question 26

What is the most important limiting factor for drug permeation why

Answer 26

lipid permeation bc of the large number of lipid barriers that separate the compartments of the body

Question 27

what determines how readily the molecule moves between aqueous and lipid media?

Answer 27

lipid: aqueous partition coefficient

Question 28

special carrier molecules exist for which substances?

Answer 28

that are important for cell function but are too large/insoluble in lipid to diffuse passively through membranes peptides amino acids glucose

Question 29

special carriers are __ and ___

Answer 29

saturable and inhibitable

Question 30

can drugs use special carriers for peptides, amino acids, and glucose to cross the membrane?

Answer 30

yes because many drugs resemble naturally occuring peptides/amino acids/sugars

Question 31

endocytosis is responsible for the transport of which endogenous molecules?

Answer 31

iron and vitamin b12

Question 32

give an example of an endogenous susbtance that undergoes exocytosis

Answer 32

many neurotransmitters

Question 33

give Fick's law of diffusion

Answer 33

FLUX = (C1-C2) * [area * permeability coefficient]/thickenss flux = # of molecules per unit time C1 = higher conc C2 = lower conc

Question 34

______ is a major determinant of the motility of a drug

Answer 34

lipid: aqueous partition coefficient determines how readily the drug enters the lipid membrane from the aqueous medium

Question 35

what is the best buffer

Answer 35

our body

Question 36

what is the most important application of the principle of ionization of weak acids and bases

Answer 36

the manipulation of drug excretion by the kidney almost all drugs are filtered at the glomerulus. if drug is in lipid soluble form, a significant portion will be reabsorbed and not excreted

Question 37

if the goal is to accelerate the excretion of the drug....

Answer 37

it is important to PREVENT reabsorption from the tubule

Question 38

explain how the prevention of drug reabsorption at the tubule can be accomplished

Answer 38

by adjusting urine pH so most of the drug is in ionized state and trapped in the urine

Question 39

weak acids are usually excreted faster in ___ urine and vice versa

Answer 39

alkaline