Pharmacodynamics

Question 1

how do drugs exert their effect

Answer 1

• drugs (ligands) initiate, enhance, diminish or terminate biological pathways by binding to receptors on PM of calls
• receptor is the target
• must have adequate size, charge, shape and atomic composition

Question 2

What is the receptor-effector system?

Answer 2

• signal transduction pathway
• the receptor its cellular target and intermediary molecules make up this pathway

Question 3

the effect of the drug is proportional to what?

Answer 3

percentage of receptors occupied by drug

fraction of drug receptors occupied by the drug is dependent on drug concentration in the extracellular fluid

Question 4

what is the limit range for the size of drugs?

Answer 4

• lower limit = 100 MW (minimum size needed to impart specificity of action
• upper limit = 1000 MW: limit allowing reasonable movement throughout the body to sites of action

*note large drugs need to be injected directly into compartments

Question 5

Drugs that mind to receptor through weak bonds must___

Answer 5

be more selective and require precise fit if an interaction is to occur

Question 6

4 types of drug receptors

Answer 6

ion channels, G-protein couples receptor, enzyme-linked, receptor, intracelular receptor

Question 7

Describe ion channel

Answer 7

• a drug binds to ion channel that spans the cell membrane
• causes change in conductance

Question 8

describe G-protein couples receptor

Answer 8

• Heptahelical receptors spanning the plasma membrane
• functionally couples to G proteins
• drugs can influence the action by binding to extracellular surfect or transmembrane region of the receptor

Question 9

describe enyme-linked receptor

Answer 9

• drug can bind to extracellular domain of a transmembrane receptor and cause a change in signaling within the cell by activatnig or inhibiting an enzymatic intracellular domain of the same receptor

Question 10

Describe intracellular receptor

Answer 10

• drugs diffuse through the plasma membrane and bind to cytoplasmic or nuclear receptors
• many lipophilic drugs use this pathway (drugs that bind to steroid hormone receptors like estrogen and progesterone receptors_
• some drugs can inhibit enzymes in the extracellular space without crossing the plasma membrane

Question 11

What are the two states of a drug receptor

Answer 11

• most drugs act on receptors that have an endogenous ligand (neurotransmitters and hormones)
• many receptors have active and inactive state existing in reversible equilibrium
• many drugs function as ligands for these receptors by influencing the probabilty that they are in the active or inactive state

Question 12

what is an agonist

Answer 12

• a drug that upon binding favours the active conformation
• full agonist activates to maximal extent possible

Question 13

what is an antagonist

Answer 13

0 drug that prevents agonist-induced activation of the receptor

• inhibits the ability of target to be activated or inactivated by physiologic or pharmacologic agonists

Question 14

what are partial and inverse agonists

Answer 14

• do not fit into agonist or antagonist
• partial agonist produces a submaximal response upon binding
• inverse cause constituatively active targets to become inactive

Question 15

How are pharmacodynamics quantified

Answer 15

• the relationship between the dose (conc) of the drug and the patient’s response to that drug
• *dose response relationship is closely related to drug-receptor binding relationship for many drugs

Question 16

what are the two major types of dose-response relationships?

Answer 16

• graded and quantal
• graded describe the effect of various doses of the drug on an individual
• quantal shows effect of various doses on a population of individuals

Question 17

what are teh axis of the DRC

Answer 17

• dose response curve
• observed drug effect (% maximal response) as function of concentration

Question 18

how do you find potency and efficacy on the DRC

Answer 18

Potency = EC50: concentration at which drug elicits 50% of maximal response

– comparison of EC50 values between drugs acting at same receptors gives a measure of relative potency

*most potent not necessarily the most efficacious

Efficacy = Emax: maximal response produced by drug

*comparison of maximal respose of drugs at the same receptor gives a measure of relative efficacy

Question 19

linear vs semilogarithmic dose response curves

Answer 19

A = linear graph of graded dose, B = Semilogarithmic graph od same dose

• EC50 = potency of drug
• Drug A is more potent bc it elicits a half-maximal effect as a lower conc then drug B
• Drug a and B exhibit the same efficacy (same maximal response)

Question 21

Describe competitive antagomism

Answer 21

• Antagonist has affinity for receptor but no efficacy
• Competes with agonist at site; higher agonist concentration can overcome the effects of a fixed dose of antagonist
• Antagonist produces parallel rightward shift in dose-response curve
• EC50 value larger in presence of antagonist
• Emax remains the same (potency reduced efficacy unaffected)

*when antagonist and antagonist are both competing the max efficacy can still be reached, just need a higher conc of agonist so dose-response shifts to the right

Question 22

Describe Non-competative antagonism

Answer 22

• antagonist very slowly dissociates or is irreversible bound
• also causes a rightward shift to DRC
• EC50 value is typically unaffected and Emax is reduced with a non-competative antagonist
• no matter how much drug you administer cant rich maximum response

(efficacy decreases, potency unchanges)

Question 23

What is desensitization

Answer 23

• effect of a drug often diminishes when given repeatedly
• tolerance = the gradual decrease in responsiveness to chronic drug administration

Question 24

what are possible mechanisms for desensitization

Answer 24

• temporary inaccessibility of receptor by phosphorylation
• sequestration of receptors in cell by internalization
• Reduce synthesis of new receptors

Question 25

what is tachyphylaxis?

Answer 25

• more rapid (acute) form of tolerance
• occurs with some drugs on the second dose

Question 26

what is supersensitivity

Answer 26

• increase in response to an agonist
• due to chornic under-stimulation of the receptor which causes the cel to expressed an increased receptor numbers
• may also occur following antagonist use