pharmacodynamics

Question 1

pharmacodynamics

Answer 1

study of effect of drugs and mechanism of action on body

“what drug does to the animal”

Question 2

physical interaction- non specific

Answer 2

• osmotic diuretics
• antacids
• radioactive iodine

Question 3

non-receptor interactions (biological)

Answer 3

• ion channels– can be physically obstructed (Lidocaine)
• enzymes–analogues may compete with real substrate for binding on enzyme, false substrates
• carrier proteins–small, polar molecules may require transport proteins

Question 4

receptor interactions (biological)

Answer 4

• recognition sites for endogenous chemical messengers
• Ligand-gated ion channels (ionotropic)- fast
• G-protein coupled receptor (Metabotropic)–slower but allows extracellular signal to be turned into intracellular signal and amplified

Question 5

G-Protein coupled receptor

Answer 5

• extracellular signal to intracellular signal
• 40% of pharmaceuticals work this way
• intracellular systems: cAMP and PIP2 with PLC
• G alpha subunits: s- stimulatory, i-inhibitory, q-couples to PLC
• s stimulates cAMP pathway, i inhibits cAMP pathway

Question 6

monoamines

Answer 6

-epinephrine, norepinephrine, dopamine, 5HT, histamine

Question 7

small neurotransmitters

Answer 7

-Acetylcholine, GABA, glutamate, adenosine

Question 8

Peptide neurotransmitter and hormones

Answer 8

-opioid, oxytocin, vasopressin

Question 9

sensory modalities

Answer 9

odorants, tastetants

Question 10

kinase-linked receptors

Answer 10

• direct activation of enzymes
• extracellular receptor intracellular enzymatic activity
• phosporylation of proteins, activates receptors
• insulin, IGF-1, cytokines, growth promoting hormones

Question 11

nuclear receptors

Answer 11

-intracellular to nucleus
-transcription factor receptors
-receptors in cytoplasm, get to nucleus
-alter gene transcription from DNA
=steroids, thyroid hormones, inflammatory mediators

Question 12

True/False– endogenous neurotransmitters are specific to one receptor

Answer 12

false- endogenous NT often bind more than one type of receptor

Question 13

receptor upregulation

Answer 13

-increase of receptors and drug effect

Question 14

receptor down regulation

Answer 14

• decrease in number of receptors and effect
• can be by internalizing, recycling, sequestration, degradation
• part of normal cell metabolism

Question 15

tolerance

Answer 15

-decrease in responsiveness of drug when given repeatedly over days to months

Question 16

tachyphylaxis

Answer 16

-acute tolerance, develops in short period of time

Question 17

ligand

Answer 17

-anything that binds to recognition site (agonist, antagonist, inverse agonist, mixed agonist-antagonist)

Question 18

agonist

Answer 18

mimics effects of endogenous ligand

-ex: fentanyl on mu opiod receptors

Question 19

full agonist

Answer 19

• ex: morphine
• titrational effect
• full cell/tissue response

Question 20

partial agonist

Answer 20

• ex: buprenorphine
• binds to receptor, does not cause as much effect as full agonist, blocks receptor from full agonist binding
• ceiling effect

Question 21

antagonist

Answer 21

binds to same receptor and prevents agonist from binding

Question 22

competitive agonist (most common)

Answer 22

-reversible, concentration dependent binding

Question 23

non-competitive agonism (less common)

Answer 23

• irreversible, covalent binding

- prevents action of agonist at any concentration

Question 24

inverse agonist

Answer 24

-binds to receptor site, produces opposite effect of agonist

Question 25

mixed agonist antagonist

Answer 25

- binds to more than one receptor - acts as agonist on one type of receptor and antagonist on others - ex: butorphanol, agonist on K opioid receptors, antagonist mu opioid receptors

Question 26

potency

Answer 26

- concentration of drug needed to produce effect - dose usually accounts for potency of drug (more potent drug will produce same effect with smaller dose/concentration than less potent drug )

Question 27

slope of drug- concentration-effect curve

Answer 27

linear in ~20-80% range

Question 28

maximal effect (ceiling)

Answer 28

-point at which increasing concentration does not give greater response

Question 29

efficacy

Answer 29

- maximal effect a drug can have | - partial agonist may never be able to achieve full efficacy

Question 30

effective concentration (EC50)

Answer 30

- 50% maximal response in vitro | - relates to concentration of drug at site

Question 31

effective dose (ED50)

Answer 31

- desired effect in 50% of population - relates to dose given to individuals and observed effect - similarly can look at dose that causes toxic effect/death (LD50)

Question 32

therapeutic index

Answer 32

(TI=LD50/ED50) - ratio used to evaluate safety of drug - narrow therapeutic index (small number, closer to 1) dose required to cause death is close to that to cause therapeutic effect - wide therapeutic effect: dose required to cause death is much higher than that to cause therapeutic effect

Question 33

standard safety margin

Answer 33

- more comprehensive and accurate assessment of drug safety | - SSM= LD1-ED99/ED99

Question 34

onset of action

Answer 34

-time required after drug administration for response to be observed (latent period)

Question 35

duration of action

Answer 35

-length of time that drug is effective (onset to termination of action)