pharmacodynamics

Question 1

partial agonists

Answer 1

elicit less than max response.

can act as competitive inhibitor

Question 2

inverse agonist

Answer 2

reverse constitutive activity

can act as competitive inhibitor

Question 3

wafarin

Answer 3

has very low TI ~1 meaning that ED is right at LD.

used to prevent clots after surgery and atrial fibrillation

Question 4

Diazepam/Valium

Answer 4

allosteric activator of GABAa
Increase opening of GABAa Cl- channels for increased inhibition
Good TI ~100

Question 5

Serotonin 5HT-3

Answer 5

Excitatory ligand-gated ion channel (LGIC)

non-selective cation channel

Question 6

glutamate-AMPA

Answer 6

Excitatory LGIC
non-selective LG Na+ channels
fast excitatory CNS transmission - desensitize rapidly
FASTEST known channel

Question 7

glutamate-NMDA

Answer 7

Excitatory ligand-gated ion channel (LGIC)
non-selective cation channel
Ca2+ entry: good for memory, bad for excitotoxicity (Alzheimers)

Question 8

GABAa

Answer 8

inhibitory LGIC

allows Cl- entry for inhibition

Question 9

familial startle disease (hyperekplexia)

Answer 9

due to defective glycine receptors. over exaggerated response to noise

Question 10

all the a and B adrenoreceptors and muscarinic receptors for ACh

Answer 10

GPCR

Question 11

GPCR Membrane Delimited

Answer 11

2nd fasted signaling after LGIC
subscript 2 or B
Inhibitory motif - stimulate K+ channels, inhibit Ca2+ channels, inhibit adenylyl cyclase

Question 12

GPCR Synthesis of 2nd messengers

Answer 12

• 3rd fastest
• subscript 1 or odd#
• aG-protein + GTP -> IP3 -> Ca2+ release -> smooth muscle contraction
• aG-protein also stimulates creating cAMP

Question 13

GPCR protein phosphorylation

Answer 13

• aG-protein activate adenylyl cyclase -> produce cAMP -> activate PKA -> phosphorylate proteins -> cardiac muscle contraction B1 AND smooth muscle relaxation B2
• phosphorylated proteins also activate phophatase that dephosphorylates proteins.
• phosphodiesterase recycles cAMP -> AMP

Question 14

RTKs and transmembrane receptors

Answer 14

ligand binds -> receptors dimerize -> Y phosphorylation -> scaffold protein recruited and activate 3 kinases -> altered genes -> biological response

• Constitutively active Y kinase often seen in cancer

Question 15

RTKs and transmembrane receptors pathway

Answer 15

ligand binds -> receptors dimerize -> Y phosphorylation -> scaffold protein recruited and activate 3 kinases -> altered genes -> biological response

• Constitutively active Y kinase often seen in cancer

Question 16

EGF / Growth Factors pathway

Answer 16

use the RAS/MAPK pathway primarily -> alter gene transcription

Question 17

insulin pathway

Answer 17

via RTK use PI3-KINASE/RAS/mTOR pathway -> increase in gene translation -> increase fuel storage

Question 18

cytokine and IL/interferon pathway

Answer 18

• use the JAK/STAT pathway -> increase gene transcription coordinate immune response.
• IL6 helps with wound healing

Question 19

cytoplasmic and nuclear receptors

Answer 19

• corticosteroid binds to glucocorticoid receptor -> HSP-90 inhibitor dissociate -> receptor-steroid complex dimerize -> translocate to nucleus -> changes gene behavior
• involved in inhibiting inflammatory reponses

Question 20

cytoplasmic and nuclear receptors

Answer 20

• corticosteroid binds to glucocorticoid receptor -> HSP-90 inhibitor dissociate -> receptor-steroid complex dimerize -> translocate to nucleus -> changes gene behavior
• involved in inhibiting inflammatory responses

Question 21

Mg2+, Mn2+, Co2+ etc (multivalent cations)

Answer 21

impermanent cations block voltage-gated Ca2+ channels by competing with Ca2+ -> reduces release of neurotrans

Question 22

decrease bulk [Na+]

Answer 22

decrease size of AP

Question 23

increase bulk [K+]

Answer 23

cell membrane depolarize due to changes in K+ leak channels - less K+ flows out of cell bc concentration gradient not as big -> K+ stay in cell causing depolarization

Question 24

changes in conductance on membrane and bulk concentraion

Answer 24

• does affect local membrane

- does NOT change bulk solution and Nernst potential same

Question 25

GABAa receptors

Answer 25

Cl- for developing and adult

Question 26

block K+ channels in cardiac and smooth muscle

Answer 26

cells cannot repolarize properly?? longer AP

Question 27

``` Katp channel (activates and inhibits) ```

Answer 27

in pancreas and smooth muscle - Targets for sulfonylureas - drug used to treat diabetes - Low ATP -> channels open -> K+ efflux -> membrane hyperpolarize -> reduce energy consumption for ion pumps to restore membrane after AP - Large role in insulin secretion in islet B-cells. Sulfonylureas INHIBIT channel -> allow membrane depolarization -> insulin secretion - Minoxidil - antihypertensive that activates channels in smooth muscle to relax arterioles