Pharmacodynamics 2 (ppt 8)

Question 1

Synergism

Answer 1

• combined effect of 2 drugs is greater than the sum of their effects when given separately

Question 2

Additivity

Answer 2

A drug adds to the potency of the first drug

Question 3

Potentiation

Answer 3

One drug doesn’t cause a response on its own, but enhances the response of another drug

Question 4

Prodrugs must be metabolized by…

Answer 4

Liver

Question 5

Magnitude of pharmacological response is proportionally related to

Answer 5

Drug conc. @ receptor site

Question 6

5 types of receptors or signaling mech. for drug actions

Answer 6

• steroid
• tyrosine kinase
• JAK-STAT
• ion channel
• GPCR

Question 7

Ligand gated ion-channel

Answer 7

• 5 subunits: alpha, beta, gamma, delta
• ACh binding to extracellular a subunit site=open channel

Question 8

G-protein coupled receptor

Answer 8

• regulate effector proteins via mediation of transducers (g proteins)
• ligands: hormones, pheromones, neurotransmitters, autacoids, xenobiotics

Question 9

G proteins

Answer 9

• heterotrimeric molecules
• 3 subunits attached to inner surface: alpha, beta, gamma
• beta gamma comples
• 4 families: G-alphas, G-alphai/G-alpha0, G-alpha q, G-alpha 12/13

Question 10

Enzyme-linked effector systems

Answer 10

Second messengers

Question 11

Enzyme-linked effector system types

Answer 11

• adenylate cyclase: cAMP system
• Phospholipase C: IP3-DAG system
• Phospholipase A2: A A system

Question 12

Gs family

Answer 12

• alpha s subunit
• positive action on adenylate cyclase & calcium channels
• increase heart rate, stim. neuronal activity
• ex: adrenergic beta-R

Question 13

Gi/G0 family

Answer 13

• alpha subunit: i & 0
• negative effect on adenylate cyclase and Ca2+ channels
• positive effect on K+ channel
• smooth m. relaxant, depresses neuronal activity
• ex: muscarinic M2-R, Opioid

Question 14

Gq/11 family

Answer 14

• alpha subunits: q, 11, 14, 15, 16
• positive effect on Phospholipase C
• smooth m. contraction, Ca2+ flux
• ex: adrenergic alpha 1R, Histamine H1

Question 15

G12/13 family

Answer 15

• alpha subunits: 12 and 13
• positive effects on Rho family of GTPases, and Na+/H+ exchange
• cytoskeletal funct., smooth m. contraction

Question 16

Tyrosine kinase receptor (TKR) states

Answer 16

• C1 State: inactive
• C2 state: active

Question 17

C-1 state

Answer 17

• transmembrane receptors have large extracellular binding sites, intracellular tails, and enxyme

Question 18

C-2 state

Answer 18

• ligan binds to both receptors, dimer formed, tyrosine kinase portion activated, ATP phosphorylates tyrosines on tail of other polypeptide, downstream signaling

Question 19

Nuclear receptors

Answer 19

• may be located in cytosol and migrate to nucleus post-binding
• long-lasting effect
• Ex: glucocorticoid receptos

Question 20

Up-regulation of receptors

Answer 20

• body increases # of receptors
• seen when receptors continuously deprived of ligands or continued antagonist use
• state of supersensitization
• ex: rebound hypertension in K9s following withdrawal of beta-adrenoceptor blockers (atenolol)

Question 21

Down-regulation

Answer 21

• cell decreases # receptors or protein population
• diminishes drug effects (tissues continuously exposed to agonist-> over-activation)
• drug-receptor complex undergoes endocytosis then metabolized
• leads to desensitization or refractoriness
• ex: continuous exposure to insulin