Darmani - Pharmacodynamics

Question 1

What are the binding forces in drug receptor interactions

Answer 1

1. covalent bond: long lasting bond between e-; cant be seperated
2. ionic bond: electrostatic force attraction between charged ions; can be sep under physiological conditions
3. hydrogen bond: special kind of ionic bond; ability of a proton to accept an e- from donor atoms such as O or N.
4. van der waals bond; between nonpolar moleclues; very weak

Question 2

An ____ binds a receptor and produces a signal. Allosteric molecule can alter the affinity or efficacy of an agonist.

Answer 2

agonist

Question 3

What are four diff receptor superfamilies

Answer 3

1. Receptors coupled to ion channels aka ionotropic receptors. Control the fastest synaptic events in the nervous system.
2. G protein coupled receptors
3. Enzyme linked receptors: mediate action of growth factors, cytokines, and insulin
4. Intracellular receptors:

Question 4

The two impt signaling pathway for enzyme linked receptors are

Answer 4

1. Ras/Raf mitogen activated protein (MAPk)

2. Jak/Stat

Question 5

what do Type 1 intracellular receptors target

Answer 5

sex hormones, glucoriticoid receptors and mineralocorticoid receptors

Question 6

what do type 2 intracellular receptors include

Answer 6

thyroid hormone, vitamin A, D, and retinoid receptors

Question 7

How are G proteins divided

Answer 7

1. heterotrimer: alpha, beta, gamma
2. small G proteins; bind guanine nucleotides, possess intrinsic GTPase activity and cycle through GDP and GTP bound forms

Question 8

the alpha subunits bind and hydrolyze activities, beta and gamma subunits are very ____ and for beta gamma complex which serve to ____ the G protein to the membrane.

Answer 8

hydrophobic; anchor

Question 9

In the resting state, G protein exists as a alpha beta gamma trimer with GDP. when a drug binds to and activates a receptor, it produces a conformational change in the receptor which causes it associate with ____ complex which causes GDP to be replaced with GTP.

Answer 9

alpha beta gamma

Question 10

what is an impt hallmark of G protein mediated signal transduction

Answer 10

amplification of the primary signal

Question 11

GPCRS can also activate the ____G protein dependent pathway such as the mitogen activated protein kinase cascade

Answer 11

non

Question 12

What is functional selectivity

Answer 12

agonist may activate a specific signaling pathway via a GPCR that is involved in multiple intracellular signaling

Question 13

What are some targets of G proteins

Answer 13

1. Adenyl cyclase
2. Guanylly cyclase
3. phospholipase C
4. phospholipase A
5. ion channels

Question 14

what are the second mesengers

Answer 14

1. cAMP
2. cGMP
3. IP3
4. DAG
5. Ca++

Question 15

what are the third messengers

Answer 15

PKA
PKC
PKG

Question 16

Persistent agonist stimulation ____regulate and decrease receptor number of density. Chronic deprivation of receptor excitiation ____ regulate an increase receptor number or density

Answer 16

up; down

Question 17

what are the 2 types of densitization? what does it depend on?

Answer 17

1. homologous; GPCR kinases; only phosphyorylate agonist occupied receptors
2. heterologous; 2nd messenger kinases: PKA and PKC; agonist independent and other receptors
   - protein phosphorylation