Unit 2 - Autonomics IV Flashcards Preview

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Flashcards in Unit 2 - Autonomics IV Deck (45):
1

explain synthesis of NE and E in adrenergic varicosity?

tyrosine (into cytoplasm) --> DOPA --> dopamine --> NE (vesicle) --> E (adrenal medulla)

2

is NE or E a neurotransmitter or a neurohormone?

NE is a neurotransmitter
E is a neurohormone

3

what is the receptor interaction and effector cell response of NE and E?

second messenger amplification

4

how do D1 (dopamine) exert its second messenger effect?

stimulatory GPCR increases cAMP (like beta1/2/3)

5

what is the adrenergic receptor excitation response?

constriction; Ca++ is made available to myofibrils and increases tension
-Ca++ from intracellular stores and/or transport from extracellular

6

what is the adrenergic receptor inhibition response?

relaxation; Ca++ is made unavailable to myofibrils and reduces tension
-Ca++ is taken into intracellular stores and/or pumped out

7

what is the adrenergic receptor metabolic response?

activation of AC
-increased liver glycogenolysis
-increase in plasma glucose and FFA

8

what are the 3 ways specifically NE can "terminate" its action?

1. neuronal reuptake (neuron-specific)
2. effector cell uptake (non-specific and high capacity); extra-neuronal
3. diffusion into capillaries

9

what is the primary mechanism for terminating ACh? how is this different from NE?

enzymatic hydrolysis
-NE is reuptake

10

what and where is MAO?

monoamine oxidase on mitochondria surface
-metabolize NE, E, and other exogenous adrenergic drugs

11

what and where is COMT?

catechol-o-methyltransferase in cytoplasm of many cells, especially liver
-metabolize NE, E, and other exogenous adrenergic drugs

12

what are the major metabolites of NE/E that are measured in urine/plasma?

normetanephrine, metanephrine, VMA, MHPG
-for diagnostic purposes (increased plasma metanephrine indicates pheochromocytoma)

13

what does alpha-me-tyrosine do to modify chemical transmission?

decreases synthesis of NE (sympathetic) by decreasing pre-synaptic Ca++ influx

14

what does amphetamine do to modify chemical transmission?

increases release of NE (sympathetic)

15

what does isoproterenol do to modify chemical transmission?

combine with receptor to increase NE (sympathetic)
-increases post-synaptic Ca++ influx and second messengers

16

what does propranolol do to modify chemical transmission?

antagonist to beta-receptor sites to decrease NE (sympathetic)
-decreases post-synaptic Ca++ influx and second messengers

17

what does cocaine do to modify chemical transmission?

increases termination step such that synapse activity increases

18

what is the prominent effector organ and response to receptor activation of beta 1?

heart - increased heart rate and force of contraction
kidney - renin secretion

19

what is the prominent effector organ and response to receptor activation of beta 2?

arterioles (and arteries in skeletal muscle, coronary) - dilation
bronchial muscle - relaxation
pregnant uterus - N/A
several other sites - metabolic effects increase

20

what is the prominent effector organ and response to receptor activation of beta 3?

adipose tissue (lipocytes) - lipolysis and thermogenesis increase

21

what is the prominent effector organ and response to receptor activation of alpha 1?

arterioles in skin, mucosa, viscera, and kidney - constriction (resistance vessels)
veins - constriction
uterus and spleen - contraction

22

what is the prominent effector organ and response to receptor activation of alpha 2?

presynaptic nerve endings - inhibit NE release and ACh release (gut)
postsynaptic in CNS - decreased peripheral sympathetic tone

23

what is the prominent effector organ and response to receptor activation of D1?

renal, mesenteric, and cerebral arterioles - dilation

24

what are the agonist/antagonist for a1?

agonist: phenylephrine
antagonist: prazosin

25

what are the agonist/antagonist for a2?

agonist: clonidine
antagonist: yohimbine

26

what are the agonist/antagonist for D1?

agonist: fenoldopam
antagonist: N/A

27

what are the agonist/antagonist for B1?

agonist: dobutamine
antagonist: atenolol

28

what are the agonist/antagonist for B2?

agonist: albuterol
antagonist: butoxamine

29

what are the agonist/antagonist for B3?

N/A for both

30

what are the agonist/antagonist for BOTH B1/2?

non-selective
agonist: isoproterenol
antagonist: propranolol

31

explain presynaptic and postsynaptic autoreceptor regulation of NE release?

stimulation of presynaptic a2 receptors inhibits NE release from nerve terminal, while drugs that block postsynaptic a2 receptors enhance NE release

32

how are organ responses to neurotransmitters/drugs determined?

by differences in receptor populations and receptor densities

33

explain the adrenergic receptors on skeletal muscle vessels?

have both a1 and B2
-low concentration: B2 (lower threshold, for physiologic response from sympathetic (adrenal) stimulation) --> relaxation and dilation
-high concentration: a1 (higher threshold and "dominant constriction" only seen in high pharmacological EPI in lab or shock

34

what is the guiding principle to therapeutic drugs?

selectivity to get max effects with minimum side effects

35

for NE drugs, what does methylation at N seem to do?

NE (no methyl) is a1/2 (and less so B1)
E (1 methyl) is a1/2 and B2
isoproterenol (3 methyl) is B1/2 only (no a1 b/c too much methyl)

36

what are the characteristic sympathomimetics for phenylephrine?

a1

37

what are the characteristic sympathomimetics for clinidine

a2

38

what are the characteristic sympathomimetics for NE?

a1, B1, (a2)

39

what are the characteristic sympathomimetics for E?

a1, B1, B2, (+a2)

40

what are the characteristic sympathomimetics for isoproterenol?

B1/2

41

what are the characteristic sympathomimetics for dopamine

D1, a1, B1

42

what are agonist potencies at adrenergic receptors for B1?

ISO > E >= NE > D

43

what are agonist potencies at adrenergic receptors for B2?

ISO > E >> NE >> D

44

what are agonist potencies at adrenergic receptors for a1?

E >= NE > D >> ISO

45

what are agonist potencies at adrenergic receptors for a2?

CLON > E >= NE >> ISO