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CV PHARM...Functional Aspects of ANS > General > Flashcards

General Flashcards

1
Q

What is the major disadvantage of clinical therapy involving drugs that act on ANS?

A

Lack of specificity

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2
Q

Parasympathetics control…

A

cardiac and smooth muscle
gland cells
nerve terminals

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3
Q

Parasympathetic presynaptic

A

nicotinic cholinergic

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4
Q

Parasympathetic postsynaptic

A

muscarinic cholinergic

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5
Q

Sympathetic (sweat glands) postsynaptic

A

muscarinic cholinergic

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6
Q

postsynaptic motor neurons

A

nicotinic cholinergic

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7
Q

sympathetic (cardiac and smooth muscle, gland cells, nerve terminals) postsynaptic motor neurons

A

adrenergic (alpha and beta)

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8
Q

Sympathetic (renal vascular smooth muscle) postsynaptic motor neuron

A

dopamine receptor

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9
Q

Adrenal medulla

A

nicotinic cholinergic receptor

releases Epi, NE

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10
Q

Cholinergic receptor types

A

muscarinic

Nicotinic

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11
Q

muscarinic subtypes

A

M1, M3, M5…Gq coupled

M2, M4….Gi coupled

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12
Q

Gq coupled muscarinic receptors

A

M1
M3
M5

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13
Q

Gi coupled muscarinic receptors

A

M2

M4

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14
Q

Nicotinic subtypes

A

Nm (neuromuscular/muscle type)

Nn (neuronal, or ganglion type)

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15
Q

Adrenergic subtypes

A

alpha 1, alpha 2

beta 1, beta 2, [beta 3]

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16
Q

Dopamine receptor subtypes

A

D1-D5

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17
Q

Other receptors

A

for NANC transmitters

  • -NO
  • -vasoactive intestinal peptide
  • -neuropeptide Y
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18
Q

5 key features of neurotransmitter function that provide targets for drug therapy?

A 
Synthesis
Storage
Release
Reuptake
Degredation
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19
Q

If Synthesis and Storage blocked…

A

usually rate-limiting steps, so…

produce long-term effects, but not immediately effective

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20
Q

If release blocked…

A

Rapid action and effective

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21
Q

If reuptake blocked…

A

Increased synaptic neurotransmitter concentrations (selective or non-selective)

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22
Q

If metabolism blocked…

A

reversible or irreversible:

increases transmitter levels

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23
Q

If recognition is blocked…

A

Receptor antagonists and agonists…high specificity

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24
Q

Sympathomimetic

A

mimicks… effects of impulses conveyed by adrenergic postganglionic fibers

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25
Q

Sympatholytic

A

anti adrenergic…

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26
Q

Fundamental difference b/w methods of inactivation of acetylcholine vs. norepinephrine

A

acetylcholine–>degraded

NE–>reuptake

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27
Q

hemicholiniums

A

EXPERIMENTAL, NOT CLINICAL

block CHT (that transports Na and choline in)

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28
Q

Vesamicol

A

EXPERIMENTAL,, NOT CLINICAL

blocks VAT

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29
Q

Cotransmitters

A

modulation (enhance or diminish cholinergic activity)

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30
Q

Cholinergic Autoreceptors

A

ACh activates the receptors, but this inhibits further release of ACh

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31
Q

Blocking the Ca channels…

A

inhibits sweating?

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32
Q

Metabotropic

A

function through secondary messanger system

Muscarinic receptors

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33
Q

Ionotropic

A

ion channels

nicotinic

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34
Q

M1, M3, M5

A

Metabotropic

Gq
–>PLC–>IP3–>INCREASES INTRACELLULAR CALCIUM!!!

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35
Q

M2, M4

A

Metabotropic

Gi
blocks adenylate cyclase from making cAMP
inhibitory response
opens K channels (GiRK)

36
Q

nicotinic receptors

A

ionotropic

increase intracellular Calcium, Na, PKC
amplifies effect

37
Q

If drug not susceptible to cholineterase, then…

A

improves longevity of drug

i.e. carbachol chloride and bethanechol chloride

38
Q

metyrosine

A

inhibits tyrosine hydroxylase

tyrosine synthesis to dopamine

39
Q

Reserpine

A

Blocks VMAT

40
Q

Cocaine, tricylic antidepressants

A 
block NET
(prevents neurotransmitters from being broken down/ repackaged)
41
Q

What process is critical for catecholamine neurotransmission?

A

reuptake!

42
Q

Phenylephrine
Methoxamine
(receptor affinity)

A

alpha agonists

alpha1>alpha2»»»»»>beta

43
Q

Clonidine
methylmorepinephrine
(receptor affinity)

A

alpha agonists

alpha2>alpha1»»»»»»beta

44
Q

Norepinephrine (receptor affinity)

A

mixed alpha and beta agonists

alpha1=alpha2

beta1»beta2

45
Q

epinephrine (receptor affinity)

A

mixed alpha and beta agonists

alpha1=alpha2

beta1=beta2

46
Q

Does norepinephrine widen pulse pressure?

A

no

47
Q

Why does epiniephrine widen the pulse pressure?

A

b/c of beta 2 receptors

48
Q

dobutamine (receptor affinity)

A

beta agonists

beta1>beta2»»»>alpha

49
Q

isoproterenol

A

beta agonist

beta1=beta2»»»alpha

50
Q

Albuterol,
terbutaline
metaproterenol
(receptor affinity)

A

beta agonists

beta2»beta1»»»alpha

51
Q

dopamine

A

dopamine agonist

d1=d2»beta»alpha

52
Q

Fenoldopam

A

dopamine agonist

D1»D2

53
Q

ACh and muscarinic receptors have inhibitory effect on…

A

adrenergic and enteric neuron terminals

54
Q

NE and alpha2 receptors have inhibitory effect on…

A

adrenergic neuron terminals

55
Q

alpha1 adrenergic receptors

A

metabotrophic
Gq
GDP–>GTP–>phospholipase C–>IP3–>Calcium!!!–>protein kinase activation

56
Q

beta catechloamine receptors

A

Metabotrophic
stimulatory
Gs
–>GDP–>GTP–>adenylate cyclase–>cAMP–>protein kinease–>enzyme-PO4–>biologic effect

57
Q

alpha2 adrenergic receptors

A

Metabotrophic
inhibitory
Gi
–>GDP–>GTP–>BLOCKS adenylate cyclase!!!

58
Q

beta2 agonist effect on smooth muscle

A

relaxes

asthma treatment!

59
Q

Ca channel blockers effect on smooth muscle

A

relaxes

60
Q

COMT

catechol-O-methyl transferase

A

drug target

involved in catecholamine degredation/ synthesis

61
Q

MAO

monoamine oxidase

A

drug target

involved in catecholamine degredation/ synthesis

62
Q

Pheochromocytma

A

chromaffin tumors typically arising in adrenal glands secreting excessive catecholamines

63
Q

how to diagnose pheochromocytoma

A

look for urinary catecholamine metabolites metanephrine and vanillylmandelic acid

64
Q

L-DOPA

A

dopamine precursor
can be used in treatment of Parkinson’s
–b/c can cross blood brain barrier (unlike dopamine)
–give w/ inhibitors in the periphery (where we don’t want its effects)

65
Q

MAOA inhibitors

A

block tyramine metabolism

  • ->increased tyramine in blood circulation
  • ->cheese rxn!! (must avoid many many foods)
66
Q

Desensitization process

A
  1. G-protein coupled receptor
  2. drug ligand binds (dynamics of binding somewhat different than endogenous ligand)
  3. duration and extent of drug binding causes…
  4. accumulation of BETA-ARRESTINS
  5. Receptors taken down from cell surface into cell in vesicles
  6. fewer receptors means “less bang for the buck”
67
Q

beta-arrestins

A

proteins involved in desensitization

68
Q

Tachyphylaxis

A

“loss of activity” in relatively short space of time (tolerance to drug b/c of chronic, constant administration)

  • -changes of metabolism
  • -clonal expansion of resistant tumor
  • -ect
69
Q

what can stimulate glycogenolysis and gluconeogenesis in liver and why?

A

alpha1 and beta2 receptors in response to hypoglycemia

70
Q

Why are beta blockers a problem for diabetics?

A

–nonselective beta blockers delay recovery from hypoglycemia in type 1 diabetics

–can interfere w/ counter-regulatory effects by blunting perception of hypoglycemic symptoms (tremor, tachycardia, nervousness)

Beta1-selective antagonist is preferred!

71
Q

Pancreatic beta cells and insulin…

alpha2 activation significantly…

A

decreases insulin secretion

72
Q

Pancreatic beta cells and insulin…

beta-2 activation…

A

inreases insulin secretion

73
Q

The target tissue and insulin sensitivity…

beta receptor activation…

A

increases receptor sensitivity

74
Q

The target tissue and insulin sensitivity…

beta-blockers

A

decrease insulin sensitivity

75
Q

The target tissue and insulin sensitivity…

beta-blockers (vasodilating…3rd generation… drugs

A

increase insulin sensitivity in pts w/ insulin resistance

76
Q

Hormone sensitive lipase…

non-selective beta-blockers…

A

lower HDL cholesterol and increase TGs

little effect on LDL and total cholesterol

77
Q

alpha1 receptors involved in…

A

vascular tone
urethral tone
ejactulation process
maintaining contractile state of penile arteries

78
Q

alpha1 receptor blockage can result in…

A

orthostatic hypotension
relieved symptoms of BPH
sexual dysfunction
persistent priapism

79
Q

Why, when alpha1-receptors blocked by promethazine, does the blood pressure drop, but the heart rate is still able to increase?

A

the receptors blocked are dominant in vessels but not in heart

80
Q

peripheral anticholinergic effects

A

no innervation of blood vessels, but there are still receptors

xerostomia caused by ACh inhibition in salivary glands

treatment of hypersalivation

blurred vision; cycloplegia; mydriasis

constipation (b/c inhibition of GI smooth muscle)
IBS
urinary retention secondary to decreased muscle tone

muscarinic agonist or AChE inhibitor

81
Q

NO

A

vasodilator

GDP–>cGMP–>smooth muscle relaxation

82
Q

Sidenafil (viagra)

A

vasodilator
inhibits cGMP break down to GMP
–>prolonged smooth muscle relaxation

83
Q

what can blocking cholinergic and GABAergic pathways connected in hippocampus and basal forebrain complex do?

A

make us sleepy

84
Q

Drugs w/ anticholinergic activity

A

1st generation antihistamines
antidepressants
etc.

85
Q

Sumpathetic NS drugs

A 
alpha-blockers
beta-blockers
centrally-acting drugs
transmitter depleting drugs
ganglionic blocking drugs
86
Q

cardiotonic drugs

A

beta-agonists
alpha-agonists
muscarinic antagonists

CV PHARM...Functional Aspects of ANS (3 decks)

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