ANS: Presynaptic Drugs Flashcards
(72 cards)
1
Q
Mecamylamine MOA
A
Noncompetitive antagonist of Nn receptors (no effect on Nm)
2
Q
Mecamylamine therapeutic use
A
Antihypertensive, tobacco smoking cessation
3
Q
Mecamylamine blocks…
A
Both PNS and SNA postganglionic
Reveals dominant ANS division
4
Q
Side effects Mecamylamine
A
- tachycardia
- mydriasis
- cycloplegia
- constipation
- urinary retention
- dry mouth
- increased BT
- peripheral pooling in veins
- vasodilation
5
Q
Vesamicol
A
- experimental
- inhibit ACh storage
- fusion of empty vesicles with PM
6
Q
OnabotulinumtoxinA MOA
A
- Inhibit Ach release
- inactivate SNAP-25
- temporary state of cholinergic denervation
7
Q
SNAP-25
A
Required for docking of vesicle (ACh) with presynaptic membrane
8
Q
Drug action of OnabotulinumtoxinA
A
- flaccid paralysis of skeletal muscle
- inactivate sweat gland
9
Q
Restoration of function from OnabotulinumtoxinA
A
- requires sprouting of new nerve terminals
- 3-4 months
10
Q
Therapeutic uses of OnabotulinumtoxinA
A
- cosmetic
- muscle spasms/dystonias
- axillary hyperhidrosis,
Overactive bladder
11
Q
Side effects of OnabotulinumtoxinA
A
- dysphagia (BOXED warning)
- breathing difficulties (BOXED warning)
- muscle weakness (ptosis)
- pain
- allergic reaction rare
12
Q
Muscarine
A
- Prototype agonist of muscarinic receptors
- mushroom
13
Q
Atropine
A
Prototype antagonist
- belladona (deadly nightshade)
- blocks all subtypes equally
14
Q
What are the two drugs that affect M cholinergic receptors?
A
Muscarine, atropine
15
Q
What are the drugs that affect N receptors
A
- nicotine
- mecamylamine
- d-tubocurarine
16
Q
All muscarinic receptors have ______ response. All nicotinic have _______ response
A
GPCR
Ligand gated ion channels
17
Q
Which drugs affect the Nn receptor
A
Nicotine
Mecamylamine
18
Q
Which drugs affect the Nm receptor?
A
Nicotine
D-tubocurarine
19
Q
Nicotine in Nn
A
- prototype agonist (high affinity)
- causes receptor desensitization
20
Q
Mecamylamine of Nn
A
Prototype antagonist
21
Q
Nn structure
A
2a, 3b
22
Q
Nm structure
A
2a, b, y, d
23
Q
Nicotine Nm
A
Prototype agonist (low affinity) - desensitization, skeletal muscle paralysis
24
Q
D-tubocurarine Nm
A
- Prototype antagonist
- (Curare)
- Non-depolarizing (competitive) Nm blockade
25
Termination of cholinergic transmission
- AChE rapidly terminates by hydrolysis of transmitter
| - allows for next depolarization and prevent lateral diffusion
26
Inhibition of AChE
- accumulation of Ach in synapse
| - increased receptor stimulation and desensitization
27
BuChE
- plasma, glial cells, liver
- drug metabolizing enzyme
- deficient in some
28
Succinylcholine-induced apnea is prolonged in those deficient in what?
BuChE
29
Where is NE formed?
Adrenergic postganglionic neurons
30
Where is DA formed?
Basal ganglia & renal vasculature
31
Where is Epi formed?
Adrenal medulla
32
Formation of catecholamines
Tyrosine —> DOPA —> DA —> NE —> Epi
33
What is the rate limiting step of synthesis of catecholamines?
Tyrosine —> DOPA
Tyrosine hydroxylase
- regulated by stress
34
What is the synthesis of Epi increased by?
PNMT
35
What dose vesicular storage protect DA, NE, and Epi from?
Degradation by MAO
36
What are DA, NE and Epi transported into storage vesicles by?
VMAT-2
37
What drug is an inhibitor of NE transmitter storage?
Reserpine
38
MOA of reserpine
- irreversible inhibitor of VMAT-2 (prevents uptake of DA and NE)
- depletes catecholamines from all terminals
- decreases CO & peripheral resistance —> lowers BP
39
Therapeutic use of reserpine
Antihypertensive
| Antipsychotic
40
Side effects of reserpine
- sedation
- unopposed cholinergic effects (cramping, diarrhea)
- psychotic depression (high doses)
- orthostatic hypotension
41
Release of catecholamines
- AP, Ca2+ influx, exocytosis
42
Negative feedback inhibition of catecholamines
- NE stimulation of presynaptic a2 autoreceptors
| - occurs via Gi mediated inhibition of Ca influx
43
Which drug stimulates NE release?
Tyramine
44
Which drug inhibits NE release?
Methyldopa
45
Where is tyramine found?
Fermentation byproduct of tyrosine in protein rich foods
| - aged cheese, beer/wine, soy/fish sauce, sauerkraut/kimchee, cured meats
46
Why is there low oral bioavailability of tyramine?
GI/hepatic MAO
- systemic abs can occur in patients taking MAOI (avoid taking)
47
MOA of tyramine
- displaces NE from vesicles
| - causes non-vesicular release from nerve terminals by REVERSE transport through NET
48
High systemic exposure of tyramine can cause what?
```
Hypertensive crisis (abrupt NE release)
- dietary restrictions for those on MAOIs prevent this
```
49
Where does methyldopa come from?
Prodrug converted to methyl-NE (mNE, active form) by DBH
50
MOA of methyldopa
A2 receptor agonist
| - reduces sympathetic outflow to periphery
51
Therapeutic use of methyldopa
Gestational HTN
52
Side effects of methyldopa
- sedation
- dry mouth
- edema
- autoimmune hemolytic anemia (Coomb’s test positive) with long term use
53
Drug that affects termination of NE
Cocaine
54
Synaptic NE termination
- re-uptake via NET
| - diffusion away from adrenergic receptors
55
Termination of circulating NE and Epi
- ENT in smooth muscle and glands
| - metabolism (liver, kidney)
56
Stimulant effects from cocaine are due to what?
Excess NE remaining in synapse
57
3 metabolism mechanisms of catecholamines
- MAO
- COMT
- VMA
58
Where are MAO?
Mitochondrial
59
Where are COMT?
Cytosolic (liver, kidney)
60
What is the major metabolite excreted in urine?
VMA
61
MAO
- deaminates catecholamines, tyramine, histamine
| - clear catecholamines in nerve terminals
62
What are MAOIs used for ?
Depression
63
COMT
- o-mthylates catecholes
| - clearence of circulating catecholamines
64
What are COMT inhibitors used for?
Parkinson’s
65
Significance of VMA
Clinical test of fractional metanephrines used to diagnose pheochromocytoma
66
RLS of synthesis of Ach
Choline transported into pre-synaptic nerve ending by high affinity Na choline co-transporter
67
Hemicholinium
- Experimental
- inhibit Ach synthesis
- inhibit choline uptake
- depletes Ach from nerve terminal
68
Cocaine action
Inhibits NE re-uptake
69
Therapeutic use of cocaine
Anesthetic/vasoconstrictor
70
Action of amphetamine
Promote NE release/inhibits re-uptake
71
Therapeutic use of amphetamine
ADHD
| Narcolepsy
72
Where does onabotulinumtoxin A come from?
Protein neurotoxin (protease) from C. Botulinum
