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Autonomic Drugs Flashcards

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1
Q

Nicotinic ACh receptors - type of receptor?

A

Ligand-gated Na/K channel

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2
Q

What are the two subtypes of nicotinic ACh receptors and where are they found?

A

Nn - autonomic ganglia, adrenal medulla

Nm - NMJ of skeletal muscle

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3
Q

Muscarinic ACh - type of receptor?

A

G-protein-coupled receptors; usually act through 2nd messengers

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4
Q

Where are muscarinic ACh receptors found?

A

Smooth muscle, gland cells, nerve terminals, cardiac muscle, sweat glands (cholinergic sympathetic)

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5
Q

What receptors do NE bind to? Where are these found?

A

A1, A2, B1 (smooth muscle, gland cells, nerve terminals, cardiac muscle, vessels)

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6
Q

What receptors does EPI bind to? Where are these found?

A

A1, A2, B1, B2 (cardiac muscle, vessels)

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7
Q

List the receptors + the G protein class associated with it. (Use the pneumonic)

A

“after QISSeS, you get a QIQ out of SIQ SQS (super qinky sex)”

A1, A2, B1, B2, B3
M1, M2, M3
D1, D2, H1
H2, V1, V2

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8
Q

What are the effects of binding to Gq receptors?

A

Activates PLC
Lipids -> PIP2; PLC converts this to DAG and IP3
DAG activates PKC; IP3 increases intracellular calcium, which leads to smooth muscle contraction (and further activates PKC)

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9
Q

What are the effects of binding to Gs receptors? Gi?

A

Gs activates AC, which converts ATP to cAMP -> PKA -> increased intracellular calcium in the heart and activation of MLCK in smooth muscle; Gi inhibits this

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10
Q

Function of A1

A

Increases contraction of: vascular smooth muscle, pupillary dilator (mydriasis), intestinal/bladder sphincters

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11
Q

Function of A2

A

Decreases sympathetic outflow, insulin release, lipolysis, aqueous humor production

Increases platelet aggregation

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12
Q

Function of B1

A

Increased HR, contractility, renin release, lipolysis

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13
Q

Function of B2

A

Dilation of vascular smooth muscle, bronchi, ciliary muscle (relaxation)

Increases lipolysis, insulin release, aqueous humor production

Decreases uterine tone

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14
Q

Function of B3

A

Increases lipolysis, thermogenesis in skeletal muscle, bladder relaxation

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15
Q

Function of M1

A

Mediates higher cognitive function

Stimulates enteric nervous sytem

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16
Q

Function of M2

A

Decreases HR/atrial contractility

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17
Q

Function of M3

A

Increases exocrine gland secretions, peristalsis, bladder contraction, bronchoconstriction, pupillary sphincter contraction (miosis), ciliary muscle contraction (accommodation), insulin release

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18
Q

Function of D1

A

Relax renal vascular smooth muscle

Activate direct striatum pathway

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19
Q

Function of D2

A

Modulates transmitter release; inhibits indirect striatum pathway

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20
Q

Function of H1

A

Increase nasal/bronchial mucus production, vascular permeability, contraction of bronchioles, pruritis, pain

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21
Q

Function of H2

A

Increase gastric acid secretion

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22
Q

Function of V1

A

Increase vascular smooth muscle contraction

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23
Q

Function of V2

A

Increase water permeability and reabsorption in collecting tubules of kidneys

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24
Q

List the 4 cholinomimetics - direct agonists.

A
  1. Bethanechol
  2. Carbachol
  3. Methacholine
  4. Pilocarpine
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25
List the 5 (+3) cholinomimetics - indirect agonists (anticholinesterase)
1. Galantamine, donepezil, rivastigmine, tacrine 2. Edrophonium 3. Neostigmine 4. Physostigmine 5. Pyridostigmine
26
What is the general AE of any cholinomimetic?
May exacerbate COPD, asthma, peptid ulcers
27
MOA and indications of bethanechol
Activates bowel and bladder smooth muscle Postoperative or neurogenic ileus, urinary retention
28
MOA and indication of methacholine
Bronchoconstriction via stimulation of muscarinic receptors; inhaled to diagnose asthma (challenge test)
29
Edrophonium- indication?
Diagnose myasthenia gravis (historically)
30
Neostigmine - indication?
Postoperative/neurogenic ileus Urinary retention Myasthenic gravis Reversal of NMJ blockade postoperatively
31
Physostigmine - indication?
Anticholinergic toxicity antidote (ie, atropine overdose)?
32
Pyridostigmine - indication?
Myasthenia gravis (long-acting)
33
List the muscarinic antagonists.
1. Atropine (homatropine, tropicamide) 2. Benztropine, trihexyphenidyl 3. Glycopyrrolate 4. Hyoscyamine/dicyclomine 5. Ipratropium/tiotropium 6. Oxybutynin, solifenacin/tolterodine 7. Scoplamine
34
Which muscarinic antagonists decrease ACh activity in the CNS primarily?
1. Benztropine/trihexyphenidyl | 2. Scopolamine
35
Which muscarinic antagonists decrease ACh activity in the GI system?
1. Glycopyrrolate (and respiratory) | 2. Hyoscyamine, dicyclomine
36
Which muscarinic antagonists decrease ACh activity in the respiratory system?
1. Glycopyrrolate | 2. Ipratropium/tiotropium
37
Which muscarinic antagonists decrease ACh activity in the GU system?
Oxybutynin, solifenacin, tolterodine
38
Indications for atropine?
Cholinesterase inhibitor poisoning (too much ACh), bradycardia, ophthalmic uses to produce mydriasis and cycloplegia
39
What are the key AE of atropine?
Hot as a hare, dry as a bone, red as a beet, blind as a bat, mad as a hatter (increased body temperature, decreased sweating, rapid pulse, dry mouth, dry flushed skin, cycloplegia (paralysis of ciliary muscle), constipation, disorientation
40
What specific AE can atropine have on the elderly, men with prostatic hyperplasia, and hyperthermia in infants?
Elderly - acute angle-closure glaucoma (mydriasis) Men - prostatic hyperplasia Infants - hyperthermia
41
Indications - glycopyrrolate?
Parenteral - reduce airway secretions pre-op Oral - drooling, peptic ulcer disease
42
Indication - oxybutynin, solifenacin, tolterodine
Reduce bladder spasms and urge incontinence by inhibiting M3 receptors on smooth muscle in the bladder (decreases involuntary detrusor contraction)
43
Indication - scopolamine?
Motion sickness
44
Sympathomimetic effect of albuterol/salmeterol?
B2 > B1
45
Sympathomimetic effect of dobutamine?
B1 > B2, A1, A2 | Inotropic > chronotropic (contractility increases more than HR)
46
Indication of dobutamine?
Heart failure, cardiac stress testing
47
Sympathomimetic effect of dopamine (low dose vs. high dose)?
D1 = D2 > B1, B2 > A1, A2 Low - inotropic and chronotropic High - vasoconstriction
48
Indications of dopamine?
Unstable bradycardia, HF, shock
49
Sympathomimetic effect of epinephrine?
B1, B2 > A1, A2
50
Which receptor effect predominates at a higher dose of EPI?
Alpha
51
Indications of epinephrine?
Anaphylaxis, asthma, open-angle glaucoma
52
Sympathomimetic effect of fenoldopam?
D1
53
Sympathomimetic (direct) effect of isoproterenol?
B1 = B2 (non-selective)
54
Indication of isoproterenol?
Electrophysiologic evaluation of tachyarrhythmias (caution, as it can worsen ischemia)
55
Sympathomimetic (direct) effectof midodrine?
A1 agonist
56
Indications of midodrine?
``` Autonomic insufficiency Postural hypotension (may exacerbate supine HTN) ```
57
Sympathomimetic (direct) effect of mirabegron?
B3
58
Indication of mirabegron?
Urge incontinence
59
Sympathomimetic (direct) effect of NE?
A1 > A2 > B1
60
Indications of NE?
Hypotension, septic shock
61
Sympathomimetic (direct) effect of phenylephrine?
A1 > A2
62
List the 3 indirect sympathomimetics.
1. Amphetamine 2. Cocaine 3. Ephedrine
63
MOA - amphetamine; what other sympathomimetic has the same MOA?
Uses the NE transporter to enter the presynaptic terminal, uses VMAT to enter vesicles, which displaces NE, increasing the [NE] in the terminal, leading to transporter reversal; ultimately increases release and inhibits reuptake Same as ephedrine
64
Three indications for amphetamines?
ADHD Narcolepsy Obesity
65
MOA - cocaine?
Inhibits reuptake of NE
66
What is strongly contraindicated if cocaine intoxication is suspected and why?
Beta-blockers - can lead to unopposed A1 activation and extreme hypertension
67
Indications - ephedrine?
Nasal decongestion (pseudoephedrine) Urinary incontinence Hypotension
68
MOA - clonidine, guanfacine, alpha-methyldopa
A2 agonist (sympatholytic)
69
Indications - clonidine, guanfacine?
``` Hypertensive urgency (limited situations) ADHD, Tourette syndrome ```
70
Indication - alpha-methyldopa?
Hypertension in pregnancy
71
Major AE - clonidine, guanfacine?
Rebound hypertension with abrupt cessation | CNS depression, bradycardia, hypotension, respiratory depression, miosis
72
What are the two non-selective alpha antagonists? Which is irreversible?
Phenoxybenzamine - irreversible | Phentolamine - reversible
73
Indication - phenoxybenzamine?
Pre-operatively in pheochromocytoma to prevent catecholamine (hypertensive) crisis
74
Indication - phentolamine?
Given to patients on MAOIs who eat tyramine containing food
75
AE - non-selective alpha blockers?
Orthostatic hypotension, reflex tachycardia
76
List the 4 alpha-1-selective blockers.
Prazosin Terazosin Doxazosin Tamsulosin
77
What are the 3 indications of alpha-1-selective blockers?
Urinary symptoms of BPH PTSD (prazosin) HTN (except tamsulosin)
78
What AE may occur with the first dose of an A1 selective blocker?
Orthostatic hypotension
79
What is the one A2 blocker?
Mirtazapine
80
List the 6 beta blockers with B1 selectivity (B1>B2).
1. Acebutolol 2. Atenolol 3. Betaxolol 4. Bisoprolol 5. Esmolol 6. Metoprolol (A-M)
81
List the major indications of beta-blockers.
1. Angina pectoris 2. MI 3. SV tachycardia 4. HTN 5. Glaucoma 6. Variceal bleeding 7. Decrease mortality of heart failure (some)
82
How do beta-blockers address angina pectoris?
Decrease HR and contractility, resulting in decreased O2 consumption
83
What is the MOA of beta-blockers in treating HTN?
Decreases CO, decreases renin secretion via blockade on JGA cells
84
How do beta-blockers treat variceal bleeding?
Decrease hepatic venous pressure gradient and portal hypertension
85
Which three beta-blockers decrease mortality of heart failure?
Bisoprolol Esmolol Metoprolol
86
List the non-selective beta blockers (4).
1. Nadolol 2. Pindolol 3. Propranolol 4. Timolol (N-Z)
87
What is the unique indication/mechanism of propranolol?
Inhibits 5' monodeiodinase in peripheral tissue, reducing the conversion of T4 to T3; treats thyroid storm
88
List the two non-selective alpha and beta blockers.
Carvedilol | Labetalol
89
List the two partial beta agonists.
Acebutolol | Pindolol
90
List the B1 blocker/B3 agonist.
Nebivolol

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