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Pharmacology > Block 1 Autonomics > Flashcards

Block 1 Autonomics Flashcards

1
Q

Primary NTs in autonomic and somatic NS

A

ACh, NE, epi (adrenal)

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2
Q

Direct acting drugs

A

Activate or block receptors directly

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3
Q

Cholinergic receptor types & locations

A

Muscarinic - neuroeffector junctions

Nicotinic - all autonomic ganglia and somatic NMJ

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4
Q

Sympathetic NTs

A

Pregang: ACh -> nicotinic
Postgang: NE -> adrenergic, ACh -> muscarinic (sweat glands)

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5
Q

Parasympathetic NTs

A

Pregang: ACh -> nicotinic
Postgang: ACh -> muscarinic

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6
Q

Somatic NTs

A

ACh -> nicotinic

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7
Q

SNS location, length & ratio of fibers, discharge pattern

A

Thoracic, lumbar region SC; short pre-gang, long post-gang, low pre to post ratio; unit discharge = diffuse activation targets

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8
Q

PSNS location, length & ratio of fibers, discharge pattern

A

Cranial, sacral SC; long pre-gang, short post-gang, high pre to post ratio; can discretely activate targets

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9
Q

Baroreceptor reflex & importance for BP drugs

A 
Stretch receptors (aortic arch, carotid sinus) w/ inc arterial pressure -> brain stem VMC -> vagal dec heart rate (reflex bradycardia)
*Drugs affecting BP can cause reflex brady- or tachycardia
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10
Q

Vesamicol & Botulinum toxin

A

V: blocks ACh/H+ exchange so no ACh in vesicles
B: blocks ACh vesicle fusion/release

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11
Q

AChE inhibitor & Hemicholinium

A

I: blocks ACh breakdown to choline + acetate by AChE on post-syn neuron
H: blocks choline/Na+ cotransport back into pre-syn neuron

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12
Q

Muscarinic receptor subtypes

A

M1 - CNS and autonomic ganglia
M2 - cardiac muscle
M3 - SM and glandular tissue
M4, 5 - CNS

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13
Q

Muscarinic receptor effects on: heart SA and AV nodes, blood vessels, GI, iris, ciliary mm, bladder, lung, exocrine glands

A

SA: bradycardia
AV: slow conduction
BV: vasodilation
GI: increased tone, secretions, sphincters relax
Iris: miosis (contraction)
CM: accommodation (contraction)
UB: detrusor contraction, sphincter relaxes
Lung: bronchi contract, increase secretions
Glands: increase tears, sweat, saliva

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14
Q

Nicotinic receptor effects on ganglia, adrenal medulla, skeletal muscle

A

Gang: at high doses -> SNS and PSNS responses
AM: release epi and NE
SkM: depolarization of end plate

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15
Q

Types of cholinergic receptor agonists and antagonists

A

Ag: direct-acting, indirect-acting reversible, indirect irreversible
Ant: muscarinic, nicotinic

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16
Q

Main types of direct and indirect cholinergic receptor agonists

A

Direct: choline esters (highly polar 4’ amines), plant alkaloids (lipid soluble)
Indirect: reversible and irreversible cholinesterase inhibitors

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17
Q

Acetylcholine

A

Choline ester, short duration, nonselective, no therapeutic use

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18
Q

Methacholine

A

Choline ester, muscarinic, longer duration than ACh

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19
Q

Carbachol

A

Choline ester, predominantly nicotinic, topical agent for glaucoma

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20
Q

Bethanechol

A

Choline ester, predominantly muscarinic, to stimulate bladder/GI without cardiac effects

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21
Q

Muscarine

A

Plant alkaloid, from poisonous mushrooms

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22
Q

Nicotine

A

Plant alkaloid, from tobacco; oral, nasal, transdermal for smoking cessation

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23
Q

Pilocarpine

A

Plant alkaloid, from a small shrub, predominantly muscarinic, topical agent for glaucoma, oral agent for xerostomia

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24
Q

Cevimeline (Evoxac)

A

Synthetic direct cholinergic agonist for xerostomia, dry eyes after radiation or Sjogren’s syndrome

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25
Q

Primary open angle glaucoma & treatment

A

Inc intraoc pressure due to narrowed ant chamber angle, decreased aq humor outflow -> optic nerve damage
Tx: inc AH outflow w/ PG analogs, muscarinic receptor agonist; dec AH production w/ a2 agonists, beta antagonists, carbonic anhydrase inhibitors

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26
Q

Neostigmine

A

Indirect reversible chol inh, 4’ amine - poor CNS penetration, antidote for NMJ blocking-drugs like d-tubocurarine
Contra: GI/bladder obstruction, asthma

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27
Q

Edrophonium (Tensilon)

A

Neostigmine analog with shorter duration of action

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28
Q

Physostigmine

A

Indirect reversible chol inh, 3’ amine - can penetrate CNS, alkaloid from alabar bean

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29
Q

Myasthenia gravis & treatment

A

AI ab’s against nicotinic receptor in skm -> weakness
Edrophonium - to diagnose MG
Tx: neo-, pyridostigmine

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30
Q

Donepezil (Atricept)

A

Once daily reversible chol inh for dementia/AD a/w dec ACh production in brain; high doses can cause adverse effects (GI, bladder fxn, dec heart rate)

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31
Q

Galantamine (Rizatidine)

A

Reversible chol inh for dementia/AD a/w dec ACh production in brain; high doses can cause adverse effects (GI, bladder fxn, dec heart rate)

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32
Q

Rivastigmine (Exelon)

A

Reversible chol inh for dementia/AD a/w dec ACh production in brain; high doses can cause adverse effects (GI, bladder fxn, dec heart rate)

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33
Q

Examples of irreversible chol inh

A

Organophosphates (pesticides, sarin gas), malathion

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34
Q

Signs and symptoms of organophosphate toxicity

A

Musc: bradycardia, hypotension, salivation, sweating, lacrimation, miosis
Nic: muscle fibrillation, fasciculation, paralysis
CNS: confusion, ataxia, coma, resp paralysis
SLUDGE: salivation, lacrimation, urination, diarrhea, gastric emptying

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35
Q

Muscarinic receptor antagonists

A

*Most common cholinergic drug aka “anticholinergic”, most are competitive antagonists
Belladonna alkaloids, semi- and synthetic antagonists

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36
Q

Nicotinic receptor antagonists

A

Ganglionic blocking agents, non depolarizing and depolarizing neuromuscular blocking agents

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37
Q

Atropine

A

Belladonna alkaloid anticholinergic, widely distributed, T½ 2 hours, blocks M1,2,3; for sinus bradycardia, chol inh overdose antidote

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38
Q

Scopolamine

A

Anticholinergic plant alkaloid; greater CNS effects than atropine, isolated from henbane; for motion sickness

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39
Q

Anticholinergic response from eye, sweat, secretions, lungs, heart, GI, bladder

A 
Eye: mydriasis, no accommodation
Sweat: blocked, inc body temp
Sec: drying (*COPD)
Lungs: bronchodilation, reduced secretions
Heart: increased rate
GI: decreased motility
UB: atony, urinary retention
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40
Q

Hyoscyamine

A

L isomer of atropine, for GI spasms

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41
Q

Belladonna alkaloid toxicity profile

A

Tox: dry mouth, blurred vision, tachycardia, palpitations, urinary retention, delirium, hallucinations

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42
Q

Belladonna alkaloid relative contraindications

A

Glaucoma, prostatic hyperplasia, dementia, delirium

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43
Q

Ipratropium (Atrovent) & tiotropium (Spiriva)

A

Inhaled synthetic musc ant for asthma, COPD

44
Q

Dicyclomine (Bentyl)

A

Synthetic musc ant for IBS

45
Q

Tropicamide (Mydriacyl)

A

Topical synthetic musc ant to facilitate eye exams

46
Q

Benztropine (Cogentin)

A

Synthetic musc ant for drug-induced PD from antagonism of DA receptors

47
Q

Drugs used for overactive bladder

A

Oxybutinin (Ditropan)
Tolterodine (Detrol)
Solifenacin (VESIcare)

48
Q

Drugs with anticholinergic properties

A

Diphenhydramine (Benadryl), antidepressant amitriptyline (Elavil), antipsychotic olanzapine (Zyprexa), muscle relaxant carisoprodol (Soma)

49
Q

2 common drugs given 3 points on anticholinergic risk scale

A

Chlorpheniramine, diphenhydramine

50
Q

Ganglionic blocking agents

A

Block nicotinic receptors at ganglia, useful only for research

51
Q

Neuromuscular blocking agents

A

Nicotinic receptor antagonist, inhibit neurotransmission at skeletal NMJ, cause mm weakness, paralysis

52
Q

Non-depolarizing neuromuscular blocking agents

A

Competitive antagonists of ACh at nic rec; d-tubocurarine (surgical mm relaxant)

53
Q

Pancuronium, vecuronium, rocuronium, mivacurium; & antidote

A

Non-depolarizing neuromuscular blocking agents; P is long-acting (2-3 hr), V,R are int (60-90, 30-60 min), M short acting (10-20 min); antidote is neostigmine, other cholinesterase inh

54
Q

Succinylcholine

A

Only depolarizing neuromuscular blocking agent of 2 linked ACh molecules; causes persistent depol of nic -> sustained paralysis; 5-10 min dur of action; used in ER but no antidote; can cause hyperkalemia

55
Q

Catecholamine synthesis order

A

Phe -> Tyr -> *DOPA -> DA -> NE -> epi

56
Q

Location alpha 2 receptor

A

Sympathetic postganglionic presynaptic cholinergic and adrenergic neurons (negative feedback of NT release); platelets (aggregation), vascular SM (contraction), fat cell (inhibition of lipolysis)

57
Q

Location alpha 1 receptor

A

Smooth muscle (contraction): vascular, iris dilator, pilomotor mm, lower urinary tract (urethra, prostate)

58
Q

Location beta 1 receptor

A

Cardiac tissue - increase force and rate of contraction, increase conduction velocity

59
Q

Location beta 2 receptor

A

Resp, uterine, vascular smooth muscle (relaxation), skeletal mm K+ uptake, liver (activates glycogenolysis)

60
Q

Distribution of beta 3, D1, D2 receptors

A

B3 in fat cells - activate lipolysis
D1 in SM - dilate renal blood vessels
D2 in nerve endings - modulate NT release in CNS

61
Q

Classes of adrenergic receptor agonists and antagonists

A

Agonists (sympathomimetic): direct- and indirect-acting, mixed-acting
Antagonists: nonselective a-blockers, selective a1-blockers, nonselective b-blockers, selective b1-blockers, a- and b- blockers

62
Q

Direct-acting adrenergic agonists

A

Selective or not for a/b receptors, catecholamines metabolized rapidly by MAO, COMT; non-cats not metabolized by MAO, COMT = oral administration, longer duration of action

63
Q

Non-selective direct adrenergic agonists

A

Epinephrine, NE, isoproterenol

64
Q

Epinephrine

A

Non-selective direct adrenergic agonist; IV or SC; a1 = a2, b1 = b2; @ low dose B effects, high dose A effects
Used for: anaphylactic shock, cardiac arrest, topical vasoconstriction, extends local anesthetic duration
Adverse: tremor, palpitations, headache, arrhythmias

65
Q

Norepinephrine

A

Non-selective direct adrenergic agonist; IV; a1 = a2, b1&raquo_space; b2; greater PVR than epi, increased heart rate, conduction
For: hypotension, shock
Adverse: tremor, palpitations, headache, arrythmias

66
Q

Isoproterenol

A

Synthetic non-selective direct adrenergic agonist; IV; b1 = b2
For: potent vasodilator, inotropic agent
Adverse: tachycardia, arrhythmia

67
Q

Low dose NE effect on HR, BP, PVR

A

HR: reflex bradycardia
BP: increase overall, systolic, diastolic
PVR: large increase (A1)

68
Q

Low dose epi effect on HR, BP, PVR

A

HR: reflex tachycardia
BP: increase sys, decrease dias, overall no change
PVR: mild decrease (B2)
High dose: alpha stimulation -> increase PVR

69
Q

Low dose isoproterenol effect on HR, BP, PVR

A

HR: reflex tachycardia
BP: mild sys inc, dias dec, mild overall dec
PVR: large decrease (B2)

70
Q

Low dose dopamine effect on HR, BP, PVR

A

HR: mild increase
BP: sys increase, dias no change, overall increase
PVR: mild decrease (D1, B2)

71
Q

Dobutamine

A

Synthetic selective direct B1-adrenergic agonist; IV; B1 > B2&raquo_space;» A
For: acute HF (potent inotropic agent)
Adverse: HTN, tachycardia

72
Q

Albuterol, levalbuterol (Xopenex), salmeterol (Serevent)

A

Selective direct B2-adrenergic agonists; inhaled for bronchodilation (asthma, COPD)

73
Q

Terbutaline

A

Selective direct B2-adrenergic agonist; PO for asthma bronchodilation (systemic effects, tachycardia), IV for relaxation of uterus in late pregnancy to delay premature labor

74
Q

Phenylephrine

A

Selective direct A1-adrenergic agonist; vasoconstriction with increased PVR, BP; IV for HTN, shock; PO is OTC decongestant
Contra: uncontrolled HTN

75
Q

Oxymetazoline (Afrin)

A

Selective direct A1-adrenergic agonist; topical nasal decongestant (vasoconstriction); tachyphylaxis over several days -> rebound congestion

76
Q

Clonidine

A

Selective direct A2-adrenergic agonist; centrally acting antiHTN, used in withdrawal, oral or transdermal patch
For: HTN emergencies
Adverse: stopping -> rebound HTN -> stroke

77
Q

a-methyldopa

A

Selective direct A2-adrenergic agonist; centrally acting antiHTN useful during pregnancy (most others are teratogenic)

78
Q

Amphetamine & methamphetamine

A

Indirect adrenergic agonists; stimulate release of NE and DA; lipid soluble (enter CNS); stimulate mood & alertness, depress appetite, peripherally vasoconstrictive, cardiac stimulant; reverse NET

79
Q

Methylphenidate (Ritalin)

A

Indirect adrenergic agonist; amphetamine derivative with similar actions

80
Q

Cocaine

A

Indirect adrenergic agonist; inhibits reuptake of NE, DA, 5-HT by blocking NET, DAT; peripheral vasoconstriction, cardiac stimulant; similar effects to amphetamine but shorter, more intense; local anesthetic (ocular surgery)

81
Q

Tyramine

A

Indirect adrenergic agonist in fermented products (cheese, wine, bananas); increases NE release, blocks destruction by MAO
Contra: MAOIs -> HTN crisis

82
Q

Dopamine

A

Mixed-acting adrenergic agonist; IV; D1 = D2&raquo_space; B1&raquo_space; A1
Low dose: DR = inc renal blood flow (shock)
Med: D + B1-R (HR, CO)
High: D + B1 + A1 (peripheral vasoconstriction)
Use: cardiogenic shock, acute renal failure
Adverse: tremor, palpitations, headache, arrhythmia

83
Q

Selective adrenergic agonists

A

B1: dobutamine
B2: albuterol, levalbuterol (Xopenex), salmeterol (Serevent), terbutaline
A1: phenylephrine, oxymetazoline
A2: clonidine, a-methyldopa

84
Q

Indirect acting adrenergic agonists

A

Amphetamine, methamphetamine, methylphenidate (Ritalin), cocaine, tyramine

85
Q

Mixed-acting adrenergic agonists

A

Dopamine, ephedrine, pseudoephedrine (Sudafed)

86
Q

Ephedrine

A

Mixed-acting adrenergic agonist; A, B agonist, enhances release NE
High dose -> similar to epi

87
Q

Pseudoephedrine (Sudafed)

A

Mixed-acting adrenergic agonist; stereoisomer of ephedrine

Contra: HTN, cardiomyopathy

88
Q

Nonselective a-blockers

A

Phenoxybenzamine, phentolamine

89
Q

Selective a1-blockers

A

Prazosin, terazosin (Hytrin), Doxazosin (Cardura), tamsulosin (Flomax)

90
Q

Nonselective b-blockers

A

Propranolol, nadolol (Corgard), timolol, pindolol

91
Q

Selective b1-blockers

A

Metoprolol, atenolol, bisoprolol (Zebeta), esmolol, acebutolol

92
Q

A- and B-blockers

A

Labetalol, carvedilol (Coreg)

93
Q

Phenoxybenzamine

A

Nonselective a-blocker; non-competitive, irreversible, lasts 4 days; a1 > a2
Use: catecholamine excess (pheo)
Adverse: postural hypotension, reflex tachycardia

94
Q

Phentolamine

A

Nonselective a-blocker; competitive; a1 = a2
Use: pheo, reversal of ischemia from extravasation/injection adrenergic agonist (epi)
Adverse: postural hypotension, reflex tachycardia

95
Q

Prazosin, terazosin (Hytrin), doxazosin (Cardura)

A

Selective a1-blockers; relax vasc, bladder neck, & prostate SM
Use: BPH, last resort for HTN (inc morbidity)
Adverse: 1st dose syncope, reflex tachycardia

96
Q

Tamsulosin (Flomax)

A

Selective a1A-blocker in prostate; causes less vasodilation vs. other a1-blockers; little effect on BP at normal dose
Use: decrease urinary obstruction in BPH

97
Q

Propranolol

A

Nonselective b-blocker; b1 = b2; high lipid solubility; 1st pass effect (oral&raquo_space; IV dose); negative inotropic, chronotropic; bronchoconstriction, dec glycogenolysis
Use: HTN, arrhythmia, angina, migraine, essential tremor; HF (small dose)
Adverse/contra: bradycardia, insomnia, HF, asthma, COPD, DM

98
Q

Nadolol (Corgard)

A

Nonselective b-blocker; low lipophilicity (low CNS adverse effects), renal excretion, long T½

99
Q

Timolol

A

Nonselective b-blocker; topical agent for glaucoma

100
Q

Pindolol

A

Nonselective b-blocker; partial agonist of b1, b2; intrinsic sympathomimetic activity = less bradycardia

101
Q

Metoprolol

A

Selective b1-blocker; B1&raquo_space; B2; cardioselective-blocker (low dose)
Use: HTN (high dose), HF (low), angina, A-fib, *safer for DM, asthma, COPD than nonselective b-blockers
*T½ varies depending on CYP 2D6 phenotype (8-10% pop need lower dose)

102
Q

Atenolol

A

Selective b1-blocker; low lipophilicity (less CNS vs. propranolol); renal excretion, long T½
Use: HTN (monitor serum creatinine)

103
Q

Bisoprolol (Zebeta)

A

Selective b1-blocker; moderate lipophilicity

104
Q

Esmolol

A

Selective b1-blocker; short acting, IV only

105
Q

Acebutolol

A

Selective b1-blocker; partial B1 agonist; intrinsic sympathomimetic activity (less brady)

106
Q

Labetalol, carvedilol (Coreg)

A

A- and B-adrenergic blockers; b1 = b2, a1 > a2; a1 blockade = more pronounced vasodilation vs. other b-blockers
Lab: IV, PO for rapid reduction of BP (HTN emergency) and resistant HTN
Carv: HF
Adverse/contra: bradycardia, insomnia, HF, asthma, COPD, DM

107
Q

Factors determining choice of b-blocker

A 
Receptor selectivity (lost at higher doses)
Lipid solubility (CNS adverse effects)
Half-life (doses per day)
Elimination route (renal vs. liver)

Pharmacology (4 decks)

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