Block 1 Autonomics Flashcards
(107 cards)
1
Q
Primary NTs in autonomic and somatic NS
A
ACh, NE, epi (adrenal)
2
Q
Direct acting drugs
A
Activate or block receptors directly
3
Q
Cholinergic receptor types & locations
A
Muscarinic - neuroeffector junctions
Nicotinic - all autonomic ganglia and somatic NMJ
4
Q
Sympathetic NTs
A
Pregang: ACh -> nicotinic
Postgang: NE -> adrenergic, ACh -> muscarinic (sweat glands)
5
Q
Parasympathetic NTs
A
Pregang: ACh -> nicotinic
Postgang: ACh -> muscarinic
6
Q
Somatic NTs
A
ACh -> nicotinic
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
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
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
10
Q
Vesamicol & Botulinum toxin
A
V: blocks ACh/H+ exchange so no ACh in vesicles
B: blocks ACh vesicle fusion/release
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
12
Q
Muscarinic receptor subtypes
A
M1 - CNS and autonomic ganglia
M2 - cardiac muscle
M3 - SM and glandular tissue
M4, 5 - CNS
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
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
15
Q
Types of cholinergic receptor agonists and antagonists
A
Ag: direct-acting, indirect-acting reversible, indirect irreversible
Ant: muscarinic, nicotinic
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
17
Q
Acetylcholine
A
Choline ester, short duration, nonselective, no therapeutic use
18
Q
Methacholine
A
Choline ester, muscarinic, longer duration than ACh
19
Q
Carbachol
A
Choline ester, predominantly nicotinic, topical agent for glaucoma
20
Q
Bethanechol
A
Choline ester, predominantly muscarinic, to stimulate bladder/GI without cardiac effects
21
Q
Muscarine
A
Plant alkaloid, from poisonous mushrooms
22
Q
Nicotine
A
Plant alkaloid, from tobacco; oral, nasal, transdermal for smoking cessation
23
Q
Pilocarpine
A
Plant alkaloid, from a small shrub, predominantly muscarinic, topical agent for glaucoma, oral agent for xerostomia
24
Q
Cevimeline (Evoxac)
A
Synthetic direct cholinergic agonist for xerostomia, dry eyes after radiation or Sjogren’s syndrome
25
Primary open angle glaucoma & treatment
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
26
Neostigmine
Indirect reversible chol inh, 4' amine - poor CNS penetration, antidote for NMJ blocking-drugs like d-tubocurarine
Contra: GI/bladder obstruction, asthma
27
Edrophonium (Tensilon)
Neostigmine analog with shorter duration of action
28
Physostigmine
Indirect reversible chol inh, 3' amine - can penetrate CNS, alkaloid from alabar bean
29
Myasthenia gravis & treatment
AI ab's against nicotinic receptor in skm -> weakness
Edrophonium - to diagnose MG
Tx: neo-, pyridostigmine
30
Donepezil (Atricept)
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)
31
Galantamine (Rizatidine)
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)
32
Rivastigmine (Exelon)
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)
33
Examples of irreversible chol inh
Organophosphates (pesticides, sarin gas), malathion
34
Signs and symptoms of organophosphate toxicity
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
35
Muscarinic receptor antagonists
*Most common cholinergic drug aka "anticholinergic", most are competitive antagonists
Belladonna alkaloids, semi- and synthetic antagonists
36
Nicotinic receptor antagonists
Ganglionic blocking agents, non depolarizing and depolarizing neuromuscular blocking agents
37
Atropine
Belladonna alkaloid anticholinergic, widely distributed, T½ 2 hours, blocks M1,2,3; for sinus bradycardia, chol inh overdose antidote
38
Scopolamine
Anticholinergic plant alkaloid; greater CNS effects than atropine, isolated from henbane; for motion sickness
39
Anticholinergic response from eye, sweat, secretions, lungs, heart, GI, bladder
```
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
```
40
Hyoscyamine
L isomer of atropine, for GI spasms
41
Belladonna alkaloid toxicity profile
Tox: dry mouth, blurred vision, tachycardia, palpitations, urinary retention, delirium, hallucinations
42
Belladonna alkaloid relative contraindications
Glaucoma, prostatic hyperplasia, dementia, delirium
43
Ipratropium (Atrovent) & tiotropium (Spiriva)
Inhaled synthetic musc ant for asthma, COPD
44
Dicyclomine (Bentyl)
Synthetic musc ant for IBS
45
Tropicamide (Mydriacyl)
Topical synthetic musc ant to facilitate eye exams
46
Benztropine (Cogentin)
Synthetic musc ant for drug-induced PD from antagonism of DA receptors
47
Drugs used for overactive bladder
Oxybutinin (Ditropan)
Tolterodine (Detrol)
Solifenacin (VESIcare)
48
Drugs with anticholinergic properties
Diphenhydramine (Benadryl), antidepressant amitriptyline (Elavil), antipsychotic olanzapine (Zyprexa), muscle relaxant carisoprodol (Soma)
49
2 common drugs given 3 points on anticholinergic risk scale
Chlorpheniramine, diphenhydramine
50
Ganglionic blocking agents
Block nicotinic receptors at ganglia, useful only for research
51
Neuromuscular blocking agents
Nicotinic receptor antagonist, inhibit neurotransmission at skeletal NMJ, cause mm weakness, paralysis
52
Non-depolarizing neuromuscular blocking agents
Competitive antagonists of ACh at nic rec; d-tubocurarine (surgical mm relaxant)
53
Pancuronium, vecuronium, rocuronium, mivacurium; & antidote
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
Succinylcholine
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
Catecholamine synthesis order
Phe -> Tyr -> *DOPA -> DA -> NE -> epi
56
Location alpha 2 receptor
Sympathetic postganglionic presynaptic cholinergic and adrenergic neurons (negative feedback of NT release); platelets (aggregation), vascular SM (contraction), fat cell (inhibition of lipolysis)
57
Location alpha 1 receptor
Smooth muscle (contraction): vascular, iris dilator, pilomotor mm, lower urinary tract (urethra, prostate)
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Location beta 1 receptor
Cardiac tissue - increase force and rate of contraction, increase conduction velocity
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Location beta 2 receptor
Resp, uterine, vascular smooth muscle (relaxation), skeletal mm K+ uptake, liver (activates glycogenolysis)
60
Distribution of beta 3, D1, D2 receptors
B3 in fat cells - activate lipolysis
D1 in SM - dilate renal blood vessels
D2 in nerve endings - modulate NT release in CNS
61
Classes of adrenergic receptor agonists and antagonists
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
Direct-acting adrenergic agonists
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
Non-selective direct adrenergic agonists
Epinephrine, NE, isoproterenol
64
Epinephrine
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
Norepinephrine
Non-selective direct adrenergic agonist; IV; a1 = a2, b1 >> b2; greater PVR than epi, increased heart rate, conduction
For: hypotension, shock
Adverse: tremor, palpitations, headache, arrythmias
66
Isoproterenol
Synthetic non-selective direct adrenergic agonist; IV; b1 = b2
For: potent vasodilator, inotropic agent
Adverse: tachycardia, arrhythmia
67
Low dose NE effect on HR, BP, PVR
HR: reflex bradycardia
BP: increase overall, systolic, diastolic
PVR: large increase (A1)
68
Low dose epi effect on HR, BP, PVR
HR: reflex tachycardia
BP: increase sys, decrease dias, overall no change
PVR: mild decrease (B2)
High dose: alpha stimulation -> increase PVR
69
Low dose isoproterenol effect on HR, BP, PVR
HR: reflex tachycardia
BP: mild sys inc, dias dec, mild overall dec
PVR: large decrease (B2)
70
Low dose dopamine effect on HR, BP, PVR
HR: mild increase
BP: sys increase, dias no change, overall increase
PVR: mild decrease (D1, B2)
71
Dobutamine
Synthetic selective direct B1-adrenergic agonist; IV; B1 > B2 >>>> A
For: acute HF (potent inotropic agent)
Adverse: HTN, tachycardia
72
Albuterol, levalbuterol (Xopenex), salmeterol (Serevent)
Selective direct B2-adrenergic agonists; inhaled for bronchodilation (asthma, COPD)
73
Terbutaline
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
Phenylephrine
Selective direct A1-adrenergic agonist; vasoconstriction with increased PVR, BP; IV for HTN, shock; PO is OTC decongestant
Contra: uncontrolled HTN
75
Oxymetazoline (Afrin)
Selective direct A1-adrenergic agonist; topical nasal decongestant (vasoconstriction); tachyphylaxis over several days -> rebound congestion
76
Clonidine
Selective direct A2-adrenergic agonist; centrally acting antiHTN, used in withdrawal, oral or transdermal patch
For: HTN emergencies
Adverse: stopping -> rebound HTN -> stroke
77
a-methyldopa
Selective direct A2-adrenergic agonist; centrally acting antiHTN useful during pregnancy (most others are teratogenic)
78
Amphetamine & methamphetamine
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
Methylphenidate (Ritalin)
Indirect adrenergic agonist; amphetamine derivative with similar actions
80
Cocaine
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
Tyramine
Indirect adrenergic agonist in fermented products (cheese, wine, bananas); increases NE release, blocks destruction by MAO
Contra: MAOIs -> HTN crisis
82
Dopamine
Mixed-acting adrenergic agonist; IV; D1 = D2 >> B1 >> 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
Selective adrenergic agonists
B1: dobutamine
B2: albuterol, levalbuterol (Xopenex), salmeterol (Serevent), terbutaline
A1: phenylephrine, oxymetazoline
A2: clonidine, a-methyldopa
84
Indirect acting adrenergic agonists
Amphetamine, methamphetamine, methylphenidate (Ritalin), cocaine, tyramine
85
Mixed-acting adrenergic agonists
Dopamine, ephedrine, pseudoephedrine (Sudafed)
86
Ephedrine
Mixed-acting adrenergic agonist; A, B agonist, enhances release NE
High dose -> similar to epi
87
Pseudoephedrine (Sudafed)
Mixed-acting adrenergic agonist; stereoisomer of ephedrine
| Contra: HTN, cardiomyopathy
88
Nonselective a-blockers
Phenoxybenzamine, phentolamine
89
Selective a1-blockers
Prazosin, terazosin (Hytrin), Doxazosin (Cardura), tamsulosin (Flomax)
90
Nonselective b-blockers
Propranolol, nadolol (Corgard), timolol, pindolol
91
Selective b1-blockers
Metoprolol, atenolol, bisoprolol (Zebeta), esmolol, acebutolol
92
A- and B-blockers
Labetalol, carvedilol (Coreg)
93
Phenoxybenzamine
Nonselective a-blocker; non-competitive, irreversible, lasts 4 days; a1 > a2
Use: catecholamine excess (pheo)
Adverse: postural hypotension, reflex tachycardia
94
Phentolamine
Nonselective a-blocker; competitive; a1 = a2
Use: pheo, reversal of ischemia from extravasation/injection adrenergic agonist (epi)
Adverse: postural hypotension, reflex tachycardia
95
Prazosin, terazosin (Hytrin), doxazosin (Cardura)
Selective a1-blockers; relax vasc, bladder neck, & prostate SM
Use: BPH, last resort for HTN (inc morbidity)
Adverse: 1st dose syncope, reflex tachycardia
96
Tamsulosin (Flomax)
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
Propranolol
Nonselective b-blocker; b1 = b2; high lipid solubility; 1st pass effect (oral >> 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
Nadolol (Corgard)
Nonselective b-blocker; low lipophilicity (low CNS adverse effects), renal excretion, long T½
99
Timolol
Nonselective b-blocker; topical agent for glaucoma
100
Pindolol
Nonselective b-blocker; partial agonist of b1, b2; intrinsic sympathomimetic activity = less bradycardia
101
Metoprolol
Selective b1-blocker; B1 >> 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
Atenolol
Selective b1-blocker; low lipophilicity (less CNS vs. propranolol); renal excretion, long T½
Use: HTN (monitor serum creatinine)
103
Bisoprolol (Zebeta)
Selective b1-blocker; moderate lipophilicity
104
Esmolol
Selective b1-blocker; short acting, IV only
105
Acebutolol
Selective b1-blocker; partial B1 agonist; intrinsic sympathomimetic activity (less brady)
106
Labetalol, carvedilol (Coreg)
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
Factors determining choice of b-blocker
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Receptor selectivity (lost at higher doses)
Lipid solubility (CNS adverse effects)
Half-life (doses per day)
Elimination route (renal vs. liver)
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