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First Aid > Pharmacology - Autonomic Drugs > Flashcards

Pharmacology - Autonomic Drugs Flashcards

1
Q

Central and peripheral nervous system

  • The adrenal medulla and sweat glands
  • Botulinum toxin
A
  • The adrenal medulla and sweat glands
    • Part of the sympathetic nervous system but are innervated by cholinergic fibers.
  • Botulinum toxin
    • Prevents release of neurotransmitter at all cholinergic terminals.
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2
Q

ACh receptors

  • Nicotinic ACh receptors
    • Mechanism
    • Subtypes
  • Muscarinic ACh receptors
    • Mechanism
    • Subtypes
A
  • Nicotinic ACh receptors
    • Mechanism
      • Ligand-gated Na+/K+ channels
    • 2 subtypes
      • NN (found in autonomic ganglia)
      • NM (found in neuromuscular junction)
  • Muscarinic ACh receptors
    • Mechanism
      • G-protein–coupled receptors that usually act through 2nd messengers
    • 5 subtypes
      • M1, M2, M3, M4, and M5
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3
Q

α1 receptor

  • Type
  • G-protein class
  • Major functions
A
  • Type
    • Sympathetic G-protein–linked 2nd messenger
  • G-protein class
    • q
  • Major functions
    • Increase vascular smooth muscle contraction
    • Increase pupillary dilator muscle contraction (mydriasis)
    • Increase intestinal and bladder sphincter muscle contraction
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4
Q

α2 receptor

  • Type
  • G-protein class
  • Major functions
A
  • Type
    • Sympathetic G-protein–linked 2nd messenger
  • G-protein class
    • i
  • Major functions
    • Decrease sympathetic outflow
    • Decrease insulin release
    • Decrease lipolysis
    • Increase platelet aggregation
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5
Q

β1 receptor

  • Type
  • G-protein class
  • Major functions
A
  • Type
    • Sympathetic G-protein–linked 2nd messenger
  • G-protein class
    • s
  • Major functions
    • Increase heart rate
    • Increase contractility
    • Increase renin release
    • Increase lipolysis
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6
Q

β2 receptor

  • Type
  • G-protein class
  • Major functions
A
  • Type
    • Sympathetic G-protein–linked 2nd messenger
  • G-protein class
    • s
  • Major functions
    • Vasodilation
    • Bronchodilation
    • Increase heart rate
    • Increase contractility
    • Increase lipolysis
    • Increase insulin release
    • Decrease uterine tone (tocolysis)
    • Ciliary muscle relaxation
    • Increase aqueous humor production
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7
Q

M1 receptor

  • Type
  • G-protein class
  • Major functions
A
  • Type
    • Parasympathetic G-protein–linked 2nd messenger
  • G-protein class
    • q
  • Major functions
    • CNS
    • Enteric nervous system
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8
Q

M2 receptor

  • Type
  • G-protein class
  • Major functions
A
  • Type
    • Parasympathetic G-protein–linked 2nd messenger
  • G-protein class
    • i
  • Major functions
    • Decrease heart rate and contractility of atria
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9
Q

M3 receptor

  • Type
  • G-protein class
  • Major functions
A
  • Type
    • Parasympathetic G-protein–linked 2nd messenger
  • G-protein class
    • q
  • Major functions
    • Decrease exocrine gland secretions (e.g., lacrimal, salivary, gastric acid)
    • Increase gut peristalsis
    • Increase bladder contraction
    • Bronchoconstriction
    • Increase pupillary sphincter muscle contraction (miosis)
    • Ciliary muscle contraction (accommodation)
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10
Q

D1 receptor

  • Type
  • G-protein class
  • Major functions
A
  • Type
    • Dopamine G-protein–linked 2nd messenger
  • G-protein class
    • s
  • Major functions
    • Relaxes renal vascular smooth muscle
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11
Q

D2 receptor

  • Type
  • G-protein class
  • Major functions
A
  • Type
    • Dopamine G-protein–linked 2nd messenger
  • G-protein class
    • i
  • Major functions
    • Modulates transmitter release, especially in brain
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12
Q

H1 receptor

  • Type
  • G-protein class
  • Major functions
A
  • Type
    • Histamine G-protein–linked 2nd messenger
  • G-protein class
    • q
  • Major functions
    • Increase nasal and bronchial mucus production
    • Increase vascular permeability
    • Contraction of bronchioles
    • Pruritus
    • Pain
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13
Q

H2 receptor

  • Type
  • G-protein class
  • Major functions
A
  • Type
    • Histamine G-protein–linked 2nd messenger
  • G-protein class
    • s
  • Major functions
    • Increase gastric acid secretion
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14
Q

V1 receptor

  • Type
  • G-protein class
  • Major functions
A
  • Type
    • Vasopressin G-protein–linked 2nd messenger
  • G-protein class
    • q
  • Major functions
    • Increase vascular smooth muscle contraction
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15
Q

V2 receptor

  • Type
  • G-protein class
  • Major functions
A
  • Type
    • Vasopressin G-protein–linked 2nd messenger
  • G-protein class
    • s
  • Major functions
    • Increase H2O permeability and reabsorption in the collecting tubules of the
      kidney
    • V2** is found in the 2 kidneys**
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16
Q

G-protein–linked 2nd messengers (224)

A
  • “Qiss (kiss) and qiq (kick) till you’re siq (sick) of sqs (super qinky sex).”
  • α1 q
  • α2 i
  • β1 s
  • β2 s
  • M1 q
  • M2 i
  • M3 q
  • D1 s
  • D2 i
  • H1 q
  • H2 s
  • V1 q
  • V2 s
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17
Q

Autonomic drugs (245)

A
  • Release of norepinephrine from a sympathetic nerve ending is modulated by norepinephrine itself, acting on presynaptic α2-autoreceptors, angiotensin II, and other substances.
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18
Q

Bethanechol

  • Type of agent
  • Clinical applications
  • Action
A
  • Type of agent
    • Direct cholinomimetic agent
  • Clinical applications
    • Postoperative ileus, neurogenic ileus, and urinary retention
  • Action
    • Activates bowel and bladder smooth muscle
    • Resistant to AChE.
    • “Bethany, call (bethanechol) me, maybe, if you want to activate your bowels and bladder.”
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19
Q

Carbachol

  • Type
  • Clinical applications
  • Action
A
  • Type of agent
    • Direct cholinomimetic agent
  • Clinical applications
    • Glaucoma, pupillary constriction, and relief of intraocular pressure
  • Action
    • Carbon copy of acetylcholine.
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20
Q

Pilocarpine

  • Type
  • Clinical applications
  • Action
A
  • Type of agent
    • Direct cholinomimetic agent
  • Clinical applications
    • Potent stimulator of sweat, tears, and saliva
    • Open-angle and closed-angle glaucoma
  • Action
    • Contracts ciliary muscle of eye (open-angle glaucoma), pupillary sphincter (closed-angle glaucoma)
    • Resistant to AChE.
    • “You cry, drool, and sweat on your ‘pilow.’ ”
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21
Q

Methacholine

  • Type
  • Clinical applications
  • Action
A
  • Type of agent
    • Direct cholinomimetic agent
  • Clinical applications
    • Challenge test for diagnosis of asthma
  • Action
    • Stimulates muscarinic receptors in airway when inhaled.
22
Q

Neostigmine

  • Type
  • Clinical applications
  • Action
A
  • Type of agent
    • Indirect cholinomimetic agent (anticholinesterase)
  • Clinical applications
    • Postoperative and neurogenic ileus and urinary retention, myasthenia gravis, reversal of neuromuscular junction blockade (postoperative)
  • Action
    • Increases endogenous ACh.
    • Neo CNS = No CNS penetration.
23
Q

Pyridostigmine

  • Type
  • Clinical applications
  • Action
A
  • Type of agent
    • Indirect cholinomimetic agent (anticholinesterase)
  • Clinical applications
    • Myasthenia gravis (long acting)
    • Does not penetrate CNS
  • Action
    • Increases endogenous ACh
    • Increases strength.
    • Pyridostigmine gets rid of myasthenia gravis.
24
Q

Physostigmine

  • Type
  • Clinical applications
  • Action
A
  • Type of agent
    • Indirect cholinomimetic agent (anticholinesterase)
  • Clinical applications
    • Anticholinergic toxicity (crosses blood-brain barrier –>Ž CNS)
  • Action
    • Increases endogenous ACh.
    • Physostigmine “phyxes” atropine overdose.
25
Q

Donepezil, rivastigmine, galantamine

  • Type
  • Clinical applications
  • Action
A
  • Type of agent
    • Indirect cholinomimetic agent (anticholinesterase)
  • Clinical applications
    • Alzheimer disease
  • Action
    • Increases endogenous ACh.
26
Q

Edrophonium

  • Type
  • Clinical applications
  • Action
A
  • Type of agent
    • Indirect cholinomimetic agent (anticholinesterase)
  • Clinical applications
    • Historically, diagnosis of myasthenia gravis (extremely short acting).
    • Myasthenia now diagnosed by anti-AChR Ab (antiacetylcholine receptor antibody) test.
  • Action
    • Increases endogenous ACh.
27
Q

Cholinomimetic agents caution

A
  • With all cholinomimetic agents, watch for exacerbation of COPD, asthma, and peptic ulcers when giving to susceptible patients.
28
Q

Cholinesterase inhibitor poisoning

  • Often due to…
  • Causes…
  • Organophosphates
  • Antidote
A
  • Often due to…
    • Organophosphates, such as parathion, that irreversibly inhibit AChE.
  • Causes…
    • Diarrhea, Urination, Miosis, Bronchospasm, Bradycardia, Excitation of skeletal muscle and CNS, Lacrimation, Sweating, and Salivation.
    • DUMBBELSS.
  • Organophosphates
    • Components of insecticides
    • Poisoning usually seen in farmers.
  • Antidote
    • Aropine (competitive inhibitor) + pralidoxime (regenerates AChE if given early).
29
Q

Muscarinic antagonists

  • For each
    • Organ system(s)
    • Application(s)
  • Atropine, homatropine, tropicamide
  • Benztropine
  • Scopolamine
  • Ipratropium, tiotropium
  • Oxybutynin, darifenacin, and solifenacin
  • Glycopyrrolate
A
  • Atropine, homatropine, tropicamide
    • Organ system(s): Eye
    • Application(s): Produce mydriasis and cycloplegia.
  • Benztropine
    • Organ system(s): CNS
    • Application(s): Parkinson disease
      • “Park my Benz.”
  • Scopolamine
    • Organ system(s): CNS
    • Application(s): Motion sickness.
  • Ipratropium, tiotropium
    • Organ system(s): Respiratory
    • Application(s): COPD, asthma
      • “I pray I can breathe soon!”
  • Oxybutynin, darifenacin, and solifenacin
    • Organ system(s): Genitourinary
    • Application(s):
      • Reduce urgency in mild cystitis and reduce bladder spasms.
      • Other agents: tolterodine, fesoterodine, trospium.
  • Glycopyrrolate
    • Organ system(s): Gastrointestinal, respiratory
    • Application(s):
      • Parenteral: preoperative use to reduce airway secretions.
      • Oral: drooling, peptic ulcer.
30
Q

Atropine

  • Definition
  • Action(s) in each organ system
    • Eye
    • Airway
    • Stomach
    • Gut
    • Bladder
  • Toxicity
A
  • Definition
    • Muscarinic antagonist.
    • Used to treat bradycardia and for ophthalmic applications.
    • Blocks DUMBBeLSS.
      • Diarrhea, Urination, Miosis, Bronchospasm, Bradycardia, Lacrimation, Sweating, and Salivation
    • Skeletal muscle and CNS excitation mediated by nicotinic receptors.
  • Action(s) in each organ system
    • Eye –> increase pupil dilation, cycloplegia
    • Airway –> decrease secretions
    • Stomach –> decrease acid secretion
    • Gut –> decrease motility
    • Bladder –> decrease urgency in cystitis
  • Toxicity
    • Increase body temperature (due to decreased sweating); rapid pulse; dry mouth; dry, flushed skin; cycloplegia; constipation; disorientation
      • ​Hot** as a hare**
      • Dry as a bone
      • Red as a beet
      • Blind as a bat
      • Mad as a hatter
    • Can cause acute angle-closure glaucoma in elderly (due to mydriasis), urinary retention in men with prostatic hyperplasia, and hyperthermia in infants
    • Jimson weed (Datura) –>Ž gardeners pupil (mydriasis due to plant alkaloids)
31
Q

Epinephrine

  • Type of drug
  • Effect
  • Applications
A
  • Type of drug
    • Direct sympathomimetic
  • Effect
    • β > α
  • Applications
    • Anaphylaxis
    • Open angle glaucoma
    • Asthma
    • Hypotension
    • α effects predominate at high doses
32
Q

Norepinephrine

  • Type of drug
  • Effect
  • Applications
A
  • Type of drug
    • Direct sympathomimetic
  • Effect
    • α1 > α2 > β1
  • Applications
    • Hypotension (but decrease renal perfusion)
33
Q

Isoproterenol

  • Type of drug
  • Effect
  • Applications
A
  • Type of drug
    • Direct sympathomimetic
  • Effect
    • β1 = β2
  • Applications
    • Electrophysiologic evaluation of tachyarrhythmias.
    • Can worsen ischemia.
34
Q

Dopamine

  • Type of drug
  • Effect
  • Applications
A
  • Type of drug
    • Direct sympathomimetic
  • Effect
    • D1 = D2 > β > α
  • Applications
    • Unstable bradycardia, heart failure, shock
    • Inotropic and chronotropic α effects predominate at high doses
35
Q

Dobutamine

  • Type of drug
  • Effect
  • Applications
A
  • Type of drug
    • Direct sympathomimetic
  • Effect
    • β1 > β2, α
  • Applications
    • Heart failure (inotropic > chronotropic)
    • Cardiac stress testing
36
Q

Phenylephrine

  • Type of drug
  • Effect
  • Applications
A
  • Type of drug
    • Direct sympathomimetic
  • Effect
    • α1 > α2
  • Applications
    • Hypotension (vasoconstrictor)
    • Ocular procedures (mydriatic)
    • Rhinitis (decongestant)
37
Q

Albuterol, salmeterol, terbutaline

  • Type of drug
  • Effect
  • Applications
A
  • Type of drug
    • Direct sympathomimetic
  • Effect
    • β2 > β1
  • Applications
    • Albuterol for acute asthma
    • Salmeterol for long-term asthma or COPD control
    • Terbutaline to reduce premature uterine contractions
38
Q

Amphetamine

  • Type of drug
  • Effect
  • Applications
A
  • Type of drug
    • Indirect sympathomimetic
  • Effect
    • Indirect general agonist
    • Reuptake inhibitor
    • Releases stored catecholamines
  • Applications
    • Narcolepsy
    • Obesity
    • Attention deficit disorder
39
Q

Ephedrine

  • Type of drug
  • Effect
  • Applications
A
  • Type of drug
    • Indirect sympathomimetic
  • Effect
    • Indirect general agonist
    • Releases stored catecholamines
  • Applications
    • Nasal decongestion
    • Urinary incontinence
    • Hypotension
40
Q

Cocaine

  • Type of drug
  • Effect
  • Applications
A
  • Type of drug
    • Indirect sympathomimetic
  • Effect
    • Indirect general agonist
    • Reuptake inhibitor
  • Applications
    • Causes vasoconstriction and local anesthesia
    • Never give β-blockers if cocaine intoxication is suspected
      • Can lead to unopposed α1 activation and extreme hypertension
41
Q

Norepinephrine vs. isoproterenol

A
  • Norepinephrine causes increases in systolic and diastolic pressures as a result of α1-mediated vasoconstriction Ž–> increased mean arterial pressure –>Ž bradycardia.
  • However, isoproterenol (no longer commonly used) has little α effect but causes β2-mediated vasodilation, resulting in decreased mean arterial pressure and increased heart rate through β1 and reflex activity.
42
Q

Clonidine

  • Type of drug
  • Applications
  • Toxicity
A
  • Type of drug
    • Sympatholytic (α2-agonist)
  • Applications
    • Hypertensive urgency (limited situations)
      • Does not decrease renal blood flow
    • ADHD, severe pain, and a variety of offlabel indications
      • e.g., ethanol and opioid withdrawal
  • Toxicity
    • CNS depression
    • Bradycardia
    • Hypotension
    • Respiratory depression
    • Small pupil size
43
Q

α-methyldopa

  • Type of drug
  • Applications
  • Toxicity
A
  • Type of drug
    • Sympatholytic (α2-agonist)
  • Applications
    • Hypertension in pregnancy
    • Safe in pregnancy
  • Toxicity
    • Direct Coombs (+) hemolytic anemia
    • SLE-like syndrome
44
Q

Phenoxybenzamine

  • Type of drug
  • Applications
  • Toxicity
A
  • Type of drug
    • Irreversible nonselective α-blocker
  • Applications
    • Pheochromocytoma (used preoperatively) to prevent catecholamine (hypertensive) crisis
  • Toxicity
    • Orthostatic hypotension
    • Reflex tachycardia
45
Q

Phentolamine

  • Type of drug
  • Applications
A
  • Type of drug
    • Reversible nonselective α-blocker
  • Applications
    • Give to patients on MAO inhibitors who eat tyramine-containing foods
46
Q

Prazosin, terazosin, doxazosin, tamsulosin

  • Type of drug
  • Applications
  • Toxicity
A
  • Type of drug
    • α1 selective (-osin ending) α-blocker
  • Applications
    • Urinary symptoms of BPH
    • PTSD (prazosin)
    • Hypertension (except tamsulosin)
  • Toxicity
    • 1st-dose orthostatic hypotension
    • Dizziness
    • Headache
47
Q

Mirtazapine

  • Type of drug
  • Applications
  • Toxicity
A
  • Type of drug
    • α2 selective α-blocker
  • Applications
    • Depression
  • Toxicity
    • Sedation
    • Increased serum cholesterol
    • Increased appetite
48
Q

a-blockade of epinephrine vs. phenylephrine

A
  • Image: the effects of an α-blocker (e.g., phentolamine) on blood pressure responses to epinephrine and phenylephrine.
  • The epinephrine response exhibits reversal of the mean blood pressure change, from a net increase (the α response) to a net decrease (the β2 response).
  • The response to phenylephrine is suppressed but not reversed because phenylephrine is a “pure” α-agonist without β action.
49
Q

β-blockers

  • Examples
  • Selectivity
    • β1-selective antagonists (β1 > β2)
    • Nonselective antagonists (β1 = β2)
    • Nonselective α- and β-antagonists
    • Nebivolol
A
  • Examples
    • Metoprolol, acebutolol, betaxolol, carvedilol, esmolol, atenolol, nadolol, timolol, pindolol, labetalol.
  • Selectivity
    • β1-selective antagonists (β1 > β2)
      • Acebutolol (partial agonist), atenolol, betaxolol, esmolol, metoprolol
      • Selective antagonists mostly go from A to M (β_1_ with 1st half of alphabet)
    • Nonselective antagonists (β1 = β2)
      • Nadolol, pindolol (partial agonist), propranolol, timolol
      • Nonselective antagonists mostly go from N to Z (β_2_ with 2nd half of alphabet)
    • Nonselective α- and β-antagonists
      • Carvedilol, labetalol
      • Nonselectives α- and β-antagonists have modified suffixes (instead of “-olol”)
    • Nebivolol
      • Combines cardiac-selective β1‑adrenergic blockade with stimulation of β3‑receptors, which activate nitric oxide synthase in the vasculature
50
Q

β-blockers

  • Toxicity
  • Effects
    • Angina pectoris
    • MI
    • SVT (metoprolol, esmolol)
    • Hypertension
    • CHF
    • Glaucoma (timolol)
A
  • Toxicity
    • Impotence, cardiovascular adverse effects (bradycardia, AV block, CHF), CNS adverse effects (seizures, sedation, sleep alterations), dyslipidemia (metoprolol), and asthmatics/ COPDers (may cause exacerbation)
    • Avoid in cocaine users due to risk of unopposed α-adrenergic receptor agonist activity
    • Despite theoretical concern of masking hypoglycemia in diabetics, benefits likely outweigh risks; not contraindicated
  • Effects
    • Angina pectoris 
      • Decrease heart rate and contractility, resulting in decreased O2 consumption
    • MI
      • β-blockers (metoprolol, carvedilol, and bisoprolol) decrease mortality
    • SVT (metoprolol, esmolol)
      • Decrease AV conduction velocity (class II antiarrhythmic)
    • Hypertension 
      • Decreases cardiac output
      • Decreases renin secretion (due to β1-receptor blockade on JGA cells)
    • CHF
      • Slows progression of chronic failure
    • Glaucoma (timolol) 
      • Decreases secretion of aqueous humor

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