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Flashcards in Pharmacology - Autonomic Drugs Deck (50):
1

Central and peripheral nervous system

  • The adrenal medulla and sweat glands
  • Botulinum toxin

  • 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.

2

ACh receptors

  • Nicotinic ACh receptors
    • Mechanism
    • Subtypes
  • Muscarinic ACh receptors
    • Mechanism
    • Subtypes

  • 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

3

α1 receptor

  • Type
  • G-protein class
  • Major functions

  • 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

4

α2 receptor

  • Type
  • G-protein class
  • Major functions

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

5

β1 receptor

  • Type
  • G-protein class
  • Major functions

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

6

β2 receptor

  • Type
  • G-protein class
  • Major functions

  • 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

7

M1 receptor

  • Type
  • G-protein class
  • Major functions

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

8

M2 receptor

  • Type
  • G-protein class
  • Major functions

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

9

M3 receptor

  • Type
  • G-protein class
  • Major functions

  • 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)

10

D1 receptor

  • Type
  • G-protein class
  • Major functions

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

11

D2 receptor

  • Type
  • G-protein class
  • Major functions

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

12

H1 receptor

  • Type
  • G-protein class
  • Major functions

  • 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

13

H2 receptor

  • Type
  • G-protein class
  • Major functions

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

14

V1 receptor

  • Type
  • G-protein class
  • Major functions

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

15

V2 receptor

  • Type
  • G-protein class
  • Major functions

  • 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

16

G-protein–linked 2nd messengers (224)

  • 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

17

Autonomic drugs (245)

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

18

Bethanechol

  • Type of agent
  • Clinical applications
  • Action

  • 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.”

19

Carbachol

  • Type
  • Clinical applications
  • Action

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

20

Pilocarpine

  • Type
  • Clinical applications
  • Action

  • 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.’ ”

21

Methacholine

  • Type
  • Clinical applications
  • Action

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

22

Neostigmine

  • Type
  • Clinical applications
  • Action

  • 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

Pyridostigmine

  • Type
  • Clinical applications
  • Action

  • 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

Physostigmine

  • Type
  • Clinical applications
  • Action

  • 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

Donepezil, rivastigmine, galantamine

  • Type
  • Clinical applications
  • Action

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

26

Edrophonium

  • Type
  • Clinical applications
  • Action

  • 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

Cholinomimetic agents caution

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

28

Cholinesterase inhibitor poisoning

  • Often due to...
  • Causes...
  • Organophosphates
  • Antidote

  • 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

Muscarinic antagonists

  • For each
    • Organ system(s)
    • Application(s)
  • Atropine, homatropine, tropicamide
  • Benztropine
  • Scopolamine
  • Ipratropium, tiotropium
  • Oxybutynin, darifenacin, and solifenacin
  • Glycopyrrolate

  • 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

Atropine

  • Definition
  • Action(s) in each organ system
    • Eye
    • Airway
    • Stomach
    • Gut
    • Bladder
  • Toxicity

  • 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 skincycloplegia; 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

Epinephrine

  • Type of drug
  • Effect
  • Applications

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

32

Norepinephrine

  • Type of drug
  • Effect
  • Applications

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

33

Isoproterenol

  • Type of drug
  • Effect
  • Applications

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

34

Dopamine

  • Type of drug
  • Effect
  • Applications

  • 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

Dobutamine

  • Type of drug
  • Effect
  • Applications

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

36

Phenylephrine

  • Type of drug
  • Effect
  • Applications

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

37

Albuterol, salmeterol, terbutaline

  • Type of drug
  • Effect
  • Applications

  • 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

Amphetamine

  • Type of drug
  • Effect
  • Applications

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

39

Ephedrine

  • Type of drug
  • Effect
  • Applications

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

40

Cocaine

  • Type of drug
  • Effect
  • Applications

  • 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

Norepinephrine vs. isoproterenol

  • 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

Clonidine

  • Type of drug
  • Applications
  • Toxicity

  • 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

α-methyldopa

  • Type of drug
  • Applications
  • Toxicity

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

44

Phenoxybenzamine

  • Type of drug
  • Applications
  • Toxicity

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

45

Phentolamine

  • Type of drug
  • Applications

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

46

Prazosin, terazosin, doxazosin, tamsulosin

  • Type of drug
  • Applications
  • Toxicity

  • 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

Mirtazapine

  • Type of drug
  • Applications
  • Toxicity

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

48

a-blockade of epinephrine vs. phenylephrine

  • 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

β-blockers

  • Examples
  • Selectivity
    • β1-selective antagonists (β1 > β2)
    • Nonselective antagonists (β1 = β2)
    • Nonselective α- and β-antagonists
    • Nebivolol

  • 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 M1 with 1st half of alphabet)
    • Nonselective antagonists (β1 = β2)
      • Nadolol, pindolol (partial agonist), propranolol, timolol
      • Nonselective antagonists mostly go from N to Z (β2 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

β-blockers

  • Toxicity
  • Effects
    • Angina pectoris
    • MI
    • SVT (metoprolol, esmolol)
    • Hypertension
    • CHF
    • Glaucoma (timolol)

  • 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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