Autonomic Drugs

Question 1

What is the general function of cholinomimetic agents and what are potential side effects?

Answer 1

Cholinomimetic agents increase cholinergic outflow-> “Wet picture” Parasympathetic: miosis, diarrhea, urination, bronchospasm, lacrimation; Sympathetic: sweating *Can exacerbate COPD, asthma and peptic ulcers (M3 increases bronchoconstriction and gastric acid release)

Question 2

Which drugs are direct cholinomimetic agonists?

Answer 2

Bethanechol, carbachol, methacholine, pilocarpine

Question 3

Bethanechol - what is the mechanism and action? clinical applications?

Answer 3

Direct cholinomimetic agonist Activates bowel and bladder smooth muscle -> increases urination and defication “Bethany, call (bethanechol) me to activate your bowels and bladder.” Uses: postoperative ileus, neurogenic ileus, urinary retention

Question 4

Carbachol- what is the mechanism and action? clinical applications?

Answer 4

Direct cholinomimetic agonist Contricts pupil and relieves intraocular pressure in glaucoma

Question 5

Methacholine - what is the mechanism and action? clinical applications?

Answer 5

Direct cholinomimetic agonist Stimulates muscarinic receptors (M3) in airway when inhaled -> used as challenge test for diagnosis of asthma (exacerbates asthma)

Question 6

Pilocarpine - what is the mechanism and action? clinical applications?

Answer 6

Direct cholinomimetic agonist

Action: Contracts ciliary muscle (open-angle glaucoma), contracts pupillary sphincter (closed-angle glaucoma); resistant to AChE.

Uses: Potent stimulator of sweat, tears and saliva. Open-angle and closed-angle glaucoma

“You cry, drool, and sweat on your pillow”

Question 7

What is the mechanism for indrect cholinomimetic agonists?

Answer 7

Inhibit cholinesterase -> increase synaptic levels of ACh

Question 8

Which anticholinesterases are used for Alzheimer’s disease? What is the mechanism?

Answer 8

Donepezil, galantamine, rivastigmine

Improve cognition and behavior by compensating for decreased ACh from neuronal death. *Does NOT alter progression of disease, only addresses symptoms

Question 9

Edorphonium - what is the mechanism and clinical use?

Answer 9

Indirect cholinomimetic agnoist - anticholinesterase -> increases ACh

Historically used to diagnose myasthenia gravis (very short acting), would relieve MG symptoms for short period of time by increasing ACh

Question 10

Neostigmine - what is the drug class? what are the clinical uses?

Answer 10

-stigmine: anticholinesterase, indirect agonist of ACh

Uses: postoperative and neurogenic ileus and urinary retention, myasthenia gravis, reversal of NMjunction blockade (post-op)

*Does not cross BBB b/c charged*

Question 11

Physostigmine - drug class? clinical uses?

Answer 11

-stigmine: anticholinesterase (indirect ACh agonist)

Used to treat anticholinergic toxicity like atropine overdose, crosses BBB

“Physostigmine “phyxes” atropine overdose

Question 12

Pyridostigmine - drug class? clinical uses?

Answer 12

drug class: -stigmine: anticholinesterase (ACh indirect agonist, cholinomimetic agent)

Used to treat myasthenia gravis (long acting), increases muscle strength, *Does NOT cross BBB, similar to neostigmine

“Pyridostigmine gets rid of myasthenia gravis”

Question 13

What can cause cholinesterase inhibitor poisoning? What are the symptoms? What is the antidote?

Answer 13

Usually caused by organophosphates (parathion, malathion)- components of insecticides–> Farmers

irreversibly inhibit AChE

Symptoms: “wet picture” Diarrhea, Urination, Miosis, Bronchospasm, Bradycardia, Excitation of skeletal muscle and CNS, Lacrimation, Sweating and Salivation (DUMBBELSS)

Antidote: Atropine (competitive inhibitor) + pralidoxime (regenerates AChE if given early)

Question 14

What is the function of muscarinic antagonists? What are some examples?

Answer 14

Function: decrease parasympathetic activity -> mimic sympathetic effects

Examples: Atropine, homatropine, tropicamide, benztropine, glycopyrrolate, hyoscyamine, dicyclomine, ipratropium, tiotropium, oxybutynin, solifenacin, tolterodine, scopolamine

Question 15

Which muscarinic antagonists are used for the eye? What are the clinical effects?

Answer 15

Atropine, homatropine, tropicamide.

Produce mydriasis (dilate pupil during ophthalmic exam) and cycloplegia (paralysis of ciliary muscle-> loss of acommodation)

Question 16

Benztropine - drug class? clinical use?

Answer 16

Muscarinic antagonist

Used for Parkinson disease “Park my Benz” and acute dystonia

Question 17

Glycopyrrolate - what is the drug class? clinical use?

Answer 17

Class: muscarinic antagonist, cannot cross BBB

Parenteral: peroperative use to decrease airway secretions

Oral: treat drooling, peptic ulcers

Question 18

Hyoscyamine and dicyclomine are muscarinic antagonists use for what application?

Answer 18

GI - Antispasmodics for IBS

Question 19

Which muscarinic antagonists are used to treat COPD and asthma?

Answer 19

Ipratropium, tiotropium

Block M3-> decrease bronchoconstriction

“I pray I can breathe soon”

Question 20

Which muscarinic antagonists are used to treat urinary incontinence and what is the mechanism?

Answer 20

Oxybutynin, solifenacin, tolterodine

Muscarinic antagonists are sympathetic mimetics -> relax detrussor muscle -> reduce bladder spasms

Question 21

Scolpamine - what is the drug class and clinical use?

Answer 21

Muscarinic antagonist

Used for motion sickeness

Question 22

Atropine - what are the actions, uses and toxicity of the drug?

Answer 22

Uses: treat bradycardia and for ophthalmic applications

Actions:

Eye - increase pupil dilation, cycloplegia

Airway - decrease secretions

Stomach - decrease acid secretion

Gut - decrease motility

Bladder - decrease urgency in cystitis

Toxicity: “Hot as a hare, Dry as a bone, Red as a beet, Blind as a bat, Mad as a hatter” Increase body temp (from decreased sweating), increase HR, Dry mouth, dry flushed (vasodilation to decrease temp) skin, cycloplegia, constipation, disorientation

• Can cause acute angle-closure glaucoma in elderly (mydriasis), urinary retention in men with prostatic hyperplasia, and hypertemia in infants
• Jimson weed (Datura) -> gardner’s pupil

Question 23

Tetrodotoxin - what is the source? mechanism? symptoms? treatment?

Answer 23

Source: ingestion of poorly prepared pufferfish - Japanese delicacy

Mechanism: toxin binds voltage-gated sodium channels in cardiac and nerve tissue -> blocks AP

Symptoms: typical food poisoning symptoms (nausea, vomiting, weakeness) + neuro symptoms: dizziness, paresthesias, loss of deep tendon relfexes

Treatment is supportive

Question 24

Ciguatoxin - what is the source? mechanism? symptoms? treatment?

Answer 24

Source: consumption of reef fish (barracuda, snapper, moray eel)

Mechanism: Opens sodium channels -> depolarization

Symptoms: mimic cholinergic poisoning + _*temperture-related dysesthesia (cold feels hot and visversa)*_

Treatment is supportive

Question 25

Scombroid poisoning - what is the source? mechanism? symptoms? treatment?

Answer 25

Source: consumption of dark-meat fish (bonito, mackerel, mahi-mahi, tuna) improperly stored at warm temps Mechanism: bacterial histidine decarboxylase converts histidine -\> histamine Symptoms: Increased histamine -\> acute-onset burning sensation of mouth, flushing of face, erythema, urticaria, pruritius, HA. May have anaphylaxis presentation - bronchospasm, angioedema, hypotension Treatment: antihistamines (loratadine, diphenhydramine) and antianaphylactics if needed (bronchodilators, epinephrine)

Question 26

What are examples of direct sympathomimetics?

Answer 26

Albuterol, salmeterol, dobutamine, dopamine, epinephrine, isoproternol, NE, phenylephrine

Question 27

Albuterol, salmeterol: what receptors do they act on and what are the clinical applications?

Answer 27

beta2\>beta1 --\> bronchodilatory effect Albuterol has shorter t1/2 and is used for acute asthma; salmeterol has longer t1/2 and is used for long-term asthma or COPD control

Question 28

Dobutamine - what is the function and application?

Answer 28

Direct sympathomimetic works on: beta1\>beta2, alpha Applications: heart failure (inotropic/contractility \>chronotropic/HR), cardiac stress testing

Question 29

Dopamine - what is the function and clinical application?

Answer 29

Direct sympathomimetic, works at D1=D2 \> beta \> alpha Applications: unstable bradycardia, HF, **shock\*** (increases BP WITHOUT decreasing renal perfusion since D1 relaxes renal vasculature); inotropic and chronotropic alpha effects predominate at high doses

Question 30

Epinephrine - what is the function and clinical application?

Answer 30

Function: direct sympathomimetic, beta\>alpha at low doses, alpha\>beta at high doses Used for anaphylaxis, asthma, open-angle glaucoma, \*stronger effect at beta2 receptor than norepinephrine

Question 31

Isoproterenol - what is the function and application?

Answer 31

Direct sympathomimetic: beta1=beta2 \***iso**lated beta agonist Rarely used clinically (can worsen ischemia), can be used for electrophysiologic evaluation of tachyarrhythmias

Question 32

Norepinephrine - what is the function and application?

Answer 32

direct sympathomimetic: alpha1 (vasoconstriction)\>alpha2\>beta1 (increase renin) used for hypotension, but decreases renal perfusion so contraindicated with renal problems. Weaker effect at beta2 (vasodilation) than epinehrine

Question 33

Phenylephrine - what is the function and clinical use?

Answer 33

direct sympathomimetic: alpha1\>alpha2 Used for hypotension (vasoconstriction), ocular procedures (mydriatic), rhinitis (decongestant) (\*does not cause cycloplegia bc under parasympathetic control)

Question 34

What are examples of indirect sympathomimetics and what are their mechanisms of action and clinical uses?

Answer 34

_Amphetamine_: **mechanism:** increases release of stored catecholamines and prevents reuptake at presynaptic terminal; **Uses**: narcolepsy, obesity, ADHD _Cocaine_: **mechanism**: prevents reuptake of catecholamines at presynaptic terminal; **uses**: causes vasoconstriction and local anesthesia _Ephedrine_: **mechanism:** increases release of stored catecholamines; **uses:** nasal decongestion, urinary incontinence, hypotension

Question 35

What drug class should be avoided in the case of suspected cocaine intoxication?

Answer 35

**Beta-blockers** -\> can lead to unopposed alpha1 activation by cocaine and cause severe HTN -\> MI, stroke

Question 36

Clonidine - what is the drug class? applications? toxicity?

Answer 36

_Class:_ Sympatholytic (alpha2 agonist) inhibits sympathetic outflow: increase alpha2 stimulation -\> decreased catecholamine production -\> vasodilation, decrease BP, decrease HR _Applications_: hypertensive urgency \*does NOT decrease renal blood flow, ADHD, Tourette syndrome _Toxicity_: CNS depression, bradycardia, hypotension, respiratory depression, miosis

Question 37

alpha-methyldopa: what is the drug class? applications? toxicities?

Answer 37

_Class_: Sympatholytic (alpha2 agonist) inhibits sympathetic outflow: increase alpha2 stimulation -\> decreased catecholamine production -\> vasodilation, decrease BP, decrease HR _Applications_: **\*HTN in pregnancy** _Toxicity_**: \*Direct Coombs positive hemolysis, SLE-like syndrome**

Question 38

**alpha-blockers: non-selective** What are drug examples and what are their applications and side effects?

Answer 38

**Phenoxybenzamine** (irreversible alpha-blocker) _Applications:_ used preoperatively for pheochromocytoma resection to prevent catecholamine (HTN) crisis; Half-life 24 hours and effects can last 3-4 days **Phentolamine** (reversible alpha-blocker) _Applications_: given to patients on MAOIs (inhibit breakdown of catecholamines) who have eaten tyramine-containing foods (causes toxic build up of catecholamines) _Side effects of both_: orthostatic hypotension, relfex tachycardia

Question 39

Which drugs are alpha1 selective blockers? What are their applications and side effects?

Answer 39

alpha1 selective blocking drugs with "-osin" ending: prazosin, terazosin, doxazosin, tamsulosin Applications: urinary symptoms of BPH, PTSD (prazosin), HTN (all except tamsulosin) Side effects: 1st dose **orthostatic hypotension --\> symptoms of cerebral hypoperfusion:** dizziness, HA

Question 40

Mirtazapine - what is the drug class? application? side effects?

Answer 40

drug class: alpha-blocker, alpha2 selective --\> increases sympathetic outflow since alpha2 is inhibitory Application: depression Side effects: sedation, increases serum cholesterol, increases appetite

Question 41

Beta-blockers: what are examples? what is the mechanism of action?

Answer 41

_Drugs:_ end with **-lol**, -olol for drugs that solely beta-block; -ilol, alol for alpha and beta-blocking drugs _Mechanism:_ **blocking Beta1** -\> decrease HR, decrease contractility, decrease renin release -\> decrease BP, decrease lipolysis; **blocking Beta2** -\> decrease HR and contractility, decrease aqueous humor production, decreases intraocular P, bronchoconstriction, increase uterine tone

Question 42

What are the applications of beta-blockers?

Answer 42

**Angina pectoris:** decrease HR and contractility -\> decrease O2 consumption **MI**: (metoprolol, carvedilol and bisoprolol), decrease mortality **SVT**: (metoprolol, esmolol), decrease AV conduction velocity (class II anti-arrhythmic) **HTN:** decreases CO and BP via decreased renin secretion (beta1 block on JGA cells) **Glaucoma**: (timolol), decrease aqueous humor production and decrease intraocular pressure

Question 43

What are toxic effects of beta-blockers? When should they be avoided?

Answer 43

Toxicity: impotence, adverse cardiovascular effects (bradycardia, AV block, HF), CNS adverse effects (seizures, sedation, sleep alterations), dyslipidemia (metoprolol), asthma/COPD exacerbations (via beta2 blockage) Avoid in cocain users due to risk of unopposed alpha-adrenergic agonist activity -\> HTN emergency

Question 44

Which drugs are beta1-selective antagonists? (beta1\>beta2)

Answer 44

Drugs: acebutolol (partial agonist), atenolol, betaxolol, esmolol, metoprolol (A-M, first half of alphabet) \*Good for patients with co-morbid pulmonary diseases since little antagonism at beta2 (less bronchoconstriction)

Question 45

Which drugs are nonselective beta-blockers? (beta1=beta2)

Answer 45

Drugs: Nadolol, pindolol (partial agonist), propranolol, timolol \***N**on-selective go from **N** to Z, second half of alphabet\*

Question 46

Which drugs are nonselective alpha and beta antagonists?

Answer 46

Carvedilol, labetalol (have modified ending instead of -olol)

Question 47

What is the mechanism of action of Nebivolol?

Answer 47

**Blocks beta1** receptors --\> vasodilation and **STIMULATES beta3** receptors --\> activates NO synthase

Question 48

What other classes of drugs display antimuscarinic (atropine-like) effects?

Answer 48

Antihistamines TCAs Antipsychotics Quinidine Amantadine Meperidine