TOPIC 10-13: ANS DRUGS

Acetylcholine

Direct muscarinic and nicotinic receptor agonist, very short-acting, rapidly hydrolyzed by AChE and plasma cholinesterase, used locally to produce:

• Miosis

Bethanechol

Direct muscarinic agonist with strong M3 activity, resistant to AChE, used for urinary retention and bladder atony, increases detrusor contraction and urination, antidote is Atropine

Carbachol

Direct muscarinic and nicotinic agonist, long-acting, resistant to AChE, used for miosis and decreased intraocular pressure, antidote is Atropine

Methacholine

Direct muscarinic agonist with little or no nicotinic activity, used in humans to diagnose bronchial hyperreactivity/asthma

Pilocarpine

Direct muscarinic agonist, resistant to cholinesterase, used mainly for glaucoma, antidote is Atropine

Arecoline

Direct muscarinic and nicotinic agonist, more potent than Pilocarpine, stimulates the CNS, historically used as taeniafuge and purgative, antidote is Atropine

Muscarine

Direct muscarinic agonist from poisonous mushrooms (Amanita muscaria), no therapeutic use, antidote is Atropine

Nicotine

Direct nicotinic agonist from nicotine (Nicotiana tabacum) acts on autonomic ganglia, adrenal medulla, skeletal NMJ, and CNS, no therapeutic veterinary use

Neostigmine

Reversible anticholinesterase, does not cross the BBB, used for myasthenia gravis and reversal of non-depolarizing neuromuscular blockers, toxicity treated with Atropine

Pyridostigmine

Reversible anticholinesterase, similar to Neostigmine with slower onset and longer duration, used for myasthenia gravis

Ambenonium

Reversible anticholinesterase, more potent and longer acting than Neostigmine, historically used for myasthenia gravis

Demecarium

Topical ophthalmic reversible anticholinesterase, reduces intraocular pressure in glaucoma

Physostigmine

Reversible anticholinesterase, crosses the BBB, used for glaucoma and severe anticholinergic toxicity, toxicity treated with Atropine

Rivastigmine

Reversible anticholinesterase, mainly used for Alzheimer's disease and Parkinson's disease dementia

Carbaryl

Carbamate insecticide and reversible anticholinesterase, toxicity treated with Atropine

Propoxur

Carbamate insecticide for fleas, ticks, and other pests, toxicity treated with Atropine

Edrophonium

Reversible anticholinesterase with very short duration, used to diagnose myasthenia gravis

Tacrine

Lipophilic reversible anticholinesterase, crosses the BBB, previously used for Alzheimer's disease

Diisopropylfluorophosphate (DFP)

Irreversible anticholinesterase, previously used for glaucoma and mydriasis, rarely used due to toxicity, poisoning treated with Atropine and Pralidoxime

Echothiophate

Irreversible anticholinesterase, topical ophthalmic drug producing miosis and decreased intraocular pressure, poisoning treated with Atropine and Pralidoxime

Dichlorvos (DDVP)

Irreversible anticholinesterase, used as insecticide and anthelmintic, poisoning treated with Atropine and Pralidoxime

Malathion

Irreversible anticholinesterase, converted to malaoxon, used as insecticide and ectoparasiticide, poisoning treated with Atropine and Pralidoxime

Pralidoxime

Reactivates acetylcholinesterase, antidote for organophosphate poisoning, used with Atropine

Atropine

Competitive reversible non-selective muscarinic antagonist.

• Causes:

  • ↓ Secretions

  • Bronchodilation

  • Mydriasis

  • Cycloplegia

  • ↑ HR

• Uses:

  • Pre-anesthetic

  • Bradycardia

  • Organophosphate/carbamate poisoning

  • SM Spasm

  • Ophthalmic use

Hyoscine (Scopolamine)

Competitive muscarinic antagonist with stronger CNS effects than Atropine.

• Produces:

  • Sedation

  • Anti-motion sickness

  • Mydriasis

  • ↓ Secretions

Hyoscyamine

Competitive muscarinic antagonist, levo-isomer of Atropine, effects similar to Atropine

Homatropine, Tropicamide, Eucatropine, Cyclopentolate

Mydriatic-cycloplegic antimuscarinic, used to produce mydriasis and cycloplegia

Propantheline

Quaternary antimuscarinic.

• Decreases:

  • GI secretions + Spasms

  • Urinary Urgency

• Increases:

  • HR

• Uses:

  • Diarrhea

  • Urinary incontinence

  • Bradycardia

Antidote = Physostigmine

Isopropamide

Quaternary antimuscarinic with long antispasmodic and antisecretory action

Methylhomatropine

• Quaternary antimuscarinic.

• Decreases GI Motility + Secretions

• Relaxes Ureter + Bladder

Butylhyoscine

• Quaternary antimuscarinic.

• Decreases intestinal spasm + abdominal cramping.

• Used for spasmodic colic in horses.

Ipratropium

• Non-selective inhaled muscarinic antagonist.

• Causes:

  • Bronchodilation

  • ↓ Mucus Secretion

• Used for asthma and bronchospasm.

Glycopyrrolate

• Quaternary muscarinic antagonist.

• Decreased:

  • Salivary

  • Tracheobronchial Secretions

• ↑ HR

• Used as pre-anesthetic.

Oxybutynin

• Tertiary muscarinic antagonist.

• ↓ Detrusor overactivity.

• ↑ Bladder capacity.

• Used for overactive bladder and urinary incontinence.

Dicycloverine (Dicyclomine)

• Tertiary muscarinic antagonist.

• Decreases intestinal smooth muscle spasm.

• Used for:

  • Intestinal Hypermotility

  • Irritable Bowel Syndrome (IBS)

Pirenzepine, Telenzepine

Selective M1 muscarinic receptor antagonist
-zepine

Tripitramine, Methoctramine

Selective M2 muscarinic receptor antagonist

-tramine

Darifenacin, Solifenacin

Selective M3 muscarinic receptor antagonist

-fenacin

d-Tubocurarine

• Long-acting non-depolarizing neuromuscular blocker, competitive Nm receptor antagonist.

• Causes histamine release.

• Reversed by Neostigmine or Edrophonium with:

  • Atropine; or

  • Glycopyrrolate

Pancuronium

Long-acting non-depolarizing neuromuscular blocker, about 5× more potent than d-Tubocurarine, minimal histamine release.

Gallamine

Long-acting non-depolarizing neuromuscular blocker, less potent than d-Tubocurarine

Doxacurium

Long-acting non-depolarizing neuromuscular blocker, more potent than Pancuronium, avoid in renal disease

Atracurium

Intermediate-acting non-depolarizing neuromuscular blocker, undergoes Hofmann elimination, causes histamine release

Cisatracurium

Intermediate-acting non-depolarizing neuromuscular blocker, undergoes Hofmann elimination, does not cause histamine release

Mivacurium

Short-acting non-depolarizing neuromuscular blocker, causes mild histamine release

Suxamethonium (Succinylcholine)

Depolarizing neuromuscular blocker, used for endotracheal intubation and brief procedures, may cause malignant hyperthermia

Dantrolene

• Direct skeletal muscle relaxant.

• Inhibits RyR1.

• Decreases calcium release from the SR.

• Used for:

  • Malignant Hyperthermia

  • Functional Urethral Obstruction

  • Post-anesthetic Myositis

  • Exertional Rhabdomyolysis

Epinephrine (Adrenaline)

• Direct non-selective adrenergic agonist acting on:

  • α: 1, 2

  • β: 1, 2, 3

• Used for:

  • Anaphylaxis

  • Cardiac Arrest

  • Bronchoconstriction

• Adjunct to Local Anesthetics + Glaucoma.

Norepinephrine (Noradrenaline)

• Direct adrenergic agonist acting mainly on:

  • α: 1, 2

  • β: 1

• Used for:

  • Critical Hypotension

  • Septic + Neurogenic shock

Isoprenaline (Isoproterenol)

• Direct agonist of:

  • β: 1, 2

• Used for:

  • Bronchoconstriction

  • Bradycardia

  • AV Block

  • Heart Failure

Dopamine

• Mixed adrenergic and dopaminergic agonist.

• Low doses increase renal blood flow.

• Intermediate doses stimulate β1.

• High doses stimulate α1.

• Used for:

  • Shock

  • Hypotension

  • Acute heart failure

Amphetamine

• Indirect sympathomimetic.

• Increases Norepinephrine + Dopamine.

• Used for:

  • ADHD

  • Narcolepsy

Methylphenidate

• Blocks dopamine + norepinephrine reuptake.

• Used for:

  • ADHD

  • Narcolepsy

Ephedrine

• Mixed-acting sympathomimetic.

• Stimulates α + β receptors.

• Releases norepinephrine

• Used for:

  • Urinary Incontinence

  • Bronchoconstriction

  • Hypotension

  • Nasal Congestion

Pseudoephedrine

• Mixed-acting sympathomimetic.

• Similar to Ephedrine with fewer CNS effects.

• Used for:

  • Urinary Incontinence

  • Nasal Congestion

  • Bronchoconstriction

Phenylpropanolamine

• Predominantly α-adrenergic agonist.

• Increases urethral sphincter tone for urinary incontinence.

Metaraminol

• Mixed-acting sympathomimetic + dominant α-adrenergic vasoconstriction.

• Used for acute hypotension.

Oxymetazoline

• Direct α-adrenergic agonist.

• Topical nasal decongestant + ophthalmic vasoconstrictor.

• Prolonged use may cause rebound congestion.

Phenylephrine

• Selective α1 agonist.

• Used for:

  • Hypotension

  • Nasal decongestion

  • Mydriasis

• Toxicity treated with Phentolamine or Propranolol.

Methoxamine

• Selective α1 agonist.

• Used for hypotension during general anesthesia.

Midodrine

• Prodrug converted to selective α1 agonist.

• Used for orthostatic hypotension

Clonidine

• Selective α2 agonist.

• Used as:

  • Sedative

  • Anti-anxiety agent

Xylazine

• Selective α2 agonist.

• Used as:

  • Sedative

  • Analgesic

  • Pre-anesthetic

Detomidine

• Selective α2 agonist.

• Used in horses for:

  • Sedation

  • Analgesia

  • Standing Procedures

Medetomidine, Dexmedetomidine, Romifidine

-idine

Selective α2 agonist as Sedative-analgesic

Apraclonidine, Brimonidine

-nidine

Selective α2 agonist for Glaucoma + ↓ Intraocular Pressure

Dobutamine

• Selective β1 agonist.

• Positive inotrope.

• Used for:

  • Congestive Heart Failure

  • Cardiogenic Shock

  • Anesthesia-related Hypotension

Terbutaline

• Selective β2 agonist.

• Bronchodilator for:

  • Asthma

  • Bronchitis

  • Collapsing Trachea

• Also a tocolytic.

Clenbuterol

• Selective β2 agonist.

• Bronchodilator for equine recurrent airway obstruction.

• Also a tocolytic.

Salbutamol (Albuterol)

• Short-acting β2 agonist.

• Bronchodilator for:

  • Asthma

  • Bronchospasm

  • Bronchitis

Salmeterol

• Long-acting β2 agonist.

• Bronchodilator for long-term control of:

  • Asthma

  • COPD-type Airway Disease

Formoterol

• Long-acting β2 agonist for:

  • Chronic Asthma Control

Phenoxybenzamine

• Irreversible non-selective α1 and α2 antagonist.

• Used for:

  • Pheochromocytoma

• Reduce urethral sphincter tone.

Tolazoline

• Reversible non-selective α1 and α2 antagonist.

• Mainly used to reverse Xylazine effects.

Phentolamine

• Reversible non-selective α1 and α2 antagonist.

• Used for:

  • Vasopressor Extravasation

  • Pheochromocytoma

  • Severe Phenylephrine Toxicity

Ergotamine, Dihydroergotamine, Ergocornine, Ergocristine, Ergocryptine, Ergometrine (Ergonovine)

Ergot alkaloid α-blocker, recognized mainly as a mycotoxin

Prazosin

• Selective α1 antagonist.

• Causes vasodilation + urethral relaxation

Yohimbine

• Selective α2 antagonist.

• Reverses α2 agonist sedation and analgesia, especially Xylazine.

Atipamezole

• Selective α2 antagonist.

• Reverses α2 agonist sedation and analgesia.

Propranolol

• Non-selective β1 and β2 antagonist.

• Class II antiarrhythmic.

• Used for:

  • Hypertension

  • Hyperthyroidism

  • Anxiety

• Avoid in asthma.

Metoprolol, Atenolol

• Selective β1 antagonist.

• Used for:

  • Arrhythmias

  • Hypertension

  • Hypertrophic Cardiomyopathy

Esmolol

• Ultra-short-acting selective β1 antagonist.

• Rapidly hydrolyzed by red blood cell esterases.

Butaxamine (Butoxamine)

Selective β2 antagonist, mainly a research drug.

Labetalol

• Blocks:

  • α1

  • β1, 2

Carvedilol

• Blocks:

  • α: 1

  • β: 1, 2

• Has antioxidant and anti-apoptotic cardioprotective effects.