All ANS Drugs Midterm 2

alpha methyl tyrosine, alpha methyl DOPA

Synthesis inhibitors in adrenergic neurotransmitters

• interference with synthesis of neurotransmitters

• false neurotransmitters

• wrong NTs synthesize less NA => decreased NA release => less SNS effects

hemicholinium

Inhibition of choline reuptake from the synapse

• decreased choline => less ACh => decreased synthesis of ACh

vesamicol

Inhibition of NT storage in cholinergic transmission

• decreased release of ACh

latrotoxin (black widow spider venom)

Displacement of NT from vesicles in cholinergic transmission

• sudden increase in ACh due to displacement

• then freezes ACh vesicles and prevents release => muscle paralysis

botulinum toxin

Prevention of NT release in cholinergic transmission

• decreased ACh release => muscle paralysis

muscarine

Cholinergic receptor agonist

• stimulate muscarinic cholinergic receptors (all targets of PNS)

atropine

Cholinergic receptor antagonists

• block muscarinic cholinergic receptors

neostigmine, nerve gases

Inhibitors of enzymatic breakdown of cholinergic NTs

reserpine

Inhibition of NT storage in adrenergic transmission

• decreased release of NA => decreased SNS effects

guanethidine

Prevention of NT release

• decreased NA release => decreased SNS effects

amphetamines, methamphetamines, ecstasy, MDMA

Displacement of NT from vesicles of adrenergic transmission

• displaces stored NA and drives it into the synapse through reversal of NA reuptake transport system

• increased NA in synapse => sympathomimetic effect

dobutamine

Adrenergic receptor agonists

• stimulates beta 1 adrenergic receptors selectively

metoprolol

Adrenergic receptor antagonist

• blocks beta 1 adrenergic receptors selectively

cocaine, tricyclic antidepressants

Inhibition of NA reuptake from the synapse

• increased levels of NA in the synapse => increased sympathetic effects

pargyline

Inhibitors of enzymatic breakdown of NT in adrenergic transmission

• inhibits MAO (enzyme within neurons that destroys unpackaged NA)

• increased NA in vesicles => more released => increased SNS effects

bethanechol

Muscarinic agonist

• charged => poor absorption

• treats urinary retention and intestinal paralysis

• SLUDGE+, decreased HR, decreased force of contractility, construction of bronchi, miosis

pilocarpine

Muscarinic agonist

• treats glaucoma and xerostomia

• SLUDGE+, decreased HR, decreased force of contractility, construction of bronchi, miosis

carbachol

Muscarinic agonist

• treats glaucoma

• SLUDGE+, decreased HR, decreased force of contractility, construction of bronchi, miosis

arecoline

Muscarinic agonist

• found in betel nut from areca palm

• SLUDGE+, decreased HR, decreased force of contractility, constriction of bronchi, miosis

acetylcholine

muscarinic agonist

Muscarine

Muscarinic agonist

• found in poisonous mushrooms

  • Amanita muscaria

  • Inocybe

  • Clitocybe

neostigmine

Reversible AChE inhibitor

• charged

• temporarily inactivates acetylcholinesterase

• increased effects at muscarinic and neuromuscular cholinergic receptors

physostigmine

Reversible AChE inhibitor

• neutral

• temporarily inactivates acetylcholinesterase

• increased effects at muscarinic and neuromuscular cholinergic receptors

edrophonium

Reversible AChE inhibitor

• short-acting

• temporarily inactivates acetylcholinesterase

• increased effects at muscarinic and neuromuscular cholinergic receptors

• can be used to differentiate between cholinergic crisis (excessive neostigmine) vs. severe myasthenia (insufficient neostigmine)

galantamine (Reminyl) rivastigmine (Exelon), donepezil (Aricept)

Reversible AChE inhibitor

• treats Alzheimer’s disease

echothiophate, insecticides (ex. malathion), nerve gases (ex. sarin, XV, tabun)

Irreversible AChE inhibitor

• excessive muscarinic stimulation

• inhibition of neuromuscular transmission

pralidoxime

Treatment for EARLY exposure to irreversible AChE inhibitors

atropine

Muscarinic antagonist

• Atropa belladonna

• treatment for irreversible AChE inhibitors

• causes tachycardia, decreased GI secretions and motility, relaxation of bronchi, mydriasis, cycloplegia

• Uses: reduce urinary incontinence, decrease hypermobility of gut, pre-op/palliative care (drying out the secretions), eye exam/surgery, treatment of muscarinic poisoning, treatment of asthma

• Adverse effects: xerostomia, anhidrosis, urinary retention, constipation, blurred vision, photophobia

• High doses: excessive excitation of CNS => delirium, psychosis

oxygen/mechanical ventilation, atropine, diazepam, pralidoxime

Treatment for irreversible AChE inhibitors

diazepam

Treatment for irreversible AChE inhibitors

• suppress seizures, anxiolytic

tolterodine, oxybutynin, solifenacin

Muscarinic antagonist

• causes tachycardia, decreased GI secretions and motility, relaxation of bronchi, mydriasis, cycloplegia

• Uses: reduce urinary incontinence, decrease hypermobility of gut, pre-op/palliative care (drying out the secretions), eye exam/surgery, treatment of muscarinic poisoning, treatment of asthma

• Adverse effects: xerostomia, anhidrosis, urinary retention, constipation, blurred vision, photophobia

• High doses: excessive excitation of CNS => delirium, psychosis

scopolamine

Muscarinic antagonist

• administered as a transdermal patch as an antiemetic

  • reduce nausea and vomiting due to motion sickness

  • reduce excessive secretions

tubocurarine, cisatracurium, rocuronium

Non-depolarizing neuromuscular blocker

• antagonist for nicotinic muscle receptors

• compete with ACh to bind with muscle nicotinic receptor

• Uses:

  • antagonist for nicotinic muscle receptors

  • relaxation during surgery

  • endotracheal intubation

  • mechanical ventilation

• Adverse effects:

  • cessation of breathing

succinylcholine

Depolarizing neuromuscular blocker

• overstimulate receptors until they become inactivated

• metabolized by plasma cholinesterases

• trigger malignant hyperthermia

  • high body temp, rigid muscles/spasms, rapid heart rate

dantrolene

Treatment for depolarizing neuromuscular blockers

• blocks calcium release from intracellular sarcoplasmic reticulum stores in skeletal muscle

catecholamines

• all share similar chemical structure

• noradrenaline, adrenaline, dopamine

adrenaline

Adrenergic agonist

• Uses:

  • anaphylactic shock

    • combats bronchoconstriction, vasodilation, leaky blood vessels, edema

  • cardiac arrest

  • control bleeding

  • limits diffusion of medications by causing local vasoconstriction

• Adverse effects: arrhythmias, HTN, diabetes (high blood glucose)

phenylephrine

Alpha 1 agonist

• Mechanism:

  • stimulates alpha 1 receptors

  • vasoconstriction

• Uses:

  • control superficial bleeding

  • reduces congestion (vasoconstriction of blood vessels in sinuses)

  • mydriasis

  • treat hypotensive emergencies

• Adverse: excessive increases in BP

clonidine

Alpha 2 adrenergic agonist

• Mechanism:

  • presynaptic feedback that leads to decreased NA release

  • less sympathetic effects => vasodilation

• Uses: antihypertensive

• Adverse:

  • hypotension

  • dry mouth

  • sedation

dobutamine

Beta 1 agonist

• Effect: increased heart rate, force of contraction

• treats acute heart failure

• Adverse: arrhythmias, tachycardia

salbutamol

Beta 2 agonist

• Effect: dilation of bronchi

• Use: relieves asthma caused by bronchospasm

• Adverse: palpitations, tremor, hyperglycemia

mirabergon

Beta 3 agonist

• Effect: relaxation of detrusor muscle

• Use: urinary urgency/incontinence

• Adverse: tachycardia, increased BP

isoproterenol

non-specific beta adrenergic agonist

ephedrine, pseudoephedrine

Indirect-acting sympathomimetic displacement

• stimulate the release of NA from vesicles

• mixed-acting: displacement drugs AND agonists

• treat nasal congestion

amphetamine

Indirect-acting sympathomimetic displacement

• Uses:

  • stimulates CNS (improved concentration and focus)

  • treats ADD

  • decreased appetite => weight loss

• Adverse: insomnia, irritability, psychosis, anorexia, tachycardia, dependence, tolerance

• Treating toxicity: acidification of urine

cocaine, tricyclic antidepressants

Indirect-acting sympathomimetic; inhibits reuptake of noradrenaline

Inhibition of MAO

Indirect-acting sympathomimetic; inhibits NA breakdown

prazosin, terazosin, doxazosin

Alpha 1 antagonist

• Mechanism: reduces vasoconstriction and peripheral resistance

• Uses: treats HTN

• Adverse: orthostatic hypotension with reflex increase in heart rate

yohimbine

Alpha 2 antagonist

• Mechanism: increase perfusion of certain tissues

• Uses:

  • erectile dysfunction

  • lipolytic agent

• Adverse: tachycardia, HTN, hypoglycemia

phentolamine

Reversible non-specific alpha antagonist

• treatment of NA secreting tumour: phenoxybenzamine

phenoxybenzamine

Irreversible non-specific alpha antagonist

• treatment of NA secreting tumour: pheochromocytoma

propranolol

Non-specific beta antagonist

• Uses:

  • angina, hypertension, heart failure

  • post myocardial infarction, arrhythmia

  • stage fright, anxiety, migraine prophylaxis

• Adverse:

  • beta 1: bradycardia, heart failure, hypotension

  • beta 2 bronchoconstriction, inhibition of hepatic glycogenolysis, inhibition of symptoms of hypoglycemia, inhibition of lipolysis (increased triglycerides

  • sedation, lethargy, erectile dysfunction, nightmares

metoprolol, atenolol, bisoprolol

Beta 1 antagonist

• Mechanism:

  • decreased HR and contractility

  • decreased secretion of renin

  • decreased activation of renin-angiotensin-aldosterone system

• Uses: HTN, angina, arrhythmias