PNS Pharmacology Flashcards
4 organs with single (sympathetic) innervation
Blood vessels
Spleen
Piloerector muscles
Sweat glands
Which neurons are cholinergic?
ALL motor neurons to skeletal muscle
ALL preganglionic autonomic neurons
ALL postganglionic parasympathetic neurons
Some postganglionic sympathetic neurons (sweat glands, some blood vessels in skeletal muscle)
Carbachol Class Use Mechanism Administration Adverse rxns
Muscarinic agonist
Constricts iris and ciliary body → miosis during surgery and reduced IOP following cataract surgery
•Agonist at muscarinic receptors, but also has strong nicotinic (Nn) activity
•Administered directly to eye
•Not inactivated by AchE → long duration
•Adverse rxns: rare iritis or corneal clouding
Methacholine Class Use Mechanism Reversal Precaution
Muscarinic agonist
Used for diagnosis of airway hyperreactivity. Inhaled.
•Agonist at muscarinic receptors. Less nicotinic activity than carbachol.
•If bronchoconstriction occurs, administer albuterol (B2 agonist → bronchodilation)
•Precaution: asthma
Bethanechol Class Use Mechanism Precautions
Muscarinic agonist
Promotes GI and urine motility following surgery or due to postpartum nonobstructive urinary retention.
•Muscarinic agonist w/ zero nicotinic activity
•Precautions – urinary tract obstruction
Pilocarpine Class Use Mechanism Adverse rxns Precautions
Muscarinic agonist
Treats glaucoma by contracting ciliary and circular muscles (M3) → miosis and increased outflow of aqueous humor. Also treats xerostomia caused by Sjogren’s Syndrome and salivary gland dysfunction.
•Muscarinic agonist
•Adverse rxns: blurred vision, hypersalivation, diaphoresis, flushing
•Precautions: asthma, iritis, posterior synechiae (adhesion b/w iris and lens), retinal detachment
Nicotine Class Use Mechanism Adverse rxns Precautions
Nicotinic agonist
•Smoking cessation
•Agonist at Nm and Nn receptors
•Stimulates catecholamine release.
•Adverse rxns: CNS (dizziness, insomnia, irritability), CV (increased BP due to increased inotropic / chronotropic actions)
•Precautions: CV problems, pregnancy category D
Varenicline Use Mechanism Adverse rxns Precautions
Smoking cessation
•Partial agonist at alpha4-beta2 nicotinic receptors in brain. Moderate serotinin activity.
•Adverse rxns: GI (nausea, constipation, farts), CNS (insomnia, vivid dreams, irritability, hostility)
•Precautions – renal insufficiency and black box warning for changes in behavior, such as hostility, agitation, depression, and suicide
Physostigmine Class Use Mechanism Adverse rxns Precautions
Acetylcholinesterase antagonist
DOC to counteract toxic anticholinergic effects of other drugs. Also treats glaucoma.
•Carbamoyl ester class – Competes w/ Ach at binding site of AchE. Carbamoylates AchE to inactivate it. Mimics increased Ach.
•Adverse rxns: SLUDGE
• CNS: restlessness, seizures
• CV: irregular pulse, palpitations, bradycardia
• GI: hypersalivation, cramps, NVD
• UG: urinary urgency
• Lung: bronchospasm, dyspnea, ↑ secretions
• Eye: miosis, lacrimation, blurred vision
•Precautions: asthma, GI obstruction (obstructive ileus), urinary tract obstruction
Neostigmine Class Use Mechanism Adverse rxns Precautions
AchE inhibitor
Treats myasthenia gravis (autoantibodies target NMJ Ach receptors), neurogenic ileus, and postop reversal of NMJ blocker
•Carbamoyl ester class – same mechanism as physostigmine.
•Good to use for neurogenic ileus b/c it’s charged, so it only affects PNS, not CNS
•Adverse rxns:
• CV: irregular pulse, palpitations, bradycardia
• GI: hypersalivation, cramps, NVD
• UG: urinary urgency
• Lung: bronchospasm, dyspnea, ↑ secretions
• Eye: miosis, lacrimation, blurred vision
•Precautions: asthma, obstructive ileus, urinary tract obstruction, peptic ulcer
• Ach stimulates acid secretion → ulcers
Edrophonium Class Use Mechanism Adverse rxns
AchE inhibitor
DOC for diagnosing myasthenia gravis. Also treates ileus and reverses NMJ blockers after surgery.
•Alcohol – competitive inhibitor for Ach at AchE
• Very rapid action and short duration. Not good for tx of myasthenia gravis.
•Adverse rxns:
• Dysphonia, dysarthia, dysphagia, convulsions
• CV: irregular pulse, palpitations, bradycardia
• GI: hypersalivation, cramps, NVD
• UG: urinary urgency
• Lung: bronchospasm, dyspnea, ↑ secretions
• Eye: miosis, lacrimation, blurred vision
•Precautions: obstructive ileus, urinary tract obstruction
Echothiophate Class Use Mechanism Adverse rxns
AchE inhibitor
2nd line tx for open angle glaucoma
•Organophosphate class. Phosphorylates / inhibits AchE.
•Adverse rxns: eye stinging, blurred vision, cataracts
Pralidoxime Class Use Mechanism Time frame Adverse rxns Precautions
Opposite of other drugs. Reverses organophosphate AchE inhibition (restores function). Also reverses effects of neostigmine (myasthenia gravis tx)
•Displaces phosphoryl group via hydroxylation. Must be given w/in 24 hours of organophosphate exposure.
•Adverse rxns:
• CV: tachycardia, hypertension
• Elevated LFTs
• Eye: diplopia, blurred vision
•Precautions: renal insufficiency, myasthenia gravis
Atropine Class Use Mechanism Adverse rxns Precautions
Muscarinic antagonist
Treats bradycardia, reduces secretions for preop, promotes mydriasis and cycloplegia (lack of accommodation) for ophthalmic exams, decreases detrusor tone, decreases GI motility, and bronchodilation. Also used as antidote for AchE inhibitor or muscarinic agonist poisoning.
•Competitive antagonist at muscarinic receptors. Doesn’t effect AchE enzyme (this is main diff from pralidoxime for poison antidote).
•Blocks M2 receptors on heart → increased HR
•Don’t use atropine to produce bronchodilation for asthma b/c it affects so many other things before that occurs.
•Adverse rxns: CNS (confusion, amnesia, hallucinations, delerium, insomnia) and CV (conduction abnormalities, fibrillation, QT prolongation).
•Precautions – acute MI, bladder obstruction, urinarty tract obstruction, prostatic hypertrophy, glaucoma, obstructive ileus, hyperthyroidism.
Oxybutynin Class Use Mechanism Adverse rxns Precautions
Muscarinic antagonist
Bladder muscle relaxant. Used for neurogenic bladder to treat urge incontinence.
•Competitive muscarinic receptor antagonist. Anti-muscarinic effect not as strong as atropine, but antispasmotic activity on detrusor muscle is 4-10x stronger.
•Adverse rxns: heart palpitations, tachycardia, constipation / diarrhea
•Precautions:
• GI obstruction, ileus
• Toxic megacolon, ulcerative colitis
• Urinary retention or urinary tract obstruction
• Uncontrolled narrow-angle glaucoma
Ipratropium Class Use Mechanism Adverse rxns Precautions
Muscarinic antagonist
Tx acute asthma attacks. First line therapy for COPD. Combine w/ B2 agonists.
•Muscarinic receptor antagonist blocks Ach from causing bronchoconstriction (M3).
•Adverse rxns: xerostomia, cough, throat irritation
•Precautions: glaucoma, urinary retention, bladder obstruction
Mecamylamine Class Use Mechanism Adverse rxns
Ganglionic antagonist
Mainly treats HTN. Some use for Tourette’s Syndrome and nicotine withdrawal.
•Competitive antagonist at Nn receptors.
•Adverse rxns: orthostatic hypotension b/c baroreceptor reflex doesn’t work. Can’t vasoconstrict.
Epinephrine Class Use Mechanism Metabolism Precautions
Adrenergic agonist
Tx for bronchospasm, asthma, CPR. DOC for anaphylaxis. One of most potent vasopressors known. Often combined w/ local anesthetics to prolong duration. Decreases IOP for open-angle glaucoma and produces brief mydriasis.
•Activates both alpha and beta receptors
•Metabolized by COMT and MAO in liver
•Precautions: narrow-angle glaucoma, extravasion (skin necrosis), labor
Ephedrine
Class
Use
Mechanism
Adrenergic agonist
Tx asthma. Also works as a psychostimulant.
•Agonist at alpha and beta receptors. Also blocks NE reuptake. Both direct and indirect acting.
Phenylephrine Class Use Mechanism Precautions
Adrenergic agonist
Tx nasal congestion. Induces mydriasis for ophthalmic exam.
•Selective A1 agonist → vasoconstriction
•Adverse rxns: CV, HTN, narrow angle glaucoma, labor
Clonidine Class Use Mechanism Adverse rxns Precautions
Adrenergic agonist
Tx HTN and used as epidural agent for opioid-refractory cancer pain.
•Agonist at presynpatic A2 receptors (autoreceptors) → inhibition of sympathetic outflow / tone → decreased HR, TPR, MAP, CO and SV
•HTN effects last 7 days w/ the transdermal patch.
•Adverse rxns: CNS (sedation, lethargy, due to being lipid soluble), orthostatic hypotension (first dose syncope, gets better w/ use; A1 blocked prevents vasoconstriction)
•Precautions: abrupt DC (Rebound in catecholamines → HTN, tachycardia, etc), breast feeding, CV
Isoproterenol Class Use Mechanism Precautions
Adrenergic agonist
NE analog used to improve AV conduction during heart block and as a cardiac stimulant in cardiac arrest. Also treats acute bronchospasm, asthma, and COPD.
•Agonist at B1 & 2. No effect on alpha. Causes increase in CO w/ decrease in resistance (decreased BP)
•Precautions: arrythmias, CAD
Dobutamine
Class
Use
Mechanism
Adrenergic agonist
Inotrope used to treat acute heart failure. Increases contractility and SV.
•DA analong that acts as B1 agonist w/ minor B2 and A1 effects. Racemic mixture.
Albuterol Class Use Mechanism Adverse rxns Precautions
Adrenergic agonist
Short-acting bronchodilator for acute asthma or COPD
•B2 agonist. Relaxes SM and inhibits mast cell degranulation. Acts w/in 7 min.
•Adverse rxns: anxiety, tremor, increased BP
•Precautions: angioedema, CAD, HTN
Salmeterol Class Use Mechanism Adverse rxns Precautions
Adrenergic agonist
Long-acting bronchodilator for prophylactic asthma and COPD tx
•B2 agonist
•Adverse rxns: cough, headache, pharyngitis
•Precautions: NOT acute med for asthma attack
Phentolamine Class Use Mechanism Adverse rxns Precautions
Adrenergic antagonist
Prevent hypertensive episodes in pxs w/ pheochroocytoma. Prevent dermal necrosis following extravasion of alpha agonists.
•A1 & 2 antagonist. Inhibits vasoconstriction → decrease BP
•Adverse rxns: orthostatic hypotension
•Precautions: CV problems
Pheoxybenzamine Class Use Mechanism Adverse rxns
Adrenergic antagonist
Tx hyperhidrosis and HTN associated w/ pheochromocytoma. Given a couple days before surgery to remove pheochromocytoma in case catecholamines leak out. Also treats urinary sxs of BPH and vasospastic sxs of Raynaud’s or frostbite.
•Noncompetitive A1 antagonist (100:1 vs A2). Forms covalent bond w/ receptor. Long acting. Produces vasodilation and pupillary dilation
•Adverse rxns: reflex tachycardia, orthostatic hypotension, impotence
Prazosin Class Use Mechanism Adverse rxns
Adrenergic antagonist
Tx HTN and BPH
•Competitive antagonist at post-synaptic A1 receptors → vasodilation. Also relaxes bladder neck → increased urine flow.
•Adverse rxns: first dose syncope (blocking A1 blocks vasoconstriction upon standing; tell px to take first dose at night), orthostatic hypotension, impotence, incontinence
Tamsulosin Class Brand name Use Mechanism Precautions
Adrenergic antagonists
Flomax
DOC for treating BPH → urination.
•Competitive antagonist at postsynaptic A1 receptors. 10x selective for A1a vs A1b, good b/c 70% of receptors on prostate are A1a. Relaxes bladder neck.
•Precautions: Don’t use w/ PDE5 inhibitors (phosphodiesterase, Viagra). Food decreases bioavailability by 30%
Propranolol Class Use Mechanism Adverse rxns Precautions
Adrenergic antagonist
Tx HTN, angina, tachycardia, MI, migraine prophylaxis, anxiety, agitation, and panic attack
•Competitive nonselective B antagonist. Decreases HR, CO, BP, and skeletal muscle perfusion during exercise. Decreases anxiety sxs.
•Adverse rxns: bradycardia, cold hands / feet
•Precautions: abrupt DC (may produce MI, arrhythmias, severe HTN), acute bronchospasm, pulmonary edema, asthma, bradycardia, AV block, diabetes
•Hypoglycemia in diabetes → reflex tachycardia. Good signal telling person they should eat. Beta blockers prevent this, so people don’t know they need to eat.
Timolol Class Use Mechanism Adverse rxns Precautions
Adrenergic antagonist
First line tx for open-angle glaucoma
•Competitive, nonselective B antagonist. Reduces IOP by reducing aqueous humor production by ciliar body.
•Adverse rxns: eye pain / itching
•Precautions: acute bronchospasm, pulmonary edema, asthma, bradycardia, AV block
Metoprolol Class Use Mechanism Precautions
Adrenergic antagonist
Tx angina, HTN, migraines, MI, and tremor. More widely used than propranolol.
•Competitive B1 antagonist. Decreases HR, CO, and BP
•Precautions: abdrupt DC (MI, arrythmias, severe HTN), acute bronchospasm, pulmonary edema, asthma, bradycardia, AV block
Pindolol Class Use Mechanism Precautions
Adrenergic antagonist
Tx HTN, heart failure, heart block, and bronchospasm (when maintenance of sympathetic tone is desired)
•Nonselective B partial agonist. Attenuates tone, but does not eliminate it. Decreases HR, CO, and BP.
•Partial agonist at serotonin receptors → augmentation of anxiolytic effects of SSRI’s
•Precautions: abrupt DC (MI, arrythmias, severe HTN). Less risk of heart block than metoprolol.
Atenolol Class Use Mechanism Precaution
Adrenergic antagonist
Tx HTN and heart failure.
•B1 antagonist
•Pregnancy risk D
alpha-Methyltyrosine Class Use Mechanism Adverse rxns Precautions
Biosynthesis modifier
Tx pheochromocytoma. Preop for surgery or management for pxs in which surgery is contraindicated.
•Blocks tyrosine hydroxylase (DOPA not made) → decrease in hypertensive attacks and tachycardia. VMA marker drops.
•Adverse rxns: transient sedation, crystalluria (drink fluids to prevent)
•Precautions: alcohol, make sure to drink fluids
alpha-Methyldopa
Class
Use
Mechanism
Release modifier
Tx HTN, usually 2nd line, but DOC during pregnancy. Also tx pheochromocytoma
•Prodrug, false NT, acts on A2 autoreceptors → decreased NE → decreased tone and baroreceptor response.
•False NT’s mimic the regular NT’s. Can be taken up into vesicles and released upon neural stimulation like regular NT’s.
•ARBs can’t be used during pregnancy due to blocking RAAS
Reserpine Class Use Mechanism Adverse rxns Precautions
Release modifier
Tx HTN. Not used much anymore due to CNS effects.
•Blocks VMAT (vesicle monoamine transporter) → inhibits NT storage → depletion of 5HT, NE, and DA. Causes decrease in PVR, BP, CO, renal blood flow, and glomerular filtration. Bradycardia common.
•Adverse rxns: CNS (sedation, difficulty concentrating, depression, decreased libido), CV, (hypotension, bradycardia), GI, impotence
•Precautions: DC at first sign of depression, ECT, increased risk of seizures.
Botulinum toxin A Brand name Class Produced by? Use Mechanism Adverse rxns Precautions
Botox
Release modifier
Produced by Clostridium botulinum. Tx wrinkles, axillary hyperhydrosis, cervical dystonia, blepharospasm, and strabismus
•Specific for cholinergic neurons. Zinc protease is endocytosed → cleaves SNAP-25 (part of SNARE), inhibiting Ach release.
•Adverse rxns: ptosis, local muscle weakness, dysphagia, dystonia, immunogenic response (fever, flu)
•Precautions: preexisting neuromuscular disorders.
Amphetamine Brand name Class Use Mechanism Adverse rxns Precautions Danger of MDMA
Adderall
Uptake modifier
Mainly tx ADHD and narcolepsy. Off label for obesity tx (inhibits appetite).
•Indirect sympathomimetic: inhibits NE, DA, and 5HT uptake transporters by being taken up rather than real catecholamines. Also evokes monoamine release via reverse transport.
•Adverse rxns: insomnia, restlessness, anorexia, psychosis, tachycardia, angina
•Precautions: anorexia nervosa, CV (arteriosclerosis, CAD, HTN), MAO inhibitors, hyperthyroidism, glaucoma (increases IOP)
•Futile cycling for monoamine transporter: MDMA is amphetamine analog. Taken up in protonated form. Unprotonated in neuron. Released, and cycle recurs. Inside of cell can become acidified → toxicity.
Cocaine Class Use Mechanism Adverse rxns Precautions What should you not do w/ overdose?
Uptake modifier
First local anesthetic discovered, commonly used topically for ENT surgeries. Uniquely produces both vasoconstriction and anesthesia
•Reversibly decreases nerve permeability to Na+, inhibiting electrical conduction. Also inhibits reuptake of 5HT, E, NE, and DA (not taken up like amphetamine). Produces local vasoconstriction → decreases swelling / bleeding. CNS effects.
•Adverse rxns: CNS, CV, pulmonary edema, allergic reactions
•Precautions: Inflammation at site of application, seizures, CV disease
•If person overdoses on cocaine, don’t give them a beta blocker. Knocking out B2 leaves alpha 1 and 2 → hypertensive emergency.
Paroxetine Brand name Class Use Mechanism Precautions
Paxil
Uptake modifier
SSRI for depression, anxiety syndromes, OCD, PTSD. Off label for premature ejaculation & hot flashes.
•Highest specificity for 5HT uptake of all SSRI’s. Slight anticholinergic activity.
•Precautions: MAO inhibitor therapy, pregnancy risk D
Atomoxetine Class Use Mechanism Precaution
Uptake modifier
Nonstimulant for ADHD.
•NE reuptake inhibitor
•Black box warning for increased risk of suicidal thoughts
Phenelzine Use Mechanism Adverse rxns Precautions
2nd line Tx for depression. Good for refractory anxiety disorders, OCD, panic disorder. Doesn’t work as well as SSRI’s.
•Nonselective irreversible MAOI → increase in NE, 5HT, and DA
•Adverse rxns: sympathomimetic effects – HTN, agitation, insomnia, tachycardia, etc
•Precautions: CV, pheochromocytoma, tyramine foods
Succinylcholine Metabolism Use Adverse rxns Mechanism Phase II block: what is it, what causes it?
Rapidly metabolized by plasma cholinesterase into succinate + 2 cholines.
•Used for rapid sequence induction / intubation. Minimizes risk of aspiring vomit.
•Adverse rxns are related to agonist activity at other AchRs. SLUDGE.
• Stimulates autonomic ganglia → HTN and tachycardia
• Stimulates cardiac mAchRs → bradycardia
• Histamine release → bronchospasm and hypotension
• Hyperkalemia in certain populations – when nAchR opens, K leaks out of cell. Severe bradycardia may occur → cardiac arrest in children.
• Pxs w/ denervation (spinal cord injury or stroke), burns, trauma, prolonged immobility, or myopathies (Duchenne) have upregulated nAchR’s, which can cause problems w/ hyperkalemia.
• Others include myalgias, increased intracranial / intraocular pressures
• Phase II block is long lasting and occurs w/ prolonged administration or repeated boluses. Takes on characteristics of competitive antagonism. If repeated doses are needed, use non-depolarizing NMB instead of succinylcholine.
• Prolonged block may be due to decreased plasma ChE concentration due to liver disease or inherited “K-variant”
• Also due to decreased ChE activity due to ChE inhibitors (neostigmine, organophosphates), or the inherited “atypical variant”.
Catecholamine synthesis
Tyrosine → DOPA (via tyrosine hydroxylase) → DA (via aromatic amino acid decarboxylase, AAAD) → NE (via dopamine beta hydroxylase, DbH, occurs inside vesicle) → E (via phenylethanolamine-N-methyltransferase, PMNT, phase II enzyme [methylates])
Muscarinic Ach receptors and subtypes
Muscarinic Ach receptors use G proteins. 5 subtypes (M1-5, M2,3 do 90% of work)
Nicotinic Ach receptors and subtypes
Nicotinic Ach receptors are ligand-gated ion channels. 2 subtypes (Nm and Nn).
Serotonin Syndrome
Sxs
Treatment (4)
Causes agitation, hyperthermia, flushing, GI disturbance, myoclonus, rhabodomyolysis, tremor, seizure
•Manage by removing causative drugs, IV fluids, diazepam (controls seizures)
•Sodium nitroprusside → NO → vasodilation → lowers BP
•Esmolol is beta1 blocker → reduces tachycardia
•Vecuronium is NMJ blocker. Stops myoclonus → tx hyperthermia.
•Antipyretic agents (NSAIDs, acetaminophen) do NOT work.
Benzylisoquinoline derivatives
Ends in “-curium”
Atracurium, cisatracurium, and mivacurium. Also d-Tubocurarine.
Steroid derivatives
Ends in “-curonium”
Pancuronium, vecuronium, and rocuronium
