ANS drugs Flashcards
Norepinephrine
Pharmacologic class: direct-acting adrenergic agonist
Therapeutic Class: vasopressor, vasoconstrictor
Pharmacodynamics: major action is to stimulate peripheral alpha-1 adrenoceptors, thereby leading to vasoconstriction (resistance arterioles, increase SVR) and venoconstriction (in capacitance vessels, increase preload). This increases CO, SVR, and MAP but decreases blood flow to vulnerable tissues like skin, muscle and kidney. Also stimulates beta-1 receptors in the heart, increasing HR and contractility. Main effects are vasoconstriction and cardiac stimulation.
Pharmacokinetics: F~100%. Given IV only. Metabolized by COMT and MAO, mostly in liver. Metabolites are excreted in urine. Half-life 1~2 minutes (e.g. can be titrated quickly IV). Can cross placenta but not blood-brain barrier.
Toxicity: excessive vasoconstriction in mesenteric vessels, peripheral arterioles causing ischemia, infarction, gangrene; reflex bradycardia
Interactions: use cautiously in patients taking an MAO inhibitor such as phenelzine (use lower doses); risk of excessive hypertension in patients taking propanolol
Special considerations: correct volume depletion with IV fluids BEFORE giving NE infusion; select infusion site carefully - extravasation is a major problem; monitor patient and BP continuously in ICU setting; use cautiously in pediatric and geriatric patients
Indications and dose/route: for adults with acute hypotension and shock (related to low SVR) infuse 2-12 mcg/min
Monitor: BP, HR, infusion site, evidence of extravasation
Epinephrine
Pharmacologic class: direct acting adrenergic agonist
Therapeutic class: vasopressor, cardiac stimulant, bronchodilator, adjunct to local anesthetics, treatment for anaphylaxis
Pharmacodynamics: major action is to stimulate peripheral alpha-1 adrenoceptors, thereby leading to vasoconstriction (resistance arterioles, increase SVR) and venoconstriction (in capacitance vessels, increase preload); beta-1 receptors leading to tachycardia and increased contractility; and beta-2 receptors leading to bronchodilation; these actions are also helpful in severe allergic reactions (e.g. anaphylaxis) by stabilizing mast cells
Pharmacokinetics: can be given IV (immediate), IM (variable), SC (5-15m), and via inhalation (1-5m onset), opthalmic topical; metabolized by COMT and then excreted by urine
Toxicity: excessive vasoconstriction, HTN, hemorrhagic stroke, angina, arrhythmias
Interactions: risk of excessive hypertension in patients taking propranolol
Special considerations: utility with local anesthetics; drug of choice in severe anaphylactic reactions (along with others)
Indications and dose/route: for anaphylaxis, 0.1-0.5 mg SC or IM; for cardiac arrest, 1-5 mg IV push; for infusion, 1-4 mcg/min
Monitor: BP, HR, rhythm, infusion site, evidence of extravasation
Isoproterenol
Pharmacologic class: non-selective beta-AR agonist
Therapeutic class: lowers TPR, increases CO, prevents bronchoconstriction
Pharmacodynamics: Non-selective direct agonist of beta-adrenoceptors, low affinity for alpha-receptors. Positive chronotropic and ionotropic effects, bronchodilates via beta2-receptors. No BP rise due to vasodilation.
Pharmacokinetics: readily absorbed via injection/aerosol. Metabolized by liver.
Toxicity: Sympathomimetics-parenteral; Can cause vasoconstriction causing ischemia/hypoxia; HTN; tachycardia; gangrene secondary to extravasation.
Interactions: Contraindicated for angina pectoris, digitalis-induced tachycardia, tachyarrhythmias. Use caution with convulsive disorders, coronary insufficiency, DM, HTN, hyperthyroidism
Special considerations:
Indications and dose/route: IV only for bronchospasm (anesthesia), asthma, cardiac arrest, cardiogenic shock, CHF, decreased vascular flow, heart block, shock, Stokes-Adams
Monitor: BP, HR, ECG; electrolyte panel; CVP
Dopamine
Pharmacologic class: Direct acting and adrenergic agonist; indirect adrenergic agonist
Therapeutic class: vasopressor, vasoconstrictor, cardiac stimulant
Pharmacodynamics: low doses stimulate DA to cause renal and mesenteric vasodilation; medium doses stimulate Beta-1 receptors by increasing release of NE from sympathetic nerves, increasing HR and contractility; High doses stimulates alpha-adrenoceptors to vasoconstrict
Pharmacokinetics: Widely distributed; metabolism via hepatic, renal, plasma (MAO + COMT), metabolized to NE; excreted via urine, mostly as metabolites.
Toxicity: similar to all sympathomimetics (risk of tachycardia, HTN, ischemia/hypoxia due to vasoconstriction)
Interactions: MAOI, cardiac stimulants
Special considerations: Caution/contraindicated for angina pectoris, extravasation, hypovolemia, occlusive vascular dz, MAOIs, sulfite sensitivity, ventricular arrhythmias, pheochromocytoma,
Indications and dose/route: Shock (cardiogenic, septic, MI, trauma, surgical, etc); CHF, decreased CO, renal failure; Non-FDA: bradyarrhythmia, cardiac arrest, cardiac catheterization, hypotension, organ transplant
Monitor: ECG, BP, HR, urine output/renal fxn, CVP, CO, extravasation
phenylepherine
Pharmacologic class: selective direct acting alpha-receptor agonist
Therapeutic class: vasoconstrictor, mydriatic fxn,
Pharmacodynamics: direct agonism of post-synaptic alpha1-receptors, with little/no effect on beta-receptors. Causes increase in HR and reduction in CO. Potent vasoconstrictor.
Pharmacokinetics: F = 38%; Hepatic metabolism via MAO, but not COMT. Half-life 2 - 3.5 hours.
Toxicity: similar to sympathomimetics (tachycardia, nausea, vomiting, HTN, etc)
Interactions: MAOI contraindicated.
Special considerations: caution with cardiovascular disease, htn, hyperthyroid, narrow opthalmic angle, ventricular tachycardia
Indications and dose/route: Glaucoma (eye drops 2.5% solution), hypotension (.1-.5mg IV; 2-5mg subq; 100-180mcg/min continuous IV)), mydriasis induction (eye drops 2.5%), nasal congestion (0.25-0.5% nasal spray; 10-20mg orally), paroxysmal supraventricular tachycardia (up to 0.5mg IV), shock (100-180mcg/min continuous IV), spinal anesthesia (2-5mg to anesthetic solution), regional anesthesia (1mg per 20mL anesthetic), priapism (injection into corpus cavernosum)
Monitor: hypotension during anesthesia, mydriasis, congestion improvement, blood pressure
clonidine
Pharmacologic class: selective direct acting alpha-receptor agonist
Therapeutic class: reduced sympathetic outflow from CNS, decreased TPR, decreased renal vascular resistance, decreased HR, decreased BP, analgesia
Pharmacodynamics: selective alpha 2-adrenergic receptor agonist. Decreases release of NE and stimulates imidazoline receptor, both of which decrease CNS sympathetic outflow
Pharmacokinetics: F(oral) = 75-100% F(rectal) = 95%; Hepatic 50% metabolism; Excretion 22% fecal, 40-60% unchanged renal; elimination half-life 12.5-16 hours (oral)
Toxicity: confusion, hallucinations, dry mouth, hypotension, nausea/vomiting, constipation, contact dermatitis, sedation
Interactions: avoid beta-blockers, tetracycline antidepressants, tricyclic antidepressants, calcium channel blockers
Special considerations: avoid use with anticoagulant therapy, caution with bleeding diathesis; stop therapy slowly (taper down) to avoid withdrawal
Indications and dose/route: ADHD, Cancer pain, HTN, menopausal flushing, migraine
Monitor: HTN, pain, HR, BP
Dobutamine
Pharmacologic class: selective direct acting B1-agonist; synthetic catecholamine, related to dopamine
Therapeutic class: inotropic agent
Pharmacodynamics: Stimulates B1 receptors only; causes hypertension, mild chronotropic effects, inotropic effects, mild vasodilation, arrhythmogenic effects
Pharmacokinetics: methylation and conjugation; excreted as metabolites;
Toxicity: vasoconstriction leading to ischemia and hypoxia in end organs, toxic effects from htn/hypotension, cardiac strain. Can cause arrhythmias.
Interactions: Linezolid (antibiotic) and Isocarboxazid (MAOI)
Special considerations: Can cause arrhythmias; increases conduction via AV node, so avoid use with patients with a fib; Contraindicated in patients with hypersensitivity to corn; avoid in patients with subaortic stenosis; can cause hypokalemia
Indications and dose/route: Indicated for decreased CO (initial 0.5 to 1mcg/kg/min IV, maintain at 2 to 40 mcg/kg/min IV; titrate dose), CHF (same as CO, unless post-cardiac arrest, then 5-10 mcg/kg/min IV)
Monitor: ECG, BP, HR, wedge pressure, CO, potassium
Albuterol
Pharmacologic class: direct acting B2-agonist
Therapeutic class: bronchodilator, short acting; anti-hyperkalemia agent
Pharmacodynamics: increases smooth muscle cyclic AMP via B2 receptors, causing relaxation; also stabilizes mast cells (limits hypersensitivity mediator release)
Pharmacokinetics: F for MDI is below quantitation, less than 20% for nebulizer; preferentially metabolized in GI tract to 4-O-sulfate ester; primarily renal excretion
Toxicity: over stim of beta-adrenergic receptors causes loss of selectivity; can cause tremors, tachycardia, etc; tolerance develops over time.
Interactions: avoid with beta-blockers, MAOI,
Special considerations: caution with: cardiovascular dz, especially coronary dz; diabetes + ketoacidosis; convulsive disorders; hyperthyroidism; hypokalemia;
Indications and dose/route: Asthma, hyperkalemia, COPD
Monitor: proper inhalation technique, PFTs
Mirabegron
Newly FDA approved B3-agonist for treatment of overactive bladder; relaxes the detrusor muscle. Can cause tachycardia, HTN
Ephedrine
Indirect acting adrenergic agonist
Increases NE release (binds to end of boutons, receptors and causes Ca+ influx), direct agonism of adrenoceptors
prolonged action, potent CNS stimulant
used in nasal decongestion; treatment of hypotension
causes HTN, insomnia, tachyphylaxis
Amphetamine
Indirect acting adrenergic agonist
Releases biogenic amines from storage to cause, but no direct stimulation
potent CNS stimulation
prolonged action duration
Treats obesity, narcolepsy, ADD
Causes restlessness, tremor, irritability, insomnia, dependency, tolerance
Tyramine
Indirect acting adrenergic agonist
Release biogenic amines from storage, no direct stimulation
byproduct of tyrosine metabolism, and can be found in high concentration in fermented foods (cheese and wine)
metabolized by MAO ***Contraindicated with MAOI, can cause severe HTN
Cocaine
Indirect acting adrenergic agonist
Inhibits NE and DA reuptake
local anesthetic + potent CNS stimulant
shorter lasting that amphetamine, more intense
causes HTN, AMI, arythmie, seizure
a1-AR
constricts smooth muscles of the blood vessels, bronchi, GI sphincter, uterus, urinary sphincter, seminal tract, iris (radial)
causes liver glycogenolysis, K+ release
salivary gland K+ release
a2-AR
Inhibits NE release
constricts smooth muscles of blood vessels
relaxes smooth muscles of GI tract
causes platelet aggregation
b1-AR
Increases heart rate and contractility
relaxes smooth muscles of GI tract
increases heart rate, force, av node conduction velocity
Promotes lipolysis, and amylase
b2-AR
Relaxes smooth muscles of airway/uterus
Relaxes smooth muscles of blood vessels, bronchi, GI sphincter, Uterus, detrusor, seminal tract, ciliary muscle (pupillary dilation)
causes liver glycogenolysis, inhibits histamine release in mast cells
a-AR blockers
Vasodilation, decrease BP
Non-selective: Phentolamine (reversible, not used) and Phenoxybenzamine (irreversible, used for peripheral vasospasm)
adverse reactions include hypotension and tachycardia
Prazosin
a1-AR selective blocker
antihypertensive
can cause first-dose postural hypotension
a1-AR selective blockers generally vasodilator and reduce BP; do not cause reflex tachycardia; useful for HTN and BPH; no decrease in cardiac fxn
B1-AR blockade
Reduces HR, delays AV node, decreases depolarization, decreases force, decreases O2 consumption, decrease BP, inhibit renin
B2-AR blockade
Vasoconstriction in arterioles, increased airways resistance, decreased glycogenolysis + gluconeogenesis, inhibit insulin release
Beta blockers
- Use for HTN, arrhythmias, IHD, also useful for hyperthyroidism, glaucoma, migraine, anxiety
- well absorbed after oral administration, peak concentration 1-3 hours
- extensive first-pass metabolism, half-lives around 3-10 hours
- gradually taper doses when d/c; do not stop cold turkey due to receptor up regulation
- dangerous drug interactions, ie verapamil
- caution w/ airway disease, diabetes, heart failure
- tend to be big, clunky molecular structures
