Adrenergic Agonists Flashcards
Pseudoephedrine
Description: Synthetic derivative of ephedrine •
Actions: Acts indirectly to release NE from adrenergic nerve endings, also some direct agonism at alpha- and beta-adrenergic receptors •
Indications: • Nasal and sinus decongestant • Less ability to dilate bronchioles than ephedrine •
Other facts: • FDA approval in 1959 • 1996 need to report bulk sales • 2005 stored behind counter or locked cabinet, need photo ID, need to maintain purchaser log, risk of diversion to produce methamphetamine (Breaking Bad) • 2008 labeled as risk of injury or death, no cold products for kids <2 yo
Salmeterol
Description: synthetic selective β2 (β2>>β1) receptor agonist (with relatively little β1 stimulation at normal doses) •
Actions: Potent agonist at β2 receptors on smooth muscle cells in airways (e.g. bronchioles) • increased mucociliary clearance, decrease vascular permeability, decrease mediator release
Metabolism: COMT/MAO,
Pharmacokinetics: F 15-75, 1/2 life is 6-8 hours. only 8-15% reaches systemic circulation
Pharmacodynamics: duration is 12 hours
Indications: • Prompt-acting rescue inhaler for asthma, COPD (bronchodilator) • Inhibit premature labor (relaxes smooth muscle cells in uterus as well) •
Other facts: • Most often given as MDI (metered dose inhaler) • Can be given via nebulizer • Rarely given any more as iv infusion • Side effects include CVS: tachycardia, palpitations, tremor, angina, arrhythmias, vasodilate pulm arterioles CNS: anxiety, headache and tremor. Metabolic- hypokalemia, hyperglycemia can develop tolerance.
Norepinephrine
• Drug class: pharmacologic class—direct-acting adrenergic agonist; therapeutic class— vasopressor, vasoconstrictor •
Pharmacodynamics/MOA: 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 the placenta, but not the blood/brain barrier. •
Toxicity: excessive vasoconstriction in mesenteric vessels, peripheral arterioles causing ischemia, infarction, digital 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 propranolol •
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
Ephedrine
Description: Alkaloid obtained from plant (Ephedra) •
Actions: Acts indirectly to release NE from adrenergic nerve endings, also some direct agonism at receptors •
Indications: • Mild to moderate hypotension during surgery • Nasal congestion
Other facts: • Has somewhat prolonged duration of action • Potent CNS stimulant (NE) •
Side effects include hypertension, insomnia • OTC Ephedra products now banned by the FDA dye to deaths d/t hyperthermia
Albuterol
Description: synthetic selective β2 (β2>>β1) receptor agonist (with relatively little β1 stimulation at normal doses) •
Actions: Potent agonist at β2 receptors on smooth muscle cells in airways (e.g. bronchioles) • increased mucociliary clearance, decrease vascular permeability, decrease mediator release
Metabolism: COMT/MAO,
Pharmacokinetics: F 15-75, 1/2 life is 6-8 hours. only 8-15% reaches systemic circulation
Pharmacodynamics: ORAL; 1 hr onset/ peak 3 hours/duration 6-8 hrs INHALED; 1 minute onset/ 30 min peak/ 4-6 hour duration
Indications: • Prompt-acting rescue inhaler for asthma, COPD (bronchodilator) • Inhibit premature labor (relaxes smooth muscle cells in uterus as well) •
Other facts: • Most often given as MDI (metered dose inhaler) • Can be given via nebulizer • Rarely given any more as iv infusion • Side effects include CVS: tachycardia, palpitations, tremor, angina, arrhythmias, vasodilate pulm arterioles CNS: anxiety, headache and tremor. Metabolic- hypokalemia, hyperglycemia can develop tolerance.
Epinephrine
• Drug class: pharmacologic class—direct-acting adrenergic agonist; therapeutic class—vasopressor, cardiac stimulant, bronchodilator, adjunct to local anesthetics, treatment for anaphylaxis •
Pharmacodynamics/MOA: major action is to stimulate peripheral alpha-1 adrenoceptors, thereby leading to vasoconstriction (resistance arterioles, increase SVR) and venoconstriction (in capacitance vessels, increase preload); stimulate 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 (5-15 min), and via inhalation (1-5 min onset), ophthalmic topical; metabolized by COMT and then renally excreted; •
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
Dopamine
Class: adrenergic and dopaminergic receptor agonist; therapeutic class: inotropic agent; vasopressor (Note: not useful in treatment of Parkinson’s Disease, why not???) •
Indications, dose: shock, CHF; 1 mcg/kg/min up to 30 mcg/kg/min (
PD: stimulates DA receptors (renal blood flow), beta-1, and alpha-1 receptors at different infusion rates (low, med, high infusion rates) •
PK: can only be infused IV; acts quickly within minutes; halflife brief (minutes), hence continuous infusion •
Toxicity: ectopy, tachycardia, angina, nausea, peripheral gangrene (excess vasoconstriction); extravasation •
Special issues: correct hypovolemia first; administer through large vein; prevent extravasation; monitor patient closely •
Dobutamine
Description: synthetic β1 receptor agonist (with very little alpha simulation at high doses) • positive inotropic agent;
Actions: Potent agonist at β1 receptors in heart (increase contractility) and blood vessels (dilates renal and mesenteric vessels); increases contractility more than HR •
Indications: • Increase cardiac contractility more than HR • Useful in CCU for patients in cardiogenic shock, where you do not want to produce tachycardia (e.g. post MI) •
correct hypovolemia first
Other facts: • Given as intravenous infusion •
Side effects include unwanted tachycardia, hypertension, ectopy, PVC
Tyramine
Description: Naturally occurring byproduct of tyrosine metabolism; present in many aged or fermented foods like red wine, smelly cheeses, pickled herring •
Actions: Acts indirectly to release NE from adrenergic nerve endings • Indications (none are FDA approved): • Obesity • Narcolepsy • ADHD •
Other facts: • Metabolized in the liver by MAO • Watch out in patients on MAO inhibitor drugs (e.g. phenelzine) • Chance of food/drug interaction
Isoproterenol
• Description: synthetic β1 and β2 receptor agonist •
Actions: Potent agonist at both beta receptors •
Indications: • Increase cardiac contractility • Increase HR • Increase cardiac conduction •
Other facts: • Given intravenously • No longer used as much in CCU • Remember will also cause vasodilatation • Remember will also cause tachyarrhythmias
Clonidine
Description: synthetic and selective α2 receptor agonist • Actions:
Stimulate α2 receptors in brainstem, cause downregulation of sympathetic nervous system •
Indications: • Treat hypertension • Treat or prevent migraine •
Other facts: • May be given orally or patch • Causes sedation and dry mouth • If given intravenously or OD can cause BP
Phenylephrine
Description: synthetic alpha-receptor agonist, α1 > > α2
- Actions: Produce vasoconstriction and venoconstriction by stimulating contraction of vascular smooth muscle cells
- Indications: • Nasal decongestant • Mydriatic (dilate pupil for eye exam) • Increase BP in vasodilated state •
Other facts: • Less potent vasoconstrictor than NE • Not inactivated by COMT • Topical (eye, nose), intravenous infusion (increase BP)
Mirabegron
Description: synthetic selective β3 receptor agonist (with much less activity at β1 and β2 receptors) •
Actions: Stimulation of β3 receptors in smooth muscle of bladder, reduces detrusor muscle tone • Indications: • Treatment of patients with overactive bladder with features of urinary urgency or frequency • Increases bladder capacity • Does not produce bothersome anticholinergic symptoms like tolteridine •
Other facts: • Approved by FDA in June 2012 • Administered orally as extended release tablets
Cocaine
Description: Naturally occurring but purified alkaloid extracted from the coca plant •
Actions: Acts indirectly to block reuptake of NE (also Epi, DA) at the synapse, and can stimulate release of NE, Epi, and DA from neuron; also acts as a local anesthetic and CNS stimulant •
Indications: • Nose bleeds (anesthesia plus vasoconstriction) • Anesthesia for corneal surgery •
Other facts: • CNS stimulation more intense, shorter lasting than amphetamine • Can be smoked, snorted, or injected • Side effects hypertension, tachycardia, arrhythmias, seizures, MI • Controlled substance
Amphetamine
Description: Synthetic compound similar to ephedrine •
Actions: Acts indirectly to release NE from adrenergic nerve endings •
Indications (none are FDA approved): • Obesity • Narcolepsy • ADHD •
Other facts: • FDA approval in 1939 • Very high risk of dependence • Insomnia, restlessness, tremor
