2013-08-30 Adrenergic Drugs Flashcards
Objective 1: For catecholamines, describe their:
- -synthesis
- -storage
- -release
- -removal
- -interactions w/ drugs
Catecholamine
terminal NE stores replenished via:
a) reuptake
b) de novo synthesis
- -de novo synthesis:
1. tyrosine actively transported in
2. — tyr hydroxylase —> DOPA —> decarboxylase —> dopamine
–storage: the dopamine synth’d in cytosol is then stored in vesicles where it is…
–synth: …made into NE via dopamine β-hydroxylase in the vesicle
–storage: stored in vesicle until AP arrives
–release: AP —> Ca2+ influx —> triggers fusion of vesicle w/ PM = exocytosis of NE
–removal: diffusion, reuptake, metabolization (via MAO and COMT, catechol-o-amine methyl transferase which are both high in liver —> S and glucuronate conjugates —> urine)
–interactions w/ drugs
Pharm card: Epinephrine
SEE ALSO LANG CARD 2.03
Drug class: pharmacologic class—direct-acting, non-selective 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 5-15 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; also for allergy-induced asthma
Monitor: BP, HR, rhythm, infusion site, evidence of extravasation
Pharm card: Norepinephrine
NO LANG CARD
Drug class: pharmacologic class—direct-acting, non-selective 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 the placenta, but not the 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 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
Pharm card: dopamine
NO LANG CARD
endogenous, non-selective catecholamine
- -actiavtes β1-AR in heart
- -tx: shock, acute HF
Pharm card: isoproterenol
extremely potent β-AR (non-selective for β-ARs)
- -potent vasodilator
- -poz chronotropy
- -adverse: tachy, BP, arrythmias
Pharm card: phenylepherine (neosynephrine, Sudafed PE)
See LANG card
Pharm card: clonidine (Catapress)
NO LANG CARD
MOA: α2-AR agonist; epidurally prevents pain signal transmission to the brain, producing analgesia at spinal presynaptic and postjunctional α2-adrenergic receptors
indications: HTN, menopausal flushing, migraine (severe cancer-related pain, ADHD in kids, Tourettes syndrome in kids)
- -po: prolonged hypotensive response
- -i.v: acute hypertensive response followed by hypotension
- -dermal patch - ?
adverse effects: dry mouth, sedation, contact dermatitis
precautions: rebound HTN w/ abrupt d/c
Pharm card: dobutamine
see LANG card
Pharm card: albuterol
β2-AR agonist
bronchodilator: oral, inhalation or IV
adverse: tachy, tremor, tolerance
Pharm card: Ephedrine
No LANG Card (similar to amfetamine lang card)
- -indirect-acting agonist
- -alkaloid obtained from plant
- -increase NE release —> direct agonism
- -prolonged action duration, potent CNS stimulant
Uses: nasal decongestant (psuedoephedrine), tx of hypotension
Adverse: HTN, insomnia, tachyphylaxis (an acute (sudden) decrease in the response to a drug after its administration.)
Pharm card: Amphetamine
See LANG card
Pharm card: Tyramine
Not a drug. No Lang card.
Indirect acting adrenergic agonist
- -causes release of catecholamines from storage
- -high conc in fermented foods; made from fermentation of Tyrosine
- -metabolized by liver MAO
- -caution to pts on MAOIs—> severe HTN
Per wiki: “Foods containing considerable amounts of tyramine include meats that are potentially spoiled or pickled, aged, smoked, fermented, or marinated (some fish, poultry, and beef); most pork (except cured ham); chocolate; alcoholic beverages; and fermented foods, such as most cheeses (except ricotta, cottage, cream and Neufchâtel cheeses), sour cream, yogurt, shrimp paste, soy sauce, soybean condiments, teriyaki sauce, tofu, tempeh, miso soup, sauerkraut, broad (fava) beans, green bean pods, Italian flat (Romano) beans, snow peas, avocados, bananas, pineapple, eggplants, figs, red plums, raspberries, peanuts, Brazil nuts, coconuts, processed meat, yeast, and an array of cacti.”
Pharm card: cocaine
See Lang card
Clicker Q: What are s/sx in EtOH/TCA interaction?
What is best pharm mgmt? A. timolol B. metoprolol C. prazosin D. phentolamine E. isoproterenol
D
Which drug is absolutely contraindicated in EtOH/TCA interaction? A. phenozybenzamine B. metoprolol C. prazosin D. phentolamine E. labetolol
B - metoprolol is contraindicated; it will lower HR, but all the epi that can’t bind β ARs will be freed up and bind to α ARs further increasing HTN
