Heart failure and shock drugs Flashcards
Atropine
Class: Alkaloid derived from belladonna, muscarinic receptor blocker
MOA: blocks the ability of acetylcholine to bind to and stimulate muscarinic receptors throughout body
Indications: symptomatic bradycardia; pre-op patients to reduce bronchial secretions and to block vagal reflexes (e.g. during intubation); to block muscarinic effects of anticholinesterases given to reverse effects of neuromuscular blockers; antidote for poisoning by anticholinesterase insecticides or poisons (e.g. Sarin); to manage pupil size in patients with acute iritis or uveitis
PK: most commonly given iv, but also topically to eye; >50% metabolized in liver; after iv dose, onset immediate, peak 2-4 min, duration 4 h
Contraindications and ADRs: avoid in patients with acute angle-closure glaucoma, urinary or GI tract obstruction, ileus, toxic megacolon, or ophthalmic prep in patients with eye adhesions between iris and lens; can cause wide range of anticholinergic side effects, including agitation, confusion, delirium, blurred vision
Other facts: overdose can cause delirium and tachycardia; physostigmine is occasionally given for severe overdose
Dose: for bradycardia, 0.5 -1 mg iv push; for pre-op use, 0.4 mg IM 3o minutes before anesthesia; for insecticide poisoning, may need 2-6 mg iv, repeated every 5 minutes
Nitroprusside (Nipride™, Nitropress™; not given chronically)
Drug class: pharmacologic class– vasodilator; therapeutic class–antihypertensive, management of severe CHF, management of pulmonary hypertension, produce controlled hypotension to reduce bleeding during surgery •
Pharmacodynamics: acts “directly” on vascular smooth muscle to cause dilatation of both veins and arterioles; metabolized to release CN- and NO, which activates guanylate cyclase, leads to production of cGMP from GTP, which then leads to vasodilation; cGMP then hydrolyzed to GMP by PDE •
Pharmacokinetics: only route is iv; rapid onset (minutes) and cessation (minutes), thereby allowing minute-by-minute titration; CN- metabolite is converted to SCN in liver, then excreted in urine; must be given by continuous infusion •
Toxicity: excessive hypotension; accumulation of CN- and thiocyanate; headache; decreased blood flow to brain •
Interactions: additive effects with most other antihypertensives •
Special considerations: monitor patient VERYclosely—must be in ICU with arterial line; avoid high infusion rates or prolonged infusions, to prevent accumulation of CN-; use with caution in patients with increased intracranial pressure •
Indications and dose/route: for treatment of hypertensive crisis, given as IV infusion at 0.3-10 mcg/kg per minute •
Monitoring: BP, HR, metabolic acidosis; most often requires arterial line
Carvediolol (Coreg)
Drug class: pharmacologic class— “specific” β1-adrenoceptor blocker; therapeutic class–antihypertensive, antiarrhythmic, primary and secondary prevention of MI, anti- anginal •
Pharmacodynamics: binds directly to β1-receptors, with a preference for beta-1 over beta-2, leading to lower blood pressure via several potential mechanisms (less cardiac output, less activation of the RAA system); recent evidence suggests less effective in preventing strokes than other drugs used as monotherapy for HTN •
Pharmacokinetics: available po or iv; variable oral F; onset 1-2 hours h, duration 12-24 h; can be given once per day; renally excreted (longer half-life); metoprolol has hepatic metabolism (and shorter half-life) •
Toxicity: excessive hypotension; bradycardia; heart block; can worsen severe CHF (but indicated for mild to moderate and stable CHF); worsen bronchospasm in severe asthmatics •
Interactions: additive effects with most other anti-hypertensives; additive AV block with CEB’s •
Special considerations: may be especially useful in HTN patients with exertional angina, MI, atrial fibrillation; watch out for abrupt withdrawal; may no longer be “first line” drug for essential HTN unless other indications exist (recent data); metoprolol (needs to be taken several times per day) has more data for use in patients s/p MI •
Indications and dose/route: for treatment of hypertension, 25-100 mg per day, in one or two doses •
Monitoring: BP, HR, exercise 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 • also used for cardiac arrest or restarting heart after open heart surgery
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
Hydrochlorothiazide, chlorthalidone
Drug class: pharmacologic class–thiazide diuretic; therapeutic class–diuretic, antihypertensive •
Pharmacodynamics: block reuptake of Cl and Na from tubular fluid after glomerular filtration; also appears to cause decrease in SVR via unclear mechanism; will lower BP by up to 10-15 mm in many patients; useful as monotherapy or in combinations; HCTZ most commonly used, but perhaps some slight edge to chlorthalidone (duration, efficacy)(see Flack et al: Hypertension 2011; 57:665-6) •
Pharmacokinetics: F ~70%, excreted unchanged in urine; short half-life (hours); HCTZ not available in IV formulation; onset 2 h, peak 5 h, duration 10 h •
Toxicity: allergy to sulfa antibiotics (?); cause K and Mg depletion; cause Na and Cl depletion, metabolic alkalosis; volume depletion; worsen hyperuricemia •
Interactions: additive effects with most other antihypertensives •
Special considerations: more side effects in geriatric patients; Pregnancy Class D; much less effective in patients with reduced GFR •
Indications and dose/route: 12.5 mg or 25 mg po every morning; little benefit (and more toxicity) when given in higher doses •
Monitor: BP, weight, edema, K, Mg, BUN, creatinine
Lisinopril, captopril, enalapril, ramipril
• Drug class: pharmacologic class–ACE inhibitor; therapeutic antihypertensive, treatment of CHF (improves survival), preserving renal function, preserving LV function after MI, acute management of MI •
Pharmacodynamics: inhibits conversion of AT I to AT II by ACE; diminishes both vasocontriction and stimulation of aldosterone secretion by AT II •
Pharmacokinetics: well absorbed; onset 1 h, peak 6 h, duration 24 h; once a day is fine; excreted primarily in urine as unchanged drug •
Toxicity: orthostatic hypotension; use with caution in patients with impaired renal function, or renal artery stenosis; be careful in patients on diuretics, or those with aortic stenosis; angioedema, cough; acute renal failure •
Interactions: additive effects with most other antihypertensives; NSAIDs may reduce ability to lower BP; hyperkalemia with KCL, others •
Special considerations: often discontinue diuretics prior to beginning use to reduce hypotension; Category C/D in pregnancy, abnormal cartilage development •
Indications and dose/route: begin 10 mg per day, titrate slowly upward to 40 mg per day max •
Monitor: BP, weight, edema, K, BUN, creatinine!!!!!
Dopamine (Intropin™)
Class: adrenergic and dopaminergic receptor agonist; therapeutic class: inotropic agent; vasopressor (Note: not useful in treatment of Parkinson’s Disease, why not???) •
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 •
Indications, dose: shock, CHF; 1 mcg/kg/min up to 30 mcg/kg/min ( low 1-2, moderate 2-10, high 10-30 mcg/kg/min)
Dobutamine (Dobutrex™)
Class: adrenergic receptor agonist; positive inotropic agent; •
PD: selectively stimulates beta-1 adrenergic receptors to increase contractility and SV resulting in increased cardiac output; interestingly, HR usually remains unchanged •
PK: can only be infused IV; acts quickly within minutes; halflife brief (minutes), hence continuous infusion •
Toxicity: ectopy, PVC’s, tachycardia, hypertension, hypotension • Special issues: correct hypovolemia first; monitor patient closely •
Indications, dose: for CHF, most patients 2.5-10 mcg/kg/min; rarely doses up to 40 mcg/kg/min may be needed
Bidil
hydralazine plus isosorbide dinitrate- both produce vasodilation via NO
Indication: CHF in african americans
Improves mortality
Furosemide
Loop diuretic
Spironolactone
aldosterone antagonist
improves survival
blocks remodeling
