Lecture 21 - Inotropic drugs Flashcards
Inotrope definition?
changing the force of muscle contraction; positive or negative
Shock definition?
characterised by inadequate organ perfusion to meet the tissue’s oxygenation demand leading to organ dysfunction
Types of shock?
hypovolemic (haemmorrhage), cadiogenic (heart failure), distributive (anaphylaxis), obstructive (PE)
Goals of shock resuscitation?
restore blood pressure (euvolaemia), normalise systemic perfusion (inotropes and vasopressors), preserve organ function (renal perfusion), treat underlying cause (antibiotics) - important to individualise treatment
Cardiogenic shock?
high systemic resistance, low cardiac output - caused by ischaemia, valve dysfunction or acute VSD
Inotropic Agents?
augments contractility, after preload established thus improving cardiac function -> improving global perfusion; risk of tachycardia and increased myocardial oxygen consumption
B1 agonists?
in heart, increase contractility (positive inotrope), increase HR (positive chronotrope) e.g. dobutamine
A1 agonists?
mostly in BV, increase tone/resistance (vasopressor), e.g. norepinephrine
Norepinephrine?
potent a-agonist, minimal B1 agonist, increases peripheral resistance and sys/dias BP, intravenous infusion
Epinephrine?
mixed a- and b- effects, can vasoconstrict and dilate, potent inotrop and chronotrope (for MI), increase myocyte oxygen consumption particularly in coronary heart disease, continuous IV infusion
Epinephrine and anaphylaxis?
activating both receptors, potent vasopressor, BP increase, dilates bronchi, IM epipen
Dobutamine?
B1 agonist, potent inotrope, variable chronotrope, 2min half life, hepatic metabolism, caution in hypotension as may precipitate tachycardia or worsen hypotension due to inadequate volume
Dopamine?
short half life, low dose increase renal blood flow via D1, mod. dose B effects, high dose a effects
Vasopressor side effects?
vasoconstriction (a- agonism) leading to ischaemia (cardiac, limb, gut, cerebral), and increased cardiac work (a- and b- activation) leading to cardiac ischemia and arrhythmias
Other vasopressor agents?
Vasopressin (VA1 receptor, IP3 mechanism, Liver/Renal metabolism) and Angiotensin II (catecholamine-resistant shock)
Amrinone/Milrinone?
Phosphodiesterase III inhibitor, vasodilation, positive inotrope, Increase cAMP -> PKA -> Ca flux, most often added with dobutamine, i.v.
Phosphodiesterase inhibitors - side effects?
Thrombocytopenia, hypotension, arrhythmias (linked to cAMP), increased mortality
Levosimendan?
i.v., treatment of shock, Ca sensitiser (increased troponin sensitivity to Ca and also inotropy); side effects of arrhythmias and increased mortality
Digoxin?
indicated by AF signalling acute/chronic heart failure (slows HR, improve cardiac work), no affect on life span, improve symptoms, reduce hospital admissions - 3rd line after B blocker then diltiazem
Digoxin mechanism of action 1?
@ cardiac myocyte, blocks Na extrusion through ATPase, promoting Na/Ca exchange to bring in more Ca, contributing to contractile apparatus, toxicity risk in hypokalaemia
Digoxin mechanism of action 2?
augment vagal tone at AV node, slow AV conduction, and slow ventricular rate
Digoxin toxicity - cardiac?
arrhythmias, 2nd/3rd degree heart block, ECG changes
Digoxin toxicity - non cardiac?
nausea, anorexia, diarrhoea, abdo pains, fatigue, visual complaints, muscular weakness, dreams
Digoxin interactions?
toxicity risk w low K/Mg, quinidine, verapamil, erythromycin, cyclosporin, PGP inhibitors - linked to multi-drug carrier P-glycoprotein
