Lecture 21 - Inotropic drugs

Question 1

Inotrope definition?

Answer 1

changing the force of muscle contraction; positive or negative

Question 2

Shock definition?

Answer 2

characterised by inadequate organ perfusion to meet the tissue’s oxygenation demand leading to organ dysfunction

Question 3

Types of shock?

Answer 3

hypovolemic (haemmorrhage), cadiogenic (heart failure), distributive (anaphylaxis), obstructive (PE)

Question 4

Goals of shock resuscitation?

Answer 4

restore blood pressure (euvolaemia), normalise systemic perfusion (inotropes and vasopressors), preserve organ function (renal perfusion), treat underlying cause (antibiotics) - important to individualise treatment

Question 5

Cardiogenic shock?

Answer 5

high systemic resistance, low cardiac output - caused by ischaemia, valve dysfunction or acute VSD

Question 6

Inotropic Agents?

Answer 6

augments contractility, after preload established thus improving cardiac function -> improving global perfusion; risk of tachycardia and increased myocardial oxygen consumption

Question 7

B1 agonists?

Answer 7

in heart, increase contractility (positive inotrope), increase HR (positive chronotrope) e.g. dobutamine

Question 8

A1 agonists?

Answer 8

mostly in BV, increase tone/resistance (vasopressor), e.g. norepinephrine

Question 9

Norepinephrine?

Answer 9

potent a-agonist, minimal B1 agonist, increases peripheral resistance and sys/dias BP, intravenous infusion

Question 10

Epinephrine?

Answer 10

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

Question 11

Epinephrine and anaphylaxis?

Answer 11

activating both receptors, potent vasopressor, BP increase, dilates bronchi, IM epipen

Question 12

Dobutamine?

Answer 12

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

Question 13

Dopamine?

Answer 13

short half life, low dose increase renal blood flow via D1, mod. dose B effects, high dose a effects

Question 14

Vasopressor side effects?

Answer 14

vasoconstriction (a- agonism) leading to ischaemia (cardiac, limb, gut, cerebral), and increased cardiac work (a- and b- activation) leading to cardiac ischemia and arrhythmias

Question 15

Other vasopressor agents?

Answer 15

Vasopressin (VA1 receptor, IP3 mechanism, Liver/Renal metabolism) and Angiotensin II (catecholamine-resistant shock)

Question 16

Amrinone/Milrinone?

Answer 16

Phosphodiesterase III inhibitor, vasodilation, positive inotrope, Increase cAMP -> PKA -> Ca flux, most often added with dobutamine, i.v.

Question 17

Phosphodiesterase inhibitors - side effects?

Answer 17

Thrombocytopenia, hypotension, arrhythmias (linked to cAMP), increased mortality

Question 18

Levosimendan?

Answer 18

i.v., treatment of shock, Ca sensitiser (increased troponin sensitivity to Ca and also inotropy); side effects of arrhythmias and increased mortality

Question 19

Digoxin?

Answer 19

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

Question 20

Digoxin mechanism of action 1?

Answer 20

@ cardiac myocyte, blocks Na extrusion through ATPase, promoting Na/Ca exchange to bring in more Ca, contributing to contractile apparatus, toxicity risk in hypokalaemia

Question 21

Digoxin mechanism of action 2?

Answer 21

augment vagal tone at AV node, slow AV conduction, and slow ventricular rate

Question 22

Digoxin toxicity - cardiac?

Answer 22

arrhythmias, 2nd/3rd degree heart block, ECG changes

Question 23

Digoxin toxicity - non cardiac?

Answer 23

nausea, anorexia, diarrhoea, abdo pains, fatigue, visual complaints, muscular weakness, dreams

Question 24

Digoxin interactions?

Answer 24

toxicity risk w low K/Mg, quinidine, verapamil, erythromycin, cyclosporin, PGP inhibitors - linked to multi-drug carrier P-glycoprotein