Inotropic drugs

Question 1

Define inpotrope and shock

Answer 1

Inotrope: changing force on contraction of heart

Shock: inadequate organ perfusion to meet the tissue’s oxygenation demand leading to organ dysfunction

Question 2

Categories of shock

Answer 2

Hypovolemic: haemorrhage, dehydration
Cardiogenic: HF
Distributive: sepsis, anaphylaxis ** most common type
Obstructive: cardiac tamponade, PE in RV obstructing flow

Question 3

Features of patients with shock

Answer 3

ICU, HDU with central lines, catheters, etc

• Hypotension
• LV impairment
• Changes in vascular resistance
• Poor renal/peripheral perfusion
• Confused/sedated

Question 4

How do inotropes work, rationale and risks

Answer 4

Once euvolemic (preload established), augments contractility, increasing CO

Rationale: ^ CO ^ global perfusion
Risk: Tachycardia and increased myocardial O2 consumption

Question 5

Examples of vasopresser/ inotropic agents

Answer 5

alpha and beta receptor agonists

NE, E, dobutamine; dopamine

Question 6

Receptors and location

Answer 6

A1: vascular SM, increase tone, NE
A2: presynaptic
B1: heart, increase chronotropy and inotropy- dobutamine
B2: respiratory and uterine SM
B3: adipocytes

Question 7

Drug affinities for receptors

Answer 7

Alpha1: Phenylephrine > NE > E > dopamine > dobutamine > isopreterenol

beta is opposite

Question 8

NE: what line in shock; results in; administration

Answer 8

1st line in shock, potent vasoconstrictor, a1 agonist. Minimal beta effect.
Increase TPR, increases BP
Continuous IV infusion, can titrate according to BP, short half life but fast uptake by presynaptic

GPCR, increase phospholipase C and IP3, increased calcium

Question 9

E: effects what receptors; causes what?; used for

Answer 9

Alpha and beta receptors, can cause vasoconstriction and dilation. Net effect is constriction when infused. (NB ramchandra leccy)
Inotrope and chronotrope, so cardiac arrest.
IV dose
So vasopression + inotropy on heart + relaxes bronchi

Anaphylactic shock (0.5mg 1:1000 IM), uptake 2 mechanism on post synaptic. Short t1/2

Question 10

Dobutamine: ? agonist; half life; metabolism; caution in ?; mechanism

Answer 10

B1 agonist, potent. Is a potent inotrope, variable chronotrope
2 mins
Hepatic (glucoronide)
Hypotension, may cause tachy or worsen hypotension

Adenylyl cyclase, increasing cAMP and subsequent effect occurs.

Question 11

cAMP breakdown and significance

Answer 11

Phosphodiesterase breaks down. If blocked, can prolong activity, whatever it may be

Question 12

Dopamine: precursor?; low dose; moderate dose; high dose

Answer 12

NE precursor
Low dose: dopaminergic receptors in kidneys, vasodilating in kidney, increasing renal blood flow
Moderate: B agonist (+ inotropy and chronotropy)
High: alpha agonist (vasopresser)

Question 13

Vasopresser side effects

Answer 13

• In shock, adding to what is already a high sympathetic drive
• Vasoconstriction through alpha agonism, ischaemia in heart, limb, gut, brain
• Increase cardiac work (alpha and beta agonism), cardiac ischaemia, or arrythmias

Question 14

Other vasopresser agents

Answer 14

vasopressin

A2

Question 15

Phosphodiesterase inhibitiors for shock

Answer 15

Amrinone and milrinone
often used with dobutamine IV

However: thrombocytopenia; hypotension as vasodilates; arrythmias due to ^ cAMP; mortality risk up

Question 16

Levosimendan

Answer 16

Calcium sensitiser, new and IV use.

enhances tropnonin sensitivity to ca2+, increases inotropy. However pro-arrythmic

Question 17

Digoxin class and inication

Answer 17

Glycoside, from a plant, is lipophilic and long half life

Atrial fibrillation as slows HR, improves cardiac work. Acute and chronic HF

Question 18

Mechanism of action of digoxin 2.

For first, if hypokalaemic, result is?

Answer 18

1: Blocks Na+/K+ ATPase. Normally, three sodium out, 2 K+ in. Block will cause [Na+]i (intacellular) to increase. This is noted by NCX. Result is more Na+ extrusion, and increased calcium in the cell, this increases inotropy
NB: hypokalaemia, allows digoxin to inhibit more, more liekly to have side effects

2: Acts at AVN, by augmenting vagal tone, slows conduction and thus ventricular rate

Question 19

Digoxin: half life and clinicaluse

Answer 19

Long half life, up to 36 hours with 1.5mg. Dependent on renal function though. Fast effect will be maintenance dose

Acute heart failure with atrial fibrillation
Afib 3rd line rate control (note 1st line beta blocker, 2nd line diltiazem for RATE CONTROL), often to us synergy if can not stand one

Question 20

Digoxin toxicity/side effets

Answer 20

Cardiac:

• Various arrythmias: bigeminy, NSVT, VT, 2nd or 3rd degree heart block
• ECG change: reverse tick sign in ST segment

Non cardiac: Nasuea/vomiting/anorexia; fatigue; visual complaints; muscular weakness; abdo pain; dizziness; funny dreams; diarrhoea

Question 21

Digoxin drug interactions and why

Answer 21

Excreted by P-glycoproteins in kidney. Also decreases GI absorption, increases biliary loss and decreases CNS access.

PGP inhibitors: quinidine, amiodarone, verapamil, diltiazem, erythromycin, cyclosporin. Will increase digoxin levels, more likely to be toxic

Metabolic: also low K+ like said above and low magnesium, so be careful with diuretic use