positive inotropic drug

Question 1

Acute heart failure- positive inotropic drugs

Answer 1

• beta adrenergic receptor stimulants
• cardiac glycosides
• calcium sensitizers
• PDE3 inhibitors

Question 2

beta adrenergic receptor stimulant- MOA

Answer 2

stimulate the beta1 receptor in the heart

• activate the adenylyl cyclase and increase in cAMP, increase in PKA function
• increase in calcium influx and CICR -> increase in intracellular calcium concentration
• increase in contractility

Question 3

dobutamine

Answer 3

• (-) enantiomer is an agonist of alpha 1, (+) is partial agonist
  both are non-selective agonist of beta receptors
  the vasoconstriction effect is offset by the vasodilator effect -> reduction in peripheral resistance

Question 4

dopamine

Answer 4

• only at intermediate dose, can have beta 1 agonist effect, if too low -> vasodilation , too high -> vasoconstriction

Question 5

beta adrenergic receptor stimulant- good

Answer 5

rapid onset and short duration of action

Question 6

beta adrenergic receptor stimulant- adverse effects

Answer 6

• pro arrhythmic, pro-angina, tachyphylaxis after 4 days (need to replace by PDE3 inhibitor)

Question 7

PDE3 inhibitors- example

Answer 7

milrinone, enoximone

Question 8

PDE3 inhibitor- MOA

Answer 8

• prevent the breakdown of cAMP by PDE3
• increase in intracellular ca level
• vasodilation effect

Question 9

PDE3 inhibitor- side effects

Answer 9

• pro-arrhythmic

Question 10

cardiac glycosides (digoxin)- MOA

Answer 10

• inhibit the Na K ATPase, therefore increase in intracellular Na conc -> increase the efflux of Na and influx of Ca by Na Ca exchanger
• increase in the Ca2+ storage in SR -> next contraction -> increase in intracellular Ca level

Question 11

digoxin- side effects

Answer 11

• very narrow safety margin
• pro-arrhythmic
  not 1st line treatment for heart failure (but can be used for chronic heart failure)

Question 12

digoxin- good

Answer 12

anti-arrhythmic

Question 13

calcium sensitizer- example

Answer 13

levosimendan

Question 14

Calcium sensitizer- MOA

Answer 14

• stabilise the binding between troponin C and calcium
• increase troponin C affinity for calcium
• increase in contractility without increasing the intracellular Ca level

Question 15

Calcium sensitizer- good

Answer 15

coronary and systemic vasodilation: activate the potassium channels in VSMC -> hyperpolarization -> prevent activation of voltage gated Ca channel and thus prevent vasoconstriction
- it is not pro-arrhythmic

Question 16

Calcium sensitizer- contraindications and bad

Answer 16

• baseline hypotension/ low bp patient

- headache and hypotension

Question 17

Calcium sensitizer- administration

Answer 17

IV

Question 18

Chronic heart failure

Answer 18

Adaptive changes/ compensatory mechanism/ maladaptation

• increase in sympathetic output (increase in heart rate and force of contraction; vasoconstriction)
• increase in RAAS output to reabsorption more water and sodium -> increase in blood volume

these are trying to restore and increase the Cardiac output

• however, both lead to increase in arterial pressure and thus decrease in CO
• increase in cardiac workload and myocardial hypertrophy (both RAAS and sym)
• peripheral oedema (RAAS) -> lungs -> reduction in oxygenation of blood -> further increase cardiac workload cos more blood needed to carry enough oxygen

Question 19

Chronic heart failure drugs

Answer 19

ivabradine

LCZ696

Question 20

LCZ696- MOA

Answer 20

• dual angiotensin receptor neprilysin inhibitor
• 1:1 ratio of valsartan and sacubitril
• inhibition of neprilysin by sacubitril -> reduce the breakdown of vasoactive peptides (bradykinin and substance P) -> vasodilation
• reduce breakdown of natriuretic peptides to increase the excretion of Na and water, reducing the blood volume
• have to use with ang receptor blocker because it also blocks the breakdown of AngII

Question 21

LCZ696- side effect

Answer 21

hypotension
angioedema
hyperkalemia, renal dysfunction (related to the Ang receptor blocker)

• > do not use with ACEI
• > correct and check the Na level volume depletion status before using this to minimise the effect of hypotension