07 The heart: anti-angina drugs

Question 1

7.01 NITRATES

Glyceryl trinitrate, isosorbide mononitrate - actions

Answer 1

dilate and relax vascular (especially venular) smooth muscle and thus (i) reduce cardiac work and therefore metabolic demand and (ii) increase the perfusion and oxygenation of heart muscle

Question 2

7.01 NITRATES

Glyceryl trinitrate, isosorbide mononitrate - MOA

Answer 2

gives rise to nitric oxide (NO) in the cell, which activates protein kinase G (PKG) and reduces contraction

Question 3

7.01 NITRATES

Glyceryl trinitrate, isosorbide mononitrate - abs/distrib/elim

Answer 3

glyceryl trinitrate (GTN): sublingual tablet or spray, acts immediately - effects last ~30 min, can be given by transdermal patch - effects last 24h, can be given IV
isosorbide mononitrate: given orally, half-life 4h, slow-release preparation available

Question 4

7.01 NITRATES

Glyceryl trinitrate, isosorbide mononitrate - clinical use

Answer 4

given sublingually to prevent/treat stable angina
GTN is given IV to treat unstable angina and acute pulmonary oedema
(nitrates are also used in chronic heart failure)

Question 5

7.01 NITRATES

Glyceryl trinitrate, isosorbide mononitrate - adverse effects

Answer 5

headache due to vasodilatation
postural hypotension due to decreased vasomotor tone
prolonged usage leads to tolerance
methaemoglobinaemia (rare) with continued high doses

Question 6

7.02 SINUS NODE If INHIBITOR

Ivabradine - actions

Answer 6

slows the heart rate by inhibiting the sinus node

Question 7

7.02 SINUS NODE If INHIBITOR

Ivabradine - MOA

Answer 7

selective and specific inhibition of the cardiac pacemaker (If) current that controls the spontaneous diastolic depolarisation in the sinus node and regulates heart rate
the cardiac effects are specific to the sinus node with no effect on intra-atrial, atrioventricular or intra­ventricular conduction times, nor on myocardial contractility or ventricular repolarisation

Question 8

7.02 SINUS NODE If INHIBITOR

Ivabradine - abs/distrib/elim

Answer 8

rapidly and almost completely absorbed after oral administration with a peak plasma level reached in ~1h under fasting condition
extensively metabolised by the liver and the gut by oxidation through cytochrome P450 3A4 (CYP3A4) only

Question 9

7.02 SINUS NODE If INHIBITOR

Ivabradine - clinical use

Answer 9

symptomatic treatment of chronic stable angina (has no benefits on cardiovascular events)
treatment of chronic heart failure
can be used as an alternative to β-adrenoceptor antagonist

Question 10

7.02 SINUS NODE If INHIBITOR

Ivabradine - adverse effects

Answer 10

headache, dizziness, blurred vision, bradycardia, uncontrolled blood pressure
should not be used in patients with atrial fibrillation

Question 11

7.03 LATE SODIUM CURRENT BLOCKER

Ranolazine - actions

Answer 11

increases efficiency of myocardial energy production through metabolic modulation

Question 12

7.03 LATE SODIUM CURRENT BLOCKER

Ranolazine - MOA

Answer 12

inhibits the late sodium current, thereby indirectly reducing intracellular calcium and force of contraction, without affecting the heart rate

Question 13

7.03 LATE SODIUM CURRENT BLOCKER

Ranolazine - abs/distrib/elim

Answer 13

extensively metabolised by cytochrome P450 (CYP) 3A enzymes and, to a lesser extent, by CYP2D6, with approximately 5% excreted renally unchanged
elimination half-life 1.4-1.9h

Question 14

7.03 LATE SODIUM CURRENT BLOCKER

Ranolazine - clinical use

Answer 14

stable angina pectoris (as an adjunct to other anti-anginal agents)

Question 15

7.03 LATE SODIUM CURRENT BLOCKER

Ranolazine - adverse effects

Answer 15

headache, dizziness, constipation, nausea