Pharmacology of HTN + coronary artery disease

Question 1

What drugs decrease the cardiac workload?

Answer 1

beta-blockers
calcium channel blockers
other channel inhibitors: Ivabradine, Ranolazine

indirectly = drugs that reduce blood pressure

Question 2

What drugs are coronary vasodilators?

Answer 2

nitrates
potassium channel opener: Nicorandil

Question 3

Mechanism of action of calcium channel blockers

Answer 3

targets L-type voltage-gated Ca2+ channels

present in:
- arterial smooth muscle (vasodilation)
- cardiac muscle (reduce force of cardiac muscle contraction)
- cardiac pacemaking tissue (reduce HR, block AV node)

Question 4

What are the 2 types of calcium channel blockers?
Give some examples

Answer 4

non-dihydropyridine (negative-inotropic)
- Verapamil (mainly cardiac effects)
- Diltiazem (cardiac + vascular)
- useful for angina and arrhythmias (and some BP effect)

dihydropyridine (non-inotropic)
- act mainly on vascular smooth muscle to decrease BP
- Amlodipine
- Nifedipine (little to no cardiac effect)
- widely used for HTN

Question 5

Adverse effects of calcium channel blockers

Answer 5

negative inotropic/cardiac:
- slow HR
- decreased contraction (mau worsen heart failure)

non-inotropic/vascular:
- headache
- flushing
- peripheral oedema
- reflex tachycardia (may be harmful to those with CAD)

Question 6

What is the effect of stimulating Beta-1 receptors?

Answer 6

present in cardiac muscle –> increased contraction
present in pacemaker tissue and conduction –> pump faster

Question 7

What do beta-blovkers target?

Answer 7

blocking beta-1 in the heart to decrease heart rate and decrease force of contraction

Question 8

Name some commonly used beta-blockers

Answer 8

non-selective: propranolol (old generation, can worsen asthma as targets beta-2 too)

cardioselective (selective for beta-1): atenolol, bisoprolol, metoprolol

vasodilator activity (alpha-blocking properties): carvedilol, labetalol

Question 9

Indications for beta blockers?

Answer 9

demonstrated decreased mortality following:
- ACS/MI
- chronic heart failure

symptomatic benefit in angina
resistant hypertension (4th line)

Question 10

Adverse effects of beta blockers

Answer 10

cardiac cause:
- bradycardia
- initially worsens heart failure

sympathetic blockade:
- bronchoconstriction (blocking B-2 adrenoceptors)
- tiredness, feel cold

Question 11

Nitrates MOA

Answer 11

get converted to nitric oxide which diffuses to smooth muscle cells of veins and arteries, causing wall relaxation and vasodilation

Question 12

What are the effects of nitrates

Answer 12

arterial dilation:
- increased coronary supply
- decreased afterload by lowering BP

venous dilation:
(decreases blood return to heart)

Question 13

Commonly used nitrates

Answer 13

Glyceryltrinitrate (GTN)
Isosorbide mononitrate

Question 14

How is Isosorbide mononitrate taken?

Answer 14

oral formulation
once daily

Question 15

How is GTN taken?

Answer 15

sublingual, spray, buccal
fast but short-acting
rapid relief of symptoms for angina/ACS

most common = spray under tongue

Question 16

Adverse effects of nitrates?

Answer 16

hypotension
reflex tachycardia
headache
flushing

Question 17

What specialist drugs can be used 3rd-4th line for angina?

Answer 17

potassium channel opener: Nicorandil (also has nitrate action)

late sodium current inhibitor: Ranolazine

Specific sinus node inhibitor: Ivabradine (blocks cardiac conduction, similar to beta-blocker in slowing heart rate)

Question 18

What does mean arterial pressure depend on?

Answer 18

cardiac output
vascular resistance

Question 19

What drug classes can be used in hypertension management and why do they work?

Answer 19

diuretics (thiazides) = decrease intravascular volume

alpha + beta blockers = decrease sympathetic tone that is causing arterial constriction and increased cardiac output

calcium channel blockers = relax peripheral arteries

ACE-i/ARBs = block neuroendocrine mediators of BP

Question 20

ACE inhibitors examples

Answer 20

[angiotensin converting enzyme inhibitors]
captopril
enalapril
ramipril

Question 21

Indications for ACE-is?

Answer 21

1st line in hypertension unless patient >55 or African descent

1st line if previous heart failure or cardiac damage

Question 22

ACE inhibitors safety considerations

Answer 22

drops BP (1st dose) - give small test dose, check pt not too volume depleted

worsens renal function - check U&Es before + 1 week after

retains potassium - stop K supplements of K+-sparing diuretics

causes cough + other allergies

Question 23

What are ARBs?

Answer 23

angiotensin 2 receptor blockers
used in patients who cannot tolerate ACE-is
block type 1 angiotensin 2 receptors

Question 24

List 4 types of diuretics

Answer 24

loop
thiazides
thiazide-like
potassium-sparing

Question 25

Describe loop diuretics

Answer 25

can be used in renal impairment high efficacy for heart failure works in 30min-1h (IV) can be used orally for long-term control OD in the morning eg. furosemide, bumetanide

Question 26

Which diuretics are not as effective in renal failure?

Answer 26

thiazides thiazide-like

Question 27

Name a thiazide diuretic and an indication for use

Answer 27

bendroflumethiazide for hypertension

Question 28

Name a thiazide-like diuretic, when should they be avoided?

Answer 28

indapamide ineffective and should be avoided if eGFR<30

Question 29

Name a potassium-sparing diuretic and indications for their use

Answer 29

spironolactone blocks aldosterone for heart failure and hypertension used together with more effective diuretics

Question 30

Safety considerations for diuretics

Answer 30

hypovolaemia dehydration hypotension electrolyte imbalance: low potassium/sodium, high urea monitor BP, urea, urine output, body weight check electrolytes regularly if on high dose

Question 31

Other hypertension drugs for specialist use

Answer 31

beta-blocker alpha-blocker eg. doxazosin renin inhibitor eg. aliskiren central sympathetic outflow eg. clonidine, methyldopa potassium channel openers eg. minoxidil