Pharmacology of HTN + coronary artery disease Flashcards
What drugs decrease the cardiac workload?
beta-blockers
calcium channel blockers
other channel inhibitors: Ivabradine, Ranolazine
indirectly = drugs that reduce blood pressure
What drugs are coronary vasodilators?
nitrates
potassium channel opener: Nicorandil
Mechanism of action of calcium channel blockers
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)
What are the 2 types of calcium channel blockers?
Give some examples
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
Adverse effects of calcium channel blockers
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)
What is the effect of stimulating Beta-1 receptors?
present in cardiac muscle –> increased contraction
present in pacemaker tissue and conduction –> pump faster
What do beta-blovkers target?
blocking beta-1 in the heart to decrease heart rate and decrease force of contraction
Name some commonly used beta-blockers
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
Indications for beta blockers?
demonstrated decreased mortality following:
- ACS/MI
- chronic heart failure
symptomatic benefit in angina
resistant hypertension (4th line)
Adverse effects of beta blockers
cardiac cause:
- bradycardia
- initially worsens heart failure
sympathetic blockade:
- bronchoconstriction (blocking B-2 adrenoceptors)
- tiredness, feel cold
Nitrates MOA
get converted to nitric oxide which diffuses to smooth muscle cells of veins and arteries, causing wall relaxation and vasodilation
What are the effects of nitrates
arterial dilation:
- increased coronary supply
- decreased afterload by lowering BP
venous dilation:
(decreases blood return to heart)
Commonly used nitrates
Glyceryltrinitrate (GTN)
Isosorbide mononitrate
How is Isosorbide mononitrate taken?
oral formulation
once daily
How is GTN taken?
sublingual, spray, buccal
fast but short-acting
rapid relief of symptoms for angina/ACS
most common = spray under tongue
Adverse effects of nitrates?
hypotension
reflex tachycardia
headache
flushing
What specialist drugs can be used 3rd-4th line for angina?
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)
What does mean arterial pressure depend on?
cardiac output
vascular resistance
What drug classes can be used in hypertension management and why do they work?
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
ACE inhibitors examples
[angiotensin converting enzyme inhibitors]
captopril
enalapril
ramipril
Indications for ACE-is?
1st line in hypertension unless patient >55 or African descent
1st line if previous heart failure or cardiac damage
ACE inhibitors safety considerations
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
What are ARBs?
angiotensin 2 receptor blockers
used in patients who cannot tolerate ACE-is
block type 1 angiotensin 2 receptors
List 4 types of diuretics
loop
thiazides
thiazide-like
potassium-sparing
Describe loop diuretics
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
Which diuretics are not as effective in renal failure?
thiazides
thiazide-like
Name a thiazide diuretic and an indication for use
bendroflumethiazide
for hypertension
Name a thiazide-like diuretic, when should they be avoided?
indapamide
ineffective and should be avoided if eGFR<30
Name a potassium-sparing diuretic and indications for their use
spironolactone
blocks aldosterone for heart failure and hypertension
used together with more effective diuretics
Safety considerations for diuretics
hypovolaemia
dehydration
hypotension
electrolyte imbalance: low potassium/sodium, high urea
monitor BP, urea, urine output, body weight
check electrolytes regularly if on high dose
Other hypertension drugs for specialist use
beta-blocker
alpha-blocker eg. doxazosin
renin inhibitor eg. aliskiren
central sympathetic outflow eg. clonidine, methyldopa
potassium channel openers eg. minoxidil
