10. Antihypertensives Flashcards
What are the 10 drug classes of antihypertensives?
- Thiazide diuretics- hydrochlorothiazide
- β1-adrenergic blocker- atenolol, metoprolol
- α1-adrenergic blocker- prazosin
- Vasodilators- hydralazine, sodium nitroprusside (SNP)
- Ca channel blocker- amlodipine, cilnidipine
- ACE inhibitors- enalapril, lisinopril, ramipril
- Ang II receptor [AT1] blocker- irbesartan
- Direct renin inhibitor (DRI)- aliskiren
- α2-adrenergic agonist- clonidine
- Hypertensive emergency- SNP, clonidine, prazosin
Slide 8 AHT
What is hypertension?
Sustained BP of 130/90 or 140/90 mmGg and over
Silent killer, no symptoms when it is mild
Essential hypertension- cause unknown, increase sympathetic nervous system, increase RAS, increase blood volume
For each 10mmHg increase in systolic blood pressure, risk of stroke double ms
Heart failure and renal failure increase with hypertension
What are the stages of hypertension?
Normal- 120/80 Mild- 121-139/81-90 Diet, salt restrict, exercise Moderate- 140-159/91-99 Mono-drug therapy Severe- 160-179/100-109 Multiple drug therapy Crisis/emergency- >180/>110 Attention within 24 hours
Slide 5 AHT
What is the pathophysiology of essential hypertension?
Early phase has increased CO due to increase plasma volume
⬆️plasma volume leads to ⬆️venous return due to defective renal handling of Na and H2O
⬆️renal sympathetic activity is TPR is ⬆️
Renin and SNS activity are connected with eachother and BP keeps going up caught in a viscious cycle of renal defect in Na handling
Slide 6 AHT
What are the 5 things activation of the sympathetic nervous system (SNS) leads to?
Release of norepinephrine from nerve ending:
- Vasoconstriction of resistance type arterioles (α receptor mediated increase TPR, BP and afterload)
- Reabsorption of tissue fluid as a result of decrease in cap. pressure
- Increased venoconstriction which causes increase venous return and increase preload
- Increase release of renin and increase in renin-angiotensin II-aldosterone activity (increase blood volume and plasma Na)
- Increase in HR and cardiac contractility (β adrenergic effect)
Slide 7 AHT
What are thiazide diuretics?
Reduce Na/H2O absorption, early DCT
Reduce plasma volume, venous return, CO, and BP initially
After 4 weeks, TPR goes down and CO up while BP stays lower
Very cheap, works with other classes
Drawback- increases renin and SNS activity- which dampens the BP lowering effect
Plasma low K, high Ca, high uric acid, hyperglycemia
Slide 10 AHT
What does angiotensin II do for hypertension?
Ang II contributes to hypertension
Causes vasoconstriction and vascular remodelling
Increase sympathetic drive, more Ang II
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What are β1-adrenergic antagonists (β1 blockers)?
β1 blocking ⬇️renin release, ⬇️central sympathetic discharge, ⬇️work load on heart, ⬇️renin-Ang-aldosterone system activation
Over period of time reduces CO and TPR by decreasing both afterload and preload
Great when angina or chronic CHF are present
Used in angina, hypertension, tachycardia
What are adverse effects of β1 blockers?
Hyperlipidemia- insulin resistance, impaired glucose tolerance, not so good to use in diabetics
Bronchospasm- watch plasma K in ESRD patients can aggravate the incidence of hyperkalemia
Peripheral artery disease
Cold hand/feet
Erectile dysfunction
Depression
What are ACE inhibitors?
Adverse effects?
About 15 types (captopril, enalapril…)
ACE blocks Ang II and increases bradykinin (BK)
⬇️Ang II- also blocks AT2 receptor
⬆️BK- vasodilation, dry cough, angioedema, hyperkalemia
Cheap, but gives dry cough and AT2 blockade
Escape on long use
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What are angiotensin receptor antagonists (ARBs)?
Adverse effect?
Losartan, irbesartan, telmisartan
Selective AT1 blockade
No BK effect (less cough)
Leave good AT2 alone
Decrease aldosterone, block sodium potassium exchange (potassium conserving)
Hyperkalemia exists in these too
About as effective as ACE inhibitor
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What is direct renin inhibitor (DRI)?
Aliskiren
Inhibits renin release
Lowers BP
Shuts off Ang I, Ang II, aldosterone effects
Renin is Ali’s supposed to have direct inhibitory effect in vascular smooth muscle cells for vasoconstriction
Thus it is claimed to be superior to ACE inhibitors
Clinical evidence doesn’t support the above, all theory
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What are the differences between ACE inhibitors, ARBs, DRI, and β1 antagonists in terms of renin, Ang I, Ang II, aldosterone, and bradykinin?
ACE-I:
⬆️renin ⬆️Ang I ⬇️Ang II ⬇️aldo ⬆️BK
ARBs:
⬆️renin ⬆️Ang I ⬆️Ang II ⬇️aldo
DRI:
⬇️renin ⬇️Ang I ⬇️Ang II ⬇️aldo
β1 antagonists:
⬇️renin ⬇️Ang I ⬇️Ang II ⬇️aldosterone
Only ACE-I have effect on BK
Slide 17 AHT
What are calcium channel antagonists?
Adverse effects?
CCBs- amplidipine, cilnidipine, diltiazem, verapamil
Vascular smooth muscle relaxation by blocking L type Ca channels to prevent influx
Cilnidipine blocks L and N channels
Adverse effects- constipation, headache, flushing
What are direct vasodilators?
Nitrovasodilators- hydralazine, minoxidil, sodium nitropruside
Not useful alone (increase HR, Na retention)
Ineffective- long term often used as 3rd drug
