1. Antihypertensive Drugs

2. Secondary hypertension is hypertension due to an identifiable cause
Hypertension or arterial hypertension is a chronic medical condition in which the blood pressure in the arteries is persistently elevated.
Hypertension is present if the blood pressure is persistently at or above 140/90 mmHg 
Hypertension is classified as either primary (essential) hypertension (90–95%) or secondary hypertension (5–10%).
Primary hypertension is high blood pressure with no obvious underlying cause.
Secondary hypertension is hypertension due to an identifiable cause

5. Complications of Hypertension

6. Hypertensive crisis -severely elevated blood pressure (equal to or greater than a systolic 180 or diastolic of 110).
Hypertensive crisis is categorized as :
Hypertensive urgency
There is no evidence of end organ damage resulting from the elevated blood pressure. In these cases, oral medications are used to lower the BP gradually over 24 to 48 hours.
Hypertensive emergency
There is evidence of direct damage to one or more organs.The most affected organs include the brain, kidney, heart and lungs, producing symptoms which may include confusion, drowsiness, chest pain and breathlessness. In hypertensive emergency, the blood pressure must be reduced rapidly to stop ongoing organ damage.

8. CLASSIFICATION 1. Diuretics
Thiazides: Hydrochlorothiazide, Chlorthalidone, Indapamide
High ceiling: Furosemide, etc.
K+ Sparing: Spironolactone, Amiloride
2. ACE inhibitors
Captopril, Enalapril, Lisinopril, Perindopril, Ramipril, Fosinopril, etc.
3. Angiotensin (AT1 receptor) blockers
Losartan, Candesartan, Irbesartan, Valsartan, Telmisartan
4. Direct renin inhibitor
Aliskiren
5. Calcium channel blockers
Verapamil, Diltiazem, Nifedipine, Felodipine, Amlodipine, Nitrendipine, Lacidipine, etc.
6. β Adrenergic blockers
Propranolol, Metoprolol, Atenolol, etc.
7. β + α Adrenergic blockers
Labetalol, Carvedilol
8. α Adrenergic blockers
Prazosin, Terazosin, Doxazosin, Phentolamine, Phenoxybenzamine
9. Central α2 Adrenomimetics
Clonidine
10. Vasodilators
Arteriolar: Hydralazine, Minoxidil, Diazoxide
Arteriolar + venous: Sodium nitroprusside
Sympatholytics (Reserpine, Guanethidine, etc.) and ganglion blockers (Pentolinium, etc.) are only of historical importance.

10. DIURETICS
Only the thiazide and thiazide-like diuretics should usually be the first choice when selecting a diuretic to treat hypertension.
The reason why thiazide-type diuretics are better than the others is (at least in part) thought to be because of their vasodilating properties.
Loop diuretics should be used only in case of severely elevated blood pressure (hypertensive crisis).
Potassium sparing diuretics are used only in conjunction with a thiazide diuretic to prevent K+ loss.

11. ANGIOTENSIN CONVERTING ENZYME (ACE) INHIBITORS
inhibit the activity of angiotensin-converting enzyme (ACE), an enzyme responsible for the conversion of angiotensin I into angiotensin II, a potent vasoconstrictor.

12. ACE-INHIBITORS

14. ACE-INHIBITORS Captopril Enalapril Lisinopril Ramipril Perindopril
Clinical use:
Hypertension
Cardiac conditions such as congestive heart failure
Myocardial infarction
Adverse effects:
Hypotension
Cough: a persistent brassy cough is caused by inhibition of bradykinin breakdown in the lungs
Hyperkalemia
Teratogenicity
Acute renal failure

16. Angiotensin II receptor antagonists
Angiotensin II receptor antagonists  also known as angiotensin receptor blockers (ARBs), AT1-receptor antagonists or sartans
Work by antagonizing the activation of angiotensin receptors.
Losartan
Telmisartan
Irbesartan
Valsartan

17. Mechanism of action Blockage of AT1 receptors directly causes:
Vasodilation
Reduce production and secretion of aldosterone
Medical uses
primarily for the treatment of patients that is intolerant of ACE inhibitor therapy
They do not inhibit the breakdown of bradykinin ⇒ there are no the persistent dry cough or angioedema that limit ACE inhibitor therapy.
Adverse effects:
Hypotension
Hyperkalemia
Headache
Dizziness

18. Calcium channel blockers (CCB)
Block the entry of Ca2+ into:
Smooth muscle cells in artery walls
SA, A-V node, atrial and ventricular cardiac fibres
Classes of calcium channel blockers:
Dihydropyridines :
Amlodipine
Felodipine
Isradipine
Nicardipine
Nifedipine
Nimodipine
Non-dihydropyridines:
Verapamil ⇒
Diltiazem ⇒
Act only on arteries ⇒reduce systemic vascular resistance and arterial pressure
selective for myocardium
Act both on arteries and heart

19. Comparative properties of representative calcium channel blockers
Nifedipine
Verapamil
Diltiazem
Vascular smooth muscle
relaxation
++++ - ++
Cardiac effects :
Heart rate ↓
AV conduction velocity↓
Contractility↓
Clinical use in
Hypertension
Angina
Arrhythmia Angina
(Hypertension)
Arrhythmia
ADR
Hypotension
Tachycardia
Edema
Bradycardia
A-V block
CHF
Cardiac arrest

20. β-ADRENERGIC BLOCKERS
Nonselective (β1 and β2)
a. Without intrinsic sympathomimetic activity:
Propranolol
Sotalol
Timolol
b. With intrinsic sympathomimetic activity:
Pindolol
Cardioselective (β1):
Metoprolol
Atenolol
Acebutolol
Bisoprolol
Esmolol
Betaxolol
Nebivolol
α and β blockers (with additional vasodilator property):
Labetalol
Carvedilol

21. αβ ADRENERGIC BLOCKERS
Labetalol
acts faster than pure β blockers. It has been used i.v. for rapid BP reduction in hyperadrenergic states, cheese reaction, clonidine withdrawal, eclampsia, etc. Oral labetalol therapy is restricted to moderately severe hypertension not responding to a pure β blocker.
Carvedilol
produces vasodilatation and has additional antioxidant/free radical scavenging properties. Carvedilol is a frequently selected drug for long-term treatment of CHF, and is approved as an antihypertensive as well.

22. α-ADRENERGIC BLOCKERS
A. Nonselective
Phentolamine
Phenoxybenzamine
B. α1 selective— Prazosin, Terazosin, Doxazosin, Alfuzosin

23. Central α2 Adrenomimetics
Clonidine
Use
Clonidine was a popular antihypertensive in the late 1960s and 1970s, but frequent side effects, risk of withdrawal hypertension and development of tolerance have relegated it to a 3rd or 4th choice drug. There is no data on prognostic benefits, if any, of clonidine. At present, it is occasionally used in combination with a diuretic.
Clonidine has also facilitated alcohol withdrawal and smoking cessation.
ADR:
Orthostatic hypotension
Sedation
Rebound effect

24. VASODILATORS
Vasodilators act directly on the smooth muscle of arteries and veins to relax their walls
They are only used in hypertensive emergencies or when other drugs have failed.
Arteriolar: Hydralazine, Minoxidil, Diazoxide
Hydralazine and its derivatives are used in the treatment of severe hypertension, although they should be avoided in emergencies. They are no longer indicated as first-line therapy for high blood pressure due to side effects and safety concerns.
Arteriolar + venous: Sodium nitroprusside
Sodium nitroprusside, a very potent, short-acting vasodilator, is most commonly used for the quick, temporary reduction of blood pressure in emergencies (such as malignant hypertension or aortic dissection).

25. VASODILATORS

26. Adverse effects of vasodilators
Facial flushing, throbbing headache, dizziness, palpitation, nasal stuffiness, edema, CHF, weakness, disorientation
Angina and MI may be precipitated in patients with coronary artery disease.
Postural hypotension
Paresthesias, tremor, muscle cramps, rarely peripheral neuritis.

27. TREATMENT OF HYPERTENSION
4 groups of first choice antihypertensive drugs:
A—ACE inhibitor/ARB
B—β-blocker
C—CCB
D—diuretic
A and B are preferred in younger patients (<55 years), C and D are preferred in the older (> 55 years)

28. Combination therapy
Though guidelines emphasise on single drug therapy, the addition of a second (and third or even fourth) drug is also highlighted when monotherapy fails.
In practice, a large majority of hypertensives ultimately require 2 or more drugs (70% patients who achieved target BP were being treated with 2 or more drugs)

29. The preferred combinations
Thiazide diuretic and ACE inhibitor
Thiazide diuretic and angiotensin receptor antagonist
Calcium antagonist and ACE inhibitor
Calcium antagonist and angiotensin receptor antagonist
Calcium antagonist and thiazide diuretic
β-blocker and calcium antagonist (dihydropiridine)

30. Combinations to be avoided
1. An α adrenergic blocker with clonidine: apparent antagonism of clonidine action has been observed. 2. Hydralazine with a DHP or prazosin; because of similar pattern of haemodynamic action (huge risk of orthostatic hypotension and collapse). 3. Verapamil or diltiazem with β blocker, because marked bradycardia, A-V block can occur. 4. Any two drugs of the same class.

31. Hypertensive emergencies and urgencies
Oral therapy
Nifedipine (10 mg orally or s.l. every 30 min). Adverse consequences - abrupt fall in BP.
Captopril (25 mg oral every 1–2 hours) - risk of excessive hypotension.
Clonidine (100 mg every 1–2 hours oral) acts mostly in 30–60 min, but produces sedation and rebound rise in BP on stopping the drug.

32. Parenteral therapy
1. Sodium nitroprusside (slow i.v. injection) is the drug of choice for most hypertensive emergencies.
2. Hydralazine (i.m. or slow i.v. injection) acts in 20–30 min and keeps BP low for 4–8 hours, but is less predictable, and not a first line drug. It has been especially used in eclampsia. It causes tachycardia and should be avoided in patients with myocardial ischaemia.
3. Phentolamine .This nonselective α1 + α2 blocker is the drug of choice for hyperadrenergic states, e.g. hypertensive episodes in pheochromocytoma, cheese reaction or clonidine withdrawal. Injected i.v.
4.Furosemide (oral or i.v.)
Nicardipine and clevidipine (parenteral DHPs),
Enalaprilat (a parenteral ACE inhibitor)
Trimethaphan (a ganglion blocker)