1. Anti Hypertensive Drugs
Dr.hasem mansour

4. Drugs used to treat Hypertension
HTN = BP > 140/90
complications: premature death
vascular disease of brain, heart,kidneys

7. Improve life expectancy.
Goal of treatment
Improve life expectancy.
Preventing cardiovascular problems by reducing BP < 140/90
Prevent cerebrovascular accidents and kidney damage

8. Initial treatment of hypertension
Lifestyle modification first including exercise.
No smoking
Weight control
Reduce alcohol intake
Decrease stress
Sodium control

9. Drugs to treat hypertension
Diuretics
Calcium channel blockers
Angiotesin converting enzyme inhibitors (ACEI).
Angiotensin receptor blockers (ARB).
Autonomic nervous system agents
Direct acting vasodilators

10. Diuretics action
Thiazide diuretics, such as hydrochlorothiazide & chlorthalidone , lower blood pressure initially by increasing sodium and water excretion.
This causes in extracellular volume, resulting in cardiac output & renal blood flow .
The net result is hypotensive.

11. The Nephron

13. Loop diuretics The loop diuretics (furosemide, torsemide)
Block sodium and chloride reabsorption in the kidneys, even in patients with poor renal function.
Loop diuretics cause decreased renal vascular resistance and increased renal blood flow.
The net result hypotension.

14. Treatment mild to moderate HTN First drug of treatment is thiazide.
Diuretics use
Treatment mild to moderate HTN
First drug of treatment is thiazide.
Treatment heart failure or kidney disease(loop diuretics).
Reduce edema associated with CHF (loop diuretics).

15. Diuretics side effects
Loop diuretics: ototoxicity, blood dyscriasis, hypokalemia, hyperurecemia, hypotension.
Thiazide diuretics: Hypokalemia, headache, hepatotoxicity, hyperglycemia , hypotension and hyperurecemia.

16. Potassium sparing diuretics
Spironolactone, Amiloride (inhibits sodium transport at the late distal and collecting ducts)
Spironolactone and eplerenone prevent potassium loss.
Used to treat resistant HTN
Used in combination with other diuretic.

17. Orthostatic hypotension Dry mouth, irritation Hyperkalemia
Side effects
Orthostatic hypotension
Dry mouth, irritation
Hyperkalemia
Disorientation
Dehydration
Gynecomastia

18. Optimal time to admin.= AM Accurate intake and output Daily weights
Implications for use
Optimal time to admin.= AM
Accurate intake and output
Daily weights
Monitor electrolyte imbalances
Pregnancy risk : c

20. Calcium Channel Blockers
Block the inward movement of calcium in the heart and in smooth muscle of the coronary and peripheral arteriolar vasculature.
This causes smooth muscle to relax, dilating mainly arterioles.

21. Calcium Channel Blockers types
Non dihydropyridine: Verapamil and Diltiazem
Have a much greater affinity for heart.
Dihydropyridines: nifedipine , amlodipine.
Have a much greater affinity for vascular calcium channels.

22. Bradycardia extremely May precipitate A-V block
SIDE EFFECTS
Decrease BP
Bradycardia extremely
May precipitate A-V block
Headache, flushing and dizziness
Abdominal discomfort
Peripheral edema
Constipation with verapamil

23. 2nd and 3rd degree heart block Pregnancy category: C
C.I and pregnancy
Cardiogenic shock.
CHF
2nd and 3rd degree heart block
Pregnancy category: C

24. ACE INHIBITORS
Captopril, enalapril, and ramipril
ACE inhibitors decrease angiotensin II causing Vasodilation of both arterioles and veins.
Also decrease the secretion of aldosterone, resulting in decreased sodium and water retention.
ACE inhibitors reduce cardiac work

25. ACEI and ARB mechanism of action

26. Therapeutic uses Treatment of HTN.
Prevention of ventricular remodeling after MI.
ACE inhibitors are first-line drugs for treating heart failure, hypertensive patients with chronic kidney disease.
ACE inhibitors slow the progression of diabetic nephropathy.

27. Orthostatic hypotension-infrequent Dry Cough 10- 20 % of pts.
Side effects
Headache
Rash, angioedema
Orthostatic hypotension-infrequent
Dry Cough % of pts.
GI distress and disturbance of taste.
Hyperkaleemia
Need frequent monitoring of renal function

28. ANGIOTENSIN II RECEPTOR BLOCKERS
The ARBs, such as losartan and irbesartan and valsartan are alternatives to the ACE inhibitors.
Their pharmacologic effects, use are similar to those of ACE inhibitors
Adverse effects are similar to those of ACE inhibitors, except the risks of cough and angioedema are significantly decreased.

30. ACEI and ARB
These agents are also teratogenic and should not be used by pregnant women.

31. Sympathetic Nervous System Alpha 1 = vasoconstriction
Adrenergic receptors
Sympathetic Nervous System
Alpha 1 = vasoconstriction
Alpha 2 = vasodilation
Beta 1 = increases heart rate
Beta 2 = bronchodilation

32. Mechanism of action of B blockers
Blockade of β1-adrenoceptors in heart
reduces heart rate and myocardial contractility.
Blockade of renal β1- receptors reduces renin secretion(vasoconstrictor).
Blockade of presynaptc β2-adrenoceptors
inhibits exocytose of NA.
Carvedilol and labetalol also block
a-receptors and produce vasodilation.

34. Beta Adrenergic Blocking Agents
The nonselective β-blockers, such as propranolol and nadolol.
Selective blockers of β1 receptors, such as metoprolol, bisoprolol and atenolol .

35. Therapeutic uses
The primary therapeutic benefits of β-blockers are seen in hypertensive patients with concomitant heart disease, such as
Arrhythmia : (atrial fibrillation),
Previous myocardial infarction, angina pectoris, and chronic heart failure.

36. Warning and contra indication
Asthma (nonselective β-blockers)
Second- and third-degree heart block
Severe peripheral vascular disease.

37. Side effects Intermittent claudication. Bradycardia, AV block
Bronchospasm, wheezing
Hypoglycemia.
Heart failure: edema,dyspnea
Insomnia
Fatigue
Sexual dysfunction

38. Most β-blockers raise plasma concentration
Side effects
Most β-blockers raise plasma concentration
of triglycerides and lower concentration of
antiatherogenic HDL.
Sudden withdrawal syndrome:
beta-blockers should be stopped gradually.
Pregnancy category: C

39. Alpha-1 Adrenergic Blocking Agents
Block postsynaptic alpha-1 adrenergic receptors to produce arteriolar and venous vasodilation
Reduces peripheral-vascular resistance

40. Dizziness,tachycardia,fainting Weakness,lethargy Palpitation.
Side effects
Drowsiness
Headache
Dizziness,tachycardia,fainting
Weakness,lethargy
Palpitation.
Pancreatitis.

41. Centrally Acting Alpha-2 Agonists
Stimulate Alpha-2 receptors in brainstem
Decreases HR, SBP and DBP
More frequent side effects – drowsiness, dry mouth, dizziness
Never suddenly stop = rebound HTN
Clonidine.
Methyldopa : the safest drug in pregnancy

42. Direct Acting Vasodilators
Action: direct arteriolar smooth muscle relaxation, decreasing peripheral venous resistance
Uses: HTN, renal dx., toxemia of pregnancy
Minoxidil is used topically to treat male pattern baldness

43. Direct Acting Vasodilators
Apresoline(hydralasine), Minoxidel
SE: tachycardia, orthostatic hypotension,dizziness, palpitations, nausea, nasal congestion
These undesirable side effects can be blocked by concomitant use of a diuretic and a β-blocker

45. AB/CD Rule – HT Treatment=
ACEi, Beta-blocker
Ca++-blocker, Diuretic)
AGE
Renin
Younger (< 55)
High Renin HT
Older (> 55)
Low Renin HT I
ACEi BB
CCB
Diuretic I
III
III II
A + B
A + B + D
D + C + A
D + C II
Resistant HT /
Intolerance
Add / substitute alpha blocker
Re-consider 20 causes  trial of spironolactone
IV: V:
Dickerson et al. Lancet 353: ;1999

46. CLINICAL RELEVANCE FOR REHABILITATION
Adverse Drug Reactions
• Orthostatic hypotension is a common problem with
some classes of antihypertensive drugs (prazosin).
• Broncho constriction is a problem with beta-receptor
antagonists.
• Beta-receptor antagonists blunt the early manifestations
of hypoglycemia.
• Several antihypertensive drug classes depress heart
rate and contractility.
Loop and thiazide diuretics can cause hypokalemia.
• Potassium-sparing diuretics and ACEI can cause hyperkalemia.

47. Effects Interfering with Rehabilitation
• Orthostatic cause patients to faint when position change, exiting from a warm aquatherapy area, or if aerobic exercise is terminated without an appropriate cool-down period.
• Dyspnea may decrease aerobic capacity.
• Manifestations of hypoglycemia occurring during aerobic activities may be delayed.
• Heart rate cannot be used as a marker of exertion for patients taking beta-receptor antagonists.
• Cardiac output may be depressed during aerobic activities by several drug groups.
• Altered plasma potassium levels can cause paresthesias, decrease skeletal muscle function, increase cramps, and increase the risk of cardiac dysfunction.

48. Possible Therapy Solutions
• Check blood pressure and heart rate prior to and following aerobic activities.
• Monitor heart rate during aerobic activities.
• To prevent fainting associated with orthostatic hypotension , assist patients with positional changes and when exiting a warm pool.
Always provide a cool-down period following exercise.
• Allow increased time to complete aerobic tasks to prevent dyspnea and account for depressed cardiac activity.

49. Possible Therapy Solutions
• Use percieved exertion ( Borg rating of Perceived Exertion Scale) when determining aerobic activity in patients being treated with beta – receptor antagonists.
• Check glucose levels prior to aerobic activities if the patients are taking hypoglycemic drugs.
• Review the clinical manifestations of altered plasma potassium levels and determine if patients are taking medications that may alter these levels.