Cardiovascular pharma

1. CARDIOVASCULAR
PHARMACOLOGY
by Abdulewhab Jemal
(BPHARM, MSC)

2. Objective
After Completing this chapter the students are
expected to know about
1. Describe the different cardiovascular disorders.
2. Understand the basic pharmacological principles of
cardiovascular drugs.
3. Learn the rational use of cardiovascular drugs.
4. Describe the side effects of cardiovascular drugs

3. Introduction
In the Past decades, cardiovascular diseases were
considered as major health problems mainly for
western countries.
However, the problem of cardiovascular disorders is
also increasing in developing countries including
Ethiopia.
The most commonly encountered cardiovascular
disorders include
 hypertension
congestive heart failure
angina pectoris
cardiac arrhythmias.

4. I. Antihypertensive Drugs

5. Introduction
Hypertension is the most common cardiovascular
disease.
Hyprtention is defined as sustained diastolic pressure
>90mmHg accompanied by an elevated systolic blood
pressure >140mmHg.

6. Diagnosis
The diagnosis of hypertension is based on repeated,
reproducible measurements of elevated blood pressure.
It should be noted that the diagnosis of hypertension
depends on measurement of blood pressure and not on
symptoms reported by the patient.
Classification of HTN determined based on the average
of two or more properly measured seated BP
measurements from two or more clinical encounters.
For patients with diabetes mellitus or chronic kidney
disease, values ≥130/80 mm Hg are considered above
goal.

7. Types of Hypertension
Primary (essential) hypertension
 Over 90% of individuals with hypertension have essential
hypertension (primary hypertension).
 Hypertension often runs in families, indicating that genetic
factors may play an important role in the development of
essential hypertension.
 This form of hypertension cannot be cured, it can be controlled.

8. Cont…
Secondary hypertension
 Fewer than 10% of patients have secondary hypertension
 There are many potential secondary causes
 Concurrent medical conditions or disease
 Certain drugs
 Known cause
Renal artery stenosis - excessive release of rennin
Phaeochromocytoma (Tumor of the adrenal medulla)
Excess glucocorticoids: water reabsorption
Dietary factors, stress etc….
 If the cause of secondary hypertension can be identified,
hypertension in these patients potentially can be cured.

9. Hypertensive Emergencies
 A clinical situations where BP values are greater than
180/120mmHg
 Extreme elevations in BP that are accompanied by acute or
progressing target-organ damage.
 These are situations that require immediate blood pressure
reduction to prevent or limit organ damage.
 The conditions include intracranial hemorrhage, unstable angina,
acute myocardial infarction, pulmonary edema.

10. Complications of hypertension
 The most dangerous complications are end organ damage.
 Cardiac failure due to myocardial infarction
 Renal failure (kidney damage)
 Stroke ( sudden blocking of or bleeding from a blood
vessel in the brain resulting in temporary or permanent
paralysis or death.
 Damage to the eye, Blood Vessels etc…
Arterial pressure is the product of cardiac
output and peripheral vascular resistance.
BP = CO × PVR

11. Treatment of HTN
Non Pharmacologic Approach;
In patients with mild elevation in blood pressure (95
DBP), non-pharmacological treatment methods may
be applicable (5-10mmHg reduction):
Free from side effect compared with drug therapy
 Stop smoking
 Lose weight
 Exercise
 Reduce salt intake
 Decrease consumption of alcohol
 Psychological relaxation
 Dietary decrease in saturated fat
In serious increases in BP; drug treatment is involved.

12. Pharmacologic Therapy
Most patients with hypertension require drug
treatment to achieve sustained reduction of blood
pressure.
Currently available drugs lower blood pressure by
decreasing either cardiac output (CO) or total
peripheral vascular resistance (PVR) or both.

13. 1. Diuretics
Diuretics, which lower blood pressure by
depleting the body of sodium and reducing blood
volume and perhaps by other mechanisms.
Diuretics are effective in lowering blood pressure
by 10–15 mm Hg in most patients.
 diuretics alone often provide adequate treatment
for mild or moderate essential hypertension.
 In more severe hypertension, diuretics are used in
combination with other drug.

14. Thiazides
Thiazides and related drugs, e.g.hydrochlorthiazide
Initially, thiazide diuretics reduce blood pressure
increase in urinary water and electrolyte particularly
sodium excretion.
by reducing blood volume and cardiac out put.
Thiazides are appropriate for most patients with mild
or moderate hypertension and normal renal and
cardiac function.

15. Hydrochlorothiazide
 Well absorbed from the GIT, excreted in the urine mainly
by tubular secretion. (Competes with uric acid for tubular
secretion).
Clinical uses:
 Hypertention
 Mild heart failure
 Oedema
Unwanted effects
 Hypokalemia, increase plasma uric acid, hyperglycemia,
increased plasma cholesterole.

16. Loop Diuretics
 Loop diuretics, e.g. furosemide
 acts by inhibiting the reabsorbtion of NaCl.
 They are more potent than thiazides as diuretics.
 The antihypertensive effect is mainly due to reduction of blood
volume.
 Used in cases of severe hypertension which is associated with
renal failure, heart failure or liver cirrhosis.
Clinical uses
Hypertention ( thiazides are usually prefered)
Acute pulmonary oedema
Chronic heart failure
Cirhosis of the liver
Nephrotic syndrome and renal failure

17. Cont…
Unwanted effects
 Potassium loss --> hypokalemia (usually corrected by using
potassium suppliment or potassium sparing diuretics).
 Hypovolumia and hypotention.
Drug interaction:
 Ototoxicity may result when furesamide is taken along with
aminoglycosides.

18. Potassium sparing diuretics
Spironelactone
A potassium sparing diuretic with limited diuretic action so
often used along with thiazide or loop diuretics.
 To Avoid hypokalemia
Mechanism of action:
Spironolactone is an aldosterone antagonist.
N.B. Aldosterone is a hormone secreted by the adrenal cortex
that enhances Na+ reabsorption and K+ secretion by the kidney.

19. 2. Sympathetic nervous system suppressors
Methyldopa
 Methyldopa is an α 2 agonist
 Decrease adrenergic out put from the CNS.
 It Decrease of peripheral resistance or cardiac output.
Uses:
 Mild to moderate hypertention.
 Methyldopa is a preferred drug for treatment of hypertension
during pregnancy based on its effectiveness and safety for both
mother and fetus.
Side effects:
 CNS - Sedation,headache, dizzyness
 GIT - dry mouth,nausea,vomiting
 Others - Postural hypotention, impotence, allergic reactions.

20. β-adrenoceptor blockers
Propranolol
 Competitively blocks beta-adrenergic receptors in the heart
 Decrease cardiac ouput
 blocking β2 receptors in the lungs of susceptible patients
causes contraction of the bronchial smooth muscles.
 contraindicated in patients with asthma.
 β -blockade leads to decreased glycogenolysis and decreased
glucagon secretion.
 Contranidicated patients who are receiving insuline or oral
hypoglycemic agents.

21. Cont…
Therapeutic uses
Hypertention- lowers BP. by decreasing cardiac
output.
 Angina pectoris -decreases oxygen requirement of
heart muscle.
 Cardiac arrhythmias (tachyarrhythmias).
Prophylaxis for migraine headache.
Adverse effects
Bronchoconstriction in susceptible patients
Arrhythmia
Disturbance in metabolism

22. Metoprolol
 Metoprolol is more selective to β1.
 Cardioselectivity is not complete.
 Metoprolol is effective in reducing mortality from heart failure
 It is very useful in patients with hypertension and heart
failure.

23. Atenolol
Selective β1 antagonist.
Therapeutic use
Useful for hypertensive patients with impaired pulmonary
function.
Useful in diabetic hypertensive patients who are receiving
insuline or oral hypoglycemic agents.
Treatment of angina pectoris
Sid effects
 Bradycardia, Cardiac arrhythmia.

24. Alpha adrenergic antagonists
Prazosine, Doxazocine and Terazosine
They are α1 blocking agent
They are useful in patients with urinary retention
associated with Benighn prostatic hypertrophy(BPH).
Side effects
 postural hypotention (first dose), nasal stuffiness,
failure of ejaculation in males.

25. 3. Vasodilators
Hydralazine
 Causes direct relaxation of arteriolar smooth muscle, but does
not relax veins.
 Decrease PVR
 Well absorbed after oral administration
Uses:
Severe HTN & hypertensive emergencies in pregnant
women
Adverse effects
Tachycardia, aggravation of angina, fluid retention,
headache, sweating, flushing, nausea, anorexia

26. Sodium nitroprusside
Potent , parentally administered vasodilator
Dilates both arteriolar & venular vessels
Has rapid onset (30 s) & brief duration of effect (3 min)
Causes only a modest in HR and an overall reduction in
myocardial demand for oxygen
Therapeutic use
Treatment of hypertensive emergencies (continuous IV
infusion)
Sever heart failure

27. Ca2+ channel blockers (CCB)
 Cause arteriolar dilatation; hence reduce TPR
Nifedipine, Nicardipine
 Potent arteriolar vasodilators
 Less effect on heart rate & contractility
Therapeutic uses
 Maintenance (long term) treatment of HTN
 hypertensive emergencies
Adverse effects
 Tachycardia, headache, flushing, peripheral edema

28. 4. Renin-angiotensin system targeting
drugs
Angiotensin converting enzyme inhibitors (ACE-I)
 Inhibit conversion of AG-I to AG-II
 Drugs include Captopril, Enalapril, Fosinopril…..
 All ACEIs have similar
 Efficacy, therapeutic use
Adverse effect profile, contraindications
 Pharmacokinetics
orally effective;
Differ in absorption & hepatic first pass effect
Elimination is in the urine;
 Therapeutic uses: HTN, Left ventricular hypertrophy,
Acute MI , CRF

30. Cont…
Therapeutic uses
 HTN, Left ventricular hypertrophy, Acute MI , CRF
Adverse effects generally well tolerated
 Hypotension, dry Cough, Angioedema, hyperkalemia, Acute
renal failure, Fetal damage, Skin rashes, proteinuria,
glycosuria, etc
 ACE inhibitors are contraindicated during pregnancy.

31. Angiotensin II receptor blockers
 Antagonize the effects of angiotensin II
 Block preferentially AT1 receptors
 Vasodilation, Increase salt and water excretion
 They do not cause dry cough & angioedema
Losartan, Valsartan, Telmisartan, Irbesartan

32. SUMMRY OF HPERTENSION
THERAPY
 Initial treatment with non-pharmacologic approach
 When non-pharmacologic approaches do not satisfactorily
control blood pressure, drug therapy begins in addition to non-
pharmacological approaches.
 The selection of drug(s) depends on various factors such as the
severity of hypertension, patient factors (age, race, coexisting
diseases, etc.).

33. Cont…
 Drug therapy in mild hypertension with mono-therapy of:
– Thaizide diuretic
– beta blockers [ patients with tachycardia, angina]
– Calcium channel blockers
– Angiotensin converting enzyme inhibitor
– Central sympathoplegic agent
 If monotherapy is unsuccessful, thiazide diuretic can be combined
with beta-blockers, CCB, or ACE inhibitors, Ag II antagonists
 If hypertension is still not under control, a vasodilator such as
hydralazine can be combined.

34. Cont…
Treatment of Hypertensive Emergency
 Hydralazine, 5-10 mg initial dose, repeated every 20 to 30 minutes (with
maximum dose of 20 mg) should be given until the mean arterial blood pressure
is reduced by 25% (within minutes to 2 hours), then towards 160/100 mm Hg
within 2-6 hours.
Treatment of Hypertensive Urgency
First line
Captopril, 6.25-12.5 mg P.O. single dose
Alternative
Furosemide, 40mg IV single dose
 To be followed by longer acting agents such as CCBs (eg nifedipine) or a beta
blocker or ACEI.

35. Conditions Need special emphasis
 Pregnancy: Drugs used to be taken prior to pregnancy can be continued
 Except ACEIs & AT1 receptor antagonists
 Methyldopa is commonly used
 Elderly: use smaller doses; simpler regimens
 Monitor for adverse drug effects
 DM: use drugs with fewer adverse effect on carbohydrate metabolism
 ACEIs, AT1 receptor blockers, CCB, and α1-AR blockers
 Asthma: avoid β- blockers

36. II. Drugs used in heart failure
 Heart failure : inability of the heart to maintain cardiac out put
sufficient to meet requirement of metabolizing tissue
 CHF is characterised by inadequate contractility, so that the
ventricles have difficulty in expelling sufficient blood
 Heart failure usually caused by:
 Ischemic heart disease
 Hypertension
 Heart muscle disorders
 Valvular heart disease

37. Cont…
 Two major types of failure may be distinguished.
 In systolic failure, the mechanical pumping action (contractility)
and the ejection fraction of the heart are reduced.
 Approximately 50% of younger patients have systolic failure
 In diastolic failure stiffening and loss of adequate relaxation
plays a major role in reducing cardiac output
 The proportion of patients with diastolic failure increases
with age.

38. Cont…
Symptoms
Fatigue
 shortness of breath
Congestion (Pulmonary, extremities etc
Decreased exercise tolerance with rapid muscular fatigue
is the major direct consequence of diminished cardiac
output.
The other manifestations result from the attempts by the
body to compensate for the intrinsic cardiac defect.
The primary cause of inadequate perfusion and retention
of fluid is an impairment of the heart's ability to fill or
empty the left ventricle properly

39. Cont…
AHA Staging of heart failure
Stage A
 Patients at high risk for developing heart failure
 Hypertension, coronary artery disease, diabetes
Stage B
 Patients with structural heart disease but no HF
symptoms
 Previous MI, left ventricular hypertrophy,
asymptomatic left ventricular systolic dysfunction

40. Cont…
Stage C
 Patients with structural heart disease and current or
previous symptoms.
 Left ventricular systolic dysfunction and dyspnea, fatigue,
fluid retention, or other signs/symptoms of HF.
 Stage C includes asymptomatic patients who have
previously received treatment for HF symptoms.
Stage D
 Patients with symptoms despite maximal medical therapy
 Patients requiring recurrent hospitalization, specialized
interventions required

41. Cont…
Classification of severity
I – no limitation of physical activity
II – slight limitation of physical activity
III – marked limitation of physical activity
IV – symptoms occur at rest

42. Drugs with positive inotropic effect
1. Cardiac glycosides
 Includes digoxin and digitoxin
 Mechanism: increase in intracellular Ca++.
 slow the heart rate and increase the force of contraction
Adverse drug effect
 GI: anorexia, nausea, vomiting, diarrhea
 Cardiac effect: heart block, arrhythmia
 CNS: headache, hallucination, delirium, visual disturbance

43. Cont…
2. Beta-adrenergic stimulants, e.g. dobutamine & dopamine
Increase in myocardial contractility and increase cardiac
output together with a decrease in ventricular filling pressure.
 Positive chronotropic effect of these drugs minimizes their
use
 Reserved for the management of acute failure or resistant to
other agents

44. Drugs without positive inotropic effect
Diuretics
aldosterone antagonists
 ACE inhibitors
angiotensin receptor antagonists
β blockers.
vasodilators

45. 1. Diuretics
Patients who do not have fluid retention would not require
diuretic therapy.
 Mild failure: thaizides; moderate/severe: furosemide
 In acute failure, diuretic reduces ventricular preload
 Spironolactone and eplerenone, the aldosterone
antagonist diuretics , have the additional benefit of
decreasing morbidity and mortality in patients with severe
heart failure who are also receiving ACE inhibitors and other
standard therapy.

46. 2. Angiotensin converting enzyme (ACE)
inhibitors
ACE inhibitors are the cornerstone of pharmacotherapy of
patients with heart failure.
These drugs reduce the long-term remodeling of the heart and
vessels,
They are considered a head of cardiac glycosides in chronic heart
failure.
It reduce in mortality and morbidity.
Angiotensin receptor blockers should be considered in patients
intolerant of ACE inhibitors because of incessant cough

47. 3. Vasodilators
 Hydralazine: direct arteriodilator; reduce vascular
resistance
 Sodium nitroprusside: mixed venous and arteriolar dilator
used for acute reduction of BP.
 Vasodilator agents: reserved for patients who are intolerant
of or who have contraindications to ACE inhibitors.

48. 4. β-Blockers
 Most patients with chronic heart failure respond favorably to
certain β blockers
 Metoprolol , carvedilol, and bisoprolol have been shown to
reduce mortality in heart failure.
 Stable patients are initiated on low doses of a β-blocker, with
slow upward dose titration over several weeks.
 A full understanding of the beneficial action of β blockade is
lacking

49. Summary of CHF
 Non-drug treatment:
 Reduce sodium intake and physical activity.
 Most patients with symptomatic heart failure should be treated
routinely with four medications: an angiotensin converting
enzyme (ACE) inhibitor, a β-blocker, a diuretic, and digoxin.
 In patients with heart failure, ACE inhibitors improve survival,
slow disease progression, reduce hospitalizations, and improve
quality of life.
 Digoxin does not improve survival in patients with heart failure
but does provide symptomatic benefits.

50. III. Pharmacotherapy of Angina Pectoris
 Angina pectoris is the principle symptom of ischemic heart disease
 It is characterized by sudden, severe and pressing substernal pain
that is usually felt beneath the upper sternum.
 The ischemic condition results from an imbalance between
myocardial oxygen demand and supply to it via the coronary vessel.
 This imbalance may be due to a decrease in myocardial oxygen
delivery, an increase in myocardial oxygen demand, or both.
 It has become apparent that spasm of the coronary arteries is
important in the production of angina.

51. Types of angina pectoris
 Stable Angina (exertional , typical and classic angina):
 The underlying pathology is usually atherosclerosis
 Can be precipitated by exercise, cold, stress, emotion
 Therapeutic rationale: decrease cardiac load and
increase myocardial blood flow, reduce cholesterol
level, inhibit platelet function.

52. Cont…
 Organic nitrates (nitroglycerin, isosorbide dinitrate) , beta-
blockers and/or calcium channel blockers can be used
 Statins (lovastatin, simvastatin, atrovastatin, rosuvastatin ),
antiplatelet drugs (aspirin, clopidogril)

53. Cont…
 Vasospastic angina (variant, Prinzmetal's angina):
 Caused by vasospasm of the coronary vessels
 May or may not be associated with severe atherosclerosis
 Chest pain may develop at rest
 Therapeutic rationale: decrease vasospasm of coronary
vessels.

54. Cont…
 Unstable angina (Pre-infraction angina, acute coronary
syndrome):
 The Patient with this condition typically requires no stress
to provoke episodes of ischemic pain.
 Pathology : platelet-fibrin thrombus associated with
ruptured plaque, without complete occlusion.
 The course and the prognosis of unstable angina are
variable and associated with a high risk of myocardial
infarction and death.

55. Cont…
 Nitrates & beta-blockers for controlling pain, Ca2+-
channel blockers (vasospasm) but may not decrease
mortality.
 So, therapy directed towards reduction of platelet
function and thrombotic episode appears to decrease
morbidity and mortality in patients with unstable angina.
 Since risk of infraction is substantial and therapy should
aim at this (aspirin, clopidogril)

56. Drugs used in angina pectoris
1. Organic nitrates [e.g. nitroglycine, isosorbide dinitrate]
 They are potent vasodilators
 Onset of nitrates:2-3minute
 Duration lasts for 2hrs from tongue or when chewed
 Adverse effect: flushing, weakness, dizziness, tachycardia,
palpitation, vertigo, sweating, syncope, localized burning
with sublingual preparation

57. Cont…
2. Adrenergic blocking agents
 Atenolol, propranolol, metoprolol.
 In most patients the net effect is a beneficial reduction in
cardiac workload and myocardial oxygen consumption
 Adverse effects: Lethargy, fatigue, rash, cold hands and feet,
nausea, breathlessness, nightmares and bronchospasm.

58. Cont…
3. Calcium channel blockers
 Interfere with calcium entry into myocardial and vascular
smooth muscle
 Nifedipine, felodipine, verapamil and diltiazem
Adverse effect
 flushing, nausea/vomiting, headache, ankle swelling,
dizziness, constipation, etc
4. Miscellaneous drugs,
e.g. aspirin, clopidogril
 Aspirin Decreases thromboxane A2
 Aspirin 81mg per day produce antiplatelet activity and reduce
the risk of myocaridial angina
 Clopidogril 300mg stat and 75mg once daily

59. Arrhythmia and anti-arrhthymic drugs
 arrhythmia – problem in impulse generation and/or conduction
 Cardiac arrhythmia is an abnormality of the heart rhythm.
 Bradycardia – heart rate slow (<60 beats/min)
 Tachycardia – heart rate fast (>100 beats/min)

60. Cont…
Drugs used in the treatment of cardiac arrhythmias are traditionally
classified into:
1. Class I: Na+ channel blockers [quinidine, lidocaine, phenytoin, flecainide,]
2. Class II: Block -adrenergic Receptors.
Propranolol, Acebutolol, Metoprolol
3. Classs III: K+-channel blockers
Amiodarone, Ibutilide, Dofetilide, Sotalol, Bretylium
4. Class IV: Selective Ca++ channel blockers
Verapamil, Diltiazem
5. Miscellaneous: Actions do not fit to any of the above classes
Digoxin (digitalis), Adenosine

61. Thanks A lot!!