DRUGS AFFECTING THE

CARDIOVASCULAR SYSTEM

Hypertension
 OVERVIEW
 Hypertension is a common disease that is simply
defined as persistently elevated arterial blood
pressure (BP).
 Hypertension occurs when resting systolic blood
pressure exceeds 130 mm Hg or diastolic blood
pressure exceeds 80 mm Hg.

 Hypertension results from increased peripheral
vascular arteriolar smooth muscle tone lead to :
1. increased arteriolar resistance

2. reduced capacitance of the venous

system.
 Hypertension It is not a disease in itself, but is
an important risk factor for cardiovascular
disease mortality and morbidity
HYPERTENSION COMPLICATION
1. Risk of stroke
2. myocardial infarction
3. Angina
4. heart failure
5. kidney failure
 ETIOLOGY OF HYPERTENSION
 Primary hypertension( Secondary hypertension
essential) :- :-
 account for fewer than 2-
▪ N o identifiable cause
10%.
▪ Approximately 90-95% of  several factors have been
associated with
patients.
secondary hypertension.
 possibly multi-factorial Ex: pheochromocytoma,
defects genetics ,smoking Cushing’s disease,
caffeine , stress , salt primary aldosterone's,
intake, alcohol ,obesity renal artery stenosis,
, age and coarctation
of aorta
 NORMAL REGULATION OF BLOOD PRESSURE

 blood pressure is maintained by moment-to-moment

regulation of cardiac output and peripheral vascular
resistance, exerted at four anatomic sites:
1. Arterioles
2. Venous capacitance
3. Heart
4. Kidney
 Thesefour control sites coordinate to
maintain normal blood pressure through :
1. Humoral mechanisms

2. Neuronal regulation

3. Peripheral autoregulatory
component
4. Vascular endothelial mechanisms

5. Electrolytes and other chemicals

 CLINICAL PRESENTATION OF HYPERTENSION

 General
The patient may appear very healthy, or may have the
presence of additional CV risk factors:
✓ Age (≥55 years for men and 65 years for women)
✓ Diabetes mellitus
✓ Dyslipidemia (elevated low-density lipoprotein-cholesterol,
total cholesterol, and/or triglycerides; low highdensity
lipoprotein-cholesterol)
✓ Obesity
✓ Physical inactivity
✓ Tobacco use
Symptoms
 Most primary hypertension patients are asymptomatic
 Patients with secondary hypertension may have symptoms
of the underlying disorder.
MANAGEMENT OF
HYPERTENSION
JOINT NATIONAL COMMITTEE FOR PREVENTION ,
DETECTION, EVALUATION AND TREATMENT OF
HIGH BLOOD PRESSURE ( JNCVII)
( HYPERTENSION ACCORDING TO GRADE)
Category Blood Pressure ( mmHg)
Normal SBP < 120 and DBP < 80

Prehypertension SBP 120 -140or DBP 80-90

Stage 1 HTN SBP 140 -160 / DBP 90-100

Stage II HTN SBP 160 – 180 / DBP 100 – 110

Severe hypertension SBP >180 / DBP > 110

 TREATMENT STRATEGIES

 The overall goal of antihypertensive therapy is to reduce

cardiovascular morbidity and mortality.
 Surrogate Goal of Therapy to achieve a desired target
BP value
➢ Age < 60 yrs SBP < 140 mm Hg DBP < 90 mm Hg

➢ Age ≥ 60 yrs SBP < 150 mm Hg DBP < 90 mm Hg

➢ All ages, diabetes present, no CKD SBP < 140 mm Hg DBP
< 90 mm Hg
➢ All ages CKD present with or without diabetes SBP < 140
mm Hg DBP < 90 mm Hg
➢ Patients heart failure <120/80 mm Hg
 Non pharmacological treatment

modification Recommendation
Weight reduction Maintain normal body weight ( BMI 18.5-
24.9 kg/m2 )
Adopt DASH diet • Consume a diet rich in fruit , vegetable ,
and low fat dairy product with reduced
content of saturated fat
• Low salt intake.

Physical activity Engage in regular aerobic physical

(Exercise) activity ( at least 30 min/day , most day of
the week)
Moderation of Limit consumption to ≤2 drinks/day in
alcohol intake men and ≤1 drink/day in women and
lighter-weight persons
PHARMACOTHERAPY
 FIRST LINE ANTI HYPERTENSIVE DRUGS:-

 ACE inhibitor, angiotensin II receptor

blocker (ARB).
 calcium channel blocker (CCB)

 Diuretics

 β-Blocker s : effective previously were considered

primary agents. They are now preferred to a specific
indication, or in combination.
 Choosingfrom first line often depends on
individual patient factors like age, ethnicity,
comorbidities, and potential side effects.
 These agents used to treat the majority of
patients with hypertension because:
1. Effective Blood Pressure Lowering
2. Strong evidences demonstrated reduction
in cardiovascular event.
3. Well-Tolerated
4. cost-effectiveness
SECOND LINE ANTIHYPERTENSIVE DRUGS
 α1-Blockers
 Direct renin inhibitor

 Centrally Acting Sympathoplegic Drugs,(α2-

agonists
 Direct arterial vasodilators

these agents are potent, but a much greater incidence

of adverse effects. Moreover, they do not have
compelling outcomes data showing reduced morbidity
and mortality in hypertension.
WHEN TO USE SECOND-LINE ANTIHYPERTENSIVE
AGENTS:

1. Inadequate Blood Pressure Control with First-

Line Monotherapy.
2. Intolerable Side Effects with First-Line Agents
3. Specific Comorbidities or Compelling
Indications.
4. Resistant Hypertension
DRUGS TARGETING RAAS
SYSTEM
1) ANGIOTENSIN-CONVERTING ENZYME
INHIBITORS (ACEIS)

 The ACE inhibitors are one of the first choice

drugs in all grades of essential
 ACE inhibitors block conversion of angiotensin I
to angiotensin II, a potent vasoconstrictor and
stimulator of aldosterone secretion
 ACE inhibitors are classify in to :-

 Sulfa hydryl group :- captopril

 Non sulfa hydryl group: Enalapril, Lisinopril ,

Ramipril.
 MECHANISM OF ACTION IN HYPERTENSION
 ACE inhibitors block All this result in to :-
conversion of  Vasodilation of both
angiotensin I to arterioles and veins
angiotensin II  Reduce peripheral
 block degradation of resistance
bradykinin  Decreased sodium and
 stimulate synthesis of water retention.
other vasodilating  reduce both cardiac
substances preload and afterload
(prostaglandin E2 and
 reduce the long-term
prostacyclin nitric oxide)
remodeling of the heart
THERAPEUTIC USES
1. All of the ACE inhibitors are equally effective in
the treatment of hypertension.
2. ACE inhibitors are first-line drugs for treating
heart failure, hypertensive patients with
chronic kidney disease, and patients at
increased risk of coronary artery disease.
3. Diabetic nephropathy
4. first-line agents in the treatment of patients
with systolic dysfunction
5. ACE inhibitors are a standard in the care of a
patient following a myocardial infarction
ADVERSE EFFECT :-

1. Dry cough sometimes accompanied by wheezing.

2. angioedema.

3. Skin rash

4. Taste change

5. Hyperkalemia

6. Bone marrow depression

 The use of ACE inhibitors is contraindicated

during pregnancy .
2) ANGIOTENSIN II RECEPTOR BLOCKERS
 The ARBs, block the AT1 receptors, decreasing
the activation of AT1 receptors by angiotensin II.
 Losartan and valsartan were the first marketed
blockers of the angiotensin II type 1 .
 Others : candesartan , Telmisartan , Olmesartan
Irbesartan.
 Their pharmacologic effects are similar to those
of ACE inhibitors in
➢ Dilation of artery and vein
➢ block aldosterone secretion.
➢ first-line agents for the treatment of
hypertension, especially in patients with
diabetes, heart failure, or chronic kidney
disease
 key advantages of ARBs over ACEIs:
1. Lower Incidence of Cough

2. Lower Risk of Angioedema

3. Increased Stimulation of AT2 Receptors

4. Alternative for ACEI Intolerance

3) RENIN INHIBITOR
 Aliskiren is the only available for the treatment of
hypertension.
 Aliskiren directly inhibits renin .
 Prevents the formation of Angiotensin I and,
consequently, Angiotensin II.
 Aliskiren provides dose dependent antihypertensive
efficacy
 Aliskiren is approved for the treatment of essential
hypertension
 Aliskiren should not be combined with an ACE
inhibitor or ARB in the treatment of hypertension.
 Aliskiren can cause diarrhea ,cough and
angioedema,
BETA-ADRENOCEPTOR–
BLOCKING
AGENTS
Mechanism in hypertension :-
 Decreased Cardiac Output:. Negative
Chronotropy and inotropy
 Reduced Renin Release

 Central Sympathetic Inhibition: Reducing

sympathetic outflow from the brain.
INDICATION :-

beta-blockers are considered first-line for

hypertension when compelling indications or co-
morbidities exist:
1. Ischemic Heart Disease (Angina Pectoris,
Post-Myocardial Infarction)
2. Heart Failure with Reduced Ejection
Fraction
3. Arrhythmias

4. Younger Patients with High Heart Rate

 PREFERENCE OF BETA BLOCKER
 Cardioselective beta-blockers (metoprolol,
Bisoprolol):
ischemic heart disease, heart failure
,arrhythmias
 Third-generation beta-blockers (carvedilol,
nebivolol):
diabetes, heart failure, or peripheral
vascular disease
 Non-selective beta-blockers not preferred for
hypertension
unless there's a specific non-cardiac compelling
indication (tremor, portal hypertension.
CALCIUM CHANNEL
BLOCKERS
CALCIUM CHANNEL BLOCKERS (CCBS),
 also known as calcium antagonists
 are a group of drugs widely used in
cardiovascular disease
 They exert their effects by inhibiting the influx of
calcium ions into cells, primarily through voltage-
gated L-type calcium channels.
 CCBs used as one of the first line monotherapy

 option in black patients

 Rapid onset and long acting antihypertensive

action.
 CLASSIFICATION
CCBs are categories in to :-

❖ Selective CCBs
1. Cardio selective (Non-dihydropyridines):
Verapamil, diltiazem
2. Vascular selective(Dihydropyridine)
amlodipine, felodipine, isradipine,
nifedipine

❖ Nonselective :- Flunarizine
 Mechanism of action
Dihydropyridines Non-
(DHPs) Dihydropyridines
(Non-DHPs)
Primary Target Vascular smooth muscle Cardiac (myocardium,
L-type Ca2+ channels SA/AV nodes) and
vascular L-type Ca 2+
channels
Vasodilation Potent and direct Moderate (less potent
than DHPs)

Cardiac Contractility mild increase in heart Decreased (Negative

contratatility reflex Inotropy)
increase
Heart Rate reflex tachycardia Decreased (Negative
Chronotropy

AV Conduction No effect Decreased

 CLINICAL USE:
1. Hypertension:(African/ elder Patients)
2. Raynaud’s episodes( vascular selective)
3. Arrhythmias(Cardioselective)
4. Angina Pectoris ( both cardio/vascular selective)
5. Hypertrophic Cardiomyopathy (Verapamil)
6. Hypertension during pregnancy (Nifedepine ).
7. cerebral vasospasm following subarachnoid
haemorrhage (Nimodipine )
8. Migraine and Vertigo treatment ( flunarizine)
ADVERSE EFFECT
Dihydropyridines (DHPs):
 Common: ankle edema, headache, flushing, dizziness,
reflex tachycardia
Non-dihydropyridines (Non-DHPs):
 Common: Constipation (verapamil), bradycardia,

General (both classes):

Dizziness nausea, fatigue
CONTRAINDICATIONS:
 Grapefruit Juice
 Beta-blockers

 sick sinus syndrome

 heart failure
DIRECT ARTERIAL
VASODILATORS
 Direct arterial vasodilators are a class of
antihypertensive medications that act by directly
relaxing the smooth muscle of arterioles.
 This action leads to a decrease in afterload and
systemic vascular resistance.
 These drugs are generally potent and typically
reserved for severe hypertension, hypertensive
emergencies.
 Direct arterial vasodilators are : hydralazine,
Sodium Nitroprusside , Minoxidil , Fenoldopam
, Diazoxide
 Mechanism of action
Drugs Mechanism of action

Hydralazine ✓ opening potassium channels (smooth

muscle hyperpolarization)
✓ inhibits the release of calcium from the
sarcoplasmic reticulum
✓ increase the bioavailability of nitric oxide
(NO)

Sodium ✓ a prodrug that breaks down in the body to

Nitroprusside release nitric oxide (NO)
✓ NO increase cGMP causing smooth
muscle relaxation and vasodilation
Minoxidil ✓ increase efflux of potassium ions leads to
hyperpolarization of the cell membrane
✓ decrease in intracellular calcium
concentration causes the smooth muscle to
relax
MECHANISM OF ACTION

Drugs Mechanism of action

Fenoldopam is a selective dopamine-1 (D 1 ) receptor agonist.
Activation of D 1 increase cAMP leading to smooth
muscle relaxation and vasodilation
Diazoxide is a potassium channel activator. leading to
vasodilation
CLINICAL USES
 Hydralazine: pregnancy-induced hypertension
(preeclampsia) and hypertensive emergencies.
 Minoxidil: used topically for hair loss and
treatment-resistant hypertension combine with
diuretic and a β-blocker.
 Sodium Nitroprusside: short-acting agent used
for acute hypertensive crises and severe heart
failure.
 Fenoldopam: Used intravenously for
hypertensive crises
 Diazoxide: Primarily used for hypertensive
crises and hypoglycemia
ADVERSE EFFECT
 Direct arterial vasodilators :
✓ Reflex Tachycardia

✓ Sodium and Water Retention

 Hydralazine: long-term use with high doses, is

a lupus-like syndrome.
 Minoxidil: excessive hair growth

 Sodium Nitroprusside: risk of cyanide toxicity

 Fenoldopam: flushing, tachycardia, and

headache.
 Diazoxide: hyperglycemia
CENTRALLY ACTING
SYMPATHOPLEGIC DRUGS
(Α2-AGONISTS)
 Centrally acting Sympathoplegic drugs are a
class of medications that lower blood pressure by
acting on the central nervous system (CNS).
 They are also known as central alpha agonists or
central adrenergic inhibitors.
 These drugs are generally not considered first-
line treatments for hypertension due to their side
effects.
 They have important uses in specific clinical
situations.
MECHANISM OF ACTION

Drug Mechanism of action

Clonidine ✓ Decreases sympathetic out flow → fall in

✓ BP and bradycardia.
✓ Decreased cardiac output
✓ Enhanced vagal tone
✓ contributes to bradycardia.
Methyldopa ✓ reduces NA synthesis and forms
the false transmitter methyl-NA

✓ reducing peripheral resistance.

CLINICAL USES
 Clonidine:
✓ antihypertensive (3rd or 4th choice drug).

✓ Opioid withdrawal

✓ analgesic activity

✓ attenuates vasomotor symptoms of menopausal

syndrome.
 Methyldopa

treat hypertension during pregnancy

ADVERSE EFFECT
 CNS Effects: Sedation , drowsiness, dry
dizziness , vertigo ,nightmares (methyldopa).
 Cardiovascular Effects:

orthostatic hypotension , bradycardia

 Withdrawal Syndrome:

clonidine, can lead to a severe rebound

hypertension.
 Methyldopa : increased prolactin secretion and
hepatotoxicity
HYPERTENSION DURING
PREGNANCY
TYPES OF HYPERTENSION DURING
PREGNANCY:

1. Chronic Hypertension:
High blood pressure (≥140/90 mmHg) that exists
before pregnancy or is diagnosed before 20 weeks of
gestation.
1. Gestational Hypertension:

High blood pressure that develops after 20 weeks of

gestation in a woman who previously had normal
blood pressure.
1. Preeclampsia:

A multisystem disorder characterized by new-onset

hypertension (after 20 weeks of gestation) and
proteinuria or other signs of end-organ damage
GOALS OF PHARMACOTHERAPY
 Prevent maternal complications:
reducing the risk of stroke, seizures (eclampsia),
and other organ damage.
 Prolong the pregnancy:

Safely extending the pregnancy to allow for fetal

maturation.
 Prevent progression to severe
hypertension:
particularly critical in cases of gestational
hypertension and preeclampsia.
FIRST-LINE AND SAFE MEDICATIONS
 Methyldopa:
often considered a first-line agent, though it may be less
effective in lowering blood pressure than other options.
 Labetalol

a faster onset of action than methyldopa and is effective

for both chronic and acute hypertension.
 Nifedipine

often used as a first-line or second-line agent.

 Aspirin Prophylaxis

Low-dose aspirin is recommended for pregnant women

with chronic hypertension or other risk factors for
preeclampsia
MANAGEMENT OF SEVERE HYPERTENSION
AND PREECLAMPSIA

 Labetalol (IV):
A common first-line agent for acute management
due to its rapid onset and effectiveness.
 Hydralazine (IV):

It has a longer onset of action than IV labetalol.

 Nifedipine (Oral):

oral nifedipine can be used to manage severe

hypertension.
 Magnesium sulfate:

standard treatment to prevent and manage

eclamptic seizures.
 MEDICATIONS TO AVOID DURING
PREGNANCY
 Angiotensin-Converting Enzyme (ACE) Inhibitors
and Angiotensin Receptor Blockers (ARBs):
cause severe fetal and neonatal renal dysfunction, anuria,
hypocalvaria
 Renin Inhibitors
Similar to ACE inhibitors and ARBs
 Diuretics
increase risk of foetal wastage, placental infarcts,
miscarriage, stillbirth.
 Nonselective β blockers: Propranolol
cause low birth weight, decreased placental size, neonatal
bradycardia and hypoglycaemia.
 Sod. nitroprusside:
Contraindicated in eclampsia
PEDIATRIC HYPERTENSION
PATHOPHYSIOLOGY OF PEDIATRIC
HYPERTENSION
 Primary (essential) hypertension
• is becoming more common, in older children and
adolescents who are overweight or have a family
history.
 Secondary Hypertension:

• most frequent cause, particularly in younger

children.
• The most common cause kidney disease,
pheochromocytoma , hyperthyroidism ,
genetic syndromes , coarctation of the aorta
.
PHARMACOTHERAPY OF PEDIATRIC
HYPERTENSION
 The initial choice of medication depends on the
child's age, the underlying cause of hypertension,
and potential side effects.
 he goal is to lower blood pressure to below the
95th percentile for age, sex, and height.
 Most drugs used in children are the same as
those used in adults, but doses must be carefully
calculated based on weight.
FIRST-LINE AGENTS:
 ACE Inhibitors:
effective in cases of renovascular hypertension or
kidney disease.
 Angiotensin Receptor Blockers (ARBs):
often a good alternative for patients who develop a
persistent cough from ACE inhibitors.
 Calcium Channel Blockers (CCBs) :
often a preferred choice, especially for adolescents
 Diuretics:
they are often used as a second-line agent or in
combination with other medications.
 Beta-Blockers:
used in specific situations, such as for children with
a history of heart issues.
HYPERTENSIVE CRISIS:

 In cases of severely elevated blood pressure with

acute symptoms or organ damage (hypertensive
crisis).
 intravenous medications like labetalol or
nicardipine are used
 safely and rapidly lower blood pressure to
prevent complications like stroke or
encephalopathy.