PHARMACOLOGY OF THE

CARDIOVASCULAR SYSTEM
DRUGS FOR HYPERTENSION
Kirsten Culver,
PhD
Science Lead
BScN Program
 HYPERTENSION
Almost 1 in 4 Canadian adults have high blood pressure
 Most prevalent risk factor for cardiovascular disease in Canada
 Common risk factors include; diabetes mellitus, chronic kidney disease, diet and
sedentary behavior
Primary “essential” hypertension
 No known cause – represents 90 - 95% of cases
 Genetic predisposition, dietary salt intake, adrenergic tone
Secondary hypertension
 Known cause – represents 5 - 10% of cases
 Examples: pheochromocytoma, adrenal cortical tumours, drugs
 HYPERTENSION
Most patients asymptomatic - why change if you feel fine?
Physiological effects of hypertension
 Prolonged force on vessels thickens muscles in the arterial system; reduced
responsiveness
 Heart constantly works harder to expel blood against a greater force, increasing
the workload of the heart; left ventricle thickens
 Increased force damages inner lining of arteries; susceptible to atherosclerosis
and narrowing of the vessel lumen
 Microvascular damage leading to losses in vision, kidney and cerebral function
Sequelae; cerebrovascular disease, coronary artery disease, congestive heart
failure, cardiac death, renal failure, peripheral vascular disease, dementia
FACTORS THAT CONTROL BLOOD
PRESSURE

Blood Pressure = CO x TPR

Cardiac Output = HR x SV
REGULATION OF BLOOD PRESSURE
HYPERTENSION - DIAGNOSTIC
ALGORITHM
Automated Office BP (AOBP) refers
to multiple BP readings (3-6) with a
fully automated sphygmomanometer
with the patient resting alone
quietly. AOBP eliminates the white
coat effect and provides readings
which are more accurate/similar to the
awake ambulatory BP and home BP.

Ambulatory BP monitoring (ABPM)

worn by the patient for a 24-hour
period. Measurements taken at 20-to-
30 minute intervals.
Hypertension Canada’s 2020 Comprehensive Guidelines for the Prevention, Diagnosis,
Risk Assessment, and Treatment of Hypertension in Adults and Children
Rabi, Doreen M. et al. Canadian Journal of Cardiology, Volume 36, Issue 5, 596 – 624.
 LIFESTYLE RECOMMENDATIONS
 Reduce sodium intake (2000 mg/day)
 Smoking cessation
 Abstaining from alcohol, or limit alcohol intake to less than 2 drinks/day
 Maintenance of weight and waist circumference
 Physical exercise 30-60 min of moderate-intensity, dynamic exercise 4-7
days/week
 Healthy diet; low in saturated fats & cholesterol, high in vegetables and
fruit, protein from plant sources, low-fat dairy products, whole grain food
rich in dietary fiber
 Stress management/Relaxation therapies
 THRESHOLDS AND TARGETS

Hypertension Canada’s 2020 Comprehensive Guidelines for the Prevention, Diagnosis, Risk Assessment, and Treatment of Hypertension in Adults and Children
Rabi, Doreen M. et al. Canadian Journal of Cardiology, Volume 36, Issue 5, 596 – 624.
PHARMACOTHERAPY FOR
HYPERTENSION
HEMODYNAMIC CONTROLS OF BP

Blood Pressure = CO x TPR

Cardiac Output = HR x SV
 DIURETICS
Thiazide and Thiazide-like Diuretics
 First line therapy for the management of hypertension
 Reduce stroke volume
 Block sodium/chloride transporter in the distal tubule, facilitating the urinary
excretion of electrolytes (Na + , K + , Cl - , Ca 2+ ) and water; thereby reducing
blood volume
 Use with caution in patients with severe renal disease, diabetes, gout, liver
disease, hyperlipidemia
 Administer during the day to prevent nocturia
 DIURETICS
Thiazide and Thiazide-like Diuretics
 Adverse effects
 GI upset, orthostatic hypotension, hyperglycemia, fluid and electrolyte
imbalance (hypokalemia; potassium-rich diet or potassium sparing diuretic)
 Drug-Drug interactions
 Lithium, NSAIDS, antidiabetic drugs (hyperglycemic effects)
 Monitor sodium & potassium levels, kidney function and blood pressure
within 4 – 6 weeks of starting therapy
 Patients should monitor fluid output and weight gain/loss, report dizziness or
light-headedness
 TOTAL PERIPHERAL RESISTANCE
Renin-Angiotensin-Aldosterone System
 Renin; released in response to decreased blood pressure
 Angiotensin II
 Increases blood pressure by; 1) increasing peripheral
resistance in the vasculature and 2) stimulating
secretion of aldosterone and ADH
 Aldosterone increases sodium and water retention
 ADH increases water reabsorption
 Pharmacological inhibition of RAAS decreases TPR and ADH

blood volume; reducing BP

 ACE inhibitors & Angiotensin II Receptor Blockers
 ACE INHIBITORS
Angiotensin Converting Enzyme (ACE) Inhibitors
 Decrease peripheral resistance & decrease blood volume
 Block conversion of Angiotensin I to Angiotensin II
 Increase production of vasodilatory kinins
 Inhibit aldosterone secretion
 Contraindicated in pregnancy
 Use caution with potassium-sparing diuretics & supplements
 Decreased antihypertensive activity with NSAIDs
 ACE INHIBITORS
Angiotensin Converting Enzyme (ACE) Inhibitors
 Adverse effects
 Some drugs may induce a persistent dry cough (up to 30%)
 Can cause hyperkalemia
 GI irritation and constipation
 First dose phenomenon; sudden drop in blood pressure, tachycardia
 Allergic reaction of lips, mouth and throat (angioedema) occurring during
the first month of administration; medical emergency
ANGIOTENSIN II RECEPTOR BLOCKERS
Angiotensin II receptor blockers (ARBs)
 Decrease peripheral resistance & decrease blood volume
 Block angiotensin II (AT 1 ) receptors in arteriolar smooth muscle and in adrenal
cortex
 Inhibit the release of aldosterone
 No effect on bradykinin (lower incidence of cough)
 Equal efficacy compared to ACE inhibitors
 Similar adverse effect profile & drug-drug interactions as ACE inhibitor drugs
 Contraindicated in pregnancy
 Commonly prescribed to patients who cannot tolerate adverse effects of ACE
inhibitor drugs
 CALCIUM CHANNEL BLOCKERS

Calcium Channel Blockers

 Block calcium ion channels
 Relax vascular smooth muscle, decreasing peripheral resistance
 Slow heart rate, reducing cardiac output and cardiac workload
 Non-selective CCBs (heart and arterioles) - effective in the treatment of angina
 Use with caution in those with liver and kidney impairment
 Adverse effects
 Dizziness, light-headedness, fatigue, (hypotension & reflex tachycardia),
flushing, nausea
 Avoid grapefruit juice – increases serum CCB levels
 Usually not used as monotherapy for HTN
 BETA BLOCKERS
Sympathetic division of the autonomic nervous system (SANS) increases heart
rate & smooth muscle constriction of arterial walls
Alpha- and Beta-Adrenergic Antagonists
 Alpha α1 receptor antagonists
 Cardio-selective β1 receptor antagonists Some beta antagonists exhibit antagonism
at alpha receptors (carvedilol)
 Non-selective β1 & β2 receptor antagonists
 Block effect of norepinephrine on arterioles
 Block action of NE and E on cardiac muscle reducing speed & force of
contraction (HR)
 Decrease renin secretion by the kidneys, reducing the production of
angiotensin I and decreasing TPR
 BETA BLOCKERS
Beta adrenergic antagonists
 Beta-blockers are most effective in patients under the age of 60 with
concomitant cardiovascular conditions
 Previous history of MI, angina
 Reduction in heart rate may cause fatigue & activity intolerance
 Use with precaution in those with diabetes, depression, asthma or COPD (use
cardioselective drugs only)
 Sleep disturbances