Pharmacological Management of
Hypertension
Objectives
1. Blood pressure
2. Drug Treatment of Hypertension
3. General points on treating Hypertension
4. Don’t forget lifestyle advice
Blood Pressure = CO X PVR
• Cardiac Output = SV (stroke volume)x HR (heart
rate)
• PVR (peripheral vascular resistance) = Afterload
When to treat
1. BP consistently ≥ 160/100
2. BP consistently ≥ 140/90 AND
▫ with existing CVD
or
▫ target organ damage
or
▫ raised CVD Risk of 20% or more
Targets
1. 140/90
2. 135/85 for type 1 diabetics
3. 130/80 type 1 diabetics with nephropathy
4. 140/80 for type 2 diabetics
5. 135/75 for type 2 diabetics with
microalbuminuria or proteinuria
Antihypertensive Classes
1. Angiotensin-converting enzyme (ACE)
inhibitors
2. Angiotensin receptor –blocking
agents (ARBs)
3. Calcium channel blockers
4. Diuretics
5. Antiadrenergics
1- Angiotensin- converting enzyme (ACE)
inhibitors
Inhibitors of renin angiotensin system
• Angiotensin converting enzyme inhibitors (ACEI).
▫ Inhibits ACE which lead to :
1. Inhibits the synthesis of angiotensin II Vasodilatation
2. Decreasing SVR (systemic venous return)& decrease afterload
• Examples:
1. Captopril (Capoten®),
2. Enalapril (Vasotec®)
3. Lisinopril (Prinivil® & Zestril®),
4. Quinapril (Accupril®)
5. Ramipril (Altace®),
6. Benazepril (Lotensin®)
7. Fosinopril (Monopril®)
ACEi’s
Clinical uses
1. Generally recommended for people < 55 yrs and Caucasian
2. Safely used in patients with ischemic heart disease.
3. Are useful in treating patients with diabetic nephropathy
4. Treatment of heart failure.
Pharmacokinetics
1. Captopril, Enalapril, Moxepril, Lisinopril.
• Absorbed from GIT after oral administration.
• Food reduce their bioavailability.
• All are pro-drugs, converted to the active
agents by hydrolysis in the liver (Except Captopril).
• Captopril is short acting (2-3times/daily) & The others are long acting.
• Enalaprilat is the active metabolite of enalapril is available only for intravenous use
for hypertensive emergency.
NB: All ACEI are distributed to all tissues except CNS & are eliminated by the
kidney except moexpril [Excretion: Feces (50%); urine (13%)].
Adverse effects
1. Severe hypotension
2. Acute renal failure
3. Hyperkalemia
4. Dry cough, wheezing ,and angioedema
5. Captopril may cause loss of taste & in high
doses may cause neutropenia , proteinuria .
ACEi’s – Drug Interactions
Avoid ACEI’s with
1. K+ sparing diuretics and aldosterone
antagonists (spironolactone) – severe
hyperkalaemia
2. Lithium – lithium excretion ↓- lithium toxicity
3. NSAIDs impair their hypotensive effects
Contraindications
1. During the second and third trimesters of
pregnancy because of the risk of fetal
hypotension ,anuria ,renal failure , fetal
malformations and death.
2. Bilateral renal artery stenosis or stenosis of the
artery of a solitary kidney.
2-Angiotensin receptor –blocking agents
(ARBs)
• Mechanism of action :
▫ Block AT1 receptors.
• Advantages over ACEI :
1. They have no effect on bradykinin system: No
cough, wheezing or angioedema.
2. Complete inhibition of angiotensin action compared
with ACEI
Angiotensin receptor –blocking agents
• Losartan, Valsartan, Irbesartan etc
• Effects similar to ACEi’s
• Works by blocking angiotensin 2 (potent vasoconstrictor)
from entering receptors in the smooth muscles of blood
vessels
• Primarily SHOULD be considered where an ACEi is
indicated but not tolerated
Losartan
• Orally effective
• Long half-life , taken once daily.
• Can not cross BBB
Adverse effects & contraindications-
• As ACEI except for cough ,wheezing ,and
angioedema.
• Same contraindications as ACEI.
ARB’s – Adverse Effects
1. Hyperkalaemia
2. Symptomatic hypotension – dizziness or light-
headedness
Contra-indications
1. Pregnancy
2. Hepatic impairment for some agents
Much the same as the ACEi’s
3-CALCIUM CHANNEL BLOCKERS
• Diltiazem (Cardizem®)
• Verapamil (Calan®, Isoptin®)
• Nifedipine (Procardia®, Adalat®)
• Amlodipine (Norvasc)
• Can be split into 2 groups dependant
on their properties:
▫ Dihydropyridines (e.g. amlodipine, nifedipine)
▫ Non-dihydropyridines (diltiazem, verapamil)
• Dihydropyridines potent vaso-dilators, relax the vascular
smooth muscle and dilates the arteries
• Non-dihydropyridines are more myocardial selective
CCB Action
• Diltiazem & verapamil
1. Decrease automaticity & conduction in SA & AV nodes
2. Decrease myocardial contractility
3. Decreased smooth muscle tone
4. Decreased peripheral resistance
• Nifedipine
1. Decreased smooth muscle tone
2. Decreased peripheral resistance
Side Effects of CCBs
1. Cardiovascular
• Hypotension, palpitations & tachycardia
2. Gastrointestinal
• Constipation & nausea
3. Other
• Rash, flushing & peripheral edema
Indications of CCBs
• Used for:
1. Angina
2. Tachycardias
3. Hypertension
Drug interactions: Antifungals & Grapefruit Juice ↑ plasma conc of dihydropyridines
4- DIURETICS
DIURETICS
• Initially they increase sodium & water excretion this cause :
Reduction blood volume & C.O.
Late - Reduce peripheral resistance
1. Thiazides:
• Chlorothiazide (Diuril®) & hydrochlorothiazide (HCTZ®,
HydroDIURIL®)
2. Loop Diuretics
• Furosemide (Lasix®), bumetanide (Bumex®)
3. Potassium Sparing Diuretics
• Spironolactone (Aldactone®)
Side effects
1. Hypokalaemia
2. Postural hypotension
3. Mild GI effects
Drug Interactions
1. Cyclosporine - ↑ risk of nephrotoxicity
2. Lithium - lithium excretion ↓- ↑ plasma conc- -
lithium toxicity
5- Antiadrenergics
a) Beta receptors Blockers
Beta blockers work by blocking the effects of the hormone
epinephrine, also known as adrenaline. Beta blockers cause the
heart to beat more slowly and with less force, which lowers blood
pressure. Beta blockers also help widen veins and arteries to
improve blood flow.
• β adrenoceptors are very useful in mild to
moderate hypertension.
• In severe cases used in combination with other
agents.
• They lower blood pressure:
1. Primarily by decreasing cardiac output.
2. Inhibiting the release of renin from kidney.
❖ E.g. Propranolol , atenolol , metoprolol
Side effects
1. Bradycardia
2. Shortness of breath
3. Coldness of extremities
4. CNS effects with lipid soluble drugs
(propranolol)
Contra-Indications
1. Asthma/severe COPD
2. Marked bradycardia
3. Severe peripheral artery disease
4. Heart Block
BB’s – place in Therapy
• No longer recommended first line treatment
• BUT they are an option for:
1. Younger patients with C/I’s for ACEi’s or ARB’s
2. Women of child bearing age
3. Pts with compelling indications for their use (e.g.
ischaemic heart disease)
Central sympatholytic drugs
➢ Stimulate alpha2 receptors
➢ Reduce blood pressure mainly by stimulating central α2‐adrenergic
receptors in the brainstem centers, reducing sympathetic nerve
activity and neuronal release of norepinephrine to the heart and
peripheral circulation.
➢ Eg. methyldopa (Aldomet®): It is one of the
preferred treatments
for high blood pressure in pregnancy
Alpha blockers
➢Block alpha1 receptors
Alpha 1 receptors are found on vascular smooth muscle. Alpha-1
blocker lowers the blood pressure by blocking alpha-1 receptors so
norepinephrine cannot bind the receptor, causing the blood vessels to
dilate. Without the resistance in the blood vessels the blood runs
more freely.
➢ Eg. clonidine (Catapress®)
Hypertensive Emergency Drugs
1. Sodium nitroprusside (Nitropress): relaxation in smooth muscle,
intravenously for therapy of severe hypertension
2. Diazoxide: relaxation in smooth muscle, injection is used when
hypertension is severe. is a thiazide drug, but has no diuretic
("water pill") effects like other thiazides, is used to treat low
blood sugar (hypoglycemia) caused by certain cancers or other
conditions that can make the pancreas release too much insulin
3. Labetalol( α & β blocker ): injection is used when hypertension
is severe.
4. Nicardipine: (slow channel blocker or calcium channel blocker)
Injection: It is used to treat sever hypertension.
Blood pressure by age
Effect for Lifestyle Interventions
Intervention Avg % with 10mmHg Other Comments
reduction in reduction in (from NICE
SBP & DBP SBP (<1 year) 2006)
Diet (Healthy, Low 5-6mmHg ~40% Avg wt changes 2-9Kg
calorie)
Exercise (Aerobic, 2-3mmHg ~30%
30-60mins, 3-
5x/week)
Relaxation Therapy 3-4mmHg ~33% Cost & availability to
(Structured) PCO unknown
Multiple 4-5mmHg ~25% Education alone unlikely
Interventions to be effective
Alcohol Reduction 3-4mmHg ~30%
Salt Reduction 2-3mmHg ~25% Effects diminish over
(<6g/day) time (2-3yrs)
Other: Caffeine (> 5cups/day inc BP by ~2-1mmHg, Smoking (per se) no effect on BP.
