HYPERTENSION BY MUSHABE REAGAN

CONTENTS
1. Introduction
2. Pathophysiology
3. Approach to the patient
4. Antihypertensive drugs
5. Treatment of hypertension
INTRODUCTION
A single elevated blood pressure reading is not sufficient to establish the
diagnosis of hypertension. The major exceptions to this rule are hypertensive
emergency, or hypertensive urgency.
Category Systolic BP Diastolic BP
Normal < 120 < 80
Pre HTN 120 – 139 80 – 89
Stage 1 140 – 159 90 - 99
Stage 2 160 > 100 >

QN; How can white coat HTN be curbed?

ESSENTIAL HYPERTENSION
Reps 95% of cases. Onset usually between 25–55 yrs.
Positive family history is not uncommon.
Risk factors
Obesity Cigarette smoking
Sleep apnea Polycythemia
Increased salt intake NSAID therapy
Excessive alcohol use Low potassium intake.
Metabolic syndrome
PATHOPHYSIOLOGY
1. Increased sympathetic nervous system activity
2. Abnormalities in RAAS
3. Endothelial dysfunction
4. Sodium water retention
5. Genetics
SECONDARY HYPERTENSION
1. Endocrine eg Hyperaldosteronism, Cushing syndrome, Thyroid disease,
Pheochromocytoma, hypercalcemia
2. Renal eg PCKD, Parenchymal renal disease, page kidney, scleroderma
3. Vascular eg renal artery sclerosis, Coarctation of aorta
4. Autonomic eg stress, Neurogenic
5. Medications eg NSAIDS, steroids, Stimulants, decongestants, estrogen,
alcohol
6. Pregnancy
7. Obstructive sleep apnea
8. Idiopathic
SYMPTOMATOLOGY
Symptoms: Mostly asymptomatic, headache, somnolence,
confusion, visual disturbance, nausea, vomiting, PND in chronic
HTN with LVH, (anxiety, palpitations, perspiration, pallor in
pheochromocytoma)
Signs: Elevated BP
Retina: Narrowing of arterioles, silver wire appearance, exudate,
hemorrhage
Heart: aortic regurgitation, presystolic s4 gallop
Pulses: radial femoral delay(Coarctation), loss of peripheral
pulses(Artherosclerosis)
COMPLICATIONS
Hypertensive CVD (LVH, MI, arrhythmias, HF)
Hypertensive cerebrovascular disease
Dementia
Hypertensive kidney disease
Aortic dissection
Artherosclerotic complications
APPROACH TO TREATMENT
1. Non pharmacological therapy
Weight loss to target BMI 18.5-24.9
DASH diet eg fruit, vegetables, low fat diary products
Reducing sodium intake to <6g of salt per day
Reduces alcohol intake <2drinks for male <1 drink for females
Exercise aerobic or dynamic
Mindfulness eg meditation and breathing control
2. Pharmacotherapy
Medication should be started in all persons whom blood pressure reduction,
irrespective of initial blood pressure levels, will reduce cardiovascular risk and have
low medication associated side effects
GOALS OF TREATMENT
1. Target BP <140/90mmHg is the global standard
2. Treatment of other cardiovascular risk factors
3. Lower target in people with cardiovascular risk factors to 130/80mmHg
Cardiovascular risk factors
Major risks eg Cigarette smoking, Obesity(BMI >30), dyslipidemia, Diabetes
mellitus, age >55yrs men and 65yr women, family history of premature
cardiovascular disease < 55/65
Target organ damage eg LV hypertrophy, angina, MI, HF, coronary
revascularization, stroke, CKD, peripheral arterial disease, retinopathy
ANTI HYPERTENSIVES
Diuretics
Sympathoplegic agents
Direct vasodilators
Agents blocking production or action of angiotensin
SYMPATHOPLEGIC DRUGS
1. Centrally acting eg Methyldopa, clonidine etc
2. Adrenergic neuron blocking agents eg Guanethidine, Reserpine etc
3. Adrenergic receptor blockers ie alpha α and beta β
α- blockers eg prazosin, terazosin
β-blockers eg propranolol, carvedilol, atenolol
CENTRALLY ACTING
SYMPATHOPLEGIC AGENTS
•These agents reduce sympathetic outflow from vasomotor centers in the
brainstem. They spare sensitivity to baroreceptor control
1. METHYLDOPA
MOA: Replaces the action of norepinephrine at postsynaptic alpha
adrenoceptors
Effect: Peripheral sympathetic dilation of arterioles and venules, lower HR,
lower CO
Use: Hypertension in pregnancy
Dose:
S/E: Sedation, nightmares, impaired concentration, lactation
.

2. CLONIDINE
MOA: Partial agonist at alpha adrenergic receptors
Effect: Reduced vascular resistance, bradycardia, reduced renal vascular
resistance
Dosage:
S/Es: Dry mouth, sedation, depression, withdrawal effects
ADRENERGIC NEURON
BLOCKING AGENTS
These lower BP by preventing normal release of NE from post ganglionic
synaptic neurons.
1. GUANETHIDINE
MOA: Prevents release of NE from sympathetic nerve endings
Dose:
S/Es: Pharmacologic sympathectomy (diarrhea, hypotension, impaired
ejaculation)
2. RESERPINE
Read about it
ADRENERGIC RECEPTOR
ANTAGONISTS
Drugs Receptor affinity
Alpha antagonists
Prazosin, terazosin,doxazosin, phentolamine α1
Phenoxybenzamine α1, α2
Mixed antagonists
Labetalol, carvedilol β1, α1, α2
Beta antagonists
Metoprolol, acebutolol, alprenolol, atenolol, β1
betaxolol, esmolol, celiprolol, nebivolol
Propranolol, cartenolol, nadolol, penbutolol, β1, β2
pindolol, timolol
ALPHA ADRENERGIC
RECEPTOR BLOCKERS
Examples: Prazosin, Terazosin, Doxazosin, Tamsulosin, [phentolamine,
phenoxybenzamine*]
MOA: Reversibly or irreversibly block alpha adrenergic receptors in arterioles and
venules
Effect: Vasodilation(Resistance and capacitance), lower heart rate*
Doses:
S/Es: Postural hypotension, dizziness, palpitations, reflex tarchycardia
NOTABLE: Alpha blockers relax prostatic smooth muscle and relieve bladder neck
obstruction from BPH. Its important to consider them in a male with BPH and HTN
BETA ADRENERGIC
BLOCKERS
Examples: Metoprolol, acebutolol, alprenolol, atenolol, betaxolol, esmolol,
celiprolol, nebivolol, Propranolol, cartenolol, nadolol, penbutolol, pindolol, timolol,
Labetalol, carvedilol
MOA: Reversibly block beta adrenergic receptors in the heart reducing NE binding.
Effect: Reduce heart rate, vasoconstriction*, suppress renin relase, ↓cardiac output
Doses:
Other effects: ↓IOP in glaucoma, Inhibit glycogenolysis
Other therapeautic uses: Glaucoma, IHD, Cardiac arrhythmias, HF,
Hyperthyroidism, migraine, tremors, stage fright
S/Es: Bradycardia, Cold feet, hypoglycaemia, worsening asthma
NOTE
1. Should not be used as first line agents in HTN except if compelling
indications such as CAD.
2. Carvedilol and nebivolol also block alpha receptors and release of nitric
oxide
3. Reduce mortality in patients with chronic stable HF
4. In treatment of pheochromocytoma, beta blockers should not be
administered until alpha blockade has been established.
5. They should also not be used to treat HTN arising from cocaine use.
DRUGS THAT WORK ON THE
RAAS
1. Angiotensin Converting Enzyme (ACE) Inhibitors eg Captopril,
Enalapril etc
2. Angiotensin Receptor Blockers (ARBs) eg Losartan,
Olmesartan etc
3. Renin inhibitors eg Aliskiren
RENIN INHIBITORS
Aliskiren
MOA: Blocks conversion of angiotensinogen to angiotensin I
ANGIOTENSIN CONVERTING
ENZYME INHIBITORS
Examples: Captopril, Enalapril, Benazepril, Fosinopril, Meoxipril, Perindopril,
Quinapril, Ramipril, Trandolapril
MOA: Inhibits peptidyl dipeptidase enzyme from converting angiotensin 1 to
angiotensin 2. Also blocks deactivation of bradykinin
Effect: Vasodilation, Release of nitric oxide
Dose:
S/Es: dry cough, angioedema, severe hypotension, AKD, hyperkalemia
Notable: NSAIDS can impair effects of ACE inhibitors
ACE inhibitors are drugs of choice in diabetic patients
ANGIOTENSIN RECEPTOR
BLOCKERS
Examples: Losartan, Telmisartan, Azilsartan, Candesartan, Eprosartan, Irbesartan,
Olmesartan
MOA: Block the effect of angiotensin ii at the AT1 receptor
Effect: Vasodilation
Dose:
S/Es: Same as for ACEs
Notable:
1. They are more selective blockers of angiotensin effects than ACEIs
2. Are always used in patients who have had adverse reactions to ACEIs
DIRECT VASODILATORS
1. Calcium channel blockers eg Verapamil, amlodipine
2. Nitrates eg Sodium nitroprusside
3. Misc.. Hydralazine, minoxidil, fenoldopam
CALCIUM CHANNEL
BLOCKERS
Classes
1. Non dihydropyridines: Examples: Verapamil, Diltiazem
2. Dihydropyridines: Examples: Nifedipine, Amlodipine, Felodipine, Isradipine,
Nicardipine, Nisoldipine, Clevidipine
MOA: Inhibit influx of calcium into blood vessel smooth muscle by blocking
voltage gated L type calcium channel.
Effect: Vasodilation, Lower cardiac contractility,
Dose:
S/Es: Reflex tarchycardia, AV block, HF, (extension of effects)
HYDRALAZINE
MOA: Dilates arterioles by release of nitric oxide from vessel endothelium
Dose:
Therapeutic use: Severe hypertension, HF
S/Es: Headache, N,V, palpitations, reflex tarchycardia
MISCELLANEOUS
VASODILATORS
Write short notes on mechanism of action, clinical effects, dosing and side effects the
following;
1. Minoxidil
2. Fenoldopa
3. Diazoxide
4. Nitrates in hypertension
DIURETICS
1. Carbonic anhydrase inhibitors eg acetazolamine
2. Loop diuretics eg furosemide, bumetanide etc
3. Thiazide diuretics eg HCTZ, bendroflumethiazide etc
4. Potassium sparing diuretics eg spirolonolactone, triamterene etc
5. Osmotic diuretics eg mannitol
CARBONIC ANHYDRASE
INHIBITORS
Examples: Acetazolamide, methazolamide, dichorphenamide
MOA: Inhibits blocks the action of carbonic anhydrase hence blocks reabsorption of
NAHCO3 in the PCT.
Effect: Diuresis
Doses:
Other uses: Glaucoma, urinary alkalinisation, metabolic acidosis, mountain sickness
S/Es: Renal potassium wasting, renal stones, metabolic acidosis, drowsiness,
paraesthesias.
LOOP DIURETICS
Examples: Furosemide, Ethacynic acid, Bumetadine, Torsemide
MOA: Selectively inhibit NaCl reabsorption in the thick ascending limb of LOH
Effect: Diuresis
Dose:
Other uses: Hyperkalemia, Acute renal failure, anion overdose
Toxicity: Hypokalemic metabolic alkalosis, ototoxicity, hyperuricemia,
hypomagnesemia, allergic reactions*.
Contraindications: Hypersensitivity to sulphonamides,
THIAZIDE DIURETICS
Examples: Bendroflumethiazide, Chlorothiazide, Chlorthalidone,
Hydrochlorothiazide(HCTZ), Hydroflumethiazide, Indapamide, Methylclothiazide,
Metolazone, Polythiazide, Quinethazone, Trichlormethiazide
MOA: Inhibit reabsorption NaCl reabsorption by blocking Na/Cl transporter in the
PCT
Effect: Diuresis
Dose:
Therapeautic use: HF, nephrolithiasis, nephrogenic diabetes insipidus
S/Es: hypercalcemia, hyponatremia, impaired carbohydrate tolerance,
hyperlipidemia, gout, allergic rxns
POTASSIUM SPARING
DIURETICS
Examples: Spironolactone, eplerenone, amiloride, triamterene
MOA: Spironolactone and eplerenone prevent K+ secretion by antagonism of
mineralocorticoid (androgen) receptors.
Amiloride and triamterene inhibit Na+ influx through ion channels in luminal
membrane of CCT.
Effect: Diuresis
Dose:
Therapeautic uses: Hyperaldosteronism,
S/Es: Gynecomastia, decreased libido, hyperkalemia,kidney stones, acute renal
failure
OSMOTIC DIURETICS
Examples: Mannitol
MOA: Create osmotic force and prevent water reabsorption in PCT and loop of
Henle
Dose:
Therapeutic uses: Reducing ICP and IOP (Alteration of Starling forces)
S/Es: hyponatremia, acute renal failure, extra cellular, dehydration, hyperkalemia,
hypernatremia
 CHOICE OF AGENT
Step Drug class
Step 1 ACEI/ARB/B blocker or CCB or Thiazide
Step 2 ACEI/ARB/B blocker plus CCB or Thiazide
Step 3 ACEI/ARB/B blocker plus CCB plus Thiazide
Step 4 ACE/ARB/B blocker plus CCB plus Thiazide plus Spironolactone

ABCD A-ACE/ARB, B- Beta blocker, C-CCB, D- Diuretic

AB + CD. Combination of drugs from different categories is more effective
than from within same category.
Beta blockers are not ideal first line agents except with compelling indication
such as HF or CAD
HYPERTENSION IN DIABETES
1. Targets for BP should be lower ie 130/80mmHg
2. ACEIs/ARBs have benefit in diabetic nephropathy so should be
considered.
3. Do not combine ACE and ARB. Progression to end organ
damage and death happens.
4. Usually need more than one drug to control HTN
5. Other combinations are Diuretic plus CCB plus Beta blocker
HYPERTENSIVE URGENCY
AND EMERGENCY
Hypertensive urgency includes asymptomatic patients with BP Sys
220mmHg and Dia 125mmHg, optic disk edema and progressive target organ
complications.
Hypertensive emergency is an elevated BP with multiple end organ injury.
MEOI include: hypertensive encephalopathy, hypertensive nephropathy and
AKD, intracranial hemorrhage, eclampsia, PE, MI, unstable angina
Note: Initial goal is to reduce BP by not more than 25% in 1hr and then
160/100 within 2-6hrs.
Excessive reductions may cause coronary or cerebral ischemia
Sublingual or other fast acting Nifedipine is best avoided
 DRUGS FOR HTN URGENCY
AND
Drug
EMERGENCY
Dosage Onset Duration
Hypertension emergencies
Labetalol 20-40mgIV q10min to 300mg 5-10min 3-6hrs
Esmolol Loading 500mcg/kgIV over 1 min. 1-2min 10-30min
maintenance 25-200mcg/kg/min
Furosemide 10-80mg PO or IV 15min 4hrs
Hydralazine 5-20mg IV , repeat after 20 mins 10-30mins 2-6hrs
Nitroglycerin 0.25-5mcg/kg/min IV 2-5 min 3-5 min
Hypertensive urgency
Captopril 12.5-25mg PO 15-30min 4-6 hrs
Nifedipine 10mg PO, may be repeated after 30 15 mins 2-6hrs
mins
ADIOS!