Anti hypertensive

• Hypertension


  Systolic blood pressure＞ 140 mm Hg, diastolic blood pressure＞90 mm Hg
• Normal blood pressure


  120/80 mmHg systolic/diastolic
• Categories of Hypertension According to European Society of Cardiology

  • Pre-hypertension (120-139 mmHg systolic, 80 mmHg diastolic)
  • Hypertension - Stage 1 (140-159 mmHg systolic, 90-99 mmHg diastolic)
  • Hypertension - Stage 2 (160-179 mmHg systolic, 100-109 mmHg diastolic)
  • Hypertension - Stage 3 (>180 mmHg systolic, >110 mmHg diastolic)
• Symptoms of hypertension


  • Confusion
  • Ear noise or buzzing
  • Fatigue
  • Headache
  • Irregular heartbeat
  • Nosebleed
  • Vision changes
• Hypertension is not scary, what's scary is damage to target organs
• Organs damaged by hypertension

  • Heart (arrhythmia, heart failure)
  • Kidney (early asymptomatic, chronic kidney failure as condition progresses)
  • Brain (cerebral small vasospasm, hypertensive encephalopathy, stroke)
  • Retina (fundus bleeding, exudation, papilledema)
  • Blood vessels (atherosclerosis, coronary heart disease, cerebral thrombosis)
• Treatment Strategies for High Blood Pressure

  • Lower the blood pressure
  • Protect the target organ
  • Reduce the morbidity and mortality rates
  • Best therapy and minimal risk
• Approach to Treatment


  • Life style modification
  • Pharmacological therapy
• 5 first-line antihypertensive drugs

  • Angiotensin converting enzyme inhibitors (ACEIs) - Priles
  • Angiotensin II Receptor Blockers (ARB) - Sartans
  • β Receptor blocker (β-RB) - Loral class
  • Calcium Channel Blockers (CCB) - Diphenyls
  • Diuretics - hydrochlorothiazide, spironolactone
• Baroreflexes


  Act by changing the activity of the sympathetic nervous system to regulate blood pressure
• Renin–angiotensin–aldosterone system


  The kidney provides long-term control of blood pressure by altering the blood volume
• Renin–angiotensin–aldosterone system


  1. Baroreceptors in the kidney respond to reduced arterial pressure (and to sympathetic stimulation of β1-adrenoceptors) by releasing the enzyme renin

  2. Renin converts angiotensinogen to angiotensin I, which is converted in turn to angiotensin II, in the presence of angiotensin-converting enzyme(ACE)

  3. Angiotensin II causes direct constriction of renal arterioles and stimulation of aldosterone synthesis – sodium absorption and increase in intravascular blood volume
• Drugs Acting on RAAS

  • ACE inhibitors: captopril, enalapril, lisinopril
  • Renin inhibitors: Aliskiren, remikinen
  • AT1 receptor antagonists: losartan, candesartan
• ACE inhibitors


  Decrease angiotensin II and increase bradykinin levels, reducing vasoconstriction and increasing vasodilation
• ACE inhibitors


  • Decrease the secretion of aldosterone, resulting in decreased sodium and water retention
  • Reduce both cardiac preload and afterload, thereby decreasing cardiac work
• Adverse Effects of ACE inhibitors

  • Dry cough, rash, fever, altered taste, hypotension, and hyperkalemia
• AT1 receptor antagonists


  Block the AT1 receptors, decreasing the activation of AT1 receptors by angiotensin II, producing similar effects to ACE inhibitors
• ARBs do not increase bradykinin levels
• Adverse Effects of AT1 receptor antagonists

  • Similar to ACE inhibitors, but risk of cough is significantly decreased
  • Teratogenic, should not be used by pregnant women
• Renin Inhibitors


  Directly inhibit renin and act earlier in the renin–angiotensin–aldosterone system than ACE inhibitors or ARBs
• Adverse Effects of Renin Inhibitors


  • Diarrhea, especially at higher doses, cough, angioedema
• Diuretics


  Act on V-2 receptor in kidneys (vasopressin receptor), leading to diuresis, increased secretion of Na & H2O, decreased blood volume, and decreased BP
• Adverse Effects of Diuretics

  • Dizziness, electrolyte imbalance/depletion, hypokalemia, hyperlipidemia, hyperglycemia (Thiazides)
• Central Sympatholytics (α-2 Agonists)

  CNS α2 adrenergic stimulation leads to decreased sympathetic outflow, decreased norepinephrine release, vasodilation, and decreased BP
• Adverse Effects of Central Sympatholytics

  • Dry mouth, sedation, drowsiness, nasal congestion
• α-1 Adrenergic Blockers


  Block α-1 receptors in post synaptic neurons and vascular smooth muscles, causing vasodilation, decreased preload, and decreased BP
• Adverse Effects of α-1 Adrenergic Blockers

  • Nausea, drowsiness, postural hypotension, headache
• β-Adrenergic Blockers


  Block β-1 receptors in the heart, reducing heart rate and cardiac output, and block β-1 receptors in the kidney, decreasing renin production and depressing the RAAS system, leading to decreased BP
• Adverse Effects of β-Adrenergic Blockers

  • Impotence, bradycardia, fatigue, exercise intolerance
• Dual α & β Receptor Antagonists

  Block both α-1 and β-1/β-2 receptors, producing vasodilation and decreased cardiac output to lower BP
• Vasodilators


  Release nitric oxide, stimulate guanylyl cyclase, increase cGMP, inhibit myosin light chain kinase phosphorylation, and cause relaxation of vascular smooth muscles, leading to vasodilation and decreased BP
• Adverse Effects of Vasodilators

  • Headache, tachycardia, nausea, sweating, arrhythmia
• Calcium Channel Blockers


  Block influx of Ca2+ in smooth muscle cells, leading to relaxation of SMCs and decreased BP
• Adverse Effects of Calcium Channel Blockers


  • Flushing, dizziness, headache, hypotension, peripheral edema
• A combination of 2 first line drugs may be considered as initial therapy if the blood pressure is >= 20 mmHg systolic or >=10 mmHg diastolic above target
• Target blood pressure is < 140/90 mmHg