Hypertension (HT)

1. Hypertension (HT) Definition Hypertension is a condition in which blood pressure (BP) in the arteries is persistently elevated. It can lead to cardiovascular, renal, and cerebrovascular complications. Risk Factors ●​ ●​ ●​ ●​ ●​ ●​ ●​ Obesity High salt intake Alcohol consumption Sedentary lifestyle Age >55 years Family history of HT Diabetes mellitus Stepwise Treatment Approach Lifestyle Modifications ●​ ●​ ●​ ●​ Reduce body weight Reduce salt and alcohol consumption Smoking cessation Regular physical activity Step 1: Initial Drug Choice ●​ Asian and Caucasian <55 years → High renin HT → RAS-targeting drugs (ACE inhibitors or ARAs) ●​ Asian and Caucasian ≥55 years / Afro-Caribbean → Low renin HT → Calcium channel blockers Step 2: Combination Therapy ●​ Use one drug from each class if BP is uncontrolled Step 3: Triple Therapy ●​ Combination of three antihypertensive drugs Step 4: Resistant HT ●​ Addition of spironolactone ●​ Note: Combining beta-blockers and diuretics may worsen diabetes Drug Classes 1. ACE Inhibitors Examples: captopril, enalapril, lisinopril, ramipril MoA: ●​ Inhibit angiotensin-converting enzyme → reduces Angiotensin II ●​ ↓ Vasoconstriction, ↓ Aldosterone → ↓ BP Side Effects: ●​ First-dose hypotension ●​ Dry cough (bradykinin accumulation) ●​ Angioedema Cautions/Contraindications: ●​ Pregnancy ●​ Bilateral renal artery stenosis ●​ Potassium-sparing diuretics (risk hyperkalemia) 2. Angiotensin Receptor Antagonists (ARAs) Examples: losartan, valsartan, candesartan MoA: ●​ Block AT1 receptors → Angiotensin II cannot act → ↓ BP Side Effects: ●​ Dizziness, headache, fatigue, hyperkalemia Cautions: ●​ Pregnancy, breastfeeding, renal artery stenosis 3. Calcium Channel Blockers Dihydropyridines: nifedipine, amlodipine → vascular smooth muscle​ Non-dihydropyridines: verapamil, diltiazem → cardiac & vascular MoA: ●​ Block L-type Ca²⁺ channels → ↓ intracellular Ca²⁺ → ↓ vascular tone Side Effects: ●​ Peripheral edema, hypotension, reflex tachycardia Cautions: ●​ Drug interactions (CYP450 metabolism) 4. Alpha-1 Blockers Examples: prazosin, doxazosin MoA: ●​ Block alpha-1 receptors → vasodilation → ↓ BP Side Effects: ●​ Postural hypotension ●​ Doxazosin improves lipid profile 5. Vasodilators Hydralazine: interferes with vascular smooth muscle Ca²⁺ release​ Minoxidil: opens K⁺ ATP channels → hyperpolarization → vasodilation Side Effects: ●​ Reflex tachycardia, fluid retention, headaches, hirsutism (minoxidil) 6. Beta-Blockers Examples: atenolol, propranolol, carvedilol MoA: ●​ Antagonize B1-adrenoceptors → ↓ HR, ↓ CO → ↓ BP ●​ Chronic: ↓ sympathetic outflow, ↓ renin Side Effects: ●​ Fatigue, bradycardia, bronchospasm (non-selective) Cautions: ●​ Asthma (non-selective), diabetes (mask hypoglycemia) 7. Centrally Acting Drugs Examples: clonidine, methyldopa MoA: ●​ Stimulate presynaptic a2 receptors in vasomotor center → ↓ sympathetic tone → vasodilation Side Effects: ●​ Orthostatic hypotension, sedation 8. Diuretics Types: ●​ Thiazides (hydrochlorothiazide) → moderate Na⁺ excretion ●​ Loop diuretics (furosemide) → high ceiling, potent ●​ Potassium-sparing (spironolactone, amiloride) → prevent hypokalemia MoA: ●​ ↑ Urine output → ↓ blood volume → ↓ BP Side Effects: ●​ Thiazides: hyperglycemia, hypokalemia ●​ Loop: hypokalemia, hypotension ●​ K-sparing: hyperkalemia 2. Ischaemic Heart Disease (IHD) Definition IHD is a condition where coronary arteries are narrowed by atheromatous plaques, reducing blood flow to the myocardium. Risk Factors ●​ ●​ ●​ ●​ ●​ ●​ ●​ Hypertension Hypercholesterolemia Diabetes mellitus Obesity Smoking Physical inactivity Family history Angina Pectoris Pain due to myocardial ischaemia caused by reduced oxygen supply. Symptoms: ●​ Chest pain: heavy, crushing, radiating to jaw, neck, arm ●​ Shortness of breath ●​ Sweating, anxiety Types of Angina: 1.​ 2.​ 3.​ 4.​ 5.​ Stable Angina: predictable, occurs with exertion, relieved by rest Unstable Angina: unpredictable, occurs at rest, may progress to MI Prinzmetal (Variant) Angina: due to coronary artery spasm Decubitus Angina: occurs when lying down (associated with heart failure) Nocturnal Angina: occurs during sleep or dreams Treatment of Angina Aim: Reduce cardiac workload and oxygen demand. Drug Classes: 1.​ Nitrates: GTN, isosorbide mononitrate ○​ MoA: release NO → vasodilation → ↓ preload → ↓ myocardial O₂ demand ○​ SE: hypotension, headache, reflex tachycardia ○​ Administration: sublingual tablets/sprays, oral for prophylaxis 2.​ Beta-blockers: atenolol, metoprolol ○​ MoA: ↓ HR & contractility → ↓ O₂ demand ○​ Avoid in Prinzmetal’s angina 3.​ Calcium channel blockers: amlodipine, nifedipine, verapamil, diltiazem ○​ MoA: block L-type Ca²⁺ channels → ↓ vascular tone and/or cardiac contractility 4.​ Ivabradine: inhibits If current in SAN → ↓ HR without affecting contractility 5.​ Ranolazine: inhibits late inward Na⁺ currents → ↓ Ca²⁺ → negative inotropy 6.​ Nicorandil: NO donor + K⁺ ATP channel opener → vasodilation Sublingual & Buccal Drug Formulations Sublingual: under the tongue, rapid absorption, avoids first-pass metabolism​ Buccal: between lip & gum, local or systemic action​ Counseling: ●​ Keep tablets in original bottle ●​ Administer during angina attacks, repeat 5 mins if pain persists (max 3 doses) 3. Myocardial Infarction (MI) Definition Occlusion of a coronary artery, leading to myocardial cell necrosis. Pathophysiology: ●​ Plaque rupture → thrombus formation → vessel occlusion → ischemia → cell death Treatment: ●​ ●​ ●​ ●​ ●​ Thrombolytics: alteplase, streptokinase → dissolve clot Antiplatelets: aspirin, clopidogrel → prevent new thrombus formation ACE inhibitors: reduce cardiac workload, prevent remodeling Beta-blockers: reduce sympathetic stimulation, arrhythmia risk Pain management: opioids 4. Heart Failure (HF) Definition Inability of the heart to pump sufficient blood to meet the body’s needs. Symptoms: ●​ Dyspnea, fatigue, ankle swelling ●​ Orthopnea, paroxysmal nocturnal dyspnea Types: ●​ ●​ ●​ ●​ ●​ Systolic: LV cannot eject adequately (post-MI) Diastolic: LV fails to relax (hypertension-induced) Left-sided: pulmonary congestion Right-sided: systemic venous congestion Biventricular: both sides involved Treatment of HF Goals: ↓ mortality, ↓ symptoms, ↓ hospitalizations Drugs: 1.​ 2.​ 3.​ 4.​ 5.​ ACE inhibitors: ↓ preload & afterload, ↑ renal perfusion Beta-blockers: protect against sympathetic overactivation Diuretics: ↓ volume overload Aldosterone antagonists: spironolactone → prevent remodeling Cardiac glycosides: digoxin → positive inotropy, vagal stimulation Acute HF treatment: ●​ Dobutamine: IV infusion, B1 agonist → ↑ contractility ●​ Monitor BP & HR 5. Arrhythmias Definition Deviations from the normal heart rhythm due to disturbances in impulse generation or conduction. Risk Factors ●​ ●​ ●​ ●​ ●​ Heart failure Myocardial infarction Valve disease Endocarditis Recent heart surgery Symptoms ●​ ●​ ●​ ●​ Palpitations Chest pain Dyspnea Syncope Types of Arrhythmias 1.​ Bradyarrhythmias – slow heart rate ○​ Often asymptomatic unless severe ○​ Causes: heart block, increased vagal tone 2.​ Tachyarrhythmias – fast heart rate ○​ Symptoms more noticeable with sustained rapid rhythm ○​ Causes: stress, ischemia, electrolyte imbalance Mechanisms 1.​ Accelerated automaticity – faster depolarization than normal 2.​ Triggered activity – oscillations due to myocardial damage 3.​ Re-entry – circular conduction loops causing repetitive excitation Antiarrhythmic Drug Classes Class I – Sodium Channel Blockers ●​ Use-dependent: selective for frequently activated channels ○​ 1A (Disopyramide): slow phase 0, lengthen AP, prolong refractory ○​ 1B (Lidocaine): target inactivated channels, shorten AP, treat post-MI ventricular arrhythmias ○​ 1C (Flecainide): strong conduction depression, prophylaxis of atrial fibrillation Class II – Beta-blockers ●​ Reduce sympathetic activity, slow HR ●​ Prevent sudden death post-MI Class III – Potassium Channel Blockers ●​ Amiodarone, Sotalol ●​ Prolong repolarization & AP duration Class IV – Calcium Channel Blockers ●​ Verapamil, Diltiazem ●​ Shorten phase 2 of AP, effective on nodal tissue Other Antiarrhythmic Agents ●​ Adenosine: IV, activates ACh-sensitive K⁺ channels → slows AV nodal conduction ●​ Digoxin: stimulates vagus → ↓ AV conduction, controls atrial fibrillation 6. Haemostasis & Thrombosis Haemostasis ●​ Arrest of bleeding via vascular spasm, platelet plug formation, and clotting cascade ●​ Platelets: adhere, swell, release 5-HT, ADP, thromboxane A2 ●​ Fibrin formation: stabilizes platelet plug Venous Thromboembolism (VTE) ●​ Formation of thrombi in veins due to stasis or hypercoagulability ●​ Symptoms: pain, swelling, warmth in leg ●​ Pulmonary embolism: sharp chest pain, shortness of breath, hemoptysis Virchow’s Triad: 1.​ Stasis 2.​ Hypercoagulability 3.​ Endothelial injury Treatment 1.​ Anticoagulants ○​ Heparin/LMWH: bind antithrombin III → inhibit thrombin & factor Xa ○​ Warfarin: vitamin K antagonist → inhibits factors II, VII, IX, X ○​ Direct oral anticoagulants (DOACs): dabigatran, rivaroxaban, apixaban 2.​ Antiplatelet Drugs ○​ Aspirin: inhibits COX → ↓ thromboxane A2 ○​ Clopidogrel, Prasugrel, Ticagrelor: P2Y12 inhibitors ○​ GP IIb/IIIa inhibitors: Abciximab, Tirofiban, Eptifibatide 3.​ Thrombolytics ○​ Convert plasminogen → plasmin → fibrin breakdown ○​ Streptokinase, Alteplase Stroke Types: ●​ Ischaemic: thrombotic or embolic ●​ Haemorrhagic: intracerebral or subarachnoid Signs/Symptoms: ●​ ●​ ●​ ●​ Facial drooping Weakness/numbness Aphasia, confusion Sudden headache Treatment: ●​ Ischaemic: thrombolysis (alteplase), aspirin, secondary prevention (statins, antihypertensives) ●​ Haemorrhagic: reverse anticoagulants, manage ICP, surgical intervention if needed ●​ Supportive care: BP monitoring, glucose control, mobilization, swallowing assessment 7. Peripheral Vascular Disease (PVD) Definition ●​ Narrowing or blockage of arteries outside the heart and brain, reducing blood flow to limbs. ●​ Common sites: legs (intermittent claudication), fingers/toes (Raynaud’s disease). Symptoms ●​ ●​ ●​ ●​ Pain on walking or exertion (intermittent claudication) Cold, pale extremities Non-healing ulcers or gangrene in severe cases Weak or absent peripheral pulses Risk Factors ●​ ●​ ●​ ●​ ●​ ●​ Smoking Diabetes mellitus Hypertension Hyperlipidemia Age > 50 years Obesity Complications ●​ Critical limb ischemia ●​ Ulceration and gangrene ●​ Increased risk of cardiovascular events Management 1.​ Lifestyle ○​ Smoking cessation ○​ Exercise therapy to improve collateral circulation ○​ Healthy diet and weight management 2.​ Medications ○​ Antiplatelets: Aspirin, Clopidogrel ○​ Vasodilators: Cilostazol (phosphodiesterase III inhibitor) ○​ Lipid-lowering: Statins 3.​ Interventions ○​ Endovascular procedures: angioplasty, stenting ○​ Surgical bypass in severe disease 8. Lipid-lowering Therapy Apolipoproteins ●​ Proteins that bind lipids → form lipoproteins → transport through blood. ●​ ApoB: Low-density lipoproteins (LDL, “bad”) ●​ ApoA1: High-density lipoproteins (HDL, “good”) Statins (HMG-CoA Reductase Inhibitors) ●​ Examples: Atorvastatin, Simvastatin, Rosuvastatin ●​ MoA: inhibit HMG-CoA reductase → ↓ cholesterol synthesis → ↑ LDL receptor expression → ↓ plasma LDL ●​ Effects: lower LDL, reduce cardiovascular risk, stabilize plaques ●​ Side Effects: myalgia, liver enzyme elevation, rare rhabdomyolysis Other Lipid-lowering Drugs ●​ Ezetimibe: inhibits intestinal cholesterol absorption ●​ Fibrates: increase HDL, lower triglycerides (Gemfibrozil, Fenofibrate) ●​ PCSK9 inhibitors: monoclonal antibodies that increase LDL receptor recycling → ↓ LDL 9. Patient Counselling Points (Pharmacy Perspective) Antihypertensives ●​ How to take: same time daily, with/without food as instructed ●​ Side effects: hypotension, dizziness, cough (ACE inhibitors), edema (CCBs) ●​ Avoid abrupt withdrawal of beta-blockers Anticoagulants ●​ Warfarin: monitor INR, avoid sudden changes in diet, report bleeding ●​ DOACs: adherence is critical, no routine monitoring ●​ Avoid NSAIDs without consulting doctor Sublingual/Buccal Tablets ●​ GTN sublingual: place under tongue, do not swallow, repeat every 5 mins if needed ●​ Store in original container, protect from heat, light, moisture Lifestyle Advice ●​ Diet: reduce salt, saturated fats, sugar ●​ Exercise: improve cardiovascular health and PVD symptoms ●​ Smoking cessation: reduces cardiovascular risk