Hypertension Drugs PDF

**Ch16** -------- Hypertension ------------ (B-blockers are 1st-line in Patients with Cardiac issues, diuretics and ACE inhibitors are 1st-line in Patients with other conditions) -----------------------------------------------------------------------------------------------------------------------...

**Ch16** -------- Hypertension ------------ (B-blockers are 1st-line in Patients with Cardiac issues, diuretics and ACE inhibitors are 1st-line in Patients with other conditions) -------------------------------------------------------------------------------------------------------------------------------------- **1. Diuretics** - **Chlorthalidone** - **Category:** Thiazide diuretic - **Mechanism of Action:** Increases H₂O and Na⁺ excretion initially; long-term use reduces peripheral resistance. - **Side Effects:** Hypokalemia, hyperuricemia, hyperglycemia, hypercalciuria - **Hydrochlorothiazide** - **Category:** Thiazide diuretic - **Mechanism of Action:** Increases H₂O and Na⁺ excretion initially; long-term use reduces peripheral resistance. - **Side Effects:** Hypokalemia, hyperuricemia, hyperglycemia, hypocalciuria - **Metolazone** - **Category:** Thiazide diuretic - **Mechanism of Action:** Increases H₂O and Na⁺ excretion initially; long-term use reduces peripheral resistance. - **Side Effects:** Hypokalemia, hyperuricemia, hyperglycemia, hypocalciuria - **Note:** Effective in renal insufficiency - **Furosemide** - **Category:** Loop diuretic - **Mechanism of Action:** Blocks Na⁺/Cl⁻ symporter; more effective in renal patients compared to thiazides. - **Side Effects:** Hypokalemia, hypercalciuria - **Torsemide** - **Category:** Loop diuretic - **Mechanism of Action:** Blocks Na⁺/Cl⁻ symporter; more effective in renal patients compared to thiazides. - **Side Effects:** Hypokalemia, hypercalciuria - **Bumetanide** - **Category:** Loop diuretic - **Mechanism of Action:** Blocks Na⁺/Cl⁻ symporter; more effective in renal patients compared to thiazides. - **Side Effects:** Hypokalemia, hypercalciuria - **Ethacrynic Acid** - **Category:** Loop diuretic - **Mechanism of Action:** Blocks Na⁺/Cl⁻ symporter; more effective in renal patients compared to thiazides. - **Side Effects:** Hypokalemia, hypercalciuria - **Amiloride** - **Category:** Potassium-sparing diuretic - **Mechanism of Action:** Reduces K⁺ loss in urine by inhibiting epithelial Na⁺ channels. - **Triamterene** - **Category:** Potassium-sparing diuretic - **Mechanism of Action:** Reduces K⁺ loss in urine by inhibiting epithelial Na⁺ channels. - **Spironolactone** - **Category:** Potassium-sparing diuretic - **Mechanism of Action:** Reduces K⁺ loss in urine; Aldosterone antagonist. - **Eplerenone** - **Category:** Potassium-sparing diuretic - **Mechanism of Action:** Reduces K⁺ loss in urine; Aldosterone antagonist. **2. Beta-blockers (B-blockers)** - **Mechanism of Action:** Blocks β₁ receptors, reducing cardiac output and renin release, thus lowering BP. Used in patients with heart issues. - **Side Effects:** Decreased libido, erectile dysfunction, low HDL, high TAG. Abrupt withdrawal can cause severe hypertension and arrhythmias. **3. ACE Inhibitors** - **First-line treatment** for patients with diabetes, CAD, kidney disease, and systolic dysfunction. - **Captopril** - **Category:** ACE inhibitor - **Mechanism of Action:** Lowers production of angiotensin I, reduces aldosterone release, and breaks down bradykinin. - **Side Effects:** Dry cough, angioedema, hyperkalemia, fetal malformations - **Enalapril** - **Category:** ACE inhibitor - **Mechanism of Action:** Lowers production of angiotensin I, reduces aldosterone release, and breaks down bradykinin. - **Side Effects:** Dry cough, angioedema, hyperkalemia, fetal malformations - **Lisinopril** - **Category:** ACE inhibitor - **Mechanism of Action:** Lowers production of angiotensin I, reduces aldosterone release, and breaks down bradykinin. - **Side Effects:** Dry cough, angioedema, hyperkalemia, fetal malformations - **Fosinopril** - **Category:** ACE inhibitor - **Note:** Not eliminated by the kidneys. **4. Angiotensin II Receptor Blockers (ARBs)** - **Losartan** - **Category:** ARB - **Mechanism of Action:** AT₁ receptor blocker; similar to ACE inhibitors but with lower risk of cough and angioedema. Teratogenic. - **Irbesartan** - **Category:** ARB - **Mechanism of Action:** AT₁ receptor blocker; similar to ACE inhibitors but with lower risk of cough and angioedema. Teratogenic. **5. Renin Inhibitors** - **Aliskiren** - **Category:** Renin inhibitor - **Mechanism of Action:** Similar to ACE inhibitors and ARBs. - **Contraindicated:** In pregnancy. - **Metabolized by:** CYP3A4. **6. Calcium Channel Blockers (CCBs)** - Most CCBs have a short half-life (3-8 hours). - **Verapamil** - **Category:** Phenylalkylamine - **Mechanism of Action:** Blocks L-Ca²⁺ channels in the heart and arteries. Does not act on veins. - **Side Effects:** 1st degree AV block, constipation, headache, fatigue, edema, gingival hyperplasia - **Diltiazem** - **Category:** Benzothiazepine - **Mechanism of Action:** Blocks L-Ca²⁺ channels in the heart and arteries. Does not act on veins. - **Side Effects:** 1st degree AV block, constipation, headache, fatigue, edema, gingival hyperplasia - **Nifedipine** - **Category:** Dihydropyridine (prototype) - **Mechanism of Action:** Blocks L-Ca²⁺ channels in the heart and arteries. Does not act on veins. - **Side Effects:** 1st degree AV block, constipation, headache, fatigue, edema, gingival hyperplasia - **Amlodipine** - **Category:** Dihydropyridine - **Mechanism of Action:** Blocks L-Ca²⁺ channels in the heart and arteries. Does not act on veins. - **Side Effects:** 1st degree AV block, constipation, headache, fatigue, edema, gingival hyperplasia - **Felodipine** - **Category:** Dihydropyridine - **Mechanism of Action:** Blocks L-Ca²⁺ channels in the heart and arteries. Does not act on veins. - **Side Effects:** 1st degree AV block, constipation, headache, fatigue, edema, gingival hyperplasia **7. Alpha-blockers** - **Mechanism of Action:** Relax arteries and veins, but less effective than other classes. - **Side Effects:** Sodium retention and other unwanted side effects. **8. Alpha and Beta Blockers (A, B-blockers)** - **Carvedilol** - **Category:** Alpha and beta blocker - **Use:** Heart failure and hypertension. - **Labetalol** - **Category:** Alpha and beta blocker - **Use:** Gestational hypertension and hypertensive emergencies. **9. Centrally Acting Agents** - **Clonidine** - **Category:** α₂-agonist - **Mechanism of Action:** Reduces sympathetic outflow. - **Side Effects:** Sedation, drowsiness, dry mouth, constipation - **Methyldopa** - **Category:** α₂-agonist - **Mechanism of Action:** Reduces sympathetic outflow. - **Side Effects:** Sedation, drowsiness, dry mouth, constipation **10. Vasodilators** - Due to side effects, these are not first-line treatments. - **Hydralazine** - **Category:** Vasodilator - **Mechanism of Action:** Directly relaxes blood vessels. - **Side Effects:** Angina, heart failure, increased plasma renin, lupus-like symptoms in high doses, reflex tachycardia - **Minoxidil** - **Category:** Vasodilator - **Mechanism of Action:** Directly relaxes blood vessels. - **Side Effects:** Reflex tachycardia **Diuretics:** **Thiazide Diuretics:** - **Mechanism**: Inhibit Na⁺/Cl⁻ cotransporter in distal convoluted tubule, increasing Na⁺ excretion, leading to diuresis and lowering blood volume. - **Common : Chlorothiazide** - **Other drugs**: Hydrochlorothiazide, Chlorthalidone, Metolazone, Indapamide (thiazide-like diuretics) - **Indications**: - **Hypertension** (due to reduced blood volume and peripheral resistance) - **Heart failure** (adjunct to loop diuretics) - **Kidney stones** (reduce Ca²⁺ in urine) - **Nephrogenic diabetes insipidus** (reduces urine volume) - **Adverse effects**: **Loop Diuretics:** - **Mechanism**: Act on the ascending limb of the Loop of Henle, inhibiting Na⁺/K⁺/2Cl⁻ cotransporter, the most potent diuretics. - **Most common : Furosemide** - **Other drugs**: Bumetanide, Torsemide, Ethacrynic acid - **Indications**: - **Pulmonary and peripheral edema** - **Hyperkalemia** - **Hypercalcemia** - **Adverse effects**: - **Hypokalemia** ,**Hypomagnesemia** , **Hyponatremia**, **Hyperuricemia** ,**Hypovolemia** , **Ototoxicity** (mainly by Ethacrynic acid) **Potassium-Sparing Diuretics:** - **Aldosterone Antagonists**: - **Spironolactone** (also blocks androgen receptors) - **Eplerenone** (more selective, metabolized by CYP3A4) - **Indications**: - **Edema** (e.g., nephrotic syndrome, heart failure, cirrhosis) - **Hypokalemia** - **Resistant hypertension** - **Polycystic ovarian syndrome** - **Adverse effects**: - **Hyperkalemia** - **Gynecomastia** (with Spironolactone) - **Epithelial Na⁺ Channel (ENaC) blockers**: - **Triamterene** and **Amiloride** (used in combination with other diuretics) **Carbonic Anhydrase Inhibitors:** - **Prototype: Acetazolamide** - **Mechanism**: Inhibit carbonic anhydrase, which leads to increased HCO₃⁻ and Na⁺ excretion. - **Indications**: - **Open-angle glaucoma** (though topical agents are preferred) - **Altitude sickness** (for prophylaxis) - **Adverse effects**: - **Mild acidosis** - **Renal stones** - **Paresthesia** - **Exacerbation of cirrhosis** **Osmotic Diuretics:** - **Common : Mannitol** - **Mechanism**: Create osmotic pressure, leading to increased urine output. - **Indications**: - **Intracranial pressure management** - **Acute toxicity** Heart Failure **1. RAAS Inhibitors (First-line treatment)** - **ACE Inhibitors** (End in \"-pril\") - **Mechanism of Action**: Inhibit ACE enzyme, reducing angiotensin I production, aldosterone release, and bradykinin breakdown. - **Example**: Enalapril, Lisinopril - **Side Effects**: Dry cough, angioedema, hyperkalemia, fetal malformations - **ARBs** (End in \"-sartan\") - **Mechanism of Action**: AT1 receptor blockers, similar effects to ACE inhibitors but with lower risk of cough and angioedema. - **Example**: Losartan, Irbesartan - **Side Effects**: Teratogenic, hyperkalemia - **Aldosterone Antagonists** - **Example**: Spironolactone, Eplerenone - **Mechanism of Action**: Prevents salt retention, hypokalemia, and myocardial hypertrophy. **2. Beta-Blockers** - **Mechanism of Action**: Block beta receptors, reduce cardiac output, decrease heart rate, and prevent cardiac remodeling. - **Example**: Carvedilol - **Side Effects**: Initially exacerbates symptoms but improves long-term function. **3. Diuretics** - **Mechanism of Action**: Lower preload and afterload; used to treat symptoms, not the underlying condition. - **Example**: Loop diuretics (e.g., Furosemide, Bumetanide) - **Side Effects**: Hypokalemia, dehydration, renal impairment **4. Angiotensin Receptor-Neprilysin Inhibitors (ARNI)** - **Example**: Sacubitril/Valsartan - **Mechanism of Action**: Combines ARB with neprilysin inhibitor. Neprilysin degrades angiotensin, bradykinin, and natriuretic peptides. - **Side Effects**: Hypotension, angioedema, dizziness **5. HCN Blockers** - **Example**: Ivabradine - **Mechanism of Action**: Slows heart rate by inhibiting HCN channels in the SA node. - **Used For**: HFrEF with heart rate ≥70 bpm - **Side Effects**: Bradycardia, luminous phenomena, pregnancy and breastfeeding contraindicated. **6. Positive Inotropic Drugs (Used in acute cases)** - **Digitalis (Digoxin)** - **Mechanism of Action**: Na/K-ATPase inhibitor, increases intracellular calcium and contractility, decreases heart rate. - **Side Effects**: Nausea, anorexia, blurred yellow vision, arrhythmias, hypokalemia increases toxicity. - **Beta-Agonists** - **Example**: Dobutamine, Dopamine - **Used For**: Acute heart failure in emergencies to increase contractility. - **Phosphodiesterase Inhibitors** - **Example**: Milrinone - **Mechanism of Action**: Increases cAMP to improve contractility. **7. Recombinant B-Type Natriuretic Peptide** - **Example**: Nesiritide - **Mechanism of Action**: Facilitates fluid homeostasis by promoting natriuresis and diuresis. - **Used For**: Acute congestive heart failure when IV diuretics are ineffective. - **Side Effects**: Hypotension, dizziness, worsened renal function **8. Vasodilators** - **Example**: Hydralazine, Nitrates - **Mechanism of Action**: Reduce preload and afterload by dilating blood vessels. - **Used For**: Acute HF cases or when other medications are ineffective. Heart Action Potentials and Electrocardiogram (EKG) Waves **Antiarrhythmic Drugs Classification:** 1. **Class I (Na⁺ Channel Blockers)**: - **Class IA**: Quinidine, Procainamide, Disopyramide. They slow phase 0 depolarization, useful for both atrial and ventricular arrhythmias. - **Class IB**: Lidocaine, Mexiletine. They bind rapidly to Na⁺ channels and shorten phase 3. They are especially useful for ventricular arrhythmias. - **Class IC**: Flecainide, Propafenone. They slow phase 0 depolarization, often used for atrial arrhythmias and refractory ventricular arrhythmias but are pro-arrhythmic in certain patients. 2. **Class II (β-Blockers)**: - Block β-adrenergic receptors, reducing heart rate and contractility. Used for atrial and AV arrhythmias and to prevent post-myocardial infarction arrhythmias. - Examples: Metoprolol, Esmolol. 3. **Class III (K⁺ Channel Blockers)**: - Prolong the action potential duration and repolarization. They are useful for a variety of arrhythmias but can be pro-arrhythmic. - Examples: **Amiodarone** (also has Class I, II, IV effects), **Dronedarone**, **Sotalol**, **Dofetilide**. 4. **Class IV (Ca²⁺ Channel Blockers)**: - Inhibit Ca²⁺ influx, slow conduction in the SA and AV nodes, and are particularly effective for atrial arrhythmias. - Examples: **Verapamil**, **Diltiazem**. 5. **Other Drugs**: - Digoxin: Inhibiting ATPase Shortens refractory Period in the myocardium and slows AV node conduction. Its used to control the response of ventricles in atrial arrhythmias. oto toxicity, it can result in ectopic ventricular beats and V-fib. - Adenosine: At high doses, adenosine slows conduction, Prolongs the refractory Period, and decreases AV node automaticity. Its half-life is 10-15 seconds. IV adenosine is the drug of choice for acute SVT. - Magnesium Sulfate: Mg is necessary for Na⁺, K⁺, and Ca²⁺ transport. It slows SA node impulse generation and myocardial conduction. It treats torsades de pointes and digoxin-induced arrhythmias. - Ranolazine: An antianginal (with properties similar to amiodarone). It shortens repolarization and action potential duration like mexiletine. Metabolized by CYP3A, CYP2D6. Treats refractory arrhythmias. Angina Pectoris - **β-Blockers**: - **Mechanism**: By reducing oxygen demand and improving cardiac function, β-blockers reduce the frequency and severity of angina attacks. - **Indication**: First-line treatment, except for vasospastic angina. - **Contraindications**: Severe bradycardia. Agents with intrinsic sympathomimetic activity (ISA) are avoided. - **Common Drugs**: Metoprolol and Atenolol. - **Calcium Channel Blockers**: - **Mechanism**: During ischemia, hypoxia increases calcium influx, which worsens ischemia. Calcium channel blockers prevent this, reducing ischemic damage. - **Indication**: Effective for all types of angina. - **Types**: - **Dihydropyridines** (e.g., Amlodipine, Nifedipine): Primarily work as vasodilators, commonly used for acute cases. - **Verapamil**: A weak vasodilator. - **Diltiazem**: A stronger vasodilator than verapamil. - **Nitrates**: - **Mechanism**: Nitrates reduce oxygen demand by converting to nitric oxide (NO) inside cells, which increases cyclic GMP (cGMP) levels. This results in the phosphorylation of myosin light chains and vasodilation of coronary arteries and veins, thereby improving blood flow. - **Indication**: Effective for all types of angina. - **Common Drugs**: Nitroglycerin (sublingual), Isosorbide Mononitrate, and Isosorbide Dinitrate. - **Side effects**: Common side effects include headaches, orthostatic hypotension, flushing, and tachycardia at high doses. Tolerance can develop quickly, necessitating nitrate-free intervals (typically at night, except in variant angina). - **Caution**: Avoid concurrent use with PDE-5 inhibitors (e.g., sildenafil) due to the risk of severe hypotension. - **Sodium Channel Blockers**: - **Mechanism**: These drugs block sodium channels, reducing the amount of calcium entering the heart muscle, which decreases myocardial workload. - **Indication**: Used less commonly, but may be considered in some angina patients. Platelet Inhibitors **1. Aspirin** - **Mechanism**: Aspirin inhibits **COX-1** by acetylating its serine residue. This is the only **irreversible** anti-platelet action and has a cumulative effect. - **Indications**: Prophylaxis of transient ischemic attack (TIA), recurrent MI, and other cardiovascular conditions. - **Pharmacokinetics**: The half-life (t½) is 15-20 minutes for low dose and 3-12 hours for high doses. - **Adverse Effects**: Bleeding, asthma exacerbation, Reye syndrome, angioedema. Other NSAIDs may block aspirin's effect by competing for COX-1 binding. **2. P2Y12 Receptor Blockers** - **Mode of Action**:\ These drugs prevent ADP from binding to its P2Y12 receptor, which prevents the activation of **glycoprotein (Gp) IIb/IIIa** receptors that are necessary for fibrinogen binding and platelet aggregation.These drugs inhibit the ADP receptors (P2Y12), which are involved in platelet activation and aggregation. - **Common Drugs**: - **Clopidogrel** (Prodrug): Used for atherosclerosis prevention, acute coronary syndrome (ACS), and after PCI (Percutaneous Coronary Intervention). It's metabolized by **CYP2C19**. - **Ticlopidine**: Used in severe TIA and stroke, but associated with risks like **aplastic anemia** and **thrombotic thrombocytopenic purpura (TTP)**. - **Prasugrel**: Used to prevent thrombosis in ACS patients, but contraindicated in those with a history of stroke or TIA. - **Ticagrelor**: Reversible blocker, used to reduce arterial emboli in unstable angina and MI. - **Cangrelor**: IV-only P2Y12 inhibitor used during PCI procedures. **3. Gp IIb/IIIa Inhibitors** - **Common Drugs**: - **Abciximab**: A chimeric monoclonal antibody, used intravenously (IV) for PCI and unstable angina. - **Eptifibatide**: A cyclic peptide used IV for PCI and unstable angina. - **Tirofiban**: Non-peptide, used IV for similar indications. - **Adverse Effects**: Bleeding, thrombocytopenia. **4. Dipyridamole** - **Mechanism**: Inhibits **phosphodiesterase (PDE)**, leading to increased cAMP levels in platelets, which inhibits thromboxane A2 (TXA2) synthesis. - **Indications**: Used in combination with aspirin for stroke prevention, but contraindicated in **unstable angina** due to the **coronary steal phenomenon** (where blood flow is redirected away from ischemic tissue). - metabolized by the liver, excreted via feces. **5. Cilostazol** - **Mechanism**: Inhibits **PDE3**, which increases cAMP levels in platelets and vascular smooth muscle, promoting vasodilation and inhibiting platelet aggregation. - **Indications**: Primarily used for **intermittent claudication** (pain caused by poor circulation). - **Adverse Effects**: Headache, GI upset, leukopenia, edema. Contraindicated in heart failure. **Anticoagulants** **1. Heparin & Low-Molecular-Weight Heparin (LMWH)** - **Mechanism**: Heparin binds to **antithrombin III**, increasing its ability to inactivate **thrombin** and **factor Xa**. LMWHs are smaller fractions of heparin and are more specific for factor Xa inhibition. - **Indications**: Used for **DVT**, **PE**, and prophylaxis after surgery. LMWHs (e.g., **Enoxaparin**, **Dalteparin**) are preferred in pregnancy. - **Adverse Effects**: Bleeding, **heparin-induced thrombocytopenia (HIT)**, osteoporosis with long-term use. - **Antidote**: **Protamine sulfate** can reverse the effects of heparin. **2. Direct Thrombin Inhibitors** - **Argatroban**: Synthetic L-arginine derivative, used for **HIT** or during PCI. - **Bivalirudin & Desirudin**: Analogues of **hirudin** (from leech saliva), used in patients undergoing PCI or with **HIT**. **3. Factor Xa Inhibitors** - **Apixaban**, **Betrixaban**, **Edoxaban**, **Rivaroxaban**: Oral agents used for DVT, PE treatment, and stroke prevention. - **Adverse Effects**: Bleeding, no specific antidote, used with caution in patients with renal impairment. **4. Warfarin (Vitamin K Antagonist)** - **Mechanism**: Warfarin inhibits **vitamin K epoxide reductase** (VKOR), decreasing the synthesis of clotting factors II, VII, IX, and X. - **Indications**: Long-term prevention of DVT, PE, and stroke, particularly in patients with atrial fibrillation or mechanical heart valves. - **Adverse Effects**: Bleeding, skin necrosis, purple toe syndrome, teratogenic. - **Reversal**: **Vitamin K**, **fresh frozen plasma**, or **prothrombin complex concentrate**. **5. Dabigatran (Direct Thrombin Inhibitor)** - **Indication**: Prevents strokes in non-valvular atrial fibrillation, and treats DVT and PE. - **Adverse Effects**: Bleeding, GI upset. - **Reversal**: **Idarucizumab** (monoclonal antibody to dabigatran). **Thrombolytics (Fibrinolytics)** Used in the acute treatment of thromboembolic events like MI, stroke, and PE. - **Alteplase & Tenecteplase**: Recombinant tissue plasminogen activators (tPA), which activate plasminogen to plasmin, breaking down fibrin and dissolving clots. - **Indications**: **Alteplase** is used for MI, PE, and ischemic strokes. **Tenecteplase** is used for MI. - **Adverse Effects**: Bleeding, angioedema (especially with alteplase). - **Contraindications**: Active bleeding, pregnancy, recent surgery, and certain cerebrovascular events. **Drugs for Bleeding** 1. **Aminocaproic Acid & Tranexamic Acid**: Inhibit plasminogen activation, used to reduce bleeding in surgeries or trauma. 2. **Protamine Sulfate**: Antagonizes heparin, used to reverse heparin-induced anticoagulation. 3. **Vitamin K**: Used to reverse warfarin-induced bleeding, takes 24 hours to reduce INR. 4. **Idarucizumab**: Reverses the effects of dabigatran. **Types of Inhalers:** 1. **Metered-Dose Inhalers (MDIs):** - **Instructions for Use:** - Shake the inhaler 5-10 times before use. - Forcefully exhale before inhaling. - Press the inhaler and start inhaling slowly and deeply. - A spacer may be used to reduce the risk of depositing the medication in the mouth and increase delivery to the lungs. - **Usage:** Typically, MDIs are used to deliver medication such as short-acting beta agonists (SABAs) for quick relief. 2. **Dry Powder Inhalers (DPIs):** - **Instructions for Use:** - No shaking is needed. - Inhale quickly and deeply to ensure the medication reaches the lungs. - **Usage:** DPIs are often used for long-acting treatments like LABAs. **Drugs for Asthma:** 1. **Short-Acting Beta Agonists (SABAs):** - **Common Drugs:** Albuterol (Salbutamol) and Levalbuterol. - **Mechanism of Action:** These drugs relax bronchial muscles to dilate the airways for quick relief from acute asthma symptoms. 2. **Long-Acting Beta Agonists (LABAs):** - **Common Drugs:** Salmeterol and Formoterol. - **Usage:** These are used in combination with corticosteroids to manage chronic asthma. They provide bronchodilation for up to 12 hours. - **Mechanism of Action:** They activate beta-2 receptors, leading to muscle relaxation and airway dilation. 3. **Inhaled Corticosteroids (ICS):** - **Common Drugs:** Beclomethasone, Budesonide, Fluticasone, Mometasone, Triamcinolone. - **Usage:** These are the first-line therapy for long-term asthma control and reduce inflammation and hypersensitivity in the airways. - **Side Effects:** Can cause oral thrush and hoarseness. Patients are advised to \"swish and spit\" after use to prevent these side effects. 4. **Leukotriene Modifiers:** - **Common Drugs:** Montelukast, Zafirlukast, Zileuton. - **Mechanism of Action:** These drugs block leukotrienes, which are inflammatory mediators that cause bronchoconstriction, mucus production, and airway edema. - **Side Effects:** Liver dysfunction (for Zileuton), headache, dyspepsia, and interactions with liver enzymes. 5. **Cromolyn Sodium:** - **Mechanism of Action:** Cromolyn stabilizes mast cells, preventing the release of inflammatory mediators like histamine and leukotrienes. - **Usage:** It\'s used as a prophylactic agent for asthma and allergic conditions, with minor side effects such as coughing and throat irritation. 6. **Theophylline:** - **Mechanism of Action:** Theophylline is a bronchodilator with anti-inflammatory properties. - **Side Effects:** Overdose can cause seizures and arrhythmias, so blood levels need to be monitored. 7. **Cholinergic Antagonists:** - **Common Drugs:** Ipratropium (SAMA), Tiotropium, Aclidinium, Glycopyrrolate (LAMAs). - **Usage:** These are used as add-on therapy, especially in chronic obstructive pulmonary disease (COPD) but can also be used in asthma for bronchodilation. 8. **Biologic Antibodies:** - **Common Drugs:** - Omalizumab (binds IgE, used for allergic asthma) - Mepolizumab, Benralizumab, Reslizumab (IL-5 antagonists for eosinophilic asthma) - **Side Effects:** May include anaphylaxis, arthralgia, fever, rash, infections, and malignancies. **Drugs for COPD:** 1. **Bronchodilators:** - LABAs (e.g., Indacaterol, Olodaterol) and LAMAs (e.g., Tiotropium) are the first-line treatment for COPD. 2. **Corticosteroids:** - Used for improving lung function in patients with severe COPD 3. **Roflumilast:** - **Mechanism of Action:** Oral PDE-4 inhibitor that reduces inflammation and exacerbations in chronic bronchitis. - **Side Effects:** Weight loss, nausea, and headaches. **Drugs for Allergic Rhinitis:** 1. **Antihistamines (H1 Blockers):** - **Common Drugs:** Fexofenadine, Loratadine, Cetirizine (2nd-generation), and Olopatadine (nasal spray). - **Usage:** Used to block histamine receptors, reducing allergic symptoms such as sneezing, itching, and nasal congestion. 2. **Corticosteroids:** - Nasal corticosteroids like Fluticasone, Mometasone are the most effective for managing chronic allergic rhinitis. 3. **Decongestants:** - **Common Drugs:** Phenylephrine (short-acting), Oxymetazoline (long-acting). - **Usage:** Used for relieving nasal congestion, but not for more than 3 days to avoid rebound congestion. **Drugs for Cough:** 1. **Opioids (e.g., Codeine, Dextromethorphan):** - **Mechanism of Action:** Centrally acting antitussives that suppress cough reflex. - **Side Effects:** Constipation, sedation, and abuse potential (especially with codeine). 2. **Expectorants:** - **Common Drug:** Guaifenesin. - **Mechanism of Action:** Loosens mucus in the airways to facilitate its clearance. 3. **Benzonatate:** - **Mechanism of Action:** A peripherally acting antitussive that anesthetizes stretch receptors in the lungs. - **Side Effects:** Dizziness, and numbness in the mouth and throat. **Drugs for Peptic Ulcers and GERD** **Proton Pump Inhibitors (PPIs):** - **Mechanism of Action**: PPIs inhibit H⁺-K⁺ ATPase (the proton pump) in the parietal cells, decreasing gastric acid secretion. - **Characteristics**: - Weak bases, prodrugs activated in acidic environments. - Taken 30-60 minutes before the largest meal for optimal effect. - Common examples: **Dexlansoprazole, Lansoprazole, Omeprazole, Esomeprazole, Pantoprazole, Rabeprazole**. - **Side Effects**: Headaches, nausea, diarrhea, low B12, magnesium, and calcium, osteoporosis (long-term), and risk of Clostridium difficile infection. - **Drug Interactions**: **Omeprazole** can interact with **Clopidogrel** (via CYP2C19 inhibition), reducing its effectiveness. **Histamine H2 Receptor Antagonists (H2 Blockers):** - **Mechanism of Action**: H₂ blockers reduce gastric acid secretion by blocking histamine receptors on parietal cells. - **Drugs**: **Famotidine**, **Cimetidine** (prototype), **Nizatidine**, **Ranitidine**. - **Uses**: Peptic ulcers, GERD, and acute stress ulcers. - **Side Effects**: Cimetidine has notable side effects like antiandrogenic effects and CYP450 inhibition, whereas others are generally well-tolerated. **Antimicrobials for H. pylori Eradication:** - **First-line Regimen** (Bismuth-based quadruple therapy): - **Bismuth subsalicylate**, **Metronidazole**, **Tetracycline**, and a **PPI**. - **Second-line** (if resistance is low): **PPI + Amoxicillin (or Metronidazole if allergic) + Clarithromycin**. **Prostaglandins:** - **Misoprostol** (PGE₁ analog): Inhibits gastric acid secretion, increases mucus and bicarbonate production. - **Uses**: Primarily for NSAID-induced ulcers. - **Side Effects**: Diarrhea, uterine contractions (avoid in pregnancy). **Antacids:** - **Mechanism of Action**: Weak bases that neutralize stomach acid and reduce pepsin activity. - **Examples**: **Aluminum hydroxide (Al(OH)₃)**, **Magnesium hydroxide (Mg(OH)₂)**, **Calcium carbonate (CaCO₃)**. - **Side Effects**: - **Aluminum**: Constipation. - **Magnesium**: Diarrhea. - **Calcium**: Risk of kidney stones and hypercalcemia. **Mucosal Protectors:** - **Sucralfate**: Forms a gel-like barrier that protects the mucosa from acid. Requires low pH to activate. - **Bismuth subsalicylate**: Antimicrobial, forms a protective coating over ulcers, and increases mucus production. **Drugs for Chemotherapy-Induced Nausea and Vomiting (CINV)** **Antiemetics:** - **Phenothiazines**: **Prochlorperazine** (D₂ receptor blocker), effective for low-to-moderate emetogenic chemotherapy. - **Benzamides**: **Metoclopramide** (D₂ antagonist, 5-HT₄ agonist), used for gastroparesis and CINV, though less effective with cisplatin. - **Butyrophenones**: **Haloperidol**, **Droperidol**: Used for moderate emetogenic chemotherapy but can prolong QTc. - **Serotonin (5-HT₃) Antagonists**: **Ondansetron**, **Granisetron**, **Dolasetron**, **Palonsetron**: Effective in 50-60% of cisplatin-induced nausea and vomiting. - **Neurokinin-1 (NK-1) Receptor Antagonists**: **Aprepitant**, **Fosaprepitant**, **Rolapitant**: Effective for highly emetogenic chemotherapy (e.g., cisplatin), side effects include fatigue, diarrhea, and abdominal pain. **Drugs for Diarrhea** **Antimotility Drugs:** - **Diphenoxylate** and **Loperamide**: Opioid-like drugs that slow gut motility. Should be avoided in cases of infectious diarrhea due to the risk of toxic megacolon. **Adsorbents:** - **Methylcellulose**: Binds toxins and irritants in the gut. Used for mild diarrhea. **Laxatives:** - **Stimulant Laxatives**: **Senna**, **Bisacodyl**: Used for opioid-induced constipation. - **Bulk-forming Laxatives**: **Methylcellulose**, **Psyllium**: Increase stool bulk and water content. - **Osmotic Laxatives**: **Magnesium citrate**, **PEG**, **Lactulose**: Draw water into the intestines, promoting stool softening. - **Stool Softeners**: **Docusate sodium**: Used prophylactically to soften stools. **Drugs for Irritable Bowel Syndrome (IBS)** **IBS-C (Constipation Predominant):** - **Linaclotide**: A guanylate cyclase-C agonist, increases fluid secretion in the intestines. - **Lubiprostone**: Chloride channel activator, used for constipation in women. **IBS-D (Diarrhea Predominant):** - **Alosetron**: A 5-HT₃ antagonist, reduces bowel movement frequency. - **Eluxadoline**: Mu- and kappa-opioid receptor agonist, helps control motility. - **Rifaximin**: A non-absorbable antibiotic that reduces bacterial load. **Drugs for Inflammatory Bowel Disease (IBD)** **5-Aminosalicylates (5-ASAs):** - **Sulfasalazine**: Prototype drug, used for mild-to-moderate ulcerative colitis. - **Mesalamine**: Encapsulated to deliver the active ingredient directly to the intestines. **Corticosteroids:** - **Budesonide**: Preferred in localized ileal and right colonic Crohn's disease. - **Prednisone**: Used for more extensive disease but not for long-term use due to side effects. **Biologic Agents:** - **TNF-α Inhibitors**: **Infliximab**, **Adalimumab**, **Certolizumab**: Used in moderate-to-severe Crohn\'s disease and ulcerative colitis. - **Integrin Inhibitors**: **Vedolizumab**: Targets α4β7 integrin to prevent white blood cell migration into the intestines. - **IL-12/23 Inhibitors**: **Ustekinumab**: For refractory cases of Crohn's disease. **Immunomodulators:** - **Methotrexate**, **Azathioprine**, **6-Mercaptopurine**: Immunosuppressive agents used to maintain remission in IBD. **Drugs for Anemia** **Iron Supplements:** - **Oral Iron:** - For patients with iron-deficiency anemia, a dose of 150-180 mg of oral iron per day, divided into 2 or 3 doses, is recommended. The absorption of iron is dependent on body stores---if iron stores are low, absorption is better. - Common oral forms of iron: - **Ferrous sulfate** (most common) - **Ferrous fumarate** - **Ferrous gluconate** - **Polysaccharide iron** - **Carbonyl iron** - These supplements can take several weeks to show effects. - **Parenteral (Injectable) Iron:** - Parenteral iron is used when oral supplementation is not effective or suitable. It provides more rapid effects. - Available formulations: - **Iron dextran** - **Sodium ferric gluconate** - **Ferumoxytol** - **Ferric carboxymaltose** - **Iron sucrose** - **Iron antidote:** **Deferoxamine** (used to treat iron overdose) is the antidote for iron toxicity. - **Side Effects of Iron Therapy:** - Common side effects of iron therapy include gastrointestinal irritation, pain, nausea, dark stool, infections, and allergies (particularly with iron dextran). **Folate (Vitamin B9):** - Folate is absorbed in the jejunum of the small intestine. Certain medications like phenytoin and phenobarbital can reduce folate absorption. - Parenteral folate (B9) is rarely associated with allergies. **Cobalamin (Vitamin B12):** - Vitamin B12 (B12) is essential for red blood cell production and neurological function. - **Hydroxocobalamin** is the intramuscular (IM) or subcutaneous (SC) form of vitamin B12, while **Cyanocobalamin** is the oral form. **Erythropoietin:** - **Erythropoietin (Epoetin alfa)** is a recombinant human erythropoietin used for anemia, especially in patients with: - End-stage renal disease - HIV - Bone marrow disorders - Prematurity - Cancer-related anemia - **Darbepoetin** is a longer-acting form of erythropoietin, produced by adding two carbohydrate chains to the structure of erythropoietin. - Both Epoetin alfa and Darbepoetin are administered subcutaneously (SC) or intravenously (IV), with SC being common for dialysis patients. - **Side Effects of Erythropoietin:** - Potential side effects include **hypertension**, **arthralgia** (joint pain), and **serious cardiovascular events**