LRR Pharmacology Complete

Pharmacokinetics

• Bioavailability (BA): IV route has 100% BA. First pass metabolism reduces BA.
• High First Pass Metabolism Drugs (FPM):
  • Fentanyl
  • Propranolol
  • Morphine / Lignocaine (Oral Lignocaine not given).
• Z-Track Injection: Used for deep IM to prevent staining/backflow. Drugs: Iron, Haloperidol.
• Loading Dose: Depends on Volume of Distribution (Vd).
• Maintenance Dose: Depends on Clearance (CL).

Poisoning & Antidotes

Zero Order Kinetics

Rate of elimination is constant. Mnemonics: ATP

• Alcohol (Ethanol)
• Theophylline
• Phenytoin

Cholinergic System

• Botulinum Toxin: Inhibits ACh release. Used for muscle spasm, wrinkles, achalasia.
• Myasthenia Gravis:
  • Diagnosis: Edrophonium (Tensilon) test.
  • Treatment: Pyridostigmine + Atropine.
  • Crisis: IVIg or Plasmapheresis.
• Alzheimer's Drugs (DGR):
  • Donepezil (DOC)
  • Galantamine
  • Rivastigmine (Patch).
  • Memantine: NMDA antagonist added later.

Drug of Choice Scenarios

• Scorpion Sting: Prazosin (Alpha blocker) for HTN/Pulmonary edema.
• Organophosphate Poisoning: Atropine (Crosses BBB) + Pralidoxime (Enzyme regenerator).
• Atropine Poisoning: Physostigmine (Crosses BBB).
• Beta Blocker Poisoning: Glucagon.
• Anaphylactic Shock: Adrenaline (IM 1:1000).

Glaucoma Management

• DOC Open Angle: Prostaglandin Analogues (Latanoprost).
  Side Effects: Heterochromia (Iris color change), Cystoid Macular Edema.
• Alpha-2 Agonists: Brimonidine. Contraindicated in Children < 2yrs (CNS depression).
• Beta Blockers: Timolol. (Avoid in Asthma).
• Carbonic Anhydrase Inhibitors: Dorzolamide.

Asthma & COPD

• Beta-2 Agonists (Salbutamol): Side effects 3T & 2H.
  • Tremors (MC), Tachycardia, Tolerance.
  • Hypokalemia, Hyperglycemia.
• Inhaled Corticosteroids (ICS): DOC for chronic asthma. Side effect: Oral Candidiasis (Thrush). Rx: Gargle/Nystatin.
• Theophylline: PDE4 inhibitor. Side effects (Headache, Arrhythmia, Seizures).
• Omalizumab: Anti-IgE antibody.

Diuretics

• Mannitol: Osmotic. DOC for Cerebral Edema. Contraindicated in Heart Failure.
• Acetazolamide: CA Inhibitor. DOC for Mountain Sickness. Urine becomes Alkaline.
• Loop Diuretics (Furosemide): Acts on TAL. DOC for Acute Pulmonary Edema/HF.
• Thiazides: Acts on DCT. DOC for Hypertension (Elderly). Side effect: Hypercalcemia (Good for stones), Hyperglycemia, Hyperuricemia.
  Metolazone: Thiazide safe in Renal Failure.
• Spironolactone: K+ sparing. SE: Gynecomastia.

Heart Failure (Cardioprotective Drugs)

Mnemonic: SAHIBS

• Sacubitril (Neprilysin inhibitor) + Valsartan (ARNI)
• ACE Inhibitors / ARBs
• Hydralazine + Isosorbide Dinitrate
• Ivabradine
• Beta Blockers (Metoprolol, Bisoprolol, Carvedilol, Nebivolol)
• Spironolactone / SGLT2 Inhibitors (Dapagliflozin).

Anti-Arrhythmics & Angina

• PSVT Acute: Adenosine (IV bolus).
• PSVT Maintenance: Verapamil/Diltiazem.
• Amiodarone: DOC for VT/VF. Side Effects BITCH.
  • Blue man syndrome (Skin)
  • Interstitial Lung Disease (Fibrosis)
  • Thyroid (Hypo/Hyper)
  • Corneal microdeposits
  • Hepatotoxicity / Hypotension.
• Torsades de Pointes: Magnesium Sulfate.

Anti-Platelets

• Aspirin: Irreversible COX inhibitor.
• Clopidogrel: P2Y12 blocker. Prodrug. Activated by CYP2C19.
  Interaction: Omeprazole inhibits CYP2C19 (Reduces Clopidogrel effect). Use Pantoprazole instead.
• Abciximab: GP IIb/IIIa inhibitor.

Anti-Coagulants & Antidotes

Diabetes Mellitus

• Metformin: DOC. SE: Lactic Acidosis, B12 deficiency. CI in Renal Failure.
• SGLT2 Inhibitors (-gliflozins): Urinary glucose loss. Cardioprotective & Renoprotective.
  SE: UTI, Fournier's Gangrene, Euglycemic DKA.
• GLP-1 Agonists (-glutide): Liraglutide, Semaglutide. Weight Loss benefit.
• DPP-4 Inhibitors (-gliptins): Weight neutral. Linagliptin is safe in Renal Failure.

Thyroid

• Pregnancy 1st Trimester: Propylthiouracil (PTU).
• Pregnancy 2nd/3rd Trimester: Carbimazole / Methimazole (Risk of Aplasia Cutis in 1st).
• Thyroid Storm Rx (PPID):
  • Propranolol
  • PTU
  • Iodides (Lugol's)
  • Dexamethasone

Epilepsy

• GTCS / Myoclonic: Valproate or Levetiracetam.
  Valproate is highly teratogenic (Neural Tube Defects).
• Absence Seizures: Ethosuximide or Valproate.
• Focal Seizures: Carbamazepine or Oxcarbazepine.
• Pregnancy: Levetiracetam or Lamotrigine (Safest).

Drugs & Alcohol

• Alcohol Withdrawal: Benzodiazepines (Diazepam/Chlordiazepoxide). Use Lorazepam in liver failure.
• Disulfiram: Aldehyde dehydrogenase inhibitor (Acetaldehyde accumulation -> Vomiting).
• Opioid Overdose: Naloxone (IV).
• Opioid Maintenance: Methadone or Buprenorphine. Relapse prevention: Naltrexone.

Antibiotics Highlights

• Penicillin (Benzathine): DOC for Syphilis & Rheumatic Fever prophylaxis.
• Ceftriaxone: DOC for Meningitis, Typhoid, Gonorrhea.
• Vancomycin: DOC for MRSA. Oral Vancomycin for Pseudomembranous Colitis.
  SE: Red Man Syndrome (Rapid IV).
• Linezolid: For VRSA/VRE. SE: Bone marrow suppression, Serotonin syndrome.
• Macrolides (Azithro/Erythro): DOC for Atypical pneumonia, Chlamydia, Pertussis. SE: QT prolongation.

Tuberculosis (RNTCP)

• H (Isoniazid): Neuropathy (Give B6), Hepatotoxic.
• R (Rifampicin): Orange urine, CYP inducer.
• Z (Pyrazinamide): Most Hepatotoxic, Hyperuricemia (Gout).
• E (Ethambutol): Optic Neuritis (Red-Green color blindness). Bacteriostatic.
• Bedaquiline: ATP synthase inhibitor. SE: QT prolongation.

Identification: Drugs ending in -tinib or -fenib.

• Imatinib: Inhibits BCR-ABL Tyrosine Kinase.
  Use: DOC for CML (Chronic Myeloid Leukemia) & GIST (Gastrointestinal Stromal Tumor).
• Sorafenib / Sunitinib: Inhibits Angiogenesis (VEGF).
  Use: RCC (Renal Cell Carcinoma) & HCC.
• Erlotinib / Gefitinib: EGFR Inhibitors.
  Use: Non-Small Cell Lung Cancer.
• Bortezomib: Proteasome Inhibitor.
  Use: Multiple Myeloma.
  Side Effect: "Zombie" → Reactivation of Herpes Zoster.

Monoclonal Antibodies (-mab)

• Bevacizumab: Inhibits VEGF (Vascular Endothelial Growth Factor) → Stops Angiogenesis.
  Mnemonic: "Bevafa Ramu Ki Rani" (Bevacizumab, Ranibizumab).
  Use: Colorectal Cancer, Diabetic Retinopathy.
• Trastuzumab: Inhibits HER2/neu receptor.
  Mnemonic: "Trust Her" (HER2 positive).
  Use: HER2+ Breast Cancer.
  Side Effect: Cardiotoxicity.
  Resistant Cases: If she breaks your trust, give her a "Lapa" → Lapatinib.
• Rituximab: Inhibits CD20 (B-Cells).
  Mnemonic: "Ritu is 20 years old".
  Use: Non-Hodgkin's Lymphoma, Rheumatoid Arthritis.
• Cetuximab: EGFR Inhibitor.
  Use: Head & Neck Cancer, Colon Cancer.
• Pembrolizumab: PD-1 Inhibitor (Immune Checkpoint Inhibitor).
  Use: Lung Cancer.

Calcineurin Inhibitors

They inhibit T-cell activation by blocking IL-2 production.

• Cyclosporine: DOC for Organ Transplant.
  Side Effects: Nephrotoxicity (Major), HTN, Hyperkalemia.
  Cosmetic SE: Gum Hypertrophy & Hirsutism.
• Tacrolimus (FK506): More potent than Cyclosporine.
  Side Effects: Nephrotoxicity, Diabetes (Hyperglycemia), Alopecia (No cosmetic side effects like Cyclosporine).

mTOR Inhibitors

• Sirolimus / Everolimus:
  Mechanism: Blocks mTOR pathway (Signal transduction).
  Advantage: Kidney Safe (Non-nephrotoxic).
  Side Effect: Bone Marrow Suppression (Thrombocytopenia/Hyperlipidemia).

Anti-Metabolites

• Mycophenolate Mofetil: Inhibits IMP Dehydrogenase (Purine synthesis).
  Side Effect: Diarrhea, Bone Marrow Suppression.