💊🌟 ASPECTS OF PHARMACOLOGY & NEW DRUG DEVELOPMENT —
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🌟💊 INTRODUCTION TO PHARMACOLOGY
🔹💊 Pharmacology = Drugs का scientific study
✔️ इसमें drugs का अध्ययन किया जाता है:
🌿 Source
🧠 Mechanism of action
💉 Pharmacological effects
🎯 Therapeutic uses
⚠️ Toxicity
❗ Adverse effects
⚙️ Metabolism
🚽 Excretion
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🧠💊 PHARMACODYNAMICS vs PHARMACOKINETICS
🔵💊 PHARMACODYNAMICS
✔️ “Drug body पर क्या effect करती है”
🌟 Mechanisms:
➤ Receptor interaction
➤ Enzyme inhibition
➤ Ion channel modulation
➤ Cellular response
💊 Examples:
➤ Salbutamol → β2 stimulation → Bronchodilation
➤ Atenolol → β1 blockade → ↓ Heart rate
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🟣💊 PHARMACOKINETICS
✔️ “Body drug के साथ क्या करती है”
🌟 ADME:
✔️ Absorption
✔️ Distribution
✔️ Metabolism
✔️ Excretion
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💉🌟 DRUG DOSE
✔️ Drug dose = required quantity for therapeutic effect
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🌟💊 FACTORS AFFECTING DOSE
🔴👶 1. Age
✔️ Children → immature liver/kidney → toxicity ↑
👴 Elderly → metabolism ↓, clearance ↓
💊 Examples:
➤ Diazepam → sedation ↑ in elderly
➤ Aminoglycosides → toxicity ↑
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🔵⚖️ 2. Body Weight
✔️ Obese → lipophilic drugs distribution ↑
💊 Examples:
➤ Diazepam
➤ Thiopentone
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🟣⚧️ 3. Sex
✔️ Females → fat ↑ → drug effect changes
💊 Example:
➤ Alcohol → stronger effect in females
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🟠🧬 4. Genetics
✔️ Polymorphism → metabolism change
💊 Examples:
➤ Isoniazid → slow acetylator toxicity
➤ Primaquine → G6PD hemolysis
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⚫🧫 5. Disease State
✔️ Liver disease → metabolism ↓
✔️ Kidney disease → excretion ↓
💊 Examples:
➤ Digoxin → renal failure accumulation
➤ Morphine → liver toxicity ↑
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💊🌟 TYPES OF DRUG DOSE
🟢 Therapeutic Dose → safe + effective
🔴 Toxic Dose → harmful effects
⚫ Lethal Dose → death (LD50 = 50% animals kill dose)
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🔵💉 LOADING DOSE
✔️ Rapid therapeutic level achieve करने के लिए
💊 WHY?
✔️ Long half-life drugs slow act करते हैं
📌 Examples:
➤ Digoxin
➤ Phenytoin
➤ Amiodarone
💊 FORMULA:
Loading Dose = (Vd × Target Plasma Concentration) / Bioavailability
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🟡💊 MAINTENANCE DOSE
✔️ Drug level maintain करने के लिए
📌 Examples:
➤ Lithium
➤ Valproate
💊 FORMULA:
Maintenance Dose = (Clearance × Target Plasma Concentration × Dosing Interval) / Bioavailability
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💊🌟 Titrated Dose
✔️ Patient response के अनुसार dose adjustment
💊 Examples:
➤ Insulin → glucose based
➤ Warfarin → INR based
➤ Levothyroxine → TSH based
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🌟💊 PLACEBO EFFECT
✔️ Dummy treatment से improvement
🧠 Mechanism:
✔️ Dopamine release
✔️ Endorphins release
✔️ Brain expectation
💊 Examples:
➤ Sugar tablet
➤ Saline injection
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⚫💊 NOCEBO EFFECT
✔️ Negative expectation → symptoms develop
💊 Symptoms:
✔️ Headache
✔️ Vomiting
✔️ Anxiety
✔️ Palpitations
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🔥💊 DRUG TOLERANCE
✔️ Same effect के लिए higher dose needed
🧠 Reasons:
✔️ Receptor downregulation
✔️ Enzyme induction
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🟢 Pharmacokinetic Tolerance
✔️ Liver enzyme induction
💊 Example: Rifampicin, Alcohol
🔵 Pharmacodynamic Tolerance
✔️ Receptor sensitivity ↓
💊 Example: Morphine, Nitroglycerin
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🟣⚡ TACHYPHYLAXIS
✔️ Rapid tolerance (short time)
💊 Examples:
➤ Ephedrine
➤ Nicotine
➤ Nitroglycerin
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🦠💊 DRUG RESISTANCE
✔️ Drug ineffective हो जाना
🧬 Mechanism:
✔️ Mutation
✔️ Enzyme production
✔️ Efflux pump
💊 Examples:
➤ MRSA
➤ MDR-TB
➤ VRE
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🧪💊 NEW DRUG DEVELOPMENT
🌟 Step 1: Drug Discovery
✔️ Target identification
✔️ Lead compound selection
🌟 Step 2: Preclinical Studies
✔️ Animal testing
✔️ Toxicity + PK studies
Toxicity Types
🔴 Acute → single dose
🔵 Subacute → weeks
🟣 Chronic → months/years
⚫ Carcinogenicity → cancer
🧬 Mutagenicity → DNA damage
👶 Teratogenicity → fetal defects
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🧬💊 CLINICAL TRIALS
🟢 Phase 0 → microdose PK
🔵 Phase I → safety + dose
🟣 Phase II → efficacy
🟠 Phase III → large population + comparison
🔴 Phase IV → post marketing surveillance
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⚠️💊 ADVERSE DRUG REACTIONS (ADR)
✔️ Normal dose पर harmful effect
🔵 Type A (Augmented)
✔️ Dose dependent + predictable
💊 Insulin → hypoglycemia
💊 Warfarin → bleeding
🟣 Type B (Bizarre)
✔️ Allergy/genetic
💊 Penicillin → anaphylaxis
💊 Sulfonamides → SJS
🟠 Type C (Chronic)
💊 Steroids → adrenal suppression
⚫ Type D (Delayed)
💊 Carcinogenicity/teratogenicity
🔴 Type E (End of use)
💊 Withdrawal syndrome
🔵 Type F (Failure)
💊 Antibiotic resistance, OCP failure
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👶💊 TERATOGENIC DRUGS
🔴 Thalidomide → limb defects (phocomelia)
🔵 Valproate → neural tube defects
🟣 Isotretinoin → craniofacial defects
🟠 Tetracycline → teeth discoloration
⚫ Warfarin → bone defects
🔵 Lithium → Ebstein anomaly
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💊🧪 ANTIDOTES
🔴 Paracetamol → N-acetylcysteine
🔵 Opioids → Naloxone
🟣 Benzodiazepines → Flumazenil
🟠 Organophosphate → Atropine + Pralidoxime
⚫ Cyanide → Hydroxocobalamin
🔵 Methanol → Fomepizole
🟣 Iron → Deferoxamine
🟠 Lead → EDTA
⚫ Digoxin → Digoxin immune Fab
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🌟📌 FINAL QUICK REVISION
✔️ Pharmacodynamics = body on drug
✔️ Pharmacokinetics = drug on body
✔️ Loading dose → fast effect
✔️ Maintenance dose → maintain level
✔️ Tolerance → dose ↑ needed
✔️ Resistance → drug failure
✔️ Phase IV → rare ADR detection
✔️ Type A → common ADR
✔️ Type B → dangerous ADR
✔️ Teratogens → fetal defects
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