Pharmacokinetics of Drug Absorption: Drug Absorption Mechanism, Weak Acidic & Weak Basic Drugs, Bioavailability, First Pass Metabolism, Factors Affecting Drug Absorption & Enterohepatic Circulation

🌈 Pharmacokinetics of Drug Absorption: Drug Absorption Mechanism, Weak Acidic & Weak Basic Drugs, Bioavailability, First Pass Metabolism, Factors Affecting Drug Absorption & Enterohepatic Circulation

🌟 Introduction to Pharmacokinetics

🔷 Pharmacokinetics का मतलब है:

➡️ “Body drug के साथ क्या करती है”

🔷 Pharmacokinetics के 4 major steps:

✔️ Absorption

✔️ Distribution

✔️ Metabolism

✔️ Excretion

➡️ इसे short form में ADME कहते हैं।

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🌟 What is Drug Absorption?

🔷 Drug absorption वह process है जिसमें drug administration site से blood circulation में enter करती है।

🔷 Main purpose:

✔️ Drug को systemic circulation तक पहुँचाना

✔️ ताकि drug target organ तक पहुँच सके

✔️ और pharmacological action produce कर सके

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🌟 Importance of Drug Absorption

🔷 यदि drug absorb नहीं होगी:

✔️ Blood में नहीं जाएगी

✔️ Target tissue तक नहीं पहुँचेगी

✔️ Therapeutic effect नहीं होगा

➡️ इसलिए absorption determine करता है:

✔️ Onset of action

✔️ Duration of action

✔️ Intensity of action

✔️ Bioavailability

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🌟 Complete Process of Drug Absorption

🔶 Step 1 → Drug Administration

🔷 Drug विभिन्न routes से दी जा सकती है:

✔️ Oral

✔️ Sublingual

✔️ Intravenous

✔️ Intramuscular

✔️ Subcutaneous

✔️ Rectal

✔️ Inhalational

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🔶 Step 2 → Disintegration

🔷 Tablet छोटे particles में टूटती है।

➡️ Tablet → Granules → Fine particles

🔶 Step 3 → Dissolution

🔷 Drug particles body fluid में dissolve होते हैं।

🔷 केवल dissolved drug ही absorb होती है।

🌟 Important Point

✔️ “No dissolution = No absorption”

🔶 Step 4 → Membrane Penetration

🔷 Drug biological membrane cross करती है।

Main membranes:

✔️ Gastric mucosa

✔️ Intestinal mucosa

✔️ Cell membrane

🔶 Step 5 → Entry into Blood

🔷 Drug capillaries में enter करती है।

➡️ फिर systemic circulation में जाती है

➡️ फिर target organ तक पहुँचती है

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🌟 Structure of Biological Membrane

🔷 Cell membrane mainly बनी होती है:

✔️ Phospholipid bilayer

✔️ Cholesterol

✔️ Proteins

🔷 Membrane nature:

✔️ Lipophilic

➡️ इसलिए lipid soluble drugs आसानी से membrane cross करती हैं।

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🌟 Mechanisms of Drug Absorption

🔷 1. Passive Diffusion

🌈 Definition

🔷 Drug high concentration से low concentration की तरफ move करती है।

🌈 Characteristics

✔️ Energy required नहीं

✔️ Carrier required नहीं

✔️ Most common mechanism

✔️ Non-saturable process

🌈 Mechanism

🔷 Non-ionized lipid soluble drug membrane में dissolve होती है।

➡️ Membrane cross करती है

➡️ Blood में enter करती है

🌈 Examples

✔️ Aspirin

✔️ Diazepam

✔️ Phenytoin

🌟 Important Exam Point

✔️ Most drugs passive diffusion से absorb होती हैं।

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🔷 2. Facilitated Diffusion

🌈 Definition

🔷 Carrier mediated transport without ATP.

🌈 Characteristics

✔️ Carrier required

✔️ ATP required नहीं

✔️ Saturable process

🌈 Example

✔️ Vitamin B12

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🔷 3. Active Transport

🌈 Definition

🔷 Drug concentration gradient के against move करती है।

Low concentration → High concentration

🌈 Characteristics

✔️ ATP required

✔️ Carrier required

✔️ Saturable

✔️ Specific process

🌈 Examples

✔️ Levodopa

✔️ Methyldopa

✔️ Iron

🌟 Important Exam Point

✔️ Active transport requires ATP.

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🔷 4. Endocytosis

🌈 Definition

🔷 Cell membrane drug molecule को engulf करती है।

🌈 Example

✔️ Vitamin B12–Intrinsic factor complex

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🌟 pH Partition Theory

🌈 Principle

✔️ Non-ionized drugs better absorb होती हैं

✔️ Ionized drugs poorly absorb होती हैं

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🌟 Why Non-Ionized Drugs Absorb Better?

🔷 Non-ionized drugs:

✔️ Lipid soluble होती हैं

✔️ Membrane आसानी से cross करती हैं

🔷 Ionized drugs:

✔️ Water soluble होती हैं

✔️ Membrane cross नहीं कर पाती

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🌟 Weakly Acidic Drugs Absorption

🌈 Rule

✔️ Weak acids acidic medium में non-ionized रहती हैं।

➡️ Better absorption

HA ⇌ H+ + A-

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🌈 Mechanism

🔷 Stomach acidic pH maintain करता है।

✔️ Excess H+ ions present होते हैं

➡️ Reaction left side shift करती है

➡️ More HA form होता है

✔️ HA = Non-ionized form

➡️ Better absorption

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🌈 Examples

✔️ Aspirin

✔️ Phenobarbital

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🌟 Weakly Basic Drugs Absorption

🌈 Rule

✔️ Weak bases alkaline medium में non-ionized रहती हैं।

➡️ Better absorption

BH+ ⇌ B + H+

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🌈 Mechanism

🔷 Intestinal alkaline environment में:

➡️ More free base (B) form होता है

✔️ B = Non-ionized form

➡️ Better absorption

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🌈 Examples

✔️ Quinidine

✔️ Amphetamine

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🌟 Henderson–Hasselbalch Equation

🔷 Weak Acid Formula

pH = pKa + log (A- / HA)

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🔷 Weak Base Formula

pH = pKa + log (B / BH+)

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🌟 Important Concept

🌈 यदि pH = pKa

✔️ 50% ionized

✔️ 50% non-ionized

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🌟 Why Small Intestine is Main Site of Absorption?

🔷 Although stomach acidic होता है…

✔️ फिर भी most drugs small intestine में absorb होती हैं।

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🌈 Reasons

✔️ Huge surface area

✔️ Villi & microvilli present

✔️ Rich blood supply

✔️ Thin membrane

✔️ Long contact time

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🌟 Factors Affecting Drug Absorption

🔷 1. Lipid Solubility

✔️ More lipid soluble drug

➡️ Better absorption

🌈 Example

✔️ Thiopentone rapidly CNS में enter करता है

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🔷 2. Degree of Ionization

✔️ Non-ionized drugs तेजी से absorb होती हैं

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🔷 3. Surface Area

✔️ Large surface area = Better absorption

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🔷 4. Blood Flow

✔️ More blood flow = Faster absorption

🌈 Example

✔️ Deltoid IM injection तेजी से absorb होती है

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🔷 5. Gastric Emptying Time

✔️ Fast gastric emptying:

➡️ Drug जल्दी intestine में पहुँचती है

➡️ Faster absorption

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🔷 6. Food

✔️ Food absorption को:

✔️ Increase

✔️ Decrease

✔️ Delay

कर सकता है

🌈 Examples

✔️ Tetracycline + Milk

➡️ Calcium chelation

➡️ Reduced absorption

✔️ Griseofulvin + Fatty meal

➡️ Increased absorption

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🔷 7. Dosage Form

🌈 Absorption Order

Solution > Suspension > Capsule > Tablet > Coated tablet

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🌟 Bioavailability

🔷 Definition

🔷 Fraction of administered drug that reaches systemic circulation unchanged.

Bioavailability (F) =

(Amount of drug reaching systemic circulation / Administered dose) × 100

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🌟 Types of Bioavailability

🔷 Absolute Bioavailability

✔️ Oral dose को IV dose से compare करता है

🔷 Relative Bioavailability

✔️ Different formulations को compare करता है

🌟 Important Point

✔️ IV route bioavailability = 100%

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🌟 Parameters of Bioavailability

🔷 Cmax

✔️ Maximum plasma concentration

🔷 Tmax

✔️ Time required to reach Cmax

🔷 AUC (Area Under Curve)

✔️ Total drug exposure show करता है

➡️ Bioavailability indicate करता है

Bioavailability ∝ AUC

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🌟 Noyes–Whitney Equation

🔷 Formula

dC/dt = DA(Cs − C) / h

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🌟 Meaning

✔️ Smaller particle size

➡️ Faster dissolution

➡️ Faster absorption

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🌟 First Pass Metabolism

🔷 Definition

🔷 Oral drug intestine से absorb होने के बाद liver में metabolize हो जाती है before systemic circulation.

➡️ इसे first pass metabolism कहते हैं।

🌟 Mechanism of First Pass Metabolism

🔶 Step 1

✔️ Oral drug intestine में absorb होती है

🔶 Step 2

✔️ Portal vein के through liver में जाती है

🔶 Step 3

✔️ Liver enzymes drug metabolize कर देते हैं

Main enzymes:

✔️ CYP450 enzymes

🔶 Step 4

✔️ Remaining active drug systemic circulation में जाती है

🌟 Consequences of First Pass Metabolism

✔️ Decreased bioavailability

✔️ Higher oral dose required

✔️ Some drugs orally ineffective

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🌟 Drugs Showing High First Pass Metabolism

🌈 Cardiovascular Drugs

✔️ Nitroglycerin

✔️ Propranolol

✔️ Verapamil

✔️ Lidocaine

🌈 Opioids

✔️ Morphine

🌈 Hormones

✔️ Testosterone

🌈 CNS Drugs

✔️ Imipramine

✔️ Chlorpromazine

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🌟 Why Nitroglycerin Given Sublingually?

🔷 Nitroglycerin liver में rapidly metabolize हो जाती है।

➡️ Oral bioavailability बहुत low होती है

✔️ Sublingual route liver को bypass करता है

➡️ Rapid action मिलता है

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🌟 Enterohepatic Circulation

🔷 Definition

🔷 Drug liver → bile → intestine → reabsorption pathway follow करती है।

🌟 Importance

✔️ Drug action prolonged होता है

🌈 Examples

✔️ Morphine

✔️ Oral contraceptives

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🌟 Ion Trapping

🔷 Definition

✔️ Ionized drug particular pH environment में trap हो जाती है।

🌟 Clinical Importance

🌈 Aspirin Poisoning

✔️ Urine alkalinization की जाती है

➡️ Aspirin ionized हो जाती है

➡️ Reabsorption decreases

➡️ Excretion increases

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🌟 Important Exam One-Liners

✔️ Most common absorption mechanism = Passive diffusion

✔️ Most important absorption site = Small intestine

✔️ IV route bioavailability = 100%

✔️ Non-ionized drugs absorb better

✔️ First pass metabolism mainly liver में होता है

✔️ Nitroglycerin sublingual route से दी जाती है

✔️ Active transport requires ATP

✔️ Lipid soluble drugs rapidly membrane cross करती हैं

✔️ Weak acids acidic pH में better absorb होती हैं

✔️ Weak bases alkaline pH में better absorb होती हैं

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