Pharmacokinetics- Absorption Lecture Notes PDF

# Field of Veterinary Medicine ## Veterinary Medicine Program ### Lecture 3: General Pharmacology (Pharmacokinetics- Absorption) #### Dr. Asmaa Elsayyad Assistant Professor of Pharmacology 10/27/2024 Prepared By Dr. Asmaa Elsayyad Date: 27/10/2024 ## Terminology - Latent period: the time between...

# Field of Veterinary Medicine ## Veterinary Medicine Program ### Lecture 3: General Pharmacology (Pharmacokinetics- Absorption) #### Dr. Asmaa Elsayyad Assistant Professor of Pharmacology 10/27/2024 Prepared By Dr. Asmaa Elsayyad Date: 27/10/2024 ## Terminology - Latent period: the time between administration and the onset of action. - Duration of action: The time between the onset of action and elimination. - Half life (t 1/2): The time during which the drug concentration in the blood is reduced to 50%. - Withdrawal time: The time between stopping of drug administration until the drug is eliminated from the body. - Drug residue: the amount of a drug/metabolites deposited in animal tissues or products following its use. - Bioavailability: the fraction of dose that enters the systemic circulation in a chemically unchanged form. ## First-pass hepatic effect (First-pass metabolism): - Def., The 1st partial metabolism of a drug in the liver before it reaches systemic circulation. - Oral drugs → absorbed from the intestine → liver (1st metabolism) → ↓drug bioavailability. - E.g., Propranolol (Inderal). - Clinical significance of first-pass metabolism: - ↑oral therapeutic dose. - Liver disease → ↓therapeutic dose than normal. ## Enterohepatic circulation (recycling): - The drug is metabolized in the liver (by conjugation) → bile excretion → intestine (deconjugation) → free drug → reabsorbed again (2ry absorption) → to liver (portal circulation) →excreted again. - E.g., Purgatives (e.g. Phenolphthalein). - E.g., NSAIDs (e.g., Phenylbutazone). - Clinical significance of Enterohepatic circulation : - Longer duration of drug action. - Decrease the initial therapeutic dose. ## A. Drug absorption Def. the process of drug transfer from the site of administration to the systemic circulation. ### Factors affecting drug absorption: #### 1. Factors related to the absorptive membrane: - Nature & composition. - Blood flow. - Surface area. - Contact time. - Pathological state of the membrane. #### 2. Factors related to the drug: - Lipid solubility. - pH & ionization. - Molecular size. - Solubility & form. - Route of administration. - Interaction with other medications. ### A. Factors related to the absorptive membrane: #### 1. Nature & composition of the cell membrane: - The cell membrane is formed from a central lipid sheet (hydrophobic) and two outer layers of protein (hydrophilic) with many minute pores in between. - The central phospholipid bilayer → passage of lipophilic drugs. - Water pores → passage of hydrophilic non-fat soluble drugs. #### 2. Blood flow - ↑blood supply → ↑ absorption. #### 3. Surface area - ↑surface area → ↑absorption #### 4. Contact time - ↑contact time → ↑absorption. #### 5. Pathological state of the membrane: - Inflammatory conditions of the GIT → variable drug absorption, due to: - Damage of intestinal villi → ↓surface area. - ↑permeability. - Impaired transporter function. - Changes in pH. ### B. Factors related to the drug: #### B.1. Degree of lipid solubility: - ↑lipid-soluble (non-ionized) drugs→ ↑easily & rapidly absorbed (through the lipid bilayer by diffusion). - ↑Water-soluble (ionized) drugs cannot pass through the lipid bilayer (they pass through membrane pores or by carriers). **Lipid: water partition coefficient:** - It is a measure of the degree of lipid solubility of the drug. - Calculated by: solubility in lipid/solubility in water. - High coefficient → ↑lipophilic → ↑cross cell membranes (e.g., Steroids). - Low coefficient → ↑hydrophilic → ↓cross cell membranes (e.g., Insulin). #### B.2. pH & ionization (polarity) of the drug: - ↑Non-ionized (lipid-sol) drugs → ↑easily cross cell membrane. - 个lonized (water-sol) drugs → ↓cross cell membrane. - The degree of drug ionization is determined by the pH of the medium: - Acidic drugs (e.g., Aspirin) – Not ionized in the acidic pH of the stomach → rapidly absorbed. - Alkaline drugs (e.g., Antacids) - Not ionized in the alkaline pH of intestine⇒ rapidly absorbed. - Alkaline drugs ionize in the acidic pH of the stomach → not absorbed in the intestine & vice versa. **Clinical significance:** treatment of drug toxicity. E.g., - Amphetamine+ Ammonium chloride → ttt of amphetamine toxicity. - Sulfonamides+ Na-bicarb → ttt of slufonamides toxicity #### 3. Molecular size: - ↓molecular size → ↑easily cross cell membrane. #### 4. Solubility & pharmaceutical form: - Gaseous form > aqueous solution > oily solution/suspension > solid form (capsule, tablet). #### 5. Route of administration: - Generally, parenteral route > Oral. - IV, inhalation, sublingual > IM > SC > oral > Rectal > Topical. #### 6. Interaction with other drugs & food: - Full/empty stomach → delay/fasten absorption. - Interactions e.g., - Milk/milk products → ↓tetracycline absorption (chelation). - Vit.C → ↑iron absorption, while tannic acid → ↓iron absorption. - Antacids (alkaline) → ↓ absorption of acidic drugs (ionization). ## Mechanisms of drug absorption | | A. Passive transport | B. Facilitated diffusion (carrier-mediated) | C. Active transport | D. Pinocytosis | |----------------------------|------------------------------|----------------------------------------------|---------------------|--------------------------------------------------------------| | **Drug** | Lipid-sol Non-ionized | Non-lipid soluble lonized | | Fat-/water- sol ↑M.wt or drug aggregates | | **Site** | Lipid bilayer | Lipid bilayer | | Pinocytotic vesicle | | **Conc gradient** | With | Against | With | With | | **Carrier** | - | + | + | - | | **ATP** | - | + | + | - | | **E.g.** | • Aspirin <br> • Diazepam | • Some vitamins (vit. B12) <br> • Some amino acids (L-dopa into brain) | • Iodine into thyroid.<br> • Catecholamines into neurons.<br> • Electrolytes (Na+ & K+).<br> • Iron. | • Polypeptides (insulin & Igs) | ## Simple Diffusion - Movement of particles from high to low concentration without a protein ## Passive, Facilitated and Active Transport - **Passive diffusion** : Down the gradient, No carrier involved, No energy used - **Facilitated diffusion**: Down the gradient, Carrier mediated, No energy used / needed - **Active transport**: Up the gradient, Carrier mediated, Energy dependant