| Drug metabolism phase I | Phase I: Small chemical changes and functionalise molecule for phase II
-Functionalisation – addition of reaction group (oxidation) , unmasking of reactive group (reduction ) and hydrolysis . This leads to low lipophilicity , higher excretion and change in pharmacological effect. Oxidation by Cytochrome p450, non P450 oxidation , reduction and hydrolysis |
| Drug metabolism phase II | Phase II: - Conjugation reactions , increase water solubility , increase excretion
Glucuronidation , sulphation , acetylation , amino acid conjugation , glutathione conjugation . Adding of large group often charges caused large decrease in lipophilicity , higher excretion , lower pharmacological effect. |
| Drug Absorption | Definition: Process by which a drug moves from the site of administration into the bloodstream. |
| factors affecting absorption | Route of administration (oral, IV, IM, etc.).
Lipid solubility of the drug.
Presence of food in the stomach.
pH and ionization of the drug. |
| drug distribution | Definition: Dispersion of a drug throughout the body fluids and tissues. |
| Factors affecting drug distribution | Key Factors:
Blood flow to tissues.
Plasma protein binding (e.g., albumin binding limits free drug concentration).
Volume of distribution (Vd): Relates the amount of drug in the body to plasma concentration. |
| Drug metabolism | Biotransformation of a drug into more water-soluble compounds for excretion. |
| Summary of phases in metabolism | Phase I (Functionalization): Oxidation, reduction, hydrolysis (e.g., via cytochrome P450 enzymes).
Phase II (Conjugation): Addition of hydrophilic groups (e.g., glucuronidation, sulfation).
Liver Role: Major site of metabolism due to high enzyme concentration.
First-Pass Effect: Significant metabolism in the liver before reaching systemic circulation. |
| drug excretion | Removal of drugs and metabolites from the body. |
| routes and processes in drug excretion - Routes - think greys
processes - kidney - STEPS | Primary Routes:
Renal (urine).
Hepatic (bile, feces).
Minor routes: Sweat, saliva, breast milk.
Renal Processes:
Filtration (glomerulus).
Reabsorption (tubules).
Secretion (active transport mechanisms) |
| Bioavailability - a in availability = administered | Proportion of the administered dose that reaches systemic circulation |
| factors affecting bioavailability - ADME | Absorption efficiency.
First-pass metabolism.
Drug solubility. |
| Half life definition and importance | Time required for the plasma concentration of a drug to decrease by half.
Importance: Determines dosing frequency and duration of action. |
| factors overall affecting drug distribution and metabolism - PATIENT AND DRUG | Patient Factors:
Age (neonates and elderly have reduced metabolism).
Genetic polymorphisms (e.g., variations in CYP enzymes).
Liver and kidney function.
Drug Interactions:
Enzyme inducers (e.g., rifampin) increase metabolism.
Enzyme inhibitors (e.g., ketoconazole) decrease metabolism. |
| Mechanisms of absorption ( think of the letters in the word) | Trans cellular such as diffusion and active transport
And Paracellular |
| Routes of administration | Oral
Sublingual (spray)
Rectan
Skin
Injection
Inhalation |
| Topical and systemic administration | Topical - on the skin
Systems - in the body |
| Toxic effect of drug metabolism | Phase I and II often has toxic products rather than a parent drug administration |
| Phase 1 metabolism summary - purpose and processes | Purpose: Introduces or exposes a functional group (e.g., hydroxyl, amine) on the drug molecule to make it more reactive for Phase 2 metabolism. THEY ALL REQUIRE NADPH and oxygen
Key Processes:
Oxidation: Addition of oxygen (e.g., by cytochrome P450 enzymes in the liver).
Codeine to morphine - first pass affect - N DEALKALATION CYP2D6
Reduction: Gain of electrons (less common).
Hydrolysis: Splitting a molecule with water.
Outcome: Produces a slightly modified, often more polar (but sometimes still active) drug. |
| Phase 2 metabolism summary purpose and processes | Purpose: Attach a large, water-soluble molecule to the drug or its Phase 1 product to enhance excretion via urine or bile.
Key Processes:
Glucuronidation: Addition of glucuronic acid (most common).
Sulfation: Addition of a sulfate group.
excretion.
Phase 2 reactions are catalysed by TRANSFERASE ENZYMES |
