Basic Pharmacology Lecture 2 PDF

Basic Pharmacology CPB 303 Lecture 2 Hadeer Osama Abou-Hany  Pharmacokinetic (Absorption) Absorption is the movement of a drug from the site of administration to the systemic circulation through a biological membrane. Site of administration → Routes of administration System...

Basic Pharmacology CPB 303 Lecture 2 Hadeer Osama Abou-Hany  Pharmacokinetic (Absorption) Absorption is the movement of a drug from the site of administration to the systemic circulation through a biological membrane. Site of administration → Routes of administration Systemic circulation → Bioavailability Biological membrane → Mechanisms of Transport  What happens after administration of the drug? AUC Minimum toxic concentration (MTC) Onset Duration Cmax Tmax MEC MTC The Y-axis shows the plasma drug concentration, and the X-axis shows the time in hours ❑AUC, the area under the curve, represents the total drug exposure integrated over time and is an important parameter for both pharmacokinetic and pharmacodynamic analyses. ❑MEC (Minimum Effective Concentration): The lowest concentration of a drug in the bloodstream that produces a desired therapeutic effect. Below this concentration, the drug is considered ineffective. ❑Onset, time form drug administration till appearance its pharmacological effect. ❑Duration, time form appearance of the drug pharmacological effect till the disappearance of this action. i.e. the time between two MEC. ❑Cmax , the maximum concentration of the drug in plasma. ❑The time it takes to reach the Cmax is called the Tmax. ❑MTC (Minimum Toxic Concentration): The lowest concentration of a drug that produces toxic effects. Test Your Knowledge! Absorption of IV preparation = …………….. Bioavailability of IV route = ………………  Routes of Drug Administration Systemic Local Topical/skin Enteral Ocular drops Enteral Parenteral Inhalation Oral Intravenous Rectal Intramuscular Sublingual Subcutaneous Intradermal Intrathecal Routes of administration Oral Route: The drug is administered through the gastrointestinal tract (stomach or intestines), e.g. tablets, capsules, and syrup. Intravenous Route: Medication is directly injected into the bloodstream, bypassing the need for absorption. Intramuscular: The drug is delivered into a muscle. Subcutaneous: Medication is introduced beneath the skin. Sublingual: The drug is placed beneath the tongue for absorption.  Route Advantages Disadvantages Factors affecting absorption Oral 1. Most common 1. Unsuitable for many patients → 1. GIT motility and emptying: 2. Convenient Unconscious, Children, Elderly, and ↑ the motility → ↓ the absorption ✓ Tablets ✓ Capsules 3. Cheap and patients suffering from vomiting 2. Food: ↓ absorption of many economic 2. Unsuitable for many drugs like drugs like tetracycline in the ✓ Syrups 4. For local action a) Irritant drugs presence of Ca. ✓ Effervescent on GIT and b) Undergoing 1st pass metabolism 3. Intestinal blood flow (splanchnic granules systemic actions c) Decomposed by HCl ex: Penicillin blood flow) 5. Reversible. d) Digested by gastric enzymes ex: insulin 4. Particle size: ↓ particle size → ↑ (proteins) absorption e) Highly polar (water soluble) 5. Dosage from 3. Delayed onset of action 6. Chemical interactions with food or other drugs that may affect pH and dissociation First Pass Metabolism (Enterohepatic Circulation) ✓ After drug absorption from upper part of the GIT → it will reach the portal circulation WHY AUC of oral route is ✓ Then portal vein will reach the liver where the lower than AUC of IV drug may be metabolized before reaching the site route? of action ✓ Ex: nitroglycerine  Route Advantages Disadvantages Factors affecting absorption Sublingual 1. Direct absorption from 1. The drug must be palatable. 1. Blood flow sublingual mucosa 2. The dose must be small 2. Rapid onset 3. No 1st pass metabolism → suitable for nitroglycerine Rectal 1. No 1st pass metabolism if 1st pass metabolism if the drug 1. Blood flow the drug is absorbed from absorbed form upper part lower part 2. Rapid absorption 3. for unconscious patients 4. Systemic or local effect Route Advantages Disadvantages Factors affecting absorption IM 1. Common 1. Not suitable for irritant drugs 1. Blood flow to the muscle 2. Rapid onset 2. Small volume of injection 2. Amount of fat deposition 3. Suitable for suspensions (maximum 10 ml) around the muscle 4. Long duration 3. Delayed onset compared to IV ✓ The lower the fat content, the 5. Suitable for sustained route higher the absorption rate release preparations 6. Easy IV 1. Rapid onset 1. Injected drug cannot be removed 2. Suitable for from body (Irreversible) emergencies 2. Drug should be water soluble 3. Large volume of 3. Not suitable for drugs which injection a) cause hemolysis 4. Suitable for b) suspension or emulsion unconscious patients c) containing pyrogen 5. Suitable for irritant d) lipid soluble drugs 6. No 1st pass metabolism 1- Which of these routes could be reversible (IV- IM- Sublingual- Oral) 2- Oral preparations should be pyrogen free? (True – False) 3- Oral route is the most suitable route for large volume preparations (True – False) 4- High amount of fat deposition around the muscle increase the absorption of IM preparations? (True – False)  Route Advantages Disadvantages SC 1. More rapid onset compared to oral route 1. Small volume of injection 2. Long duration of action (1.5 ml maximum) 3. Self-administered 2. Not suitable for irritant 4. Suitable for lipid soluble and water soluble drugs drugs Intraperitoneal 1. Used experimentally only IP 2. Large surface area of the peritoneum 3. High blood flow Route Inhalation Intranasal Intrathecal Topical Aerosols Drops Injection Cream form Dose Sprays Spray Ointments Inhaler Lotion 1) Large surface area The action of the drug Administration of 1. Targeted leading to rapid may be the drug directly application absorption a) Local action in the into the (application at the 2) May be used for nasal cavity cerebrospinal fluid site of action) Advantage a) local action: b) Systemic action (CSF) 2. Small amount (albuterol is used as through absorption required bronchodilator for from the nasal mucosa 3. Less systemic side treating asthma effects with low systemic side effects b) systemic action: general anesthetics ▪ General anesthetics ▪ nasal decongestant ▪ Pain ▪ Clotrimazole is ▪ ▪ Examples Albuterol for desmopressin Management applied as a cream asthma ▪ calcitonin (Morphine) to treat ▪ cocaine by intranasal ▪ Local dermatophytosis sniffing Anesthesia ▪ Tropicamide: drops to dilate the pupil. Factors affecting drug absorption Factors Related to the Patient: Factors Related to the Drug: Site of Administration Ionization: The drug must exist in a unionized, lipid-soluble form for effective absorption 1. Vascularity: Lipid Solubility: ▪ Increased blood flow enhances drug A drug must exhibit lipid solubility with some water absorption. solubility to facilitate absorption. Drugs with complete water insolubility, like BaCl2, ▪ For example, beneath the tongue (sublingual) are not absorbed. facilitate rapid absorption. Surface Area: Valence: ▪ A larger surface area generally leads to Some drugs, such as iron, are absorbed in specific increased absorption. ionic states. For example, ferrous iron (Fe++) is absorbed, while ▪ For instance, the alveoli in the lungs, with their ferric iron (Fe+++) is not. extensive surface area of 200 square meters, promote rapid absorption. 1- Oral Bacl2 is completely absorbed? (True – False) 3- The onset of oral nitroglycerine (NG) is lower than the sublingual NG. (True – False) 4- The concentration of drug where the abortion rate is equal to the elimination rate? (Cmax – Tmax – MIC- MTC) Factors Related to the Patient: Factors Related to the Drug: Circulation: The presence of shock can reduce Molecular Weight: absorption. Smaller drugs are generally absorbed more efficiently Consciousness than those with higher molecular weight. Presence of Nausea and Vomiting Food intake: Pharmaceutical Preparation: → For example, Griseofulvin, an antifungal medication, Factors like dosage form (tablet, capsule, syrup), has increased absorption when taken with fatty meals manufacturing method, particle size, and shape influence drug absorption. Presence of Other Drugs: Physical Characteristics: ▪ Some medications can decrease the absorption of Amorphous drug forms are typically absorbed more other drugs. readily than crystalline forms. ▪ For instance, epinephrine reduces the absorption of Chemical Properties: Some drugs can form non-absorbable complexes with local anesthetics by causing localized ions like calcium. vasoconstriction, leading to decreased blood flow and absorption. 1- Why adrenaline is combined with local anesthetic preparation for tooth extraction? 2- ………….. decreases the absorption of Tetracycline while ……….. increases the absorption of Griseofulvin.