General Pharmacology (Pharmacokinetics-1) PDF

General pharmacology (pharmacokinetics-1)  Pharmacology: Branch of science that deals with drugs. Subdivisions of Pharmacology Pharmacokinetics Pharmacodynamic (effect of the body on the drug) (effect of the drug on the bo...

General pharmacology (pharmacokinetics-1)  Pharmacology: Branch of science that deals with drugs. Subdivisions of Pharmacology Pharmacokinetics Pharmacodynamic (effect of the body on the drug) (effect of the drug on the body) (ADME ) - mechanism of action. Absorption Distribution - pharmacological actions. Metabolism - Therapeutic uses. Excretion - adverse effect. - Contraindications. Importance of Pharmacokinetics Tailor a dose regimen to the individual requirements of a patients (e.g. renal failure and liver disease). Find out a possible cause of treatment failure. Find out a cause of drug toxicity.  I- Absorption Definition: Transfer of drug from site of administration to blood stream. Factors affecting: A. Factors related to the drug: B. Factors related to the patient: Lipid solubility: lipid soluble Route of administration: I.V is the faster. drugs are readily absorbed. Absorbing surface area. Degree of ionization; the greater the lesser the Specific factors: Intrinsic factor is needed absorption. for Vitamin B12 absorption. Stability of gastric acid and digestive enzymes (benzyl- penicillin and insulin are destroyed in GIT).  pH, pKa and drug ionization: Basic drug Acidic drug Most drugs are weak acids or bases. Weak acids are better absorbed in acidic media where it is less ionized and Basic Acidic so more lipid soluble. media media Weak bases better absorbed in alkaline media where it is less ionized and so more lipid soluble. Unionized-lipid soluble Unionized-lipid soluble pKa is the pH at which 50% of the drug is ionized and 50% is unionized e.g: Pka of aspirin 3.5. Ionized- less lipid soluble Clinical significance of pKa and pH: 1- Knowing site of drug absorption: Acidic drugs as aspirin are largely unionized in gastric acidic PH and are absorbed from stomach, while bases, e.g. atropine are largely ionized and are absorbed only when they reach the intestines. Aspirin 2- Ion trapping: Acidic drugs as aspirin are largely Acidic unionized in gastric lumen which is acidic, so basic aspirin passes into cells lining stomach. But once entered cells finds the pH is alkaline where it is ionized and trapped. First pass metabolism (presystemic elimination): Metabolism of drugs in GIT or liver before reaching systemic circulation Gut first pass effect: First pass effect - Gastric acidity: destroys benzyl penicillin - Digestive enzymes: destroy insulin. Hepatic first pass effect: As Nitroglycerine To avoid: - change the route of administration. ex,. Give nitroglycerine sublingual. Portal circulation - increase the oral dose. bioavailability Bioavailability: It is the fraction of the drug that reaches the systemic circulation in the unchanged form. Bioavailability is 100% after IV administration. Variable after oral administration. For example, if 100 mg of a drug are administered orally and 70 mg of this drug are absorbed unchanged, the bioavailability of this drug is 70%. Factors affecting bioavailability: - Absorption - First pass metabolism  Which one of the following refers to “Percent fraction of the drug that reach systemic circulation in an unchanged form”? a. Half life b. Bioavailability c. First pass metabolism d. Lag time Which of the following is FALSE regarding fist pass effect? a. Nitrogycerin is an example of hepatic first pass effect b. Penicillin is an example of gut first pass effect through gastric acidity c. Changing route of administration is an option to overcome it d. Decreasing dose of drug administration is an option to overcome it  True or false 1-Pharmacokinetics means action of the drug on the body (--) 2- Acidic drugs are largely unionized in gastric acidic PH and are absorbed from stomach (--) 3- pKa is the pH at which 75% of the drug is ionized and 25% is unionized (--) Thank you