Pharmacokinetics pharmacology for bSc nursing students

Pharmacology

1. Pharmacokinetics Dr. Akash Sinha

2. P/K Pharmacokinetics is the quantitative study of drug movement in, through and out of the body. It is what the body does to a drug. The processes involved are: A) Absorption B) Distribution C) Metabolism D) Elimination/ Excretion

3. Absorption Movement of drugs from the site of administration to the systemic circulation.

4. Vesicular Transport

5. Bioavailability Is the rate and extent to which drug reaches the systemic circulation is demonstrated by a graph Cmax on the graph is the description of Rate of absorption The area under the curve is the amount of drug that is reaching the systemic circulation.

6. Factors affecting bioavailability and absorption Pharmaceutical Factors Particle Size Salt Form Crystal Form Water of Hydration Nature of Excipients Degree of Ionization. Pharmacological Factors Gastric Emptying and gastrointestinal motility Gastrointestinal Disease Food and Other Substances First Pass Effect Drug to Drug interaction Vascularity of the absorption surface Surface area of the absorption surface Route of Absorption

7. Distribution Once a drug has gained access to the blood stream, it gets distributed to other tissues that initially had no drug, concentration gradient being in the direction of plasma to tissues. The extent of distribution of a drug and its pattern of tissue distribution depends on its: • lipid solubility • ionization at physiological pH (a fun5ction of its pKa ) • extent of binding to plasma and tissue proteins • presence of tissue-specific transporters • differences in regional blood flow.

8. Apparent volume of distribution (V) Presuming that the body behaves as a single homogeneous compartment with volume V into which the drug gets immediately and uniformly distributed V = dose administered i.v. / plasma concentration

9. Metabolism Biotransformation means chemical alteration of the drug in the body. It is needed to render nonpolar (lipid-soluble) compounds polar (lipid-insoluble) so that they are not reabsorbed in the renal tubules and are excreted. In the absence of metabolism, body will not be able to get rid of lipophylic substances, and they will become very long acting. Most hydrophilic drugs, e.g. streptomycin, neostigmine, pancuronium , etc. are little biotransformed and are largely excreted unchanged. Mechanisms which metabolize drugs (essentially foreign substances or Xenobiotics) have developed to protect the body from ingested toxin an other environmental chemicals.

10. The primary site for drug metabolism is liver; Others are-kidney, intestine, lungs and plasma. Biotransformation leads to the following- ( i ) Inactivation: Most drugs and their active metabolites are rendered inactive or less active, e.g. ibuprofen, paracetamol, lidocaine, chloramphenicol, propranolol and its active metabolite 4-hydroxypropranolol. Thus, biotransformation provides an alternative method of terminating drug action to excretion. (ii) Active metabolite from an active drug: Many drugs have been found to be partially converted to one or more active metabolite; the effects observed are the sum total of that due to the parent drug and its active metabolite(s) (iii) Activation of inactive drug: Few drugs are inactive as such and need conversion in the body to one or more active metabolites. Such a drug is called a prodrug (see box). The prodrug may offer advantages over the active form in being more stable, av·ng better bioavailability or other desfrable phamacokinetic properties or less side effects and toxicity. Some prodrugs are activated selectively at the site of action.

11. First Pass Metabolism This refers to metabolism of a drug during its passage from the site of absorption into the sys temic circulation. All orally administered drugs are exposed to drug metabolizing enzymes in the intestinal wall and liver (where they first reach through the portal vein). Presystemic metabolism in the gut and liver can be avoided by administering the drug through sublingual, transdermal or parenteral routes. However, limited presystemic metabolism can occur in the skin ( transdermally administered drug) and in lungs (for drug reaching venous blood through any route). The extent of first pass metabolism differs for different drugs (Table 3.2) and is an important determinant of oral bioavailability.