Summary
Highlights
The video introduces pharmacokinetics as the study of ADME (Absorption, Distribution, Metabolism, and Excretion) of drugs. It explains the first-pass effect where a drug is absorbed and passes through the liver before reaching systemic circulation, leading to metabolism.
Pharmacokinetics is defined as the study of absorption, distribution, metabolism, and excretion of a drug (ADME). It includes biotransformation in the organism, the distribution of drugs, and the excretion of substances.
Most drugs are absorbed in the GI tract through passive diffusion due to their lipid solubility. Hydrophilic substances (water-soluble) cannot easily penetrate cell membranes, which are primarily lipid-based. Active transport involves moving substances against a concentration gradient and requires energy.
Bioavailability refers to the fraction of an unchanged drug reaching systemic circulation after administration. It is determined to understand the extent of absorption and the impact of the hepatic first-pass effect, where drugs are metabolized in the liver before reaching systemic circulation.
Rectal administration minimizes the first-pass effect. Oral administration is most likely to lead to a significant first-pass effect as the drug passes through the liver before entering systemic circulation.
Intrathecal is a parental route of administration. Parental administration, such as intravenous or intramuscular, generally produces a more rapid response compared to oral administration, which involves slower processes of disintegration, absorption, and metabolism. Also, oily solutions can be injected via the intramuscular route.
Biological barriers include capillary walls, cell membranes, and the placenta. Renal tubules are not considered a biological barrier. The blood-brain barrier is difficult for some drugs to penetrate due to the absence of pores in the brain capillary endothelial cells, regardless of lipid or water solubility.
The volume of distribution relates the amount of drug in the body to the concentration of the drug in the plasma.
Biotransformation (metabolism) is the process of physicochemical and biochemical alteration of drugs in the body, primarily in the liver. It converts lipid-soluble drugs into less lipid-soluble, water-soluble forms to facilitate excretion. Microsomal oxidation predominantly acts on lipid-soluble drugs, increasing their ionization and water solubility, thus aiding excretion.
Stimulation of liver microsomal enzymes increases drug metabolism, requiring a higher dose of some drugs. Phase 1 metabolic transformations involve oxidation, reduction, and hydrolysis. Phase 2 reactions, or conjugation, include processes like acetylation, glucuronidation, sulfation, and methylation, which make drugs more water-soluble for excretion. Hydrolysis, however, is a Phase 1 process.
In liver disorders, a decline in microsomal enzyme activity enlarges the duration of action of some drugs because their metabolism and excretion are reduced, leading to prolonged presence in the body.
Half-life is the time required for the amount of drug in plasma to decrease by half due to elimination. It depends on biotransformation, drug concentration in plasma, and elimination rate, but not on the time of absorption. Elimination is the clearance of xenobiotics from an organism. The elimination rate constant is related to half-life. Systemic clearance is related to the volume of distribution, half-life, and elimination rate constant.