chapter 4-8

• xenobiotics- foreign compounds/ compounds that are not naturally found in the body.
• phase I biotransformation- modification

  phase II biotransformation- conjugation
• modification - converts parent drug into a more polar metabolite.

  this process alter the chemical structure of the drug to a more simple one so that they can easily excreted by the body.
• liver- the principal organ for metabolism.
• kidney- principal organ for excretion.
• NADPH- Nicotinamide Adenine Dinucleotide Phosphate

  FMN- Flavin Mononucleotide

  FAD- Flavin Adenine Dinucleotide
• flavoprotein and hemoprotein - two microsomal enzyme that play an important role in oxidation-reduction process.
• P450 enzymes - they are responsible for catalyzing the bulk hepatic drug and xenobiotic metabolism.
• most important forms of P450

  • CYP1A2
  • CYP2A6
  • CYP2B6
  • CYP2C9
  • CYP2D6
  • CYP2E1
  • CYP3A4
• CYP3A4 - a P450 that is responsible for the metabolism of over 50% of the drugs metabolized by liver.
• induction - when there is an increase in the rate of synthesis of one or more of these enzymes.
• drug interactions - can be caused by inhibition or induction of cytochrome p450 activity.
• cytochrome p450 system - it plays a major role in the biotransformation of many drugs, including those with high therapeutic index (TI).
• pharmacokinetics - the movement of drugs into, out of, and within the body.
• enzyme inducers - substances that stimulate the production of new enzyme molecules.
• pharmacokinetics - the movement of drugs into, through, and out of the body.
• bioavailability - refers to the amount of drug reaching the circulation following oral dosing.
• first pass effect - the loss of drug due to its metabolism during absorption.
• first pass effect - occurs when a drug is absorbed from the GI tract but then undergoes extensive metabolism in the liver before reaching the general circulation.
• bioavailability - refers to the amount of drug that reaches the bloodstream from its site of administration.
• absorption - the process by which drugs enter the bloodstream from their site of administration.
• excretion - the removal of drugs from the body.
• metabolism - the chemical alteration of drugs within the body.
• 2 types of oxidation - aromatic hydroxylations and aliphatic hydroxylations
• aromatic hydroxylations - acetanilide, propronolol, phenobarbital, phenytoin, phenylbutazone, amphetamine, warfarin, naphthalene, benzpyrene
• aliphatic hydroxylations - amobarbitol, pentobarbitol, secobarbitol, chlorpropamide, ibuprofen, meprobamate,glutethimide, phenylbutazone, digitoxin
• epoxydation - aldrin
• types of oxidative dealkylation - n-dealkylation, o-dealkylation, s-dealkylation
• n-dealkylation - morphine, ethylmorphine, benzphetamine, aminopyrine, caffeine, theophyline
• o-dealkylation - codeine, p-nitroanisole
• s-dealkylation - 6-methylthiopurine, methitural
• n-oxidation - primary amines, secondary amines, tertiary amines
• primary amines - aniline, chlorphentermine
• secondary amines - 2-acetylaminoflourence, acetaminophen
• tertiary amines - nicotine, methaqualone
• s-oxidation - thioridazine, cimetidine, chlorpromazine
• deamination - amphetamine, diazepam
• desulfuration - thiopental, parathion
• dechlorination - carbon tetrachloride
• flavine monooxygenase/zeiglers enzyme - chlorpromazine, amitriptyline, benzphetamine, desipramine, nortrityline, methimazole, propylthiouracil