1 - Biotransformation Flashcards
These are dependent on metabolism to convert an inactive drug to an active one.
Prodrugs
Potentially harmful chemicals and toxins ingested pass via portal vein to liver, where they’re altered by enzymes before passing to heart for circulation. Some oral drugs may undergo extensive metabolism (90%+), reducing bioavailability. Those showing extensive effect must be dosed higher or administered via alternative manner.
First-Pass Metabolism
Also called biotransformation. Occurs primarily as a result of metabolic processes in liver as well as other organs and tissues. Amount of drug in body at any one time is dependent on dynamic balance between absorption and ____. It influences both the intensity and the duration of drug effects.
Inactivation
Occur when a constant proportion of the drug is eliminated per unit time. Rate of elimination is a constant fraction (50%) proportional to the amount of drug in the body. The higher the concentration, the greater the amount of drug eliminated per time unit.
First Order Kinetics
A pharmacokinetic parameter that is defined as the time it takes for the concentration of the drug in the plasma or the total amount in the body to be reduced by 50%.
Half-Life
Occurs primarily in the liver and produces chemical changes in the drug moleculte that make it inactive and more water soluble.
Enzymic Drug Metabolism | Biotransformation
Family of enzymes consisting of most important type of liver enzyme for transforming psychotropic drugs
Cytochrom P450
Non-synthetic modification of drug molecule by oxidation, reduction, or hydrolysis (1 of 3 processes). Oxidation is by far most common reaction; usually produces a metabolite less lipid soluble and less active, but it may produce a metabolite with equal or greater activity than parent drug.
Phase 1 Drug Metabolism
- Oxidation
- Reduction
- Hydrolysis
Involves conjugation of the drug with a simple molecule provided by the body, such as glucuronide or sulfate. Products are always inactive and more water soluble.
Phase II Metabolism
Metabolites may be excreted in 2 ways
- Filtration by Kidney into urine
- Into bile and eliminated with feces
Factors that change biotransformation rate may alter magnitude and duration of drug effects or cause drug inteactions. They may also explain variability in individual response to drugs (4).
- Chronic use of drugs can induce quantity of liver enzymes, thereby decreasing bioavailability
- Drugs that inhibit liver enzymes increase blood levels of a drug, enhancing its action
- Competition among drugs for metabolism by same enzyme increases blood levels of one or both drugs
- Genetic diffences and differences in age, sex, nutrition, and organ function may influence rate of drug metabolism
With some drugs clearance occurs at a constant rate regardless of drug concentration.
Zero Order Kinetics
Associated with the endoplasmic reticulum. They exhibit particular characteristics on biochemical analysis, lack strict specificity, and can metabolize a wide variety of xenobiotics (chems foreign to living organism), including ingested toxins, environmental pollutants, carcinogens, and drugs. Among most important ones are Cytochrome P450 (CYP450) enzyme family.
Microsomal Enzymes
Biotransformation Capacity Modifyers (4)
(1) enzyme induction
(2) enzyme inhibition
(3) drug competition
(4) Individual differences; age, gender, genetics\
Many psychoactives used repeatedly cause an increase in numbers of __.
__ __ not only causes drugs to speed up their own biotransformation rate but can increase rate of metabolism of other drugs.
Enzymes | Enzyme Induction
Drugs directly affect their action and reduce metabolism of other drugs taken at same time if metabolized by same one.
Enzyme Inhibition
The liver metabolites are eliminated from the body with urine or feces. Some drugs are excreted in an unaltered form by kidneys.
Excretion
Occurs for drugs sharing a metabolic system. Number of enzyme molecules is limited, so elevated concentration of either drug reduces metabolic rate of second, causing potential toxic levels.
Drug Competition
Differences in drug metabolism due to genetic/environmental factors that can explain why some individuals seem to be extremely sensitive to certain drugs, but others may need much higher doses than normal to achieve effect.
Genetic Polymorphisms
Metabolic process through which prodrugs are converted from an inactive drug to an active one. The strategy is used by Pharma to develop prodrugs that cross the blood–brain barrier if the active drug cannot easily.
Bioactivation
Most important route of elimination. Liver biotransformation of drugs into ionized (water-soluble) molecules traps metabolites in kidney tubules so they can be expelled along with waste products in urine. Most drugs readily filtered unless bound to plasma proteins or are large molecular size.
Renal Excretion
