Drug Metabolism Flashcards
(29 cards)
What is drug metabolism, and why is it important?
Drug metabolism refers to the biochemical modification of drugs within the body to facilitate their elimination. It is crucial because it helps in converting drugs into more water-soluble forms (metabolites) that can be excreted easily through urine or bile. Metabolism can also affect the drug’s pharmacological activity, making it more or less active.
What are the possible effects of drug metabolites on the body?
Drug metabolites can have different effects: (1) More active than the parent drug (e.g., Prontosil is metabolized into sulfonamide, which is pharmacologically active). (2) Less active or inactive. (3) Toxic. (4) Changed in activity.
Why are most drug metabolites water-soluble?
Most drug metabolites are water-soluble to facilitate their excretion through urine (via the kidneys) or bile. Water solubility ensures that the drug does not accumulate in fatty tissues and can be efficiently removed from the body.
What is the primary site of drug metabolism in the body? Are there any other sites?
The liver is the main site of drug metabolism because it contains a high concentration of metabolizing enzymes, such as cytochrome P450. Other sites include the brain, skin, gastrointestinal tract, kidneys, lungs, and plasma.
Why is drug metabolism not simply a detoxification process?
Metabolism is often mistaken for detoxification, but it is not always the case. While some metabolites are inactive or excreted as waste, others can be more active, toxic, or even change the drug’s effect. For example, Prontosil is metabolized into an active drug, sulfonamide.
What is drug latentiation, and how is it used in drug design?
Drug latentiation is the process of modifying a drug to make it inactive or less active in its parent form, knowing that the body will metabolize it into an active drug. This is often used to mask unpleasant tastes, improve drug stability, and prevent premature degradation before reaching the target site.
How can drug metabolism convert a non-toxic drug into a toxic one?
Some drugs, when metabolized, produce toxic metabolites. For example, certain painkillers and anti-inflammatory drugs can be metabolized into compounds that cause liver damage.
Where are drug-metabolizing enzymes located in the liver?
Drug-metabolizing enzymes are located in the microsomal fraction of the liver, which includes the smooth endoplasmic reticulum. The major enzyme system responsible for drug metabolism is cytochrome P450.
What is the role of cytochrome P450 in drug metabolism?
Cytochrome P450 (CYP450) is a group of enzymes responsible for the oxidative metabolism of many drugs. It helps in converting lipophilic drugs into more hydrophilic forms for excretion.
Why is cytochrome P450 referred to as ‘P450’?
It is called P450 because its reduced form binds with carbon monoxide (CO) and absorbs light at 450 nm in a spectrophotometer.
What are the major components of the drug metabolism system?
The drug metabolism system comprises: (1) NADPH (a coenzyme providing reducing power). (2) NADPH-Cytochrome C dehydrogenase (an enzyme containing flavoprotein). (3) Cytochrome P450 (the terminal oxidase responsible for oxidation reactions).
How does NADPH contribute to drug metabolism?
NADPH provides the electrons needed for oxidative metabolism, helping cytochrome P450 enzymes catalyze the oxidation of drugs.
What happens when cytochrome P450 is reduced?
When cytochrome P450 is reduced, it binds to oxygen and forms an active oxygen complex, which participates in the oxidation of drugs.
What is the function of NADPH cytochrome C reductase in drug metabolism?
This enzyme reduces cytochrome P450 either directly or through an intermediate electron carrier, facilitating oxidation reactions.
What are the three main types of Phase I metabolic reactions?
(1) Oxidation (e.g., hydroxylation, dealkylation). (2) Reduction (e.g., azo and nitro reduction). (3) Hydrolysis (e.g., ester and amide hydrolysis).
How do oxidation, reduction, and hydrolysis contribute to drug metabolism?
Oxidation introduces an oxygen atom, making the drug more polar. Reduction adds hydrogen or removes oxygen, affecting drug activity. Hydrolysis breaks down esters and amides, producing smaller, more water-soluble molecules.
What is the main purpose of Phase I metabolism?
To introduce or expose a functional group (e.g., hydroxyl, amine, carboxyl) that increases polarity and facilitates further metabolism or excretion.
Why do some drugs only undergo Phase I metabolism without Phase II?
Some drugs become sufficiently water-soluble after Phase I metabolism and do not require further conjugation for elimination.
What are examples of drugs that undergo only Phase I metabolism?
Pethidine undergoes only Phase I metabolism because it becomes polar enough after oxidation for excretion.
What is the significance of hydroxylation in drug metabolism?
Hydroxylation introduces hydroxyl (-OH) groups, increasing the drug’s solubility and preparing it for further metabolism.
What is the main purpose of Phase II metabolism?
To further increase the water solubility of the drug by adding conjugating groups such as glucuronic acid, sulfate, or acetyl groups.
Why do Phase II reactions require energy?
Phase II metabolism involves the synthesis of conjugates, which requires ATP to drive the reaction.
What are the major types of Phase II reactions?
Glucuronidation, Sulfation, Acetylation, Methylation, Amino acid conjugation.
What is glucuronidation, and which enzyme catalyzes it?
Glucuronidation is the conjugation of glucuronic acid to drugs, catalyzed by glucuronyl transferase.
