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What is primarily responsible for the non-uniform distribution of drugs in the body?
Which of the following factors does NOT contribute to physiological barriers affecting drug distribution?
How do physiological barriers influence drug therapy effectiveness?
In the context of drug distribution, what is a likely outcome of physiological barriers?
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Which statement best describes the impact of physiological barriers on drug pharmacokinetics?
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What factor significantly increases the hepatic concentration of mepacrine compared to its plasma level?
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Which tissue is noted for having a significantly higher concentration of iodine?
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How does the concentration of mepacrine in the liver compare to its concentration in blood plasma?
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What is a potential consequence of chronic administration of mepacrine?
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What similarity exists between mepacrine and iodine in terms of tissue concentration?
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Which barrier allows the passage of non-ionized drugs with a high lipid/water partition coefficient to the fetus?
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Which of the following substances can easily cross the blood-brain barrier (BBB)?
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What type of diffusion process is primarily involved with the placental barrier for applicable drugs?
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Which of the following statements is true regarding the blood-brain barrier and its permeability?
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Which drug is mentioned as having difficulty crossing the blood-brain barrier?
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Which types of functional groups in drugs are likely to undergo sulfate conjugation?
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What is the primary enzyme responsible for transferring sulfate groups during sulfate conjugation?
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In which organs is sulfotransferase notably present for drug metabolism?
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Which of the following drugs is specified as undergoing sulfate conjugation?
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What type of chemical modification does sulfate conjugation represent in drug metabolism?
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Why are fetuses or neonates particularly vulnerable to the toxic effects of drugs?
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What is likely to happen to the drug metabolism in elderly individuals?
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In general, how does male drug metabolism compare to that of females?
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Which condition can significantly impair drug metabolism?
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What genetic factor can influence drug metabolism rates in individuals?
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Increased protein binding results in enhanced clearance of a drug from the body.
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Clearance is defined as the volume of plasma cleared of the drug by metabolism and excretion per unit time.
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Protein binding does not affect drug excretion through the kidneys.
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The process of metabolism is solely responsible for drug clearance without any role of excretion.
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Reduced drug clearance can lead to an accumulation of the drug in the body.
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Acetyl conjugation involves the enzyme acetyl transferase, which is located in the kupffer cells of the brain.
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Glucuronyl transferase is classified as a non-microsomal enzyme.
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The process of acetylation requires acetic acid to be activated by CoA to form acetyl CoA.
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Phenols and catechols are examples of substances involved in the acetylation process.
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Cytochrome P450 is a type of hydroxylase enzyme.
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Acetyl transferase is primarily responsible for the process of sulfation in drug metabolism.
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Esterases and amidase are examples of microsomal enzymes found in the cytoplasm.
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Dehydrogenase enzymes are primarily found in the mitochondria of different organs.
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Acetyl CoA can serve as a substrate in various metabolic pathways beyond conjugation.
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Hydrolase is a type of enzyme that aids in the breakdown of compounds through hydrolysis.
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The concentration of a drug in specific tissues can remain high even when its plasma concentration is low.
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Both alcohol and morphine have the same affinity for all organs in the body.
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A drug can have significant tissue concentration without a corresponding increase in its amount in the plasma.
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Endogenous substrates are solely derived from the body's internal processes and not from the diet.
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Glucuronide conjugation is considered the least common conjugation reaction of drugs.
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The persistence of drug concentration in tissues is unrelated to the drug's dosage or administration frequency.
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Nutrition has no impact on the regulation of drug conjugation.
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A reduced plasma concentration of a drug indicates that it has likely completely exited the body.
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The regulation of drug conjugation is influenced by external factors like diet and nutrition.
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Glucuronide conjugation is the only conjugation reaction that is essential for drug metabolism.
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What are the primary reactions involved in Phase-II drug metabolism?
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How does acetylation facilitate drug metabolism?
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Identify the enzyme primarily responsible for glucuronidation in drug metabolism.
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What is the significance of sulfate conjugation in drug metabolism?
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Discuss the role of endogenous substrates in drug conjugation.
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How does protein binding affect drug clearance in the body?
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What is the function of Cytochrome P450 in drug metabolism?
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What is the mechanism through which the placental barrier allows the transfer of drugs to the fetus?
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How does the permeability of the blood-brain barrier (BBB) to thiopental sodium compare to that of dopamine?
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What impact does diet have on drug conjugation processes?
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Explain why fetuses or neonates are more susceptible to drug toxicity.
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Why are non-ionized drugs able to cross the placental barrier more readily than ionized drugs?
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What is meant by glucuronide conjugation being the least common drug conjugation reaction?
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What role does lipid solubility play in the ability of drugs to cross both the blood-brain barrier and the placental barrier?
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What implication does a drug's high lipid/water partition coefficient have on its pharmacological effects during pregnancy?
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What is the role of cytochrome P450 enzymes in drug metabolism, and how much of the liver’s drug metabolism is attributed to Cyp3A4?
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Describe the impact of enzyme inducers on drug metabolism with an example of an inducer.
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What types of drugs undergo hydrolysis, and what is the product formed from pethidine through this process?
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How does the presence of cytochrome P450 enzymes differ among body tissues, and where are they commonly found?
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What is the significance of drug hydrolysis and which two drugs, in addition to pethidine, are mentioned as undergoing this process?
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What role does acetyl transferase play in drug metabolism, particularly in the liver?
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Explain the process by which acetic acid is involved in drug acetylation.
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Describe the significance of phenols and catechols in the context of acetylation.
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How does the presence of acetyl CoA influence various metabolic pathways beyond conjugation?
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What factors influence the regulation of drug conjugation processes such as acetylation?
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The hepatic concentration of mepacrine is more than 200 times that of ______.
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High concentrations of drugs may occur with ______ administration.
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Iodine is concentrated in the ______ tissue.
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Mepacrine's concentration in the liver may reach a very high ______.
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In biotransformation, reactions are classified into phase-I and phase-______ reactions.
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The phase-I reaction converts the drug to a more ______ metabolite.
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Mepacrine's concentration in the liver is significantly higher than in ______.
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Phase-II reactions involve the process of ______ to enhance the excretion of drugs.
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The enzyme ______ is involved in acetyl conjugation, which is significant in drug metabolism.
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The conversion of a drug in phase-I to a polar metabolite often makes it more suitable for ______.
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The conversion of salicylic acid into ______ acid involves specific enzyme activity.
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The enzyme ______ catalyzes the reduction of azo and nitro compounds.
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An example of a compound that undergoes reduction to form sulfonamide is ______.
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Reduction reactions involve the conversion of compounds, such as azos and ______ compounds.
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Drug metabolism by hydrolysis is restricted to esters and ______.
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The transformation from prontosil to sulfonamide is facilitated by the enzyme ______.
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The process of hydrolysis involves the splitting of a drug molecule after adding ______.
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Esterases and amidases are examples of enzymes found in ______.
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Hydrolysis can occur in tissues like the ______.
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Hydrolysis is part of the broader category of ______ encountered in drug metabolism.
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Fetuses or neonates have under-developed ______ which makes them vulnerable to toxic drug effects.
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As individuals age, their hepatic ______ and other organs deteriorate, affecting drug metabolism.
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Genetic differences such as being a slow ______ can impact drug metabolism rates.
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Diseases such as ______ can negatively affect drug metabolism by altering blood flow to the liver.
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Generally, ______ metabolize drugs faster than women, which is evident with substances like alcohol.
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Match the following drug metabolism processes with their characteristics:
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Match the following factors influencing drug concentration with their descriptions:
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Match the following terms with their relevant processes:
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Match the following statements with their implications:
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Match the following drug conjugation reactions with their characteristics:
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Match the following types of drug conjugation with their primary characteristics:
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Match the following enzymes with their primary location or function in drug metabolism:
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Match the following statements about drug pharmacokinetics with their implications:
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Match the following factors influencing drug metabolism with their effects:
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Match the following statements regarding drug distribution with the correct barrier or outcome:
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Match the following drugs with their protein binding characteristics and action duration:
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Match the following enzymes with their respective descriptions in drug metabolism:
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Match the following statements about drug clearance and metabolism:
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Match the following conjugation reactions with their characteristics:
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Match the following statements regarding drug interactions and effects:
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Match the following drug metabolism processes with their respective characteristics:
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Match the following types of enzymes with their roles in drug metabolism:
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Match the following drugs with their specific metabolic challenges:
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Match the following statements regarding drug clearance with their implications:
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Match the following conditions with their effects on drug metabolism:
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Match the following patient populations with their characteristics regarding drug metabolism:
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Match the following effects of drug metabolism with their corresponding patient characteristics:
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Match the conditions affecting drug metabolism with their implications:
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Match the following factors with their influence on drug metabolism:
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Match the following statements about drug metabolism with their corresponding attributes:
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Study Notes
Physiological Barriers to Drug Distribution
- Blood-Brain Barrier (BBB) prevents certain drugs from entering the central nervous system; thiopental sodium can cross, whereas dopamine cannot.
- Placental Barrier allows non-ionized, lipid-soluble drugs to diffuse to the fetus; e.g., mepacrine's hepatic concentration can exceed plasma levels by over 200 times with chronic use.
- Iodine concentrations in the thyroid tissue highlight selective distribution; drugs with hydroxyl, amino, or carboxyl groups (e.g., phenobarbitone) can also utilize this diffusion process.
- Sulfate conjugation aids in drug metabolism; sulfotransferases in the liver, intestinal mucosa, and kidneys transfer sulfate groups to drug molecules.
Variations in Drug Metabolism
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Fetal and Neonatal Biotransformation:
- Underdeveloped liver and enzymes increase vulnerability to drug toxicity.
- Poorly developed blood-brain barrier increases risk for adverse effects, such as hyperbilirubinemia leading to encephalopathy.
- Immature kidneys may impair drug excretion, resulting in jaundice.
-
Elderly Biotransformation:
- Deterioration of hepatic enzymes and organ function with age can slow drug metabolism.
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Sex Differences:
- Generally, men metabolize substances like alcohol faster than women.
-
Disease Impact:
- Certain diseases can alter drug metabolism; for example, hepatitis can impair liver function, while cardiac conditions can reduce liver blood flow.
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Genetic Variations:
- Genetic differences influence metabolism rates, such as the presence of slow acetylators; an autosomal recessive trait more common in individuals from Northern Europe and approximately 50% of African American and European American populations in the U.S.
Clearance and Drug Excretion
- Clearance refers to the volume of plasma cleared of a drug through metabolism and excretion per unit time.
- Protein binding of drugs decreases the amount available for glomerular filtration, thus reducing drug clearance and delaying excretion.
Drug Affinity and Tissue Concentration
- Certain drugs, such as alcohol and morphine, may have a strong affinity for specific organs, resulting in prolonged tissue concentration even when plasma levels decline.
Metabolism Enzymes
- Major metabolic enzymes include glucuronyl transferase, dehydrogenase, hydroxylase, and cytochrome P450.
- Non-microsomal enzymes are found in the cytoplasm and mitochondria of organs; examples include esterases, amidase, and hydrolase.
Nutrition's Role in Drug Metabolism
- Endogenous substrates for drug conjugation derive from dietary sources, highlighting the importance of nutrition in regulating drug metabolism.
Conjugation Reactions
- Glucuronide conjugation is the most prevalent and significant conjugation process for drugs, particularly involving phenols and catechols.
- Acetylation involves the enzyme acetyl transferase, predominantly located in Kupffer cells of the liver, where acetic acid is conjugated to drugs via acetyl CoA activation.
Drug Distribution Barriers
- Blood-brain barrier (BBB) allows easy passage for thiopental sodium but does not permit dopamine.
- Placental barrier permits non-ionized drugs with high lipid/water partition coefficients to diffuse to the fetus.
Phase I Reactions
- Oxidation involves the introduction of oxygen or removal of hydrogen atoms, including hydroxylation, dealkylation, or demethylation.
- Example: Pethidine undergoes hydrolysis to form pethidinic acid; similar hydrolysis occurs with atropine and acetylcholine.
- Cytochrome P450 is a family of isoenzymes critical for drug oxidation and reduction.
Cytochrome P450 Enzymes
- Found in gastrointestinal epithelium, lungs, and kidneys.
- Cyp3A4 accounts for over 60% of drugs metabolized by the liver.
Enzyme Induction
- Certain drugs stimulate hepatic drug metabolism, known as enzyme induction.
- Inducers accelerate their own metabolism and that of other drugs.
- Examples of enzyme inducers include phenobarbital, rifampin, phenytoin, carbamazepine, griseofulvin, and compounds found in cigarette smoke.
Acetyl Conjugation
- Acetyl transferase enzyme, crucial for acetylation, is present in the liver's Kupffer cells.
- Acetic acid is activated by CoA to form acetyl CoA, which conjugates to various drugs.
Hepatic Concentration and Biotransformation
- Mepacrine concentration in the liver exceeds plasma levels by over 200 times, indicating significant hepatic uptake.
- Chronic administration can lead to very high concentrations of certain drugs in the liver, similar to iodine accumulation in thyroid tissue.
Types of Biotransformation
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Phase-I Reactions: Involve the conversion of drugs into more polar metabolites, enhancing solubility.
- Example: Salicylic acid is metabolized to gentisic acid.
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Reduction Reactions: Catalyzed by the enzyme reductase; involves modifications like the reduction of azo and nitro compounds.
- Example: Prontosil is reduced to sulfonamide.
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Hydrolysis: Metabolism process for esters and amines, facilitated by esterases and amidases found in plasma and liver.
- Process involves adding water to split drug molecules.
Variations in Drug Metabolism
-
Fetal and Neonatal Biotransformation:
- Vulnerable to drug toxicity due to under-developed liver and metabolizing enzymes.
- Poorly developed blood-brain barrier increases vulnerability to drug effects, potentially leading to hyperbilirubinemia and encephalopathy.
- Immature kidneys may alter drug excretion and contribute to jaundice.
-
Elderly Biotransformation:
- Age-related deterioration of hepatic enzymes and organ function can affect drug metabolism.
-
Gender Differences:
- Metabolic rates vary, with men typically metabolizing substances like alcohol more rapidly than women.
-
Disease Impact:
- Certain health conditions can impair drug metabolism; examples include hepatitis and cardiac issues leading to reduced liver blood flow.
-
Genetic Differences:
- Variations such as slow acetylators, an autosomal recessive trait, are predominantly seen in populations from northern latitudes and among certain racial groups in the U.S.
Drug Distribution and Binding
- Active concentration is the fraction of a drug that is unbound, crucial for diffusion from plasma to the site of action.
- High protein-binding drugs, such as phenylbutazone, exhibit prolonged action due to reduced diffusion.
- Drugs with low protein binding, like thiopental sodium, have a shorter duration of action.
Drug Metabolism (Biotransformation)
- Drug metabolism refers to bodily changes in drug molecules, crucial for eliminating drugs from the body.
- First-pass metabolism occurs as drugs cross the intestines or are processed by the liver, affecting drug efficacy (e.g., nitroglycerin).
- Some drugs can be inactivated before absorption (e.g., penicillin).
- Enzymes responsible for drug metabolism include microsomal enzymes located in the smooth endoplasmic reticulum of the liver, kidney, and gastrointestinal tract.
Variations in Drug Metabolism
-
Fetuses and Neonates:
- Vulnerable to drug toxicity due to underdeveloped liver and metabolic enzymes.
- Poorly developed blood-brain barrier increases susceptibility to adverse effects.
- Risks of hyperbilirubinemia leading to encephalopathy.
- Immature kidneys affect drug excretion and contribute to jaundice.
-
Elderly:
- Decline in hepatic enzymes and organ function reduces drug metabolism efficiency.
-
Gender Differences:
- Men tend to metabolize drugs faster than women (example: alcohol).
-
Diseases Impacting Metabolism:
- Conditions such as hepatitis or cardiac issues can reduce blood flow to the liver, impairing drug metabolism.
- Pulmonary diseases can also affect the efficiency of drug processing.
-
Genetic Factors:
- Genetic variations can lead to differences in metabolism rates, such as slow acetylators, primarily seen in individuals from high northern latitudes and among 50% of black and white populations in the US.
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Description
This quiz explores physiological barriers to drug distribution, including the Blood-Brain Barrier and the Placental Barrier. It also covers variations in drug metabolism, particularly in fetal and neonatal biotransformation. Test your understanding of how these factors influence drug therapy and safety.