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Questions and Answers
What is a consequence of inhibiting drug metabolism over an extended period?
What is a consequence of inhibiting drug metabolism over an extended period?
Which phase of drug metabolism involves the addition of hydroxyl groups?
Which phase of drug metabolism involves the addition of hydroxyl groups?
Which of the following routes is NOT primarily associated with drug elimination by the body?
Which of the following routes is NOT primarily associated with drug elimination by the body?
How do Phase II metabolic reactions increase drug polarity?
How do Phase II metabolic reactions increase drug polarity?
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Which process is involved in the renal elimination of drugs?
Which process is involved in the renal elimination of drugs?
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What primarily determines the rate at which a drug leaves the bloodstream to enter tissues?
What primarily determines the rate at which a drug leaves the bloodstream to enter tissues?
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Why does thiopental produce a short duration of action after intravenous administration?
Why does thiopental produce a short duration of action after intravenous administration?
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How does capillary permeability influence drug distribution?
How does capillary permeability influence drug distribution?
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What characterizes capillaries in the blood-brain barrier?
What characterizes capillaries in the blood-brain barrier?
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Which factor is most likely to prevent a drug from entering the central nervous system?
Which factor is most likely to prevent a drug from entering the central nervous system?
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What should occur for a large neutral amino acid to be transported into the brain?
What should occur for a large neutral amino acid to be transported into the brain?
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What is the effect of high hydrophobicity on drug distribution?
What is the effect of high hydrophobicity on drug distribution?
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Which of the following is NOT a factor influencing drug distribution?
Which of the following is NOT a factor influencing drug distribution?
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What primarily prevents ionized or polar drugs from entering the CNS?
What primarily prevents ionized or polar drugs from entering the CNS?
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How do hydrophobic drugs primarily cross biological membranes?
How do hydrophobic drugs primarily cross biological membranes?
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What is the major drug-binding protein in plasma?
What is the major drug-binding protein in plasma?
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What effect does binding to plasma proteins have on drug activity?
What effect does binding to plasma proteins have on drug activity?
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What happens to the free-drug concentration when a bound drug dissociates from albumin?
What happens to the free-drug concentration when a bound drug dissociates from albumin?
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What is a characteristic of hydrophilic drugs in relation to cell membranes?
What is a characteristic of hydrophilic drugs in relation to cell membranes?
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What occurs when two drugs compete for binding to plasma albumin?
What occurs when two drugs compete for binding to plasma albumin?
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What effect do drugs like phenobarbital and rifampin have on CYP isozymes?
What effect do drugs like phenobarbital and rifampin have on CYP isozymes?
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What is the impact of hypoalbuminemia on drug levels in the plasma?
What is the impact of hypoalbuminemia on drug levels in the plasma?
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Which of the following is a consequence of increased drug metabolism through CYP isozymes?
Which of the following is a consequence of increased drug metabolism through CYP isozymes?
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What is a common mechanism by which drugs inhibit CYP isozyme activity?
What is a common mechanism by which drugs inhibit CYP isozyme activity?
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Which drug is a potent inhibitor of multiple CYP isozymes responsible for warfarin metabolism?
Which drug is a potent inhibitor of multiple CYP isozymes responsible for warfarin metabolism?
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Which substance can induce CYP1A2, affecting the metabolism of amitriptyline and warfarin?
Which substance can induce CYP1A2, affecting the metabolism of amitriptyline and warfarin?
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What is a potential consequence of taking a CYP inhibitor like erythromycin with another medication?
What is a potential consequence of taking a CYP inhibitor like erythromycin with another medication?
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Which of the following is NOT a common CYP inhibitor?
Which of the following is NOT a common CYP inhibitor?
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What is the result of increased biotransformations of drugs via CYP isozymes?
What is the result of increased biotransformations of drugs via CYP isozymes?
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What defines Class I drugs in relation to their binding to albumin?
What defines Class I drugs in relation to their binding to albumin?
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Which drug is considered a Class I drug under standard classifications?
Which drug is considered a Class I drug under standard classifications?
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What is a major consequence of administering a Class II drug to a patient already taking a Class I drug?
What is a major consequence of administering a Class II drug to a patient already taking a Class I drug?
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How are lipophilic drugs typically transformed during metabolism?
How are lipophilic drugs typically transformed during metabolism?
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Which organ is primarily responsible for drug metabolism?
Which organ is primarily responsible for drug metabolism?
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What happens to warfarin when a sulfonamide is administered?
What happens to warfarin when a sulfonamide is administered?
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What does the term 'induction' refer to in the context of cytochrome P450 enzymes?
What does the term 'induction' refer to in the context of cytochrome P450 enzymes?
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Pro-drugs must undergo what process to become active?
Pro-drugs must undergo what process to become active?
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Study Notes
Drug Distribution
- Drug distribution is the reversible movement of a drug from the bloodstream into the interstitial fluid and/or cells of tissues.
- Factors affecting drug delivery from plasma to interstitial fluid:
- Blood flow to the tissue
- Capillary permeability
- Drug's hydrophobicity
- Binding to plasma and tissue proteins
Blood Flow
- Blood flow to tissues varies, influenced by the unequal distribution of cardiac output.
- Higher blood flow to the brain, liver, and kidneys compared to skeletal muscle and adipose tissue.
- Differences in blood flow influence the duration of drug effects, like the short duration of thiopental hypnosis.
- High blood flow and high lipid solubility of thiopental allows rapid CNS entry and anesthesia induction.
Slower Distribution to Skeletal Muscle and Adipose Tissue
- Slower distribution to skeletal muscle and adipose tissue decreases plasma concentration and returns consciousness.
- Redistribution is a phenomenon with various compounds with similar properties.
Capillary Permeability
- Capillary permeability is influenced by the structure and chemical nature of the drug.
- Capillaries in the brain are continuous, lacking slit junctions, differing from the liver and spleen with their large, discontinuous capillaries and exposed basement membranes.
- Lipid-soluble drugs readily permeate the CNS, while charged or polar drugs face barriers due to the tight junctions.
Blood-Brain Barrier
- For drugs to enter the brain, they must pass through the CNS endothelial cells or be actively transported.
- Lipid-soluble drugs readily cross, while ionized drugs or polar substances are impeded.
- The specific transporter carries levodopa into the brain.
- The blood-brain barrier is critical for protecting the brain from many substances.
Drug Structure
- Hydrophobic drugs readily cross cell membranes due to a uniform electron distribution and lack of charge.
- Hydrophilic drugs, with their uneven electron distribution and charge, must use slit junctions for passage.
- High blood flow directly influences the distribution of hydrophobic drugs.
Binding of Drugs to Plasma Proteins
- Reversible binding to plasma proteins sequesters drugs in an inactive form in the vascular compartment, slowing transfer.
- Binding is non-selective regarding chemical structure.
- Plasma albumin is the principal binder and acts as a reservoir.
- If free drug concentration decreases, bound drug dissociates to maintain a relatively constant free-drug level.
Binding of Class I and Class II Drugs to Albumin
- Class I drugs have a lower dose than binding sites, resulting in a low dose/capacity ratio with high bound-drug fraction. These are common in clinical use.
- Class II drugs have a much higher dose than binding sites, resulting in a high dose/capacity ratio with a high free-drug fraction.
Competition for Binding Between Drugs
- When two drugs with high affinity for albumin are administered, they compete for binding sites.
- Drug dose relative to albumin binding capacity dictates the resultant free drug/bound drug ratio and subsequent pharmacological effect.
Drug Metabolism
- Drugs are often eliminated through biotransformation or excretion in the urine or bile.
- The liver primarily metabolizes lipophilic drugs into polar, excretable products.
- Some drugs, known as pro-drugs, are initially inactive and must be metabolized into their active forms.
- Biotransformation occurs in phases I and II, with phase I modifying drugs and phase II conjugating to increase polarity.
P450 Isozymes
- P450 isozymes are a group of liver enzymes crucial for drug metabolism.
Drug Metabolism and Induction/Inhibition of P450
- Certain drugs like phenobarbital, rifampin, and carbamazepine increase CYP isozyme synthesis increasing drug metabolism, which can lead to decreased drug levels.
- Inhibitors of certain isozymes block drug metabolism, which can cause elevated plasma levels and increase risk of adverse drug effects.
Consequences of Increased Drug Metabolism
- Increased drug metabolism can decrease drug activity if the metabolite is inactive.
- Increased drug activity if the metabolite is active.
- Decreased therapeutic effects.
- Polycyclic aromatic hydrocarbons (air pollutants) can induce CYP1A. This affects drugs like amitriptyline and warfarin, decreasing their therapeutic concentration.
Drug Elimination
- Drug removal from the body occurs via various routes, but primarily through the kidneys into the urine.
- Other routes include the intestines, bile, and lungs.
- Renal elimination involves glomerular filtration, proximal tubular secretion, and distal tubular reabsorption.
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Description
This quiz explores the principles of drug distribution within the body, focusing on how various factors impact drug delivery from the bloodstream to tissues. Key topics include the effects of blood flow, capillary permeability, and the implications of drug hydrophobicity. Test your understanding of how these factors influence drug effects and duration.
