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Questions and Answers
What is the primary purpose of the Leuprolide acetate implant?
What is the primary purpose of the Leuprolide acetate implant?
Which of the following describes absolute bioavailability?
Which of the following describes absolute bioavailability?
What does bioavailability specifically measure?
What does bioavailability specifically measure?
Which of the following factors is known to affect drug absorption?
Which of the following factors is known to affect drug absorption?
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What characterizes relative bioavailability?
What characterizes relative bioavailability?
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How long does the Leuprolide acetate implant supply last?
How long does the Leuprolide acetate implant supply last?
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Which method is likely to have an impact on drug absorption?
Which method is likely to have an impact on drug absorption?
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What is the significance of the area under the curve (AUC) in pharmacokinetics?
What is the significance of the area under the curve (AUC) in pharmacokinetics?
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Which characteristic defines extensive metabolizers (EM)?
Which characteristic defines extensive metabolizers (EM)?
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Which of the following drugs would likely be poorly metabolized by poor metabolizers (PM)?
Which of the following drugs would likely be poorly metabolized by poor metabolizers (PM)?
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What is the primary characteristic of ultra metabolizers (UM)?
What is the primary characteristic of ultra metabolizers (UM)?
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Which of the following is associated with NAT2 polymorphism?
Which of the following is associated with NAT2 polymorphism?
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Which genetic characteristic significantly affects the metabolism of isoniazid?
Which genetic characteristic significantly affects the metabolism of isoniazid?
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How does smoking influence drug metabolism?
How does smoking influence drug metabolism?
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Which substances are categorized as enzyme inhibitors?
Which substances are categorized as enzyme inhibitors?
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Which demographic group generally has a higher rate of rapid acetylation?
Which demographic group generally has a higher rate of rapid acetylation?
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Which enantiomer of ibuprofen is over 100-fold more potent as a cyclooxygenase I inhibitor?
Which enantiomer of ibuprofen is over 100-fold more potent as a cyclooxygenase I inhibitor?
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What is the relationship between (R)-methadone and (S)-methadone in terms of affinity for the µ opioid receptor?
What is the relationship between (R)-methadone and (S)-methadone in terms of affinity for the µ opioid receptor?
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Which statement about the bioavailability of verapamil is true?
Which statement about the bioavailability of verapamil is true?
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Which enantiomer of fluoxetine has a higher clearance rate?
Which enantiomer of fluoxetine has a higher clearance rate?
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What is a characteristic of drug complexes regarding membrane permeability?
What is a characteristic of drug complexes regarding membrane permeability?
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What is a primary reason a chelate of tetracycline with calcium has poor absorption?
What is a primary reason a chelate of tetracycline with calcium has poor absorption?
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How does the dissolution rate of anhydrous ampicillin compare to its hydrated form?
How does the dissolution rate of anhydrous ampicillin compare to its hydrated form?
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What role do cyclodextrins play in drug formulation?
What role do cyclodextrins play in drug formulation?
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Which statement is true regarding the physical and chemical properties of a drug?
Which statement is true regarding the physical and chemical properties of a drug?
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What is the impact of the route of administration on bioavailability?
What is the impact of the route of administration on bioavailability?
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Which enantiomer of citalopram is significantly more potent as a serotonin reuptake inhibitor?
Which enantiomer of citalopram is significantly more potent as a serotonin reuptake inhibitor?
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What aspect of drug formulation does complex formation alter?
What aspect of drug formulation does complex formation alter?
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What is an effect of reduced hepatic first-pass metabolism on the bioavailability of (R)-verapamil?
What is an effect of reduced hepatic first-pass metabolism on the bioavailability of (R)-verapamil?
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Study Notes
Drug Metabolism
- Biotransformation, one of two elimination methods, converts drugs into less active, inactive, less toxic or non-toxic, and water-soluble forms for easier excretion.
- Active forms of drugs that require metabolization are called prodrugs.
- Prodrugs are converted into active forms by the body—for instance, enalapril to enalaprilat
- Metabolism is a critical process that reduces the activity of drugs and eliminates them from the body.
- Important organs for drug metabolism include the liver, gastrointestinal tract (GIT), blood (plasma), kidneys, lungs, placenta, and aqueous humor of the eyes.
Exemption to Metabolism
- Some drugs do not need to be metabolized to become active.
- Some drugs are metabolized to become toxic instead of active.
- The metabolism of some drugs results in a non-toxic, inactive form.
Drug Biotransformation Reactions
- These are chemical reactions that convert drugs into more polar forms, including oxidation, reduction, and hydrolysis.
Phases of Drug Metabolism
- Phase 1 reactions include non-synthetic reactions like functionalization (addition or unmasking of functional groups), involving oxidation, reduction, and hydrolysis.
- Phase 2 reactions are synthetic conjugation reactions that involve addition of a polar conjugate to the drug molecule.
- Examples of phase 2 reactions include glucoronidation, sulfation, conjugation with glycine or glutamine, and methylation.
Enzyme Inducers and Inhibitors
- Enzyme inducers stimulate the activity or production of enzymes, thus impacting drug metabolism.
- Enzyme inhibitors decrease the activity of metabolizing enzymes, thus impacting drug metabolism.
- Examples of enzyme inducers include phenobarbital, phenytoin, rifampicin, carbamazepine, chronic alcoholism, charcoal-broiled foods, St. John's wort, and smoking.
- Examples of enzyme inhibitors include metronidazole, macrolides, erythromycin, disulfiram, diazepam, valproic acid, vancomycin, isoniazid, clarithromycin, chloramphenicol, cimetidine, ketoconazole, fluconazole, miconazole, saquinavir, grapefruit juice, allopurinol, and acute alcoholism.
Genetic Polymorphism
- Genetic variability affects enzyme expression and production, thus potentially influencing how individuals metabolize drugs.
- Two important enzymes affected are N-acetyltransferase 2 (NAT2) and cytochrome P450 2C19 (CYP2C19).
First Pass Effect/Metabolism
- A phenomenon where drugs are metabolized initially following absorption, but before reaching systemic circulation.
- The significance of the first pass effect is its ability to decrease oral bioavailability of a drug.
Phases of Drug Metabolism
- Phase 1 reactions include oxidative reactions (involving cytochrome P450 enzymes).
- Phase 2 reactions include glucoronidation, sulfation, and conjugation, making drugs more water-soluble for excretion.
Reduction, Oxidation, Hydrolysis
- Reduction reactions (e.g., nitro reduction, carbonyl reduction, azo dye reduction).
- Oxidation reactions.
- Hydrolysis reactions (e.g., hydrolysis of esters, amides).
Glucoronidation
- A major phase 2 reaction that uses glucuronosyl transferase (GluCAT) to add glucuronic acid.
- Poorly developed in neonates.
Other Phase 2 Reactions
- Acetylation (involving N-acetyltransferase).
- Sulfate conjugation.
- Methylation.
- Amino acid conjugation (glycine, glutamine conjugation).
Glutathione and Mercapturic Acid Conjugation
- Reactions with electrophilic oxygen intermediates (important for detoxification).
- Important for detoxification of reactive oxygen species.
Enzyme Inducers/Inhibitors
- Stimulate enzyme activity/production (e.g., drugs, smoking).
- Decrease enzyme activity/production (e.g., grapefruit juice).
Genetic Polymorphism
- Variations in enzyme expression/production due to genetics.
Drug Elimination and Clearance (Excretion)
- Renal excretion (glomerular filtration, tubular secretion, tubular reabsorption).
- Biliary excretion (recycling/enterohepatic recirculation).
- Excretion via lungs, skin, mammary glands, and GIT.
GFR (Glomerular Filtration Rate)
- Rate at which substances are filtered through the kidneys.
- Important for drug elimination.
- Assessed using methods like creatinine clearance and MDR method.
- Low GFR implies poorer kidney function and drug retention.
Biopharmaceutics Considerations of Drug Design
- The study of the in vitro impact of drugs and their products on drug delivery to the body.
- Discusses important aspects to consider like the physical and chemical properties of the drug, route of administration, desired effects, toxicologic properties, safety of excipients, effect of excipients on drug delivery, and manufacturing.
- Includes considerations for dosage form, excipients, physicochemical properties, and route of drug administration.
Rate-Limiting Steps in Drug Absorption
- This focuses on the steps in drug absorption crucial for bioavailability, including disintegration, dissolution, and absorption of the drug across cell membranes.
- The factors affecting dissolution rate include the physical and chemical nature of the drug, excipients, and manufacturing techniques.
Dissolution
- A process where a solid dissolves into a given solvent
- Key considerations include the rate of dissolution, which is important for systemic absorption and bioavailability of solid dosage forms.
- This process occurs in the body after the solid disintegration of the drug.
- Key factors include drug properties, excipients, and manufacturing methods.
Noyes-Whitney Equation
- A mathematical equation useful for calculating the rate of drug dissolution.
- Key variables (drug diffusion constant, surface area, stagnant layer thickness) define the rate of dissolution.
Absorption
- Permeation across the gut wall (lipid membrane)- critical for bioavailability.
- Partition coefficient (K oil/water) affects drug absorption across the membrane.
- An increase in temperature increases kinetic energy of molecules and enhances the rate of drug dissolution.
Physicochemical Properties
- Particle size and surface area, impacting dissolution and absorption.
- Partition coefficient and extent of ionization, affecting drug solubility and membrane permeability.
- Salt formation, commonly used to improve drug solubility.
- Polymorphism, drug forms existing in multiple crystalline structures.
Hydrates
- Solvated/anhydrous forms of certain drugs have different dissolution rates.
Complex Formation
- Associations between drugs and other molecules, altering physical and chemical characteristics (e.g., chelates, affecting solubility).
Drug Product and Drug Delivery Systems
- Types of dosage forms (solutions, suspensions, capsules, compressed tablets) and their impact on drug bioavailability.
Coating
- Sugar coating, film coating, and enteric coating.
- Purpose: protection, appearance, masking taste/odor, and altering drug release.
Enteric Coating
- Coating to protect from gastric acids; release in the intestines
- Minimize gastric irritation or inactivation within the stomach.
Modified-Release Dosage Forms
- Drug formulations that alter drug release rate or timing
- Different types exist including controlled-release, sustained-release, and long-acting systems.
Transdermal DDS
- Drug delivery systems applied to the skin for systemic absorption.
Targeted (site-specific) DDS
- Deliver drugs specifically to target sites through encapsulation or bonding to molecules.
Inserts, Implants, and Devices
- Drug delivery methods offering controlled drug release for localized or systemic effects.
- Examples include implants and inserts.
Bioavailability
- The rate and extent to which the active ingredient is absorbed from a drug product into the systemic circulation.
- Factors that affect bioavailability include the physicochemical properties of the drug and excipients, production manufacturing methods, and the route of administration.
- Strategies for determining bioavailability are essential to understand and optimize drug performance in vivo and relate it to clinical use. This relates to how the drug acts in the body.
Bioavailability Studies
- Techniques for evaluating the rate and extent of drug absorption.
- Involves methods like calculating area under the curve (AUC), determining peak plasma concentration (Cmax), and time of peak concentration (Tmax).
- Blood or plasma samples and urine samples are collected over time after administration.
- Various techniques used include Planimeter, counting squares, cutting weighing, and Trapezoidal Rule for calculating AUC.
Relative Bioavailability
- The ratio of the bioavailability of a test drug to a reference drug, used to calculate a ratio.
Absolute Bioavailability
- The fraction of an administered dose that reaches systemic circulation after extravascular administration.
Bioequivalence
- A specialized type of relative bioavailability study used to assess the performance of one drug product (test) to another one (reference).
Equivalence
- Refers to a comparative relationship between two or more substances, which may refer to how similar their characteristics or function.
Pharmaceutical Equivalents
- Drug products containing the same active ingredients, and identical strength/concentration in the same dosage form, via the same route of administration.
Pharmaceutical Alternatives
- Drug products containing the same therapeutic moiety (active component), but are different salts, esters, complexes, dosage forms, or strengths.
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Description
Test your knowledge on the pivotal concepts of pharmacokinetics and drug metabolism, including bioavailability, drug absorption, and genetic factors influencing drug metabolism. This quiz covers essential questions related to the Leuprolide acetate implant and various metabolic profiles. Challenge yourself to deepen your understanding in this critical area of pharmacology!
