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Questions and Answers
What is the primary route for the excretion of water-soluble substances?
What is the primary route for the excretion of water-soluble substances?
Which of the following processes is involved in renal drug excretion?
Which of the following processes is involved in renal drug excretion?
How does urinary pH influence the reabsorption of drugs?
How does urinary pH influence the reabsorption of drugs?
What type of drugs is typically not filtered in the glomerular filtration process?
What type of drugs is typically not filtered in the glomerular filtration process?
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Which drug excretion route involves the secretion through bile, especially when conjugated?
Which drug excretion route involves the secretion through bile, especially when conjugated?
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What factors mainly determine the degree of ionization of drugs?
What factors mainly determine the degree of ionization of drugs?
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Which type of drugs are absorbed faster in the stomach?
Which type of drugs are absorbed faster in the stomach?
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What happens to acidic drugs in alkaline urine?
What happens to acidic drugs in alkaline urine?
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What characterizes active transport?
What characterizes active transport?
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What type of transporters are ATP-Binding Cassette Transporters (ABC) mainly associated with?
What type of transporters are ATP-Binding Cassette Transporters (ABC) mainly associated with?
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Which statement about drug filtration is correct?
Which statement about drug filtration is correct?
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What is a characteristic feature of facilitative transporters?
What is a characteristic feature of facilitative transporters?
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Which statement correctly describes primary active transporters?
Which statement correctly describes primary active transporters?
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What is the primary factor that influences the movement of drugs from circulation to tissues?
What is the primary factor that influences the movement of drugs from circulation to tissues?
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What is the formula to calculate the Volume of Distribution (Vd)?
What is the formula to calculate the Volume of Distribution (Vd)?
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Which drug has the largest Volume of Distribution?
Which drug has the largest Volume of Distribution?
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How does the Blood Brain Barrier (BBB) affect drug penetration?
How does the Blood Brain Barrier (BBB) affect drug penetration?
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What role does pKa play in drug distribution?
What role does pKa play in drug distribution?
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Which drug is least likely to penetrate the central nervous system due to its properties?
Which drug is least likely to penetrate the central nervous system due to its properties?
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What is the total body fluid volume approximately in liters?
What is the total body fluid volume approximately in liters?
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Which factor does NOT influence the Volume of Distribution?
Which factor does NOT influence the Volume of Distribution?
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What factor does NOT influence the oral route of drug administration?
What factor does NOT influence the oral route of drug administration?
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Which of the following describes first pass metabolism?
Which of the following describes first pass metabolism?
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Which route of administration provides the highest bioavailability?
Which route of administration provides the highest bioavailability?
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What is the primary reason for lower bioavailability in oral drug administration compared to intravenous?
What is the primary reason for lower bioavailability in oral drug administration compared to intravenous?
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What does the area under the curve (AUC) represent in pharmacokinetics?
What does the area under the curve (AUC) represent in pharmacokinetics?
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Which administration route ranks lowest according to the rate of absorption?
Which administration route ranks lowest according to the rate of absorption?
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Which physiological factor can decrease the bioavailability of an orally administered drug?
Which physiological factor can decrease the bioavailability of an orally administered drug?
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What effect does the first pass metabolism have on drug concentration in systemic circulation?
What effect does the first pass metabolism have on drug concentration in systemic circulation?
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What is the formula for calculating the loading dose?
What is the formula for calculating the loading dose?
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In which scenario is monitoring of plasma concentration most useful?
In which scenario is monitoring of plasma concentration most useful?
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Which enzymes are responsible for the phase I oxidation of drugs?
Which enzymes are responsible for the phase I oxidation of drugs?
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What is a consequence of inhibiting CYP 3A4?
What is a consequence of inhibiting CYP 3A4?
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Which type of drugs does NOT typically require monitoring of plasma concentration?
Which type of drugs does NOT typically require monitoring of plasma concentration?
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Which of the following is NOT a phase II metabolism reaction?
Which of the following is NOT a phase II metabolism reaction?
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What can prolong the action of a drug?
What can prolong the action of a drug?
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Which drug type is associated with a significant individual variation in plasma concentration?
Which drug type is associated with a significant individual variation in plasma concentration?
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Which of the following compounds can undergo enterohepatic recirculation?
Which of the following compounds can undergo enterohepatic recirculation?
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What reaction does xanthine oxidase participate in?
What reaction does xanthine oxidase participate in?
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Which drug is primarily metabolized by amidase in the context of hydrolysis?
Which drug is primarily metabolized by amidase in the context of hydrolysis?
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Which factor is critical for glucuronide conjugation in phase II metabolism?
Which factor is critical for glucuronide conjugation in phase II metabolism?
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Which of the following drugs is an inducer of CYP 3A4?
Which of the following drugs is an inducer of CYP 3A4?
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Study Notes
Pharmacokinetics Overview
- Pharmacokinetics is the quantitative study of drug movement in, through, and out of the body
- Intensity of effect depends on drug concentration at the site of action, which is determined by pharmacokinetic properties
- Important to determine route of administration, dose, onset of action, peak action time, duration of action, and frequency of dosing
ADME
- Absorption Absorption is transfer of a drug from its site of administration into the bloodstream
- Distribution Distribution is the passage of a drug from the circulation to the tissue and site of action
- Metabolism Metabolism is the chemical alteration of a drug in the body Aim to convert nonpolar lipid-soluble compounds to polar lipid-soluble compounds to prevent reabsorption in renal tubules
- Excretion Excretion is the elimination of drug or its metabolites from the body
Factors Affecting Drug Absorption
- Drug properties: lipid solubility, molecular weight, polarity
- Blood flow to the absorption site
- Total surface area available for absorption
- Contact time at the absorption surface
- Affinity with special tissue
Routes of Administration
- Topical: depends on lipid solubility; only lipid-soluble drugs penetrate intact skin
- Subcutaneous and intramuscular: drugs directly reach capillaries, pass through capillary endothelium, and reach circulation, faster and more predictable than oral absorption
- Oral: physical properties (physical state, lipid or water solubility), dosage forms (particle size, disintegration time and dissolution rate, formulation-biopharmaceutics), and physiological factors (ionization, pH effect, presence of food and other agents)
First Pass Metabolism
- Before drugs reach systemic circulation, they can be metabolized in the liver or intestine, reducing concentration in systemic circulation
Bioavailability (AUC)
- Bioavailability refers to the rate and extent of absorption of a drug from a dosage form. It is determined by concentration-time curve in blood or by its excretion in urine
- Measured by fraction (F) of administered dose of a drug that reaches systemic circulation unchanged
- Bioavailability of drug injected IV is 100%, but oral bioavailability may be lower due to incomplete absorption or first-pass metabolism in intestinal wall and/or liver
Volume of Distribution (Vd)
- Represents the apparent volume that would be required to contain all the drug in the body if the concentration were the same as in the plasma
- Affected by factors such as lipid solubility, pKa of the drug, affinity for different tissues, blood flow to tissues, disease states, and plasma protein binding
Redistribution
- Highly lipid-soluble drugs distribute to brain, heart, and kidney immediately, followed by muscle and fat tissues
- Redistribution happens when bound drug is released from tissues and distributes to the plasma
Blood-Brain Barrier (BBB)
- A barrier limiting the entry of non-lipid-soluble drugs into the central nervous system
- Only lipid-soluble unionized drugs penetrate and have actions on the CNS
Placental Transfer
- Only lipid-soluble drugs can penetrate the placental barrier
- Placental P-gp serves as limiting factor for hydrophillic drugs
Plasma Protein Binding
- Most drugs bind to plasma proteins (mainly albumin for acidic drugs and a1-glycoprotein for basic drugs)
- Extent of binding depends on different compounds and increasing drug concentration can saturate binding sites
- Clinically significant implications include:
- High PPB drugs are restricted to vascular compartment, low Vd
- PPB fraction is not available for action
- Equilibration between PPB fraction of drug and free molecules
Tissue Storage
- Drugs can accumulate in specific organs or get bound to specific tissue constituents Examples include heart, liver, kidney, thyroid, brain, etc
Biotransformation (Metabolism)
- Chemical alteration of drugs in the body, often converting them into inactive or more polar metabolites
- Aim is to convert non-polar lipid-soluble drugs into polar lipid-soluble compounds to prevent reabsorption in renal tubules
- Required for protection of body from toxic metabolites
- Two phases (Phase I and Phase II)
Phase I Reactions
- Oxidation
- Reduction
- Hydrolysis
- Cyclization
- Decyclization
Phase II Reactions
- Conjugation - most important synthetic reaction
- Glucuronidation
- Acetylation
- Sulfation
- Methylation
Factors Affecting Biotransformation
- Concurrent drug use (induction and inhibition)
- Genetic polymorphisms
- Pollutant influences
- Age
- Pathological status
Enzyme Inhibition and Induction
- Inhibition: one drug can inhibit the metabolism of other drugs if they use the same enzyme or if a drug inhibits one isoenzyme while being a substrate of another isoenzyme
- Induction: drugs can induce the synthesis of metabolizing enzymes
- Rifampicin, phenytoin, and carbmazepine are examples of inducers
Excretion
- Elimination of drug or metabolites from the body
- Principal routes: kidney, biliary, sweat, saliva, milk, pulmonary
Renal Excretion
- Glomerular filtration: filtration of non-protein-bound drugs
- Tubular reabsorption: passive reabsorption of lipid-soluble drugs
- Tubular secretion: active secretion of drugs
Kinetics of Elimination
- First-order kinetics: rate of elimination is directly proportional to drug concentration (constant fraction of drug eliminated per unit time)
- Zero-order kinetics: rate of elimination is constant irrespective of drug concentration
Plasma Half-Life
- Time required for plasma concentration of a drug to reduce to half of its original value
- Important in determining dosing intervals
Target Level Strategy
- Maintains drug concentration within therapeutic range
- Suitable for drugs with narrow therapeutic index and short half-lives
- Uses loading and maintenance doses
Monitoring of Plasma Concentration
- Useful for drugs with a narrow therapeutic index or large individual variations
Summary
- Key concepts include drug transport, absorption, distribution, metabolism, excretion, and elimination kinetics
- Important factors include bioavailability, Vd, and half-life.
Prolongation of Drug Action
- Prolonging absorption
- Increasing plasma protein binding
- Retarding metabolism
- Retarding renal excretion.
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Description
Test your understanding of pharmacokinetics, the study of drug movement in the body. This quiz covers key concepts such as absorption, distribution, metabolism, and excretion, along with factors that influence drug absorption. Perfect for students in pharmacology or related fields.
