Podcast
Questions and Answers
Passive movement along a concentration gradient is known as facilitated diffusion.
Passive movement along a concentration gradient is known as facilitated diffusion.
False
The blood-brain barrier allows water-soluble small molecules to pass through easily.
The blood-brain barrier allows water-soluble small molecules to pass through easily.
False
Pharmacokinetics refers to the effects of the body on the drug.
Pharmacokinetics refers to the effects of the body on the drug.
True
Active transport processes require ATP to move substances against a concentration gradient.
Active transport processes require ATP to move substances against a concentration gradient.
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The U.S. Food & Drug Administration (FDA) recognizes less than 100 distinct routes of administration.
The U.S. Food & Drug Administration (FDA) recognizes less than 100 distinct routes of administration.
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Bioavailability refers to the concentration of a drug in urine after excretion.
Bioavailability refers to the concentration of a drug in urine after excretion.
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Topical administration involves applying a substance directly to the skin or mucosal surfaces.
Topical administration involves applying a substance directly to the skin or mucosal surfaces.
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The four key processes involved in pharmacokinetics are Absorption, Distribution, Metabolism, and Elimination.
The four key processes involved in pharmacokinetics are Absorption, Distribution, Metabolism, and Elimination.
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First pass metabolism refers to the initial breakdown of a drug in the stomach before it enters the bloodstream.
First pass metabolism refers to the initial breakdown of a drug in the stomach before it enters the bloodstream.
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Sublingual administration involves placing a substance under the tongue for rapid absorption.
Sublingual administration involves placing a substance under the tongue for rapid absorption.
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Passive diffusion is a method by which drugs can cross cellular membranes.
Passive diffusion is a method by which drugs can cross cellular membranes.
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Intramuscular injections are best for slower absorption and prolonged effects.
Intramuscular injections are best for slower absorption and prolonged effects.
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The apparent volume of distribution, Vd, measures the total clearance of a drug from the body.
The apparent volume of distribution, Vd, measures the total clearance of a drug from the body.
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Organic anion transporters (OATs) facilitate transport against a concentration gradient.
Organic anion transporters (OATs) facilitate transport against a concentration gradient.
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Metabolism and excretion together make up the process of elimination in pharmacokinetics.
Metabolism and excretion together make up the process of elimination in pharmacokinetics.
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Drug absorption is the transfer of a drug from the general circulation to various organs of the body.
Drug absorption is the transfer of a drug from the general circulation to various organs of the body.
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Bioavailability is defined as the fraction of the administered dose that reaches the systemic circulation as intact drug.
Bioavailability is defined as the fraction of the administered dose that reaches the systemic circulation as intact drug.
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The AUC with oral dosing is always higher than with IV dosing.
The AUC with oral dosing is always higher than with IV dosing.
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Propranolol has a bioavailability of 25% when taken orally.
Propranolol has a bioavailability of 25% when taken orally.
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The fractional availability (F) has units associated with its measurement.
The fractional availability (F) has units associated with its measurement.
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First pass metabolism affects how much drug reaches systemic circulation.
First pass metabolism affects how much drug reaches systemic circulation.
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AUC is the area under the curve representing the total drug exposure in plasma over time.
AUC is the area under the curve representing the total drug exposure in plasma over time.
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Bioavailability is irrelevant to the effects of the drug.
Bioavailability is irrelevant to the effects of the drug.
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Intravenous administration has a bioavailability of 50%.
Intravenous administration has a bioavailability of 50%.
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Oral administration is the most common but faces many barriers to entry into systemic circulation.
Oral administration is the most common but faces many barriers to entry into systemic circulation.
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First-pass metabolism occurs after drugs are absorbed and before they reach systemic circulation.
First-pass metabolism occurs after drugs are absorbed and before they reach systemic circulation.
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Intravenous administration ensures that 0% of the drug is bioavailable.
Intravenous administration ensures that 0% of the drug is bioavailable.
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Weak acids and bases do not undergo pH partitioning during absorption.
Weak acids and bases do not undergo pH partitioning during absorption.
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Food generally slows down the absorption rate of orally administered drugs.
Food generally slows down the absorption rate of orally administered drugs.
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Sublingual administration bypasses first-pass metabolism.
Sublingual administration bypasses first-pass metabolism.
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Highly polar or ionized compounds are well absorbed in the gut.
Highly polar or ionized compounds are well absorbed in the gut.
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Drugs can be absorbed through the skin by intradermal administration.
Drugs can be absorbed through the skin by intradermal administration.
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The intravenous route of administration avoids first pass metabolism.
The intravenous route of administration avoids first pass metabolism.
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Sublingual administration provides a rapid onset of action.
Sublingual administration provides a rapid onset of action.
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Transdermal administration is suitable for all types of drugs.
Transdermal administration is suitable for all types of drugs.
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The area under the curve (AUC) measures the total amount of drug that enters the body after administration.
The area under the curve (AUC) measures the total amount of drug that enters the body after administration.
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Bioavailability refers to the proportion of a drug that is absorbed into the systemic circulation.
Bioavailability refers to the proportion of a drug that is absorbed into the systemic circulation.
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Maximum safe concentration (MSC) is reached immediately after oral administration.
Maximum safe concentration (MSC) is reached immediately after oral administration.
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Intramuscular administration has controlled release properties.
Intramuscular administration has controlled release properties.
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First pass metabolism increases the concentration of the drug in systemic circulation.
First pass metabolism increases the concentration of the drug in systemic circulation.
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The inhalation route of administration is exclusively for localized drug effects.
The inhalation route of administration is exclusively for localized drug effects.
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The drug plasma concentration should remain below the minimum effective concentration (MEC) for effectiveness.
The drug plasma concentration should remain below the minimum effective concentration (MEC) for effectiveness.
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Pharmacodynamics refers to the effects of the body on the drug.
Pharmacodynamics refers to the effects of the body on the drug.
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The primary role of absorption in pharmacokinetics is the transfer of a drug from the general circulation to various organs of the body.
The primary role of absorption in pharmacokinetics is the transfer of a drug from the general circulation to various organs of the body.
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Elimination is the process that includes both metabolism and excretion of drugs from the body.
Elimination is the process that includes both metabolism and excretion of drugs from the body.
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Bioavailability is defined specifically as the percentage of a drug that is lost during metabolism.
Bioavailability is defined specifically as the percentage of a drug that is lost during metabolism.
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First pass metabolism occurs after drugs are absorbed but before they reach systemic circulation.
First pass metabolism occurs after drugs are absorbed but before they reach systemic circulation.
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The clearance rate (Cl) measures the volume of distribution (Vd) of a drug in the body.
The clearance rate (Cl) measures the volume of distribution (Vd) of a drug in the body.
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Passive diffusion requires energy input to occur.
Passive diffusion requires energy input to occur.
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Intravenous administration ensures that the drug is completely absorbed into the systemic circulation.
Intravenous administration ensures that the drug is completely absorbed into the systemic circulation.
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The FDA recognizes over 100 distinct routes of administration for drugs.
The FDA recognizes over 100 distinct routes of administration for drugs.
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Transdermal administration can only provide local effects.
Transdermal administration can only provide local effects.
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Carrier-mediated processes transport substances against a concentration gradient.
Carrier-mediated processes transport substances against a concentration gradient.
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Bioavailability (F) can reach up to 100% for intravenous administration.
Bioavailability (F) can reach up to 100% for intravenous administration.
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First pass metabolism decreases the concentration of the drug in systemic circulation.
First pass metabolism decreases the concentration of the drug in systemic circulation.
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Active transport is a process that does not require ATP.
Active transport is a process that does not require ATP.
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Intravenous administration provides a rapid onset of action.
Intravenous administration provides a rapid onset of action.
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The fractional availability (F) of a drug is expressed as a percentage and does not have any units.
The fractional availability (F) of a drug is expressed as a percentage and does not have any units.
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Topical administration is used when a systemic effect is desired.
Topical administration is used when a systemic effect is desired.
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Bioavailability is only relevant for intravenous routes of drug administration.
Bioavailability is only relevant for intravenous routes of drug administration.
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Sublingual administration bypasses first-pass metabolism.
Sublingual administration bypasses first-pass metabolism.
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Oral administration of drugs typically results in higher bioavailability than intravenous administration.
Oral administration of drugs typically results in higher bioavailability than intravenous administration.
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Inhalation is the least effective route for achieving high drug concentrations in the bloodstream.
Inhalation is the least effective route for achieving high drug concentrations in the bloodstream.
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The percentage of bioavailability for a drug taken orally can be as low as 0%.
The percentage of bioavailability for a drug taken orally can be as low as 0%.
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Intramuscular injections are best for slower absorption and prolonged effects.
Intramuscular injections are best for slower absorption and prolonged effects.
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First pass metabolism increases the effective concentration of the drug in systemic circulation.
First pass metabolism increases the effective concentration of the drug in systemic circulation.
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The area under the curve (AUC) represents the total drug exposure in plasma over time.
The area under the curve (AUC) represents the total drug exposure in plasma over time.
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Organic cation transporters (OCTs) facilitate transport down a concentration gradient.
Organic cation transporters (OCTs) facilitate transport down a concentration gradient.
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AUC (area under the curve) is used to represent total drug exposure in plasma over time.
AUC (area under the curve) is used to represent total drug exposure in plasma over time.
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Oral administration is the fastest route of drug administration.
Oral administration is the fastest route of drug administration.
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P-glycoproteins are a common cause of drug resistance.
P-glycoproteins are a common cause of drug resistance.
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The percentage bioavailability of a drug is always higher when taken sublingually compared to orally.
The percentage bioavailability of a drug is always higher when taken sublingually compared to orally.
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Maximum safe concentration (MSC) is reached immediately after intravenous administration.
Maximum safe concentration (MSC) is reached immediately after intravenous administration.
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Sublingual administration can bypass first-pass metabolism.
Sublingual administration can bypass first-pass metabolism.
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The bioavailability of propranolol is higher when taken orally compared to when it is administered intravenously.
The bioavailability of propranolol is higher when taken orally compared to when it is administered intravenously.
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Adrenaline is typically administered via oral routes.
Adrenaline is typically administered via oral routes.
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Highly polar or ionized compounds are well absorbed in the gut.
Highly polar or ionized compounds are well absorbed in the gut.
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First pass metabolism increases the amount of drug that reaches systemic circulation.
First pass metabolism increases the amount of drug that reaches systemic circulation.
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Drugs administered intravenously have 100% bioavailability.
Drugs administered intravenously have 100% bioavailability.
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Sublingual administration of drugs can help avoid first-pass metabolism.
Sublingual administration of drugs can help avoid first-pass metabolism.
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Aspirin is poorly absorbed in the stomach because it is charged.
Aspirin is poorly absorbed in the stomach because it is charged.
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Intradermal administration has the shortest absorption time of all parenteral routes.
Intradermal administration has the shortest absorption time of all parenteral routes.
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Gastric emptying does not affect the total quantity of drug absorbed, only the rate of absorption.
Gastric emptying does not affect the total quantity of drug absorbed, only the rate of absorption.
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Pethidine is well absorbed in the stomach due to its uncharged state.
Pethidine is well absorbed in the stomach due to its uncharged state.
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Absorption refers to the transfer of drug from the site of administration to the general circulation.
Absorption refers to the transfer of drug from the site of administration to the general circulation.
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Elimination consists solely of metabolism of the drug within the liver.
Elimination consists solely of metabolism of the drug within the liver.
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Carrier-mediated processes in drug absorption do not require energy to occur.
Carrier-mediated processes in drug absorption do not require energy to occur.
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The blood-brain barrier allows lipid-soluble molecules to easily cross into the brain.
The blood-brain barrier allows lipid-soluble molecules to easily cross into the brain.
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First pass metabolism enhances the bioavailability of a drug as it enters systemic circulation.
First pass metabolism enhances the bioavailability of a drug as it enters systemic circulation.
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Vd, or apparent volume of distribution, is a critical parameter that assesses the distribution of a drug throughout body tissues.
Vd, or apparent volume of distribution, is a critical parameter that assesses the distribution of a drug throughout body tissues.
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Intravenous administration guarantees that no metabolism or elimination occurs in the systemic circulation.
Intravenous administration guarantees that no metabolism or elimination occurs in the systemic circulation.
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Passive diffusion occurs when drugs move across membranes without energy expenditure, following a concentration gradient.
Passive diffusion occurs when drugs move across membranes without energy expenditure, following a concentration gradient.
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Passive movement along a concentration gradient in drug absorption is known as facilitated transport.
Passive movement along a concentration gradient in drug absorption is known as facilitated transport.
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Organic cation transporters (OCTs) facilitate transport up a concentration gradient without the need for ATP.
Organic cation transporters (OCTs) facilitate transport up a concentration gradient without the need for ATP.
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Subcutaneous administration is more suitable for rapid absorption than intramuscular injections.
Subcutaneous administration is more suitable for rapid absorption than intramuscular injections.
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The U.S. Food & Drug Administration (FDA) recognizes more than 200 distinct routes of administration.
The U.S. Food & Drug Administration (FDA) recognizes more than 200 distinct routes of administration.
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Active transport processes move substances along a concentration gradient using energy.
Active transport processes move substances along a concentration gradient using energy.
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P-glycoproteins are a type of solute carrier transporter (SLC) involved in passive diffusion.
P-glycoproteins are a type of solute carrier transporter (SLC) involved in passive diffusion.
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Enteral administration refers to delivering a substance through routes other than the digestive tract.
Enteral administration refers to delivering a substance through routes other than the digestive tract.
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The absorption of drugs involves their transfer from the systemic circulation to the site of action.
The absorption of drugs involves their transfer from the systemic circulation to the site of action.
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Insulin is a highly polar compound that is well absorbed in the gut.
Insulin is a highly polar compound that is well absorbed in the gut.
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Intravenous administration of drugs ensures 100% bioavailability.
Intravenous administration of drugs ensures 100% bioavailability.
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First pass metabolism occurs in the stomach, preventing drugs from entering the bloodstream.
First pass metabolism occurs in the stomach, preventing drugs from entering the bloodstream.
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Aspirin is absorbed better in the stomach due to its uncharged state.
Aspirin is absorbed better in the stomach due to its uncharged state.
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Pethidine is always well absorbed in the stomach because it is an uncharged compound.
Pethidine is always well absorbed in the stomach because it is an uncharged compound.
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Sublingual administration allows drugs to bypass both the gastrointestinal tract and first pass metabolism.
Sublingual administration allows drugs to bypass both the gastrointestinal tract and first pass metabolism.
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Capsules and tablets must disintegrate for drug absorption to occur effectively.
Capsules and tablets must disintegrate for drug absorption to occur effectively.
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Food intake enhances the absorption rate of orally administered drugs by increasing gastric emptying.
Food intake enhances the absorption rate of orally administered drugs by increasing gastric emptying.
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Transdermal administration is effective for all types of drugs.
Transdermal administration is effective for all types of drugs.
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Bioavailability is the measure of the total amount of drug that enters the body after administration.
Bioavailability is the measure of the total amount of drug that enters the body after administration.
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The inhalation route of administration guarantees localized drug effects.
The inhalation route of administration guarantees localized drug effects.
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Intramuscular administration is known for rapid absorption and a prolonged effect.
Intramuscular administration is known for rapid absorption and a prolonged effect.
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The area under the curve (AUC) is solely related to how quickly a drug is eliminated from the body.
The area under the curve (AUC) is solely related to how quickly a drug is eliminated from the body.
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First pass metabolism significantly increases the availability of a drug in systemic circulation.
First pass metabolism significantly increases the availability of a drug in systemic circulation.
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The maximum safe concentration (MSC) is reached immediately following intravenous administration.
The maximum safe concentration (MSC) is reached immediately following intravenous administration.
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Oral administration of a drug has the highest bioavailability compared to other routes.
Oral administration of a drug has the highest bioavailability compared to other routes.
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Sublingual administration allows drugs to bypass hepatic metabolism and achieve rapid effects.
Sublingual administration allows drugs to bypass hepatic metabolism and achieve rapid effects.
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Diazepam is effectively absorbed intramuscularly in patients who are vomiting.
Diazepam is effectively absorbed intramuscularly in patients who are vomiting.
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The percentage of bioavailability for intravenous administration is always less than 100%.
The percentage of bioavailability for intravenous administration is always less than 100%.
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Bioavailability is a measure that can range from 0% to 100% depending on the route of administration.
Bioavailability is a measure that can range from 0% to 100% depending on the route of administration.
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Propranolol has a higher bioavailability when taken orally compared to when given sublingually.
Propranolol has a higher bioavailability when taken orally compared to when given sublingually.
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First-pass metabolism typically increases the amount of a drug available in systemic circulation.
First-pass metabolism typically increases the amount of a drug available in systemic circulation.
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The AUC for oral dosing is typically lower than for intravenous dosing.
The AUC for oral dosing is typically lower than for intravenous dosing.
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Food intake can enhance the absorption rate of orally administered drugs by modifying their bioavailability.
Food intake can enhance the absorption rate of orally administered drugs by modifying their bioavailability.
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The term 'bioavailability' is synonymous with the concentration of a drug in urine after it has been excreted.
The term 'bioavailability' is synonymous with the concentration of a drug in urine after it has been excreted.
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Sublingual administration allows for a rapid onset of drug effects by circumventing first-pass metabolism.
Sublingual administration allows for a rapid onset of drug effects by circumventing first-pass metabolism.
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Study Notes
Pharmacokinetics vs Pharmacodynamics
- Pharmacokinetics describes the body's action on the drug, including how the drug moves into, around, and out of the body.
- Pharmacodynamics describes the drug's action on the body, specifically how it interacts with the body's systems and processes.
Four Key Processes of Pharmacokinetics (ADME)
- Absorption: The transfer of a drug from the site of administration to the general circulation.
- Distribution: The transfer of a drug from the general circulation into different organs of the body.
- Metabolism: The breakdown of a drug by the body, often by enzymes in the liver.
- Excretion: The removal of a drug from the body, usually through the kidneys in urine, but also through feces, breath, or sweat.
Routes of Administration
- Topical: Applied directly to the site of desired action, for local effects.
- Enteral: Administered via the digestive tract for systemic effects.
- Parenteral: Administered by routes other than the digestive tract for systemic effects.
Oral Administration
- Most common and convenient route.
- Drugs face several barriers to entering the systemic circulation, including:
- Dissolution of the drug.
- Digestive enzymes breaking down the drug.
- First-pass metabolism in the liver.
First-Pass Metabolism
- Occurs when a drug is absorbed from the gastrointestinal tract and passes through the liver before reaching systemic circulation.
- The liver metabolizes the drug, reducing the amount of active drug reaching the bloodstream.
Bioavailability
- The fraction of an administered dose that reaches the systemic circulation as intact drug.
- Bioavailability can be determined by comparing plasma levels of a drug after different routes of administration.
- Drugs administered intravenously (IV) have 100% bioavailability, while other routes have varying bioavailability.
Bioavailability Formula
- % Bioavailability = AUCoral / AUCIV x 100
- Fractional availability = F
- No units, quoted as percentage (e.g., 25%) or decimal (e.g., 0.25)
- Bioavailability influences the effective dose of a drug.
Importance of Bioavailability
- The effective dose of a drug is determined taking bioavailability into account.
- Different routes of administration require different dosages to achieve the same therapeutic effect because of varying bioavailability.
Introduction
- Pharmacokinetics studies drug movement in the body including absorption, distribution, metabolism, and elimination (ADME).
- Pharmacodynamics studies the effects of drugs on the body.
Absorption
- Absorption is the movement of a drug from its site of administration to the general circulation.
- The bioavailability (F) of a drug refers to the fraction of the administered dose that reaches the systemic circulation as intact drug.
Routes of Administration
- Topical: Applied directly where the desired effect is.
- Enteral: Given via the digestive tract.
- Parenteral: Given by routs other than the digestive tract.
- Oral: Most common route, drug absorbed into the bloodstream after passing through the gut, portal vein and liver.
- Intravenous: 100% bioavailability, directly into a vein.
- Sublingual: Avoids first-pass metabolism because it goes directly into systemic circulation.
- Rectal: Avoids first-pass metabolism, but unreliable absorption.
- Transdermal: Used for local effects, but can cause systemic effects.
- Intramuscular: Rapid absorption.
- Inhalation: Rapid and efficient.
First-Pass Metabolism
- The breakdown of a drug by the liver, gut, or intestinal enzymes before reaching the circulation.
- Significant for orally administered drugs, often reducing the amount of drug that reaches the systemic circulation.
Bioavailability (F)
- Determines the dose required for different routes of administration.
- Measured by comparing the area under the curve (AUC) of plasma concentration versus time plots after different routes of administration.
- F is expressed as a percentage or decimal.
- For IV administration: F is 100%.
Factors Affecting Absorption
- Drug structure: highly polar/ionized poorly absorbed; weak acids and bases undergo pH partitioning; peptides broken down by digestive enzymes.
- Formulation: capsules/tablets must disintegrate; modified-release formulations.
- Gastric emptying: delays gastric emptying, slowing absorption rate.
Drug Plasma Concentration vs. Time Plots
- Helps understand the onset and duration of action of a drug.
- Onset of action: The time it takes for a drug's concentration to reach the minimum effective concentration (MEC).
- Duration of action: The time during which the drug concentration remains at or above the MEC.
- Maximum safe concentration (MSC): The highest concentration of a drug that can be achieved without causing adverse effects.
- Area under the curve (AUC): A measure of the total amount of drug entering the body.
Importance of Understanding Pharmacokinetics
- Essential for determining the appropriate dose, route of administration, and frequency of drug administration.
- Enables clinicians to optimize drug therapy to achieve the desired therapeutic effects and minimize adverse effects.
Pharmacokinetics vs. Pharmacodynamics
- Pharmacokinetics: Deals with the movement of drugs within the body which includes how the body affects the drug.
- Pharmacodynamics: Focuses on the drug's effects on the body. This involves the drug's interactions with biological targets and its resulting physiological and biochemical effects.
Four Key Processes of Pharmacokinetics (ADME)
-
Absorption: The transfer of a drug from its administration site to the general circulation.
- Bioavailability (F): Represents the fraction of administered drug that reaches the systemic circulation intact.
-
Distribution: The transfer of a drug from the general circulation to various organs in the body.
- Apparent volume of distribution (Vd): A measure of how much drug distributes in the body.
- Metabolism: The process of altering the drug's structure within the body, often by enzymatic reactions.
-
Excretion: The elimination of the drug and/or its metabolites from the body.
- Clearance (Cl): Measures the volume of plasma cleared of drug per unit time.
- Plasma half-life (t1/2): The time required for the plasma concentration of the drug to decrease by half.
Drug Passage Across Membranes (Absorption Processes)
-
Passive Diffusion: Drugs move across membranes down their concentration gradient. This requires some lipid solubility.
- Movement through pores or ion channels: Water-soluble, small molecules can pass through aquaporins.
- Direct diffusion through the lipid bilayer: Requires the drug to be somewhat lipid-soluble.
-
Carrier-Mediated Processes: Involve specialized transport proteins facilitating drug movement across membranes.
- Solute Carrier Transporters (SLCs): Facilitate transport DOWN a concentration gradient.
- Organic anion transporters (OATs)
- Organic cation transporters (OCTs)
- ATP Binding Cassette Transporters (ABCs): Require ATP for transport.
- P-glycoproteins: A common cause of multidrug resistance.
- Solute Carrier Transporters (SLCs): Facilitate transport DOWN a concentration gradient.
Routes of Administration
- Topical: Direct application of the drug to the desired site for a local effect.
-
Enteral: Given via the digestive tract for a systemic effect.
- Oral (PO): Swallowing the drug.
- Sublingual: Placement under the tongue.
- Rectal: Administration via a suppository or enema.
-
Parenteral: Given by routes other than the digestive tract for a systemic effect.
- Inhalation: Breathing in the drug.
- Injection:
- Intramuscular (IM): Injected into a large muscle mass for faster absorption.
- Subcutaneous (SC/SQ): Injected beneath the skin for a slower, more prolonged effect.
- Intravenous (IV): Injected directly into a vein.
- Intradermal (ID): Injected into the dermis for the slowest absorption, used for allergy tests or local anesthesia.
Oral Administration Considerations
-
Factors influencing drug absorption from the gut:
- Drug structure:
- Highly polar/ionized compounds are poorly absorbed.
- Weak acids and bases undergo pH partitioning.
- Peptides can be broken down by digestive enzymes.
- Formulation:
- Capsules/tablets must disintegrate for release.
- Modified-release formulations adjust drug release.
- Gastric emptying:
- Food generally slows absorption due to delayed gastric emptying and increased gastric acid secretion.
- Fasting or malnutrition also influence absorption.
- Drug structure:
First-Pass Metabolism (Presystemic Metabolism)
- Oral drugs are absorbed from the GI tract, enter the portal vein, and pass through the liver before reaching systemic circulation.
- Many drugs are metabolized in the liver, reducing the amount reaching systemic circulation.
- First-pass metabolism affects the bioavailability of oral drugs.
- Alternative routes of administration (e.g., IV, IM, sublingual) bypass first-pass metabolism.
- Sites of first-pass metabolism:
- Intestinal lumen (digestive enzymes)
- Intestinal wall (MAO)
- Liver (multiple enzymes, including CYP450)
- Lung (MAO, peptidases)
Advantages of Various Routes of Administration
- Oral: Convenient and avoids first-pass metabolism but has a slower onset of action.
- Intravenous: 100% bioavailability, controlled release, rapid onset, but can be less convenient.
- Sublingual: Escapes first-pass metabolism, rapid onset, but not always suitable for all drugs.
- Intramuscular: Avoids first-pass metabolism, controlled release, and a faster onset than oral.
- Transdermal: Avoids first-pass metabolism, slow, controlled release, but expensive with limited applications.
- Per rectum: Avoids first-pass metabolism, slower onset, but less reliable absorption.
- Inhalation: Avoids first-pass metabolism, rapid onset, and suitable for localized effect.
Bioavailability (F)
- The fraction of the administered dose that reaches the systemic circulation as intact drug.
- Bioavailability influences the required dose for different routes of administration.
- Determined by comparing plasma levels of the drug after different routes of administration (e.g., oral, IM) with plasma levels following IV administration.
- Calculated as: % Bioavailability = (AUCoral / AUCIV) x 100
- Fractional availability (F): No units, expressed as a decimal or percentage (e.g., 0.25 or 25%).
- IV administration: 100% bioavailability, other routes: 0 to 100%.
Importance of Bioavailability
- The true dose is not the amount swallowed, but the drug available to exert its effects.
- Example: Propranolol 80mg/day oral (F 25%) vs. Sublingual 40mg (F 63%) vs. IV 20mg (F 100%).
Drug Plasma Concentration vs. Time Plots
- Typical plasma level curve after IV bolus dose: Maximum plasma concentration occurs at time = 0, immediately after dosing.
- Typical plasma level curve after single oral dose: Maximum plasma concentration (Cmax) is reached at a time tmax after administration.
Drug [Plasma] - Time Curve After Oral Administration
- Onset of action: When the plasma level reaches the minimum effective concentration (MEC).
- Duration of action: The time period for which the plasma level is at or above the MEC.
- Maximum safe concentration (MSC): The upper limit of therapeutic range to minimize adverse reactions.
Area Under the Curve (AUC)
- A measure of the total amount of drug entering the body after administration, calculated from a plasma concentration-time curve.
- Units: concentration × time (e.g., mg.hr L−1)
- AUC is higher with IV dosing than with oral dosing, reflecting the full bioavailability of the IV route.
Further Reading
- Pharmacology, Rang, Dale, Ritter, Moore (Section 1, General Principles, Chapter 7: Absorption and distribution of drugs)
- Pharmacokinetics Texts:
- Introduction to Pharmaceutical Sciences: An Integrated Approach
- Merck Manual – Clinical Pharmacology
- Absorption and Bioavailability Videos:
- https://accessmedicine.mhmedical.com
- https://www.youtube.com/watch?v=eya9jR3v7i8 (advanced detail)
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Description
Test your understanding of pharmacokinetics and pharmacodynamics, two crucial concepts in pharmacology. This quiz covers the key processes of pharmacokinetics, including absorption, distribution, metabolism, and excretion, as well as routes of drug administration. Perfect for students in health sciences and pharmacy courses!
