Podcast
Questions and Answers
At which pH does a drug's pKa equal, in terms of ionization and unionization?
At which pH does a drug's pKa equal, in terms of ionization and unionization?
- pH where 75% is ionized and 25% is unionized
- pH where 25% is ionized and 75% is unionized
- pH where 50% is ionized and 50% is unionized (correct)
- pH where all of the drug is ionized
How do weak bases behave in an acidic solution?
How do weak bases behave in an acidic solution?
- They are more unionized
- They have no effect
- They are more ionized (correct)
- They become lipophilic
What is the effect of ionization on a drug's solubility in water?
What is the effect of ionization on a drug's solubility in water?
- Ionization decreases solubility in water
- Ionization makes the drug lipophilic
- Ionization increases solubility in water (correct)
- Ionization has no effect on solubility in water
How does ionization affect a drug's ability to cross the blood-brain barrier (BBB)?
How does ionization affect a drug's ability to cross the blood-brain barrier (BBB)?
What is the effect of ionization on a drug's activity?
What is the effect of ionization on a drug's activity?
How does the hepatic biotransformation of a drug change with ionization?
How does the hepatic biotransformation of a drug change with ionization?
What is the effect of ionization on a drug's renal elimination?
What is the effect of ionization on a drug's renal elimination?
Can an ionized drug diffuse across the placenta?
Can an ionized drug diffuse across the placenta?
What is the main limitation of using half-times to determine the offset of anesthetic drugs?
What is the main limitation of using half-times to determine the offset of anesthetic drugs?
What is the primary factor that affects the ionization of a weak acid or weak base?
What is the primary factor that affects the ionization of a weak acid or weak base?
What happens to a drug that is a weak acid when it is placed in water?
What happens to a drug that is a weak acid when it is placed in water?
What is the term for the process by which a molecule gains a positive or negative charge?
What is the term for the process by which a molecule gains a positive or negative charge?
What is the relationship between pKa and pH?
What is the relationship between pKa and pH?
What is the purpose of considering context sensitive half-times of opioids?
What is the purpose of considering context sensitive half-times of opioids?
What is the significance of the pKa of lidocaine?
What is the significance of the pKa of lidocaine?
What happens to the remaining fraction of a weak acid or weak base when placed in water?
What happens to the remaining fraction of a weak acid or weak base when placed in water?
What happens to a drug when it is released from a protein?
What happens to a drug when it is released from a protein?
Which of the following factors is affected by the extent of plasma protein binding?
Which of the following factors is affected by the extent of plasma protein binding?
Which protein plays the larges role in maintaining plasma oncotic pressure?
Which protein plays the larges role in maintaining plasma oncotic pressure?
Which condition is associated with decreased plasma albumin levels?
Which condition is associated with decreased plasma albumin levels?
Which type of drugs bind to alpha-1 acid glycoprotein?
Which type of drugs bind to alpha-1 acid glycoprotein?
What is the turnaround time of albumin?
What is the turnaround time of albumin?
Which condition is associated with increased plasma albumin levels?
Which condition is associated with increased plasma albumin levels?
Which protein binds to basic drugs?
Which protein binds to basic drugs?
What is the primary assumption of the volume of distribution (Vd)?
What is the primary assumption of the volume of distribution (Vd)?
A drug with a volume of distribution (Vd) of 50 L in a 70 kg patient is likely to be which type of drug?
A drug with a volume of distribution (Vd) of 50 L in a 70 kg patient is likely to be which type of drug?
What is the unit of measurement for the volume of distribution (Vd)?
What is the unit of measurement for the volume of distribution (Vd)?
What is the relationship between the volume of distribution (Vd) and the loading dose required to achieve a given plasma concentration?
What is the relationship between the volume of distribution (Vd) and the loading dose required to achieve a given plasma concentration?
What is the primary factor that determines the volume of distribution (Vd) of a drug?
What is the primary factor that determines the volume of distribution (Vd) of a drug?
What is the plasma volume of a 70 kg patient?
What is the plasma volume of a 70 kg patient?
What is the total body water of a 70 kg patient?
What is the total body water of a 70 kg patient?
A drug with a volume of distribution (Vd) of 20 L in a 70 kg patient is likely to be which type of drug?
A drug with a volume of distribution (Vd) of 20 L in a 70 kg patient is likely to be which type of drug?
The body converts an inactive molecule into a pharmacologically active molecule. What type of molecule?
The body converts an inactive molecule into a pharmacologically active molecule. What type of molecule?
What is the purpose of a phase 2 reaction in drug metabolism?
What is the purpose of a phase 2 reaction in drug metabolism?
What is the term for the process by which a conjugated drug is excreted into the bile, reactivated in the intestine, and then reabsorbed into the systemic circulation?
What is the term for the process by which a conjugated drug is excreted into the bile, reactivated in the intestine, and then reabsorbed into the systemic circulation?
What is the purpose of alkaline phosphatases in the metabolism of fospropofol?
What is the purpose of alkaline phosphatases in the metabolism of fospropofol?
What is the purpose of ATP-dependent carrier proteins in drug metabolism?
What is the purpose of ATP-dependent carrier proteins in drug metabolism?
Which of the following is an example of a conjugation reaction?
Which of the following is an example of a conjugation reaction?
What is the purpose of glucuronic acid in drug metabolism?
What is the purpose of glucuronic acid in drug metabolism?
What type of antagonism is reversible?
What type of antagonism is reversible?
What is the effect of an inverse agonist?
What is the effect of an inverse agonist?
What is the term for the dose that produces the expected clinical response in 50% of the population?
What is the term for the dose that produces the expected clinical response in 50% of the population?
What is the term for the simultaneous administration of two drugs, resulting in an effect greater than the sum of their individual effects?
What is the term for the simultaneous administration of two drugs, resulting in an effect greater than the sum of their individual effects?
What is the effect of a noncompetitive antagonist?
What is the effect of a noncompetitive antagonist?
What is the term for the dose that produces death in 50% of the population?
What is the term for the dose that produces death in 50% of the population?
What is the term for the effect of two drugs given at the same time, where the total effect is equal to the sum of their individual effects?
What is the term for the effect of two drugs given at the same time, where the total effect is equal to the sum of their individual effects?
What is the term for the effect of one drug that enhances the effect of another drug, but has no effect on its own?
What is the term for the effect of one drug that enhances the effect of another drug, but has no effect on its own?
What is the TD50?
What is the TD50?
What is the repentonic index?
What is the repentonic index?
What is chirality?
What is chirality?
What are enantiomers?
What are enantiomers?
What is a racemic mixture?
What is a racemic mixture?
Why is levobupivacaine less cardiotoxic than bupivacaine?
Why is levobupivacaine less cardiotoxic than bupivacaine?
What are R and S enantiomers?
What are R and S enantiomers?
What does the slope of the dose-response curve indicate?
What does the slope of the dose-response curve indicate?
What is the main difference between a full agonist and a partial agonist?
What is the main difference between a full agonist and a partial agonist?
What is the result of continuous administration of an agonist?
What is the result of continuous administration of an agonist?
What is the effect of a competitive antagonist on the dose-response curve of an agonist?
What is the effect of a competitive antagonist on the dose-response curve of an agonist?
What is the difference between an antagonist and an inverse agonist?
What is the difference between an antagonist and an inverse agonist?
What is an example of a full agonist?
What is an example of a full agonist?
What is individual variability in pharmacodynamics?
What is individual variability in pharmacodynamics?
What is the effect of an antagonist on the receptor?
What is the effect of an antagonist on the receptor?
What is the term for the ability of a drug to elicit a given clinical effect?
What is the term for the ability of a drug to elicit a given clinical effect?
What is the significance of the ED50 in a dose-response curve?
What is the significance of the ED50 in a dose-response curve?
What is the result of a right-shifted dose-response curve?
What is the result of a right-shifted dose-response curve?
What is the significance of a left-shifted dose-response curve?
What is the significance of a left-shifted dose-response curve?
What is the term for the study of the effect of a drug on the body?
What is the term for the study of the effect of a drug on the body?
Study Notes
Pharmacokinetics
- The volume of distribution (Vd) describes the relationship between the administered dose of a drug and the resulting plasma concentration.
- Vd is a theoretical measure of how a drug distributes throughout the body, assuming instantaneous distribution and no metabolism or elimination.
- A drug with a Vd that exceeds total body water (> 0.6 L/kg or > 42 L) is assumed to be lipophilic and requires a higher dose to achieve a given plasma concentration (e.g., Propofol).
- A drug with a Vd that is less than total body water (< 0.6 L/kg or < 42 L) is assumed to be hydrophilic and requires a lower dose to achieve a given plasma concentration (e.g., NMB).
Ionization
- Ionization is the process where a molecule gains a positive or negative charge, affecting its ability to pass through cell membranes.
- Weak acids or bases ionize in water, and the degree of ionization depends on the pH of the solution and the pKa of the drug.
- pKa is a constant property of a molecule, while pH is a changeable property of a solution.
Solubility and Pharmacologic Effects
- Ionized molecules are lipophobic and hydrophilic, while non-ionized molecules are lipophilic and hydrophobic.
- Ionized molecules have reduced pharmacologic activity, are more likely to undergo hepatic biotransformation, and are less likely to be eliminated by the kidneys.
- Non-ionized molecules have increased pharmacologic activity, are less likely to undergo hepatic biotransformation, and are more likely to be eliminated by the kidneys.
Plasma Protein Binding
- Only when a drug is released from plasma protein binding can it travel elsewhere in the body.
- The extent of plasma protein binding affects the intensity and duration of drug effect.
- Albumin is the most plentiful plasma protein and primary determinant of plasma oncotic pressure.
- α1-Acid Glycoprotein and Beta-Globulin also bind basic drugs.
Metabolism
- Phase 1 reactions prepare the molecule for a phase 2 reaction, including oxidation, reduction, and hydrolysis.
- Phase 2 reactions conjugate an endogenous, highly polar, water-soluble substrate to the molecule, inactivating the drug and readying it for elimination.
- Phase 3 reactions involve ATP-dependent carrier proteins that transport a drug across a cell membrane.
- Enterohepatic circulation occurs when conjugated compounds are excreted in the bile, reactivated in the intestine, and reabsorbed into the systemic circulation (e.g., Valium and warfarin).
Pharmacodynamics
- Pharmacodynamics explains the effect of drugs on the body.
- The biophase, or effect site, is the specific area of the body where the drug engages its receptor.
Dose-Response Curve
- The dose-response curve illustrates the relationship between the drug dose and its clinical effects.
- Efficacy is the ability of a drug to elicit a given clinical effect.
- Potency is the dose required to achieve a given clinical effect (ED50 and ED90 are measures of potency).
- A left-shifted dose-response curve indicates higher potency and a lower required dose to achieve ED50.
- A right-shifted dose-response curve indicates lower receptor affinity and higher dose required for ED50.
Agonists and Antagonists
- A full agonist instructs the receptor to produce its maximal response.
- A partial agonist is only capable of partially activating a cellular response.
- An antagonist binds to a receptor and prevents an agonist from binding to it.
- Inverse agonist binds to the receptor and causes an opposite effect to that of a full agonist.
Types of Antagonism
- Competitive antagonism is reversible and shifts the dose-response curve for the agonist to the right.
- Noncompetitive antagonism is not reversible and shifts the dose-response curve for the agonist downwards.
Drug Interactions
- Synergism: The effects of two drugs given at the same time are greater than the sum of their individual effects.
- Addition: The effect of two drugs given at the same time are added together.
- Potentiation: The effect of one drug is enhanced by a drug that has no effect on its own.
- Antagonism: The simultaneous administration of one drug negates the effects of the other.
ED50, LD50, and TD50
- ED50 is the dose that produces the expected clinical response in 50% of the population.
- LD50 is the dose that produces death in 50% of the population.
- TD50 is the dose that produces toxicity in 50% of the population.
- Therapeutic index is the ratio between the TD50 and the ED50, a measure of drug safety.
Chirality
- Chirality is the tetrahedral bonding of carbon (carbon binding to 4 different atoms).
- Enantiomers are chiral molecules that are non-superimposable mirror images of each other.
- Receptors that are stereospecific may respond differently to different enantiomers.
- Racemic mixture contains two enantiomers in equal amounts.
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Description
Learn about the volume of distribution, a theoretical measure of how a drug distributes throughout the body, and its relationship with the administered dose and resulting plasma concentration.
