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Questions and Answers
What is the driving force behind the distribution of a drug?
What is the driving force behind the distribution of a drug?
- Osmotic pressure
- Electrochemical gradient
- Concentration gradient (correct)
- Active transport
Which factor does NOT significantly influence the onset of a drug's pharmacological action?
Which factor does NOT significantly influence the onset of a drug's pharmacological action?
- Rate of metabolism (correct)
- Distribution
- Concentration at the site of action
- Drug dosage
Why is the distribution of a drug not uniform throughout the body?
Why is the distribution of a drug not uniform throughout the body?
- All tissues absorb the drug equally
- Different tissues have varying blood flow rates (correct)
- Different tissues have different absorption capacities
- Organs with higher density absorb more drug
What does the term 'apparent volume of distribution' refer to?
What does the term 'apparent volume of distribution' refer to?
What is the effect of doubling the drug dose on its concentration in the plasma?
What is the effect of doubling the drug dose on its concentration in the plasma?
By which process does a drug distribute until equilibrium is established?
By which process does a drug distribute until equilibrium is established?
Which of the following drugs is given as an example of one with a large volume of distribution?
Which of the following drugs is given as an example of one with a large volume of distribution?
Why are drugs with a large volume of distribution more difficult to remove by dialysis?
Why are drugs with a large volume of distribution more difficult to remove by dialysis?
What might be required for drugs with a large volume of distribution to achieve a quick onset of action?
What might be required for drugs with a large volume of distribution to achieve a quick onset of action?
Which of the following best describes the process of redistribution for highly lipid-soluble drugs?
Which of the following best describes the process of redistribution for highly lipid-soluble drugs?
Which property does NOT affect the tissue permeability of a drug?
Which property does NOT affect the tissue permeability of a drug?
Which statement about lipid solubility and redistribution of drugs is TRUE?
Which statement about lipid solubility and redistribution of drugs is TRUE?
What does the Volume of Distribution (Vd) quantify in pharmacokinetics?
What does the Volume of Distribution (Vd) quantify in pharmacokinetics?
Why is the Volume of Distribution referred to as 'Apparent Volume'?
Why is the Volume of Distribution referred to as 'Apparent Volume'?
Which of the following is a rate-limiting step in drug distribution?
Which of the following is a rate-limiting step in drug distribution?
What is the primary site of drug absorption mentioned in the diagram?
What is the primary site of drug absorption mentioned in the diagram?
Which of the following would not be directly involved in the initial steps of drug distribution?
Which of the following would not be directly involved in the initial steps of drug distribution?
According to the content, which of the following best describes the final step indicated in the diagram?
According to the content, which of the following best describes the final step indicated in the diagram?
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Study Notes
Drug Distribution
- Drug distribution is a passive process driven by the concentration gradient between blood and extravascular tissues.
- Distribution occurs through diffusion of the free drug until equilibrium is established.
Pharmacological Action
- Pharmacological action depends on drug concentration at the site of action.
- Distribution plays a significant role in the onset, intensity, and duration of action.
Drug Distribution is not Uniform
- Distribution is not uniform throughout the body due to different tissue rates and extents of receiving the drug from plasma.
Dose Proportionality
- A simple relationship exists between the amount of drug in the body (A) and drug concentration in plasma, described by A = VC.
- The proportionality constant is called the "Apparent volume of distribution."
- Doubling the dose usually results in a doubling of drug concentration in plasma, known as dose proportionality.
Volume of Distribution
- The apparent volume of distribution (Vd) can be much more than the actual body volume.
- Widely distributed drugs include Digoxin, Imipramine, Phenobarbitone, and morphine analogues (e.g., Codine).
- These drugs are difficult to remove by dialysis if toxicity occurs.
- Drugs with low Vd and low plasma protein bound are good candidates for dialysis.
Clinical Significance of Large Volume of Distribution
- A loading dose may be required initially for a quick onset of action.
- Example: Chloroquine used in Malaria, with a 600mg stat loading dose followed by 300mg after 8hrs and then 300mg daily for the next 2 days.
Redistribution
- Highly lipid-soluble drugs initially distribute to organs with high blood flow (e.g., brain, heart, kidney).
- Later, less vascular but more bulky tissues (muscles, fat) take up the drug, causing plasma concentration to fall.
- Redistribution can terminate drug action if the site of action is in a highly perfused organ.
- Greater lipid solubility leads to faster redistribution.
Factors Affecting Drug Distribution
- Tissue permeability of the drug affects distribution, influenced by physiochemical properties like molecular size, pKa, and o/w Partition coefficient.
Steps in Drug Distribution
- Permeation of free or unbound drug into interstitial extracellular fluid
- Permeation of drug present in extracellular fluid into intracellular fluid (rate-limiting step)
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