59 Questions
What percentage of drugs in clinical usage today are oxidised by CYP3A4?
50%
What is the primary factor that influences drug formulation when drugs cross biological membranes?
Route of administration
What is the base unit for glucuronidation in Phase II metabolism?
Glucose-1-phosphate
Why are basic or acidic groups useful in drug design?
They improve drug absorption by facilitating crossing of biological membranes
What is the effect of depleting the GSH pool in glutathione conjugation?
Toxicity
What is the primary application of the theory of volume of distribution (VD)?
Identifying the best therapy for a given condition
What is the effect of metabolism on drugs?
Can either activate or inactivate drugs
What is the primary focus of the learning outcome 'Explain how drugs cross the biological membrane by different routes and how this influences drug formulation'?
The mechanisms of drug transport across biological membranes
What determines the net effect of renal excretion?
The balance of glomerular filtration, tubular secretion, and tubular re-absorption
What is the primary benefit of applying knowledge of drug design modification to improve penetration of target tissue?
Optimized therapy for a given condition
What is the effect of multiple metabolic pathways on a single molecule?
Can either activate or inactivate the molecule
What is the primary reason why ADME is important in drug development?
It informs the development of effective and safe drug therapies
What is the primary factor that determines the glomerular filtration rate?
Hydrostatic pressure gradient
What is the significance of the fraction of unbound drug in plasma in glomerular filtration?
It changes the rate of renal elimination
What is the primary route of excretion for drugs that are not excreted via the kidney?
Bile and then intestine
What is the consequence of changes in the amount of plasma protein on glomerular filtration?
It changes the rate of renal elimination
What is the result of displacement from plasma protein by other drugs?
Changes in the fraction of unbound drug in plasma
What is the characteristic of the hepatic sinusoids that enables first-pass metabolism?
Nutrient-rich environment
What is the primary function of the hepatic vein in the context of drug metabolism?
To receive blood from the portal vein
What type of transport is involved in liver excretion, as well as kidney route?
Transporter mediated
What is the term for the process by which a drug is reabsorbed into the bloodstream after being excreted into the bile?
Enterohepatic circulation
Which of the following references is NOT a primary source for the topic of drug metabolism?
Allocati et al.(2018) Glutathione transferases: substrates, inihibitors and pro-drugs in cancer and neurodegenerative diseases.
What is the term for the process by which the liver metabolizes a drug before it reaches the systemic circulation?
First-pass effect
Which of the following is a type of enzyme involved in drug metabolism?
Glutathione S-transferases
What is the primary mechanism by which P-glycoprotein confers multidrug resistance in tumors?
By actively effluxing anticancer drugs out of tumor cells
What is the primary application of nanomedical solutions in the context of multidrug resistance?
Targeted delivery of anticancer drugs to tumor cells
What is the primary role of CYP3A4 enzymes in the context of drug metabolism?
Phase I metabolism of xenobiotics
What is the primary consequence of multidrug resistance in cancer therapy?
Decreased efficacy of chemotherapy
What is the primary factor contributing to the development of multidrug resistance in cancer cells?
Overexpression of P-glycoprotein
Plasma binding protein increases pharmacological action of a drug
False
Increased volume of distribution indicates poor distribution of a drug throughout the body
False
The primary role of albumin is to maintain colloidal osmotic pressure of blood
True
Metabolism of a drug always leads to its activation
False
Glomerular filtration rate is the primary factor that determines the rate of excretion of a drug
False
Displacement of other drugs from plasma protein can increase their pharmacological action
True
Rifampicin is a substrate of CYP3A4.
True
Glucuronidation requires inorganic sulphate.
False
Glutathione conjugation is a high energy conjugate reaction.
False
The liver is a minor route of excretion.
False
Tubular re-absorption is a passive process.
False
GST conjugates can be used as a marker of efficacy.
False
Dr. Sarah Bailey's consultation hours are on Wednesdays from 14.00 - 15.00.
False
The theory of volume of distribution (VD) is used to identify the best therapy.
True
Basic or acidic groups are not useful for improving drug absorption.
False
The primary focus of the learning outcome is on the excretion of drugs.
False
ADME is not important in drug development.
False
Lipid solubility does not affect drug absorption or efficacy.
False
Glomerular filtration is a dependent process.
False
Large molecules (Mr >300) are often eliminated via the kidney.
False
Changes in the fraction of unbound drug can affect the rate of liver elimination.
False
Expression levels of drug transporters can change rapidly due to genetic mutations.
False
The hepatic sinusoids are responsible for first-pass metabolism due to their characteristic of being nutrient-poor.
False
Liver excretion is a type of active transport.
False
Enterohepatic recirculation is a process where the liver excretes the drug and it gets reabsorbed into the bloodstream.
True
The hepatic artery is responsible for carrying oxygenated blood to the liver.
True
Glutathione S-transferases are involved in antioxidant defenses and xenobiotic metabolism.
True
The Erythromycin Breath Test is used to predict the volume of distribution of a drug.
False
P-glycoprotein is involved in the efflux of drugs from the liver.
True
The portal vein carries deoxygenated blood from the liver to the heart.
False
Study Notes
CYP3A4 - Phase I Enzyme
- CYP3A4 is the most abundant P450 in human liver, responsible for oxidizing >50% of drugs in clinical usage today
- It has a very wide substrate specificity
- Rifampicin and Metyrapone are examples of inducers of CYP3A4
Phase II Metabolism
- Phase II metabolism involves the addition of conjugates to increase hydrophilicity, resulting in a more polar metabolite that can be easily excreted
- Glucuronic acid, sulphate, amino acids, glutathione, and acetylation are common conjugates used in Phase II metabolism
- Multiple different enzymes are involved in Phase II metabolism, and these enzymes are inducible
- The goal of Phase II metabolism is to produce a metabolite that is polar enough to be excreted via urine or faeces
Types of Phase II Metabolism
Glucuronidation
- Glucuronidation is a high-energy conjugate reaction that uses glucose-1-phosphate as a base unit
- It is a ubiquitous and highly expressed reaction in most species, except for cats
- Glucuronidation is important in enterohepatic recirculation
Sulphation
- Sulphation has a similar substrate profile to glucuronidation
- It is a high-energy conjugate reaction that may be limited by inorganic sulphate availability
- Sulphation has a large variability in species and tissue expression
Glutathione Conjugation
- Glutathione conjugation involves the tripeptide Glu-Gly-Cys (GSH)
- It is a low-energy conjugate reaction that is specific for halides and epoxides
- GSH is ubiquitous and has a good conjugate pool, with both cytosolic and membrane-bound variants
- Depletion of GSH pool can lead to toxicity, and GST conjugates may be a marker of toxicity
Multiple Possibilities
- Metabolism can occur at multiple sites within one molecule
- Metabolism can activate or deactivate drugs, and the balance determines the outcome
- Cyclophosphamide is an example of a drug that is activated in the liver, resulting in no adverse effects in the GIT
Excretion
- Excretion is the final clearance of drugs from the body
- It is also the final chance to keep drugs in the body
- Metabolism, kidney, liver, and GI tract are the major routes of excretion
- Lungs, sweat, lacrimal fluid, and milk are minor routes of excretion
Renal Excretion
- Renal excretion is the net effect of glomerular filtration, tubular secretion, and tubular re-absorption
- These processes are both passive and active
- Multiple factors affect the rate of elimination, including kidney integrity, molecule size, urine flow, urine pH, and other compounds being excreted
Glomerular Filtration
- Glomerular filtration is a passive process dependent on hydrostatic pressure gradient
- It has a size cut-off, allowing small molecules (most drugs) to pass through while removing plasma proteins
- Filtration is dependent on the free drug in plasma, and changes in the fraction of unbound drug may change the rate of renal elimination
Liver Excretion
- Liver excretion is generally the route for drugs not excreted via the kidney
- Large molecules (Mr >300) are often excreted via the liver, and may involve glucuronide conjugates
- Liver excretion can be transporter-mediated, and may involve enterohepatic recirculation
Learn about the basics of drug metabolism, including routes of administration, crossing biological membranes, and influencing factors. Understand the pros and cons of different routes and how they affect drug metabolism.
Make Your Own Quizzes and Flashcards
Convert your notes into interactive study material.
Get started for free
