p.18
Prodrugs and Their Utility
What is a prodrug?
A prodrug is an inactive compound that, after administration, is metabolized in the body to produce an active drug.
p.10
Renal Elimination of Drugs
What is energy-dependent in drug renal elimination?
Active transport or secretion.
p.10
Renal Elimination of Drugs
What does protein binding prevent in drug elimination?
It prevents glomerular filtration.
p.20
Single Nucleotide Polymorphisms (SNPs)
How can SNPs influence pharmacokinetics?
SNPs can influence drug metabolism, drug transport, and drug targets, affecting drug efficacy and toxicity.
What is first-pass metabolism?
First-pass metabolism is the process by which a drug's concentration is significantly reduced before it reaches systemic circulation.
p.24
Single Nucleotide Polymorphisms (SNPs)
What effect does the OCT1 gene variant have on metformin?
The OCT1 gene variant results in reduced uptake of metformin in the liver.
p.6
P-Glycoprotein and Drug Interactions
What does the activation of P-glycoproteins lead to?
Activation of P-glycoproteins leads to decreased absorption and increased excretion of drugs.
p.14
Cytochrome P450 3A4 Enzyme
How does grapefruit juice affect the bioavailability of felodipine?
It increases the bioavailability.
p.19
Prodrugs and Their Utility
What is one potential use of mitochondria-targeted prodrugs?
They can be used for cellular imaging (fluorescent).
p.18
Prodrugs and Their Utility
Why are prodrugs useful?
Prodrugs are useful because they can improve the bioavailability, solubility, and stability of drugs, reduce side effects, and allow for targeted delivery.
p.6
P-Glycoprotein and Drug Interactions
How do P-glycoproteins affect drug absorption?
P-glycoproteins reduce drug absorption.
p.6
P-Glycoprotein and Drug Interactions
What is the potential benefit of P-glycoprotein modulation at the kidney and intestinal levels?
It can optimize the therapeutic concentration of drugs by balancing absorption and excretion.
p.19
Prodrugs and Their Utility
How can a prodrug be beneficial in terms of stomach degradation and absorption?
It avoids degradation/absorption in the stomach.
p.19
Prodrugs and Their Utility
What is a potential therapeutic application of mitochondria-targeted prodrugs?
They can have anticancer activity.
Which administration routes can bypass first-pass metabolism?
Intravenous (IV), sublingual, and transdermal routes can bypass first-pass metabolism.
p.14
First-Pass Metabolism
Why is CYP3A4 significant for bioavailability?
Due to its high expression and strategic location, CYP3A4 is involved in first-pass metabolism.
p.20
Single Nucleotide Polymorphisms (SNPs)
Provide an example of an SNP influencing drug transport.
An SNP in the ABCB1 gene can alter the activity of P-glycoprotein, impacting the transport and bioavailability of drugs like digoxin.
p.21
Single Nucleotide Polymorphisms (SNPs)
What is a Single Nucleotide Polymorphism (SNP)?
The substitution of a single nucleotide at a specific position in the genome, common in at least 1% of the population.
p.21
Single Nucleotide Polymorphisms (SNPs)
How do SNPs contribute to pharmacokinetic variability?
SNPs can cause differences in how individuals absorb, metabolize, and excrete drugs, leading to pharmacokinetic variability.
p.9
Clinical Relevance of Drug Dosing Adjustments
Why is the clinical relevance of renal elimination important for drug use in different patient populations?
Renal function varies with age, disease states, and concurrent medications, influencing drug dosing and efficacy.
p.9
Clinical Relevance of Drug Dosing Adjustments
Why must concurrent medications be considered in renal drug elimination?
Some medications can compete for renal transport mechanisms or alter renal blood flow, affecting drug clearance.
p.23
Cytochrome P450 3A4 Enzyme
What is an inhibitor of CYP2C19?
Ketoconazole, Fluvoxamine (SSRI), and Moclobemide (MAO-A inhibitor).
p.24
Clinical Relevance of Drug Dosing Adjustments
What is VKORC1 important for?
VKORC1 is important for dose adjustment of warfarin since warfarin has a low therapeutic index.
p.13
Cytochrome P450 3A4 Enzyme
Besides the liver, where else is Cytochrome P450 3A4 (CYP 3A4) expressed?
In the small and large intestines.
p.6
P-Glycoprotein and Drug Interactions
What is the effect of P-glycoproteins on drug excretion?
P-glycoproteins increase drug excretion.
p.14
Cytochrome P450 3A4 Enzyme
What is the effect of inductors like rifampicin on bioavailability?
They reduce bioavailability.
p.20
Single Nucleotide Polymorphisms (SNPs)
How can an SNP affect drug targets?
An SNP in the VKORC1 gene can change the sensitivity of the target enzyme for warfarin, influencing the required dosage for effective anticoagulation.
p.19
Prodrugs and Their Utility
What is an example of a prodrug used for cholesterol management?
Simvastatin (prodrug) is metabolized to Simvastatin-β-hydroxy-carboxylate (active form).
p.9
Renal Elimination of Drugs
What factors influence glomerular filtration in drug elimination?
Molecular size, charge, and plasma protein binding of the drug.
p.21
Single Nucleotide Polymorphisms (SNPs)
Why are SNPs important for personalized medicine?
SNPs can help tailor medical treatments to individual genetic profiles, improving the effectiveness and safety of therapies.
p.5
P-Glycoprotein and Drug Interactions
What is the function of p-glycoproteins?
Efflux of substances and protection from toxicity.
p.25
Single Nucleotide Polymorphisms (SNPs)
What effect does the CYP2C9 polymorphism have on warfarin?
It reduces anticoagulant effect.
p.25
Single Nucleotide Polymorphisms (SNPs)
What is the pharmacokinetic outcome for poor metabolizers of codeine due to the CYP2D6 polymorphism?
Decreased analgesic effect.
p.8
P-Glycoprotein and Drug Interactions
Which opioids are recognized as P-glycoprotein substrates?
Loperamide, Morphine, Methadone, Pentazocine, Fentanyl.
p.20
Single Nucleotide Polymorphisms (SNPs)
Give an example of an SNP affecting drug metabolism.
An SNP in the CYP2C9 gene can affect the metabolism of warfarin, leading to variations in drug response and the risk of bleeding complications.
p.19
Prodrugs and Their Utility
How can prodrugs be targeted for specific therapeutic effects?
They can be targeted, for example, 5-fluorouracil prodrugs can be used for antitumoral effects.
p.21
Single Nucleotide Polymorphisms (SNPs)
What role do SNPs play in drug-related proteins?
SNPs can affect proteins involved in the absorption, metabolism, and excretion of drugs.
p.9
Renal Elimination of Drugs
Which factors affect tubular reabsorption of drugs?
Drug's lipid solubility, ionization, and urine pH.
p.11
Clinical Relevance of Drug Dosing Adjustments
Why do most dosing guidelines not discriminate based on renal clearance except for patients with end-stage renal disease?
Because patients with end-stage renal disease have significantly reduced renal function, which greatly affects drug elimination and dosing requirements.
What is the main organ involved in first-pass metabolism?
The liver is the main organ involved in first-pass metabolism.
p.16
Paracetamol Pharmacokinetics and Overdose
What are the main metabolites of paracetamol?
The main metabolites are sulfate and glucuronide conjugates.
What is the result of a drug being metabolized by the hepatic portal veins?
The drug is partially metabolized before it can reach the systemic circulation, reducing its bioavailability.
p.10
Renal Elimination of Drugs
What influences passive reabsorption of drugs in the kidneys?
Molecular weight of the drugs, lipid solubility, urine flow, and pH.
p.19
Prodrugs and Their Utility
What is one advantage of using a prodrug in terms of first-pass metabolism?
It avoids first-pass metabolism of the active compound.
p.17
Paracetamol Pharmacokinetics and Overdose
What happens to the paracetamol metabolites after conjugation?
They are excreted in the urine.
p.11
Clinical Relevance of Drug Dosing Adjustments
Why should the doses of drugs with 50% or more renal clearance be reduced in patients with renal disease or advanced age?
Because these patients may not be able to efficiently eliminate the drugs, leading to potential toxicity.
p.17
Paracetamol Pharmacokinetics and Overdose
What drug interactions are important to consider with paracetamol?
Phenobarbitone, carbamazepine, phenytoin, and rifampicin.
p.16
Paracetamol Pharmacokinetics and Overdose
What is the primary route of metabolism for paracetamol?
Paracetamol is primarily metabolized in the liver.
p.3
Pharmacokinetics and Bioavailability
What is the systemic circulation fraction of the drug dose?
The systemic circulation fraction of the drug dose is the fraction of the drug dose that reaches the systemic circulation.
p.8
P-Glycoprotein and Drug Interactions
Which β-Adrenoceptor antagonists are P-glycoprotein substrates?
Bunitrolol, Carvedilol, Celiprolol, Talinolol.
p.8
P-Glycoprotein and Drug Interactions
Name some antitumor agents that are P-glycoprotein substrates.
Doxorubicin, Daunorubicin, Vinblastine, Vincristine, Actinomycin D, Docetaxel, Etoposide, Imatinib.
p.7
P-Glycoprotein and Drug Interactions
Which antibiotics are P-glycoprotein substrates?
Erythromycin, Tetracycline, Rifampin, and Levofloxacin.
p.12
Cytochrome P450 3A4 Enzyme
Where is the cytochrome P450 3A4 (CYP 3A4) enzyme found?
The CYP 3A4 enzyme is primarily found in the liver and intestines.
p.24
Single Nucleotide Polymorphisms (SNPs)
What is the consequence of a reduced function OATP1B1 (SLC01 B1 gene) variant on simvastatin?
It leads to reduced intake of simvastatin by the liver, increasing plasma concentrations and the risk of myopathy by 2-12 fold.
p.4
P-Glycoprotein and Drug Interactions
Where is P-glycoprotein commonly located in the body?
P-glycoprotein is commonly located in the intestines, liver, kidneys, and blood-brain barrier.
p.4
P-Glycoprotein and Drug Interactions
Can you give some examples of drugs that are substrates, inhibitors, or inducers of P-glycoprotein?
Examples include substrates like digoxin and cyclosporine, inhibitors like verapamil and ketoconazole, and inducers like rifampin and St. John's Wort.
p.17
Paracetamol Pharmacokinetics and Overdose
Name three clinical conditions that can affect paracetamol metabolism.
Alcoholism, chronic hepatic disease (e.g., viral hepatitis), and malnutrition.
p.11
Clinical Relevance of Drug Dosing Adjustments
What parameters are typically used in dosing guidelines for patients with renal impairment?
Estimates of renal function (creatinine), clinical and biochemical measures, and measured drug concentrations.
p.3
Pharmacokinetics and Bioavailability
How does first-pass metabolism affect bioavailability?
First-pass metabolism reduces the bioavailability of a drug by metabolizing part of the drug dose before it reaches the systemic circulation.
p.5
P-Glycoprotein and Drug Interactions
How do p-glycoproteins contribute to the blood-testis barrier?
They help in the efflux of substances to protect the testis.
p.8
P-Glycoprotein and Drug Interactions
What are common therapeutic agents that are substrates of P-glycoprotein?
Antiacids, β-Adrenoceptor antagonists, Immunosuppressants, Diuretics, Antibiotics, Opioids, Antiemetic, Cardiac drugs/Antiarrhythmics, Antitumor agents, Steroids, Protease inhibitors, Others like colchicine and ivermectin.
p.25
Single Nucleotide Polymorphisms (SNPs)
How does the polymorphism in N-acetyltransferase affect procainamide and hydralazine?
Increased risk of the lupus syndrome in slow acetylators.
p.7
P-Glycoprotein and Drug Interactions
Which opioids are P-glycoprotein substrates?
Loperamide, Domperidone, and Morphine.
p.18
Prodrugs and Their Utility
Can you give an example of a prodrug?
An example of a prodrug is codeine, which is metabolized in the body to produce morphine.
p.24
Single Nucleotide Polymorphisms (SNPs)
How do VKORC1 variants affect warfarin metabolism?
VKORC1 variants can either decrease or increase the metabolism of warfarin.
p.4
P-Glycoprotein and Drug Interactions
What type of transporter is P-glycoprotein?
P-glycoprotein is an ABC-transporter.
p.19
Prodrugs and Their Utility
What is a prodrug?
An inactive compound that, after administration, is metabolized to a pharmacologically active drug.
p.17
Paracetamol Pharmacokinetics and Overdose
What two pathways produce non-toxic metabolites of paracetamol?
Glucuronide and sulfate pathways.
p.9
Clinical Relevance of Drug Dosing Adjustments
How does age affect renal drug elimination?
Elderly patients often have reduced renal function, requiring dosage adjustments.
p.16
Paracetamol Pharmacokinetics and Overdose
How is paracetamol absorbed in the body?
Paracetamol is rapidly absorbed from the gastrointestinal tract.
p.3
Pharmacokinetics and Bioavailability
What anatomical feature in the ileum enhances drug absorption compared to the stomach?
The enormous absorptive surface area of the villi and microvilli in the ileum enhances drug absorption compared to the stomach.
p.5
P-Glycoprotein and Drug Interactions
What is the role of p-glycoproteins in enterocytes?
They efflux substances from intestinal epithelial cells to the intestinal lumen.
p.25
Single Nucleotide Polymorphisms (SNPs)
What is a common effect of the HERG (KCNH2) and KCNE2 polymorphisms on drugs like sotalol?
Increased risk of arrhythmias.
p.7
P-Glycoprotein and Drug Interactions
Name two antiacids that are P-glycoprotein substrates.
Cimetidine and Ranitidine.
p.1
Pharmacokinetics and Bioavailability
What are the four main processes involved in pharmacokinetics?
Absorption, distribution, metabolism, and genetics.
Why is first-pass metabolism pharmacokinetically significant?
Because it can greatly reduce the bioavailability of a drug, affecting its efficacy and required dosage.
p.10
Renal Elimination of Drugs
What type of drugs are independent of protein binding in renal elimination?
Non-lipid soluble (more polar) drugs.
p.13
Cytochrome P450 3A4 Enzyme
Which organs prominently express Cytochrome P450 3A4 (CYP 3A4)?
Liver, gallbladder, and pancreas.
p.12
Cytochrome P450 3A4 Enzyme
What is the importance of CYP 3A4 for drug bioavailability?
CYP 3A4 is important for drug bioavailability because it metabolizes a large proportion of drugs, affecting their clearance and systemic availability.
p.4
P-Glycoprotein and Drug Interactions
What role does P-glycoprotein play in drug absorption?
P-glycoprotein plays an important role in drug absorption by actively transporting drugs out of cells.
p.4
P-Glycoprotein and Drug Interactions
What is the pharmacokinetic significance of the simultaneous intake of several drugs that are substrates, inhibitors, or inducers of P-glycoprotein?
The simultaneous intake can lead to altered drug absorption, distribution, and excretion, affecting drug efficacy and toxicity. For example, inhibitors can increase the absorption of substrates, leading to potential toxicity, while inducers can decrease the absorption, reducing drug efficacy.
p.19
Prodrugs and Their Utility
What is an example of a prodrug and its active form for anti-inflammatory purposes?
Prednisone (prodrug) is metabolized to Prednisolone (active form).
p.9
Renal Elimination of Drugs
What are the main processes involved in the renal elimination of drugs?
Glomerular filtration, tubular secretion, and tubular reabsorption.
p.15
P-Glycoprotein and Drug Interactions
Name three anaesthetic drugs that have a high risk of interaction with grapefruit juice.
Alfentanil, Fentanyl, Amiodarone
p.9
Renal Elimination of Drugs
How does urine pH affect drug elimination?
It can alter drug ionization, affecting reabsorption and excretion rates.
p.15
P-Glycoprotein and Drug Interactions
Which type of drugs generally have a high risk of interaction with grapefruit juice?
(Examples: Statins, Immunosuppressants, Antidepressants)
p.16
Paracetamol Pharmacokinetics and Overdose
What happens to paracetamol in case of an overdose?
In overdose, paracetamol is metabolized by cytochrome P450 enzymes to a toxic metabolite called NAPQI.
p.23
Cytochrome P450 3A4 Enzyme
What is an inhibitor of CYP2C9?
Fluconazol and Amiodarone.
p.23
Cytochrome P450 3A4 Enzyme
What is an inductor of CYP2C19?
Rifampicine, St. John's wort (Perikon).
p.13
Cytochrome P450 3A4 Enzyme
Where is Cytochrome P450 3A4 (CYP 3A4) primarily expressed?
In the endoplasmic reticulum.
p.10
Renal Elimination of Drugs
How does urine pH affect drug excretion?
Acidic urine leads to more excretion of basic drugs.
p.6
P-Glycoprotein and Drug Interactions
What happens when P-glycoproteins are inhibited?
Inhibition of P-glycoproteins increases drug absorption and decreases excretion.
p.17
Paracetamol Pharmacokinetics and Overdose
What is the toxic metabolite produced from paracetamol?
NAPQI (N-acetyl-p-benzoquinone imine).
p.22
Cytochrome P450 3A4 Enzyme
In which population can 'hyper-extensive metabolizers' due to the CYP2D6 gene make up to 20% of the population?
Some African populations.
p.11
Clinical Relevance of Drug Dosing Adjustments
Why is renal function estimation important in drug dosing?
It helps identify patients who may need shorter dose intervals or smaller dose amounts due to high or low clearance rates.
p.16
Pharmacokinetics and Bioavailability
What is pharmacokinetics?
Pharmacokinetics is the study of how a drug is absorbed, distributed, metabolized, and excreted in the body.
Which route of administration bypasses first-pass metabolism?
Intravenous administration bypasses first-pass metabolism.
p.5
P-Glycoprotein and Drug Interactions
How do p-glycoproteins function in tumors?
They contribute to drug resistance by effluxing chemotherapy agents.
What happens to drugs administered orally in terms of metabolism?
Drugs administered orally are subjected to first-pass metabolism in the gut and liver, which can reduce the amount of active drug reaching the bloodstream.
p.8
P-Glycoprotein and Drug Interactions
List some steroids that are P-glycoprotein substrates.
Dexamethasone, Methylprednisolone, Progesterone, Hydrocortisone, Cortisol, Corticosterone.
p.8
P-Glycoprotein and Drug Interactions
What are some other agents that act as P-glycoprotein substrates?
Colchicine, Phenothiazines, Ivermectin.
p.7
P-Glycoprotein and Drug Interactions
List two inducers of P-glycoprotein.
Rifampicin and St John's wort.
p.24
Single Nucleotide Polymorphisms (SNPs)
What effect does the OCT2 gene variant have on metformin?
The OCT2 gene variant results in reduced uptake of metformin in the kidneys.
p.20
Single Nucleotide Polymorphisms (SNPs)
What is a Single Nucleotide Polymorphism (SNP)?
A Single Nucleotide Polymorphism (SNP) is a variation in a single nucleotide that occurs at a specific position in the genome, where each variation is present to some degree within a population.
p.14
Cytochrome P450 3A4 Enzyme
How do inhibitors such as protease inhibitors (used in HIV treatment) affect bioavailability?
They increase bioavailability.
p.20
Single Nucleotide Polymorphisms (SNPs)
Why is it important to consider SNPs in pharmacotherapy?
Considering SNPs can help personalize medicine, optimizing drug efficacy and minimizing adverse drug reactions based on individual genetic variability.
p.17
Paracetamol Pharmacokinetics and Overdose
What is the antidote for paracetamol overdose and what does it replenish?
N-acetylcysteine, which replenishes glutathione.
p.11
Clinical Relevance of Drug Dosing Adjustments
What are examples of drugs with an intermediate therapeutic index that require careful dosing in renal impairment?
Acyclovir and related antivirals, allopurinol, atenolol, dabigatran, sitagliptin, gabapentin, pregabalin, low molecular weight heparins, metformin, and morphine-6-glucuronide.
p.15
P-Glycoprotein and Drug Interactions
List the anti-cancer drugs with a high risk of interaction with grapefruit juice.
Dasatinib, Everolimus, Nilotinib, Pazopanib, Sunitinib, Vandetanib
What is first-pass metabolism?
First-pass metabolism is the process by which a drug is partially metabolized before it reaches the bloodstream.
p.5
P-Glycoprotein and Drug Interactions
What role do p-glycoproteins play in hepatocytes?
They transport substances to canals that lead to the gallbladder.
p.5
P-Glycoprotein and Drug Interactions
What is the role of p-glycoproteins in the blood-brain barrier?
They efflux substances to protect the brain parenchyma.
p.8
P-Glycoprotein and Drug Interactions
Identify some P-glycoprotein inhibitors.
Ranitidine, Verapamil, Valspodar (PSC), Ketoconazole, Rifampin, Domperidone, Mibefradil, Ondansetron, Asunaprevir, Paclitaxel, Doxorubicin, Daunorubicin, Vinblastine, Vincristine, Docetaxel, Etoposide, Imatinib, Amprenavir, Indinavir, Nelfinavir, Saquinavir, Ritonavir, Itraconazole, Phenothiazines, St John's wort.
p.25
Single Nucleotide Polymorphisms (SNPs)
How does the G6PD polymorphism affect the response to antimalarials?
Increased risk of hemolysis.
p.7
P-Glycoprotein and Drug Interactions
List three immunosuppressants that are P-glycoprotein substrates.
Cyclosporine A, Sirolimus, and Tacrolimus.
p.17
Paracetamol Pharmacokinetics and Overdose
What occurs during a paracetamol overdose?
The glucuronide pathway is saturated, large amounts of NAPQI are produced, and liver reserves of glutathione are depleted.
p.11
Clinical Relevance of Drug Dosing Adjustments
Which types of drugs require particular attention to dosing adjustments in patients with renal impairment?
Drugs with a narrow or intermediate therapeutic index.
p.5
P-Glycoprotein and Drug Interactions
Where are p-glycoproteins physiologically important?
Hepatocytes, blood-testis barrier, placenta, tumors, enterocytes.
p.16
Cytochrome P450 3A4 Enzyme
Which enzymes are involved in the metabolism of paracetamol?
Cytochrome P450 enzymes, particularly CYP2E1, CYP1A2, and CYP3A4.
p.16
Paracetamol Pharmacokinetics and Overdose
What is NAPQI?
NAPQI is a toxic metabolite formed during the metabolism of paracetamol in overdose situations.
p.5
P-Glycoprotein and Drug Interactions
How do p-glycoproteins function in renal tubular cells?
They efflux substances into the urine for excretion.
p.23
Cytochrome P450 3A4 Enzyme
What is an inductor of CYP2C9?
Rifampicine and St. John's wort (Perikon).
p.7
P-Glycoprotein and Drug Interactions
What are two calcium channel blockers that are P-glycoprotein substrates?
Diltiazem and Mibefradil.
p.9
Renal Elimination of Drugs
What is the role of tubular secretion in renal drug elimination?
Actively transports drugs from blood into the renal tubules.
p.25
Single Nucleotide Polymorphisms (SNPs)
What is the impact of the CYP2C19 polymorphism on omeprazole?
Enhanced cure rate of Helicobacter pylori.
p.8
P-Glycoprotein and Drug Interactions
Name some immunosuppressants that are substrates of P-glycoprotein.
Cyclosporine A, Sirolimus, Tacrolimus.
p.7
P-Glycoprotein and Drug Interactions
Name two inhibitors of P-glycoprotein.
Cyclosporine and Ketoconazole.
p.11
Clinical Relevance of Drug Dosing Adjustments
What is a key characteristic of the anti-gout drug allopurinol regarding renal elimination?
Allopurinol is 100% renally cleared and has an intermediate therapeutic index.
p.9
Clinical Relevance of Drug Dosing Adjustments
What impact do disease states have on renal drug elimination?
Conditions like chronic kidney disease can significantly reduce renal clearance, necessitating dosage modifications.
p.15
P-Glycoprotein and Drug Interactions
Name three opioid drugs that have a high risk of interaction with grapefruit juice.
Oxycodone, Methadone, Tramadol
p.5
P-Glycoprotein and Drug Interactions
What is the importance of p-glycoproteins in the placenta?
They protect the fetus by effluxing toxic substances.
p.16
Paracetamol Pharmacokinetics and Overdose
How is NAPQI normally detoxified in the body?
NAPQI is detoxified by conjugation with glutathione.
p.23
Cytochrome P450 3A4 Enzyme
What is an inhibitor of CYP2D6?
Levomepromazine, Quinidine, and Paroxetine (SSRI).
p.7
P-Glycoprotein and Drug Interactions
List three antineoplastic agents that are P-glycoprotein substrates.
Paclitaxel, Doxorubicin, and Vinblastine.
p.7
P-Glycoprotein and Drug Interactions
Which H1 receptor antagonists are P-glycoprotein substrates?
Fexofenadine and Terfenadine.
p.7
P-Glycoprotein and Drug Interactions
Identify two HIV protease inhibitors that are P-glycoprotein substrates.
Amprenavir and Indinavir.
p.7
P-Glycoprotein and Drug Interactions
Name four steroids that are P-glycoprotein substrates.
Dexamethasone, Medroxyprogesterone, Aldosterone, and Progesterone.
p.3
Clinical Relevance of Drug Dosing Adjustments
Which factors can interfere with first-pass metabolism?
Various factors including liver function, enzyme activity, and genetic polymorphisms can interfere with first-pass metabolism, affecting the effective dose of the drug.
p.16
Paracetamol Pharmacokinetics and Overdose
Why is paracetamol overdose dangerous?
Paracetamol overdose depletes glutathione levels, leading to accumulation of NAPQI, which can cause severe liver damage.
p.8
P-Glycoprotein and Drug Interactions
Which examples of antiemetic and antiarrhythmic drugs are substrates of P-glycoprotein?
Antiemetic: Ondansetron; Antiarrhythmic: Digoxin.
p.23
Cytochrome P450 3A4 Enzyme
Are there any inductors for CYP2D6?
No, there are no known inductors.
p.7
P-Glycoprotein and Drug Interactions
Which β-Adrenoceptor antagonists are P-glycoprotein substrates?
Bunitrolol, Carvedilol, Celiprolol, Talinolol, and Reserpine.
p.23
Cytochrome P450 3A4 Enzyme
What are some substrates of CYP2C19?
Omeprazole, Diazepam, Citalopram, and Proguanil (antimalaric).
p.7
P-Glycoprotein and Drug Interactions
Identify other drugs or substances that are P-glycoprotein substrates.
Colchicine, Itraconazole, Phenothiazines, Ivermectin, and Valspodar (PSC).
p.16
Paracetamol Pharmacokinetics and Overdose
What is the clinical relevance of understanding paracetamol pharmacokinetics in overdose cases?
Understanding paracetamol pharmacokinetics helps in timely administration of antidotes like N-acetylcysteine to prevent liver damage in overdose cases.
p.8
P-Glycoprotein and Drug Interactions
What are some protease inhibitors that inhibit P-glycoprotein?
Amprenavir, Indinavir, Nelfinavir, Saquinavir, Ritonavir.
p.23
Cytochrome P450 3A4 Enzyme
What are some substrates of CYP2D6?
Codeine, Tramadol, TCA, SSRI, and Beta blockers.
