What happens to an active drug during metabolism?
It can be converted to an inactive drug or another active metabolite.
p.8
Routes of Drug Administration
What is the local route of drug administration?
Drugs act locally and are not absorbed into systemic veins.
p.19
Drug Elimination and Excretion
What is hemodialysis used for?
It is employed in the treatment of drug poisoning.
p.10
First-Pass Metabolism
How is the extraction ratio calculated?
Extraction ratio = (CA - CV) / CA, where CA is the amount of drug administered and CV is the amount entering the systemic circulation.
Give an example of an active drug that is metabolized to another active drug.
Fluoxetine is metabolized to Nor-fluvoxetine.
p.8
Routes of Drug Administration
What is an example of local drug administration in limb cancer?
Intra-arterial injection to avoid side effects of anti-cancer drugs.
p.12
Routes of Drug Administration
What is haloperidol decanoate?
A long-acting formulation of haloperidol created by attaching undecanoate to the drug.
p.19
Drug Elimination and Excretion
Will hemodialysis be allowed for drugs with low Vd and high plasma protein binding?
No, because plasma proteins will prevent the filtration of the drug.
What occurs to plasma concentration of thiopentone after redistribution?
Plasma concentration decreases.
p.30
Drug Elimination and Excretion
How are alcohols excreted?
Converted to acetone and excreted as a gaseous form.
p.34
Drug Elimination and Excretion
What is the relationship between drug concentration in plasma and elimination rate?
Elimination rate is directly proportional to concentration; more drug in plasma means more drug in urine.
p.16
Drug Absorption Mechanisms
What is the purpose of converting drugs into sustained release tablets?
To provide long-term disease management.
p.26
Drug Interactions and Bioavailability
What class of drugs do Diltiazem and Verapamil belong to?
Calcium channel blockers.
p.29
Drug Elimination and Excretion
What is elimination in pharmacokinetics?
The rate of removal of a drug from the body over time.
What is the clinical importance of pKa value?
It determines the ionization and lipid solubility of drugs, affecting their absorption and ability to cross cell membranes.
p.11
First-Pass Metabolism
How does the rectal route bypass first-pass metabolism?
Drugs absorbed through the external hemorrhoidal vein drain directly into the heart.
p.16
Drug Absorption Mechanisms
What is the effect of increasing Tinax on drug absorption?
It converts drugs to sustained release preparation by delaying the rate of absorption.
What is bio-equivalence?
Comparison of bioavailability of two brands of the same drug.
p.3
Drug Absorption Mechanisms
What role do aquaporins play in drug absorption?
They carry water-soluble drugs across the cell membrane.
p.33
Drug Elimination and Excretion
What type of drugs get excreted in urine?
Only water-soluble drugs.
p.13
Routes of Drug Administration
What is the indication for using a nitrate patch?
Long-term treatment of chronic angina.
How is pharmacodynamics defined?
As 'what a drug does to the body.'
What is redistribution in the context of pharmacology?
The process by which highly lipid-soluble drugs move from the site of action (like the brain) to other tissues (like fat).
What happens to a drug after it is absorbed in the body?
It circulates, binds to its target or receptor, and produces its effect.
p.13
Routes of Drug Administration
What is the primary advantage of the transdermal route?
Delivers a constant amount of drug continuously around the clock.
What effect does mixing amphetamine with sodium bicarbonate have on urine?
It makes urine more basic.
p.3
Drug Absorption Mechanisms
What is the primary method by which most drugs cross cellular barriers?
Simple or passive diffusion.
p.6
Drug Absorption Mechanisms
How is the pK value calculated?
Using the Henderson-Hasselbalch equation.
What is first-pass metabolism?
The process where a drug is metabolized in the liver before reaching systemic circulation.
p.6
Drug Absorption Mechanisms
What happens to a weak acidic drug in more acidic pH media?
It becomes highly non-ionic or lipid soluble.
What process in the liver is responsible for the metabolism of certain drugs?
Acetylation by N-Acetyl Transferase (NAT).
What is the focus of pharmacodynamics?
The effect produced by the drug on the body.
What is the mechanism of action for Aciclovir and Ganciclovir?
They attach to a phosphate group and block DNA synthesis.
p.1
Introduction to Pharmacology
What are the key components involved in drug development?
Clinical trials, types, and adverse effects.
p.18
Volume of Distribution
How do liver diseases affect drug distribution?
They decrease albumin production, leading to increased Vd and toxicity.
What does ADME stand for in pharmacokinetics?
Absorption, Distribution, Metabolism, Excretion.
p.9
Drug Absorption Mechanisms
What is the primary route of drug absorption in the enteral route?
Through the small intestine, due to its greater surface area.
p.13
Routes of Drug Administration
What type of drug levels does the transdermal route provide?
Non-fluctuating/constant drug levels in the blood.
p.13
Routes of Drug Administration
Where is the posterior auricular area located?
On the mastoid process behind the pinna.
p.6
Drug Absorption Mechanisms
What is the pK range for acidic, neutral, and basic drugs?
Acidic: 0-7, Neutral: 7, Basic: 7-15.
How does first-pass metabolism affect drug dosage?
If 100 mg of a drug is given orally, only a portion reaches the heart after metabolism.
How does Aspirin behave in relation to lipid solubility?
Aspirin behaves as a lipid-soluble, non-ionic drug at its pKa.
p.34
Drug Elimination and Excretion
What characterizes first-order kinetics of elimination?
Elimination equals clearance.
p.16
Drug Interactions and Bioavailability
Why is phenytoin an exception in bio-equivalence?
Small variations in absorption can lead to toxicity or rebound seizures.
p.5
Drug Absorption Mechanisms
What is the difference between facilitated diffusion and active transport?
Facilitated diffusion requires no ATP, while active transport requires ATP.
How is pharmacokinetics defined?
As 'what the body does to the drug.'
What happens to harmful molecules absorbed through the enteral route?
They are removed by the liver and intestinal enzymes.
What is Methimazole used for?
It is an antithyroid drug.
What is the significance of Dipivefrin?
It is a prodrug that converts to Epinephrine in the eyes.
p.30
Drug Elimination and Excretion
Which drugs are excreted by sweat, saliva, and tears?
Lithium and metals like mercury.
What does pharmacokinetics study?
The movement of the drug inside the body.
What does the one gene hypothesis state?
One gene can make one type of enzyme, but this hypothesis was rejected.
p.29
Drug Elimination and Excretion
What does elimination include?
Metabolism and excretion.
p.30
Drug Elimination and Excretion
What types of drugs are excreted as gases?
Anesthetic gases like isoflurane, sevoflurane, and halothane.
p.33
Drug Elimination and Excretion
What happens to lipid-soluble (non-ionic) drugs in the body?
They are reabsorbed back into the body.
p.5
Drug Absorption Mechanisms
What role does P-glycoprotein play in drug absorption?
It removes drugs and products, opposing their action.
p.34
Drug Elimination and Excretion
What is the effect of low or saturated clearance capacity on drug elimination?
It follows zero-order kinetics, resulting in slow excretion.
What is dose titration?
Changing the dose slightly according to the effect of a drug.
p.3
Drug Absorption Mechanisms
What is endocytosis in the context of drug absorption?
The cell membrane changes to allow the drug to enter the cell.
What is a notable characteristic of N-Acetyl Transferase (NAT)?
It shows genetic polymorphism.
p.17
Volume of Distribution
What happens when a drug moves into unwanted organs?
It produces an adverse effect.
p.9
Routes of Drug Administration
What is a limitation of the oral route for drug administration?
It cannot be given to an unconscious patient or in an emergency.
What is the issue with bioavailability in the oral route?
It is unpredictable due to first-pass metabolism.
p.18
Volume of Distribution
What factors can influence Volume of Distribution (Vd)?
Lipid solubility, age, gender, pregnancy, liver diseases, and kidney disease.
p.5
Drug Absorption Mechanisms
What is the most common pathway for drug absorption?
Simple/Passive diffusion.
p.4
Drug Interactions and Bioavailability
What is P-glycoprotein also known as?
MDR (Multidrug Resistance) transporter or MRP (Multidrug Resistance Protein) transporter.
p.17
Volume of Distribution
How is Vd expressed in terms of body weight?
Liters per kg of body weight.
p.3
Drug Absorption Mechanisms
What hormone increases the synthesis of aquaporins in the kidney?
Antidiuretic Hormone (ADH).
p.13
Routes of Drug Administration
What is the purpose of the hyoscine patch?
Used for motion sickness.
p.14
Routes of Drug Administration
What is an example of a drug with local action in asthma?
Bronchodilators, which act on constricted bronchi.
p.4
Drug Absorption Mechanisms
How does P-glycoprotein affect drug absorption in the gastrointestinal tract?
It decreases absorption of the drug.
p.12
Routes of Drug Administration
How can a water-soluble drug be made into a lipid-soluble drug?
By attaching a lipid moiety to it.
p.19
Volume of Distribution
Why is hemodialysis ineffective for drugs with high volume of distribution (Vd)?
Because high Vd means the drug is not present in plasma, making it difficult to filter out.
What is hepatic clearance?
The calculation of drug concentration in the portal vein versus the inferior vena cava (IVC).
What is the role of the kidneys in drug metabolism?
Excretion of water-soluble drugs occurs through the kidneys.
p.8
Routes of Drug Administration
What are some specific sites for local drug administration?
Synovial space, bladder, cerebrospinal fluid (CSF), and vitreous humor.
p.14
Routes of Drug Administration
What particle size is required for systemic action in inhalation drugs?
Smaller particle size, less than 2 microns.
p.30
Drug Interactions and Bioavailability
What effect do antibiotics have on estrogen excretion?
Antibiotics like doxycycline and ampicillin kill intestinal bacteria, inhibiting enterohepatic recirculation of estrogen, leading to its excretion in feces.
What toxicity is associated with the poor metabolism of Nol?
Toxicity is seen, leading to Drug Induced Lupus Erythematosus (DLE).
p.11
Routes of Drug Administration
What is the primary vein involved in the absorption of drugs administered via the rectal route?
External hemorrhoidal vein.
p.34
Drug Elimination and Excretion
What happens to drug elimination in organs with high clearance capacity?
More drugs are eliminated in urine.
p.10
First-Pass Metabolism
What is hepatic blood flow in relation to oral drug administration?
It refers to the continuous supply of blood to the liver by the portal vein after a drug is taken orally.
What happens to Aspirin at a pH similar to blood pH (7.2-7.4)?
It becomes ionized and water-soluble, preventing it from crossing cell membranes.
What is the volume of distribution (Vd)?
A measure of how extensively a drug is distributed in the body.
What happens to thiopentone after it enters the bloodstream from the brain?
It is redistributed into fat instead of being excreted via urine.
What is the role of plasma esterases in drug metabolism?
They help in the metabolism of certain drugs like Atracurium.
p.16
Drug Interactions and Bioavailability
Can brands of phenytoin be interchanged?
No, they should never be changed due to safety concerns.
p.29
Drug Elimination and Excretion
What are some major excretory pathways for drugs?
Bile, sweat, saliva, breast milk, and gases exhaled through lungs.
What does a downward straight line on a concentration-time graph indicate?
The concentration of the drug decreases with time.
What is the role of SSRIs?
They are a class of antidepressants.
p.12
Routes of Drug Administration
How is a drug administered via the subcutaneous route absorbed?
It enters subcutaneous fat and is then absorbed into dermal blood vessels.
What does pharmacokinetics deal with?
The movement of the drug inside the body.
How does the diet of Indian people affect drug metabolism?
A potato and protein deficient diet can lead to poor metabolism of certain drugs.
Which drugs are known to exhibit redistribution?
Thiopentone, fentanyl, and general anesthetics.
Which ACE inhibitors are not prodrugs?
Captopril and Lisinopril.
p.14
Routes of Drug Administration
What determines whether inhalation drugs have local or systemic action?
It depends on the disease and the particle size of the drug.
What is an acceptable variation in bioavailability for two brands of the same drug?
25% variation is acceptable.
p.12
Routes of Drug Administration
What is the purpose of converting a rapidly absorbed drug into a slowly absorbed one?
To extend the duration of action of the drug.
p.3
Drug Absorption Mechanisms
What is paracellular transport?
The process by which drugs cross the space between two cells.
p.14
Routes of Drug Administration
How do anesthetic gases achieve systemic action?
They are small molecules that enter the blood through alveoli and cross the blood-brain barrier.
p.4
Drug Elimination and Excretion
What effect does P-glycoprotein have in the kidneys?
It increases urinary excretion of the drug.
p.10
First-Pass Metabolism
What happens to drugs with very high first-pass metabolism in the liver?
They are either not given orally or are given in very high oral doses.
What does UDP-GT do to bilirubin?
Attaches glucuronide to bilirubin, making it water-soluble for excretion.
p.18
Drug Interactions and Bioavailability
What is the consequence of increased free drug fraction in antiepileptics?
It can lead to unwanted distribution to organs and persistent seizures.
p.30
Drug Interactions and Bioavailability
Why does rifampicin cause contraceptive failure?
Rifampicin increases the metabolism or degradation of estrogen by inducing CYP enzymes.
p.29
Drug Interactions and Bioavailability
Which drugs are contraindicated during lactation due to high excretion rates through milk?
Sulfonamides, Methotrexate, Aspirin, Lithium, and Levetiracetam.
What are the main types of Phase I reactions?
Oxidation, reduction, and hydrolysis.
p.4
Drug Interactions and Bioavailability
What is the effect of P-glycoprotein inhibitors on drug activity?
They decrease the activity of P-glycoprotein, potentially increasing drug levels.
p.3
Drug Absorption Mechanisms
What is facilitated diffusion?
Transport of drugs into the cell with the aid of a specialized transporter without requiring energy.
p.7
Drug Absorption Mechanisms
What is the significance of the surface area of the intestine in drug absorption?
The greater surface area of the intestine allows for more efficient absorption of all drugs.
p.17
Volume of Distribution
What is the Volume of Distribution (Vd)?
The apparent volume of plasma required to contain a drug at the same concentration as in plasma.
How does amphetamine behave in basic urine?
It becomes lipid soluble and is more reabsorbed.
p.16
Drug Absorption Mechanisms
What technique is used to convert drugs for sustained release?
Covering the label with inert polymer.
p.34
Drug Elimination and Excretion
What does clearance capacity indicate?
The volume of plasma that is cleared of a drug in a unit time.
p.3
Drug Absorption Mechanisms
What is required for simple diffusion of drugs across the cell membrane?
No ATP/energy is required; drugs move along the concentration gradient.
p.19
Drug Interactions and Bioavailability
Why are sulfonamides contraindicated in neonates and the last trimester of pregnancy?
They displace bilirubin from albumin, leading to bilirubin entering the neonatal brain and causing neurological damage (kernicterus).
p.11
Routes of Drug Administration
What is an example of a drug administered via the rectal route?
Rectal diazepam, used for febrile seizures in children.
p.4
Drug Absorption Mechanisms
What is the main function of P-glycoprotein?
To transport already-absorbed drugs out of the cell, inhibiting absorption and reducing drug levels and effects.
What is bioavailability (BA) of a drug?
The amount of drug reaching the bloodstream.
p.18
Volume of Distribution
What is the Volume of Distribution (Vd) of Warfarin?
Low Vd, as plasma protein binding predominates over lipid solubility.
How does a change in pH affect drug ionization?
A change in pH by 1 unit changes ionization by 10% (log10).
How does chronic alcoholism affect enzyme metabolism?
Enzymes are rapidly metabolized.
p.14
Routes of Drug Administration
What particle size is required for local action in inhalation drugs?
Large particle size, specifically 2-5 microns in diameter.
p.16
Drug Interactions and Bioavailability
What is the consequence of a small decrease in absorption of phenytoin?
It can lead to rebound seizures.
p.31
Drug Elimination and Excretion
What is Active Tubular Secretion (ATS)?
An active process requiring ATP to transport drugs from blood to urine.
Why is Alracurium safe in hepatic failure?
It does not require any organ or enzyme for metabolism.
p.33
Drug Elimination and Excretion
What is the effect of changing urine pH in weak acidic drug poisoning?
Acidic drugs in basic urine become water-soluble.
What is a loading dose?
An initial higher dose of a drug to quickly achieve therapeutic levels.
What is a maintenance dose?
The dose of a drug administered to maintain therapeutic levels after the loading dose.
p.10
Routes of Drug Administration
What is the sublingual route of drug administration?
The drug is placed under the tongue, absorbed through the sublingual veins, and reaches the heart directly through the superior vena cava.
What is the bioavailability of intravenous (IV) drug administration?
100%, as it is taken as the standard for comparison.
p.8
Routes of Drug Administration
What is the difference between transdermal and topical routes?
In topical, the drug remains on the skin; in transdermal, the drug is absorbed into the skin.
What is the main purpose of Phase II reactions?
To convert drugs into inactive forms, except for some like Morphine and Minoxidil.
p.31
Drug Elimination and Excretion
What does it indicate if NUC is greater than GFR?
Active tubular secretion is a dominant factor.
p.15
Drug Absorption Mechanisms
What is the purpose of sustained release preparations?
To convert fast-absorbing drugs into slowly absorbing or long-acting drugs.
What is the role of acetyltransferase in drug metabolism?
It adds an acetyl group during the acetylation process in Phase II reactions.
p.19
Drug Interactions and Bioavailability
What effect does aspirin have on tolbutamide?
Aspirin displaces tolbutamide from albumin, increasing free tolbutamide levels and potentially causing hypoglycemia.
What is extrahepatic metabolism?
Metabolism that occurs outside the liver.
What are prodrugs?
Inactive drugs that undergo metabolism to become active drugs.
p.29
Drug Elimination and Excretion
What is excretion?
The removal of the drug from the body through various pathways.
p.13
Routes of Drug Administration
What condition is treated with the clonidine patch?
Long-term treatment of hypertension.
p.6
Drug Absorption Mechanisms
What occurs if a weak acidic drug is kept in more basic pH media?
It becomes highly ionic or water-soluble.
What effect does smoking have on nicotine metabolism?
Increases metabolism of nicotine.
What is half-life (t1/2)?
The time it takes for the concentration of a drug in the bloodstream to reduce by half.
p.19
Drug Elimination and Excretion
Is hemodialysis allowed for drugs with low Vd and low plasma protein binding?
Yes, because they are in free form and can be filtered.
p.12
Routes of Drug Administration
What is the zigzag technique in IM injections?
A method where the skin is pulled downwards before injection to prevent drug leakage.
What happens to Succinylcholine in hepatic failure?
It is not metabolized, causing respiratory paralysis due to toxicity.
p.33
Drug Elimination and Excretion
What is Forced Acidic Diuresis used for?
To treat weak basic drug poisoning by making urine acidic.
p.5
Drug Absorption Mechanisms
What is the significance of Fick's law in drug diffusion?
It governs the rate/speed of diffusion based on concentration, area, permeability, and thickness of the cell membrane.
What is the relationship between spironolactone and canrenone?
Spironolactone is metabolized to canrenone.
p.10
Routes of Drug Administration
What is an example of a drug administered sublingually?
Sublingual nitrates like Glyceryl trinitrate and Isosorbide dinitrate.
What does Tmax represent?
The time at which the drug attains Cmax.
What does the area under the curve (AUC) represent in a concentration-time graph?
The total amount of drug that enters circulation over time.
p.31
Drug Elimination and Excretion
What does it indicate if NUC is less than GFR?
The drug is being passively reabsorbed.
p.27
Drug Interactions and Bioavailability
What is the effect of Omeprazole on Clopidogrel?
Omeprazole inhibits CYP activity, decreasing Clopidogrel's effectiveness and increasing the risk of MI and stroke.
p.32
Drug Elimination and Excretion
What are the two types of transporters involved in tubular secretion?
OATPs (Organic Anion Transport Proteins) and OCTPs (Organic Cation Transport Proteins).
p.18
Volume of Distribution
What is the effect of kidney disease on drug distribution?
It results in albuminuria, which increases Vd and toxicity.
What are CYP enzymes responsible for?
Metabolism of approximately 50% of drugs.
Where else can first-pass metabolism occur besides the liver?
In the walls of the stomach and small intestine.
p.6
Drug Absorption Mechanisms
What happens to a weak basic drug in more basic pH media?
It becomes highly non-ionic or lipid soluble.
p.33
Drug Elimination and Excretion
What is Forced Alkaline Diuresis used for?
To treat weak acidic drug poisoning by making urine alkaline.
Name a drug metabolized by CYP enzymes.
Theophylline, Clozapine, Phenytoin, Warfarin.
p.11
Routes of Drug Administration
What is the intraosseous (IO) route used for?
Administering drugs directly into a bone.
p.6
Drug Absorption Mechanisms
What is the effect of pH on strong acidic or basic drugs?
They are not influenced by the pH of the media and always remain ionic.
What happens in the body due to UDP-GT deficiency?
Bilirubin deposits in the body, leading to jaundice.
Which CYP enzyme metabolizes Tamoxifen?
Different CYP enzymes metabolize it, but not Clozapine.
p.14
First-Pass Metabolism
What happens to a drug taken orally before it reaches systemic circulation?
It undergoes first-pass metabolism.
Why is the bioavailability of routes other than IV less than 100%?
Due to cellular barriers and first-pass metabolism.
p.26
Drug Interactions and Bioavailability
What class of drugs do Ritonavir belong to?
Protease inhibitors (Anti-HIV).
What type of reactions occur outside the Smooth Endoplasmic Reticulum (SER)?
Non-microsomal reactions, except for glucuronide conjugation.
p.31
Drug Elimination and Excretion
What is the significance of glomerular filtration in drug excretion?
Only the free form of the drug is excreted into the urine.
p.32
Drug Elimination and Excretion
What is the function of OCTPs?
They excrete basic drugs, such as tubocurarine (a muscle relaxant).
p.17
Volume of Distribution
What does an increase in Vd indicate about a drug's movement?
The drug is moving out of the blood vessels.
p.8
Routes of Drug Administration
How can a local effect be produced in drug administration?
By blocking the artery above the site of injection.
What is enterohepatic recirculation?
The process where drugs excreted in bile can be reabsorbed from the intestine.
What is Remifentanil known for?
It is the shortest-acting opioid.
What does clearance capacity (CI) refer to?
The power of the body to excrete a drug.
p.18
Drug Interactions and Bioavailability
What happens when antiepileptics are used together?
They can increase each other's toxicity by displacing from albumin, increasing free drug fraction.
p.10
First-Pass Metabolism
Which drugs are known for high first-pass metabolism?
Examples include Lignocaine, Propranolol, Fentanyl, Morphine, and Natural steroids.
p.5
Drug Absorption Mechanisms
What is the function of aquaporins in drug absorption?
They facilitate aqueous diffusion.
p.8
Routes of Drug Administration
What are the common routes of systemic drug administration?
Oral, sublingual, rectal, intravenous (IV), intramuscular (IM), and inhalational.
What toxicity is associated with Irinotecan?
Bone marrow cancer and neutropenia.
p.5
Drug Absorption Mechanisms
What is the relationship between the thickness of the cell membrane and the rate of diffusion?
The rate of diffusion is inversely proportional to the thickness of the cell membrane.
p.12
Routes of Drug Administration
What is the purpose of intradermal injections?
Used for allergy testing and BCG vaccines.
p.33
Drug Elimination and Excretion
Are strong acids and strong bases influenced by urine pH?
No, they always remain water-soluble.
p.5
Drug Absorption Mechanisms
What are aminoglycosides and their absorption characteristics?
They are highly polar, water-soluble drugs that are not absorbed orally.
p.33
Drug Elimination and Excretion
What is the purpose of making a drug more water-soluble in case of poisoning?
To inhibit passive reabsorption and facilitate excretion.
p.18
Drug Interactions and Bioavailability
What is the significance of plasma protein binding?
It is non-specific and reversible, leading to drug displacement and potential toxic effects.
p.11
Routes of Drug Administration
Which routes allow for dose titration?
Intravenous and inhalational routes.
p.7
Drug Absorption Mechanisms
Where are basic drugs primarily absorbed?
From the small intestine (Duodenum).
What is an example of a prodrug that is converted to an active drug?
Codeine is metabolized to Morphine.
p.31
Drug Elimination and Excretion
What role do specialized transporters play in Active Tubular Secretion?
They pick the drug from the blood and excrete it into urine.
p.7
Drug Interactions and Bioavailability
What effect do antacids have on drug absorption?
Antacids neutralize HCl in the stomach, affecting the absorption of acidic drugs.
p.12
Routes of Drug Administration
What are some commonly used drugs that may cause staining of subcutaneous fat?
Iron dextran injections and antipsychotic drugs.
p.31
Drug Elimination and Excretion
How is Net Urinary Clearance (NUC) calculated?
NUC = Glomerular filtration + Active tubular secretion - Passive reabsorption.
What is Cmax?
The maximum concentration of a drug in plasma.
p.29
Drug Interactions and Bioavailability
What condition can aspirin lead to in newborns?
Reye's syndrome, which can cause liver damage.
p.26
Drug Interactions and Bioavailability
What is the effect of grapefruit juice on drug metabolism?
Contains furanocoumarins that can lead to interactions.
p.27
Drug Interactions and Bioavailability
What is the consequence of prescribing Erythromycin or Ketoconazole with CAT drugs?
Increased toxicity of CAT drugs and prolonged QT interval, leading to Torsades de pointes.
p.27
Drug Interactions and Bioavailability
What is Tamoxifen converted to upon activation?
Endoxifen, used as an anti-cancer drug in breast cancer.
p.32
Drug Elimination and Excretion
What type of process is filtration in the kidneys?
A passive process that does not require ATP.
p.32
Drug Elimination and Excretion
What is the role of P-glycoprotein in drug excretion?
It excretes neutral drugs, such as digoxin.
p.10
First-Pass Metabolism
If 100 mg of a drug is given orally and 40 mg enters the systemic circulation, what is the extraction ratio?
The extraction ratio is 0.6 or 60%.
p.4
Drug Elimination and Excretion
What role does P-glycoprotein play in the liver?
It increases bile excretion of the drug.
p.12
Routes of Drug Administration
What can happen if a drug leaks back from the puncture site during an IM injection?
It can lead to staining of subcutaneous fat.
Why is bioavailability expressed as a percentage?
Because it compares the amount of drug reaching systemic circulation to the intravenous route, which is 100%.
How is the action of thiopentone on the brain terminated?
By redistribution into fat.
What is the significance of oxypurinol?
It is developed separately for gout and is a metabolite of allopurinol.
p.4
Drug Interactions and Bioavailability
What is a substrate of P-glycoprotein?
Any drug identified by P-glycoprotein, such as Digoxin.
p.19
Volume of Distribution
What is the volume of distribution (Vd) of chloroquine?
Chloroquine has the highest Vd of 1500 liters of plasma.
p.2
Drug Absorption Mechanisms
What is absorption in pharmacokinetics?
The process by which a drug crosses into systemic circulation (blood vessels).
p.8
Routes of Drug Administration
What is an example of a drug administered through the vitreous humor?
Ganciclovir used to treat CMV retinitis.
p.3
Drug Absorption Mechanisms
What is an example of a drug absorbed through active transport?
Levodopa and methyldopa via dopamine transporters.
p.27
Drug Interactions and Bioavailability
Which proton pump inhibitors have low CYP inhibitor action compared to Omeprazole?
Rabeprazole and Pantoprazole.
How does estrogen get reabsorbed after being excreted in bile?
Intestinal bacteria produce glucuronidase, which removes the glucuronide group from estrogen, making it lipid-soluble.
p.13
Routes of Drug Administration
What is the indication for natural estrogen/progesterone patches?
Hormone replacement therapy in postmenopausal women.
p.4
Drug Absorption Mechanisms
How does P-glycoprotein affect drug entry into the blood-brain barrier and placenta?
It decreases entry of the drug, providing protection.
What is bioavailability?
The fraction of the drug that reaches systemic circulation in unchanged form.
p.19
Drug Elimination and Excretion
Which drugs require hemodialysis?
Barbiturates, lithium, alcohols, aspirin, salicylates, theophylline, amphetamines, and others.
p.31
Drug Elimination and Excretion
What is Passive Reabsorption in the context of drug elimination?
If a drug has lipid solubility, it can be reabsorbed into the blood instead of being excreted in urine.
p.8
Routes of Drug Administration
What is the purpose of the sublingual route?
To absorb the drug directly into the bloodstream by placing it under the tongue.
p.29
Drug Interactions and Bioavailability
What is a potential risk of sulfonamides in newborns?
They can displace bilirubin from albumin, leading to neuronal damage (kernicterus).
What condition can chloroquine cause in the retina?
Bull's eye retinopathy, which can result in permanent blindness.
What is the effect of Atazanavir on bilirubin levels?
Causes hyperbilirubinemia.
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Drug Elimination and Excretion
What types of drugs can be changed to water-soluble only with weak acid and weak base?
Weak acidic and weak basic drugs.
What is glucuronide conjugation?
A Phase II reaction where polar groups are transferred to drugs, primarily involving UDP-GT.
p.5
Drug Absorption Mechanisms
Why is oral heparin not absorbed?
It is highly acidic and not absorbed orally.
p.8
Routes of Drug Administration
What is the systemic route of drug administration?
Drugs are absorbed into systemic veins and enter the venous circulation.
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Drug Interactions and Bioavailability
Which drugs are mentioned as examples of those affected by plasma protein binding?
Aspirin, anti-arrhythmics, anti-epileptics, beta-blockers, barbiturates, calcium channel blockers, opioids, acetaminophen, imipramine, sulfonamides, and lignocaine.
Which drugs require UDP-GT for removal from the body?
Irinotecan and Atazanavir.
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Drug Absorption Mechanisms
Why are water-soluble drugs rapidly absorbed in the intramuscular route?
Due to the presence of a lot of blood vessels in the muscle.
p.27
Drug Interactions and Bioavailability
What happens to estrogen when Rifampicin is prescribed to a woman on oral contraceptives?
Estrogen rapidly gets inactive, leading to contraceptive failure.
p.33
Drug Elimination and Excretion
What happens to basic drugs in acidic urine?
They become water-soluble.
What type of drugs are Midazolam and Cyclosporine?
Midazolam is a benzodiazepine, and Cyclosporine is an immunosuppressive drug.
Where is the microsomal system located?
Inside the smooth endoplasmic reticulum (SER).
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Drug Elimination and Excretion
What structures are involved in the filtration process in the nephron?
Endothelial cells of the glomerulus and podocytes of Bowman's capsule.
p.32
Drug Interactions and Bioavailability
Why is probenecid combined with penicillin and cephalosporins?
It inhibits their excretion into urine, making them longer acting.
p.10
First-Pass Metabolism
How can first-pass metabolism be bypassed?
By administering the drug through routes other than oral, such as sublingual, rectal, or parenteral routes.
What is the effect of sulfasalazine in the intestine?
It converts to sulfapyridine and does not go to the liver.
p.5
Drug Absorption Mechanisms
How does the concentration of a drug affect its diffusion rate?
The higher the concentration of the drug, the more it enters the cell.
p.27
Drug Interactions and Bioavailability
What is the effect of CYP3A4 on certain drugs like Cisapride, Astemizole, and Terfenadine?
CYP3A4 converts them into inactive forms.
p.12
Routes of Drug Administration
What is Norplant?
A contraceptive implant consisting of rods containing levonorgestrel.
p.27
Drug Interactions and Bioavailability
What type of drug is Clopidogrel and how is it activated?
Clopidogrel is a prodrug converted to an active form by phase 1 reaction.
p.15
Drug Absorption Mechanisms
What effect does increasing Tmax have on drug absorption?
It delays the rate of absorption of the drug.
p.32
Drug Elimination and Excretion
What is active tubular secretion?
A process that requires ATP to excrete drugs from blood into urine.
p.32
Drug Elimination and Excretion
What happens to protein-bound drugs when a free form is excreted?
The protein-bound drug is converted to free form to maintain equilibrium.
p.4
Drug Interactions and Bioavailability
What can be a consequence of increased plasma concentration of Digoxin due to P-glycoprotein inhibition?
Toxicity of Digoxin, leading to arrhythmias.
p.5
Drug Absorption Mechanisms
What type of drugs are considered water-soluble?
Polar or strong ionic drugs.
What happens when light is passed through CYP450 enzymes?
All wavelengths are reflected except for 450, which is absorbed and seen as a peak on a monitor.
p.32
Drug Elimination and Excretion
What role do podocytes play in drug filtration?
They carry a negative charge that repels basic drugs (OH-).
p.3
Drug Absorption Mechanisms
What is the difference between active transport and facilitated diffusion?
Active transport requires energy (ATP) and moves drugs against the concentration gradient, while facilitated diffusion does not require energy and moves drugs along the gradient.
p.10
First-Pass Metabolism
Why is natural estrogen not used in oral contraceptive pills?
Because it has a very high first-pass metabolism.
How is the rate of absorption of a drug determined?
By evaluating Tmax; smaller Tmax indicates rapid absorption, while larger Tmax indicates slow absorption.
How does the activity of the non-microsomal system differ from the microsomal system?
The non-microsomal system is outside the SER and metabolizes fewer drugs.
p.27
Drug Interactions and Bioavailability
How does Fluoxetine affect Tamoxifen's effectiveness?
Fluoxetine inhibits CYP2D6, reducing the effect of Tamoxifen and increasing the chances of breast cancer metastasizing.
p.32
Drug Elimination and Excretion
What is the function of OATPs?
They excrete acidic drugs, such as antibiotics like penicillin and cephalosporins.
p.32
Drug Elimination and Excretion
How does plasma protein binding affect drug filtration?
It reduces filtration and leads to lower glomerular filtration of protein-bound drugs.
