Pharmacology Flashcards
Which of the following does NOT affect the bioavailability of an orally administered drug?
A. First pass metabolism B. Rate of GIT transit C. Presence of other drugs in the GIT D. Dose of the drug E. Lipid solubility of the drug
Answer: D - Dose of the drug
Bioavailability, when administered by an extravascular route, is the fraction of the dose that reaches the systemic circulation as an intact drug (usually less than 1).
The main determinants are how much drug is absorbed and how much is removed by the liver before reaching the systemic circulation (first pass metabolism).
Physical drug properties (lipid or hydro solubulity, formulation e.g. slow release), the presence of food/other drugs and intestinal motility will all affect absorption.
Oral Bioavailability = AUC (oral) / AUC (IV)
Acidic drugs, such as phenytoin, bind primary to which one of the following plasma proteins?
A. Alpha-fetoprotein (AFP) B. Lipoprotein C. Albumin D. Alpha-acid gylcoprotein (AAG) E. Gamma globulin
Answer: C - Albumin
The main drug-binding proteins in plasma are albumin, apha1-acid glycoprotein and lipoproteins.
Albumin binds drugs and ligands, reducing serum concentration of these compounds. An example is serum calcium, the free (ionised) fraction needs to be corrected for albumin.
Drugs that are important for albumin binding are warfarin, digoxin, NSAIDs and benzodiazepines.
Which of the following does NOT interact with ligand-gated ion channels?
A. Benzodiazepines B. Glutamate C. Glycine D. Insulin E. Serotonin
Answer: D - Insulin
Ligand-gated ion channels are a group of transmembrane ion channels that open or close in response to the binding of a chemical messenger (a ligand) such as neurotransmitters.
Insulin binds the extracellular portion of the alpha subunits of the insulin receptor, causing a conformation change and activating the kinase domain in the intracellular portion.
Which one of the following drugs in 100% renally cleared and has a narrow therapeutic index?
A. Amoxicillin B. Oxypurinol C. Ceftriaxone D. Lithium E. Atenolol
Answer: D - Lithium
Lithium is 100% renally cleared and has a narrow therapeutic index.
Oxypurinol is the metabolite of allopurinol and is 100% renally cleared but has an intermediate therapeutic index.
Amoxicillin is 100% renally cleared but has a wide therapeutic index
Which of the following pharmacodynamic factors is the most important in determining efficacy of lincosamides?
A. Renal clearance
B. Concentration above the minimum inhibitory concentration
C. Maximum plasma drug concentration after dosing
D. Tissue penetration
E. Time the concentration is above the minimum inhibitory concentration
Answer: E - Time the concentration is above the minimum inhibitory concentration (MIC)
Lincosamides = Clindamcyin, Lincomycin
Antibiotic dosing is dependent on the 3 pharmacological properties of the drug: 1. concentration-dependent killing, 2. total exposure and 3. time-dependent killing
The time the drug is above the MIC is the factor most correlated with efficacy in these. Free drug levels of lincosamides should exceed the MIC for at least 40-50% of the dosing interval. Beta-lactams (penicillins, cephalosporins, carbapenems) share this property.
Aminoglycosides and Quinolones are dependent on the maximum plasma drug concentrate to eradicate bacteria.
Vancomycin depends on the total body exposure to the antibiotic - as indicated by the ratio of the area under the concentration-time curve during a 24 hour period (AUC 0-24) to MIC
Which of the following is most likely to inhibit the metabolism of warfarin?
A. Oral contraceptive B. Omeprazole C. Aspirin D. Rifampicin E. Amlodipine
Answer: B- Omeprazole
Warfarin metabolism is complex and done by multiple cytochrome P450 enzymes, but notably CYP2C9.
Omeprazole, metronidazole, Cimetidine, Amiodarone all inhibit CYP2C9 and would exacerbate the anti-coagulant effects of warfarin.
Rifampicin induces Cytochrome P450 and would reduce effect.
Oestrogen can reduce the anticoagulant effec through non cytochrome P450 mechanism (pro-oestrogenic effect?)
The proportion of drug reabsorbed in the renal tubule depends on the:
A. Volume of distribution B. Urine pH C. Glomerular filtration rate D. Extent of drug secretion into the renal tubule E. Serum creatinine
Answer: B - Urine pH
Renal drug clearance is the net result of filtration clearance (at the glomerulus) plus clearance by active secretion (in the PCT) minus reabsorption (along the entire tubule).
Passive tubular reabsorption is determined by the magnitude of concentration gradient (which depends on the extent of water reabsorption) and the ease with which the drug can move through membranes. Only non-ionised drugs can pass through the lipid membrane readily and the ease with which this occurs depends on the lipid solubility. The ionised vs non-ionised component depends on the pH of the urine and the acid dissociation constant (pKa) of the drug. Therefore, for drugs that are lipid soluble enough to be reabsorbed and can ionise to an anion or a cation, renal clearance varies with the urine pH.
What is the mechanism of Ivabradine in the treatment of stable angina?
A. Coronary artery vasodilation B. Blood pressure reduction C. Decreased cardiac contractility D. Reduction in heart rate E. Increased myocardial efficiency
Answer: D - Reduction in heart rate
Ivabradine is a direct sinus node inhibitor without negative effects on LV function.
During a constant rate of IV infusion of Piperacillin/Tazobactam, which one of the following determine the steady-state drug concentration?
A. Bioavailability B. Dose rate C. Half-life D. Loading dose E. Volume of distribution
Answer: B - Dose rate
Steady state concentration (CPss)
= Dosing rate/Clearance
Volume of distribution determines half-life and helps to calculate loading doses but no effect on steady state concentration.
Beta-lactams exhibit time dependent killing - correlated with the time above the minimum inhibitory concentration (MIC)
A 25-year old man presents after intentionally taking a large dose of paracetamol (in excess of 20g) about 6 hours prior to presentation. On the Rumack-Matthew nomogram, his plasma paracetamol places him at risk of hepatic injury. He is commenced on N-acetylcysteine infusion after initial assessment. How does N-acetylcysteine prevent hepatic injury in paracetamol overdose?
A. Inhibits glucoronidation of paracetamol
B. Enhances sulphation of paracetamol
C. Inhibits Cytochrome p450 2E1
D. Reduces paracetamol absorption in the GIT
E. Restores hepatic glutathione
Answer: E - Restores hepatic glutathione
Normal paracetamol metabolism progresses down 2 pathways:
- > 90% glucoronidated and suphation to non-toxic metabolites
- 5% metabolised by cytochrome P450 2E1 to NAPQI
- Extremely hepatotoxic
- Normally rapidly detoxified by glutathione
- If Glutathione depleted, NAPQI causes hepatocyte injury and death
- Cysteine is the rate limiting factor in glutathione synthesis
- Oral absorption is poor but NAC readily absorbed
Which one of the following pharmacodynamic factors is important in determining the efficacy of aminoglycosides?
A. Ratio of the maximum concentration over the minimum inhibitory concentration
B. Renal clearance
C. Total exposure of the body to the drug
D. Tissue penetration
E. Time the concentration is above the minimum inhibitory concentration
Answer: A -Ratio of the maximum concentration over the minimum inhibitory concentration
Aminoglycoside primary site of action is the 30S subunit of the prokaryotic ribosome, interrupting bacterial protein synthesis.
Aminoglycosides (and Quinolones) are dependent on the maximum plasma drug concentrate to eradicate bacteria.
EMQ - diuretics
A. Amiloride B. Acetazolamide C. Chlothalidone D. Eplenerone E. Furosemide F. Indapamide G. Mannitol H. Spironolactone
- Which diuretic inhibits renal potassium secretion at the distal nephron by a mineralo-corticoid independent mechanism?
- Which is an osmotic diuretic that is freely filtered by the glomeruli and remains in the tubular lumen?
- Which diuretic inhibits the sodium-potassium-chloride transport in the thick ascending limb of the loop of Henle?
- Which diuretic inhibits the apical distal convoluted tubule epithelial sodium-chloride co-transporter and decreases peripheral vascular resistance?
- Answer: A - Amiloride
Amiloride is a K-sparing diuretic that inhibits renal potassium secretion at the distal nephron (mineralocorticoid-independent mechanism). It acts on the luminal side blocking sodium entry, reducing H and K excretion.
- Answer: G - Mannitol
- Answer: E - Furosemide
- F - Indapamide
A woman with Liddle syndrome presents with severe symptomatic hypokalaemia and her GP starts her on 50mg/day of spironolactone. Four days later, repeat potassium measurement shows persistent severe hypokalaemia. The ongoing hypokalaemia is best explained by:
A. Underprescribing B. Poor compliance C. Prescription writing error D. Inappropriate prescribing E. Drug-drug interaction
Answer: D - Inappropriate prescribing
Liddle syndrome is a disorder of the epithelial sodium channels (ENaC)
- Autosomal dominant
- Manifests as mineralocorticoid excess with 1. hypertension, 2. hypokalaemia, 3. metabolic alkalosis
- Apparent mineralocorticoid excess (low renin, low aldosterone)
Although Spironolactone is a K sparing diuretic it acts via aldosterone receptors (low aldosterone anyway) and is ineffective. Amiloride, which acts via the ENaC is effective.
Which one of the following best describes the pharmacologicalD properties of Azithromycin?
A. Azithromycin is bactericidal
B. Half-life of Azithromycin ins 12 hours
C. Azithromycin is a strong cytochrome p450 enzyme, CYP3A3 inhibitor
D. Azithromycin inhibits formation of the bacterial cell wall
E. Azithromycin is safe for use in pregnancy
Answer: E - Azithromycin is safe for use in pregnancy
Azithromycin acts via binding bacterial 50S ribosomal subunit to inhibit translocation of peptide-tRNA and inhibit protein synthesis.
A. - bacteriostatic B. long half life of 60h C. few drug interactions D. See above E. True
Which one of the following increases the risk of liver toxicity from Izoniazid therapy?
A. Increasing age B. Use of NSAIDs C. Co-administration of ethambutol D. Co-administration of phenytoin E. Co-administration of pyridoxine
Answer: A - Increasing age
Risk of lsoniazid liver toxicity increases with age, particularly in females >60yrs.
Isoniazid related hepatitis presents insidiously usually at 4-6 months after initiation. Commonly there are flu-like symptoms.
Abnormal AST and ALT in up to 20% of all patients on Isoniazid but often subsides.
Pyridoxine is given concurrently to prevent peripheral neuropathy.
