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Drugs A and B have the following properties in healthy individuals:
In such healthy individuals, haemodialysis shortens the half-life of drug A much more than it shortens the half-life of drug B. This difference is best explained by which of the following characteristics of drug B?
Oral medications, Drugs A and B, have the following properties in healthy individuals.
Compared to healthy individuals, patients with cirrhosis have a much higher concentration of drug A than drug B. The best explanation for this is the difference in:
The following pharmacokinetic data (normalised to a 70 kg individual) are provided for five drugs.
Which one of the following drugs is most likely to have the slowest rate of clearance from plasma?
The renal clearance of drugs that are weak bases and weak acids is affected by changes in the urine pH. The most accurate representation of how the pH changes clearance is:
A 14 year old teenager undergoes muscle biopsy under general anaesthetic for a suspected myopathy. During the procedure she develops a high temperature and generalised stiffness. Biochemical testing shows acidosis, hypercapnia and a markedly elevated serum creatine kinase (CK).
The most likely diagnosis is:
When prescribing a medicinal drug for athletes, which of the following drug is NOT permitted during competition unless a therapeutic use exemption (TUE) is obtained?
In acute paracetamol overdose, which of the following mechanism may result in hepatotoxicity?
Macrolide antibiotics have been increasingly used in the treatment of children with cystic fibrosis. The beneficial effect is most likely:
The long term use of omeprazole will most likely lead to which type of electrolyte disturbance?
You are planning to start oral Dabigatran on an 80 year old man with atrial fibrillation.
How frequent should you monitor his renal function?
Tramadol is a synthetic opioid analgesic indicated for the treatment of moderate to severe pain at step 2 of the WHO analgesic ladder. Importantly tramadol inhibits the reuptake of serotonin and noradrenaline in addition to its opioid action.
Which of the following is least likely to cause an adverse reaction to Tramadol?
A 24-year-old woman is in the orthopaedic ward following surgery for a fractured femur two days previously. She develops symptoms of agitation, abdominal cramps and diarrhoea.
On examination, she is febrile and sweaty, with stimulus-sensitive myoclonus and mild confusion. Her medical history includes depression currently treated with sertraline 200 mg/day.
Her post-operative medications include tramadol SR 200 mg twice daily, paracetamol 1 g six-hourly, naproxen 500 mg twice daily and temazepam 10 mg nocte.
The most likely diagnosis is:
Curve A represents the log dose-response curve for drug X when given alone. Curve B represents the log dose-response curve for drug X in the presence of a fixed concentration of another drug, Y.
The most likely explanation for these findings is that:
Which analgesic is most likely to lead to a serious drug interaction if combined with an MAO (monoamine oxidase) inhibitor (e.g. moclobemide)?
The concentration-response relationships for five different drugs (Drugs A-E) are shown in the graph below.
Which one of the drugs has the highest potency?
Which of the following antibiotic is most commonly associated with a photosensitivity reaction?
Quinine is no longer supported for use in the treatment of nocturnal leg cramps.
What is the most common side effect of this medication?
An 81-year-old male has moderate dementia with mild behavioural disturbances, hypertension and osteoporosis. He is living in a nursing home. His current medications are donepezil, olanzapine, enalapril, vitamin D and calcium.
A random fasting blood glucose is 11.5 mmol/L [<6 mmol/L].
The next step in the management of this elevated blood glucose level should be:
In a subject taking part in a bioavailability study, the area under the plasma concentration versus time curve (AUC) achieved after an intravenous dose of 20 mg is 100 mg/hr/L, compared with an AUC of 200 mg/hr/L after an oral dose of 50 mg.
The oral bioavailability of the drug in this subject is:
A bioavailability study has been performed to compare a proposed new generic capsule, in a strength of 50 mg, with a marketed tablet preparation in a strength of 100 mg.
The active ingredient is a drug with linear kinetics. A cross-over design was used, with each subject receiving, in random order and with an adequate wash-out period, a single oral dose of one tablet on one occasion and one capsule on the other.
The mean results for the area under the plasma concentration versus time curve (AUC) are 300 mg.h/L for the capsule, and 500 mg.h/L for the tablet.
The best estimate of the relative bioavailability of the capsule with respect to the tablet is:
Warfarin is predominantly cleared by hepatic metabolism, with a low hepatic extraction ratio and therefore a low hepatic first pass effect and high bioavailability after oral administration.
Which one of the following best describes the most likely effect on warfarin pharmacokinetics of concomitant administration of an inhibitor of warfarin metabolism, such as erythromycin?
A patient with cirrhosis is being treated with normal doses of chlormethiazole for alcohol withdrawal. Chlormethiazole has an hepatic extraction ratio of 0.9, hepatic clearance of 100 L/h, protein binding of 64% and volume of distribution of 12 L/kg.
The much higher concentrations and greater effect of chlormethiazole in people with cirrhosis is mostly due to:
A study is comparing the bioavailability of a new oral preparation of a drug (100 mg tablet) with the marketed intravenous preparation (50 mg in 2 mLs). In this crossover study, healthy volunteers were given in random order one 100 mg tablet or 50 mg intravenously (IV). The drug has linear kinetics within the range of concentrations studied. The mean results are as follows:
Which of the following is the best estimate of the oral bioavailability of the tablet?
A drug has a fraction excreted unchanged of 0.1 and a total body clearance of 50L/hr. Liver blood flow is 90/L.
What is its maximum oral bioavailability?
Allopurinol precipitates azathioprine toxicity by which one of the following mechanism?
Which one of the following is least likely to cause a reduction in the extent of protein binding of phenytoin?
In a woman receiving long-term phenytoin therapy for epilepsy, pregnancy is likely to result in a reduction in the total concentration of phenytoin measured in plasma.
The pharmacokinetic alteration most important for the interpretation of plasma concentrations during pregnancy is that there is:
The plasma concentration of a drug at steady state is mostly determined by the drug’s:
A patient is taking Drug A for a chronic condition. Drug B is added for a period of time and then stopped. The half-life of both drugs is between 6 and 12 hours.
The following graph shows the total and free concentrations of Drug A: before Drug B is added, over the time Drug B is added, and after Drug B is ceased.
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The most likely mechanism for the interaction is:
The product information for a new anticonvulsant states that in normal individuals it has a volume of distribution of around 2L/kg, hepatic clearance of 5L/hour, a renal clearance of 8L/hour, respiratory clearance of 2L/hour and has 98% protein binding. The usual half-life is stated to be six hours. The usual dose is 100 mg four times a day.
When considering efficacy, safety and compliance, what is the best dosing regime to try in someone with end stage renal disease on haemodialysis?
The following pharmacokinetic data (normalised to a 70 kg individual) are provided for five drugs.
Which one of these drugs is most likely to have the longest elimination half-life?
Punchdrunk is a hypothetical new drug for alcohol withdrawal. The pharmacokinetic section of the product information states: Punchdrunk is rapidly absorbed after oral administration but undergoes extensive hepatic metabolism before reaching the systemic circulation.
Peak plasma levels are reached within 90 minutes for the oral capsules. The bioavailability of oral capsules is low and variable (210% after two capsules in healthy adults) and may increase at higher doses.
Punchdrunk has been shown to be approximately 65% bound to plasma proteins. The volume of distribution has been shown to be of the order of 9 L/kg in healthy adults and increases to about 13 L/kg in the healthy elderly.
The half-life during the elimination phase is approximately four hours in young healthy volunteers.
Punchdrunk is metabolised extensively in the body since less than 1% of the dose is excreted unchanged in the urine. Five urinary metabolites have been found to account for 80% of an oral dose.
The metabolites each have between 10-20% of the potency of the parent drug.
Which clinical condition would lead to the largest increase in peak drug concentration with regular doses?
Drug X is given intravenously using two different regimens, to the same patient on two different occasions. Both times there is no measurable amount of the drug in plasma prior to its administration.
On both occasions the volume of distribution of X is 0.85 L/kg and the plasma half-life is six hours.
Regimen A: Continuous intravenous infusion of 10 mg/kg/hr, with no Prev loading dose.
Regimen B: A loading dose of 50 mg/kg given rapidly intravenously, then a continuous intravenous infusion of 10 mg/kg/hr.
Using regimen A, the plasma concentration of X after 48 hours was 100 mg/L.
One compartment, first order pharmacokinetics can be assumed.
The plasma concentration of X, after 48 hours, using regimen B is closest to:
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A drug X has a half-life of four hours and a volume of distribution of 0.8 L/kg. First order, one compartment pharmacokinetics can be assumed. The drug is administered by continuous intravenous infusion in a dose of Y mg/hr, starting at time zero.
After 24 hours the continuous infusion rate is halved to Y/2 mg/hr. At time 44 hours the plasma concentration of X is approaching the new steady state concentration, B (within 3%).
If, at time 24 hours, the continuous infusion rate had been reduced to Y/4 mg/hr, instead of Y/2 mg/hr, the time at which the plasma concentration of X falls to within 3% of the new steady state concentration, C, would be closest to:
The following pharmacokinetic data are provided for five drugs.
Which of the drugs is most likely to have the slowest rate of clearance from plasma?
Drug X has linear pharmacokinetics and a narrow therapeutic index and is cleared by both renal filtration (80%) and hepatic metabolism (20%). The standard daily dose required by an individual with normal renal and hepatic function to achieve a therapeutic response is 100 mg.
Which one of the following is the best estimate of the daily maintenance dose that would be required in an elderly person with a creatinine clearance one quarter of normal?