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The rate of reduction in plasma concentration of lignocaine following an intravenous bolus dose is more rapid than would be predicted from its elimination half-life.
The best explanation for this phenomenon is that lignocaine:
The delay in the onset of the anticoagulant effects of warfarin is most dependent on the:
A 50 kg person is given gentamicin 320 mg daily IV. The serum concentration measured one hour post the infusion is 20 mg/L and the serum concentration six hours post infusion is 5 mg/L. Using this data, what is the best estimate of the serum gentamicin clearance in this person?
A patient, not previously taking digoxin, is started on digoxin therapy with an intravenous loading dose of 1000 μg, followed by a maintenance dose of 250 μg/day orally. Assuming a half-life of approximately 24 hours in this patient, which one of the following is the best estimate of the time required to reach steady state after the loading dose?
A patient, previously untreated, is commenced on phenytoin therapy with an intravenous loading dose of 1000 mg, followed immediately by oral administration of 300 mg/day as a single daily dose. Assuming phenytoin has an elimination half-life of 30 hours, what is the best estimate of the length of time after the initial loading dose that the patient will achieve steady state conditions with respect to phenytoin?
The graph below shows the estimated concentrations of pralidoxime in a typical patient over the first two days when given as one gram 8th hourly.
If it was given as a two gram bolus followed by an infusion of 500 mg/hour, the best estimate of the time until the drug is in steady state is:
The steady state concentration (defined as reaching at least 95% of the ultimate steady state concentration) of a drug exhibiting first order drug elimination is achieved after which number of elimination half-lives?
A 24-year-old man is admitted to intensive care after being knocked off his bicycle by a car. He is intubated and sedated. His family tell you he has had epilepsy with generalised seizures since age 14. His only regular medication is phenytoin 300 mg daily and his last seizure was one year previously. After resuscitation the results of his blood tests include the following: Sodium (Na) 132 mmol/L [136 – 145 mmol/L] Potassium (K) 4.6 mmol/L [3.5 – 5.0 mmol/L] Creatinine 70 μmol/L [<110 μmol/L] Albumin 24 g/L [36-45 g/L] Haemoglobin (Hb) 96 g/L [130 – 175 g/L] Total Phenytoin 6 mg/L [10 – 20 mg/L] Free Phenytoin 1.5 mg/L [1 – 2 mg/L] To treat his epilepsy, the best approach is to:
Cyclosporin has very low bioavailability. It is a lipid soluble drug and a major route of metabolism is by the CYP3A4 enzyme in the liver. However, removal by the liver accounts for only approximately half of the low bioavailability. The best explanation for the other cause of low bioavailability is:
The bioavailability of a rectal preparation of an anticonvulsant is assessed in a crossover study. The results are as follows.
Which of the following is the best estimate of the rectal bioavailability of this drug?
During a phase 1 clinical trial, a drug was administered as single doses to the same patient, on two different occasions. On the first occasion it was given by rapid intravenous infusion, and on the second occasion the same dose was given by the oral route. The two plasma concentration versus time curves are shown above. Both graphs have the same scale. Area A (intravenous) is five times greater than area B (oral).
Which one of the following statements is not consistent with these findings?
What is one of the utilities of knowing the volume of distribution for a given drug?
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:
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?
A drug with a narrow therapeutic index is highly protein bound and cleared by oxidative metabolism followed by urinary excretion of the inactive metabolite.
The type of drug interaction most likely to cause problems with toxicity of this drug is:
The following graph shows the effect of a new drug measured against its concentration over the first six hours after ingestion.
Which of the following is the best explanation for this concentrationeffect loop?
The following graph shows the effect of codeine against its concentration over the first eight hours after ingestion.
What is the best explanation for this unusual concentration-effect loop for this drug?
The principal aim of a phase 1 trial of a cytotoxic agent is to:
A drug trial is designed to compare the efficacy and safety of a new antihypertensive drug (not yet marketed) to an established drug from the same class. The trial has a randomised, parallel group design with a three-month treatment period, and is to be carried out with a total of 1000 subjects in each group, spread across 50 trial centres.
This type of trial is best described as belonging to which phase of drug development?
The main purpose for performing a phase I clinical trial of a drug in patients with metastatic cancer is to:
A new drug to treat diabetes is being evaluated. In a Phase 1 study a single 100 mg oral dose was given. The concentration effect profile is shown below. The plasma half-life of the drug is four hours. For a phase 2 study the target response is defined as maintenance of >30% of maximum effect.
What dose regime is m100 mg one dailyost likely to achieve the target response and minimise the risk of toxicity?
The diagram below shows cumulative quantal dose-response curves for a hypothetical drug (drug X). The Y-axis represents the percentage of the population studied who: for curve (a) achieved the desired therapeutic effect at a given dose; and for curve (b) experienced the most important toxic effect at a given dose.
Based on this information, the best estimate of the therapeutic index of drug X is approximately:
A drug has a narrow therapeutic index. Plasma half life of 6 hours, volume of distribution of 1L/kg.Medication is renally cleared. Maintenance dose is 10mg/kg four times per day. Target plasma concentration is 80-100mg/L.
What is the best regime to achieve immediate steady state concentration without causing toxicity?
What is the pharmacokinetic property of phenytoin that is responsible for phenytoin toxicity?
The most appropriate methodology to evaluate activity of a cytotoxic cancer treatment is:
If blood is taken 72 hours following a significant paracetamol overdose, which one of the following tests will allow the best prediction of death or need for liver transplantation?
A 15-year-old boy presents to the emergency department with a brief history of being agitated and confused. He is febrile, sweating and tachycardic, and has dilated pupils. He has increased limb tone, hyperreflexia, and myoclonic jerking of limbs. He has a long history of behaviour disturbance, and has been in foster care for several months as he was unable to be contained at home. His carers report that he has been prescribed the selective serotonin reuptake inhibitor paroxetine, but they are unsure whether he has been taking it. He has been out late in the evenings recently. What is the most likely diagnosis?
An autistic child treated with clonidine and risperidone presents with a fever of 38C and myalgia. Investigations show an elevation creatine kinaese.
What is the most likely diagnosis?
A woman is brought to the emergency department having taken an overdose of an unknown amount of paracetamol and alcohol. She was last seen at 12 a.m. (before the overdose) and is found at 5 a.m. The paracetamol concentration is 1100 μmol/L at 6 a.m. (Australian Medicines Handbook (AMH) nomogram below). She took an overdose of paracetamol six months previously. At that time, she was given acetylcysteine and developed generalised urticaria. She is on no other medication and does not drink alcohol regularly.
Which one of the following is the most appropriate treatment plan?
Hyperlipidaemia is classically associated with which class of antiretroviral therapy in HIV?
An 81-year-old female has atrial fibrillation and osteoarthritis, treated with warfarin, digoxin and paracetamol. She recently complained of depressive symptoms and was commenced on the selective serotonin reuptake inhibitor, fluoxetine. Two weeks later she is brought to casualty with an extradural haematoma and her international normalised ratio (INR) is 6.9.
The most likely mechanism by which fluoxetine contributed to the haemorrhage is by its effect on:
A 30 year old male with chronic schizophrenia is well controlled on clozapine. He decides to quit smoking and develops symptoms and signs of clozapine toxicity.
Which of the following is the most likely mechanism for this?
A 26 year old female with history of epilepsy is on long term carbamazepine.She does not want to get pregnant and have therefore been commenced on Implanon(etonogestrel implant). She comes back to your practice 2 months later saying that she’s pregnant despite being on implanon.
What is the most likely reason for failure of contraception?
In a patient who is on erythromycin, combination with which of the following lipid lowering medication is most likely to cause statin induced myopathy?
A patient with long standing diabetes has been recently commenced on Exenatide about a month ago. He presents now to ED with acute abdominal pain. His serum amylase on admission was 1845.Lipase of 545.
Which of the following is the least appropriate management?
Omeprazole is not usually combined with clopidogrel.
What is the reasoning behind this?