Mock Pharmacology Module 2

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:

is rapidly distributed to adipose tissue.

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induces its own metabolism.

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is subject to marked first pass metabolism

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is rapidly bound to plasma proteins.

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has high renal clearance.

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The delay in the onset of the anticoagulant effects of warfarin is most dependent on the:

rate of catabolism of clotting factors

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loading dose of warfarin.

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rate of absorption of warfarin.

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clearance rate of the S-isomer of warfarin.

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clearance rate of the R-isomer of warfarin.

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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?

3.5 L/hour.

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37 mg/hour.

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12.5 mg/hour.

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1 L/hour.

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3 mg/L/hour.

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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?

5 days.

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Immediately.

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6 hours.

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24 hours

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2 days.

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A previously untreated patient 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?

Six days.

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Immediately.

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One day.

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Three days.

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Twelve days.

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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:

3 hours.

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8 hours.

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16 hours.

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24 hours.

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40 hours.

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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?

5

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4

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3

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2

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6

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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]
Hemoglobin (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:

continue his usual dose of phenytoin

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decrease the dose of phenytoin.

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prescribe an additional loading dose of phenytoin and continue his usual maintenance dose.

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prescribe an additional loading dose of phenytoin and increase the maintenance dose.

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replace phenytoin with sodium valproate

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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:

metabolism in the small intestine

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poor dissolution of tablets

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nucleophilic attack by stomach acids

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destruction by coliform bacteria

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circulating esterases in portal blood

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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?

30%

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12.5%

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20%

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66%

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90%

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Which of the following antibiotic has the best oral bioavailability?

Levofloxacin

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Ampicillin

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Cephalexin

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Azithromycin

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Flucloxacillin

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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?

The drug is a well-absorbed, controlled-release preparation.

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The drug has a high hepatic extraction ratio.

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The oral bioavailability of the drug is poor.

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There is a significant first pass effect.

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There is metabolic degradation of the drug by the gut mucosa.

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What is one of the utilities of knowing the volume of distribution for a given drug?

It allows for calculation of a loading dose to be given in emergency situations

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It allows for calculation of the therapeutic index

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It is used to estimate the extent of protein binding

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It allows for calculation of the drug elimination constant (k)

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It is the main determinant of the most appropriate route of administration

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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:

Y is a non-competitive antagonist of X.

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X is a competitive antagonist of Y.

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X is a non-competitive antagonist of Y.

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Y is a competitive antagonist of X.

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Y is a partial agonist.

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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?

Drug A.

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Drug B.

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Drug C.

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Drug D.

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Drug E.

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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:

inhibition of cytochrome P450 enzymes.

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displacement of the drug from plasma proteins.

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inhibition of glucuronyltransferase

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reduction in glomerular filtration rate.

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inhibition of renal tubular secretory mechanisms

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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 concentration effect loop?

Tachyphylaxis to the effects of the drug is occurring.

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The drug has active metabolites.

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There is rapid absorption of the drug after oral administration

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There is rapid distribution of the drug to adipose tissue.

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The drug competitively binds to its receptor

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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 drug has active metabolites

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There is rapid absorption of drug after oral administration.

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Tachyphylaxis to the effects of the drug is occurring

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There is slow distribution of the drug to the site of action

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The drug irreversibly binds to its receptor.

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The principal aim of a phase 1 trial of a cytotoxic agent is to:

establish the maximum tolerated dose (MTD).

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maintain the patient's hope that treatment is possible.

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determine the best schedule of administration.

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define tumour response rate

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measure progression-free survival.

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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 randomized, 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?

Clinical phase III studies.

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Preclinical efficacy studies

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Clinical phase I studies

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Clinical phase II studies

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Clinical phase IV studies

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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 most likely to achieve the target response and minimize the risk of toxicity?

100 mg one daily

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100 mg twice daily.

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200 mg once daily.

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200 mg bd

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400 mg bd

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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:

3

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1

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0.7.

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0.3.

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0.

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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?

Initial dose of 20mg/kg, then 10mg/kg every 6 hours

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Initial dose 10mg/kg, then 10mg/kg every 3 hours.

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Initial dose 10mg/kg, then 20mg/kg every 6 hours.

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Initial dose of 20mg/kg, then 10mg/kg every 3 hours.

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Initial dose of 20mg/kg, then 20mg/kg every 3 hours.

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What is the pharmacokinetic property of phenytoin that is responsible for phenytoin toxicity?

Saturation of metabolism

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Active metabolites of the drug

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First order kinetics

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Low porportion of protein bound drug

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Tachyphylaxis

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The most appropriate methodology to evaluate activity of a cytotoxic cancer treatment is:

phase II study.

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in-vitro testing.

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phase I study.

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phase III study

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phase IV study.

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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?

Prothrombin time-international normalised ratio (PT-INR).

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Blood ammonia.

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Serum alanine aminotransferase (ALT).

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Serum albumin.

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Serum bilirubin.

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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?

Serotonin syndrome

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Inhalent abuse (chroming).

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Marijuana-induced psychosis.

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Methylenedioxymethamphetamine (MDMA, ecstasy) overdose.

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Neuroleptic malignant syndrome.

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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?

Neuroleptic malignant syndrome

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Clonidine overdose

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Dystonic reaction

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Malignant hyperpyrexia.

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Serotonin syndrome

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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?

Administration of intravenous acetylcysteine

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Administration of activated charcoal.

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Administration of intravenous cimetidine

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Haemoperfusion.

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Repeat paracetamol measurement at 8 a.m. and reassess.

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Hyperlipidaemia is classically associated with which class of antiretroviral therapy in HIV?

Protease inhibitor

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Nucleoside reverse transcriptase inhibitor

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Non nucleoside reverse transcriptase inhibitor

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Integrase inhibitor fusion inhibitor

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fusion inhibitor

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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:

cytochrome P-450

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glucuronidation

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platelets.

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vitamin K.

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compliance

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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?

Reduced metabolism of clozapine in the absence of nicotine

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Treating nicotine withdrawal with additional clozapine doses

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Induction of enzymes due to nicotine replacement therapy

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Interaction with bupropion

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Improved compliance

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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?

interaction with carbamazepine

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Implanon had expired.

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low strength of implanon.

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displacement of the drug from plasma proteins.

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impaired absorption

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In a patient who is on erythromycin, combination with which of the following lipid lowering medication is most likely to cause statin induced myopathy?

simvastatin

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pravastatin

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fluvastatin

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rosuvastatin

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bezafibrate

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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 with an elevated serum Lipase of 545.

Which of the following is the least appropriate management?

Continue exenatide

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Blood culture if febrile

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Limitation of oral intake

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Intravenous fluid resuscitation

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Morphine for pain relief

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Omeprazole is not usually recommended to be used in combination with clopidogrel.

What may be the reasoning behind this?

Omeprazole inhibits CYP2C19 thereby decreasing clopidogrel's efficacy

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Omeprazole induces CYP2C19 thereby decreasing clopidogrel's efficacy

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Omeprazole induces CYP2D6 thereby increasing clopidogrel's efficacy

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Omeprazole inhibits CYP2C19 thereby increasing clopidogrel's efficacy

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Omeprazole inhibits CYP2D6 thereby decreasing clopidogrel's efficacy

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A 42-year-old man presents to the emergency department 14 hours after consuming an unlabelled home-distilled spirit at a party. He complains that his vision is “like standing in a snowstorm.” On examination he is tachypnoeic (respiratory rate 28/min), and fundoscopy reveals bilateral optic disc hyperaemia with blurred margins. His pupils are sluggishly reactive.

Arterial blood gas shows:

pH 7.18 (7.35–7.45)
HCO₃⁻ 8 mmol/L (22–26)
pCO₂ 20 mmHg (35–45)

Serum osmolality is 320 mOsm/kg (275–295); calculated osmolality is 290 mOsm/kg. Anion gap is 28 mmol/L (4–12).

Which of the following is the single most important initial intervention to prevent progression of his visual loss?

Intravenous fomepizole

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Intravenous methylprednisone

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Urgent haemodialysis

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Intravenous sodium bicarbonate

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High-dose intravenous folinic acid

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Mock Pharmacology Module 2

Pharmacology Study Notes

Pharmacokinetics Made Easy, 2nd Edition

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