One of the many known adverse effects of thiazides is postural hypotension.

Common adverse effects of thiazides worth remembering include:

• Postural hypotension

• Hyponatraemia, hypokalaemia

• gout.

THIAZIDE DIURETICS, LOOP DIURETICS, POTASSIUM-SPARING DIURETICS COMPARISON Important key points:

• Thiazide and Loop diuretics – Hyponatraemia, hypokalaemia and also gout

• Thiazide diuretics – Postural hypotension

• Spironolactone – Hyponatraemia, hyperkalaemia Thiazide diuretics The main use of bendroflumethiazide was in the management of hypertension but recent NICE guidelines now recommend other thiazide-like diuretics Commonly asked side effects include

• Postural hypotension

• Hyponatraemia

• Hypokalaemia

• Gout

• Impaired glucose tolerance Loop diuretics Example: Furosemide – Used especially in heart failure Commonly asked side effects include

• Hyponatremia

• Hypokalaemia

• Gout Potassium-sparing diuretics

Example: Spironolactone Commonly asked side effects include

• Hyperkalaemia

•Hyponatraemia

• Gynaecomastia.

ACE inhibitors can cause hyperkalaemia.

Concomitant treatment with NSAIDs increases the risk of renal damage, and potassium-sparing diuretics increase the risk of hyperkalaemia.

It would be a good idea to recognize common ACE inhibitors – Ramipril, Enalapril, Captopril, Perindopril, and Lisinopril.

If there is no option for ACE inhibitors,

then angiotensin-II receptor blockers (ARBs) would be the next best option as these can too cause hyperkalaemia.

Common ARBs to know are Losartan, Candesartan and Valsartan.

This question requires a sound understanding of mathematics and not medicine. The prescribed dose is 4 mg/kg body weight. The child weighs 10 kilograms, therefore the dose needed will be 40 mg.A preparation of 50 mg/5 ml is equivalent to 10 mg per mL.

Therefore, 40 mg is equivalent to 4 ml. It has to be given twice daily so 4 ml BD is the correct answer.

Atenolol is a beta-blocker.

Beta-blockers are known to cause bronchoconstriction. Salbutamol and salmeterol are beta agonists.

They are used to treat bronchospasm thus they have bronchodilating effects.

Ipratropium bromide inhibits bronchoconstriction Theophylline also relaxes the bronchial smooth muscle causing bronchodilation.

In general, oxycodone should be used when patients are still in pain but have side effects of opioids. This is because oxycodone has twice the potency of morphine to manage pain but with fewer side effects compared to morphine. The pain ladder consists of 3 steps:

1: Simple analgesia like paracetamol. Aspirin, NSAIDs +/- adjuvant therapy

2: Weak opiates: e.g codeine, tramadol, dihydrocodeine +/- adjuvant therapy

3. Strong opiates: morphine, fentanyl patches, diamorphine, oxycodone +/- adjuvant therapy.

If the patient is still in pain, you should never go back a step on the pain ladder, only go forward.

It is particularly important to remember how to calculate breakthrough doses in palliative care for pain relief. If someone is taking PRN morphine regularly for a while, they should have their pain relief reassessed and increased. In this stem, we all can agree that the regular oral morphine dose needs to be increased.

Calculation of the dose to give for breakthrough pain is easy once you understand it.

The dose of normal release morphine for breakthrough pain should be 1/6 of the total 24 hour morphine dose.

In this stem, increasing the oral morphine to 120 mg BD means that the total amount of morphine in 24 hours is 240 mg.

Breakthrough pain dose should be 240 mg/6 which is 40 mg.

Hence, 40 mg of oral morphine should be prescribed as 4 hourly PRN in addition to the BD dose of morphine.

INTERESTING FACT: This method of using one sixth of the total 24 hour dose as a breakthrough dose is a traditional method.

Now, with the newer modified-release analgesia, some physicians are choosing to use only 10% of the total daily regular dose as the as-required breakthrough dose as there is a better balance of analgesia with adverse effects.

One of the known side effects of calcium channel blockers is swelling of the ankle. Calcium channel blockers widen the narrow blood vessels (vasodilation), causing redistribution of fluid from the vascular space, and for some people, this can cause more fluid to leak out of the blood into the tissues around the ankle resulting in swelling.

Calcium channel blockers can be divided into two types, dihydropyridines, which are predominantly vasodilators and generally have neutral or increased effects on vascular permeability (Amlodipine and Nifedipine); and

non-dihydropyridines (verapamil and diltiazem) which reduce vascular permeability and affect cardiac contractility and conduction. All of these can cause ankle swelling.

The pain is likely due to a nerve injury during the operation. Neuropathic pain follows damage or disruption of the nervous system, and

it is often difficult to treat and responds poorly to standard analgesia.

Gabapentin is licensed for neuropathic pain which is described in this stem. Alternatively, amitriptyline could also be used if it was in the options.

Naloxone has a shorter plasma half-life than all opioid analgesics and so coma and respiratory depression often recur when naloxone wears off. Careful observation of the patient is essential and repeated doses of naloxone may be needed.

Extrapyramidal side effects are a very common side effect of metoclopramide which is an antidopaminergic drug.

Symptoms include dystonia, akathisia, parkinsonism, bradykinesia, and tremors. The high fever in this stem could represent a syndrome called neuroleptic malignant syndrome (NMS).

Neuroleptic malignant syndrome is a life-threatening reaction that occurs in response to neuroleptic or antipsychotic medications (usually haloperidol). Metoclopramide is one of the medications that may induce neuroleptic malignant syndrome

. Symptoms usually include high fevers, confusion, agitation, muscle rigidity, sweating, and tachycardia. The onset of these symptoms usually occurs after a few weeks of starting the medication but the symptoms can occur at any time.

NEUROLEPTIC MALIGNANT SYNDROME Neuroleptic malignant syndrome is a rare but life-threatening reaction to anti-dopaminergic medications.

Onset is usually within a few weeks of starting the anti-dopaminergic medication but can occur at any time. Features

• High fever

• Rigidity

• Confusion or altered consciousness

• Variable blood pressure

• Tachycardia Management

• Stop offending medication

• Rapid cooling

• Dopaminergic agents such as bromocriptine.

100 mg of tramadol is equivalent to around 5 mg of intravenous morphine. So 600 mg of tramadol would equate to 30 mg of intravenous morphine. OPIOID EQUIVALENT DOSES Below is an approximate guide for converting opioid analgesics Opioid analgesic Route Dose Codeine PO 100 mg Diamorphine IM, IV, SC 3 mg Dihydrocodeine PO 100 mg Morphine PO 10 mg Morphine IM, IV, SC 5 mg Oxycodone PO 6.6 mg Tramadol PO 100 mg

The following are important points of relative potency conversions which is a need to know for the exam:

• Oral morphine has 1/2 the potency of oral oxycodone.

 When converting from oral morphine to oxycodone, use 1/2 of the dose

• Oral morphine has 1/2 the potency of injectable morphine. When converting from oral morphine to injectable morphine, use 1/2 the dose

• Oral morphine has 1/3 the potency of injectable diamorphine. When converting from oral morphine to injectable diamorphine, divide the dose by three.

The question here is written to test your understanding of the pain ladder. As the pain is not well controlled, we should move up on the pain ladder. The pain ladder consists of 3 steps:

1: Simple analgesia like paracetamol. Aspirin, NSAIDs +/- adjuvant therapy

2: Weak opiates: e.g codeine, tramadol, dihydrocodeine +/- adjuvant therapy

3. Strong opiates: morphine, fentanyl patches, diamorphine, oxycodone +/- adjuvant therapy.

If the patient is still in pain, you should never go back a step on the pain ladder, only go forward. Dihydrocodeine is similar to codeine in its analgesic effect and would not benefit the patient.

There is no point in the patient taking 2 different types of opioids. If a patient is started on a strong opioid, the weaker opioids should be stopped. Oral oxycodone is twice the potency of oral morphine. It would not be suitable unless the patient has tried morphine for a few days first and has intolerable side effects like constipation.

Furosemide is a loop diuretic Loop diuretics The 3 main points that you need to know about loop diuretics are that it may cause:

1. Hypokalaemia

2. Hyponatraemia

3. Gout

Mnemonic: LOOP – HypOOnatraemia, HypOOkalaemia, GOOut

The pain is likely due to nerve-ending damage. Neuropathic pain follows damage or disruption of the nervous system and it is often difficult to treat and responds poorly to standard analgesia.

Gabapentin is licensed for neuropathic pain which is described in this stem.

Alternatively, amitryptiline could also be used if it was in the options as suggested by guidelines however note that although amitryptiline is used frequently for neuropathic pain. Its use is off-label. Bisphosphonates may be used as adjuvants for bone pain and radiotherapy can also be used to improve pain from bony metastases if severe, however, the history provided in this stem is more in line with neuropathic pain.

The onset of the therapeutic effect of Sertraline may be seen within 7 days. However, longer periods are usually necessary to demonstrate an appropriate therapeutic response. In general, an antidepressant effect is usually seen within 2 weeks of starting treatment. If no effect is seen after 2-4 weeks, adherence should be assessed.

Postoperative nausea and vomiting are experienced by about 25% of all patients. Administering more opioid-like substances are likely to worsen the nausea and vomiting. Intractable vomiting usually responds very well to ondansetron which is serotonin (5HT3) antagonist and

it is the most effective agent in these situations.

This is given as 4-8 mg slowly intravenously in adults. Other agents like metoclopramide can also be used. Any oral medication would not be of benefit here as she would just vomit out the medications almost immediately.

The choice of benzodiazepine here is between Buccal Midazolam and Rectal Diazepam. Guidelines do not discriminate between the two. However, Rectal Diazepam is preferred due to its availability and lesser cost as compared to buccal Midazolam.

Since this patient is unable to take oral medications at all, we can immediately eliminate (B), (C), and (D). So, we are now left with B As a guide, halve the 24-hour oral morphine dose to change to subcutaneous morphine. This patient is taking a total of 120 mg of oral morphine per 24 hours.

So the correct dose for subcutaneous morphine should be 60 mg per 24 hours (half the oral dose) by subcutaneous infusion. Please note, use one-third of the 24-hour oral morphine dose over 24 hours for conversion to subcutaneous diamorphine.

The potential adverse metabolic effects of thiazide and thiazide-like therapy include elevations in the plasma glucose.

Bendroflumethiazide may lower carbohydrate tolerance and the insulin dosage of some diabetic patients may require adjustment.

Care is required when bendroflumethiazide is administered to patients with a known predisposition to diabetes.

This patient’s symptoms have everything to do with the fact that he was given metoclopramide for his nausea. It is important to note that neck stiffness can be communicated as being anything from muscle weakness to muscle pain by the patient.

Extrapyramidal symptoms are most commonly caused by antipsychotic drugs such as haloperidol. Other anti-dopaminergic drugs, like the antiemetic metoclopramide, can also result in extrapyramidal side effects.

Acute dystonic reactions can occur as well, and these occur shortly after treatment with metoclopramide.

Antidepressant effect is usually seen within 2 weeks of starting an SSRI. If there is no effect seen after 2 to 4 weeks, it would be advisable to check patient adherence

. If there is no response after 4 weeks and the patient is compliant with his/her medication, consider increasing the dose or switching antidepressants. SSRIs do not cause hypernatraemia.

They do the opposite. They can exacerbate hyponatraemia, especially in the elderly. It is important to inform your patients to continue on the same dose of antidepressants even though they have gone into remission.

They should continue it for at least 6 months to reduce the risk of relapse after which they can reduce the dose slowly over 4 weeks. Note that fluoxetine does not require tapering of the dose over weeks because it has a long half-life.

A single antidepressant usually gives fewer side effects compared to combinations of antidepressants. If one SSRI is not effective, try an alternative SSRI.

According to the British Thoracic Society (BTS) Asthma guideline, the patient is currently on Step 1. As his asthma is not controlled (i.e. he is using his Salbutamol inhaler more than three doses per week), he should be moved up to Step 2 which is a regular low-dose corticosteroid inhaler.

Important tests to do before commencing Lithium therapy - Weight, pulse, and blood pressure - Renal function (primary excretion route) - Full blood counts, U&E - Thyroid function tests and calcium -

Baseline ECG - Baseline parathyroid hormone and magnesium As this patient has already had baseline renal function and liver function tests,

the next best test to do would be thyroid function tests (especially measurement of T4).

As Lithium can cause disease of the thyroid, it is important to exclude hypothyroidism or hyperthyroidism in a patient before commencing Lithium therapy.

Emergency contraception Copper intrauterine contraceptive device Intrauterine devices work by inhibiting fertilization or implantation.

They should be inserted within 5 days of unprotected sexual intercourse (UPSI). It is the most effective form of emergency contraception with less than 1% pregnancy rates when IUCD is used as an emergency contraception.

Progestogen-only emergency contraception - Levonorgestrel Works by inhibiting ovulation and implantation but the mode of action is not fully understood. It should be taken as soon as possible as the efficacy decreases over time.

Licensed for use within 72 hours of UPSI. Ulipristal Acetate.

The main mechanism of action is by inhibition or delay of ovulation.

It should be taken no later than 120 hours (5 days) after intercourse.

Fucidin cream is an antibacterial cream (fusidic acid). If after a week, this has no response then it is most likely a fungal infection on the skin. The red, circular, and itchy rash is most probably a ringworm infection (dermatophytosis) which should respond to Clotrimazole cream.

Percentage concentration is based on g/100 ml so a 1% solution would be 1 g/100 ml or 1000 mg/100. This gives you 10 mg/ml This patient has already been given 20 ml of a 1% solution so he has been given 20 ml at 10 mg/ml. He has been given 200 mg of the drug.

The max dose is 4 mg/kg and this patient is 80 kg. So a maximum dose of the drug for him would be 320 mg. This means that he can only be given 120 mg more of the drug.

Since the answer choices are all in ml, we need to convert 120 mg to ml. 10 mg -= 1 ml 120 mg – x ml Cross multiply and solve for x and you will get 12 ml This patient can only be given 12 ml more of lidocaine.

Combined hormonal contraceptives are less reliable during treatment with rifampicin. Breakthrough bleeding and spotting are common, and pregnancies have occurred.

Barrier methods would be appropriate here as she only requires a short amount of time for extra contraceptive protection. Progesterone implants such as NexplBatman are not recommended with the use of a hepatic enzyme inducer as progesterone released into the bloodstream can be affected by the enzyme-inducing medication.

NexplBatman is also used for 3 years and would be unsuitable for an enzyme inducer which is only prescribed for 2 days. Allergy to ciprofloxacin has no association with an allergic reaction to rifampicin.

It is thrown in here because ciprofloxacin is the preferred choice over rifampicin by most individuals for meningococcal prophylaxis due to drug interactions.

What can be done? Use alternative methods (IUDs, depot or barrier methods), an increased ethinylestradiol dose (at least 50 micrograms during and for 28 days after rifampicin is stopped), an extended or tricycling regimen, or a suitable alternative antibacterial should be given.

Please see Q- 13

The treatment of bone pain due to skeletal metastases in advanced breast cancer begins with analgesia according to the WHO’s analgesic ladder. This patient is already on paracetamol, ibuprofen, and opioids which are no longer helpful. The next step is to offer radiotherapy to provide pain relief. Bisphosphonates are an important adjunct to pain relief.

However, they take time to act (as long as six months). They do have a role in the “acute” management of metastatic bone pain, however, the indications of use are where treatment with conventional analgesia, radiotherapy, and surgery are either unsuccessful or inappropriate.

Dexamethasone is useful when there is evidence of cord compression along with radiotherapy. Vertebroplasty is useful in impending spinal fractures or if they have already occurred.

Oedema and fluid overload in third spaces, such as ascites, are managed with diuretics. The diuretic most useful in cirrhosis is spironolactone.

This is because cirrhotics have intravascular volume depletion, which results in a high aldosterone state. Spironolactone is an aldosterone antagonist.

Common indications of spironolactone - Ascites: patients with cirrhosis develop a secondary hyperaldosteronism. - Hypertension: used as one of the last treatment options (in a 'step 4' treatment) - Heart failure - Nephrotic syndrome.

She most likely started a beta agonist to treat her asthma which is known to cause tachycardia.

A headache that may result from intracranial haemorrhoage due to Warfarin is the most important adverse effect – and patients should be counseled to report any unusual or persistent headache whilst taking Warfarin.

Intravenous morphine would be the most suitable as he is not able to tolerate opioids orally due to the vomiting. There is no rationale behind picking a fentanyl patch as an option. Whilst it is true that if the pain is stable and the oral route is no longer appropriate (e.g. vomiting),

fentanyl patches are a good choice however, the pain here is not stable. The pain was well controlled with oral oxycodone which he has now started to vomit out. He will be in pain again.

Fentanyl is a strong opioid. Due to its long half-life, it will take at least 12 to 24 hours to achieve therapeutic drug levels and so is only of benefit in patients with stable pain. If you had given this to the patient, he would be in severe pain for several hours while waiting for the therapeutic drug levels to kick in.

Fentanyl patches are usually used in cancer patients who have stable pain and are not able to tolerate oral medication. It is not reasonable to use constipation as an excuse in this example to avoid the use of intravenous morphine.

The bottom line is constipation can be prevented or greatly reduced with laxatives but postoperative pain cannot be relieved with a slow-releasing transdermal patch.

In general, oxycodone should be used when patients are still in pain but have side effects of opioids. This is because oxycodone has twice the potency of morphine to manage pain but with fewer side effects compared to morphine. The pain ladder consists of 3 steps:

1: Simple analgesia like paracetamol. Aspirin, NSAIDs +/- adjuvant therapy

2: Weak opiates: e.g codeine, tramadol, dihydrocodeine +/- adjuvant therapy

3. Strong opiates: morphine, fentanyl patches, diamorphine, oxycodone +/- adjuvant therapy.

If the patient is still in pain, you should never go back a step on the pain ladder, only go forward.

This patient has symptoms of diabetic neuropathy. It is often tricky to diagnose as neuropathic pain may present in different ways such as burning, tingling, numbness, and itching.

This stem includes burning as one of the symptoms. The evidence of diabetic nephropathy and diabetic retinopathy is included here as patients with these complications are more likely to have signs of neuropathy. Amitryptiline works well with neuropathic pain, and so it is the answer here. The other medications that are NICE recommended for the initial treatment of neuropathic pain include duloxetine, gabapentin, or pregabalin however amitryptiline is usually used as first-line as it is cheaper and has a simple once-a-day dosing. Capsaicin cream is licensed for use in diabetic neuropathy but it is not the first line.

They are usually used for patients who are not able to tolerate oral treatments. Nerve blocking agents refer to local anaethetics such as lidocaine. They are usually only given as a form of temporary relief such as a femoral nerve block prior to a knee replacement.

While lidocaine does have a role in diabetic neuropathy, it is mainly used for refractory painful neuropathy. Furthermore, its administration is complex and it is given intravenously with ECG monitoring.

Aside from pharmacological interventions, good glycaemic control is vital in managing diabetic neuropathy.

Headache which may result from intracranial haemorrhage due to Warfarin is the most important adverse effect – and patients should be counselled to report any unusual or persistent headaches whilst taking Warfarin.

Sexual dysfunction is a common symptom of depression. However, in addition to this, all antidepressants can cause sexual dysfunction to varying degrees (most commonly serotonin reuptake inhibitors).

Table

1. Sexual adverse effects of antidepressants Drug - Selective serotonin reuptake inhibitors (SSRIs) Prevalence - 60 - 70% Type of the problem experienced -

• All phases of the sexual response

• Paroxetine is associated with more erectile dysfunction and vaginal dryness than other SSRIs Drug - Tricyclic anti-depressants (TCAs) Prevalence - 30% Type of the problem experienced -

• Decreased libido, erectile dysfunction, delayed orgasm, and impaired ejaculation Drug - Venlafaxine Prevalence - 70% Type of the problem experienced -

• Decreased libido, delayed orgasm, and erectile dysfunction. Rarely painful ejaculation and priapism Drug - Mirtazapine Prevalence - 25% Type of the problem encountered -

• Decreased libido, delayed orgasm, erectile dysfunction, absence of orgasm Drug - Reboxetine Prevalence - 5-10% Type of problem experienced -

• Orgasm abnormalities Drug - Duloxetine Prevalence - 46% Type of the problem encountered -

• Delayed orgasm Drug - Irreversible monoamine oxidase inhibitors (MAOIs) Prevalence - 40% Type of the problem experienced -

• Decreased libido, erectile dysfunction, delayed orgasm, and impaired ejaculation • Moclobemide is less likely to cause sexual dysfunction compared with older MAOIs (4% versus 40%).

Muscle relaxants such as Baclofen and Diazepam are very good medications to provide relief from muscle spasms. They are often used as adjuvants of pain control in palliative care.

Clarithromycin is a macrolide antibiotic and is a potent CYP3A4 inhibitor. Clarithromycin is contraindicated with the use of simvastatin. This is because clarithromycin can alter the metabolism of simvastatin leading to an increase in plasma levels and therefore increasing the risk of myopathy and rhabdomyolysis.

Note the advice regarding atorvastatin is to not exceed 20 mg daily if concomitant use with clarithromycin is required.

There is no indication to reduce his metformin dose. Unless he has developed an acute kidney injury or his blood pressure remains low (both parameters not given), there is no indication to reduce his ACE inhibitor.

The CURB-65 score has also been mentioned in this question.

It is worth knowing that the score is a predictor of 30-day mortality for community-acquired pneumonia and ranges from a score of 0 to 5.

It is made up of Confusion (AMTS < 8/10) Urea (> 7 mmol/L) Respiratory rate (30 bpm or above) BP (< 90/60) Age (65 years or above).

It was previously thought that hepatic enzyme inhibitor drugs (like azithromycin) may affect COCP but was later discovered that that there were no significant interaction Only drugs like rifampicin have an interaction with COCP. Combined hormonal contraceptives are less reliable during treatment with rifampicin.

Breakthrough bleeding and spotting are common, and pregnancies have occurred when the patient is on rifampicin and COCP.

According to latest recommendations, no additional contraceptive precautions are necessary when antibiotics that do not induce liver enzymes are used together with combined oral contraceptives, unles diarrhoea or vomiting occur.

The question is testing your knowledge of pharmacology. The area under the curve is the area underneath the graph where plasma concentration of the drug (y) is plotted against time after drug administration (x) and this is most important when looking at these types of questions.

The first-pass effect is where the concentration of a drug is reduced before it reaches systemic circulation. When a drug is administered orally, it travels through the gut, then through the portal system, and into the liver.

The liver metabolizes most drugs and toxins that enter the body and only allows a certain fraction to enter systemic circulation. This ‘first pass’ through the liver reduces the bioavailability of the drug in question. Drugs that are administered via other routes such as the intramuscular, intravenous, and sublingual route bypass being metabolized by the liver, and so the bioavailability of these drugs is greater.

Simply put, a larger area under the curve means a greater drug bioavailability and vice-versa. It would make sense that a drug administered orally would have lesser bioavailability than a drug administered intravenously, therefore hepatic first-pass elimination is the correct answer. Renal clearance of the drug does not pertain to this question at all therefore an increased renal clearance of the intravenous drug and a reduced renal clearance of the intravenous drug is incorrect.

Bioavailability increases in patients who have liver disease since the liver is unable to metabolize substances with efficacy therefore reduced hepatic absorption is incorrect. Increased bioavailability of the drug is incorrect since the oral route would have a decrease in bioavailability as compared to the intravenous route.

Gingival hyperplasia is a recognized side effect of calcium channel blockers.

Side effects known to Doxycycline include headache, nausea, diarrhoea, vomiting, and oesophageal irritation. These side effects can be minimized by advising patients to swallow Doxycycline capsules as a whole, while sitting or standing, with a full glass of water with meals. This reduces the likelihood of feeling nauseous.

In this stem, doxycycline is used however nausea is not specific to doxycycline but to a range of other antibiotics as well. Nausea is one of the most common side effects of any medication.

Virtually all medication has some ability to cause stomach issues. It is important to educate patients on how to reduce the likelihood of nausea to ensure good compliance and the optimum benefit of the medication prescribed.

Antiemetics like promethazine and prochlorperazine are not a good choice in this case.

Firstly, simple advice like taking medication on a full stomach may already do the trick and eliminate the side effects of some medications. Secondly, antiemetics are used for short-term offenders or opioid-induced nausea. This patient is likely to be taking doxycycline for a long period.

One unit equals 10 ml or 8 g of pure alcohol. It is around the amount of alcohol the average adult can process in an hour. In theory, there should be little or no alcohol left in the blood of an adult after one hour of drinking one unit.

Methadone is used to help combat withdrawal effects for opiate misusers. Methadone is an opioid medication and it reduces withdrawal symptoms in people addicted to heroin. It does not cause the “high” associated with drug addiction and thus it is especially helpful for opiate addicts to help them quit the drug addiction problem.

NICE has proposed that either methadone or buprenorphine can be offered as a first-line treatment for detoxification. Buprenorphine is not among the options, so methadone is the answer. Methadone is an opioid receptor agonist, so it acts similarly to heroin, and

hence it is used in opioid substitution therapy as part of the detoxification program. Detoxification can last anywhere from up to four weeks in an inpatient/residential setting and up to 12 weeks in the community.

METHADONE is the METHoD number ONE to detoxify Lofexidine can be used for patients who would like a shorter detoxifying period, who have mild or uncertain dependence, and

who have decided not to use methadone or buprenorphine to detoxify. Naloxone is an opioid receptor antagonist (opposite to methadone which is an opioid receptor agonist). Its main use is reversing the effects of opioids in acute opioid overdose. Naltrexone is an opioid antagonist (like naloxone) but with a longer half-life.

It has a role as an adjuvant in preventing relapses in opioid-dependent patients who have remained opioid-free for at least 7-10 days. Codeine is a weak opioid with no role in opioid detoxification.

Oral morphine is usually offered to patients with pain from progressive cancer as part of palliative care much like in this stem. If they have difficulty swallowing, oral medications would be inappropriate. Another route to deliver the same equivalent dose of the opioid should be offered.

In the scenario of a palliative patient with “stable” pain, patches would be the most appropriate way as they are easy to use and can be managed at home.

The doses of fentanyl are not likely to be asked at this level but for those who would like to know more, a transdermal fentanyl 12 microgram patch is equivalent to approximately 45 mg oral morphine daily.

When faced with a question of this type, choose the answer that makes the most sense in the context of the question. You already know that a paracetamol overdose causes liver damage. This happens because a metabolite of paracetamol decreases stores of the antioxidant glutathione. Decreased stores of glutathione cause liver cells to be damaged by free radicals. When N-acetylcysteine is given,

it is broken down into L-cysteine which then gets converted to glutathione which in turn protects from damage from free radicals.

N-acetylcysteine inhibits cytokine NF-kB and not interferon-alpha. It has a minimal effect on cytochrome P450 enzymes.

N-acetylcysteine causes the breakdown of sulfhydryl bonds.

This additional effect of N-acetylcysteine also makes it useful as a mucolytic treatment in patients with respiratory conditions.

N-acetylcysteine increases glutathione stores.

Heparin works by binding to antithrombin (AT) III, resulting in its activation. The activated antithrombin (AT) III then inactivates thrombin via the inhibition of prothrombin (coagulation factor II), factor Xa, and other proteases of the coagulation cascade.

Regardless of whether heparin is administered at a high dose or a low dose or whether it is delivered as low molecular weight heparin (LMWH) or unfractionated heparin (UFH), the initial mechanism of action is the same (the activation of antithrombin) although later interactions might differ.

During the normal coagulation cascade, thrombin is converted to fibrinogen which is, in turn, converted into strands of fibrin.

Even though heparin does decrease the conversion of fibrinogen to fibrin by inhibiting thrombin, this is indirectly done and the single best description of how heparin works is the inhibition of prothrombin to thrombin.

Ans. The key is B. Bendroflumethiazide [ Thiazide diuretics may cause hyperuricemia and thus cause or precipitate gout].

Ans. The key is C. Apnoea. [Respiratory depression may occur following lorazepam administration].

Ans. The key is A. Lithium. [Lithium overdose can cause coarse tremor].

Ans. The key is D. Thiazide. [Thiazide was prescribed for hypertension and when lithium was prescribed its level increased due to thiazide (Thiazide diuretics have a significant potential to increase serum lithium concentrations.

These diuretics induce a natriuresis that leads to a compensatory increase in the reabsorption of sodium (and lithium) in the proximal tubule) and thiazide also caused hypokalemia resulting in the given picture].

The key is A. Atenolol

Ans. The key is D. Fluoxetine. [SSRIs are frequently associated with delayed ejaculation].

The key is B. Plenty of fluids

Ans. The key is B. Cholestatic jaundice. [Flucloxacillin can cause cholestasis and hence cholestatic jaundice].

Ans. The key is A. Headache. [Headache from intracranial hemorrhage is more important complication about which patient should be careful with (it is more important than osteoporosis)].

Ans. The key is A. Ramipril. [Both ramipril and losartan can cause hyperkalemia]

The key is D. Naloxone is eliminated faster than methadone

Ans. The key is D. Sodium valproate. [As the bag is not empty but full of medicine this is not a case of over-dose. The side effect of lithium in the therapeutic range is fine tremor. Sodium valproate (a well-known mood stabilizer) can cause coarse tremors in the therapeutic range].

The key is A. Take it after a meal

The key is D. Per rectal

Ans. The key is A. Metoclopramide. [Extrapyramidal effects like neck stiffness are common side effects of metoclopramide and also there is a rise in temperature].

Ans. The key is B. Hyponatremia. [Thiazide causes hypercalcemia, hypokalemia and hyponatremia].

The key is A. Amitryptiline

Ans. The key is A. Low Na+, Low K+. [Loop diuretics causes hyponatremia and hypokalemia].

The key is B. Naloxone. [Opioid Antagonist, reverses the effects of fentanyl, though it has to be administered for a longer period due long half-/life of fentanyl]