Chapter 4 Central Nervous System Answers. 1. What advice would you provide to someone who has just been initiated on Temazepam for insomnia?

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1 Chapter 4 Central Nervous System Answers 1. What advice would you provide to someone who has just been initiated on Temazepam for insomnia? May impair judgement and increase reaction time, and so affect ability to drive or operate machinery; they increase the effects of alcohol. Moreover the hangover effects of a night dose may impair driving on the following day. Patients given sedatives and analgesics during minor outpatient procedures should be very carefully warned about the risks of undertaking skilled tasks (e.g. driving) afterwards. Responsible persons should be available to take patients home afterwards. The dangers of taking alcohol should be emphasised. Drowsiness may persist the next day and affect performance of skilled tasks (e.g. driving); effects of alcohol enhanced. Also see 2. What procedure would you suggest for withdrawing a patient who is dependent on loprazolam, they currently take 2mg each night? Benzodiazepine withdrawal should be flexible and carried out at a reduction rate that is tolerable for the patient. The rate should depend on the initial dose of benzodiazepine, duration of use, and the patient s clinical response. Short-term users of benzodiazepines (2 4 weeks only) can usually taper off within 2 4 weeks. However, long-term users should be withdrawn over a much longer period of several months or more. A suggested protocol for withdrawal for prescribed long-term benzodiazepine patients is as follows: Transfer patient stepwise, one dose at a time over about a week, to an equivalent daily dose of diazepam preferably taken at night. Reduce diazepam dose, usually by 1 2 mg every 2 4 weeks (in patients taking high doses of benzodiazepines, initially it may be appropriate to reduce the dose by up to one-tenth every 1 2 weeks). If uncomfortable withdrawal symptoms occur, maintain this dose until symptoms lessen. Reduce diazepam dose further, if necessary in smaller steps; steps of 500 micrograms may be appropriate towards the end of withdrawal. Then stop completely. For long-term patients, the period needed for complete withdrawal may vary from several months to a year or more. Approximate equivalent doses, diazepam 5 mg alprazolam 250 micrograms clobazam 10 mg

2 clonazepam 250 micrograms flurazepam mg chlordiazepoxide 12.5 mg loprazolam mg lorazepam 500 micrograms lormetazepam mg nitrazepam 5 mg oxazepam 10 mg temazepam 10 mg 3. A patient currently prescribed chlorpromazine 50mg tds is now unable to swallow. The medics want to switch to suppositories. What dose would you recommend? For equivalent therapeutic effect 100 mg chlorpromazine base given rectally as a suppository mg chlorpromazine hydrochloride by intramuscular injection mg of chlorpromazine base or hydrochloride given by mouth. 50mg tds= 150mg daily Therefore if 50mg by mouth = 100mg rectally 150mg by mouth = 300mg rectally 4. A patient who takes clozapine, 100mg bd, is admitted via A&E to ITU. He is unable to take his usual oral medication for 3 days. What advice would you give about restarting the drug? If restarting after interval of more than 48 hours, 12.5 mg once or twice on first day (but may be feasible to increase more quickly than on initiation) extreme caution if previous respiratory or cardiac arrest with initial dosing. 5. How would you monitor lithium treatment, and how should an overdose be treated? Lithium salts have a narrow therapeutic/toxic ratio and should therefore not be prescribed unless facilities for monitoring serum-lithium concentrations are available. Samples should be taken 12 hours after the dose to achieve a serum-lithium concentration of mmol/litre (lower end of the range for maintenance therapy and elderly patients). A target serum-lithium concentration of mmol/litre is recommended for acute episodes of mania, and for patients who have previously relapsed or have sub-

3 syndromal symptoms. It is important to determine the optimum range for each individual patient. Routine serum-lithium monitoring should be performed weekly after initiation and after each dose change until concentrations are stable, then every 3 months thereafter. Additional serum-lithium measurements should be made if a patient develops significant intercurrent disease or if there is a significant change in a patient s sodium or fluid intake. Monitoring of patient parameters Manufacturer advises to assess renal, cardiac, and thyroid function before treatment initiation. An ECG is recommended in patients with cardiovascular disease or risk factors for it. Body-weight or BMI, serum electrolytes, and a full blood count should also be measured before treatment initiation. Monitor body-weight or BMI, serum electrolytes, egfr, and thyroid function every 6 months during treatment, and more often if there is evidence of impaired renal or thyroid function, or raised calcium levels. Manufacturer also advises to monitor cardiac function regularly. Patients should be advised to report signs and symptoms of lithium toxicity, hypothyroidism, renal dysfunction (including polyuria and polydipsia), and benign intracranial hypertension (persistent headache and visual disturbance). Maintain adequate fluid intake and avoid dietary changes which reduce or increase sodium intake. From NICE CKS: If lithium toxicity is suspected, do an urgent lithium level immediately and seek specialist advice. Referral to secondary care may be required depending on the severity of symptoms and the certainty of toxicity. Use clinical judgement to determine the urgency of referral. o o There is no specific antidote to lithium toxicity. In secondary care the treatment is supportive and lithium levels are normally rechecked every 6 12 hours. Osmotic or forced alkaline diuresis may be required, however peritoneal or haemodialysis may be used if levels are above 3 mmol/l. 6. What is the difference in action between fluoxetine and venlafaxine? Fluoxetine SSRI -Selectively inhibit the re-uptake of serotonin (5- hydroxytryptamine, 5-HT). Venlafaxine - A serotonin and noradrenaline re-uptake inhibitor.

4 7. What drugs are available for the treatment of narcolepsy? Methylphenidate unlicensed Pitolisant Modafinil Sodium oxybate under specialist supervision Dexamfetamine sulfate 8. How does orlistat work? Orlistat, a lipase inhibitor, reduces the absorption of dietary fat. 9. What is the oral anti-emetic of choice in patients with Parkinson s Disease? domperidone 10. Which co analgesics are available over the counter, and what do they contain? Co-codamol 8/500 can be sold to the public in certain circumstances; for exemptions seemedicines, Ethics and Practice, London, Pharmaceutical Press (always consult latest edition) Paracetamol 500mg and Codeine 8mg The BP defines Co-dydramol Tablets as containing dihydrocodeine tartrate 10 mg and paracetamol 500 mg. This is a POM medicine. There is a P medicine available (Paramol) which contains Dihydrocodeine Tartrate 7.46mg and Paracetamol 500mg. This is does not meet the BP definition so cannot be called Co-dydramol. 11. What strength of fentanyl patch would you recommend for a patient whose cancer pain has been controlled by MST tablets 60mg bd + 3 x 10mg doses of Oramorph during the previous 24 hours? 60mg twice daily = 120mg 3x10mg =30mg Total daily dose = 150mg From section in BNF prescribing in Palliative Care: 120mg Fentanyl 50 patch 180mg Fentanyl 75 patch However when switching due to possible opioid-induced hyperalgesia, reduce the calculated equivalent dose of the new opioid by one-quarter to one-half. Half of 150mg = 75mg Quarter of 150mg = 112mg morphine salt 60 mg daily fentanyl '25' patch

5 morphine salt 120 mg daily fentanyl '50' patch Therefore start with 25 patch and 12. How do the actions of tramadol and dihydrocodeine differ? Tramadol has opioid effects and enhancement of seratonergic and adrenergic pathways. Dihydrocodeine weak opioid receptor agonist 13. What drugs are available for the prophylaxis of migraine? Beta-blockers propranolol recommended by NICE but also atenolol, metoprolol, nadolol, timolol. TCAs (unlicensed) Topiramate recommended by NICE Sodium valproate unlicensed Valproic acid unlicensed Gabapentin unlicensed Pizotifen Botulinum toxin type A (Botox) 14. What advice would you give a woman taking phenytoin who tells you she has just found out she is pregnant? Women of child-bearing potential should discuss with a specialist the impact of both epilepsy, and its treatment, on the outcome of pregnancy. There is an increased risk of teratogenicity associated with the use of antiepileptic drugs (especially if used during the first trimester and particularly if the patient takes two or more antiepileptic drugs). Valproate is associated with the highest risk of major and minor congenital malformations (in particular neural tube defects), and long-term developmental disorders. There is also an increased risk of teratogenicity with phenytoin, primidone, phenobarbital, lamotrigine, and carbamazepine. Topiramate carries an increased risk of cleft palate if taken in the first trimester of pregnancy. There is not enough evidence to establish the risk of teratogenicity with other antiepileptic drugs. Prescribers should also consider carefully the choice of antiepileptic therapy in prepubescent girls who may later become pregnant. Women of child-bearing potential who take antiepileptic drugs should be given advice about the need for an effective contraception method to avoid unplanned pregnancy. Some antiepileptic drugs can reduce the efficacy of hormonal contraceptives, and the efficacy of some antiepileptics may be affected by hormonal contraceptives. Women who want to become pregnant should be referred to a specialist for advice in advance of conception. For some women, the severity of seizure or the seizure type may not pose a serious threat, and drug withdrawal may be considered; therapy may be resumed after the first trimester. If treatment with antiepileptic drugs must

6 continue throughout pregnancy, then monotherapy is preferable at the lowest effective dose. Once an unplanned pregnancy is discovered it is usually too late for changes to be made to the treatment regimen; the risk of harm to the mother and fetus from convulsive seizures outweighs the risk of continued therapy. The likelihood of a woman who is taking antiepileptic drugs having a baby with no malformations is at least 90%, and it is important that women do not stop taking essential treatment because of concern over harm to the fetus. To reduce the risk of neural tube defects, folate supplementation is advised before conception and throughout the first trimester. In the case of sodium valproate and valproic acid an urgent consultation is required to reconsider the benefits and risks of valproate therapy. The concentration of antiepileptic drugs in the plasma can change during pregnancy. Doses of phenytoin, carbamazepine, and lamotrigine should be adjusted on the basis of plasma-drug concentration monitoring; the dose of other antiepileptic drugs should be monitored carefully during pregnancy and after birth, and adjustments made on a clinical basis. Plasma-drug concentration monitoring during pregnancy is also useful to check compliance. Additionally, in patients taking topiramate or levetiracetam, it is recommended that fetal growth should be monitored. Women who have seizures in the second half of pregnancy should be assessed for eclampsia before any change is made to antiepileptic treatment. Status epilepticus should be treated according to the standard protocol. Routine injection of vitamin K at birth minimises the risk of neonatal haemorrhage associated with antiepileptics. Withdrawal effects in the newborn may occur with some antiepileptic drugs, in particular benzodiazepines and phenobarbital. 15. What advice would you give a patient who has been initiated on vigabatrin? Patients and their carers should be warned to report any new visual symptoms that develop. 16. What is the claimed advantage of fosphenytoin over phenytoin? When only parenteral administration is possible, fosphenytoin sodium, a pro-drug of phenytoin, may be convenient to give. Unlike phenytoin (which should only be given intravenously), fosphenytoin sodium may also be given by intramuscular injection. 17. What warnings would you give to a patient starting pramiprexole? Treatment with dopamine-receptor agonists is associated with impulse control disorders, including pathological gambling, binge eating, and hypersexuality. Patients and their carers should be informed about the risk of impulse control disorders. There is no evidence that ergot- and nonergot-derived dopamine-receptor agonists differ in their propensity to cause impulse control disorders, so switching between dopamine-receptor agonists to control these side-effects is not recommended. If the patient

7 develops an impulse control disorder, the dopamine-receptor agonist should be withdrawn or the dose reduced until the symptoms resolve. Sudden onset of sleep Excessive daytime sleepiness and sudden onset of sleep can occur with dopaminereceptor agonists. Patients starting treatment with these drugs should be warned of the risk and of the need to exercise caution when driving or operating machinery. Those who have experienced excessive sedation or sudden onset of sleep should refrain from driving or operating machines until these effects have stopped occurring. Management of excessive daytime sleepiness should focus on the identification of an underlying cause, such as depression or concomitant medication. Patients should be counselled on improving sleep behaviour. Hypotensive reactions Hypotensive reactions can occur in some patients taking dopamine-receptor agonists; these can be particularly problematic during the first few days of treatment and care should be exercised when driving or operating machinery. 18. What is the cost of a year s treatment with riluzole tablets (Rilutek brand and generic)? 50mg bd = 2 tablets daily x 365 days = 730 tablets Pack size 56 = just over 13 packs Riluzole generic per pack = Rilutek brand per pack = What advice has the MHRA/CHM recommended about varenicline? MHRA/CHM advice: Suicidal behaviour and varenicline Patients should be advised to discontinue treatment and seek prompt medical advice if they develop agitation, depressed mood, or suicidal thoughts. Patients with a history of psychiatric illness should be monitored closely while taking varenicline. 20. What explanation would you give to a patient who asks how his naltrexone tablets work? Naltrexone is an opioid-receptor antagonist. Blocks opioid receptor agonists such as opioid analgesics.

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