Chapter 4: CNS Flashcards by Nasim Khatibi-Jah

Updates

> New - valproate safety measures apply from 31 January. Valproate must not be started in new patients (male or female) younger than 55 years, unless two specialists independently consider and document that there is no other effective or tolerated treatment, or there are compelling reasons that the reproductive risks do not apply. For the majority of patients, other effective treatment options are available.

> Dispense valproate in unbroken packs. (round up or down to cover treatment)

> New – first line treatment for focal seizures is now levetiracetam or lamotrigine. Carbamazepine is second line treatment.

> New - remind healthcare professionals prescribing the antipsychotic aripiprazole (2nd generation) of the risk of addictive gambling and other impulse control disorders (binge drinking, eating, antisocial, dopamine agonsists also cause this problem). Healthcare professionals should advise patients, their families and friends to be alert to these risks. Awareness of this risk must increase among patients and prescribers, as gambling is recognized as a common risk factor linked to suicide .

> Selective serotonin re-uptake inhibitors: breast-feeding advice for all drugs in class and individual drug monographs updated (see examples in fluoxetine and sertraline).

should not be taken for long time, after week 16/18 can be taken where there is no other alternative

> Selective serotonin re-uptake inhibitors: pregnancy advice updated (see example in citalopram).

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Dementia (over age 65)

 Become a dementia friend! Go to www.dementiafriends.org.uk
 Characterised by a widespread impairment of mental function
 Alzheimer’s disease is the most common type of dementia
 Symptoms could be cognitive or non-cognitive
 Cognitive (brain function)– memory loss, speech difficulty, difficulty with thought process
 Non- Cognitive (mechanical/physical)– Aggression (antipsychotics: haloperidol, benzos: lorazepam, alprazolam), wandering, confusion, delirium
 Alzheimer’s disease could be mild/moderate (donepezil, rivastigmine, galantamine) or moderate/ severe (memantine)

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Dementia Treatment

 Drug treatment – Acetylcholinesterase inhibitors - Donepezil, Galantamine, Rivastigmine and memantine.
 Side effects of these drugs diarrhoea, urination, teary eyes, sweating, salivation (opposite of antimuscarinic side effects)
 Galantamine can cause serious skin reactions – stop if skin rash is noticed
 Dementia affects over 65yrs. Affects more women than men.
 QUESTION: Which of these four is used to treat MILD/MODERATE dementia and which is used to treat severe dementia?

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Dementia Patches

 Rivastigmine - transdermal administration counselling
 1. Do not cut, fold or break the patch.
 2. Apply to clean, hair free skin.
 3. Do not apply to hot skin. (increases absorption)
 4. Do not apply to broken skin.
 5. Report any skin reactions
 6. Rotate the site of application. (reduce skin irritation, insulin: lipodystrophy)

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Dementia Quick Points

> ALZHEIMER’S IS THE MOST COMMON TYPE OF DEMENTIA
NB: Some cases of dementia is associated with severe behavioural disturbance such as aggression and extreme agitation. What drugs would you treat this with? benzo (avoid in pt at risk of falls bc can cause ataxia or confusion)/antipsychotic (can cause cardiac problems, avoid in pt at risk of CVD)
Q. MHRA Warning that antipsychotics can increase risk of strokes and death when given to the elderly to treat dementia.
For vascular dementia (treat with anti platelet drugs (aspirin/clopidogrel), DO NOT TREAT WITH Donepezil, Galantamine, Rivastigmine and memantine.
Dementia with lewy bodies, parkinsons – another type of dementia

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Epilepsy

 A sudden surge of electrical activity of neurons in the brain. (must have 2 or more in a year can be diagnosed)
 Two categories of seizure
 Generalised and partial seizures
 Generalised (multiple parts of brain) - tonic-clonic, absence (1st line: SEALL: ethosuxamide (1), sodium valproate, alternatively give levertiracitam/lamotrigine) , myoclonic (lamotrigine/levetiracetam, sodium valproate no longer first line), atonic/ tonic seizures
Partial (from one hemisphere of brain)– focal seizures (1st line: levetiracetam/lamotrigine)

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3 Categories

 3 categories
 Category 1 – examples are 3PC phenytoin, phenobarbital, primidone,
carbamazepine .
➢ Brand only for epilepsy, potent inducers, blood disorder symptoms
 Category 2 – valproate, lamotrigine, topiramate, clobazam, clonazepam (pt preference/clinical judgement)
 Category 3 – levetiracetam, lacosamide, gabapentin, pregabalin (not brand specific)
 * Risk of cross-sensitivity between anti-epileptic drugs* pt develops tolerance problem, switch to another medicine in another category

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Cleft Pal(ate)

topiram(ate)

levetiractam/lamotrige safe for pregnancy

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Visual Problems

vigabatrin or ethosuxamide (V for visual)

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Which drug affects sucking reflex?

phenobarbital

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Epilepsy Treatment

➢ once daily meds
➢ lamotrigine , perampanel, phenobarbital , phenytoin .
➢ monotherapy preferred .
➢ Avoid abrupt withdrawal (increase risk of seizure).
➢ combination of two or more drugs may be necessary.
➢ DVLA ADVICE !!
➢ REPORT ADVERSE REACTIONS . MHRA WARNING . YELLOW CARD SCHEME
➢ ANTI-EPILEPTIC HYPERSENSITIVITY SYNDROME/NUEROLEPTIC MALIGNANT SYNDROME (give bromocriptine) – monitor initial 2 months (dont stop drug but seek medical attention)

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ADVERSE EFFECTS OF ANTI-EPILEPTIC DRUGS

Taking anti-epileptic medication can increase risk of
i. Neural tube defects (reduce concentration of folic acid, important for formation of DNA)=>5mg
ii. Haemorrhagic disease (profuse bleeding) of new-born (give vit K to treat )
iii. Folate deficiency
 All anti-epileptic drugs are associated with a small increased risk of suicidal behaviour.
 Ethosuximide can cause blood disorder- absence and myoclonic seizures.
 Topiramate can cause cleft in 1st trimester
 Sodium valproate should be ‘’avoided’’ in women of child bearing age and in men under 55, unless 2 specialist sign-off (last line). Important !!!!

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Patients prescribed new anti-epileptic medication must be counselled adequately to report unusual side-effects. What symptom specifically related to this drug would you advise a patient taking lamotrigine regularly to seek prompt urgent medical attention if they notice?
A. Dyspepsia
B. Delirium
C. Dry mouth
D.Widespread rash
E. Constant Belching

D. Widespread rash

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Carbamazepine (high risk)

 Therapeutic range: 4 to 12mg/L (20 to 50 micromol/litre); PRESCRIBE by brand for epilepsy- specific category
➢ Toxicity (incoordination, blurred vision, double vision, drowsiness, nystagmus, ataxia, arrhythmias, nausea & vomiting, diarrhoea, **hyponatraemia: can increase hyponatratmia: SSRI, diuretic, lose water lose salt, desmopresson, TCAs) /CHARCOAL
➢ Blood disorders (fever, sore throat, unexplained bruising or bleeding)
➢ Skin disorders (mouth ulcers, rash)
➢ Hepatic disorders e.g. hepatitis (severe GI upset, fatigue, jaundice, dark urine)
➢ Antiepileptic Hypersensitivity Syndrome (fever, rash, swollen lymph nodes)
>Prescreen: carbamazepine and phenytoin for specific allele bc can increase Steven Johnsons in Thai/Han Chinese
➢ Intrxs -Increased plasma concentration with acetazolamide, cimetidine, clarithromycin (inhibitor), erythromycin
**>2 inducers: rifampicin and phenytoin=>rifampicin is more potent which reduces phenytoin and will be at risk of seizures, increase phenytoin dose
➢ Decreased plasma concentration with phenytoin, rifabutin, St. John’s Wort

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Sodium Valproate

 “Valproate should not be used in female children and women of childbearing potential unless other treatments are ineffective or not tolerated. In this case, valproate must be prescribed and dispensed according to the valproate pregnancy prevention programme”.
 Ensure patients receive Valproate PATIENT GUIDE.
 Valproate should be dispensed in the original package. 26=>30, 80=>100
 Remind patients of risk in pregnancy, PPP & use highly effective contraception.
 In case of suspected pregnancy, females should be advised NOT to stop taking the medication and contact their GP immediately. (refer to A/E> GP)
 Unborn babies exposed to valproate are at risk of neurodevelopmental disorders and congenital malfunctions - advise females accordingly
 It can cause blood disorder symptoms, pancreatic and hepatic toxicity

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Phenytoin

 GIVE SAME BRAND –bioequivalence
 Plasma conc of 10 to 20 mg/ L or 40 to 80 micromole/litre  Can cause blood disorder, hirsutism: growth of unwanted hair
 Doctor to discontinue - if rash is noticed
 contra-indicated in acute porphyrias
 interacts with lidocaine, dronaderone, amiodarone (lead to reduced HR), Azoles
 Bradycardia and hypotension ,if hypotension occurs, reduce infusion rate or discontinue
 pre-screening – Han Chinese/thai patients –HLAB 1502- RISK OF s.j.s.
 reduce dose or infusion rate in elderly, and in renal or hepatic impairment

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Gabapentin

Caution in diabetes, elderly, history of substance abuse
* is a schedule 3 CD drug
* is safe custody required: no
* Avoid excessive alcohol (opioids, olanzapine) due to CNS DEPRESSION and a times death.
* Addictive and abuse –monitor patients
* Monitor for RESPIRATORY DEPRESSION (opioids as well, olanzapine)- MHRA

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Lamotrigine

> Warn patients of Blood disorders.
Patients and their carers should be alert for symptoms and signs suggestive of bone-marrow failure, such as anaemia, bruising, or infection.
Aplastic anaemia, bone-marrow depression, and pancytopenia have been associated rarely with lamotrigine.
Skin reactions - Lamotrigine can cause skin rashes . Rash is sometimes associated with hypersensitivity syndrome. Consider withdrawal if rash or signs of hypersensitivity syndrome develop
Drug interactions – phenytoin, rifampicin, carbamazepine and sodium valproate.

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Benzodiazepines (sch. 4 pt. 1)

> Types of benzodiazepines
Short acting - Temazepam, Oxazepam, Loprazolam, Lormetazepam, and Lorazepam
Long acting- Nitrazepam, Flurazepam, Diazepam, Alprazolam, Chlordiazepoxide HCl,
and Clobazam
Overdose symptoms drowsiness, ataxia, nystagmus. ANTIDOTE: flumazonil
Withdrawal switch to diazepam should be gradual.
Paradoxical effects - Benzodiazepines can also cause a paradoxical increase in hostility and aggression e.g. talkativeness, excitement, and aggressive antisocial acts.
Elderly patients – warning - Benzodiazepines and the Z-drugs (zopiclone, zolpidem, zaleplon) (risperidone and loop diuretics cause falls) should be avoided in the elderly due to an increased risk of confusion leading to falls and injury.

**donepezil and atorvastatin: donepezil must be taken at night

***amox 500mg on rx and diazepam 5mg, 56 tabs is written on: keep rx, report, must get new rx

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You are working in a surgery and are undertaking a medicines review with a 53-
year-old woman who recently had her lithium brand changed from Priadel to
Liskonum. Now that the discontinuation of Priadel has been reversed, the
patient has asked if she can switch back to Priadel, after experiencing some
side effects from the new brand. SEE RESOURCE
Which of the following is the most appropriate course of action?
A. refer the patient to a mental health specialist for advice
B. remain on Liskonum as an ordering quota remains in place for Priadel
C. remain on Liskonum as lithium brand switching is not recommended
D. remain on Liskonum as the supply of Priadel is likely to be variable
E. switch back to Priadel with appropriate monitoring in place

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Bipolar Disorder

> aka manic depression
Extreme mood swings
 BRAND ONLY, Lithium treatment pack/ card should be given to patients on initiation of rx with lithium.
 CONTRAINDICATIONS
 Cardiac insufficiency, dehydration, low sodium diets (lill absorb lithium instead), brugada syndrome, untreated hypothyroidism, lithium and NSAIDs (NSAIDs reduce eGFR, reduces kidney function, leads to high lithium as its not being excreted)
 Hyponatraemia can lead to lithium toxicity because in the absence of sodium the body absorbs lithium
 Monitoring
 * Serum lithium concentration – weekly, then every 3 months once dose becomes stable
 * Renal function – every 6 months
 * Cardiac function – every 6 months
 * Thyroid function – every 6 months
BMI and body weight. Lithium can cause weight gain

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Lithium Quickpoints

 LITHIUM may impair performance of skilled tasks (e.g. driving,
operating machinery)
 A combination of symptoms such as visual disturbances, polyuria, muscle weakness, CNS disturbances, vomiting, diarrhoea, restlessness and stupor suggests LITHIUM OVERDOSE. (no antidote, give plenty of fluids and stop diuretics)
 Target of 0.4 – 1 mmol/ litre —– after 12 hours after a dose as lithium is a narrow therapeutic index drug.
 Target 0.8 – 1 mmol/litre —— is for acute acute episodes of mania , sub-syndromal symptoms and relapse cases, elderly pts

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Patients on mono-amine oxidase inhibitors should avoid certain foods such as ‘’mature cheese’’. The options below contain some examples of food which should be avoided by patients on mono-amine oxidase inhibitors except one? Which one has the least amount of tyramine.

A. Sauerkraut
B. Kale
C. Soya
D.Tofu
E. Marmite

B. Kale

leads to hypertensive crisis if consumes food and takes MAOI

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Depression

 Patients feel sad, low self-esteem, lack energy and interest, weight change, worry and suicidal thoughts.
Introduce: psychological help (CBT)
 The major classes of antidepressant drugs include
1. tricyclic and related antidepressants (amitriptyline, nortriptyline, doselupin)
2. 1st line: selective serotonin reuptake inhibitors (SSRIs) (citalopram, escitalopram, fluoxetine, sertraline)
3. SNRI – venlafaxine, duloxetine
4. monoamine oxidase inhibitors (MAOIs) phenelzine, Isocarboxazid e.t.c
 OTHER - Mirtazapine can cause blood disorder. (can use if pt has epilepsy as well), safer for patients with suicidnal thoughts alongside depression

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MAOI

Learn examples–Mr P.I.T.S.R moclobomide, phenelzine, isocarboazosid, tyrpramine, seregiline, rasagline >cheese, wine, sauerkraut, soy, marmite >Not very popular nowadays due to interactions >Not indicated in manic phase OF bipolar disorder >AVOID IN CEREBROVASCULAR DISEASE. Cautious in epilepsy >MAOIs have dangerous interactions with some foods and drugs. Such as sympathomimetics (Sudafed, pseudoehirdine), sumatriptan and tyramine rich food >This interaction can lead to hypertensive crisis >MAY AFFECT DRIVING AND USE OF MACHINES DUE TO DROWSINESS

MAOI

 switch / wash out period– Other antidepressants should not be started for 2 weeks after treatment with MAOIs has been stopped (3 weeks if starting clomipramine or imipramine). Conversely, an MAOI should not be started until:  at least 2 weeks after a previous MAOI has been stopped (then started at a reduced dose)  at least 7–14 days after a tricyclic or related antidepressant (3 weeks in the case of clomipramine or imipramine) has been stopped  at least a week after an SSRI or related antidepressant (at least 5 weeks in the case of fluoxetine) has been stopped

TCA

 contra-indicated in arrythmias,manic of bipolar disorder  Tricyclic antidepressants are not effective for treating depression in children. >Imipramine for noturnal enuresis  Withdrawal effects can occur within 5 days of withdrawal  can prolong QT (domperidone, SSRI, quinolones, macrolides, amiodarone)  can cause anti-cholinergic side effects: dry mouth, urinary retention, blurry vision, constipation, drowsiness  may cause drowsiness. Warn drivers !!  caution in diabetes (can cause increase in glucose levels), epilepsy and in patients with high suicide risk

SSRI

 inhibit re-uptake of 5-HT  contra-indicated in epilepsy, manic phase  Can cause hyponatraemia – sig if less 130 mmol/L  Can increase suicide in young people. Give fluoxetine under 16.  severe poisoning can cause SEROTONIN SYNDROME  may affect driving  see drug interactions in BNF 82 – omeprazole (reduces absorption of SSRI) , Nsaid (increase bleeding), NOACs, macrolides (increase SSRIs concentration)  HOW TO SWITCH between anti-depressants

Serotonin Syndrome

Drugs: Tramadol (opioids) Hates Me Tramadol, Herbal Medicines (St. John's Worts), Antidepressants (All), Triptans (sumatriptan, etc), Epileptic Drugs (Carbamazepine), Substances (illicit substances), Anti-emetics ***table  S – Sweating and Shivering  E – Excitement  R – Rigidity  O – Oculogyric crisis (spasmodic deviation of the eyeball into a fixed position)  T – Tremor (Twitching), Tachypnoea and Tachycardia  O – Oral mucosal dryness  N – Neuromuscular Excitability (Hyperreflexia and Clonus)  I – Irregular heart rhythm (arrhythmias)  N – Nausea and vomiting

A 40-year-old female patient is concerned about weight gain associated with taking olanzapine. She would like to be put on a drug with the least risk. Which drug in the options below can cause the least increase in weight? A. Quetiapine B. Amisulpiride C. Primozide D. Risperidone E. Aripriprazole

You are working as GP pharmacist. One of your patient, Mr B, has been diagnosed with depression and now complains that symptoms worsened after 1 week of taking the antidepressant, fluoxetine 20mg. You have assured him that symptoms may worsen at start of treatment and hence advised him to continue taking the medication. On his next appointment, Mr B has reported that his symptoms has improved and he is able to carry out his daily activities with ease. Mr B enquires if he can stop taking the medication. He is turning 70 years old soon.  What would be your advice? A) Advise Mr B that antidepressant should be taken for at least 6 months following remission. B) Advise Mr B that antidepressant should be taken for at least 12 months following remission. C) Reduce his fluoxetine dose gradually over few weeks before stopping. D) Switch to a herbal supplement, St John’s Wort. E) Stop taking the antidepressant and start with cognitive behavioural therapy.

B) Advise Mr B that antidepressant should be taken for at least 12 months following remission. **if less than 65=>A

Psychoses and Schizophrenia

Symptoms: Positive (never done before): hallucinations, delusions, disorganised speech, Negative (stopped doing things they use to): reduced speech, more quiet, stop socialising, reduce self care  Antipsychotic drugs relieve positive psychotic symptoms such as thought disorder, hallucinations, and delusions, and prevent relapse. Typical and Atypical are two types  Atypical antipsychotics may be better for negative symptoms such as apathy and social withdrawal.

Psychoses and Schizophrenia Management

* Typical (first-generation) Cause extra-pyramidal side effects (EPSEs) e.g. chlorpromazine, haloperidol, flupentixol, fluphenazine , sulpiride * Atypical (second-generation) Reduced risk of EPSEs, but may occur in high doses; associated more with metabolic side effects e.g. amisulpride, aripiprazole, olanzapine, quetiapine, risperidone **table with examples in WA SIDE EFFECTS * Extrapyramidal symptoms * ACUTE Psuedoparkinsonism (tremor or rigidity) ####ACUTE Dystonia (abnormal face and body movements)=>give procyclidine * ACUTE akathisia (inner restlessness) ###### CHRONIC tardive dyskinesia (rhythmic, involuntary movements of tongue, face, and jaw) * More side-effects to learn for pre-reg exam. EPS Vs metabolic side-effects

Clozapine

* Agranulocytosis * Myocarditis and cardiomyopathy Risk of fatal myocarditis and cardiomyopathy: common in first 2 months * Constipation - Intestinal obstruction ---- Risk if constipation, intestinal obstruction, faecal impaction, and fatal paralytic ileus=>refer to urgent medical attention * Hypersalivation - Can be treated with hyoscine hydrobromide aka KWELLS * Clozapine should be offered if schizophrenia is not controlled despite the sequential use of at least 2 different antipsychotic drugs (one of which should be a second- generation antipsychotic drug) ***cloze my madness, last drug to be considered * SMOKING (inducer): reduces clozapine * Weight gain, Blood disorder – monitor patient

Olanzapine

* Can cause serious weight gain * monitor - blood lipids, weight, blood glucose * monitor blood conc – MHRA warning * CNS and respiratory depression .Increased risk especially in those also receiving a benzodiazepine; blood pressure, pulse and respiratory rate should be monitored for at least 4 hours after intramuscular injection (leave at least one hour between administration of IM olanzapine and parenteral benzodiazepines) * can interact with Gabapentin , pregabalin to cause respiratory depression

Aripripazole

>Cause less weight gain >cause less increase in prolactin levels >check cost before dispensing >can interact with paroxetine and some azoles >can cause feeling of euphoria >good alternative in some cases **has better side effects compared to other similar drugs, low side effect profile Update: MHRA, impulse control disorder

Adherence

>What is the most appropriate reason to change antipsychotic patches to depot injection ? To improve adherence >use z-track technique is the technique of choice and rotate site. >Which drug can cause contact sensitization (can peel off skin, use gloves)?? Chlopromazine (1st gen)

Nausea and Vomitting

 ANTIEMETICS  Dopamine antagonists – metoclopromide , domperidone  Antipsychotic drugs – haloperidol, levomepromazine  Antihistamines – cyclizine, cinnarizine, promethazine  5HT3 Antagonists – ondansetron

Ideal Anti-Emetic

>Pamper my pregnancy=>procloperazine/promethazine, metoclopramide (2nd line) >PREGNANCY - First trimester – mild – no RX >If severe give procloperazine, metoclopramide or promethazine , cyclizine maybe but avoid ondasetron as can cause cleft palate >End of life – levomepromazine , haloperidol >QT PROLONGATION eg domperidone, macrolides, quinolones >domperidone – choice in parkinsons disease . 1 week for domperidone max >cinnarizine (Stugeron) – choice in vertigo >dexamethasone/ ondasetron/ metclopromide – choice in post – operative / chemotherapy >hyoscine (hydrobromide version, Kwells, least drowsiness), travel bands , promethazine – motion sickness

Parkinson's disease

Patients with suspected Parkinson’s disease should be reffered . Its incurable !! It takes many years to fully develop Inform DVLA  levodopa  Dopamine agonists  MAOIb (segeline, resagaline)

Parkinson's

 Patients with suspected Parkinson’s disease should be referred to a specialist and reviewed every 6 to 12 months. Its incurable !!  Parkinson's disease symptoms could be described as  Motor (physical: shaking, tremor) and non-motor symptoms.  Give levodopa if motor symptoms develop – first line  Dopamine agonists are often preferred over levodopa in early non motor-severe disease, whereas levodopa is the most effective option when symptoms are disabling.  Why is levodopa always formulated as a combined preparation with either carbidopa or benserazide? reduce breakdown of drug, helps to target dopamine receptors, reduces side effects, increase effectiveness 1:4 or 10 (takes lions share, levodopa)

A patient currently taking co-careldopa complains to his doctor that he suffers from acute dystonia from time to time . His GP decides to prescribe him an additional medication to help with this symptom. Which drug can the GP prescribe? A. Ropinirole B. Entacapone C. Haloperidol D. Metoclopromide E. Procyclidine

Parkinson's Quickpoints

 Psychotic symptoms – patients and carers should be warned that antiparkinsonian treatment can precipitate psychotic symptoms  Impulse control disorders - Patient may experience pathological gambling, binge eating, and hypersexuality. If impulse control disorder develops, the dopamine- receptor agonist or levodopa should be withdrawn or the dose reduced until the symptoms resolve.  Driving Sudden onset of sleep (CNS stimulant, modaphenel)- Excessive daytime sleepiness and sudden onset of sleep can occur; exercise caution when driving or operating machinery. Patients should be counselled on improving sleep behaviour.  Hypotensive reactions - Hypotensive reactions can occur in some patients; these can be particularly problematic during the first few days of treatment and care should be exercised when driving or operating machinery.  Drooling of saliva – offer non-drug treatment before glycopyronium / botulinium

General

* Avoid switching brands if possible – good practice * Essential to stick to same time of administering medicine. * Avoid abrupt withdrawal of treatment. * Neuroleptic malignant syndrome – don’t stop abruptly  Offer patches to patients who cannot swallow: ritigotine, 16mg MAX

Drugs

 COM-T INHIBITORS (helps with end of dose symptoms) OPICAPONE, TOLCAPONE, Entacapone – can change urine colour to reddish- brown . Caution concomitant iron containing products.  levodopa formulated as a combined preparation with carbidopa/benserazide in a 4:1 ratio respectively.  Bromocriptine – can cause pulmonary retroperitoneal and pericardial fibrotic reactions.  Pramipexole – risk of postural hypotension=>Give midodrine

Pain

WHO Pain Ladder analgesics: paracetamol, ibuprofen, NSAIDs weak opioids: codeine, tramadol strong opioids: methadone, morphone, oxycodone, fantail strongstrong: epidural **learn children doses

Opiod Analgesics

 2 types – weak and strong opiods  weak opioids – codeine, dihydrocodeine – mild to moderate pain  Strong opioids – morphine , oxycodone – moderate – severe pain  Side-effects  CNS depression, Respiratory depression, Constipation , Dependence, Drowsiness, QT prolongation.  OPIOID OVERDOSE ANTIDOTE: naloxone

Neuropathic Pain

 TRICYCLIC ANTIDEPRESSANTS  Examples - AMITRIPTYLLINE , NORTRIPTYLLINE (may be better tolerated than amitriptyline)  ANTIEPILEPTICS  GABAPENTIN and PREGABALIN  OPIOID ANALGESICS  If there is inadequate response to other drugs, opioids can be given.  TRIGEMINAL NEURALGIA  Sudden and severe facial pain described as electric shocks in the jaw, gum or teeth. Occurs in short unpredictable attacks.  Treated with Carbamazepine or Phenytoin *evidence for strong opioids is weak

 Michael comes into your diabetic clinic one morning complaining of pain in his left foot. He describes a prickling, burning sensation that has been present for one and a half months and is disrupting his night sleep increasingly. Michael bought some paracetamol over the counter, but it seems to be making no difference whatsoever. Which drug listed below is the least effective drug in managing Michael’s symptoms ?  A. Ibuprofen  B. Carbamazepine  C. Amitriptyline  D. Nortriptyline  E. Gabapentin

A. Ibuprofen

Sleep Disorder

INSOMNIA  Causes include stress, irregular sleep schedule, depression. Pain and medication  SYMPTOMS:  Difficulty initiating sleep, Difficulty maintaining sleep  Early morning awaking, Poor sleep quality  TYPES OF INSOMNIA: 3 types transient, acute and chronic.

Sleep Treatment

OTC: nytol, phenegen for 28 days, not for regular use  MELATONIN  Z-DRUGS (CD4 PART 1)  Short- term use (4 weeks max; 2 weeks if zaleplon) for severe insomnia that interferes with daily life.  ZOPICLONE (taste disturbance) bitter  ZOLPIDEM (GI disturbance, leave 8 hours before driving)  ZALEPLON (shortest acting)  BENZODIAZEPINES SEDATIVES (CD4 PART 1) – lorazepam, loprazolam , diazepam, oxazepam  Avoid Z-drugs/Benzodiazepines in elderly; ataxia and confusion = falls/ injury.

Substance Dependence

Alcohol Dependence Nicotine Dependence

Alcohol Dependence

 ACAMPROSTATE OR NALTREXONE  Alternatives:  DISULFIRAM (unpleasant systemic reaction to small amounts of alcohol = flushing, throbbing headache, palpitation, tachycardia, nausea, vomiting)  REDUCTION OF ALCOHOL CONSUMPTION IN PATIENTS WITHOUT PHYSICAL WITHDRAWAL SYMPTOMS  NALMEFENE: For patients with a high drinking risk level, who do not require immediate detoxification.  WERNICKE’S ENCEPHALOPATHY  THAIMINE (vitamin B1)  Patients with alcohol dependence are at risk.  High risk: malnourished or decompensated liver disease.

Nicotine Dependence

 Examples include Patches, Gum, lozenge, nasal spray, oral spray, sublingual tablet, inhalator  NICOTINE REPLACEMENT THERAPY (NRT)  Prolonged-release formulations: 16-hour /24-hour patches  Use 24-hour patch if strong cravings for cigarettes on waking  Immediate-release formulations: urge to smoke/prevent craving - Gum, lozenge, nasal spray, oral spray, sublingual tablet, inhalator.  SIDE EFFECTS: Mild local reactions due to irritant effects of nicotine, Gastro-intestinal disturbances: nausea, vomiting, dyspepsia, hiccup.  BUPROPION – inhibits re-uptake of dopamine and noradrenaline in the central nervous system . patients should not smoke whilst on this drug  VARENICLINE (selective nicotine receptor partial agonist)  For patients with an expressed desire to stop smoking . Given in conjunction with behavioral therapy.  MHRA/CHM advice: Suicidal behavior and varenicline  Stop and see GP for agitation, depression, suicidal thoughts.

Treatment

 CNS STIMULANTS 1.MODAFINIL 2.METHYLPHENIDATE (CD2) 3.DEXAMFETAMINE (CD2) 4.SODUIM OXYBATE (CD2) 5.PITOLISANT

Narcolepsy

 Rare long-term brain disorder that causes a person to suddenly fall asleep at inappropriate times. SYMPTOMS: 1.Sleep attacks 2.Excessive daytime sleepiness 3. Cataplexy 4.Sleep paralysis 5.Excessive dreaming

Mr K a 60-year-old patient weighing 72kg, was initiated on phenytoin capsules to treat epilepsy. Mr K’s plasma concentration was measured 5 days later. What is the ideal target therapeutic serum- phenytoin concentration. A. 0.5–1mg/L B. 2–4mg/L C. 4–12mg/l D. 10– 20 mg/l E. 8 – 15mg/l

The MHRA warned in 2017 that Gabapentin can lead to a rare but dangerous side-effect. For this reason, Gabapentin should be monitored for this particular side-effect/ adverse reaction. Which of the following is an adverse reaction being monitored by the MHRA regards Gabapentin ? A. Steven Johnson’s syndrome B. Haschimoto syndrome C. Respiratory depression D. Hypertensive crisis E. Bipolar disorder

A 70-year-old woman who suffers from Parkinson’s disease complains of nausea and vomiting. She currently takes Amlodipine and simvastatin. She contacts you and asks for your recommendation as regards antiemetic medication. Which of the following is first line in this scenario? A. Cyclizine. B. Domperidone. C. Promethazine. D. Haloperidol. E. Dexamethasone.

During a webinar, you are asked which drug Patients of Thai and Han Chinese origin must be tested for HLA-B 1502 allele due to risk of steven Johnson’s syndrome. What would your answer be? A. Gabapentin B. Phenobarbital C. Lamotrigine D. Levetiracetam E. Phenytoin

You work in hospital when a 55-year-old patient was rushed in by ambulance. You learn that the patient “mistakenly” took too many diazepam tablets, and he is now suffering terrible side-effects including slurred speech, enlarged pupils, confusion, drowsiness amongst others. Which drug would you recommend treating this patient with? A. Fluid therapy B. Naloxone C. sodium bicarbonate Flumazenil E. Protamine sulphate

A 67-year-old woman started to take lithium 200mg once daily prescribed by her GP one month ago, alongside ethosuximide tablets daily that she has been taking for the past 10 months for epilepsy. When collecting her repeat prescription, she complains of having dark urine, jaundice, nausea and fatigue for the last two weeks. She wonders if her new tablets is to blame. Which of the following is the most appropriate advice to give to this patient? A. she is experiencing a side-effect of lithium, and whilst safe to continue taking it, she may wish to see her GP for an alternative. B. she should see her GP as the dose of lithium may need to be increased. C. She is experiencing a side-effect of ethosuximide, and whilst safe to continue taking it, she may wish to see her GP for an alternative. D. stop taking ethosuximide straight away and see her GP as soon as possible. E. the symptoms described are not known to be caused by lithium.

Mr. H is a 50-year-old patient is currently suffering cellulitis. His doctor decides to prescribe clarithromycin 500mg BD for 7 days. He hands the prescription to you, but you notice on his PMR that she takes the following medication. His eGFR is currently 40ml/min and serum creatinine is 74 μmol/L. Metformin 1g BD Citalopram 40mg OD Sitagliptin 50mg OD What is the main risk of not notifying her doctor of a potential drug interaction? A. lactic Acidosis B. Hyperkalaemia C. Myopathy D. QT-prolongation E. Ototoxicity

A 14-year-old male patient is diagnosed with Absence seizure. He takes no other medication. Which of the following is the least suitable treatment for this patient? A. Lamotrigine B. Sodium valproate C. Ethosuximide D. Valproic acid E. Carbamazepine

Which statement regarding Clozapine is not true? A. Clozapine can increase the risk of agranulocytosis. B. Clozapine can cause hypersalivation. C. Clozapine can cause blood disorders such as sore throat and high temperature. D. E. Clozapine can increase the risk of seizures Clozapine is an example of typical anti-psychotic drugs.

Mr. Y. a 24-year-old male patient is diagnosed with tonic/atonic seizures. He takes no other medication. Which of the following is the least suitable treatment for this patient? A. Lamotrigine B. Sodium valproate C. Ethosuximide D. Rufinamide E. Topiramate

Benzodiazepines can cause paradoxical effects. Which of these is not an example of a symptom associated with paradoxical effects? A. Increase in hostility B. Increase in alcohol intake C. Increase in aggression D. Increase in antisocial acts E. Increase in excitement.

Adam is a 65 year-old patient who takes Priadel (lithium) 400mg tablets regularly. He walks into your pharmacy with a prescription for two medication. Rx..... 28 Amlodipine 5mg tablets Rx..... 28 Ramipril 5mg capsules What is the most serious concern as regards taking these medicines concomitantly? A. Myopathy B. Reduced eGFR C. Increased risk of blood disorder D. Hypertensive crisis E. Thrombosis

Mr. Z is a 23 year old university student. He walks into a pharmacy and explains to the pre-reg student on duty that whilst revising for his exam he could feel the onset of a migraine. He took a tablet of sumatriptan prescribed by his GP. The migraine went away but came back 3 hours later. He would like to know what to do next. What should the Pre-Reg student say? A. The Pre-Reg student should advise the patient to contact his GP at this point B. The Pre-Reg student should advise the patient to take Nurofen tablets and drink loads of water. C. The Pre-Reg student should refer the patient to A & E . D. The Pre-Reg student should advise the patient to rest in a dark room and the symptoms will eventually go away. E. The Pre-Reg student should advise the patient to take another sumatriptan tablet.

Mr. K comes into your pharmacy One afternoon and asks to buy stepsils lozenges and ibuprofen tablets. He tells you that they are for his sorethroat and he also mentions that he takes metformin, domperidone, Indapamide, carbamazepine, gliclazide. What would be your next line of action? A. Sell him both stepsils lozenges and ibuprofen tablets as there is nothing to worry about. B. Sell him strepsils lozenges but do not sell him ibuprofen tablets as he is diabetic. C. Do not sell him anything. Whilst it’s safe to continue taking his medication, he may wish to see his GP. D. Sell him stepsils lozenges but not ibuprofen tablets as ibuprofen is known to interact with ciprofloxacin. E. Do not sell him anything. Refer him to his GP immediately.

Which of the following anti-depressant can also be used to treat nocturnal enuresis in children ? A. Lofepramine B. Imipramine C. Nortriptyline D. Citalopram E. Doxepin

Mrs. T., a 63-year-old, presents in your pharmacy with severe headaches and difficulty with her vision which has lasted for about 7 days. Which drug can lead to side-effects such marked sedation, stupor, confusion, visual field defects and general encephalopathic symptoms. * A. LITHIUM * B. Galantamine * C. carbamazepine * D. Flumazenil * E. Naloxone * F. Vigabatrin * G. Selegiline * H. Donepezil * I. Glucosamine

Mr. A takes citalopram to manage depression. Which of the drugs listed above can increase the risk of hyponatremia when given concomitantly with citalopram? * A. LITHIUM * B. Galantamine * C. carbamazepine * D. Flumazenil * E. Naloxone * F. Vigabatrin * G. Selegiline * H. Donepezil * I. Glucosamine

An elderly patient with Parkinson has been advised to avoid foods high in tyramine such as mature cheese, marmite, soya, game and alcoholic drinks due to the risk of hypertensive crisis. Which drug can interact with such foods? * A. LITHIUM * B. Galantamine * C. carbamazepine * D. Flumazenil * E. Naloxone * F. Vigabatrin * G. Selegiline * H. Donepezil * I. Glucosamine

A 50-year-old was prescribed a new medication in hospital. Upon discharge he was advised to avoid a low salt diet. Which drug does this advice apply to? * A. LITHIUM * B. Galantamine * C. carbamazepine * D. Flumazenil * E. Naloxone * F. Vigabatrin * G. Selegiline * H. Donepezil * I. Glucosamine

Mrs. B takes warfarin as part of management for atrial fibrillation. Which of the drugs listed above can lower INR value when taken together with warfarin? * A. LITHIUM * B. Galantamine * C. carbamazepine * D. Flumazenil * E. Naloxone * F. Vigabatrin * G. Selegiline * H. Donepezil * I. Glucosamine

Martha a 59-year-old woman started to take lithium tablets prescribed by her GP one month ago for bipolar, alongside carbamazepine 200mg BD and metformin hydrochloride 500mg three times a day that he has been taking for the past 12 months. When collecting her repeat prescription, she complains of having dark urine, nausea and fatigue for the last 3 weeks. She wonders if her new tablet is to blame.  Which of the following is the most appropriate advice to give to this patient?  A. She is experiencing a side-effect of Lithium, and whilst safe to continue taking it, she may wish to see her GP for an alternative  B. Keep taking Lithium and see your GP urgently.  C. She should see her GP as the dose of lithium may need to be reduced.  D. stop taking lithium straight away and see a doctor urgently.  E. Keep taking carbamazepine and see your GP urgently.

Mr. K currently takes a number of different drugs such as Amlodipine, cefalexin, atorvastatin , donepezil and chlorphenamine tablets. He is 75 years old and a bit forgetful. He would like to find out which of his medicines he definitely has to take at night? Choose the most appropriate option below?  A. Amlodipine  B. Cefalexin  C. Atorvastatin  D. Donepezil E. Chlorphenamine

A 55-year-old woman is prescribed 500mg sodium valproate tabs, 1 BD for treatment of tonic-clonic seizures. You decide to give her and her carer counselling advice. Which of these is least suitable advice to give ? a) Swallow this medicine whole. Do not chew or crush b) Take with or just after food, or a meal c) Female patients taking sodium valproate for migraine prophylaxis do not need to be enrolled in Pregnancy Prevention Programme as it is for off-label use. d) Warning: Do not stop taking this medicine unless your doctor tells you to stop e) Continue taking this medicine and inform your doctor if you get pregnant.

A 15-year-old male patient suffers from depression which started 6 months ago. Despite forms of non-medical therapy his condition continues to get worse. His specialist is now thinking of prescribing a drug for his condition. Which drug is the most appropriate to prescribe?  A .Sertraline  B. Nortrytiline  C. Fluoxetine  D. Amitryptiline  E. Citalopram

A 65-year-old man with schizophrenia presents in hospital where you work. His carer explains that he was prescribed sulpiride tablets initially to manage his condition. Aripriprazole was also added to his regimen 6 months ago. Despite taking both drugs his symptoms of schizophrenia continue to persist. According to NICE guidelines, what is the most accurate next line of action to take? a) Stop both sulpiride and aripriprazole and prescribe risperidone instead. b) Switch sulpiride to risperidone and leave aripriprazole unchanged. c) Continue both drugs and add a third drug such as risperidone. d) Continue both drugs and add a third drug such as clozapine. e) Switch both drugs to rotigotine patches instead.

Jamie is a 19-year-old who has just returned from university and his mother has noticed some changes in his behaviour. His mother tells you she does not understand what’s going on with her son as he avoids everyone by locking himself up in his room, he’s lost interest in his usual everyday activities, he hasn’t had a shower in 3 days, he’s constantly accusing his dad of tampering with his things and he could be heard talking about an imaginary woman in his bedroom.  What do you think could be going on with Jamie? A. Jamie is suffering from anxiety B. Jamie is suffering from depression C. Bipolar disorder D. Jamie is displaying symptoms of schizophrenia E. Jamie is smoking marijuana at university

A transgender woman walks into your pharmacy. The patient would like the morning after pill. During the consultation, you establish that unprotected sex occurred 4 days ago and that the patient also takes amitriptyline and carbamazepine regularly for epilepsy. What would your next line of action be?  A. Supply levonelle-one-step  B. Supply Ella-one  C. Refer to another pharmacy  .D. Refer to a sexual health clinic  E. Ask the patient to book an appointment at the GP surgery

Katie is a 28-year-old with poorly controlled epilepsy who has also been battling depression for the past 7 months. She has tried psychological interventions and cognitive behavioural therapy which have both proven to be unsuccessful. Given her situation, which of the following would you consider as first line drug treatment for Katie? A.Mirtazapine B. Citalopram C. Phenelzine D.Olanzapine E. Fluoxetine

A female patient comes into your pharmacy, and you overhear her conversation with the counter assistant. She describes her symptoms as a headache which feels like a tight band around the head and a feeling of pressure behind her eyes. Which of the following should the counter assistant think is the most likely diagnosis based on information given by the patient. A. Tension Headache B. Cluster Headache C. Migraine C. Subarachnoid haemorrhage D. Sinus headache

Katie 28 a-38-year-old man enters your pharmacy requesting loperamide. He explains he has been feeling quite anxious and feverish for the past two days. He feels his heart beating faster and he is experiencing involuntary twitching movements in both hands. He currently takes the following for bipolar disorder. * Priadel MR (Lithium 200mg) tabs, 1 OD * Venlalic XL (Venlafaxine 225mg) tabs, 1 OD Which of the following is the most appropriate advice to give the patient? a) Recommend him to see his GP as symptoms of his bipolar disorder are not controlled. b) Stop taking lithium and venlafaxine and book a regular appointment to see the GP. c) Seek immediate medical attention by visiting his GP today or A&E d) Recommend oral rehydration salts and to see the GP if his symptoms do not resolve in 24 h. e) Supply the patient with loperamide and tell him to see GP if symptoms persist after 48 hours.

Mr. V. is a 40-year-old man on sodium valproate for the management of epilepsy. He is admitted in hospital due to a urinary tract infection. The junior doctor asks you about a safe choice of antibiotics for Mr. V for short term treatment? Which of the following is least suitable for Mr. V due to his current anti-epileptic medication?  A. Amoxicillin  B. Cefalexin  C. Meropenem  D. Nitrofurantoin  E. Trimethoprim

A male patient is concerned about hyperprolactinimia associated with anti-psychotic therapy. He would like to be put on a drug with the least risk. Using the resource provided, which drug in the options below can cause the least prolactin elevation? A. Quetiapine B. Amisulpiride C. Primozide D.Risperidone E. Sulpiride

A patient visits your pharmacy and enquires about purchasing ‘St John warts’ over the counter as they have heard that it will help with improving their mood.  Which of the following medication below is most likely to interact with St Johns Wart? A. Levothyroxine B. Propylthiouracil C. Fluoxetine D.Bendroflumethiazide E. Donepezil

A 65-year-old man walks into your pharmacy and asks to buy Sudafed decongestant tablets to treat his cold and flu symptoms. He explains that he has experienced the symptoms for nearly three days, and it disrupts his work as a university lecturer. He is otherwise fit and well. He hands you a piece of paper which contains a list of his current medication. Atorvastatin 40mg , Donepezil 10mg , Tranylcypromine 20mg, metoclopramide 10mg and co-codamol 15mg/500mg tablets. What would be your next line of action?  A. Refer him to his GP immediately.  B. Sell him Sudafed tablets as it is totally safe for him to take.  C. Refer him to A and E immediately.  D. Sell him olbas oil decongestant instead of Sudafed.  E. Advise him that there is nothing over the counter he can buy for his symptoms.

A 60-year-old woman has undergone hip replacement surgery and complains of nausea and vomiting. She currently takes Ramipril and simvastatin. A nurse contacts you and asks for your recommendation as regards antiemetics for this patient.  Which of the following is first line in this scenario ?  A. Cyclizine.  B. Domperidone.  C. Promethazine.  D. Haloperidol.  E. Dexamethasone.

Mr and Mrs James. Present in your pharmacy and ask to speak to you privately. Mrs. James explains that she is rather worried as Mr. James, her husband, has recently started betting regularly in the local betting shop, he also binge drinks and yesterday whilst they were out together, he shouted abuse at the cashier in the supermarket. She would like to know if any of his medicines is to blame.  Which of the following drugs could be responsible for Mr. James’ behaviour ?  A. Donepezil  B. Domperidone.  C. Memantine  D. Carbergoline.  E. Rivastigmine.

MATCH the relevant monitoring requirement to the correct drug.  i. IV AMIODARONE --- ECG  Ii. Oral Methotrexate ---- LFT  Iii. Oral lithium .......... .....? A. HBAIC B.B. CHEST XRAY C. Egfr D.Lipid levels E. BSA

Mrs. D. is an 88-year-old female patient in palliative care. She has terminal cancer and is currently suffering from acute severe pain. She also takes the following medication. Amlodipine 10mg, Ramipril 5mg, metformin 500mg , Atorvastatin 40mg and donepezil 5mg. Her most recent eGFR is 32 ml/min. See resource via link below  Which of the following drugs is the most suitable for Mrs. D. ?  A. Fentanyl transdermal patches  B. Tramadol oral capsules  C. Buprenorphine transdermal patches  D. Dihydrocodeine tablets  E. Morphine oral tablets Prescribing in palliative care | Medicines guidance | BNFC | NICE

One Sunday afternoon, an anxious patient comes into the pharmacy on a Sunday afternoon. She informs you that she has run out of her sleeping pills and is staying in the area for the week and urgently needs some tablets until she returns home where she can pick up her prescription. She shows you a box of zopiclone 3.75mg tablets labelled with her details containing one tablet. You agree to issue an emergency supply, but you only have zopiclone 7.5mg tablets in stock. What is the maximum number of zopiclone 7.5mg tablets that can legally be supplied?  A.14  B.5  C.28  D.2  E.3

A 47-year-old man is prescribed carbamazepine 200mg tab three times a day for trigeminal neuralgia. The prescription is for generic carbamazepine but on the patient records the patient has always received the branded product (Tegretol).  Which of the following is the most appropriate course of action?  a) Contact the prescriber as the bioavailability differs between the branded and generic formulation  b) Dispense the generic formulation as indicated on the prescription  c) Dispense the Tegretol branded formulation  d) Contact the prescriber to change the prescription back to Tegretol  e) prescribed

High Risk Drugs

USE YOUR BNF Write monitoring requirements for:  lithium  Carbamazepine Sodium valproate  Phenytoin