Chapter 4: CNS Flashcards
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).
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)
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?
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)
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
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)
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
Cleft Pal(ate)
topiram(ate)
levetiractam/lamotrige safe for pregnancy
Visual Problems
vigabatrin or ethosuxamide (V for visual)
Which drug affects sucking reflex?
phenobarbital
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)
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 !!!!
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
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
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
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
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
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.
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
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
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
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
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
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
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
