Central Nervous System Flashcards
Dementia
Progressive and largely irreversible syndrome characterised by impairment of mental function
Alzheimer’s disease accounts for most cases of dementia
Characterised by a range of cognitive and behavioural symptoms
Aims of dementia treatment
Promote independence
Maintain function
Manage symptoms of dementia
Symptoms of dementia
Cognitive dysfunction; memory loss, concentration, communication, problem/reasoning solving
Non-cognitive symptoms below;
Behavioural symptoms; aggression, distress, agitation and psychosis
Difficulties with activities of daily living e.g washing or dressing
Non-drug treatment of dementia
Structural cognitive stimulation programme to patients with all types of dementia presenting with cognitive symptoms = to stimulate the mind
Types of dementia
- Protein build up; decreases ACh causing dementia; treated by stopping ACh decline
- Vascular dementia; reduced blood flow to brain; treat similar to stroke and cognitive rehabilitation
What drug class to avoid in dementia?
Anticholinergics
E.g antidepressants, antihistamines, antipsychotics
As they further increase decline of Ach
TREAT DEMENTIA WITH ACETYLCHOLINESTERASE - therefore anticholinergics do the opposite
Mild to moderate dementia drugs used?
Anticholinesterase inhibitors
Donepezil - neuroleptic malignant syndrome; increase risk with concomitant antipsychotic
Galantamine - stop if rash appears SJS
Rivastigmine - GI disturbances (withhold until resolved can switch to patches)
Moderate to severe dementia drug treatment
Memantine
NMDA glutamate receptor antagonist
Anti-cholinesterase is CI in moderate or severe Alzheimer’s
Anticholinergic side effects
Diarrhoea
Urination
Muscle weakness or cramps
Bronchospasm
Bradycardia
Euresis
Lacrimation
Salvation or sweat
MHRA warning with dementia and elderly patients
Antipsychotics should only be offered if risk of harming themselves or others; experiencing, agitation, hallucination, delusion which is causing severe distress
Causes increase risk of stroke and death
Risk vs benefit
Need to closely monitor
Dementia and co-morbidities
Depression and anxiety; use antidepressants for pre-existing severe MH problems due to anticholinergic effect
Agitation, agression, distress and psychosis
Sleep disturbances; ideal mainstay of treatment would be to use non-drug interventions to avoid mental cloudiness and sedation
Management of cognitive symptoms in dementia
Should be initiated by specialists
Reassess treatment for; donepezil, galantamine, rivastigmine and mementine regularly
Only continue treatment if symptoms are improving
Avoid antipsychotics unless you have to
Avoid anticholinergics id possible
Epilepsy control
Treatment aims to prevent occurrence of seizures
Start small doses and increase gradually until seizures are controlled
Choice of epileptic drug determined by several factors; Comorbidity, concomitant medication, age, sex and epilepsy syndrome
Keep dosage frequency as low as possible to encourage patient adherence
Once daily antiepileptics
Good for compliance
Lamotrigine, Perampanel, Phenobarbital and Phenytoin
LP3
Epilepsy management
1st line is monotherapy; one drug used
2nd line addition of second drug (CAUTION; when changing and adding as withdrawal can cause rebound seizures
Combination therapy with 2/+ can increase S/E and drug interaction
Stick to regime that provided best balance between tolerability and efficacy
Prescribe a single anti epileptic drug wherever possible
MHRA advise on epileptic drugs
Potential harm between switching between brands / generic products
3 risk category to help HCP decide what to switch or not
Switching between formulations - can lead to variety in bioavailability hence should remain on specific manufacturers products
Category 1 anti epileptics
SPECIFIC BRAND - if being used for anti epileptic purposes
Report any adverse effects suspected on yellow card system
Carbamazepine, phenytoin, phenobarbital and primidone
CP3
Category 2 anti-epileptic drugs
Need for continuing on same brand depends on clinical judgement and consultation with the parent/carer
E.g valproate, lamotrigine, clobazam and clonazepam
Category 3 anti-epileptic drugs
No need for maintenance on specific brand except concerns for patient anxiety, risk of confusion or dosing errors. consult patient
E.g levetiracetam, gabapentin, pregabalin, vigabatrine, ethosuximide
Carbamazepine
Tegretol or Carbagen (restard or IR)
High risk drug
Must prescribe and maintain on specific brand if being used for epileptic control
Risk congenital malformation in pregnancy
Risk suicidal thoughts and behaviours
Risk SJS in presence HLA-B*1502 allele
Is an enzyme inducer
Used focal and secondary/primary generalised tonic-clinic seizures, prophylaxis of bipolar disorder
Carbamezapine range
4 - 12 mg/L
Carbamezapine side effects
Blood dyscarsia
Hepatoxicity
Rash
HYPOnatraemia
Thrombocytopenia
Nausea, vomiting, sedation, dizziness and ataxia; dose related most common at start of treatment
Carbamazepine monitoring
Serum carbamazepine levels not routinely monitored unless toxicity is suspected
FBC and LFTs should ideally be checked before starting treatment, and periodically thereafter
Carbamezapine toxicity
HYPOnatraemia
Ataxia
Nystagmus
Drowsiness
Blurred vision
Arryhtmias
GI
Contraindication and cautions in carbamazepine
History of bone-marrow depression
Stop treatment if leukopenia develops
Withdraw immediately in case of aggravated liver dysfunction or acute liver disease
Carbamezapine patient and carer advise
Report signs of blood, liver or skin disorder
Immediate medical attention fever, mouth ulcers, bruising or bleeding develop
Report any distressing thoughts or feelings about suicide or self-harm
Carbamazepine interactions
DOACs and warfarin
Macrolide
COC and POC
Phenytoin
Ciclosporin
Diltiazem, verapamil
Ticagrelor
Phenytoin
Tonic-clinic seizures, focal seizures and status epilepticus
AVOID in absence/ myoclonus as it exacerbates
Maintain on a specific brand
Risk suicidal behaviour and congenital malformation in pregnancy
Zero order clearance
Risk SJS with HLA-B1502* positive
Enzyme inducer
Acts as a anti-folate, highly protein bound drug increase blood dyscarsia
Phenytoin adverse effects
Gingival hyperplasia
Agranulocytosis
Thrombocytopenia
Altered taste
Change in facial appearance
Symptoms; toxicity are nystagmus, diplopia, slurred speech, ataxia, confusion and hyperglycaemia
Phenytoin monitoring
10-20 mg/L are optimum levels
Narrow therapeutic index
Small change in dosing can result in a large change in blood levels
Contraindication and cautions with phenytoin
Acute porphyria
Avoid HLA-B1502* positive allele
Sinus bradycardia
Second and third degree heart block
Patient and carer advice on phenytoin
Reports signs of blood or skin disorders
Seek immediate medication attention if symptonms; such as fever, rash mouth, ulcers, bruising or bleeding develop.
Report signs distressing thoughts or feelings about suicide or self-harm
Phenytoin interactions
COC, St John’s wart and warfarin decrease phenytoin concentration = therapeutic failure
Cimetidine, fluoxetine and TCA = increase concentration of phenytoin
Anticonvulsant effect antagonised with quinolones, SSRIs and TCAs as it reduced threshold of seizure
Hepatoxicity risk increased with tetracyclines, sulfazalazine, methotrexate and statins
POP,COC, valproate, DOAC, amiodarone
Phenobarbital
Status epilepticus and ALL forms of epilepsy EXCEPT typical absence seizures
Maintain on specific brand
Risk suicidal thoughts and behaviours
Risk congenital malformations
Avoid abrupt withdrawal as dependence may develop with prolonged us
Schedule 3 drug
Risk SJS
Phenobarbital patient and carer advise
Dispensed and collected within 28 days of appropriate date
Consider Vitamin D supplementation if immobilised or have inadequate sun exposure or dietary intake of calcium
Adverse effects of phenobarbital
Anxiety
Hallucination
Hypotension
Megaloblastic anaemia
Thrombocytopenia
Skin reactions
Folate deficiency
Known to induce hepatic cytochrome P450 enzymes
Phenobarbital and monitoring
Optimum plasma levels 15-20 mg/L
Contraindication and cautions with phenobarbital
Avoid in acute porphyrias
Children
Debilitated
elderly
Hx of alcohol and drug abuse
Cross sensitivity reported with carbamazepine
Anti-epileptic hypersensitivity syndrome
Rare but potentially fatal syndrome associated with some epileptic drugs e.g carbamezapine, phenytoin, phenobarbital, primidone, lamotrigine
Symptoms start between 1 to 8 weeks of exposure
Most common symptoms; fever, rash, liver dysfunction, renal and pulmonary abnormalities and multi organ failure
STOP IMMEDIATELY IF ANY OCCUR OR IS SUSPECTED
MHRA warning for anti epileptics
ALL associated with small increased risk of suicidal thoughts and behaviours
Symptoms occur 1 week after starting medication
Refer to Dr if changes in; mood, distressing thoughts, feelings about suicide or self harm
Anti-epileptic and it’s withdrawal
Withdraw under specialist supervision
Not to withdraw abruptly, can precipitate severe rebound seizures
Reduce dose gradually; barbiturates may take months
Withdraw only one drug at a time for patients receiving more than one drug
Epilepsy and driving
Inform DVLA when you have a seizure
First unprovoked epileptic seizure OR single isolated seizure must not drive for 6 months
To continue driving patient must be seizure free for at least a year and must not have a history of unprovoked seizure
Must not drive during medication changes or withdrawal of anti epileptic drug and for 6 months after their last dose - if seizure occurs from change or withdrawal = license revoked for 1 year or 5 year ban on large vehicle goods
Pregnancy and antiepileptics
Increased risk of teratogenicity especially during the 1st trimester and if take 2/+ anti-epileptics
Caution as they can decrease efficacy of hormonal contraception
Sodium valproate is associated with the highest risk of serious developmental disorders and congenital malformations - not to be used in female of child bearing age unless on PPP and no alternative
Topiramate can cause cleft palate in the 1st trimester; monitor foetal growth
Vitamin K injections in newborns minimise risk of neonatal haemorrhage
5mg folic acid recommended in first 12 weeks
Sodium valproate
Indicated in ALL forms of epilepsy
Highly teratogenic
PPP for those of child bearing potential and no alternative
Liver toxicity can occur especially in children under 3; bruising, jaundice, itchy skin or dark urine
Can affect clotting; discontinue if prolonged prothrombin time
Can cause pancreatitis - discontinue if this occurs
Pregnancy Prevention Plan (PPP)
Annual review of existing patients
At least one highly effective method of contraception or 2 complementary forms contraception including barrier
Vigabatrin
Visual disturbances
Causes encephalopathic symptoms; stupor, marked sedation, confusion
Visual defects persist even after stopping drug
Test before treatment and at 6 month intervals
Report any signs visual urgently
Status epilepticus
2 types; convulsive and non-convulsive status epilepticus
Convulsive status epilepticus
Is a convulsive seizure which continues for a prolonged period >5 minutes or when convulsive seizure occurs one after the other with no recovery in between
EMERGENCY REQUIRED IMMEDIATE MEDICAL ATTENTION
Treat; IV Lorzepam avoid IV diazepam as its thrombophlebitis
Non convulsive status epilepticus
Status epilepticus is less common and less urgent
What is febrile convulsion
Seizures in children who have high fever
If they last longer than 5 mins treat as status epilepticus
Convulsive status epilepticus management
Position patient to avoid injury, support respiration including providing oxygen
Maintain blood pressure and correct any hypoglycaemia
Give parenteral thiamine if alcohol abuse suspected
Give pyridoxine if caused by pyridoxine deficiency; B6 deficiency
Seizure lasting >5 minutes is urgent treat with IV lorazepam
If seizure continues give phenytoin sodium or fosphenytoin (fewer s/e, severe cardio reactions, prodrug phenytoin)
Monitor for respiratory depression and hypotension
Generalised tonic-clinic seizure
Sodium valproate as first line monotherapy; men, girls under 10 and women who cant have children
Offer lamotrigine or levetiracetam as first line in women of childbearing, 13+ or above not appropriate
Others are add on treatment if above fails such as clobazam, lamotridge, topiramate
Absence seizure
Ethosuximide as first line treatment for absence seizures
If first line unsuccessful offer sodium valproate as second-line monotherapy
Third line would be; lamotrigine or levetiracetam; off-label if under 2
Myoclonic seizures
Sodium valproate is first line treatment
Levetiracetam as first line treatment for myoclonic seizure in women and girl able who can have children offlabel if under 12
Tonic or a clonic seizures
Ensure assessed and diagnosed by neurologist
First line —-> sodium valproate
Second line ——> lamotrigine or levetiracetam
1st line adjuncts - clobazam, lamotrigine, levetiracetam, perampanel, na valproate
2nd line adjuvants - brivataceyam, lacosamide, phenobarbital. Primidone,
Anxiety
Psychological symptoms; restlessness, worry, fear, sleep disturbance, irritable on edge
Physical; palpitations, muscle ache, trembling, SOB, insomnia, muscle tension,
GAD-7 questionnaire for diagnostic tool
Benzodiazepines
CD4 part 1
Long acting; diazepam,, clonazapam, chlorazepoxide
Short acting; lorazepam, temazepam, oxeazepam
Used anxiety or other muscle spasm, epilepsy, alcohol withdrawals etc
Use short term to treat anxiety (2-4 weeks)
Short acting used in elderly, liver impairment, short term e.g dentist
Benzodiazepine cautions
Avoid in prolonged use = dependence
Avoid abrupt withdrawal; as it has strong withdrawal effects anxiety, weight loss, tremor, loss appetite
Pts with hx of drug or alcohol dependence
Paradoxical effects; increase hostility and aggression, range from being talkative to aggressive, increase anxiety and perceptual disorders; adjusting doses can diminish these symptoms
Benzodiazepine side effects
Decreased alertness
Anxiety
Ataxia and confusion
Dizziness and drowsiness
Fatigue
GI disorders, sleep disorders
Tremor
Suicidal thoughts
Contra indications for benzodiazepines
Acute pulmonary insufficiency
Unstable myasthenia gravies
Sleep apnoea syndrome
Benzodiazepine patient and carer advice
Effects are enhanced with alcohol; increased sedation or depressant effect
Drowsiness may persist next day and affect performance
Give at night for insomnia
Pregnancy / breastfeeding and use of benzodiazepines
Risk of neonatal withdrawal symptoms when used during pregnancy
Avoid regular use and only use if there’s clear indication
Neonatal hypothermia and respiratory deppresion = high doses in labour or late pregnancy
Present in breast milk so avoid unless necessary
Hepatic impairment and benzodiazepines
Can precipitate coma
Give shorter half life if necessary
Avoid in severe impairment
Short acting benzodiazepines
ATOM
Alprazolam
Temazepam
Oxazepam
Midazolam
No residual effect, less drowsiness next day etc
Benzodiazepines withdrawal
Withdraw over 1 week
Decrease in increments and small steps
What other drugs are used in anxiety?
Beta blockers; e.g propranolol for autonomic symptoms such as propranolol
Buspirone 5HT1A agonist; less risk of abuse
Antidepressants
Attention deficit hyperactivity disorder ADHD
Hyperactivity, impulsivity and Inattention - lead to social, educational or occupational impairment
Co-exist symptoms
Typically appear children in 3-7 years but not recognised till later
Must be managed to prevent; as children can grow up with adulthood difficulties which can lead to social difficulties, substance misuse, personality disorder etc
Aims of ADHD treatment
Reduce functional impairment and severity of symptoms
Improve quality of life
ADHD drug treatment
1st line is methylphenidate OR Lisdexamfetamine mesilate
If symptoms don’t improve after 6 week trial switch to alternative first line
Dexamfetamine sulfate (unliecensed) if patients have positive benefits with Lisdexamfetamine but cant cope with its longer duration of effect
2nd line Consider atomexetine after the above
Non-drug treatment for ADHD
Balanced diet
Good nutrition
Regular exercise
Environmental modifications; e.g noise reduction seating, more breaks
CBT
Atomoxetine
Works better in drug misuse patients
Monitor; sleep pattern, sexual dysfunction, stimulant diversion or misuse, appetite, weight loss, suicidal thoughts
Cause; QT prolongation, hepatoxicity, suicidal idealisations
120 mg max in adults and 100 in children
Methylphenidate
CD2
Concerta XL, Equasym CL, Medikinet XL, Xaggitin XL
Not for under 6, unliecensed over 60 mg or over 54 in concerta
MHRA alert; caution when switching brands
Monitor for psychiatric parameters, bp, pulse, weight
S/e; growth restriction in children, insomnia, increase HR/BP, agression, anxiety, depression
Caution; dysphagia, alcohol dependence, anxiety
CI; arrhythmias, cardiomyopathy, CVD, HF, mania
Lisdexamfetamine mesilate
CD2
Elvanse
Caution; bipolar disorder, hx CVD, hx substance abuse, may lower seizure threshold, caution in underlying compromised can increase BP or HR
CI; agitated states, hyperthyroidism, hypertention, symptomatic CVD
S/e; abdominal pain, anxiety, appetite decreased, dry mouth
Monitor for signs aggressive behaviour or hostility during treatment, BP, pulse
Bipolar disorder and mania
Serious long term
Chronic conditions with periods of lows and highs
Mania lasts for more than 7 days or hypomania for more than 4 days
Symptoms of mania
Grand ideas and self importance to oneself
Increased energy and less sleep
More talkative than usual
Full of new ideas and plans; often big and unrealistic
Irritation or agitation
Pleasurable activities in excess; spending money, alcohol, drugs, sexual
Accompanied by psychotic symptoms; delusions or hallucinations, flight of ideas racing
Hypomania is high but not as severe
Symptoms of depression in bipolar disorder
Low mood for most of the day,
Loss of enjoyment and interest in life of activities normally would enjoy
Abnormal sadness, often with weepiness
Feeling guilty worthless or useless
Poor motivation and difficulty in concentrating
Sleeping problems
Medication to treat bipolar disorder
Benzodiazepines and antipsychotics for acute episodes of mania
Carbamazepine for rapid cycling or unresponsivness to other treatment
Lithium
Mania and hypomania drug treatment
Control acute attacks and prevent recurrent episodes
Continue long term treatment of bipolar for at least 2 years from last manic episode and up to 5 years if patient has risk of relapse
Benzodiazepines; e.g lorazepam for agitation/behaviour disturbance, avoid in long term use =dependence
Antipsychotics; olanzapine, quietipine, risperidone
Carbamazepine; can be used for rapid cycling bipolar
Lithium
What drug would you avoid in rapid cycling bipolar disorder
Antidepressants
They will precipitate mania episodes
Lithium
Gold standard; used for prophylaxis and treatment of mania, bipolar disorder, recurrent depression
Full prophylactic effect may not occur for 6-12 months after initiation
High risk drug carry lithium card
Prescribe by brand
Lithium contraindications
Dehydration; increases lithium levels
Low sodium diet or levels; increases lithium levels
Addisons disease; lithium block fludrocortisone action
Cardiac disease as it effects electrolyte balances
Untreated hypothyroidism (as lithium can cause hypo)
Cautions with lithium
Avoid abrupt withdrawal
Diuretic treatment increase toxicity
Lowers threshold of seizure
QT prolongation
Review doses elderly, diarrhoea, vomiting, surgery and inter current infections
Thyroid disease in long term; monitor every 6 months TSH
Lithium side effects
Increased urination
Thirst
Hypothyrodism
Muscle weakness
Skin effects
Angioedema
Abdominal discomfort
Arrhythmias
Memory loss, tremors, vertigo, electrolyte imbalance
Signs of lithium toxicity
Nausea and vomiting
Fine tremor
CNS disturbances; confusion, drowsiness, lack of coordination
AV block
Visual disturbances
Lithium monitoring
Weekly Lithium levels after initiation until stable then every 3 months for 1st year then every 6 months thereafter (some pts may require 3 months)
Monitor; ABW/BMI, U&Es, EGFR and TFTs every 6 months
Cardiac, thyroid, renal, FBC and BMI before treatment
Lithium advice
Avoid dietary changes which increase sodium intake
Maintain adequate fluid intake especially when ill as there’s risk of dehydration
Lithium withdrawal
Abrupt discontinuation increases risk of relapse
Reduce gradually over a period of at least 4 weeks to 3 months
If stopped or discontinued abruptly consider changing therapy to atypical antipsychotic or valproate
Lithium and breastfeeding
Avoid
Present in milk
Risk of toxicity in infants
Lithium and pregnancy
Avoid if possible especially in 1st trimester risk of teratogenicity include cardiac abnormalities
Dose requirements increase during 2nd and 3rd trimester but return to normal on delivery
Lithium levels
0.4 - 1 mmol/L for maintenance and elderly
0.8 - 1 mmol/L for acute episodes of mania and patients who previously relapsed
Drug interactions and lithium
Increase Li concentration; ACEi/ARBs, diuretics, NSAIDs, metronidazole, amiodarones and tetracyclines
Decreased Li concentrations sodium containing antacids, theophylline
Drugs that increase QT prolongation or seizure or cause HYPOkalaemia
Increase neurotoxicity with; SSRIs, antipsychotics, carbamezapine, Triptans
Sodium levels and lithium
Low sodium = high lithium
High sodium = low lithium
Depression
Psychological; low self-esteem, worry/anxiety, suicidal thoughts, worthlessness, low mood, suicidal
Physical; lack of energy, change weight or appetite, insomnia
Diangnosel DSM-5 criteria, PHQ-9, HADS
3 major classes of antidepressants
Tricyclic and related depressants
Selective serotonin reuptake inhibitors
Monamine oxidase inhibitors
Antidepressants
Effective for moderate to severe depression
Not for mild as psychological therapy is preffered
Improvement in sleep usually 1st benefit of drug therapy
Increased potential for agitation, anxiety and suicidal thoughts during first few weeks of treatment
All classes have similar efficacy but different side effect profile
2-4 weeks for full effect
What is the first line treatment for depression
1st line is SSRIs; Better tolerated , Safer in overdose, Less sedating and Fewer antimuscarinic and cardio toxic effect
TCAs are similar to SSRis but more s/e, dangerous in overdose, more sedating and antimuscarinic and cardio toxic s.e
MOAis are specialist use and have dangerous interactions with drugs and food