CNS and psychiatric drugs Flashcards
What is the difference between a partial and generalised seizure?
Generalised= whole brain and loss of consciousness Partial= part of brain and remains conscious
What are the two types of partial seizure
Simple= remains aware Complex= altered awareness and behaviour
Give 3 secondary causes of seizures
Head injury, hypoxia, tumour, stroke, infection, hypoglycaemia, drugs, electrolyte imbalances
Why can alcohol withdrawal cause seizures?
Alcohol stimulates GABA channels, therefor alcoholics have down regulated GABA channels, when alcohol is removed there is less GABA release leading to excitation and so seizures
Name one class of drugs which inhibits seizures by stimulating GABA channels
Benzodiazepam (lorazepam and diazepam)
Name 3 drugs which inhibit seizures by inhibiting voltage gated sodium channels and so inhibit propagation of the seizure
carbemazepine, phenytoin, lamotrigine, also sodium valproate by secondary action
State the 3 ways sodium valproate acts to inhibit seizures
voltage gated sodium channel inhibition, Ca2+ channel blocker (main) and weak GABA synthesis and activation stimulation
Why do voltage gated sodium channel blockers only affect the part of the brain having the seizure?
Because they move into and block the channel when it is open, therefor those which are open more (the depolarising neurones) will be affected more, so will reduce firing rate to normal
Which seizures can carbamazepine be used on?
generalised tonic- clonic and partial seizures- not absent
What is significant about the drug interactions of carbemazepine?
It is a strong CYP450 inducer, so will decrease the effect of warfarin, oral contraceptives, steroid, phenytoin.
It will also reduce its own half life from 30hrs at the start of the regime to 15hrs with repeated use
Give 3 ADRs of carbemazepine
- GI upset/ vomiting
- headache, dizziness, ataxia, motor disturbance, numbness, tingling
- neutropenia (rare)
- rashes (rare)
When can phenytoin be used?
All partial seizures + generalised tonic clonic seizures NOT absent seizures. Also as loading dose + infusion if seizure not terminating after 10 mins
Describe the interactions of phenytoin (2)
- CYP450 inducer (warfarin, contraceptives, steroids) but doesnt affect its own metabolism
- Highly protein bound (affects NSAIDs, valporate to increase both drugs free plasma conc)
Give 3 ADRs of phenytoin
- gingival hyperplasia (20%)
- rashes (stevens johnsons syndrome in 2-5%)
- ataxia, numbness, tingling, headache, dizziness
When is lamotrigine used and not used?
All types of seizures, but avoided in children due to ADRs
Describe 2 important drug interactions with lamotrigine
- oral contraceptives reduce its effect
- valproate will increase its free plasma conc as its also protein bound
- no CYP450 induction
Give 3 ADRs of lamotrigine
- ataxia, diziness etc but less severe than other drugs
- nausea and skin rashes however more severe and more common in children
When can sodium valproate be used?
all seizure types
Give 3 interactions with sodium valproate
- anti depressants will inhibit its action
- anti psychotics will antagonise it
- aspirin will compete with it in plasma
Give 3 ADRs of sodium valproate
- highly teratogenic
- ataxia and weight gain
- may elevate LFTs, but this will only lead to liver failure in minority of cases
How can sodium valproate levels be monitored?
By saliva sample- concentration is the same as blood
When are benzodiazepams used in epilepsy?
Generally reserved for status epilepticus/ emergencies.
Describe the administration of lorazepam, diazepam and midazolam
lorazepam= IV bolus (1st choice) Midazolam= Buccal or IV Diazepam= rectal or oral
Give 3 ADRs of diazepam
- sedation
- tolerance and dependance with chronic use
- confusion
- aggression
- resp and CNS depression
Describe the 5 steps to managing seizure emergencies and status epilepticus
1st= ABCDE approach 2nd= IV lorazepam or rectal diazepam 3rd= if no termination after 5 mins give more benzodiazepam 4th= if no termination after 10-15 mins give loading dose of IV phenytoin, call ITU to get ready to sedate and intubate 5th= send to ITU
What are the 3 rules to prescribing anti epileptic drugs
- aim for monotherapy- if one drug doesnt work try a differnt one
- if all dont work alone start combining them
- start at low dose and slowly increase
Which drug is first choice for generalised seizures and which is for partial seizures?
sodium valproate is first choice for generalised, carbemazepine is for partial seizures, but can be used in generalised too
Which anti- epileptic drug is favoured in pregnancy
lamotrigine- least teratogenic, best to stop all drugs if you can. If lamotrigine need to be given, supplement with folic acid and vit K
Which anti- epileptic drugs have most and least effect on contraceptives
Phenytoin and carbamazepine both decrease efficacy of oral contraceptives.
Oral contraceptives reduce the effect of lamotrigine.
Valproate and benzodiazepines both have no interaction with oral contraceptives.
What are the cardinal features of parkinsons
Bradykinesia, ridgity, resting tremour, postural instabilty
What are the signs of parkinsons plus syndromes
Early onset dementia, early onset instability, early onset hallucinations/ psychosis, early autonomic signs (instability, incontinence) and ocular signs
Name 3 types of parkinsons plus syndromes
- multiple systems atrophy
- progressive suprenuclear palsy
- lewy body dementia
- parkinsonism dementia (amytrophic lateral sclerosis complex)
- corticobasal ganglionic degeneration
What is the pathophysiology behind Parkinson’s
- loss of dopaminergic neurones in the substantia nigra-> reduced inhibition of indirect pathway and more activation of direct pathway-> less stimulation of thalamus and cortex -> bradykinesia
How is parkinsons diagnosed (3)
Symptoms + normal CT/MRI + good response to trial of treatment.
Also other cause of parkinonsism need to be ruled out: drug induced, vascular, parkinsons plus
Describe the mode of action of levo- dopa as a treatment for parkinsons
Levo dopa passes the blood brain barrier (dopamine doesnt) and is then converted to dopamine by dopa carboxylase when it gets into neurones
What % of levodopa given reaches the CNS?
1%- most is activated in intestinal wall or peripheral dopaminergic neurones, this is increased w/ compt inhibitors and carbidopa
Give 3 ADRs of levo dopa
- dyskinesia+ dystonia+ freezing
- psychosis
- n+ v, hypotension
When is levo dopa used and not used in parkinsons
- it is first line treatment for parkinsons
- however will not work if there are no dopaminergic cells left in the STN
- it is not neuroprotective so no point rushing into treatment
What are on off fluctuations in parkinons? how are they managed?
Over time, more dopaminergic neurones are lost so the effect of levo dopa reduces, so you get periods where it doesnt work leading to dystonia and freezing, which are painful and dangerous.
You can reverse them with dopamine agonists (ropinirole)
What is carbidopa?
A peripheral dopa decarboxylase inhibitor, which prevents levo dopa breakdown in peripheries so increases levodopa reaching the CNS. It is given in combination with levo dopa.
Name one COMT inhibitor
Entacapone
How do COMPT inhibitors work?
Prevents peripheral breakdown of L- dopa into a metabolite which inhibits CNS absorbtion of L- dopa.
When are COMPT inhibitors used?
In combination with L dopa (and sometimes carbidopa) to increase L dopas effect. It also reduces wearing off of symptoms
Name 1 ergot derived and one non ergot derived dopamine receptor agonist
Ergot derived: bromocriptine
Non ergot dervied: apomorphine, ropinerole
What is the therapeutic difference between ergot derived and non ergot derived DRAs?
non ergot derived have fewer side effects
When are dopamine receptor agonists used in parkinsons
can help control on off fluctuations, not used as first line as less efficacious and more expensive
Give 3 ADRs of dopamine receptor agonists
- more sleep attacks (so cant drive with them)
- impulse control disorders become more common (more gambling, shopping etc)
- sedation, hallucinations, confusion, N+V, hypotension can all occur
Name one MAOI type B inhibitor sometimes used in parkinsons and describe its mode of action
selegiline
MAOI type B metabolises dopamine so inhibition of it leads to less breakdown of dopamine. It smoothes out motor responses and may also be neuroprotective
State one anti-muscarinic used to treat parkinsons and state which symptoms they treat the best
Procyclidine
Works well to reduce tremour, little effect on bradykinesia,
When is surgery an option for treatment of parkinsons
When L dopa is poorly tolerated but the individual is still dopamine responsive and they have no psychiatric illness
Describe the surgery options used to treat parkinsons (3)
Can create lesions on the thalamus to treat tremours, lesions on GPi to treat dyskinesia and also deep brain stimulation of the subthalamic nucleus, which improves all symptoms
What is the most common initial presentation of myasthenia gravis
weakness of extra ocular muscles leading to ptosis and diplopia
Describe how pyridostigmine works to treat myasthenia gravis
An acetylcholine esterase inhibitor- more Ach engages with receptor- better coordination of muscle
Which acetylcholinesterase inhibitor is IV and fast acting- so used in ITU
Neostigmine
Describe the time taken for maximal response of pyridostigmine and the implications of this
Peak response after 30 mins, so should be taken 30-60 mins before a meal to minimise aspiration risk
Give one ADR of acetylcholine esterase inhibitors when dose is too high? How is this reversed?
- SLUDGE syndrome as doses too high (esp with neostigmine)
- Reverse with atropine
Other than acetyl cholinesterase inhibitors, name 3 other methods of treating myasthenia gravis
- corticosteroids to decrease immune response
- IV immunoglobulins in acute decline or crisis
- Plasmaphersis to remove Achr antibodies (short term improvement)
- biological therapies emerging
Name the 4 classes of drugs used to treat depression
- Serotonin and noradrenaline reuptake inhibitors (SNRIs)
- SNRIs + other actions (TCAs)
- Selective serotonin reuptake inhibitors (SSRIs)
- noradrenaline reuptake inhibitors (NARIs)
Give 2 examples of SSRIs
fluoxetine, citalopram sertraline
What is first line treatment of moderate to severe depression
SSRI + CBT
How long can SSRIs take to work and for how long after symptoms have gone should they be taken for?
Can take up to 6 weeks to work. Should keep take for a year after symptoms gone to avoid relapse
What is serotonin syndrome?
Tachycardia, sweating, hyperthermia etc within a few weeks of starting an SSRI/ SNRI. It is an emergency as can lead to seizures, hyperthermia etc
Give 3 ADRs of SSRIs?
- Anorexia, N+V, diarrhoea
- Sexual dysfunction, sweating tremor and insomnia rarer
- dyspepsia
- citalopram prolongs QT-> arrhythmias
- Many increase bleeding and cause hyponaturaemia, esp if taken with NSAIDs.
Describe the safety of SSRIs in overdose
safe enough if its the only drug taken
Give 2 examples of tricyclic antidepressants (TCAs)
Amytriptyline, imipramine, lofepramine
other than depression, what can TCAs be used to treat?
Neuropathic pain
How do TCAs work?
Largely by inhibiting NA and serotonin reuptake but also affect a1 adrenoreceptors and muscarinic receptors
give 3 ADRs of TCAs?
- dry mouth, dry nose, blurred vision, constipation, urinary retention due to anti muscarinic effects
- sedation and impairment of psychomotor performance, lower seizure threshold
- fatigue, abdo pain, restlessness, palpitations
- extrapyramidal syndromes
Give 2 effects of TCA overdose and how you would reverse it
- CVS effects: tachycardia, postual hypotension, impaired contractility
- CNS effects: seizures, sedation, hallucinations
- Acidosis
Sodium bicarbonate can be given to help bind to drug and also helps reverse the acidosis.
Overall pretty bad so avoid giving to those who’re suicidal
Give two example of SNRIs
venlafaxine, duloxetine
Give 3 ADRs of SNRIs
- As with SSRIs (anorexia, N+V, diarrhoea, insomnia, sexual dysfunction
- increased BP, dry mouth, hyponaturaemia
- withdrawal on continuous use is common
Give 2 typical and 2 atypical antipsychotics
Typical: haloperidol, chlorpromazine
Atypical: olanzapine, risperidone, clozapine, quetiapine
What is the difference in mode of action and side effects between typical and atypical anti psychotics?
Typical= D2 receptor antagonists, extrapyramidal sie effects common Atypical= Dopamine antagonists and also serotonin receptor antagonists, Side effects less common + better at reducing negative symptoms
State and describe 3 extrapyramidal side effects?
Dystonia= abnormal posture due to muscle contraction
Akathesia= internal feeling of restlessness
Tardive dyskinesia= abnormal involuntary movements
Pseudo parkinsonism.
These occur due to inhibition of the nigrostriatal pathway
Give 3 non extra pyramidal side effects of anti- psychotics
- Anticholinergic: dry mouth, urinary retention, blurred vision
- Serotonergic: N+V, sexual dysfunction, insomnia
- Metabolic: increased blood glucose, weight gain, increased CVS risk
- Anti- dopamine: extra pyramidal side effects + hyperprolactinaemia
- clozapine also causes neutropenia so needs FBC monitoring
Describe the effects of OD on antipsychotics?
CNS depression, cardiac toxicity, risk of sudden death (esp with high doses)
Describe treatment of anxiety
1st line= CBT and treatment of any co- existing disorders
2nd= SSRIs and SNRIs
Acute declines can be treated with benzodiazepams (anxiolytic) but not suitable for long term use
3rd= pregablin if SSRIs and SNRIs dont work
Give 3 ADRs of benzodiazepams
- withdrawal and dependance
- drowsiness, dizziness, psychomotor impairment, ataxia, headache
- tolerance
- dry mouth, blurred vision, GI upset,
- amnesia, restlessness
- rash
- May be teratogenic
Describe the effect of benzodiazepam overdose and how it is reversed
- respiratory depression
Usually supportive treatment is fine but may need flumazenil to reverse (Benzodiazepam receptor antagonist)
Name 2 mood stabilisers used to treat bipolar
Sodium valproate (valproic acid) and lithium (lithum carbonate) Carbemazopine, lamotrigine and some antipsychotics can also be used
Why is monitoring required for lithium treatment of mania?
It has narrow theraputic window. TFTs, LFTs and U&Es need checking every 6 months
Give 3 ADRs of lithium
Thirst, memory problems, polyuria, tremors, drowsiness, weight gain
Describe the effect of lithium OD and its treatment
N+V, diarrhoea, coarse tremor, dysarthria, cognitive impariment, restlessness, agitiation.
Treat supportively, with anti convulsants, IV fluids and haemodialysis if very severe
What are the two classes of drugs used to treat dementia
Ach esterase inhibitors (for mild to moderate dementia) and NMDA blockers (for severe dementia)
Name 2 Ach esterase inhibitors used in dementia
Donepezil, galantamine, rivastigmine
Name one NMDA blocker used in dementia
Memantine
Give 3 ADRs of NMDA blockers
hypertension, dizziness, headache, drowsiness
Give 3 ADRs of Ach esterase inhibitors
- N+V, anorexia, diarrhoea
- Fatigue, insomnia, headache
- bradycardia
- COPD worsening
- gastric/ duodenal ulcers
Name 3 mode of actions of anti- N+V drugs and give 1 example of each
- Histamine antagonist (cyclizine)
- Dopamine (D2) antagonist (metoclopramide, domperidone)
- Serotonin antagonist (ondansertron)
- Also hyoscine (motion sickness)
