Neuro pharmacology Flashcards
Sodium valproate:
Common indications
Mechanism of action
Adverse effects
Warnings
Interactions
Common indications
- Epilepsy
- Bipolar disorder
Mechanism of action
- Blocks Na+ channels in neurons, and increases GABA
Adverse effects
- GI disturbances like nausea and diarrhoea
- Neurological problems like tremor, ataxis, behavioral problems
- thrombocytopenia
Warnings
- Avoided in pregnant women (teratogenic)
- Avoided in those with hepatic/renal impairment
Interactions
- p450 inhibitor
Carbamezipine
Common indications
Mechanism of action
Adverse effects
Warnings
Interactions
Common indications
- Epilepsy (focal seizures)
- Trigeminal Neuralgia
- Bipolar disorder
Mechanism of action
- Inhibits Na+ channels in neurons
Adverse effects
- GI disturbances like nausea and vomiting
- Neurological disturbances like tremor and ataxia
- Can cause maculopapular rash
- Antiepileptic hypersensitivity reaction (w phenytoin-> Steven Johnson’s syndrome and TEN)
- ADH like properties (hyponaatraemia and oedema)
Warnings
- avoided in pregnancy (teratogenic)
- avoided in hepatic, renal and cardiac disease
Interactions
- Cytochrome p450 inducer
Levodopa
Common indications
Mechanism of action
Adverse effects
Warnings
Interactions
Common indications
- Parkinson’s disease (Levodopa combined with periphera dopa decarboxylase inhibitor like carbidopa to prevent its conversion outside CNS)
Mechanism of action
- Dopamine precursor
Adverse effects
- Nausea, confusion and hallucinations, hypotension
- Wears off at the end off the day
Warnings
- Used in caution for those with psychiatric disease and Cardiovascular disease (because of hypotension)
selective serotonin reuptake inhibitors
Common indications
MOA
adverse effects
Warnings
important interactions
citalopram, fluoxetine, sertraline, escitalopram
Common indications
- moderate to severe depression
- panic disorder
- obsessive-compulsive disorder
MOA
- inhibit uptake of serotonin into neuron, increasing serotonin in synaptic cleft
- unlike TCAs which also inhibit uptake of NA
adverse effects
- GI disturbances, weight loss/gain, hypersensitivity reactions
- Hyponatraemia especially in elderly
- Lower seizure threshold
- citalopram prolongs QT interval
- increase risk of suicide
- Too much serotonin-> serotonin syndrome where increase in HR, sweating, pupil dilatation, myoclonus, hyperreflexia
Warnings
- Not to be taken in those with epilepsy due to reduction in seizure threshold
- Not to be taken in those with peptic ulcer disease
- Not be taken in those with cardiovascular arrhythmias
- avoided in those in hepatic impairment-> broken down
important interactions
- Not to be taken with MAOis due to risk of serotonin syndrome
- Not to be taken with drugs that prolong QT interval like antipsychotics
tricyclic antidepressants
Common indications
MOA
adverse effects
Warnings
important interactions
Amitryptiline, lofepramine
Common indications
- 2nd line for moderate-to-severe depression where SSRIs are not tolerated
- neuropathic pain
MOA
- inhibit the uptake of serotonin and noradrenaline, thus increasing the concentration
- Blocks the antimuscarinic, histamine H1, alpha receptors (alpha 1 and 2), dopamine D2 receptors
adverse effects
- Antimuscarinic side effects-blurred vision, dry mouth and constipation, urine retention
- anti H1- sleepiness
- anti alpha 1-hypotension
- cardiovascular effects like prolongation of QT interval
- induces convulsions, hallucinations, mania
- anti D2-prolactin increase therefore breast changes and sexual dysfunction and extrapyramidal symptoms (tremor etc)
- dangerous in overdose-respiratory failure, convulsions, arrhythmias
Warnings
- elderly
- those with cardiovascular problems
- those with epilepsy
- those with raised intraocular pressure, constipation and prostatic hypertrophy
important interactions
- not to be given w monoamine oxidase inhibitors-> cause serotonin syndrome
- not to be given w drugs that prolong QT interval
venlafaxine and mirtazapine
Common indications
MOA
adverse effects
Warnings
important interactions
venlafaxine and mirtazapine
Common indications
- major depression where SSRIs are not tolerated
- generalised anxiety disorder
MOA
- venlafaxine is a SNRI, inhibiting the reuptake of serotonin and noradrenaline
- mirtazapine is an antagonist of alpha 2 adrenoreceptor
adverse effects
- gastrointestinal disturbance (dry mouth, diarrhoea or constipation, weight changes)
- CNS side effects like headache, insomnia, convulsions
- serotonin syndrome (pupil dilation, increase heart rate, sweating, myoclonus and hyperreflexia)
- hyponatraemia
- venlafaxine can prolong QT interval as well
Warnings
- avoided in elderly
- avoided in cardiovascular disease due to prolongation of QT interval
- avoided in hepatic/renal impairment
important interactions
- not to be given with MAOis due to risk of serotonin reuptake inhibitors
- not to be given with drugs that prolong QT interval
antipsychotics 1st generation(haloperidol, chlorpromazine, prochlorperazine)
Common indications
MOA
adverse effects
Warnings
important interactions
antipsychotics (haloperidol, chlorpromazine, prochlorperazine)
Common indications
- psychomotor agitation
- schizophrenia and bipolar-mania and hypomania
- nausea and vomiting
MOA
- inhibit post-synaptic D2 receptors
adverse effects
- Extrapyramidal side effects-parkinsonian movements like dystonia (involuntary contractions of muscles), tardive dyskinesia (late, pointless/involuntary/repetitive movements like lip smacking); akasthisia (restlessness)
- Neuroleptic malignant syndrome (pyrexia, muscle rigidity/rhabdomyolysis, acute tubular necrosis and autonomic symptoms like hypertension, tachypnoea and tachycardia)
- prolongation of QT interval
- Prolactinoma and erectile dysfunction
Warnings
- elderly/dementia-lower dose
- avoided in parkinson’s
- avoided in cardiovascular disease
important interactions
- don’t give with other drugs like those that prolong QT interval
antipsychotics 2nd generation (risperidone, clozapine, quetiapine, olanzapine)
Common indications
MOA
adverse effects
Warnings
important interactions
antipsychotics 2nd generation (risperidone, clozapine, quetiapine, olanzapine)
Common indications
- psychomotor agitation
- schizophrenia
- bipolar disorder in mania/hypomania
MOA
- block post-synaptic dopamine D2 receptors, and have affinity to 5HT2a receptors
- clozapine and quetiapine have looser binding to D2 receptors
adverse effects
- sedation
- extrapyramidal side effects (less common)
- metabolic effects (more common)-lipid changes, weight gain, diabetes mellitus
- prolongation of QT interval
- risperidone-increases prolactin and cause breast changes and sexual dysfunction
- clozapine causes decrease in neutrophils and can cause agranulocytosis (WBC count decrease); cause myocarditis
Warnings
- not to be given in those with cardiac disease
- clozapine not to be given with those with decreased amount of neutrophils
important interactions
- not to be given w drugs that prolong QT interval
A 45-year-old woman is seen in her GP surgery with a 6-month history of moderate depression. Attempts to treat this with cognitive-behavioural therapy have proved unsuccessful. There are no psychotic features and she is assessed to be at low risk of self-harm. She has no other medical problems.
What is the most appropriate treatment?
A. Amitriptyline 25 mg daily
B. Citalopram 20 mg daily
C. Olanzapine 10 mg daily
D. Psychological interventions only
E. Mirtazapine 15 mg daily
B. Citalopram 20 mg daily. Antidepressants are indicated for moderate and severe depression, and for mild depression that has not responded adequately to psychological interventions, as in this case. A selective-serotonin re-uptake inhibitor(SSRI), such as citalopram, is first choice in most patients. Amitriptyline (a tricyclic antidepressant) and mirtazapine (an antagonist of pre-synaptic α2-adrenoceptors) are also effective antidepressants, but as they cause more side effects they are generally reserved for cases in which SSRIs are deemed unsuitable. Olanzapine is a second-generation antipsychotic which is not indicated for non-psychotic depression.
A 40-year-old man is brought to the emergency department due to a fit. He is accompanied by a friend who says the fit started about 25 minutes ago. On examination, there are findings consistent with an ongoing clonic seizure. The capillary blood glucose concentration is 5.9 mmol/L. No antiepileptic treatment has been administered so far.
What is the most appropriate immediate treatment?
A. Carbamazepine 200 mg by nasogastric tube
B. Chlordiazepoxide 30 mg by nasogastric tube
C. Lorazepam 4 mg by slow IV injection
D. Phenytoin 20 mg/kg by IV infusion
E. Valproate 10 mg/kg by slow IV injection
C. Lorazepam 4 mg by slow IV injection. Broadly, status epilepticus may be defined as a state of unrelenting seizure activity. It is a life-threatening condition that requires urgent treatment. First-line pharmacological treatment is with a benzodiazepine, which in a hospital setting should be administered intravenously. The ideal choice is lorazepam due to its long duration of effect. In adults, this is usually given in an initial dose of 4 mg by slow IV injection, which may be repeated once if the seizure does not terminate. Diazepam is a reasonable alternative if lorazepam is unavailable. Chlordiazepoxide is also a long-acting benzodiazepine, but it is not available in an intravenous formulation so is not suited to use in status epilepticus. If the seizure cannot be controlled with a benzodiazepine, the antiepileptic drug phenytoin may be given. If this is unsuccessful, the patient should be anaesthetised and managed in the intensive care unit.
Valproate and carbamazepine are alternative antiepileptic drugs. In the context of status epilepticus, valproate is sometimes used in place of phenytoin as a second-line agent. Carbamazepine has no role in the acute management of status epilepticus.
A 34-year-old man presents to the emergency department following a tonic–clonic seizure. In the course of this he knocked over a kettle of boiling water and sustained a significant burn injury to his right arm, which will need to be cleaned once adequate analgesia is established. He had a past medical history of focal epilepsy, for which he takes carbamazepine.
What analgesic is most strongly contraindicated in this setting?
A.Codeine
B.Morphine
C.Naproxen
D. Paracetamol
E. Tramadol
E. Tramadol. You need to be particularly careful when prescribing for patients with epilepsy, for two main reasons. Firstly, antiepileptic drugs (including phenytoin, carbamazepine and valproate) have many potential drug interactions. These may result in drug toxicity (either of the antiepileptic drug or the other interacting drug) or loss of seizure control. Secondly, there are a number of drugs that can lower the seizure threshold, including antidepressants, antipsychotics, and opioids, particularly tramadol. The other opioids may have an effect on seizure threshold, but this is much less significant. In the context of severe pain, their benefits are likely to outweigh their risks. Naproxen (an NSAID) and paracetamol are not known to affect seizure threshold or interact with carbamazepine.
A 19-year-old presents as she would like to start a combined oral contraceptive pill. During the history she states that in the past she has had migraine with aura. She asks why the combined oral contraceptive pill is contraindicated. What is the most appropriate response?
- increased risk of ischaemic stroke
Joanna is a 24-year-old female who presents to the emergency department with an abrupt 2-hour onset of a painful and red skin rash extending across her trunk, face, and limbs. She has never had this skin rash before and has not recently used any new skin products. Her past medical history includes epilepsy, and a viral upper respiratory infection a couple of weeks ago. Her medications include lamotrigine which was started 3 weeks ago.
On examination, Joanna’s blood pressure is 120/80mmHg, pulse 90/min, respiratory rate 18/min, and she is afebrile. There is diffuse skin erythema, macules, and flaccid blisters across the majority of her body (except the palms and soles of the feet). There are also notable ulcers on her lips and genitalia.
What is the most important immediate step in management?
- cease all medications and give IV fluids due to significant fluid loss from blisters in steven johnson’s syndrome. Side effect of carmezipine/lamotrigine
A 33-year-old woman comes to see you as she was prescribed prophylactic treatment for her migraines by her old GP. These migraines use to happen 1-2 times a week. However since she started the medication they have been reduced to 1-2 times a month. She says she has just discovered that she is pregnant and is very worried about her child having a birth defect.
Which one of the following medications is given for migraine prophylaxis and is also linked to congenital abnormalities such as cleft lip and palate?
- topiramate is contraindicated in pregnancy and linked to congenital abnormalities like cleft lip and palate
Antiemetics-D2 antagonists
Common indications
MOA
adverse effects
Warnings
important interactions
Antiemetics-D2 antagonists (metoclopramide, domperidone)
Common indications
- nausea and vomiting (in context of reduced GI motility)
MOA
- Block D2 receptors in chemoreceptor trigger zone (esp metoclopramide which crosses BBB; unlike domperidone)
- Prokinetic that causes person to vomit
adverse effects
- Diarrhoea
- extrapyramidal side effects-acute dystonia, tardive dyskinesia, akisthisia
Warnings
- not to be given in children or young adults due to higher risk of extrapyramidal side effects
- not to be given in GI perforation or GI obstruction due to higher risk of perforation
important interactions
- will antagonize parkinson’s drugs
- risk of extrapyramidal side effects increased w antipsychotics
