Nervous System - High Flashcards
What is the drug of choice for patients with severe Alzheimer’s disease?
Memantine hydrochloride
What are the first line options for the treatment of mild-moderate Alzheimer’s disease?
- Donepezil
- Galantamine
- Rivastigmine
Which drug class does memantine belong to?
NMDA receptor antagonists
(Dopaminergic)
What are the MHRA warnings associated with the use of antiepileptics?
- Risk of suicidal thoughts and behaviours (August 2008)
- Updated advice on switching between manufacturers products (November 2017)
Which MHRA risk category is Carbemazepine in?
Category 1
Which MHRA risk category is phenytoin in?
Category 1
Which MHRA risk category is phenobarbital in?
Category 1
Which MHRA risk category is primidone in?
Category 1
Which MHRA risk category is clonazepam in?
Category 2
Which MHRA risk category is clobazam in?
Category 2
Which MHRA risk category is lamotrigine in?
Category 2
Which MHRA risk category is sodium valproate in?
Category 2
Which MHRA risk category is topiramate in?
Category 2
Which MHRA risk category is gabapentin in?
Category 3
Which MHRA risk category is pregabalin in?
Category 3
Which MHRA risk category is levetiracetam in?
Category 3
What are the categories assigned by the MHRA to antiepileptic drugs and what do they signifiy?
- Catgeory 1 - Patients must be mainatined on a manufacturer’s specific product
- Category 2 - Patients can be switched but factors such as seizure frequency, treatment history, and potential implications should be considered and discussed with the patient beofre switching to another product
- Category 3 - It is unnecessary for patients to be maintained on a specific manufacturer’s product
How should treatment with antiepileptic drugs be stopped?
Withdrawn gradually under specialist supervision to prevent rebound seizures.
Which antiepileptics can be used during pregnancy?
Levetiracetam and lamotrigine
What is the difference between focal and generalised seizures?
- Focal - signals originate in one part of the brain
- Generalised - All areas of the brain are affected by an abnormal electrical impulse
What are the first line options for the treatment of focal seizures, with or without secondary generalisation?
Carbemazepine
OR
Lamotrigine
What is the first line option for the treatment of tonic-clonic seizures?
Sodium valproate
Lamotrigine (monotherapy or adjunct) where valproate not appropriate
What are the first line options for the treatment of absence seizures?
Ethosuximide
OR
Sodium valproate
What are the first line options for the treatment of myoclonic seizures?
Sodium valproate
OR
Levetiracetam
OR
Topiramate
What is the first line option for the treatment of atonic and tonic seizures?
Sodium valproate
Which seizure types is carbepazepine not recommended in?
Tonic-clonic
Atonic and tonic
Absense
Myoclonic
Which seizure type is carbemazepine the second-line treatment option for?
Focal seizures
What is ethosuximide a first line treatment for?
Absence seizures
What are pregabalin and gabapentin indicated for?
- Focal seizures
- Neuropathic pain
- Pregabalin is indicated for treatment of generalised anxiety disorder
What type of seizure is the use of gabapentin and pregabalin not recommended in?
Tonic-clonic
Atonic and tonic
Myoclonic
Absense
What are the types of generalised seizures?
- Tonic-clonic
- Atonic and tonic
- Absence
- Myoclonic
What is lamotrigine the first line treatment option for?
- Focal seizures
- Primary and secondary tonic-clonic seizures (where sodium valproate has been unsuccessful)
How does lamotrigine interact with other antiepileptic drugs?
- Sodium valproate increases lamotrigine plasma concentration
- Enzyme inducing antiepileptics decrease lamotrigine serum concentrations
What is levetiracetam indicated for?
Focal seizures as monotherapy and adjunct
What is phenobarbital indicated for?
Focal seizures
Tonic-clonic seizures
What is primidone metabolised into?
Phenobarbital
What type is seizures is phenytoin indicated for?
Focal seizures
Tonic-clonic seizures
Which type of seizures can phenytoin exacerbate?
Absence seizures
Myoclonic seizures
What type of seizures is topiramate indicated for?
Focal seizures
Tonic-clonic seizures
Sodium valproate is the first line choice for epilepsy with which seizure types?
Tonic-clonic
Myoclonic
Atonic-tonic
How should seizures lasting longer than 5 minutes be treated?
IV lorazepam
If seizures fail to respond to initial treatment after 25 minutes, what action should be taken?
Phenytoin or phenobarbital should be used and emergency services should be contacted
If seizures fail to respond to treatment 45 minutes after onset, what action should be taken?
IV midazolam should be used or another anaesthesia
What are the MHRA warnings are associated specifically with the use of gabapentin?
- (Neurontin) Risk of severe respiratory depression (October 2017)
- Risk of abuse and dependence: New scheduling requirements (April 2019)
Levels of propylene glycol, acesulfame K and saccharin sodium may exceed daily intake limits if high doses oral solution (Bosemont brand) are given to adolescents or adults with low body weight (39-50kg)
What is the MHRA warning specifically associated with the use of sodium valproate?
Contraindicated in women and girls of child bearing potential unless conditions of pregnancy prevention prgramme are met (April 2018)
List some enzyme inducing drugs
- Carbemazepine
- Rifampicin
- Phenytoin
- Phenobarbitone
- Sulphonylureas
- Griseofulvin
- St John’s wort
List some enzyme inhibiting drugs
- Metronidazole
- Sodium valproate
- Erythromycin
- Isoniazid
- Cimetidine
- Chloramphenicol
- Ciprofloxacin
- Omeprazole
- Sulfonamides
- Ketoconazole
List some drugs that have an anticholinergic burden
- Amitriptyline
- Paroxetine
- Chorphenamine
- Promethazine
- Olanzapine
- Quetiapine
- Solifenacin
- Tolterodine
What are the most commonly prescribed acetylcholinesterase inhibitors?
Donepezil
Rivastigmine
What are the acetylcholinestaerase inhibitors indicated for?
- Mild to moderate Alzheimer’s
- Mild to moderate Parkinson’s (rivastigmine)
What are some important adverse effects associated with the use of acetylcholinesterase inhibitors?
- GI upset
- Exacerbation of asthma and COPD symptoms
- Peptic ulcers
- Bradycardia
- Heart block
- Hallucinations
- Altered behaviour
- Neuroleptic malignant syndrome
When should acetylcholinesterase inhibitors be used with caution?
- Asthma and COPD
- Peptic ulcers
When should the use of acetylcholinesterase inhibitors be avoided?
- Bradycardia
- Heart block
Which drugs do acetylcholinesterase inhibitors interact with an to what extent?
- NSAIDs - increased risk of ulcers and GI blleds
- Corticosteroids - increased risk of ulcers and GI bleeds
- Beta-blockers - increased risk of bradycardia and heart block
- Antipsychotics - increased risk of neuroleptic malignant syndrome
Which drug class does donepezil belong to?
Acetylcholinesterase inhibitors
Which drug class does rivastigmine belong to?
Acetylcholinesterase inhibitors
What is phenobarbital indicated for?
All types of seizures except absence seizures
Whe should phenobarbital be used with caution?
- Elderly
- Acute porphyrias (avoid)
- Respiratory depression
- Alcohol abuse
Is phenobarbital an enzyme inducer or inhibitor?
Inducer
Which drug shares cross-sensitivity with phenobarbital?
Carbemazepine
What are some important adverse effects associated with the use of phenobarbital?
- Hepatic disorders
- Bone disorders
- Agranulocytosis
- Changes in mood
What are some adverse effects associated with the use of phenytoin?
- Blood disorders
- Skin disorders
- Bone disorders
- Cardiac disorders
- Respiratory disorders
What is are some key points when counselling a patient on the use of phenytoin?
Important that they recognise the signs and symptoms of blood and skin disorders
Can phenytoin be used in pregnancy and breastfeeding?
Pregnancy - no
Breastfeeding - yes
Phenytoin may exacerbate which kinds of seizures?
Absence
Myoclonic
How does phenytoin affect enteral feeding regimens?
Enteral feed needs to be interupted 2 hours before and after dose
Which demographic of patients can phenytoin not be used in and why?
Those of Han chinese or Thai origin - increased risk of Stevens-Johnson’s syndrome
What monitoring requirements are there for the use of phenytoin?
FBCs
What class of drugs do phenobarbital and primidone belong to?
Barbiturates
What is the MHRA warning associated with the use of benzodiazepines?
Benzodiazepines and opioids: Risk of potentially fatal respiratory depression (March 2020)
What are sodium valpraote and valproic acid indicated for?
- Prophylaxis of seizures in epilepsy
- Status epilepticus where a benzodiazepine has been unsuccessful
- Bipolar disorder
Prophylaxis of which types of seizure is sodium valproate the first line treatement for?
Focal
Tonic-clonic
Absence
Myoclonic
What are the important adverse effects associated with the use of valproate?
- GI upset
- Neurological and psychiatric effects
- Thrombocytopenia
- Severe liver injury
- Bone marrow failure
- Pancreatitis
When is the use of sodium valproate contraindicated?
- Women of child bearing potential
- Pregnancy, particularly in the first trimester
Which drugs interact with valproate?
- Drugs that are metabolised by CYP enzymes (warfarin etc)
- Enzyme inhibitors - increase the toxicity and risk of adverse effects
- Enzyme inducers - lower the efficacy valproate and increase risk of seizures
- Drugs that lower the seizure threshold (antipsychotics and tramadol)
How is sodium valproate metabolised?
By hepatic CYP enzymes
What are the key points when counselling a patient on the use of sodium valproate?
- GI upset is transient and will likely pass in a few days
- Aware of signs and symptoms of liver and blood abnormalities
- Discuss pregnancy and contraception
- Patient cannot drive unless thay have been seizure free for 12 months and for 6 months after switching or stopping treatment
What are the clinical indications for the use of carbemazepine?
- Seizure prophylaxis
- Trigeminal neuralgia
Which seizure type is the use of carbemazepine not recommended in?
Myoclonic
Absence
What are the important adverse effects associated with the use of carbemazepine?
- Antiepileptic hypersensitivity syndrome
- GI upset
- Neurological effects
- Oedema
- Hyponatraemia
Carbemazepine causes oedema and hyponatraemia through antidiuretic hormone-like effects
When should carbemazepine be used with caution?
- Renal impairment
- Hepatic impairment
- Cardiac disease
- Pregnancy
When is the use of carbemazepine contraindicated?
In patients with a history of antiepileptic hypersensitivity syndrome
Is carbemazepine an enzyme inucer or inhibitor?
Inducer
Which drugs interact with carbemazepine and to what extent?
- Drugs that are metabolised by CYP enzyme such as warfarin, oestrogen and progestogens
- CYP inhibitors - increase risk of adverse effects and toxicity
- Other antiepileptics
- Drugs that lower the seizuere threshold such as antipsychotics an tramadol
How should carbemazepine be initiated?
Started at a low dose of 100 - 200mg OD/BD then increased gradually (max 1.6g)
What are the clinical indications for the use of lamotrigine?
- Prophylaxis of focal, tonic-clonic, and absence seizures in epilepsy
- Bipolar depression
What are the important adverse effects associated with the use of lamotrigine?
- Headache
- Drowsiness
- Blurred vision
- GI upset
- Skin rash
- Hypersensitivity reactions
When is a dose reduction of lamotrigine necessary and why?
Patients with hepatic impairment as lamotrigine is metabolised by glucuronidation
Can lamotrigine be used in pregnancy?
Yes
Which drugs interact with lamotrigine and to what extent?
- Drugs that induce glucuronidation such as carbemazepine, oestrogens, rifampicin, and protease inhibitors - cause lamotrigine concentrations to fall
- Valproate inhibits glucuronidation and as such causes the concentration of lamotrigine to rise increasing the risk of toxicity
What should happen to the dose of lamotrigine if it is being coprescribed with a drug that causes glucuronidation?
It should be doubled
How is lamotrigine typically dosed?
Started at 25mg OD
Increased 2-weekly intervals up to 200mg
What should happen to the dose of lamotrigine if it is taken concurrently with valproate?
It should be halved or taken on alternative days
How is lamotrigine unique as a treatment for bipolar disorder?
It effectively treats bipolar depression without increasing the risk of switch to mania
What are the clinical indications for the use of levetiracetam?
- Prophylaxis of focal seizures
- Status epilepticus when first line benzodiazepine was ineffective
It can also be used for the treatment ofmyoclonic and tonic0clonic seizures
What are the advantages of using levetiractem compared to other antiepileptics?
It is relatively well tolerated, and most patients only suffer from mild adverse effects or none at all.
It also has very few clinically significant interactions with other drugs such as hormonal contraception, warfarin, and other antiepileptc drugs
Can levetiracetam be used during pregnancy and breastfeeding?
Yes
When is a dose adjustment of levetiracetam required?
In renal impairment
What is a typical dosing regimen of levetiracetam?
Starting dose of 500mg BD
Increased to 1g after 2 weeks (max 1.5g BD)
What is the dose equivalance between oral and IV levetiracetam
They are the same
What are gabapentin and pregabalin indicated for?
- Add-ons for the prophylaxis of focal seizures in epilepsy
- First line options for neuropathic pain
- Pregabalin is licensed in generalised anxiety disorder
What are the main adverse effects associated with the use of gabapentin and pregabalin?
Drowsiness
Dizziness
Ataxia
These improve after a few weeks of treatment
When should both gabapentin and pregabalin be dose adjusted?
In renal impairment
Which drugs interact with gabapentin and pregabalin and to what effect?
Their sedating effect maybe exacerbated by other sedating drugs such as benzodiazepines
Other than that they have relatively few significant clinical indications
How should gabapentin and pregabalin be initiated?
They should be started at a low dose and gradually titrated up to reduce adverse effects
Between gabapentin and pregabalin, which has an effect on urine dipstick testsing?
Gabapentin can cause false positives for proteins on urine dipstick tests
What are the most commonly prescribed benzodiazepines?
Chlordiazepoxide
Lorazepam
Diazepam
Temazepam
Midazolam
What are the clinical indications for the use of benzodiazepines?
- First line management of seizures and status epilepticus
- Fisrt line management of alcohol withdrawal reactions
- Sedation for intervention procedures
- Short-term treatment of severe or distressing anxiety or insomnia
What are the important adverse effects associated with the use of benzodiazepines?
- Drowsiness
- Dependence
- Withdrawal reactions
- Small chance of cardiorespiratory depression
Which benzodiazepine is the best choice for the treatment of alcohol withdrawal in a patient with liver failure and why?
Lorazepam as it depends less on liver elimination and therefore has a lesser chance of causing hepatic encephalopathy
In which patient demographic should benzodiazepines be used with particular caution and why?
The elderly as they are more susceptible tothe effects of benzodiazepines
When should the use of benzodiazepines be avoided?
- Liver failure
- Respiratory impairment
- Neuromuscular disease
Which drugs interact with benzodiazepines and to what effect?
- Other drugs with sedating effects such as opioids and alcohol
- CYP inhibitors such as metronidazole
For the treatment of alcohol withdrawal is it best to use a long- or short-acting benzodiazepine?
Long
Such as chlordiazepoxide, lorazepam, and diazepam
For the treatment of epilepsy is it best to use a long- or short-acting benzodiazepine?
Long
Usually lorazepam
For sedation is it best to use a long- or short-acting benzodiazepine?
Short
Such as midazolam
What duration of action is ideal in a benzodiazepine used to treat anxiety and insomnia?
Intermediate
Tenazepam
Which drug is a specific antagonist of benzodiazepines?
Flumazenil
Why is the use of flumazenil rarely indicated?
It should not be used to reverse benzodiazepine-induced sedation in suspected overdose as it may precipitate seizures, which having blocked the action of the benzodiazepines will extremely difficult to treat
What is the NHS Never Event regarding midazolam?
Mis-selection of high strength midazolam during conscious sedation (January 2018)
What is a typical dose of chlordiazepoxide for the treatment of alcohol withdrawal?
10 - 40mg QD
Reduced over 5 - 7 days
What are the first line options for the treatment of ADHD?
Methylphenidate
Lisdexamfetamine
What schedule of CD is methylphenidate?
Schedule 2
What drug is sold under the brand name Delmosart?
Methylphenidate
What drug is sold under the brand name Concerta?
Methylphenidate
What drug is sold under the brand name Medikinet?
Methylphenidate
When is the use of methylphenidate contraindicated?
- Cardiovascular disease
- Hyperthyroidism
- Psychosis
- Anorexia
What drug is sold under the brand name Elvanse?
Lisdexamfetamine
What schedule of CD is lisdexamfetamine?
Schedule 2
Can either methylphenidate or lisdexamfetamine be used in pregnancy or breastfeeding?
No
What is the next line option for the treatment for patients in whom stimulants have been ineffective or are unsuitable for the treatment of ADHD?
Guanfacine
Which drug class does guanfacine belong to?
Alpha2-adrenoreceptor agonists
What needs to be monitored in patients receiving treatment with guanfacine?
- QT interval
- Hypotension
- Bradycardia
- Arrythmia
- BMI
Which drugs are used to treat acute episodes or mania and hypomania?
Olanzapine
Haloperidol
Quetiapine
Risperidone
Which drugs are used for the prophylaxis of mania and hypomania?
Lithium
Valproate
What does lithium interact with and to what extent?
ACE inhibitors - increases the risk of lithium toxicity