Clinical Pharmocology Flashcards
What are examples of benzodiazepines?
- Midazolam
- Diazepam
- Lorazepam
When are benzodiazepines indicated for use?
- Seizure termination
- Severe panic disorders
- Anxiety disorders - short term only
- Insomnia - short term
- Alcohol withdrawal
- Perioperative sedation
When are benzodiazepines contraindicated for use?
- Resp muscle weakness
- Sleep apnoea
- COPD
- Pregnancy
- Breast feeding
How do Benzodiazepines work?
Potentiate GABA neurotransmission
What are edverse drug reactions to benzodiazepines?
Features of Over-sedation
- Drowsiness
- In-coordination
- Muscle weakness
- Dizziness
- Confusion
- Respiratory arrest
What is the half-life of midazolam?
2 hours
What is the half-life of lorazepam?
8 hours
What is the half-liofe of diazepam?
30 hours
What are examples of triptans?
Sumatriptan
when are triptans indicated for use?
Migraines
When are triptans contraindicated?
- IHD
- Coronary Vasospasm
- Previous MI
- Uncontrolled/severe hypertension
How do triptans work?
Triptans are 5-HT1D receptor agonists and therefore block the receptors so 5-HT is unable to bind to the receptor on the vascular endothelium. This is thought to stop 5-HT (serotonin) from stimulating the vascular endothelium to release nitric oxide, causing vasodilation with stimulation of meningeal sensory nerve endings.
What are common side effects of triptans?
- Sensations of tingling, heat, pressure or tightness in any part of the body.
- Dizziness
- Weakness
- Fatigue
- Nausea and vomiting
- Drowsiness
Can also have - dyspepsia, Abdo pain, Tachycardia, myalgia, med-overuse headache
What should you be very careful giving triptans with?
SSRI’s - both together can cause serotonin syndrome
What are indications for using carbemazepine?
- Generalised/focal seizures
- Trigeminal neuralgia
What is the mechanism of action of carbemazepine?
Acts by binding to the sodium channels of neuronal membranes and prevents the influx of sodium into the cell which normally leads to an action potential. By preventing depolarisation of these neurones, there is not the repeated “firing” of action potentials that is responsible for epileptic seizures.
What are side effects of carbemazepine?
- Stevens - Johnson syndrome
- Toxic Epidermal Necrolysis
- SIADH
- Nausea and vomiting
- Dry mouth
- Peripheral Oedema, weight gain
- Dizziness
- Drowsiness and fatigue
- Headache
- Abnormal LFTs
What are indications for the use of lamotrigine?
Partial/generalised seizures
How does lamotrigine work?
Acts as a sodium channel blocker, to reduce the influx of sodium ions into neurones, and therefore reduced action potentials. This effectively stops the neurones from repetitively “firing” and therefore prevents seizures.
What are the side effects of lamotrigine?
- Rashes
- Nausea, vomiting and diarrhoea
- Somnolence or insomnia
- Headache
- Dizziness
- Blurred vision or diplopia
- Ataxia
- Hypersensitivity syndrome
- Haematological abnormalities
When is levetiracetam indicated for use?
Monotherapy/adjunct for focal seizures
How does Levetiracetam work?
It is an effective anticonvulant but little is known about its mode of action - it does not increase GABA in the brain or have an effect of ion channels. It does appear to bind to a synaptic vesicle protein SV2A which may impede nerve conduction across synapses.
What are side effects of levetiracetam?
- Psychiatric disturbance - aggression, agitation, depression
- Nausea and vomiting and anorexia
- Tremor and hyperkinesias
- Diarrhoea
- Drowsiness
- Diplopia
- Blood dycarias
What are indications for phenytoin?
- Termination of status epilepticus
- Trigeminal neuralgia
How does phenytoin work?
Binds to this sodium channel (sodium channel blocker), and reduces the influx of sodium into the cell which would lead to an action potential, and therefore reduces the depolarisation of the neurones which are responsible for epileptic seizures.
What are side effects of phenytoin?
- Nausea and vomiting
- Constipation
- Drowsiness
- Headache
- Tremor
- Rashes
- Acne
- Hirsutism
- Gingival hypertrophy
- Hepatotoxicity
- Blood disorders (anaemia, leucopenia, thrombocytopenia)
- Stevens-Johnson syndrome
What are features of phenytoin toxicity?
- Vertigo
- Ataxia
- Nystagmus
- Confusion
What is the therapeutic window for phenytoin?
5-20 mg/L
What are indications for sodium valproate?
- Commonly used in all forms of epilepsy.
- Partial and generalised epilepsy
- Sometimes used in bipolar affective disorder.
- Occasionally in migraine prophylaxis.
What is sodium valproate particularly good at managing?
Juvenile myoclonic epilepsy
What are contraindications for sodium valproate use?
- Liver dysfunction/failure
- Pregnancy
How does sodium valproate work?
- Increasing the amount of GABA in the brain - inhibits GABA transaminase
- Blocking Sodium Channels
- Blocking Calcium Channels
What are side effects of sodium valproate?
- Most serious side effects - sudden onset of liver failure, acute pancreatitis and severe thrombocytopenia.
- Nausea and vomiting
- Diarrhoea
- Weight gain
- Oedema
- Hallucinations
What are indications for gabapentin use?
- Monotherapy or adjunctive therapy in focal seizures
- Neuropathic pain
- Migraine prophylaxis.
What is the mechanism of action of gabapentin?
The precise mechanism of Gabapentin is unknown. However the main mechanism of action seems to be by blocking T-type calcium channels and inhibiting other modulators and neurotransmitters.
What are adverse reactions to gabapentin use?
- Nausea, vomiting & diarrhoea
- Abdominal pain & constipation
- Hypertension
- Headache
- Ataxia
- Mood changes and depression
What epileptic medications act by inhibiting sodium dependent action potentials?
- Carbamazepine
- Phenytoin
- Lamotrigine
What epileptic medications act by inhibiting voltage gated calcium channels?
Phenytoin
What medications act by potentiating GABA receptor function?
Benzodiazepines
What epileptic medications work by increasing GABA availibility?
- Valproate
- Gabapentin
