Pharma 10 AEDs Flashcards
Anti-Epileptic Drugs (AEDs)
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💥💥👾Enhancement of GABA A action (Benzodiazepines, Valproate, and Phenobarbitone)
💥💥👾Inhibition of sodium channel function (Phenytoin, Carbamezepine, and Lamotrigine)
👾Inhibition of calcium channel function (Gabapentin)
👾Inhibition of glutamate release
Voltage-Gated Sodium Channel Blockers
VGSC Blockers work by binding to the internal face of the sodium channel, only binding when the channel is in its 👾inactivated state👾. They work by acting preferentially on the neurones causing the high-frequency discharge that occurs in an epileptic fit, whilst not interfering with the low-frequency firing neurones in their normal state.
👾👾Depolarisation of a neurone increases the proportion of the sodium channels in the inactivated state, and VGSC blockers bind preferentially to channels in this state, preventing them from returning to a resting state where they could continue to depolarise the neurone. They thus reduce the number of functional channels available to generate action potentials.
Carbamezepine use
generalised tonic-clonic and partial seizures, but not absence seizures.
Carbamazepine 🤮🤮
Its ADRs include affects on the CNS (drowsiness, dizziness, ataxia, motor disturbances, paresthesia, and anaesthesia),
GI (nausea and vomiting),
CVS (variation in BP),
and other (rashes and bone marrow suppression (causing potential neutropenia)).
Phenytoin pk
Phenytoin is well absorbed and binds 90% to plasma proteins, also acting as a CYP450 inducer. It has non-linear PK at therapeutic levels yet linear PK at sub-therapeutic levels; this means t 1/2 is 6-24 hours (very variable) and levels need to be watched carefully
Phenytoin use
It is used to treat generalised tonic-clonic and partial seizures, but not absence seizures.
Phenytoin 🤮🤮
Its ADRs include CNS (dizziness, ataxia, headaches, and nystagmus), gingival hyperplasia (20%), and hypersensitivity rashes (including Stevens Johnson syndrome).
Lamotrigine pk use
Lamotrigine is well absorbed and has linear PK showing a t 1/2 of 24hrs. It does not induce CYP450 so has less DDIs.
🔫🔫It is used to treat generalised tonic-clonic, partial seizures, ( and absence seizure if it present with other type of seizure )
Lamotrigine 🤮🤮
ADRS are less marked, yet still can cause some CNS effects (dizziness, ataxia, and somnolence) and nausea, as well as potential for skin rashes.
Valproate sodium
Valproate acts by 👾👾increasing the GABA content of the brain by stimulating GABA synthesising enzymes and inhibiting GABA inactivating enzymes Sodium valproate has two mechanisms of action: like phenytoin, it causes use-dependent block of voltage-gated sodium channels;
. It is absorbed well and is protein bound, with a linear PK showing t 1/2 of 15hrs. 👉🏿👉🏿It is used to treat partial and generalised seizures and absence especially if there other types but it has mor ADR
Valproate sodium
Its main ADRs are generally less severe than other AEDs, yet can cause CNS (ataxia and tremor) or hepatic (increases transaminases) effects.
Benzodiazepine
Benzodiazepines (BZDs) 👾👾act on a distinct receptor site of the GABA A -receptor channels (which also bring about positive allosteric effect, so GABA and BZDs enhance one another). They are well absorbed and are highly bound to plasma proteins, with a linear PK and t 1/2 of 15-45hrs (highly variable). 👉🏿👉🏿👉🏿They are used for status epilepticus and absence seizures (in short term use).
Benzodiazepine 🤮🤮
They produce a wide range of ADRs hence are not used as first line therapy, and the ADRs include sedation, tolerence with chronic use, confusion, impaired co-ordination, aggression, act as abrupt withdrawal seizure triggers, and respiratory and CNS depression
Basic Prescribing Rules and Treatment
🥦Valproate Sodium as first line therapy for primary generalised seizures
🥦Carbamezepine for partial seizures (although can be used for generalised seizures)
🥦Lamotrigine can be used for both generalised and partial seizures, and is probably the drug of choice for woman on childbearing age (due to reduced teratogenic effects and affect on oral contraceptives).
🥦Benzodiazepines or Phenytoin for acute life-threatening status epilepticus.
Emergency Treatment
💥ABC should be initially assessed as well as attempting to treat any underlying cause. Blood glucose, U&Es, plasma calcium, blood gases, and any imaging should also be attempted yet potentially at a later stage.
💥Treatment of the seizures is vital. First line treatment includes Benzodiazepines (e.g. Lorazepam) and then IV Phenytoin; Phenytoin can be used in the acute scenario as its zero-order kinetic means therapeutic levels can be reached quicker.
💥If these measures fail, ITU referral with paralysis, sedation, and intubation will be required.
