Lecture - Pharmacology (Anti-epileptics) Flashcards
Slide 6:
- Is the same drug used for everyone even if they have different types of seizures?
- What are the three main drugs you need to know?
- No, multiple drugs are taken if people have multiple types of seizures
- Phenytoin, carbamazepine, valproate, lamotrigine
Slide 7:
- What is epilepsy? Like, what is it characterised by?
- How do you define the thing that it is charactrised by?
Slide 8/9:
So there are generalised seizures and partial seizures
- What are two types of generalised seziures?
- what does each involve? - How does the EEG differ between the generalised vs the partial?
-
Tonic-clonic (Grand mal)
- loss of consciousness & posture
- violent motor abnormalities
- gradual recovery, confusion
(Tonic phase: increased muscle tone, rigidity. Clonic phase: synchronised jerking movements, limbs & body).
- Really crudely, tonic clonic is the hyperactivation of large amounts of the brain in what appears to be convulsions whereras absence seizures which involve a large part of the brain also – seem to involve the turning off of behavoiour.
- -To be more specific, tonic clonic seizures involve abnormal eeg activity which is widespread across nervous system – this is the stereotypical one (violent muscle activity where stiff, clonic jerking phase and then recovery and confusion)*
Absence seizures (Petit mal)
- brief loss of consciousness
- some clonic motor activity
- rapid recovery
- begin in childhood
-
Another one is the abnormal seiur = they tune out for a period of time. Some clonic motor activity in limb etc. People often find it hard to digest that it si speilepsy bc it is loss of hyperactivity – but really, you need hyperactivity in one part of the brain to turn off activity in another part (Gaba-ergic neurons etc) of the brain resulting in no behaviour. So just a particular kind that results in loss of consciousness. Particular drugs like ethasuxcamide is used only ofr absence seizures
2. The EEG for generalised tends to be abnormal and widespread. For partial, it is confined to a discrete brain region.
Slide 10:
- What are the two types of partial seizures?
- what does each involve?
-
Simple partial seizures (focal seizures)
- no loss of consciousness
- single-lmb convulsions or tremors
Complex partial (psychomotor seizures)
- consciousness is impaired
- sensory illusions
- sterotyped behaviour limbic system (temporal lobe, hippocampus)
o Partrial serizures = Abnormal Epileptic activity is confined and discrete. It can be confied to a small area of NS or involve larger areas. Eg simple partial seizures- no loss of consciousness etc so may involve just small part of the motor cortex.
o Complex partial seizures = (temporal lobe epilepsy) – hippocampus etc temporal lobe parts. Steroyted behaviour = generation of behaviour unique to the person. WE NEED TO LOSE THE IDEA THAT SEIZURE AACTIVITY IS JUST TONIC CLONIC. What we see clinically is what part of the brain is affected (so epileptic activity in the brain = seizure). It can be very idosynchratic - this kind of epilepsy is often confused with psychiatric disorders like schizophrenia etc (like a seizure can be just taking out stuff from the bag and packing it)
Imagine and tell me what the EEG looks like in partial vs complex seizures
Is this normal or an epileptic EEG?
NORMAL
Normal or epileptic?
Petit mal (absence seizure in an 8 year old child)
o Petit mal is the old term of ‘absence seizure’ I think (he said it should say absence seizure on there).
o You can instantly diagnose it bc there is 3-4s spike wave signature. So EEG critical part of diagnosing seizures so to know what drug to use
Just read this card and make sure you understand it
o Abnormal neuronal firing is what the EEG records
o So normal conditions eg hippocampal neurons will generate infrequent AP with a steady spike interval but during the epieltic activity, this becomes much more freqrnt and syndchornuc so they all fire togehrt. But synchronic epileptic activity – comes from animal experiments (various animal models which have limitations when you genrealise to humans). So even now, we still don’t know how eg phenytoin exactly work – because it is invitro.
Slide 17
- Are seizures unique and peculiar or stock standard?
No, they are peculiar - like for one lady, her seizure is packing and unpacking her bag.
Well, the complex partia serizure was anyway.
What’s status epilepticus?
Unremitting seizure activity
Slide 22:
What are the causes of neuronal hyperactivity (aka why epilepsy is a thing?)
o A lot of theories of epilepsy focus on a collapse of gaba-ergic inhibition etc (second bullet point)
o Third bullet - If you deprive a neuron of all its synaptic input – even if you have everything else – it will generate lots of activity still bc of variety of voltage dependent-conductances. Some of them are repetitive socidum conductonaces like sodium apacemaker etc – these intrinsic mechanisms keep neurons firing at a tonic level that is then modified or modulated by incoming synaptic excitation or inhibiton. So platonic neurons sit there but it is tonically active – that activity is modulated up or down
o Neurons in areas in epileptic areas have increasd excitability so they are overactive so some of the drug work on these instrinctic mechanism
♣ Baisxally wanna get drugs that will cut off that abnormal hyperactivity while leaving normal activity alon
Slide 24/25:
- What are the 4 drugs you need to know?
- what things do they control briefly (e.g. vigabatrin controls all seizure types)
- All seizure types:
- Valproate
- Diazepam
- Vabigatrin
- Lamotrigine
- All types other than absence seizures
- Phenytoin
- Carbamazepine
- Partial seizures
- Levetiracetam
Note that valproate and ethosuximide are used for absence
Slide 28:
- What is used for a lot of seizure types? Just list the bold
- What’s used in drug-resistant pateints? (this isn’t bolded)
- What’re partial seizures treated with? Just list the bold
- What about absence? (this isn’t bolded)
5. What drug is used for status epilepticus?
Slide 29:
- What’re some other uses of anti-epileptic drugs?
o In the last couple of decades, some anti-epileptic ones are used for bipolar disorder etc (even lithium was used for bipolar)
o Migraine si common and it has connections to epilepiletic-form activity
o Many anti-epi are used to treat eg tinnitus (phantom auditory sensation) or any sensory illusions that are generated by epileptiform activity in the sensory areas of the brain. Many people consider them as sensory epilepsy
♣ Eg after wisdom tooth surgery, even after it has all healed, there is still chronic pain for some people bc there is hyperactivty activity still in the trigeminal nuelecus or something so it is considered as epilepsy – reason for pain is the epileptiform activity, so doesn’t repond to opoids but rather anti-epileptic drugs
Slide 30
- What’re the three main mechanisms of actions?
- What about the mechanisms of the newer drugs?
o Neweer drugs – not understoof and even old drugs aren’t understood well.
o Phenytoin etc traisl – best evidence is in-vitor study but we don’t know if that is exactly what happens in vivo
o Second bullet- It appears that old epileptics like phenytoin work on instrici excitability that has been upregulated so they target repetitive sodium conductances that cuase hyperactivity
o Thirs bullet = ethansuxcamide so they work on t-type Ca channels
o Other drugs work by () (fourthbullet) – so reduce uptake or metabolism of GABA
Slide 31:
- So, some drugs are believed to work on sodium channels - what are these drugs?
- How do they work?
o SO if you take those three mechanisms from previous slide – three of the most common anti-epileptics work on the intrinctic excitability
Slide 32:
- Some drugs work on Calcium channels, tell me which ones
- How do these drugs actually work?
o This Levertiracetam is being theorised as a cognitive-enhancing drug. Antipeiletic action bc reduces release of glutamate (bc of the reduction in neutransmitter release) – which will reduce any increase in synaptic excitation
Slide 33:
- And finally, some drugs work on the GABA neurotansmitter thing - which ones?
- ANd how
o Vigabatrin – there are adverse side effect but minor
o Tiagabine = effectily has the sam effect on GABA but by inhibiting the reuptake of GABA
Label
GABA is released – vagibatric is working on the enzyme – influenc both GABA A and GABA B receptors
Slide 35
- How do benzodiazepines work?
- What BZDs are used in status epilepticus?
- how are they administered?
o They work on an allostric site on the GABA A receptor= mostly used for status epilepticus
o Clonzepam is also used for other epileptic things, not just status epilepticus but not commonly used
o Increase Cl- influx, potentiating the effect of GABA so causing more inhibition. Used for status epileptics IM/IV to shut off the seizure acivity – in status epilepticus, there is massive glutamate relase in the brain which will cuase brain damage so need to treat (if you don’t treat eg childhood epilepsy- then over a period of time, they develop serious brain damage)
What’re some common adverse effects of valproate?
o Antiepileptics are known for ()
Agranulocytosis = increased susceptibility for infections (blood monitoring should be done when you start the carba drug)
What about adverse effects of levetiracetam?
o Leve – the bad things is the sychotic symptoms and suicidal thought with this
What about BZDs in terms of
- therapeutic index
- common adverse effects
- tolerance
o High therapeutic index so more safe
o The adverse effects happen early when you start using it
o Problem with even clozapam (the one that can also be used to treat other types of epilepsy, not just status epilepticus) is that tolerance can be built up – people have to be changed every 6 months so,etimes bc you get the tolerance
Slide 40:
- Phenytoin - what about its therapeutic index?
- What is therefore essential?
o Need to do drug montoring bc narrow range of effective conc so need to not go in the toxic range (which is easy to do…sadly)
What’re some adverse side effects of phenytoin? (aka consequences of overdose)
o Second bullet point: This is result of effects of pheny on the central vestibuloar system so like trouble standing up etc
o Vestibulo-occular reflex abnormal = nystagmus
o Hirsutism = abnormal growth of hair on a woman’s face and body.
o Teratogenic drug
Okay, just read this about felbamate
