Parkinson's Disease and Epilepsy Flashcards
what is the MOA of levodopa?
precursor of dopamine that is able to cross the BBB. it is taken up into dopaminergic neurons and converted to dopamine.
What needs to be given alongside levodopa in PD and why?
a peripheral dopa decarboxylase inhibitor (carbidopa or benserazide) to prevent levodopa being decarboxylated in teh peripheral tissues so there is more available to cross the BBB
name two side effects from having too much peripheral dopamine in the system
N&V due to stimulation of the CTZ in teh medullary vomiting centre whcih lies outside the BBB. And arrhythmias and vasodilation whcih can lead to postural hypotension and flushing
what can be given to patients who are getting severe side effects caused by peripheral dopamine?
domperidone, a peripheral DA antagonist.
what can excessive dopamine in the CNS cause?
dyskinetic involuntary movements, akathisia (restlessness), halluciantions, anxiety, confusion, pathological gambling, increased libido and psychosis. sedation
name 3 dopamine receptor agonists
pramipexole, ropinirole, rotigotine
name two selective monoamine oxidase type B inhibitors
rasagiline, selegiline
what role do MAOs have in treatmetn of PD?
they can prolong duration of action of DA and reduce levodopa dosage requirement, but only produce modest clinical benefit when used alone.
what is an example of a COMT inhibitor
entacapone
what is the MOA of COMT inhibitors?
COMT is responsible for the breakdown of levodopa. inhibition of COMT doubles the half-life of levodopa and increases motor response to a given dose.
what is often used as the initial treatment for younger pts with PD and why?
DA receptor agonist e.g. ramipexole due to less risk of dyskinesias in the long-term compared with levodopa
what can be used to treat parkinsonian psychosis?
atypical antipsychotics e.g. clozapine or quetiapine
why does drug-induced parkinsonism (e.g. by antipsychotics) respond poorly to levodopa-?
because the causative drug occupies the D2 receptors.
name three sodium channel blocking drugs that are used in epilepsy
carbamazepine, phenytoin, lamotrigine.
what teratogenic effects are associated with carbamazepine?
neural tube defects, cardiac and urinary tract abnormalities and cleft palate
what effect does carbamazepine have on cytochrome P450?
it induces it so it will reduce teh plasma concentration and efficacy of drugs metabolised by CYP enzymes such as warfarin, oestrogens and progestogens
how long do patients have to be seizure-free for before they can drive?
12 months
after changing epilepsy meds or stopping treatment, how many is it before they are allwoed to drive?
6 months
which seizure type does phenytoin not work for?
absences
what is the MOA of sodium valproate?
weak inhibitor of neuronal sodium channels, stabilising resting membrane potentials and reducing neuronal excitability. increases brain content of GABA.
name 4 unwanted effects of sodium valproate
nausea, gastric irritation, diarrhoea, tremor, ataxia, behavioural disturbances, thrombocytopenia, transient increase in liver enzymes
what is thought to be the MOA of levetiracetam
thoguht to modulate release of excitatory neurotransmitters, such as glutamate
what is the drug of choice for status epilepticus in hosptial?
IV lorazepam
after how many seizures is epilepsy usually diagnosed and drug treatment started?
2
name two first line drugs for partial seizures
carbamazepine, lamotrigine, oxcarbazepine, sodium valproate
what is first line for tonic-clonic seizure
carbamazepine, lamotrigine or sodium valproate
what is first line for myoclonic seizures?
sodium valproate
what is first line for absence seizures
ethosuximide, or sodium valproate
what is first line for atonic generalised seizures
sodium valproate, lamotrigine, clonazepam
is a benign essential tremor better or worse on movement?
worse on movement, reduced at rest
name 4 classes of drugs that can cause drug-induced parkinsonism
SSRIs, beta-blockers, lithium, anti-psychotics
what is the pathophys of PD?
loss of dopaminergic neurons in the substantia nigra
what is the triad that characterises PD
resting tremor, bradykinesia, skeletal muscle rigidiey
TRAP = tremor, rigidity, akinesia/bradykinesia, postural instability
based on the pathophys of PD, what are the 3 targets of pharmacological managment?
increase DA levels
reduce DA break down,
act directly on DA receptors
what could you offer a pt with PD who has a disabling tremor or excessive salivation?
anticholinergic.
why can’t you give dopamine in PD?
because it can’t cross BBB
why do you need to give a dopa decarboxylase inhibitor with levodopa
to prevent levodopa being converted to dopamine in the peripheral circulation because once converted to dopamine it can’t cross BBB where it is needed to have the desired effect.
what is the effect of dopamine on prolactin?
dopamine inhibits prolactin, thus preventing lactation
what effect does dopamine have on nausea?
it has emetic action (causes nausea) whcih is why metoclopramide (a dopamine antagonist) is used as an antiemetic.
what effect does dopamine have on GI motility?
inhibits gastric stimulation (anti-kinetic effect). an example of an antagonist is domperidone.
which groups of pts should not be prescribed medications containing levodopa due to its MOA?
pts with severe psychiatric histories especially psychosis/schizophrenia.
those who are breastfeeding(as it suppresses lactation).
caution in severe pulmonary or cardiovascular disease (DA can be converted to adrenaline or NA causing tachycardia and HTN). caution in severe nausea or GI motility problems
name 3 common side effects of co-careldopa and co-beneldopa
N&V, abnormal dreams and sleep disturbances, dizziness and syncope
name 4 important side effects of co-careldopa and co-benldopa to be aware of
dyskinesia, rapid fluctuations in clinical state (“on-off” effect), postural hypotension, psychological effects (dementia, depression, schizophrenia-like syndrome)
what is the risk of using levodopa containing meds with monoamine oxidase inhibitors (MAOIs)?
risk of hypertensive crisis
what is the risk of using levodopa containing meds with general anaesthetic?
increased risk of arrhythmias
should you be careful about starting a patient on levodopa who has HTN?
yes because in combo with antihypertensives, levodopa can cause increase risk of hypotension
what do patients taking levodopa-containing drugs need to be counselled on terms of if they stop taking them?
they need to known taht they cannot stop them abruptly as it carries a small risk of neuroleptic malignant syndrome.
what 4 things do you need to communicate to a pt before starting treatmetn with a levodopa containing medication?
- side effects
- not to stop it abruptly (risk of NMS
- hypotnesion
- sleeping (risk of excessive sleepiness or sudden onset of sleep) - driving/work
how can you prevent “on-off” fluctuations occuring on levodopa therapy where pts swithc from severe dyskinesia to immobility in a few minutes?
combine levodopa with a DA agonist. fewer doses of levodopa. liquid forms of levodopa
if a PD patitent is unable to swallow so can’t take their levodopa, what can you do?
crush tablets (do not do this with modified release drugs), consider liquid, patch (Ritigotine), NJ/NG/PEG tube. DO NOT ABRUPTLY STOP PD MEDS WITHOUT SPECIALIST ADVICE
What is the pathophys of neuroleptic malignant syndrome?
depletion of DA in the hypothalamus/nigrostriatal pathway
what are the signs and sx of neuroleptic malignant syndrome?
rigidity, fever, altered GCS
what is first line AED for focal seizures?
lamotrigine or carbamazepine
what is the first line for generalised seizures?
sodium valproate
name two contraindications of using sodium valproate
history or family hx of hepatic dysfunciton, metabolic idsorders
name 4 side effects of sodium valproate
GI disturbacnes, weight gain, transient hairloss with regrowth of curly hair, neurological features, blood dyscrasias
what drug monitoring should you arrange for a pt about to start sodium valproate?
LFTs (before and during first 6 months), FBC before surgery (to assess bleeding risk)
what would be the most appropriate first line drug for generalised seizures for a woman in her reproductive years?
at loser doses, lamotrigine is relatively safer than sodium valproate, however, none of them are truly safe and women need to be counselled of this and encouraged to have contraceptive cover.
which two conditions can lamotrigine exacerbate?
myoclonic seizures and PD
name 4 side effects of lamotrigine
hypersensitivity syndrome (fever, rash, lymphadenopathy, hepatic dysfunction) , rashes, GI disturbances, CNS effects, BM suppression
what interaction can lamotrigine have with combined oral contraceptive?
it can possibly reduce contraceptive efficacy
other than avoiding AEDs in pregnancy if possible, what other advice would you give to a woman with epilepsy before she becomes pregnant?
give higher level of folic acid (5mg) rather than standard dose
if you have a seizure what does this mean in term so fdriving?
you must tell DVLA and stop driving straight away
if you have epilepsy how long do you have to be seizure free for before being able to reapply for a driving license?
12 months
if you have a single one-off siezure, how long do you have to wait before re-applying to drive?
6 months
what safety advice should you give to someone with epilepsy
advise they avoid operating dangerous machinery, avoid dangerous leisure activites, avoid unsupervised baths/showers, cycling on busy roads. also provide those around them with advice on what to do during a seizure.
