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Sem 5 > Pharmacology 11: Anti-epileptic drugs and drugs used in movement disorders > Flashcards

Pharmacology 11: Anti-epileptic drugs and drugs used in movement disorders Flashcards

1
Q

why do generalised seizures cause immediate loss of cocnsciousness?

A

the reticular system of the brain involved in consciousness is affected

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2
Q

what is the difference between partial and generalised seizures?

A 
partial= impulse discharges begin in localised area of brain, so symptoms reflect area involved e.g. abnormal sensations or thoughts, a change in behaviour, or an involuntary motor action.
generalised= whole brain affected, including reticular system- so immediate loss of consciousness. Spread quickly and generated centrally. Further divided into tonic-clonic= body goes rigid, then starts shaking due to oscillation between inhibitory and excitatory stimulation, and absence seizures= go into a trance, no shaking, unaware of things around them.
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3
Q

what is a seizure

A

episodic discharge of high frequency impulses in the brain

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4
Q

what defines epilepsy?

A

tendency towards recurrent seizures (recurrent is the key)

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5
Q

which anti-epileptics enhance the action of the inhibitory neurotransmitter GABA A?

A

benzodiazepines
phenobarbitone

so these increase Cl current into neurone causing hyperpolarisation of neurones, reducing their excitability, with an increased threshold for AP generation. Em made more -ve, and reduces likelihood of epileptic neuronal hyperactivity.

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6
Q

which anti-epileptics inhibit Na+ channel function?

A

phenytoin
valproate
carbamazepine
lamotrigine

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7
Q

which anti-epileptics inhibit Ca2+ channel function?

A

ethosuximide

gabapentin

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8
Q

1st line therapy for primary generalised seizures (both tonic-clonic and absence)?

A

valproate sodium

DON’T GIVE IN WOMEN OF CHILD BEARING AGE!*

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9
Q

1st line therapy for partial/focal seizures?

A

carbamazepine (or generalised tonic-clonic) and lamotrigine (all)
can use sodium valproate if carbamazepine or lamortrigine CI or not tolerated
if monotherapy unsuccessful with 2 of these 1st line drugs, can give adjunctive tment.

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10
Q

drug that can be used for both primary generalised seizures and partial seizures, and is probably drug of choice for women of childbearing age?

A

lamotrigine

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11
Q

1st line therapies for acute life threatening status epilepticus?

A

benzodiazepines and pheyntoin
lorazepam (0.1mg/kg) preferred- longer PD t1/2 than diazepam, IV or rectal if IV access difficult
*phenytoin= 0 order kinetics (15-20mg/kg) so can reach therapeutic and toxic levels rapidly. Must do caridac monitoring for arrhythmias and hypotension.

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12
Q

risk if patient with frequent fits stop anti-epileptic therapy during pregnancy?

A

status epilepticus, and harm to both themselves and the baby.

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13
Q

what is status epilepticus?

A

a prolonged seizure of any type

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14
Q

how is status epilepticus defined?

A

a single convulsion lasting >30mins or convulsions occurring back to back with no recovery between them

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15
Q

investigations for seizures?

A

blood gases
bedside glucose
lab Us and Es and calcium
further tests to ascertain underlying causes e.g. CT/MRI especially in trauma or focal fits

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16
Q

why can a therapeutic level of phenytoin be reached quickly, making it 1st line tment IV for emergency seizure tment?

A

has 0 order kinetics so rate of drug elimination is constant

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17
Q

precipitants of seizures in epilepsy?

A

Sensory stimuli: e.g. flashing lights/strobes or other periodic sensory stimuli
Brain Disease/Trauma: Brain Injury
Stroke / Haemorrhage
Drugs/Alcohol
Structural abnormality/Lesion
Metabolic disturbances e.g. Hypo - glycaemia/calcaemia /natraemia
Infections e.g. Febrile convulsions in infants
Therapeutics e.g. Some drugs can lower fit threshold
AEDs + Polypharmacy: PKs lower levels e.g. anti-epileptic carbamazepine= CYP450 inducer, and because of this can increase metabolism of itself, so may result in levels of drug which are not therapeutically effective, and so can result in seizures.

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18
Q

how is the firing rate of neurones brought back to normal with a voltage-operated Na+ channel blocker e.g. phenytoin?

A

prolongs inactivation state of Na+ channels so no more depolarisation can take place for a greater amount of time

carbamazepine and lamotrigine also works in this way

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19
Q

what is the initial t1/2 of carbamazepine, and why does repeated use reduce its t1/2?

A

30 hrs
carbamazepine is a strong CYP450 inducer, and via this mechanism can increase the metabolism of itself by the liver, so repeated use causes increased drug phase 1 metabolism and so reduced t1/2 to 15hrs.

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20
Q

protein binding of carbamazepine?

A

75%

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21
Q

ADRs of carbamazepine?

A 
dizziness
drowsiness
ataxia
motor disturbance
numbness
tingling
=all type A ADRs
Also GI upset= vomiting 
CV – can cause variation in BP 
Contraindicated with AV node conduction problems 
Rashes 
Hyponatraemia 
Rarely severe bone marrow depression – neutropenia
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22
Q

risk if epileptic patient treated with carbamazepine for partial or generalised seizure, and is taking warfarin for PE tment?

A

carbamazepine= CYP450 inducer, so will increase metabolism of warfarin, reducing its therapeutic effect so patient may be at risk of blood clotting.

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23
Q

risk in epileptic patient taking COCP also given carbamazepine for epilepsy?

A

may get pregnant as carbamazepine=CYP450 inducer, so increases metabolism of COCP, reducing its therapeutic effect in the body.

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24
Q

types of epilepsy carbamazepine can be used to treat?

A

all partial seizures
generalised tonic-clonic
NOT absence seizures

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25
Q

PKs of phenytoin?

A

well absorbed
highly protein bound-90%, so risk of toxicity when competitive protein binding e.g. with NSAIDs
CYP450 inducer- increase met of drugs
0 order kinetics at therapeutic concentrations (1st order at sub-therapeutic concs)- so very variable t1/2 6-24hrs.

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26
Q

phenytoin ADRs?

A 
dizziness
ataxia
headache
nystagmus
nervousness
gingival hyperplasia
rashes- hypersensitivity and Stevens Johnson- can also occur with aspirin*
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27
Q

what levels of phenytoin can be used as an indicator of its free plasma concentration?

A

salivary levels

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28
Q

types of epilepsy treated with phenytoin?

A

all partial
generalised tonic-clinic
NOT absence

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29
Q

what can reduce the level of the anti-epileptic lamotrigine in the plasma?

A

oral contraceptives- these increase the clearance of lamotrigine
however, lamotrigine has no effect on therapeutic effect of COCP as lamotrigine does not induce or inhibit the CYP450 system in the liver.

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30
Q

epilepsy types treated with lamotrigine?

A

partial

generalised tonic-clonic AND absence

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31
Q

in what 3 ways can GABA mediated inhibition be enhanced?

A

inhibit GABA inactivation
inhibt GABA re-uptake
increase rate of GABA synthesis

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32
Q

sites of action of valproate?

A

mixed sites of action:
VO Na+ channel blocker, and weak Ca2+ blocker, reducing neuronal discharge
weak inhibition of GABA inactivation enzymes and weak stimulus of GABA synthesising enzymes

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33
Q

PKs of valproate?

A

100% absorbed, than 90% protein bound
1st order kinetics, t1/2= 15hrs
CYP450 inhibitor

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34
Q

ADRs of valproate?

A

ataxia
tremor
weight gain
heaptic function- transaminases may be increased-ALT more specific to liver, AST also in skeletal and cardiac muscle, rarely hepatic failure

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35
Q

why can aspirin increase free plasma levels of valproate?

A

competitive protein binding

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36
Q

epilepsy types treated with valproate?

A

generalised tonic-clonic AND absence seizures

partial

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37
Q

how do benzodiazepines work in tment of epilepsy?

A

act at distinct receptor site on GABA Cl- channel, binding of GABA or BZD enhance each others binding. Act as +ve allosteric effectors.
increase Cl- current into neurone, increasing threshold for AP generation.

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38
Q

PKs of benzodiazepines?

A

Well absorbed 90-100%
highly plasma bound 85-100%
Linear (1st order) PK t1/2 vary 15-45 hrs

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39
Q

ADRs of benzodiazepines?

A 
sedation
tolerance with chronic use
confusion impaired co-ordination
aggression
dependence/withdrawal with chronic use
abrupt withdrawal seizure trigger
resp and CNS depression
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40
Q

how can benzodiazepine OD be reversed?

A

give IV flumazenil, but use may precipitate seizure or arrhythmia

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41
Q

epilepsy treated with benzodiazepines?

A

lorazepam/diazepam for status epilepticus

clonazepam- absence seizure ST use

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42
Q

risk of valproate use in pregancy?

A

neural tube defects in fetus

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43
Q

why should a Vit K supplement of 10mg/day be given to pregnant women in their 3rd trimester if taking anti-epileptics?

A

anti-epileptics associated with Vit K deficiency in newborn, which can cause coagulopathy and cerebral haemorrhage.

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44
Q

non motor manifestations of parkinson’s disease?

A 
mood changes e.g. depression
pain
cognitive change e.g. mild dementia
sleep disorder e.g. REM sleep disorder- muscles not paralysed, so can act out dreams
urinary symptoms
sweating

none of these will respond to typical tments to combat motor symptoms e.g. L-DOPA, dopamine receptor agonists and inhibitors of dopamine metabolism e.g. MAO-B inhibitors.

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45
Q

why can dopamine not just be given to treat Parkinson’s disease?

A

can’t cross BB barrier

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46
Q

PKs of L-DOPA?

A

Oral administration
Absorbed by active transport -in competition with amino acids (NB high protein meals)
90% inactivated in intestinal wall
monoamine oxidase & DOPA decarboxylase
T1/2= 2 hours
short dose interval
fluctuations in blood levels and symptoms
(physiologically dopamine is produced tonically)
9% converted to dopamine in peripheral tissues -DOPA decarboxylase
<1% enters CNS- Again competes with amino acids for active transport across blood brain barrier

47
Q

different type of focal/partial seizures?

A

simple= no loss of consciousness, may be associate aura e.g. smell, taste, deja vu
complex= consciousness impaired
simple or complex partial can spread through corpus callosum to cause a secondary generalised seizure- this is typically convulsive- abnormal motor response.

48
Q

ADRs of lamotrigine?

A 
dizziness
drowsiness
headache
tremor
ataxia
nausea
vomiting
49
Q

drug monotherapy in children with generalised absence seizures?**

A

lamotrigine

50
Q

considerations for driving in patients with epilepsy?

A

must notify DVLA if suffer epileptic seizure
Patients drive a motor vehicle (but not a large goods or passenger carrying vehicle) provided that they have been seizure-free for one year or, if subject to attacks only while asleep, have established a 3-year period of asleep attacks without awake attacks. Those affected by drowsiness should not drive or operate machinery.

Guidance issued DVLA recommends that patients should be advised not to drive during medication changes or withdrawal of antiepileptic drugs, and for 6 months afterwards.

Patients who have had a first or single epileptic seizure must not drive for 6 months (5 years in the case of large goods or passenger carrying vehicles) after the event; driving may then be resumed, provided the patient has been assessed by a specialist as fit to drive because no abnormality was detected on investigation.

51
Q

valproate should not be given in pregnancy due to risk of major and minor congenital malformations, but if it has to be used as no other alternative, how should it be given?

A

the lowest effective dose should be prescribed in divided doses or as modified-release tablets to avoid peaks in plasma-valproate concentrations.

52
Q

immediate management of convulsive status epilepticus?

A

Position patient to avoid injury, supporting respiration including the provision of oxygen, maintaining blood pressure, and the correction of any hypoglycaemia. Parenteral thiamine should be considered if alcohol abuse is suspected.

Seizures lasting longer than 5 minutes should be treated urgently with intravenous lorazepam (repeated once after 10 minutes if seizures recur or fail to respond). Intravenous diazepam is effective but it carries a high risk of thrombophlebitis (reduced by using an emulsion formulation). Patients should be monitored for respiratory depression and hypotension.

Where facilities for resuscitation are not immediately available, diazepam can be administered as a rectal solution or midazolam oromucosal solution can be given into the buccal cavity.

53
Q

what should happen with patient tment if after given IV benzodiazeines for status epilepticus seizures recur or fail to respond 25 mins after onset?

A

give IV phenytoin and contact intensive care unit if seizures continue
If these measures fail to control seizures 45 minutes after onset, anaesthesia with thiopental, midazolam, or in adults, a non-barbiturate anaesthetic such as propofol should be instituted with full intensive care support.
anaesthesia will stop shaking of patient, but seizure will still be taking place in brain= episodic discharge of high frequency electrical impulses.

54
Q

1st line therapy for generalised tonic-clonic seizures?

A

sodium valproate
lamortrigine is an alternative, but may exacerbate myoclonic seizures
carbamazepine may also be considered

55
Q

1st line therapy for generalised absence seizures?

A

Ethosuximide or sodium valproate are the drugs of choice in absence seizures and syndromes; lamotrigine is a suitable alternative when ethosuximide and sodium valproate are unsuitable, ineffective or not tolerated.

56
Q

cautions with sodium valproate treatment?

A

monitor liver function before therapy and during first 6 months especially in patients most at risk
measure FBC and ensure no undue potential for bleeding before starting and before surgery
avoid abrupt withdrawal
consider vitamin D supplementation in patients that are immobilised for long periods or who have inadequate sun exposure or dietary intake of calcium

57
Q

how does the tonic and clonic state come about in generalised epilepsy?

A

tonic= contractions of both agonist and antagonist muscles producing muscular rigidity as sudden loss of GABA input, so long train of firing of APs for several seconds.
GABA inhibition starts to be restored, and AMPA and NMDA mediated excitation starts to oscillate with inhibition producing shaking movements of body=clonic.

58
Q

why is status epilepticus a medical emergency?

A

can lead to brain damage or death= SUDEP= sudden death in epilepsy

59
Q

dangers in severe epilepsy?

A 
Physical injury relating to fall/crash
Hypoxia
SUDEP – sudden death in epilepsy
Varying degrees of brain dysfunction/damage 
Cognitive impairment
Serious psychiatric disease
Significant adverse reactions to medication
Stigma / Loss of livelihood
60
Q

difference between primary and secondary causes of epilepsy?

A

primary= no identifiable cause, idiopathic, but may also be channelopathies= leakage currents causing a drift to depolarisation. 65-70% of cases.
secondary=due to medical conditions affecting brain= 30-35%, e.g. tumours, vascular disease. Responsible for 60% of seizures in elderly.

61
Q

how is a focal point formed in epilepsy?

A

local loss of Em homeostasis with loss of GABA inhibitioin
relatively small number of neurones then form a generator site, the neurones heavily depolarise and hyperactivity spreads via synaptic transmission to other neurones.

62
Q

why are Na+ channel blockers used in epilepsy classed as voltage dependent?

A

only enters Na+ channel binding site when channel is depolarised
then detaches from binding site when Em back to normal

63
Q

how does carbamazepine play a role in drug-drug interactions?

A

CYP450 inducer= if given in combination with pheyntoin, it increase metabolism of phenytoin by liver so reduces its plasma concentration, and phenytoin can displace carbamazepine from protein binding sites, increasing plasma carbamazepine conc.
warfarin reduced as CYP450 induction, so increased risk of clotting, as are systemic corticosteroids and oral contraceptives.
antidepressants- carbamazepine similar in structure to tricyclic antidepressants so shouldn’t be used with MAOIs?**

64
Q

problem with administering phenytoin for epilepsy to a patient already on meloxicam for RA?

A

meloxicam= NSAID= highly plasma protein bound, as is phenytoin
NSAID will displace phenytoin from plasma protein binding sites, increasing its free conc, and exacerbating its 0 order kinetics with only small increases in free plasma conc putting patient a significant risk of toxic ADRs e.g. ataxia, confusion and gingival hyperplasia.

65
Q

how would cimetidine increase plasma levels of phenytoin?

A

cimetidine= CYP450 inhibitior, and phenytoin metabolised by CYP450 enzymes in liver.

66
Q

mechanism of action of lamotrigine?

A

prolongs inactivation state of Na+ channels
possibly Ca2+ blocker and decreases glutamate release= possible reason as to why can be used to treat generalised absence seizures.

67
Q

how does sodium valproate increase plasma levels of lamotrigine?

A

competitive protein binding

68
Q

what 2 different ways can GABA be involved in drug tments for epilepsy?

A 
1= drugs which bind at GABA A receptor to enhance GABA binding e.g. benzodiazepines and barbiturates
2= drugs which affect GABA metabolism e.g. inhibit inactivation, reuptake or increase synthesis rate, e.g. valprotate= weak inhibitor of GABA inhibition, and stimulator of synthesis enzymes.
69
Q

how does DDI between valproate and anti-psychotics take place?

A

anti-psychotics antagonise valproate by lowering convulsive threshold

70
Q

importance of monitoring for blood and hepatic disorder with valprotate?

A

Risk of ADRs and plasma Valproate not closely associated with efficacy, monitor for blood, metabolic and hepatic disorder.

71
Q

benzodiazepine that can be used ST for absence seizure in epilepsy?

A

clonazepam

72
Q

anti-epileptic drug risk of birth defects?

A

8% vs 2% normally

but lamotrigine= 2%

73
Q

what should be given to status epilepticus patient transferred to ITU?

A

anaesthetic and ventilation

74
Q

how is rigidity expressed in parkinson’s disease, and how does this contrast with that seen in pyramidal tract lesion(corticospinal and corticobulbar tracts)?

A

parkinson’s= lead pipe and cogwheel rigidity, lead pipe= rigidity throughout range of movement, cog wheel= rigidity which stops and starts as limb moved through movement range, combination of lead pipe rigidity and resting tremor?* linked to low dopamine and disturbance to levels of other NT, as is resting tremor, but bradykinesia just due to low dopamine.
clasp knife rigidity= pyramidal tract lesions= resistance to movement increases with movement until suddenly overcome- resistance diminishes, increased resistance with increased velocity.

75
Q

most profound ADR of L-DOPA?

A

dyskinesia= writhing movement, uncontrollable rhythmic movements of head, trunk and limbs. Most occur at time of max L-DOPA conc in plasma.

76
Q

what is the on/off phenomenon in Parkinson’s?

A

With continued L-DOPA therapy, more drug is required to improve symptoms as develop both a tolerance and sensitisation. Fluctuations in motor function occur, including periods of freezing and increased rigidity= off, alternating with periods of normal or dyskinetic m.ment=on.
On= occur shortly after dosing, when large bolus of dopamine being delivered to striatum. Can be overcome initially by smaller doses, but this increases likelihood of off times.
Off= occur as plasma L-DOPA declines, can compensate by increasing L-DOPA dose of frequency of dosing.

77
Q

what features develop over time with Parkinson’s?

A 
dyskinesia
falls
cognitive decline
somnolence (sleepiness)
swallowing difficulty
severe speech problems
78
Q

how can response to tment help in diagnosing idiopathic parkinson’s disease?

A

disease will respond very well to L-DOPA, other causes of parkinsonism will not

79
Q

usefulness of a DAT scan?

A

not used in diagnosing idiopathic parkinson’s, but can distinguish this from things like vascular problems, as need dopaminergic neurones to take up labelled tracer in DAT scan= no tracer taken up in Parkinson’s. should be presynaptic uptake of tracer if dopaminergic neurones present.

80
Q

other causes of parkinsonism?

A

multiple cerebral infarcts= vascular
parkinson’s-plus syndromes e.g. multiple system atrophy, Lewy body dementia
drug-induced e.g. neuroleptics
toxin-induced e.g. wilson’s disease

81
Q

how is dopamine formed from L-tyrosine?

A

L-tyrosine to L-DOPA by tyrosine hydroxylase, then to dopamine by DOPA decarboxylase

82
Q

how does neurodegeneration come about in parkinson’s?

A

lewy bodies= synucleinopathy**

83
Q

enzymes which degrade dopamine?

A

MAO

COMT

84
Q

why does L-DOPA not work if no dopaminergic neurones left?

A

to have an effect, L-DOPA must be converted to dopamine, and this takes place in dopaminergic neurones in substantia nigra pars compacta, via DOPA decarboxylase. giving L-DOPA will produce motor fluctuations (on-off).

85
Q

why might a high protein meal in parkinson’s cause limited effect of L-DOPA?

A

L-DOPA competes with aa for active uptake across BB barrier

86
Q

why do parkinson’s patients have to take lots of tablets throughout day?

A

very short t1/2 of L-DOPA (2hrs)

87
Q

what happens to most L-DOPA?

A

inactivated in intestinal wall by MAO and DOPA decarboxylase

88
Q

3 reasons for giving a peripheral DOPA decarboxylase inhibitor e.g. carbidopa, with L-DOPA (know as co-careldopa together)?

A

inhibit breakdown of L-DOPA peripherally so more can cross BB barrier to exert therapeutic action in CNS
prevent dopamine being produced peripherally which produces ADRs e.g. increase BP*
reduced dose of L-DOPA required as more reaching CNS.

89
Q

problem with main formulation of L-DOPA?

A

given as tablet (oral) but parkinson’s patients may develop swallowing difficulty, and tablets not allowed to be crushed.
can give controlled release preps to help with symptoms at night- being able to move around in bed.

90
Q

problem with giving anti-emetics to parkinson’s patients to cope with nausea induced by L-DOPA?

A

can produce parkinsonian ADRs

91
Q

ADRs of L-DOPA?

A 
Nausea/ anorexia
– Vomiting centres
• HYPOTENSION
– central and peripheral
• Psychosis
– Schizophrenia-like 
effects. 
Hallucination/ 
delusion/ paranoia
• Tachycardia

but low side effects, and drug is highly efficacious

92
Q

disadvantages of using L-DOPA?

A 
Precursor- needs enzyme 
conversion
Long term: 
• Loss of efficacy (Only 
effective in presence of 
dopaminergic neurones)
• Involuntary movements 
• Motor Complications 
– On / off
– Wearing off- before next tablet due
– Dyskinesias
– Dystonia
– Freezing
93
Q

interactions of L-DOPA?

A

vitamin B6- increases peripheral L-DOPA bdown
MAOIs increase hypertensive risk, but MAOBIs used at normal dose is ok.
antipsychotic drugs block dopamine receptors, producing parkinsonism ADRs.

94
Q

examples of dopamine receptor agonists?

A

non ergot= ropinirole
patch= rotigotine- good for patients that can’t swallow
SC=apomorphine= pump

95
Q

disadvantages of dopamine receptor agonists?

A

less efficacy than L-DOPA
impulse control disorders e.g. pathological gambling, compulsive shopping, desire to increase dose.
more psychiatric side effects than with L-DOPA, dose limiting
expensive

96
Q

advantages of dopamine receptor agonists?

A

direct acting
less dyskinesias/motor disturbances
possible neuroprotection

97
Q

ADRs of dopamine receptor agonsits?

A 
nausea
hypotension
confusion
hallucinations
sedation
98
Q

usefulness of MAOBIs in treating Parkinson’s?

A 
less ADRs than L-DOPA
prolong action of L-DOPA
can be used alone
smooth out motor response
may be neuroprotective
99
Q

how do MAOBIs act in Parkinson’s?

A

inhibit bdown of dopamine

e.g. rasagaline

100
Q

what do COMT inhibitors do?

A

Catechol-O-methyl Transferase
e.g. entacapone-doesn’t cross BB barrier, reduces peripheral bdown of L-DOPA to 3-O-methyldopa, so more available to cross BB barrier, and less 3-O-methyldopa which competes with L-DOPA to cross BB barrier. Prolongs motor response to L-DOPA, so reduces symptoms of wearing off e.g. freezing.

101
Q

why can COMT inhibitors not be given alone?

A

only works by stopping breakdown of L-DOPA, so must be given with L-DOPA to have a therapeutic effect

102
Q

why can anticholinergics be used in tment of parkinson’s?

A

may be an imbalance in parkinson’s between too high ACh in putamen (part of neostriatum) and too low dopamine in substantia nigra pars compacta.

e.g. procyclidine

103
Q

advantages of anticholinergics in parkinsons?

A

treat tremor

104
Q

disadvantages of anticholinergics in parkinsons?

A

don’t treat bradykinesia as not acting via dopamine systems

SEs= confusion, drowsiness, dehydration, blurred vision, urinary retention.

105
Q

how might amantadine treat parkinsons?

A 
enhanced dopamine release
Anticholinergic NMDA inhibition
Poorly effective
Few side effects
Little effect on tremor
106
Q

which parkinson’s patients may be selected for surgery?

A

those who are dopamine responsive, have had significant benefit with L-DOPA but just can’t tolerate its SEs.
must have had no psychiatric illness as surgery can cause depression

107
Q

types of surgery which can be used in parkinson’s?

A

deep brain stimulation- done most often in UK, for STN.

lesion= thalamus for tremor, or GPi for dyskinesias.

108
Q

presentation of myasthenia gravis?

A

Fluctuating, fatiguable- must be tested, weakness skeletal
muscle
– Extraocular muscles – commonest presentation, ptosis- usually bilateral
– Bulbar involvement – dysphagia, dysphonia, dysarthria
– Limb weakness – proximal symmetric
– Respiratory muscle involvement- this can then cause death

109
Q

drugs which can exacerbate myasthenia gravis by affecting neuromuscular transmission?

A

aminoglycosides
beta blockers
ACEIs

110
Q

complications of myasthenia gravis?

A

acute exacerbation= myasthenic crisis= drooping face, drooling, short of breath
cholinergic crisis due to overtreatment, cause depolarising block

111
Q

characterisitcs of the ACh esterase inhibitor pyridostigmine?

A 
Prevents breakdown of ACh in NMJ
ACh more likely to engage with remaining receptors 
Onset 30min- given orally so give 30 mins before meal; peak 60-120min; duration 3-6hr=t1/2
Dose interval and timing crucial
• Cholinergic side effect –
– miosis and the SSLUDGE syndrome:
» Salivation,
» Sweating,
» Lacrimation
» Urinary incontinence
» Diarrhea,
» GI upset and hypermotility
» Emesis)
=opposite effects of anticholinergics
112
Q

contrast pyridostigmine with neostigmine

A

Pyridostigmine - oral
Neostigmine – oral and IV preparations (ITU)
• Quicker action, duration up to 4 hours
• Significant cholinergic side effects e.g. urinary incontinence.

both enhance neuromuscular transmission by inhibiting bdown of ACh so less likely for autoantibodies to bind to ACh receptors.

113
Q

examples of drugs which can lower threshold for fits?

A

tricyclic antidepressants e.g. amityrptilline

isoniazid

Sem 5 (35 decks)

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