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Neurology > Principles of neuropharmacology > Flashcards

Principles of neuropharmacology Flashcards

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1
Q

How is a brain capillary different to a general capillary?

A
  • pericytes
  • more mitochondria (for active transport)
  • astrocytes
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2
Q

Which drugs enter the brain?

A

the more lipophilic the drug, the better the penetration (e.g. diazepam is very lipophlic)

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3
Q

Outline glucose and L-DOPA uptake into the brain

A

Much more reaches the brain than would be expected with their level of lipophilicty due to active transport

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4
Q

Outline phenobarbital (PB) and phenytoin uptake into the brain

A
  • quite lipophilic but not as much penetration to brain as would be expected
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5
Q

What is PGP?

A
  • p-glycoprotein
  • an efflux pump that pumps foreign material out of cells
  • expressed in BBB
  • overexpressed in epileptic focus therefore decreased anti-epileptic drug action
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6
Q

Define AED

A

anti-epileptic drug

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7
Q

Why are collies sensitive to ivermectin?

A

They lack the PGP molecule to pump ivermectin out of brain cells –> seizure activity when administered this.

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8
Q

Are the neural impulses in all seizures hypersynchronous?

A

Yes - it means all neurons are firing at the same time

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9
Q

When to treat seizures?

A
  • status epilepticus or animals with cluster seizures
  • severe postictal signs
  • when severity or frequency increases
    ? one seizure every 6 weeks?
    ? 2 or more isolated seizures within 6 months?
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10
Q

How many seizure dogs respond to AED?

A

2/3

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11
Q

How do AEDs affect epilepsy?

A

suppress seizures, don’t actually tx the epilepsy

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12
Q

Why encourage an owner to chart seizure frequency?

A

to give them something to do by de-emtoionalising the situation. You can give diazepam to owners to put in rectally (this is done in humans too)

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13
Q

Considerations for starting seizure tx

A
  • monotherapy
  • seizure frequency may influence choice of AED
  • monitor plasma levels
  • owner compliance
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14
Q

What is the best aim of seizure tx?

A

to increase inhibition in the brain (as there are no advantages to blocking excitation route)

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15
Q

Tx - refractory epilepsy

A

Ketamine (NMDA antagonist)

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16
Q

Mode of action - barbiturate

A

increases the duration of chloride ion channel opening at the GABA-A-R. This increases the efficacy of GABA.

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17
Q

Mode of action - benzodizepines

A

Increase the frequency of chloride ion channel opening at the GABA-A-R. This increases the potency of GABA. Diazepam may nt work with long seizures because GABA may already be depleted.

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18
Q

Tx for a seizure of 2 hours duration

A

give diazepam and phenobarbitone at the same time

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19
Q

Tx for a seizure of

A

Give 2 doses diazepam and then give phenobarbitone. (barbiturates need no/less GABA to act than benzodiazepines)

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20
Q

PB- half life

A

24- 40 hours

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21
Q

PB - time to steady state

A

10-14 days

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22
Q

Side effects - PB

Study These Flashcards
A

sedation, PD, polyphagia, hepatotoxicity
- TT4 and fT4 reduction, no effect on ACTH stimulation test
- hepatotoxicity
- routine biochem +/- bile acid stim. q6-12 months
- may reduce elimination half-life with chronic life
RARE, BUT SEVERE (idiocyncratic reactions):
- behavioural alterations
- immune-mediated neutropaenia, thrombocytopaenia, anaemia
- superficial necrolytic dermatitis (SND)
- idiosyncratic hepatotoxic reactions
*ACTION: stop immediately, load with alternative AED (KBr)
- withdrawal seizures due to drug dependence

23
Q

Metabolism - PB

24
Q

Administration - PB

Study These Flashcards
A
  • loading dose if indicated.
  • adjust dose if seizure frequency is equal or increased after 30 days
  • increment of 5 m, icrog/ml
25
How does PB affect metabolic clearance in liver?
increases metabolic clearance in liver so lower 1/2 life of itself and other drugs. also increases ALT and other enzymes due to generalised increased liver activity
26
Calculate oral daily dose for mg PB
= (desired concentration/ actual concentration) * total mg PB per day
27
KBr - half-life as an AED
15-20 days
28
KBr - time to steady state
100-200 days
29
Side effects - KBr AED
sedation, weakness, PU, PD, GIT irritation (V and D), (pancreatitis)
30
Outline bromide toxicity
RARE - severe ataxia, sedation, somnolence, skin reactions - dogs with renal insufficiency * ACTION: I.V. saline to enhance renal excretion
31
Why do you get a pseudohyperchloraemia with KBr?
biochem test can't distinguish Cl- from Br- so counted as one and the same.
32
What is imepitoin? How does it compare with diazepam?
- a partial benzodiazepine agonist - it is 1000x less potent than diazepam (both benzodiazepines) but patient is less dependent on imepitoin so no withdrawal seizures if tx stopped unlike diazepam.
33
Use -imepetoin
- first like tx for dogs with newly diagnsoed idiopathic epilepsy - relatively good side effect profile so can be considered is 'less severe' epilepsy cases sooner - dogs with severe side effects on PB or other anti-convulsants - alternative for dogs with unsatisfying seizure control on PB or other anti-convulsant drugs - NOT for dogs with acute seizures (cluster seizures / status epilepticus) OR in cats
34
Half- life PB
2 hours
35
Time to steady state - PB
1-2 days
36
side effects - PB
sedation, polphagia, hyperactivity
37
Reasons for AED tx failure
- incorrect diagnosis (-> perform MRI) - incorrect choice AED - incorrect dosage - low AED levels - newly developed disease (liver, kidney, pancreas) - change in BWt - patient tolerance to drug - monotherapy is insufficient - refractory seizures - poor compliance
38
Actions in case of tx failure
- monitor drug levels - adjust dose - if still failure - adjust more - if still failure - add anticonvulsant - if still failure - monitor drug levels - adjust dose - if still failure - consider new drug - keep in touch with a neurologist
39
Signs of refractory epilepsy / non-responder
- seizure frequency reduction of less than 50% | - 20-30% poorly responsive with combination of PB and KBr
40
First choice AED in cats
Phenobarbital
41
PB - side effects - cats
polyphagia, BM suppression, cutaneous hypersenstivity
42
2nd choice AED in cats
diazepam
43
Side effects - diazepam in cats
- (acute) hepatotoxicosis (important to evaluate liver enzymes 5- 7 days after initiation). Can progress to fulminant hepatic necrosis.
44
Outlien KBr in cats as an AED
contraindicated as --> bronchial asthma
45
Name 2 other AEDs in cats
- levetiracetam | - gabapentin
46
What type of damage does status epilepticus cause?
- primary | - secondary / complications (may be more important)
47
Problems experienced with seizure of 30 minutes duration
- arterial hypertension - increased cerebral BF - hypoxaemia - hypercarbaemia - hyperglycaemia - lactic acidosis
48
Problems experienced with seizure > 30 minutes duration
- continuous mm contraction - hyperthermia (--> brain damage) - acidosis (--> mm failure) - myolysis (myoglobinuria, hyperkalaemia, cause renal failure) - hypoglycaemia (energy deposition) - hypotension - cardiac arrhythmias
49
What does the initial AED tx (e.g. diazepam, PB) do?
- decreases HR - increases RR - decreases BP * the animal is then hypoxic and hypotensive so never forget to also treat with these 3 things: oxygen, cool down, fluids)
50
What causes multiple organ failure
- energy depletion - circulatory collapse - organ hypoperfusion
51
3 tx goals for seizure
- stop the seizures - protect the brain - think about the future
52
What should you monitor with seizures?
- HR - BP - O2 - electrolytes/ fluid balance - body temperature
53
How can you minimise seizure complications?
- MINIMIMISE BRAIN INJURY: - tx hypotension (volume expansion, fluid balance) - tx hypoxaemia (O2 supplementation) - MINIMISE HYPERTHERMIA (critical to reducing damage) - MINIMISE RENAL IMPAIRMENT
54
Ddx - underlying disease --> seizures
- HYPOGLYCAEMIA/ ELECTROLYTE IMBALANCE: correct - POSSIBLE TOXICITY? diuresis, decontaminate - SUSPECT INTRACRANIAL CAUSE: advanced imaging, CSF analysis - REFERRAL?

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