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Principles of Neuropharmacology Flashcards

1
Q

What is the structure of a brain capillary?

A

Tight junctions between endothelial cells, pericytes and astrocytes

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2
Q

What structures control what enters the CSF?

A

Pericytes and astrocytes

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3
Q

Which substances can diffuse across the blood brain barrier?

A

Water, some gases and lipid soluble molecules

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4
Q

Which substances are selectively transported across the blood brain barrier?

A

Glucose and amino acids

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5
Q

Which substances are actively transported out of the brain and via what mechanism?

A

Lipophilic potentially neurotoxic substances via P-glycoprotein

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6
Q

What type of drugs reach a high concentration in the brain?

A

Drugs with a high oil/water partition coefficient such as nikotin, ethanol, heroin and diazepam

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7
Q

Why do some substances have a higher than expected concentration in the brain?

A

Transported across the blood brain barrier by transport proteins

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8
Q

Which two anti-epileptic drugs have a lower than expected brain concentration? Why?

A

Phenobarbital and phenyloin
Suspected to be due to multi-drug transporters that mediate transmembrane transport of lipophilic drugs (in humans has found to be PGP)

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9
Q

When should treatment for epilepsy be started?

A

Chronic epilepsy, status epilepticus, cluster seizures or severe post-ictal signs present

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10
Q

What needs to be communicated to the client prior to starting treatment?

A

Lifetime commitment
Give them a set of instructions for if a seizure occurs
Side effects of drugs
Possibility the dog won’t respond to therapy

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11
Q

What should be considered when starting treatment?

A

Mono-therapy to start
Seizure frequency
Monitoring of plasma levels
Assess owner compliance

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12
Q

What are the limitations of AEDs (anti-epileptic drugs)?

A

Toxicity, tolerance, inappropriate pharmacokinetics, expense

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13
Q

What is phenobarbital’s method of action?

A

Increases duration of chloride ion channel opening at GABA receptor resulting in increased efficacy of GABA

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14
Q

What is the dose of phenobarbital?

A

2.5 mg/kg BID

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15
Q

How long does phenobarbital take to reach a steady state?

A

10-14 days

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16
Q

What is the therapeutic range of phenobarbital?

A

15-35 mg/kg

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17
Q

What are the side effects of phenobarbital?

A

Sedation, PD, polyphagia, hepatotoxicity (at very high doses)

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18
Q

When should the plasma levels be checked for phenobarbital?

A

At 14, 45, 90, 180 and 360 days and then check every 6 months

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19
Q

What is the loading dose of phenobarbital?

A

12-24 mg/kg within 24 hours

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20
Q

When should the dose of phenobarbital be adjusted?

A

If seizure frequency is the same or increased after 30 days

Monitor drug levels and increase by 5ug/ml at a time

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21
Q

What are the possible side effects detectable on bloods?

A

Total T4 and basal T4 reduction

Hepatotoxicity - ALP elevation

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22
Q

What idiosyncratic reactions have been associated with phenobarbital?

A

Behavioural alterations
Immune-mediated neutropenia/thrombocytopenia/anaemia
Superficial necrolytic dermatitis
Hepatotoxic reactions

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23
Q

What is the mechanism of action of potassium bromide?

A

Unknown

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24
Q

When is potassium bromide used?

A

Can be used a first line but mainly as an add on

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25
What is the dose of potassium bromide used?
30-40 mg/kg SID | Can be BID if high dose as salt intake once a day will be too much
26
How long does potassium bromide take to reach a steady state?
100-200 days
27
What is the therapeutic range of potassium bromide?
0.7-1.9 mg/ml or 2.3 mg/ml
28
What are the potential side effects of potassium bromide?
Sedation, weakness, PU/PD, GI irritation (due to salt), pancreatitis
29
How is potassium bromide excreted?
Renally
30
When should the plasma be checked for monitoring levels?
4 weeks, 8-12 weeks and then every 6 months
31
What is the loading dose of potassium bromide?
600 mg/kg over 6 days plus maintenance
32
What equation is used to calculate dose adjustment?
Full oral dose in mg/kg/day = (desired conc/actual conc) x current dose
33
What are the clinical signs of bromide toxicity?
Severe ataxia, sedation, somnolence and skin reactions
34
How does imepitoin compare to phenobarbital?
It has comparable efficacy
35
Is blood plasma level monitoring necessary when prescribng imepitoin?
No as there is no direct correlation between dose and seizure frequency
36
What has imepitoin not been tested for?
Effectiveness against status epilepticus or cluster seizures
37
What idiosyncratic reactions have been found?
None so far | Safe with good therapeutic index in healthy dogs
38
What are the potential side effects of imepitoin?
Polyphagia, hyperactivity, polyuria, polydypsia, somnolence, hypersalivation, emesis, ataxia, apathy, diarrhoea, prolapsed 3rd eyelid, decreased sight and sensitivity to sound
39
What is the dose range of imepitoin?
10-30 mg/kg BID
40
What are possible causes of treatment failure?
Incorrect diagnosis, choice of AED, dosage, AED levels, monotherapy insufficient, refractory seizures, poor compliance
41
What should you do if AED treatment fails?
Monitor drug levels and adjust dose, monitor drug levels, add anticonvulsant, monitor levels and adjust dose, consider new drug and contact neurologist
42
What percentage of dogs are refractory AED?
20-30% are refractive to phenobarbital and potassium bromide
43
What is the first choice treatment in cats?
Phenobarbital
44
What dose of phenobarbital is used in cats?
2-3 mg/kg PO SID/BID
45
How long does phenobarbital take to reach a steady state in cats?
10-14 days
46
What side effects are seen in cats on phenobarbital?
Polyphagia, bone marrow suppression and cutaneous hypersensitivities
47
What is the second choice AED for cats?
Diazepam
48
What is the dose of diazepam for cats?
5-10 mg dose PO BID/SID
49
What are the side effects of diazepam in cats?
Acute hepatotoxicosis
50
Why should potassium bromide not be used in cats?
Causes bronchial asthma but if no other choice give 30 mg/kg PO SID
51
What are two other options of AED that can be given to cats and their doses?
Levetiracetam at 10-20 mg/kg PO TID | Gabapentin at 5-10 mg/kg TID
52
What are possible adverse effects of status epilepticus?
Arterial hypertension and increased cerebral blood flow due to stress, hypoxaemia and hypercarbaemia as can't breathe properly, hyperglycaemia, lactic acidosis due to excessive muscle activity
53
What happens after 30 minutes in status epilepticus?
Excessive muscle contraction resulting in hyperthermia, acidosis, myolysis, hypoglycaemia (energy depletion), hypotension and cardiac arrhythmias
54
What should treatment for status epilepticus aim to do?
Reverse energy depletion, circulatory collapse and organ hypoperfusion, stop the seizure to prevent multiple organ failure
55
How do you stabilise a patient in status epilepticus?
``` ABC IV catheter Bloods (PCV, total protein, glucose, electrolytes, CBC, biochem and AED serum level) Fluid therpay AED (diazepam/phenobarbitone) ```
56
What dose of diazepam is used to stop status epilepticus?
0.5 mg/kg IV or 1 mg/kg if on phenobarbital every 5 minutes up to 3 times Rectally 1-2 mg/kg
57
What dose of phenobarbitone is used to stop status epilepticus?
If naive give 20 mg/kg in 24 hours | If given already give 1 mg/kg for every ug/ml and increase by 5 ug/ml each time
58
What maintenance therapy needs to be used post status epilepticus?
Phenobarbitone 2-3 mgkg BID or 2 mg/kg SID in naive animals | Potassium bromide 600mg/kg followed by 30-40 mg/kg SID
59
What second line AEDs can be used to treat status epilepticus?
Diazepam CRI 0.5 mg/kg/hr Midazolam CRI 0.3 mg/kg/hr Propofol at 4-8 mg/kg IV slow to effect followed by 4-12 mg/kg/hr Levetiracetam at 60 mg/kg IV then 20 mg/kg TID Ketamine at 5 mg/kg IV bolus then 5 mg/kg/hr CRI
60
What anaesthetics can be used to prolong anaesthesia in a status epilepticus patient?
Barbiturate | Isoflurane/sevoflurane
61
How do you minimise complications of status epilepticus?
Monitor HR, BP, O2, electrolytes, fluid balance, body temperature Treat hypotention and hypoxaemia Minimise hyperthermia and renal impairment

NOSS (27 decks)

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