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NOSS > Principles of Neuropharmacology > Flashcards

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
Q

What is the dose of potassium bromide used?

A

30-40 mg/kg SID

Can be BID if high dose as salt intake once a day will be too much

26
Q

How long does potassium bromide take to reach a steady state?

A

100-200 days

27
Q

What is the therapeutic range of potassium bromide?

A

0.7-1.9 mg/ml or 2.3 mg/ml

28
Q

What are the potential side effects of potassium bromide?

A

Sedation, weakness, PU/PD, GI irritation (due to salt), pancreatitis

29
Q

How is potassium bromide excreted?

A

Renally

30
Q

When should the plasma be checked for monitoring levels?

A

4 weeks, 8-12 weeks and then every 6 months

31
Q

What is the loading dose of potassium bromide?

A

600 mg/kg over 6 days plus maintenance

32
Q

What equation is used to calculate dose adjustment?

A

Full oral dose in mg/kg/day = (desired conc/actual conc) x current dose

33
Q

What are the clinical signs of bromide toxicity?

A

Severe ataxia, sedation, somnolence and skin reactions

34
Q

How does imepitoin compare to phenobarbital?

A

It has comparable efficacy

35
Q

Is blood plasma level monitoring necessary when prescribng imepitoin?

A

No as there is no direct correlation between dose and seizure frequency

36
Q

What has imepitoin not been tested for?

A

Effectiveness against status epilepticus or cluster seizures

37
Q

What idiosyncratic reactions have been found?

A

None so far

Safe with good therapeutic index in healthy dogs

38
Q

What are the potential side effects of imepitoin?

A

Polyphagia, hyperactivity, polyuria, polydypsia, somnolence, hypersalivation, emesis, ataxia, apathy, diarrhoea, prolapsed 3rd eyelid, decreased sight and sensitivity to sound

39
Q

What is the dose range of imepitoin?

A

10-30 mg/kg BID

40
Q

What are possible causes of treatment failure?

A

Incorrect diagnosis, choice of AED, dosage, AED levels, monotherapy insufficient, refractory seizures, poor compliance

41
Q

What should you do if AED treatment fails?

A

Monitor drug levels and adjust dose, monitor drug levels, add anticonvulsant, monitor levels and adjust dose, consider new drug and contact neurologist

42
Q

What percentage of dogs are refractory AED?

A

20-30% are refractive to phenobarbital and potassium bromide

43
Q

What is the first choice treatment in cats?

A

Phenobarbital

44
Q

What dose of phenobarbital is used in cats?

A

2-3 mg/kg PO SID/BID

45
Q

How long does phenobarbital take to reach a steady state in cats?

A

10-14 days

46
Q

What side effects are seen in cats on phenobarbital?

A

Polyphagia, bone marrow suppression and cutaneous hypersensitivities

47
Q

What is the second choice AED for cats?

A

Diazepam

48
Q

What is the dose of diazepam for cats?

A

5-10 mg dose PO BID/SID

49
Q

What are the side effects of diazepam in cats?

A

Acute hepatotoxicosis

50
Q

Why should potassium bromide not be used in cats?

A

Causes bronchial asthma but if no other choice give 30 mg/kg PO SID

51
Q

What are two other options of AED that can be given to cats and their doses?

A

Levetiracetam at 10-20 mg/kg PO TID

Gabapentin at 5-10 mg/kg TID

52
Q

What are possible adverse effects of status epilepticus?

A

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
Q

What happens after 30 minutes in status epilepticus?

A

Excessive muscle contraction resulting in hyperthermia, acidosis, myolysis, hypoglycaemia (energy depletion), hypotension and cardiac arrhythmias

54
Q

What should treatment for status epilepticus aim to do?

A

Reverse energy depletion, circulatory collapse and organ hypoperfusion, stop the seizure to prevent multiple organ failure

55
Q

How do you stabilise a patient in status epilepticus?

A 
ABC
IV catheter
Bloods (PCV, total protein, glucose, electrolytes, CBC, biochem and AED serum level)
Fluid therpay
AED (diazepam/phenobarbitone)
56
Q

What dose of diazepam is used to stop status epilepticus?

A

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
Q

What dose of phenobarbitone is used to stop status epilepticus?

A

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
Q

What maintenance therapy needs to be used post status epilepticus?

A

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
Q

What second line AEDs can be used to treat status epilepticus?

A

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
Q

What anaesthetics can be used to prolong anaesthesia in a status epilepticus patient?

A

Barbiturate

Isoflurane/sevoflurane

61
Q

How do you minimise complications of status epilepticus?

A

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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