Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

PHARMACOLOGY - 2 > 17 – Antiepileptic Drugs (AED) > Flashcards

17 – Antiepileptic Drugs (AED) Flashcards

1
Q

Who gets epilepsy?

A
  • *Dogs
  • Cats
  • Foals
  • Parrots
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

How can risk be characterized/’assessed (equation)?

A
  • Hazard X exposure
  • “severity X likelihood”
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What are some risks/issues associated WITH AED therapy?

A
  • Adverse effects
  • Cost: medication, therapeutic monitoring/bloodwork
  • Client effort: life-long administration
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What are some risks/issues associated WITHOUT AED therapy?

A
  • Progression of seizures
    o Eventual euthanasia
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What is the job of the vet as a RISK MANAGER?

A
  • Discuss therapeutic options with client
  • Understand what risk the client is willing to accept
  • Tailor drug regimen to best manage the risks
  • *COMMUNICATE!
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What are some areas of the risks you need to figure of if the client is willing to accept?

A
  • Acceptance of seizure incidents
    o Complete elimination is NOT generally feasible
    o Reduction of seizure frequency is REASONABLE
  • Acceptance of adverse drug events
  • Acceptance of therapeutic drug monitoring (TDM), cost, compliance
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What is the job of the vet before AED therapy is initiated?

A
  • Set appropriate expectations of the goals of the AED therapy
  • Expected adverse effects
  • Schedule for therapeutic drug monitoring and bloodwork
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What is the job of the vet while on AED therapy?

A
  • Check on adverse events, monitor and ADJUST therapy
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What is the ‘mechanism’ and objective of anti-convulsant therapy?

A
  • Pathogenesis not well understood
  • *objective is to raise “seizure threshold” by stabilizing neuron membrane potential
    o Enhance inhibitory NTs (ex. GABA, glycine)
    o Reduced excitatory NTs (ex. glutamate)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

How can hyperpolarization occur? (ie. Channels)

A
  • Activating post-synaptic K or Cl channels OR
  • Reducing pre- and post- synaptic Na/Ca channels
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Why is anticonvulsant therapy so challenging? (4 reasons)

A
  • Individual response is UNPREDICTABLE
    o Subpopulation of dogs (large breeds) are ‘refractory’ to therapy
  • Not a cure!
    o Chronic administration, side effects, ‘tolerance’ (PK or PD)
  • POOR COMPLIANCE
  • TDM may be required to ensure efficacy/safety
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Therapeutic drug monitoring: ‘negative’ and positive

A
  • Tough to sell to client
  • OPPORTUNITY to optimize dose regimen for ‘individual’ therapy
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What does the prognosis for dogs with epilepsy depend on? (combination of 3 things)

A
  1. Veterinary expertise
  2. Therapeutic success
  3. Owner’s motivation
    *epilepsy=implies increased risk of premature death
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Survival curve for an epileptic

A
  • If epilepsy is cause of death, it will happen quicker
  • 50% euthanized within 1-2 years
  • *significant risk factor for early euthanasia
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What anticonvulsant therapy is licensed for veterinary use?

A
  • Not much
    o Phenobarbital (Canada)
    o Pheonobarb, KBr, Primidone (USA)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What other drugs are used in Canada? (even if not licensed)

A
  • Benzodiazepines (during seizures=not for prevention)
  • Levetiracetam, GABA-type drugs
  • Others: Imepitoin, Zonisamide, CBD
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What is the efficacy of Phenobarbital and KBr?

A
  • PB: reported up to 85%
  • KBr: maybe slightly lower, but similar?
  • Newer drugs not as effective as previous drugs
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What is phenobarbital?

A
  • Barbiturate with anti-epileptic effects when used at sub-anesthetic doses
    o Mechanism? Decreases Ach, Glu, NE OR increase GABA?
  • Human generics also available
  • *don’t confuse with barbiturates (ex. pentobarbital: euthanasia)
  • **CONTROLLED DRUG
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What are the adverse effects of phenobarb in dogs?

A
  • Sedation/lethargy
  • Polyuria and polydipsia (decrease urinary smooth muscle tone), doesn’t usually persist
  • Polyphagia (*avoid obesity: PB distributes into fat)
  • Ataxia: should diminish over next 10-15 days
  • Blood dyscrasias?
  • Decrease in T4 concentration
  • HEPATOTOXICITY
  • Drug interaction: CYP enzyme INDUCTION
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Drug interactions with Phenobarb

A
  • Will get drug interactions as you are giving it CHRONICALLY
  • *INDUCTION: produces more CYP (not immediately but increases pretty fast)
    o Increases clearance capacity in the hepatocytes
    o *drugs get cleared faster (including Phenobarb)
  • Be very CAREFUL, watch the concentrations!
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

How does Phenobarb cause hepatotoxicity in dogs?

A
  • Increased ALP(++) and ALT(+)
    o Liver enzymes>3x normal!
  • Abnormal bile acid stimulation test
  • Decrease albumin, urea and cholesterol
  • *if really bad or getting worse=change dose or switch to a different drug
  • Typically DOSE dependent=we have control over the process
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Phenobarbital-induced hepatotoxicity: gross changes

A
  • Cirrhosis
  • Fibrosis
  • Nodules
  • *generally chronic and DOSE-dependent
23
Q

What are the adverse effects of Phenobarb in cats?

A
  • Sedation/lethargy
  • Polyphagia (must warn owners to avoid obesity)
  • Ataxia: diminish over next 10-15 days
  • Polyuria and polydipsia: doesn’t usually persist
  • Allergic reaction
  • Blood clotting disorders: due to platelet counts
  • Drug interactions: CYP enzyme induction
  • *hepatotoxicity is RARE in cats
24
Q

Allergic reaction in cats on Phenobarb

A
  • Blood dyscrasias: low platelet and WBC count
  • Temporary facial swelling
25
Q

What are the general PK of phenobarbital?

A
  • Good oral bioavailability (F)
  • Moderate volume of distribution (Vd)
26
Q

What are the PK of phenobarbital in dogs?

A
  • Long half-life (1.5-4 days) *measure in 2 weeks
  • *induces cytochrome P450 enzymes
    o Increase enzymes=increase clearance=decrease half-life later on
27
Q

What are the PK of phenobarbital in cats?

A
  • Non-linear kinetics can occur
    o Increase dose may NOT be proportional to increase in drug exposure
  • BEWARE: minor dosage changes can result in large fluctuations in blood levels
    o Can make drug ineffective (blood levels too low)
    o OR result in excessive sedation (blood levels to high)
28
Q

Example of Phenobarbital drug concentration vs. days graph: accumulation (predicted)

A
  • Dose interval is SHORTER than half life=ACCUMULATION OCCURS
  • *steady concentrations are reached after 5-7 HALF-LIVES (not doses!)
    o Get plasma sample at 10-14 days
29
Q

Example of Phenobarbital drug concentration vs. days graph: accumulation + INDUCTION

A
  • *hepatic enzyme induction over time
    o INCREASED CLEARANCE=DECREASED CONCENTRATIONS
  • *happen over MONTHS (not days)
30
Q

Phenobarbital PK in birds

A
  • Oral
  • Gavage: tube
  • *hard to take blood samples as they have a very small plasma volume
    o Get individual animals and make an assumption for the population
31
Q

Does it matter to switch between generic brands of Phenobarbital?

A
  • NOT a big deal in humans
  • DOGS: probably not
    o But minor difference in PK may have significant clinical effect in some dogs
32
Q

Compounded anticonvulsants examples

A
  • Lower plasma concentrations of phenobarbital even when they were increasing the dose
  • *assayed the phenobarbital=found it was half the strength it was supposed to be
    o If solution=2 weeks from shelf life
    o This one said: 3 months, and it was only 3 weeks old
    o DEGRADED OVER TIME
  • *when used new batch=seizure control restored
    q
33
Q

Potassium Bromide (KBr)

A
  • VERY old anit-epileptic drug
  • Likely, hyperpolarizes neural cell membranes
  • *none approved for vet use in Canada
    o But can get from compounding pharmacies
  • K-BroVet solution and tablets approved for dogs in USA
34
Q

What are the adverse effects of KBr in DOGS?

A
  • Sedation
  • Vomiting/diarrhea/constipation
    o Should go away quickly
  • Increased hunger/thirst : salty
  • Pelvic limb weakness or stiffness (not really ataxia)
  • Pancreatitis
  • Skin reactions: pruritic lesions
  • Occasional behavioural changes
    o Depression, irritability/aggression, attention seeking or aimless pacing
35
Q

What are the drug interactions of KBr?

A
  • NONE documented
  • *FOOD interactions
36
Q

What is the half-life of KBr?

A
  • EXTREMELY LONG (24d)
  • Can use ‘loading’ dose for first week
  • Once at steady state: missing single dose is NOT critical
37
Q

What is the elimination of KBr?

A
  • Renal
    o But reabsorbed with Cl
  • NO hepatic metabolism: so decreased drug interactions
38
Q

What is the influence of diet (SALT) with KBr? (IMPORTANT!)

A
  • Watch out for salty treats
    o Decrease Br reabsorption from renal tubule due to increased Cl competition for tubule transporters
    o Increase Br excretion = decrease plasma Br
  • Watch out for cardiac diets (low salt)
    o Increased Br reabsorption from renal tubule
     Will increase plasma KBr
39
Q

How do you treat overdose of KBr?

A
  • Use Cl to flush it out
  • *NaCl saline=flushes it out
40
Q

KBr and cats

A
  • NOT RECOMMENDED
  • 50% showed adverse reactions
    o Coughing
    o Bronchial asthma due to allergic reaction=severe
  • *watch out with compounded drugs!
41
Q

Diazepam (Valium)

A
  • Used to treat STATUS EPILEPTICUS in cats and dogs
  • NOT for seizure prevention
  • Hepatic metabolism: 2 active metabolites
    o Maybe problems if used chronically (ex. hepatotoxicity)
42
Q

How do you give diazepam?

A
  • IV: crossed BBB rapidly
    o Hard to do when they are seizing
  • Rectally: 50% bioavailability
    o Administer 2x the IV dose
    o Owners: need to tell them it binds to plastic and inactivated by light
  • Intranasal: 80% bioavailability (hard to do=dangerous to go close to mouth)
  • Oral: low bioavailability
43
Q

What else can Diazepam be used for?

A
  • Behavioural disorders
  • Appetite stimulant
  • Pre-anesthetic
44
Q

What are some ‘newer’ anticonvulsants?

A
  • Levetiracetam (Keppra)
  • Brivaracetam?
  • (Gabapentin)
  • (CBD)
45
Q

What are some warnings with ‘newer’ anticonvulsants?

A
  • *most efficacy studies are:
  • Typically administered as ADD-ONS
  • NON-CONTROLLED
  • Typically SMALL SAMPLE SIZE
  • Often not BLINDED
  • IMPRECISE OUTCOME MEASURES
46
Q

Levetiracetam (Keppra) efficacy in dogs

A
  • Usually used in combo with Phenobarbital +/- KBr
    o Makes sense to use as ADD-ON
  • Monotherapy
    o Doesn’t really work that well
  • *NEW: used for CLUSTER SEIZURES
    o Use it with Diazepam/phenobarbital when having a seizure=big effect to stop the seizure more quickly!
47
Q

Levetiracetam (Keppra) dosage regimen

A
  • 3x/day=challenge for client (cost and compliance)
  • Start at high dose: 20mg/kg
  • Short half life: if miss dose=more of a problem
  • High oral bioavailability
  • *RENAL EXCRETION!
    o Good if worried about hepatic disease
    o Decrease dosage in renal impaired patients
48
Q

Levetiracetam (Keppra) ‘safety’

A
  • No drug interactions
  • TOLERANCE may develop: ‘honeymoon period’ of 4-8months
  • Often don’t do drug/blood monitoring
49
Q

Levetiracetam (Keppra) in cats

A
  • 3x/day orally
  • Maybe transdermal will be something in FUTURE?
  • Safe but
    o Will get hypersalivation: makes sense (not a big deal)
50
Q

Brivaracetam

A
  • New more potent analogue of levetiracetam
    o Longer half life
    o Nothing about efficacy
  • *don’t recommend using it!
  • Lots of human generic versions available
51
Q

Gabapentin

A
  • Structural analogue of GABA, but doesn’t impact GABA receptors
    o Block Ca channels?
  • May be given in combination with Phenobarbital and/or KBr
  • Safe and cheap (minimal side effects)
  • *not many different formulations available (especially for cats and smaller dogs)
  • NOT much evidence! Maybe works?
52
Q

Pregabalin (Bonqat)

A
  • Oral solution approved as anxiolytic in cats before car transport
    o NOT approved as anticonvulsant
  • NOT much evidence to say it works. Maybe?
53
Q

CBD for epilepsy?

A
  • Decrease seizure frequency in Phenobarbitol/KBr treated dogs when oral CBD oil ADDED
  • PROMISING: but smaller sample size
    o Higher CBD plasma concentrations=lower seizure incidence
    o HIGH DOSE: 9mg/kg=lots of side effects
  • *human results are very promising

PHARMACOLOGY - 2 (16 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions