Week 6 - Anticonvulsants Flashcards
1
Q
A seizure is defined as an abnormal, disorderly discharging of the brain’s ____ cells, resulting
in a _______ disturbance of ____, _____, and _____ function.
A
nerve, temporary, motor, sensory, mental
2
Q
What are the symptoms of seizures in dogs?
A
3
Q
What are the characteristics of epilepsy in dogs?
A
4
Q
Anticonvulsants are used to block seizure ______ and ______ by blocking either
abnormal events in a ____ neuron or the synchronization of ______ neurons
A
initiation, propagation, single, related
5
Q
What is the goal of anticonvulsant therapy?
A
Reduction in the firing frequency of neurons.
6
Q
True or False: Only a few of the anticonvulsant drugs available for human use have been
approved for clinical use in dogs and cats.
A
True
7
Q
Some of the drugs are too ______ ______ in dogs to be effective, even in high dosages.
A
rapidly metabolized
8
Q
Cats metabolize drugs more ______ and _____ than dogs.
A
slowly, poorly
9
Q
What is the mechanism of action (MOA) of anticonvulsant drugs?
A
MOA: Stabilization of the neuronal membranes evoking hyperpolarization
* They activate GABA-gated Cl- channels
* They bind to GABAA receptor and facilitate its action (agonist)
* Inactivating Na+ and Ca++ conductance in different channels.
10
Q
What are the therapeutic uses of anticonvulsants?
A
Reduction of incidence, severity, and duration of seizures
11
Q
What are the adverse effects of anticonvulsants?
A
Adverse Effects:
* Rapid cessation effect of administration of these drugs. (Rapidly removed by liver).
* Liver and serum enzymes induction
* Hepatotoxicity in dogs
12
Q
What is the MOA of barbituates?
A
activation of GABA-gated Cl- channels
13
Q
Phenobarbital is an _______.
A
oxybarbiturate
14
Q
Pentobarbital is an ________
A
oxybarbiturate
15
Q
Primidone is an analog of ______
A
phenobarbital
16
Q
What is the MOA of Benzodiazepines?
A
Facilitating the inhibitory action of GABA
by binding to GABAA receptors
17
Q
List the drugs classified as Benzodiazepines?
A
Diazepam
Midazolam
Clonazepam
Lorazepam
“Don’t Mind Little Christine”
18
Q
What is the MOA of Hydantoins?
A
targeting sodium channels
19
Q
Phenytoin is a ______ derivative
A
hydantoin
20
Q
Valproic Acid is a derivative of?
A
carboxylic acid, via Cl- channels
21
Q
List the anticonvulsant drugs considered to be “unconventional.”
A
Gabapentin
Levetiracetam
Felbamate
Zonisamide
22
Q
Gabapentin: synthetic ____ analog acting via _____ of ____-gated ____ channels
A
GABA, inhibition, voltage, Ca++
23
Q
Levetiracetam binds to a unique synaptic vesicle protein _________
A
2A (SV2A)
24
Q
Felbamate: unknown, many mechanisms including inhibition of ____ and ____ channels
A
Na+, Ca++
25
Zonisamide: inhibition of ___ and ___ channels induction of _________.
Na+, Ca++, hyperpolarization
26
GABA is the major ______ NT in the CNS
inhibitory
27
GABA is considered our natural “_____-like” NT
Valium
28
GABA is produced mostly in the brain from _______ ____/_______
(needs Vitamin ___ for its synthesis)
glutamic acid, glutamate, B6
Found in these foods: Green tea, ? berries, tomatoes, etc.
29
GABA plays an important role in ?
behavior, cognition, and the
body response to stress. GABA controls fear and anxiety
30
The role of GABA is to _____ or _____ the activity of the neurons
inhibit,reduce
31
GABA-gated (_______ receptor) chloride channels mediate synaptic inhibition
by causing _____ ions to flow into the neuron causing its _______.
GABA A, chloride, hyperpolarization
32
GABA can bind to GABA A receptor, site for benzo, and barbituates.
Each receptor consists of 5 subunits that forms channel. When GABA like compoinds bind to receptor, channel opens, and allows charged chloride ions to pass through.
Binding of too many cells results in sedation. Neural inhibition?
Anatagonist: results in excitation of signal. EMAIL HER
33
What is the mechanism of action of barbituates?
Activation of GABA-gated Cl- channels
34
Phenobarbital is unique in that it usually produces _________ effect at _____ doses
than those necessary to cause pronounced CNS ______ (_____).
anticonvulsant, lower, depression, sedation
Depression can be in minimally severe cases.
35
What are the therapeutic uses of Barbituates?
* For long-term control of seizures
* Administered orally
* It is not useful for terminating an ongoing seizure b/c the time span
from administration until the onset of effect is too long (~ 20 min)
* When given orally, its GI absorption is practically complete in all animals
Peak levels occur in 4-8 hr after oral dosing in dogs.
36
What are the adverse effects of Barbituates?
* Sedation, polydipsia, polyuria, and polyphagia (signs of diabetes)
* Dogs develop a tolerance to the sedative effects after 1-2 weeks
37
Primidone is a _______.
deoxybarbiturate
38
Primidone
Slow absorption after ____ administration in ____
oral, dogs
39
PK: primidone is rapidly metabolized by the liver to ______
phenoparbutal
This drug is not actively ready until this occurs.
40
85% of Primidone's anticonvulsant activity is attributable to its conversion to __________
phenobarbital
41
In cats, the metabolism of Primidone to phenobarbital is ____ (?).
slow, do not use in cats
42
What are the adverse effects of Primidone?
* Prolonged use in dogs may lead to decreased serum albumin and
elevated serum concentrations of liver enzymes
* Occasionally, serious liver damage
43
What are the therapeutic uses of Pentobarbitol?
* Will terminate seizures at a dose that produces anesthesia
* Used for status epilepticus*
* It has rapid onset (< 1 min) after IV injection and short duration of action
44
What are the adverse effects of Pentobarbitol?
* CNS depressant
* May cause excitement during recovery from anesthesia
* Irritating when administered perivascularly
45
Status epilepticus is a seizure that last longer than ___ _____, or having ___ than 1 seizure
within ____ ____ period, without returning to a _____ level of consciousness ______ episodes.
5 min, more, 5 min, normal, between
46
What is the MOA of Benzodiazepines (BDZs)?
facilitating the inhibitory action of GABA by binding to GABAA
receptors and evoking hyperpolarization of the neurons
47
List the anticonvilsants classified as Benzodiazepines
Diazepam
Midazepam (ZolamR)
Clonazepam
Lorazepam
48
What are Benzodiazepines used for?
They are used as anticonvulsants in all the domestic species
49
Benzodiazepines are used to treat what specific type of seizures?
status epilepticus
50
Benzodiazepines have a very limited use as a maintenance anticonvulsant in dogs,
because the tolerance development due to rapid drug metabolism.
51
Benzodiazepines can be used as a _________ ______ in cats.
maintenance anticonvulsant
52
What are the therapeutic uses of Diazepam in cats?
In cats, it is administered orally for seizure control
53
What are the therapeutic uses of Diazepam in dogs?
In dogs, administered IV, is a drug of choice for the control of status epilepticus & cluster seizures
54
What are the adverse effects of Diazepam?
* Changes in behavior (irritability, depression and aberrant demeanor)
* Cats may develop acute fatal hepatic necrosis
55
What are the therapetic uses of Midazolam?
* More potent than diazepam
* Used for status epilepticus, muscle relaxant, tranquilizer, and appetite stimulant the
same way as diazepam
* PK: has shorter elimination t ½ of 77 min in dogs. Readily crosses BBB
56
What are the adverse effects of Midazolam?
* restless behavior, agitation
* local irritation
* mild respiratory depression
* vomiting
57
What are the therapeutic uses of Clonazepam?
* The same as diazepam
* Has limited value as a maintenance anticonvulsant because of
rapid development of drug tolerance
58
What are the adverse effects of Clonazepam?
* Drug resistance
* GI disturbance, including vomiting, hyper-salivation, and diarrhea/constipation
59
What are the therapeutic uses of Lorazepam?
* Orally for a short term at home treatment for dogs having cluster seizures
* It may be safely used in patients with compromised liver function & in geriatric dogs
because it does not produce active metabolites
* In cats as a maintenance anticonvulsant
60
What are the adverse effects of Lorazepam?
* Increased appetite
* Anxiety can occur early in therapy
61
What is the mechanism of action for Hydantoins?
targeting sodium (Na+) channels, blocking channels from recovering from
the inactive state leading to inhibition of neuron firing
62
What are the therapeutic uses of Hydantoins?
* Because of its short half-life in dogs, its use may be impractical
* Because of its lidocaine-like effects, phenytoin has been recommended for
the treatment of digitalis-induced ventricular arrhythmias in dogs
63
Valproic Acid is a derivative of _________ acid – ______ unrelated to other anticonvulsant
carboxylic, structurally
64
What is the MOA of valproic acid?
stabilizes membranes by blocking Na+ and Ca++ channels and
opening of GABA-gated Cl- channels
65
What are the therapeutic uses of valproic acid?
* In dogs, oral administration is effective in controlling seizures, however
its short t1/2 makes its impractical for long-term use
* Can be useful as a second to forth line anticonvulsant in dogs
* In cats, its clinical usefulness has not been evaluated
66
What are the adverse effects of valproic acid?
* GI toxicity: vomiting, anorexia, and diarrhea
* Hepatotoxicity: liver failure in dogs
* CNS effects: sedation, ataxia, behavioral changes
* Dermatologic effects: alopecia, rash
* Hematologic effects: thrombocytopenia, leukopenia, anemia
* Pancreatitis
* Edema
67
What is the MOA of potassium bromiade?
Br- enters neurons via Cl- channels causing hyperpolarization
of the neuronal membrane
68
What are the therapeutic uses of potassium bromiade?
* Administered orally, Br- is neither metabolized nor bound to plasma proteins,
long t1/2, it may take up to 6 months to achieve stable plasma concentrations,
eliminated by the kidneys
* Used in combination with barbiturates & BDZs to treat refractory seizures in dogs
* Not recommended in cats
69
What are the adverse effects of potassium bromiade?
* Transient sedation at the beginning of therapy
* GI toxicity: nausea, vomiting, anorexia, and constipation
* Polydipsia, polyuria, polyphagia, lethargy, irritability, and aimless walking
* Pancreatitis
* Severe asthma in cats
70
Gabapentin is a synthetic _____ analog that can cross ____ to exert its anticonvulsant effect
GABA, BBB
71
What is the MOA of Gabapentin?
Unknown
72
What are the therapeutic uses of Gabapentin?
* Administered orally
* Used as adjunctive therapy for refractory of complex partial seizures
* Treatment of chronic pain in dogs and cats
73
What are the adverse effects of Gabapentin?
* Sedation, Ataxia
* Mild polyphagia
* Abrupt discontinuation of gabapentin may cause seizures
74
Which compound is this?
GABA
75
Which compounds is this?
Gabapentin
76
What is the mechanism of action of Levetiracetam?
Inhibition of firing and propagation of seizure activity through
binding synaptic protein 2A
77
What are the therapeutic uses for Levetiracetam?
* Administered orally
* Used as adjunctive therapy for refractory canine epilepsy
* Well tolerated in dogs and cats
78
What are the adverse effects of Levetiracetam?
Adverse effects are mild
* GI disturbances: vomiting, anorexia
* Changes in behavior, drowsiness
* Abrupt discontinuation of levetiracetam may cause seizures
79
What is the MOA of Felbamate?
blockade of neural excitation, potentiation of GABA-mediated neural
inhibition through inhibition of voltage-dependent Na+ and Ca++ channels
80
What are the therapeutic uses of Felbamate?
Administered orally
* Used as adjunctive therapy for refractory canine epilepsy
* Used as sole anticonvulsant for patients with local and generalized seizures
* Particularly useful in cases with brain tumor or cerebral infarct (due to no-sedation effect)
81
What are the adverse effects of Felbamate?
* Liver dysfunction in dogs
* Rare: reversible bone marrow depression (condition: thrompocytopenia or leucopenia) in dogs
* Rare: generalized tremor and/or keratoconjunctivitis sicca (dry eye) in dogs
82
What is the MOA of Zonisamide?
nduction of neural hyperpolarization through inhibition of
voltage-dependent Na+ and Ca++ channels
83
What are the therapeutic uses of Zonisamide?
* Administered orally, twice a day
* Used as adjunctive therapy for refractory canine epilepsy (less often in cats)
* Used as sole anticonvulsant for patients with local and generalized seizures
* Particularly useful in cases with brain tumor or cerebral infarct (due to no-sedation effect)
84
What are the adverse effects of Zonisamide?
* High safety margin in dogs and cats
* Rare: Sedation, ataxia, and anorexia
85
What is the NB of Zonisamide?
Cost can be a problem for dogs
Not enough data for cats
86
What are the symptoms of seizures in dogs?
