Neurologic System Notes

I.

Seizures
A.
Seizures are periods of altered brain function characterized
by loss of consciousness, increased muscle tone and movement,
altered sensations, and other neurologic changes
B.
Convulsions are seizures that manifest themselves as
spastic muscle movement caused by stimulation of motor nerves
in the brain or spinal cord.
C.
Absence seizures lack convulsions, animal appears to be in
a state of semi-consciousness
D.
Recurrent seizures- epilepsy, recurrent seizures of unknown
cause- idiopathic epilepsy, status epilepticus- prolonged seizure
activity
E.
Phases
1.
Preictal: pacing, panting, anxiety, apprehension, behavioral
changes
2.
Ictus
a)
Partial seizure: involving only a limited area of the brain
and manifesting itself in a localized response, such as one limb
b)
Generalized seizure: involving whole brain and affecting
entire body

3.

Postictal: tired, confused, anxious, blind

F.
Causes: Hypoxia, hypoglycemia, hypocalcemia, toxicity
(organophosphates), infectious diseases (canine distemper), or
conditions of the brain (hydrocephalus, brain neoplasia)
G.
Potential dangers: hyperthermia, hypoxia, CO2 buildup,
hypoglycemia, severe acidosis from lactic acid release

II.

Anticonvulsants
A.
Phenobarbital (barbiturate): Decreases the likelihood of
spontaneous depolarization in brain cells and the spread of
electrical activity; changes threshold, brain cells more
electronegative, harder to depolarize
1.
Drug of choice for long-term control in both dogs and cats,
inexpensive and only given 1-2 times daily
2.
Concentrations of the drug must remain continuously in
therapeutic range
a)
Periodic testing of plasma concentrations of the
barbiturate is important

Neurologic System Notes

b)
Half-life for dogs is about 30-90 hours, phenobarb doses
in cats are approximately half of dogs
c)
Given orally once or twice a day
d)
Wide range in metabolism and elimination half-life; two
dogs at the exact same weight can have different dosages
e)
Converted by the liver, eliminated by the kidney

3.
Phenobarbital is biotransformed by mixed function
oxidases
a)
Mixed function oxidases: a family of enzymes found
primarily in the liver
b)
Induced: After repeated administration, the number of
enzymes increases, thus metabolizing the drug at a more rapid
rate (drug tolerance)
c)
The net result is that for a given dose, the drug
concentrations in the blood will decrease as the body becomes
more efficient at metabolizing the drug
d)
Animals treated with phenobarb may need to have the
dose of any other drugs using the same metabolic pathway
increased to compensate for their accelerated metabolism

4.

Phenobarb is highly protein bound

a)
When plasma protein levels are decreased, more
phenobarb becomes available in the free form, therefore more
phenobarb molecules are free to diffuse in the brain to produce
clinical effect
b)
Animals with hypoproteinemia may require lower dosages
of phenobarb than normal
c)
Use of salicylates such as aspirin or sulfonamide
antimicrobials also increases the amount of free phenobarb by
displacing the barbiturate from sites on plasma proteins

5.

Adverse effects
a)
Sedation and ataxia is normal for first 2-3 weeks of
therapy, may also be signs of toxicity if severe, test plasma
concentration to confirm
b)
PU, PD, PP; inhibitory effect on the release of ADH
c)
Occasionally dogs show hyperactivity, usually need to
switch drugs

6.

Dose of phenobarb is measured in grains

a)

B.

1 grain= approx. 60mg

Diazepam (Valium) - benzodiazepine tranquilizer

1.
Drug of choice for emergency treatment of animals in
status epilepticus

Neurologic System Notes

2.
Control seizures by rapidly penetrating the blood-brain
barrier and enhancing the inhibitory effect of the CNS
neurotransmitter y-aminobutyric acid (GABA)
a)
GABA helps counter the effect of stimulatory
neurotransmitters in the brain such as acetylcholine and
norepinephrine; enhancing the GABA effect quiets the activity of
the CNS

3.

Metabolism
a)

Quite effective when given IV

(1)
Rapid hepatic metabolism explains the drugs fairly
short duration of activity when it is given IV
b)
Not effective when given orally
(1)
Only 2-5% makes it to systemic circulation due to
the first pass effect
c)
Can be administered at home per rectum, gel formulation
is available
d)
Cats are less efficient at metabolizing diazepam than
dogs
e)
The body develops a tolerance to the drug very quickly;
this plus the first pass effect and quick half-life limit diazepams
use in the dog to treatment of status epilepticus
f)
Diazepam can adhere to the polyvinyl plastic of IV lines
and does not mix well with most fluids
(1)
When adding diazepam to drip bag for CRI, saturate
inner lining of IV lines before use and invert bag several
times to distribute diazepam in solution

4.

Side effects- usually minimum

a)
Fatal idiosyncratic drug induced hepatopathy from low
doses in cats
b)
Tranquilizer: animal may become more aggressive when
learned controlled behavior is inhibited by diazepam
c)
Ataxia and weakness unrelated to sedation may occur

C.

Potassium Bromide: chemical reagent

1.
One of the most commonly used adjunct therapies for
animals whose seizures are not well controlled by phenobarb
alone
a)
Phenobarb dose needs to be decreased as the potassium
bromide concentrations begin to produce clinical response

2.
Change the resting membrane potential of neurons,
making them more difficult to depolarize (similar to action of
chloride ions); net effect is a nervous system that is less likely to
spontaneously discharge and produce a seizure

Neurologic System Notes

3.

Long half-life of 21-24 days, 3-5 months for equilibrium

a)

Steady state= 5 x half-life

4.
Large loading dose can be given to establish
concentrations with the therapeutic range
5.
Narrow therapeutic index
6.
Side effects
a)
Anorexia, vomiting, diarrhea, sedation, stupor, coma
b)
Vomiting may occur even if the dose of the drug is within
an acceptable range
c)
Electrolytes may report falsely elevated Cl concentration

D.

Primidone and Dilantin: not used

1.

Dilantin metabolizes to phenobarb

Neurologic System Notes

III.

Behavior-modifying drugs
A.
Change the concentrations of selected neurotransmitters in
the brain with the intent of decreasing or enhancing specific
mental (neuronal) activity
1.
Enhancing the release of neurotransmitters (inhibitory or
excitatory)
2.
Enhancing the binding (affinity) of neurotransmitters to
their receptors
3.
Agonist effect: imitating the natural neurotransmitter and
combining with the neurotransmitters receptor to stimulate the
receptor
4.
Antagonist effect: imitating the natural neurotransmitter
and combining with the neurotransmitters receptor but
producing reduced or no stimulation of the receptor
5.
Prolonging the action of the neurotransmitter by
decreasing the breakdown or slowing the rate of termination of
the neurotransmitter itself
6.
Shortening the action of the neurotransmitter by
enhancing its breakdown or termination

B.
Antipsychotic drugs: used to decrease inappropriate
behavioral responses to stimuli
1.
Phenothiazine tranquilizers: acepromazine and
chlorpromazine
2.
Block dopamine receptors, allows other neurotransmitters
to dominate and decreases the incidence of abnormal behaviors
a)
Increased dopamine and the stimulation of dopamine
receptors in parts of the brain thought to control emotion (the
limbic system) have been shown to result in abnormal behaviors
tied to emotions

3.

Block learned behaviors but not instinctual behaviors

a)
Treatment can sometimes result in uncovering of
underlying inappropriate behaviors

4.

Side effects
a)
Have less interest in their environment, have fewer
responses to stimuli, and have a depression of complex
behaviors
b)
Instinctive aggression
c)
Other unreliable changes

C.

Antidepressant drugs

Neurologic System Notes

1.
Tricyclic antidepressants: Amitriptyline, clomipramine,
Anafranil
a)
Work by decreasing the reuptake of serotonin from the
synaptic cleft, allowing the serotonin to accumulate and
prolongs its activity
b)
Have been used to treat generalized anxiety and
separation anxiety behaviors in dogs and cats
c)
Amitriptyline also blocks reuptake of norepinephrine
(1)
Has been used to decrease inappropriate spraying
and excessive grooming in cats as well as excessive
feather plucking in birds
d)
Clomipramine has been used for OCD in dogs and
aggressive behaviors
e)
Possible increased risk for seizure activity
f)
Counterindicated with SSRIs or MAO inhibitors

2.

SSRIs: fluoxetine, fluvoxamine, paroxetine, and sertraline

a)
Enhance the effect of serotonin neurotransmitter by
blocking its removal from the synaptic cleft. The serotonin
remains for a longer period of time at its site of action,
accumulates, and extends its effect.
b)
SSRIs are more selective for blocking serotonin reuptake
without significantly blocking the other neurotransmitters such
as norepinephrine
c)
Used for OCD, anxiety, and aggression
d)
Side effects: Sleeplessness, mydriasis, nausea and
vomiting

3.

MAOI: selegiline or Anipryl

a)
Anipryl is used to treat Cushings disease and for canine
cognitive dysfunction (old-dog senility)
b)
MAOIs increase the effect of dopamine by blocking the
mechanism by which dopamine is taken up again by the
mitochondria in the neurons

D.
Anxiolytic drugs: tranquilizers belonging to the
benzodiazepine group
1.
Increases stimulation of receptors for the neurotransmitter
GABA
a)
GABA is an inhibitory neurotransmitter; stimulation of
GABA receptors has a depressant effect on the CNS

2.
At low doses, the animals become more relaxed and less
excitable

Neurologic System Notes

a)
The reduction in anxiety (nervousness in social
interactions) does not occur until moderate-level doses of
diazepam are used
b)
At high doses, animals become quite sedated and ataxic
and readily fall asleep

E.
Others: Beta blockers, antihistamines, anticonvulsants,
buspirone, and progestin