CNS (only AEDs) Flashcards
T/F: you don’t need to taper CNS drugs
FALSE
Transmission of action potentials between neurons can be electrical or chemical. In the CNS, it is primarily______
chemical
what are the four major classes of neurotransmitters
- Ach
- biogenic amines
- amino acids
4.neuropeptides
what are the 4 biogenic amines
Norepinephrine, dopamine, serotonin, histamine
what are the 3 amino acid NT
GABA, glycine, glutamate
what are the two types of neuropeptide NT
substance P
endogenous opiates (enkephalins, endorphins, dynorphins)
Excitatory neurotransmitters _______ the likelihood that a neuron will depolarize.
They are often linked to a sodium channel
increase
Inhibitory neurotransmitters ______the likelihood that a neuron will depolarize.
They are often linked to a chloride channel
decrease
many CNS drugs are only _____ selective for their target
relatively
what does indirect receptor interaction mediation refer to
changing the concentration of a NT, or regulating the receptor
With CNS drugs, initial and delayed responses may both be improtant in ultimate clinical effect. What does this mean clinically?
you need to be patient with the time to maximal effect of drugs that alter NT concentrations, and you have to taper drugs that affect the CNS
what ability of the drug is critical to its activity in the CNS
lipophilicity (how well the drug passes the BBB)
what’s important to remember about active metabolites in CNS drugs
they may have a longer half-life than the parent drug
what is a seizure
the clinical manifestation of the abnormal, excessive, hypersynchronous discharge of a group of neurons within the cerebral cortex
Seizures start when a group of neurons within the brain becomes
hyperexcitable
what is the goal of antiepileptic therapy in animals with idiopathic epilepsy
To balance reduction of seizures with quality of life of the patient
What are ALL of the antiepileptic drugs:
Phenobarbital
Potassium bromide
Diazepam
levetiracetam
zonisamide
gabapentin
What is the first choice of AED in vetmed
phenobarbital
Phenobarbital mech of action
GABA -A effects increase chloride conductance -> hyperpolarization
GABA- B effects decrease Ca++ influx -> decreased NT release
Phenobarbital is ____ lipophilic
moderately. It crosses the BBB but not as rapidly as benzodiazepines
why do the kinetics of phenobarbital change in the first few days?
It undergoes metabolic tolerance due to the induction of cytochrome p450
What is important to remember about the serum concentration of phenobarbital at any specific dose?
it is highly variable, due to metabolic tolerance
What are type 1 adverse affects of phenobarbital
behavioural changes (sedation or hyperexcitability). These are predictable
What are type 2 adverse affects of phenobarbital?
Immune-mediated anemia/neutropenia and acute hepatotoxicity. These are unpredictable and life threatening
What are type 3 adverse affects of phenobarbital
polydipsia and polyphagia, hepatotoxicity, and decreased T4. These are cumulative, and can be potentially life-threatening
what are type 4 adverse effects of phenobarbital?
carcinogenic/teratogenic, though none of htese are reported in dogs.
What kind of drugs cause phenobarbital toxicity?
Drugs that inhibit cytochrome p450 enzymes (chloramphenicol, cimetidine, ketoconazole)
What can induction of cytochrome p450 eznymes by phenobarbital do?
change the PK of other drugs (watch out for interactions/adverse effects)
WHAT IS SUPER IMPORTANT TO REMEMBER ABOUT THE DOSAGE OF PHENOBARBITAL
EFFICACY CORRELATES BETTER WITH SERUM DRUG CONCENTRAION THAN WITH DOSE. SERUM CONCENTRATIONS AT A GIVEN DOSE VARY BETWEEN INDIVIDUALS. THERAPEUTIC DRUG MONITORING IS IMPORTANT, AND DOSE ADJUSTMENTS ARE OFTEN NEEDED. (sorry for yelling)
Where is phenobarbital primarily metabolized
the liver.
75% of phenobarbital is metabolized by the liver into inactive metabolites. Where does the other 25% go?
its excreted unchanged by the kidney
How to monitor patients on phenobarbital:
monitor concentration at first steady state (approx. 2 weeks). Monitor again at clearance time point (6 weeks). Monitor every 6 months if there are 2+ seizure events or 2 weeks after any dose change.
Monitor liver function with serum biochem every 6 months.
What is the oldest known treatment for seizures
Potassium Bromide (KBr)
What is the mech of action of KBr
thought to act via GABA Cl- channels to hyperpolarize cells
What is the half-life of KBr, and what is the implication?
EXTREMELY LONG -> 15 days in dogs, 10 days in cats. This means it is very slow to reach steady state, and loading doses are often used.
T/F: KBr undergoes renal clearance with NO hepatic metabolism or protein binding
true.
When is steady state of KBr reached`
at 3 MONTHS!!
When should you monitor KBr serum concentrations
at 1 and 3 months after starting KBr, then monitor annually, orsooner if evidence of toxicity or ineffectiveness
Should you give a higher or lower dose of KBr to animals with kidney disease? Why?
You should give a LOWER dose, because KBr undergoes RENAL CLEARANCE and will likely have higher concentrations (the drug isn’t being cleared as effectively, so remains in the blood longer)
is Levetiracetam better as a monotherapy, or as an add on for epileptic dogs?
an add on.
How is Levetiracetam excreted?
renal excretion
what drug can be useful in addition
to midazolam or diazepam for status epilepticus?
Levetiracetam
which AED has a short half life and favourable pharmacodynamics that result in a rapid onset of action
Levitiracetam
Should zonisamide be used as a monotherapy or an add on for epilepsy
it can be used for both!
Approximately __% of zonisamide is excreted by the kidney.
80
WHAT MUST YOU TELL OWNERS ABOUT ADMINISTERING ZONISAMIDE
THIS IS A HAZARDOUS DRUG THAT CAN CAUSE TERATOGENIC EFFECTS. YOU NEED TO WEAR GLOVES WHEN ADMINISTERING.(sorry for yelling again.)
Zonisamide requires a ____ (higher/lower) dose when given with phenobarbital
higher.
What two AEDs are best for treating acute seizures and managing status epilepticus
Diazepam and midazolam (Benzodiazepines)
A dog is seizuring in front of you. how do you administer Diazepam
IV, per rectum, intranasal
a dog is seizuring in front of you. how do you administer midazolam
IM, IV, per rectum, intranasal
Which can be given IM: diazepam or midazolam
midazolam
What pharmacodynamic quality allows benzodiazepines to be fast acting
they are very lipophilic
Diazepam is important for treating:
acute seizures and status epilepticus.
What can oral diazepam cause in cats?
liver necrosis
What is the traditionally preferred emergency seizure treatment for dogs>
diazepam
Why should diazepam not be used for long-term therapy in dogs
After IV administration, teh half-life ranges from 15 minutes to three hours. This means it requires too frequent administration, and can lead to tolerance/dependance with chronic use. Also, there is abuse potential by owners.
Why is diazepam the preferred emergency seizure treatment?
It is more lipophilic than other benzodiazepines, so IV injection rapidly leads to high concentrations in teh CNS
How should you advise an owner to stop a seizure?
Give them a prescription for Diazepam, and tell them to administer it per rectum during a seizure episode.
What is the difference between diazepam and midazolam?
Midazolam is similar to diazepam, but is 3 x more potent. Therefore it has a faster onset of action, but a shorter duration of action.
How would you advise an owner to stop status epilepticus?
give em a prescription for INTRANASAL MIDAZOLAM because a greater percentage of patients achieve cessation of seizure than with rectal diazepam (70% vs 20%)
What are the standard treatments for status epilepticus (continuous seizures)
IV or rectal diazepam
IV, IM or IN midazolam
status epilepticus occurs when a seizure lasts longer than:
5-10 minutes
Which did the ACVIM deem more potent and safer for status epilepticus: Diazepam or midazolam?
Both are safe and potent, but they recommended Midazolam.
