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Pharmacology 1 > Drugs used to modify behaviour - Anticonvulsive, Antiepileptics > Flashcards

Drugs used to modify behaviour - Anticonvulsive, Antiepileptics Flashcards

1
Q

Drugs used to modify behaviour:

A
  • Sedatives (neuroleptics, benzodiazepines)
  • antidepressants
  • B-adrenoceptor blocking drugs (propranolol)
  • Antiepileptics (Carbamazepine, Phenobarbital)
  • Opioid antagonists (naloxone, naltrexone)
  • CNS-stimulants (Dexamphetamine)
  • Antihistamines (Megestrol, Cabergoine, Demadinon)
  • Cerebral Vasodilators (Nicergoline, Propentofylline)
  • Artificial pherormones (Feliway, Felitriend, DAP)
  • Feed supplements (alpha casozeipine, tryptophan)
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2
Q

Name some Antidepressants:

A
  1. Tricuclic antidepressants (TCAs):
    - Amitryptiline, Clomipramine, Doxepin, Imipramine
  2. Serotonin reoptake inhibitors (SRIs):
    - Fluoxetine, Flavoxamine, Sertraline
  3. Monoamine Oxidase inhibitors (MAOIs):
    - Selegiline
  4. Lithium:
    - narrow margin of safety, not used in Vet.med
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3
Q

Tricyclic Antidepressants (TCAs):

  • Mechanism of action, Pharmacokinetics
A
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4
Q

Mechanism of action:

  • Inhibition of serotonin and NA reuptake (+ anto-cholinergic, anti-adrenergic, anti-histamine)

Pharmacokinetics:

  • Oral absorption is good, high availability, bounded to albumin (90-95%), Cpss 2-3 weeks, metabolism in liver, elimination via urine.
A
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5
Q

Tricyclic Antidepressants (TCAs)

  • Side-effects, indications:
A

Side-effects:

  • moderate sedation, occasional vomitting, changes in appetite or lethargy, antimuscarinic effects, urniary retention

Indications:

  • separation relaxed anxiety, feline urine spraying, stereotypes, acral lick dermatitis
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6
Q

Serotinin reuptake inhibitors (SRIs)

  • Mechanism of action, Pharmacokinetics:
A

Mechanism of action:

  • selective inhibition of serotonin reuptake

Pharmacokinetics:

  • oral absorption is good, high availability (F=0.7)
  • bounded to albumin.
  • metabolism in liver flyoxetine –> norflyoxetin
  • elimination half-life of the metabolites 7-9 days.
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7
Q

Serotinin reuptake inhibitors (SRIs)

  • side effects, indications, dose:
A

Side-effects:

  • infrequent, occasional comiting, diarrhea, increased CYP450 activity
  • warnings: severe hepatic and/or renal imparment, diabetes mellitus, epilepsy

Indications:

  • stereotypes, aggression, depression, generalised and recurrent fears, (separation related anxiety, feline urine spraying)

Dose:

  • dogs 1-4 mg/kg (1x), caps 4 times less
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8
Q

Monoamine Oxidase Inhibitors (MAOIs)

  • mechanism of action, pharmacokinetics:
A

Mechanism of action:

  • decreased intracellular metabolism of adrenaline, noradrenaline, prolonged NT action in synapses

Pharmacokinetics:

  • Oral absorption is bad, low oral bioavailabiity (dog F= 0.1), Cpss after 3-4 weeks.
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9
Q

Monoamine Oxidase Inhibitors (MAOIs)

  • Side-effects, indications, dose:
A

Side-effects:

  • gastrointestinal signs (salivation, vomitting, diarrhea), behavioural changes, excitements.
  • interactions (eg. opioids)
  • active metabolites (amfertamines) -> missuse

Indications:

  • stereotypes, aggression, older dogs: changes in cognitive functions, older cats: vocalisation

Dose:

  • 0.5-1 mg/kg (1x)
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10
Q

What are Benzodiazepines?

A

sedative- anxiolytic- hypnotic effects- relatively safe drugs

Eg:

  • Alprazolam: faster onset, shorter action
  • diazepam: short ativity in dogs, in cats longer
  • Lorazepam
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11
Q

Difference between Grand mal seizures and Petit mal seizures:

A
  • Tonic-clonic seizures, formerly known as Grand mal seizures, are the seizures type most commonly associated with epilepsy and are a type of generalized seixure affecting the entire brain.
  • Absence seizures may occur in several forms of epilepsy = pepti mal seizures.
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12
Q

Classification of Antiepileptics:

A
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13
Q

Mechanism of action of Anticonvulsant drugs

  • Main categories:
A
  • Inhibitory synaptic processes
  • excitatory neurotransimmsion
  • stabilisation of membranes
  • modulation of the release of neurotransmitters
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14
Q

Mechanism of action of Anticonvulsant drugs.

  • Inhibitory syneptic process
A
  • BZD, PB, Imepitoin: GABA-ergic receptor agonsit (allosteric)
  • Progabide: pro-drug of GABA
  • Vigabatrin: inhibitor for GABA-transaminase
  • GABApentin: synthesis of GABA increase
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15
Q

Mechanism of action of Anticonvulsant drugs

  • Excitatory neurotransmission:
A
  • BZD: inhibition of release of excitatory neurotransmitters
  • PB, penytoin, valproate: presynaptic effect
  • Felbamate: antagonist of glutamate-receptors
  • Lamotrigiene: release of glutamate decrease
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16
Q

Mechanism of action of Anticonvulsant drugs

  • stabilisation of membrane
A
  • reduction of electrical excitability of cell membranes, possibly thorugh use-dependent block of sodium channels
  • Carbamazepine, phenytoin, valproate

Modulation of the release neutrotransmitters:

  • inhibition of the presynaptic Ca-channels
  • Lecetiracetam
17
Q

Phenobarbital:

  • Function, effective therapeutic level, kinetics
A

Function:

  • pronounced depression of the CNS
  • Ach, NE, glutamate release decreases, GABA-mimetic (allosteric)

Effective therapeutic level:

  • in dog: 15.45 ug/ml, in cat: 23-30 ug/ml

Kinetics:

  • PO bioavailability; 90% tmax 4-8 hr, long T1/2 (37-73 hr)
  • Cpss after 30-45 days, plasma binding 40-45%
  • Metabolism: liver strong micros. enzyme induction
  • Dose –> steroids, deoxycycline, quinidine, phenylbutazone
18
Q

Phenobarbital:

  • side effects, dosage
A

Side effects:

  • sedation, drowsiness, ataxia, polyphagia, polyuria, rarely: facial pruritus, thrombocytopenia, neutropenia, idiosyncrasy (hepatotoxic, pancreatitis, necrolytic dermatits)

Dosage:

  • 1-5 (40) mg/kg PO
  • Status epilepticus: 2-4 mg/kg IV bolus

Pentobarbital status epilepticus: 2-15 mg/kg IV

19
Q

Diazepam:

A

Benzodiazepines

Dogs: dugs of choice for controlling status epilepticus

  • not suitable for oram maintenance therapy (absorbed poorly, eliminated rapidly, and a tolerance to anticonvulsant effects develop rapidly
  • dose: IV bolus 5-10 mg/kg, followed by infusion 2-5 mg/hour. Per rectum: 0.5-0.2 mg/kg, up to 3 times in 24 hr.

Cats: maintennce therapy 0.25-0.5 mg/kg, PO BID-TID

  • slower elimination rate than dogs but also do not develop a tolerance.
  • tatus epilepticus: 0.5-2 mg/kg IV

Horses:

  • long elimination half-life (7-22 hr), therefore the anticonvulsant of choise (5-20 mg/dose IV)
  • for seizures: 25-50 mg/dose IV
20
Q

Clonazepam:

A

Benzodiazepines

  • in dogs tolerance develops less rapidly and it is more properly absorbed orally, can be used for oral maintenance therapy in dogs.
  • in maintenance therapy it is best used as an adjunct to phenobarital at sodages of 0.1-0.5 mg/kg/day, or alone at 0.5mg/kg TID
  • diarrhea sometimes develops, but can be avoided by increasing the dose frequency from 1 to 3 times/day
21
Q

Chlorazeopate:

A
  • adjunct to phenobarbital treatment in dogs. 2-6 mg/kg BID
22
Q

Carbamazepine

A
  • similar to that of phenytoin, but with fewer unwanted side-effects
  • not recommended
23
Q

Phenytoin:

A
  • A membrane stabilising agent (use-dependent block of sodium channels and GABA enhancing activity)

–> cardiac anti-dysrhytmic activity and anticonvulsant activity

  • absorption and metabolism are variable
  • short elimination half-life in dog, extremely long in cat (toxicity!)
  • it is difficult to avhieve therapeutic plasma-drug concentrations in dogs because of rapid elinination half-life
  • not recommended
24
Q

Primidone:

A
  • is the 2-deoxy analouge of phenobarbitone, the antipeltic activity is due to its metabolites
  • do not use together with barbiturates
25
Q

Sodium (potassium) Bromide:

A
  • in monotherapy effective blood level: 2,5 mg/ml with PB: 1-1,5 mg/ml
  • long half life: 21-24 days in dogs
  • side effects: sedation, ataxia, stupor, pruritic skin lesions, polydipsia, pancreatitis, muscle degeneration, anaphropdisia
26
Q

Drugs contraindicated in epileptic patients:

A
27
Q
A

Pharmacology 1 (12 decks)

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