11. CNS stimulant. Anticonvulsant drugs

Question 1

Seizures are caused by…

Answer 1

• Abnormal, high-frequency discharge of a group of neurons
• Starting locally → Other parts of the brain
• Progressive

Question 2

Seizures affect which nervous phenomena?

Answer 2

• Motility
• Sensation
• Behaviour

Question 3

During a seizure, unconsciousness occurs when…

Answer 3

The reticular formation (group of nuclei) is involved

Question 4

Seizures are preferred to be treated by…

Answer 4

Monotherapy

Question 5

Combination therapy during seizures involves…

Answer 5

Any 2 of:

• Phenytoin
• Phenobarbital
• Carbamazepine

Question 6

Drug treatment of: Status epilepticus

Answer 6

Diazepam

Question 7

Drug treatment of: Seizures

Answer 7

• Phenobarbital
• Phenytoin
• Valproic acid

Question 8

Phenobarbital: Summary

Answer 8

Safe, effective & inexpensive barbiturate for chronic therapy in dogs & cats

Question 9

Phenobarbital: Mechanism of action

Answer 9

1. ↑ Activity of GABA (Inhibitory neurotransmitter)
2. Opens Cl^- channels in excitatory cells
3. Neuronal inhibition
4. ↓ Neuronal excitotoxicity (via glutamate receptors)
5. Inhibition of voltage-gated Ca²⁺ channels

Question 10

Phenobarbital: Pharmacokinetics

Answer 10

• Rapidly absorbed after PO
• High bioavailability
• Metabolised primarily in the liver

Question 11

Phenobarbital: Side effects

Answer 11

• Sedation
• Drowsiness
• Ataxia (loss of body movements)
• Polyphagia
• Polyuria

Question 12

List the benzodiazepines

Answer 12

• Diazepam
• Carbamazepine
• Midazolam

Question 13

Diazepam: Clinical uses

Answer 13

• Status epilepticus: Preferred drug
• Premedication & combination (ketamine)
• Muscle relaxation
• Prevention and control of epilepsy
• Sedation

Question 14

Diazepam: Administration

Answer 14

• Rectal
• IV

Not suitable for PO

Question 15

Carbamazepine

Answer 15

Similar profile as phenytoin but with fewer unwanted side effects

Question 16

Phenytoin

Answer 16

Membrane stabilising agent

• Short elimination half-life in dog
• Extremely long in cat (toxicity)

Question 17

Midazolam

Answer 17

• Shorter effect than diazepam
• Produces less sedation than diazepam

Question 18

Drugs contraindicated in epileptic patients

Answer 18

• Phenothiazine derivatives:
  
  • Propiopromazine
  • Acepromazine
  • Chloropromazine
• Butyrophenones:
  
  • Azaperone

Question 19

CNS stimulants (analeptics) can be categorised into…

Answer 19

• Convulsants & respiratory stimulants
• Psychomotor stimulants
• Psychotomimetic (hallucinogenic) drugs

Question 20

Convulsants & respiratory stimulants

Answer 20

• Little clinical use → Used in experiments
• Doxapram = Respiratory stimulant in acute resp. failure
• Strychnine, PTZ = Induce convulsions
  
  • PTZ (tests antiepileptic drugs)

Question 21

Psychomotor stimulants

Answer 21

• Amphetamines
• Cocaine

Question 22

Amphetamines

Answer 22

• ↑ Motor activity
• Euphoria-excitement
• Anorexia
• Psychotic behaviour after prolonged use

Due to release of catecholamines

Effect for a few hours, followed by depression/anxiety

Question 23

Amphetamines: Clinical use

Answer 23

• Narcolepsy
• Hyperkinetic children

Question 24

Cocaine

Answer 24

• Inhibition of catecholamine uptake (esp. dopmine) by nerve terminals
• Shorter duration
• Similar to amphetamines
• Main importance: Abuse

Question 25

Methylxanthines: Examples

Answer 25

* Caffeine * Theophylline (bronchodilator)

Question 26

Methylxanthines: Effect

Answer 26

* ↓ Fatigue * ↑ Mental performance without euphoria * CNS stimulation * Diuresis * Stimulation of cardiac muscle * Relaxation of bronchial muscles

Question 27

Psychotomimetic drugs: Examples

Answer 27

* LSD * Mescaline * MDMA * Phencyclidine

Question 28

Psychotomimetic drugs: Effects

Answer 28

* Affects thoughts and mood without psychomotor stimulation * Some can cause acute hyperthermia and death * 2 main groups * Drugs acting on 5-Hydroxytryptamine * Catecholamines

Question 29

Effect of LSD, Mescaline and MDMA

Answer 29

* Ecstacy: Inhib 5-HT uptake * MDMA also affects many other receptors * Psychomimetic effect * Stimulant effect * Can cause acute hyperthermia and death

Question 30

Phencyclidine: Mechanism of action

Answer 30

Blocks glutamate activated NMDA receptors

Question 31

Barbiturates: Mechanism of action

Answer 31

GABA-BDZ-Barbiturate-Receptor Complex (GABA_A) * ↓ Ca²⁺ accumulation → inhibition of stimulatory transmitter release → Stimulation of membranes

Question 32

Barbiturates: Effects (general)

Answer 32

* CNS effect * Circulatory effect * Respiratory effect