Nervous system drugs

What is glutamate’s role in the CNS?

Excitatory neurotransmitter; excess → excitotoxicity → seizures; important for learning & memory.

What is GABA’s role?

Inhibitory neurotransmitter → muscle relaxation, anti-anxiety, anticonvulsant, amnesia.

What neurotransmitter is similar to GABA in the spinal cord?

Glycine

What are dopamine’s CNS functions?

Motivation, motor control, arousal, emesis.

What happens with low dopamine?

Parkinson’s-like signs.

What happens with excess dopamine?

Psychosis (e.g. schizophrenia, ADHD).

How do stimulants (e.g. amphetamine) affect dopamine?

Increase dopamine release.

What receptor is in the chemoreceptor trigger zone?

D2 receptor.

Give an example of a dopamine agonist and effect.

Apomorphine → induces vomiting

Give an example of a dopamine antagonist and effect.

Metoclopramide → anti-emetic

What is acetylcholine’s role in the CNS?

Modulates cognition, learning, memory.

Which Ach receptor is most important for cognition?

M1 receptor.

Effect of anticholinergics on memory?

Impair learning and memory.

What is norepinephrine’s role?

Alertness, arousal, reward.

How do antidepressants affect NE?

Increase NE (↓ reuptake or metabolism).

Can catecholamines cross the BBB?

No

What is serotonin involved in?

Mood, wakefulness, feeding, emesis.

How do antidepressants act on serotonin?

↓ reuptake or ↓ metabolism.

Example of serotonin antagonist use?

Ondansetron → anti-emetic.

What must CNS drugs do?

Cross the BBB.

How can drugs cross the BBB?

Lipid soluble OR carrier-mediated transport.

List main classes of sedatives

Phenothiazines, butyrophenones, benzodiazepines, α2 agonists.

Mechanism of phenothiazines?

Dopamine antagonists (+ anticholinergic, antihistamine, α-blocking effects).

Uses of phenothiazines?

Sedation, antiemetic, premedication.

Are phenothiazines useful for seizures?

No

Key side effects of phenothiazines?

Hypotension, no analgesia, penile prolapse (horses), sensitivity in Boxers/sighthounds.

Example drug?

Acepromazine.

Example of butyrophenone?

Azaperone.

Main use of azaperone?

Sedation in pigs

Key caution of Azaperone?

Vasodilation; delayed absorption in fat pigs.

Mechanism of benzodiazepines?

Enhance GABA → hyperpolarisation.<a

Main effects of Benzodiazepines?

Anxiolytic, anticonvulsant, muscle relaxant, hypnotic.

Examples of Benzodiazepines

Diazepam, midazolam, zolazepam.

Antagonists of benzodiazepines

Flumazenil

Important caution in dogs with benzodiazepines

May cause paradoxical excitement.

What is a seizure?

Abnormal excessive neuronal discharge.

Causes of seizures?

Intracranial (trauma, encephalitis) OR extracranial (toxins, hypoglycaemia)

What is epilepsy?

Recurrent seizures (idiopathic or symptomatic)

Types of generalised seizures?

Grand mal and petit mal.

4 phases of a seizure?

Prodrome → Aura → Ictal → Post-ictal.

Definition of seizure?

Seizure >1 hour (or prolonged continuous seizure).

What worses seizures?

Hyperthermia

Aim of anticonvulsant therapy?

Reduce neuronal firing via hyperpolarisation.

Effects of barbiturates?

CNS depression (sedation → anaesthesia → euthanasia).

Key issue with barbiturates?

Induce liver enzymes → tolerance.

Overdose risk of barbiturates compared to benzos?

Higher

What are barbiturates?

Anticonvulsants

Why is phenobarbitone preferred?

Effective with less sedation.

Success rate of Phenobarbitone in dogs?

60-80%

Side effects of phenobarbitone?

Polyphagia, PU/PD, hepatotoxicity

Role of Benzodiazepines in seizures?

Terminate acute seizures

Diazepam characteristics?

Short half-life in dogs; binds plastic IV lines.

Mechanism of potassium bromide

Competes with chloride → hyperpolarisation.

Role of potassium bromide

Reduces seizure activity

First line treatment of status epilepticus treatment?

Diazepam IV (0.5–1 mg/kg) or levetiracetam.

If seizures persist after administering diazepam?

Propofol or alfazalone IV

Additional management of treatment of seizures

Cool if hyperthermic (>41.4°C), ± glucose, mannitol, thiamine.

Examples of CNS neurotransmitters

Dopamine, Acetylcholine (Ach), Norepinephrine, serotonin.

Phenothiazines and butyrophenones are in what class of sedative/tranquilizer?

Dopamine antagonists

Benzodiazepines is in what class of sedative/tranquilizer?

Potentiate GABA receptor

Alpha2 agonists are in what class of sedative/tranquilizer?

Selective inhibition of NA from nerve terminals

Long-term control of epilepsy

First line long term drug —> Phenobarbitone

Second line —> Add potassium bromide

Alternative —> Levetiracetam

When should epilepsy treatment begin?

• 1 seizure every 6 weeks

• Clusters every 8 weeks

• Aggression

• Owner concern

Causes of seizure treatment failure?

• Wrong diagnosis

• Incorrect dose

• Tolerance

• Poor compliance

• Contraindicated drugs

What is KBr?

Hyperpolarises neurons

What does behavioural pharmacology focus on?

Neurotransmitters and drugs used to modify behaviour

List classes of behaviour-modifying drugs

Antipsychotics, anticonvulsants, beta blockers, amphetamines, benzodiazepines, antidepressants, hormones

What neurotransmitters are involved in behaviour?

Acetylcholine, dopamine, noradrenaline, serotonin, GABA

Function of acetylcholine in behaviour?

Cognition, memory, consciousness, skeletal muscle movement

Function of dopamine in behaviour?

Movement, behaviour, emesis, hormone release

Function of noradrenaline in behaviour?

Arousal, mood, sleep, hormone release

Function of serotonin in behaviour?

Mood, pain transmission, similar to noradrenaline

Function of GABA in behaviour?

Motor control, memory, consciousness (inhibitory)

List other drugs affecting behaviour

Antihistamines, lithium, buspirone, pheromones, propentofylline, alpha agonists

What are antipsychotics in veterinary medicine?

Dopamine antagonists (e.g. phenothiazines, butyrophenones)

What receptors do phenothiazines act on besides dopamine?

Alpha, muscarinic, H1, serotonin receptors

Use of phenothiazines in behaviour?

Short-term problems (e.g. travel sickness)

Use of butyrophenones in behaviour?

Self-mutilation, feather plucking (birds), spraying/aggression in cats

Example of butyrophenone?

Azaperone

Use of opioids in behavioural disorders?

Hydrocodone for self-mutilation and acral lick

Effect of opioid antagonists in behaviour?

May treat stereotypies/OCD (variable results)

What do amphetamines do?

Increase dopamine, noradrenaline, serotonin release

Paradoxical effect of amphetamines?

Reduce activity in true hyperactivity (e.g. methylphenidate)

Effect of benzodiazepines in behaviour?

Reduce anxiety and fear

Behavioural uses of benzodiazepines in cats?

Spraying, anxiety, grooming

Behavioural uses of benzodiazepines in dogs?

Anxiety, noise phobia, panic disorders

Tolerance pattern of benzodiazepines?

Tolerance to sedation but not anxiolytic effects

Adverse effects of benzodiazepines?

Increased appetite, ataxia, paradoxical excitement (cats), poor depth perception

Contraindications of benzodiazepines?

Liver/renal failure, aggression, human abuse risk

What are antidepressants used for?

Behaviour modification (affect serotonin and other neurotransmitters)

How long do antidepressants take to work?

~2+ weeks (often 6–8 weeks)

Main types of antidepressants?

TCAs, SSRIs, MAO inhibitors

Mechanism of tricyclic antidepressants (TCAs)?

Block reuptake of amines + anticholinergic + antihistamine + alpha blockade

Effects of TCAs?

Sedation, anticholinergic effects

Uses of TCAs in dogs?

Anxiety, aggression, separation anxiety, noise phobia, OCD

Uses of TCAs in cats?

Anxiety, spraying, over-grooming

Example of TCA?

Amitriptyline

Effect of doxepin?

Antihistamine; useful for anxious pruritus

Key feature of clomipramine?

Strong serotonin effect; used for OCD; takes 6–8 weeks

Side effects of TCAs?

Sedation, dry mouth, thirst, urinary retention, constipation, tachycardia, ataxia