INTRODUCTION TO
BEHAVIORAL PHARMACOLOGY
Dr. Yasemin SALGIRLI DEMIRBAS
Department of Physiology, Faculty of Medicine,
Ankara University
Overview
• The use of medication is essential in many cases
• Addition of psychotherapeutic agents leads to better and faster treatment outcomes
• Why?
1. Learning and behavioral medications relay on the same molecular changes
2. Serotonergic neurons are most dense in the frontal cortex and
hippocampus which primarily involved in learning
REMEMBER–
NEUROTRANSMISSION
• Neurotransmitters (NT/NM) are chemicals that travel across the synapse and allow communication between neurons.
• The most important neurotransmitters:
Serotonin
Dopamine
Norepinephrine (NE/NA), Epinephrine
GABA (Inhibitory Amino Acid)
FUNCTIONS OF NM
• Serotonin (postsynaptic reseptors predominate in limbic regions):
Sleep, appetite, sensory perception, mood, temperature regulation and pain suppression
• Dopamine: Coordinated movement (corpus striatum), emotion (pleasure/reward), learning and memory
• Acetylcholine: Muscle action, cognitive functioning, memory, and emotion
• Norepinephrine (fight/flight): Increased heart rate (arousal), learning (functional reward systems), memory, dreaming, waking from sleep, and emotion
• GABA (gama-aminobutyric acid): The major inhibitory neurotransmitter in the brain, associated with anxiety
IMPORTANT!!
• Treatment of nonspecific behavioral complaints is unacceptable!!
• Accurate diagnosis is essential - Diagnosis criteria should be met!
• Drugs/diets are not «quick fix»!
• Behavioral medication can facilitate learning-very rarely sufficient alone!
• Pharmacological intervention relies on client cooperation on
administration
CRITERIA FOR SELECTING DRUG THERAPY
• Behavioral diagnosis
• Duration of the problem
• Severity of the symptoms
• Risk of euthanasia/rehoming
• *A complete medical examination and blood workup - every six months
• Should be terminated when satisfactory results have been achieves
• 2-week washout period before starting the another class of drugs
CLASSES OF PSYCHOACTIVE DRUGS
1. Neuroleptics (Antipsychotic agents):
• Phenothiazines routinely used in practice for sedation and restraint
• Most commonly used member: Acepromazine
• Outdated for behavioral medication!!!!!
• Blocks dopaminergic receptors in the brain
***Associated with increased sensitization to noise
***Blocks the motor responses while leaving sensory perception unaffected
***Aware of the stimulus-inability to react
***Worsening of the problem-phobia
1. Neuroleptics (Antipsychotic agents):
• Major behavioral contraindication is aggression-can lead to behavioral disinhibition
• Medical contraindications: Epilepsy, hepatic
dysfunction, respiratory depression, renal compromise
and hypotension
2. Azapirones:
• Buspirone
• Mild anxiety related problem-urine spraying in cats
• Treatment of aggression with impaired social interaction in dogs?
• Ineffective when the animal is exposed to intense fear-inducing stimuli
• Exact mode of action is not known-partial serotonin agonist
• Dog: 1 mg/kg 2 to 3 times daily
• Cat: 0.5-1 mg/kg 2 to 3 times daily
• Contraindication: behavioral disinhibition-do not use in multi-cat
households
3. Benzodiazepines (BZ):
• Diazepam and Alprazolam: the two most commonly used drugs
• Short-term treatment for phobias
• Effect: Enhance GABA - increased binding affinity of the GABA receptor for GABA
• Episodic, acute, short-acting anxiolytic medication
• Interference with short term memory
• Decrease muscle tone
• Should be given at least 1 hour before the stimulus
• Approx. 3-6 hours anxiolytic benefits
3. Benzodiazepines (BZ):
• Three ways to use Alprazolam
1. Preventive: the client should anticipate when there will be provocative stimulus (guest, approaching sorm, heavy traffic hours etc)
2. Interventional: To prevent dog making a molecular memory of fear
3. Panicolytic: If the dog has a panic attack, give the full dose immediately!
3. Benzodiazepines (BZ):
• Diazepam:
• Dog: 0.55-2.2 mg/kg po
• Cat: 0.22-0.4 mg/kg po
• Alprazolam:
• Dog: 0.01-0.1 mg/kg po
• Cat: 0.12-0.25 mg/kg po
• Side effects: In cats - risk of idiopathic hepatic necrosis
• «Discontinuation syndrome»!-care should be taken over their withdrawn
3. Benzodiazepines (BZ):
• *GABAPENTIN
• GABA analogue –modulates glutamate metabolism involving impulsivity
• Common uses for Gabapentin:
• Myogenic-neurogenic pain
• Anxiety disorders
• *As an adjuvant to treatments for OCD
4. Gabapentin:
• Dog: 2-5 mg/kg po 12 h at the lower end
10-20 mg/kg po 8-12 h at the higher end
• Cat: 3-5 mg/kg po 12-24 h
• *a few side effects
5. *Trcyclic antidepressants (TCAs)
• Clomipramine
• One of the most widely used behavioral medicine
• Treatment of anxiety related problems and compulsive disorders
• Antidepressant action by blocking the re-uptake of serotonin and norepinephrine
• Long acting anxiolytic medication
• Dog: 1-3 mg/kg po q 12 hours
• Cat: 0.25-0.5 mg/kg po q 12 hours
5. *Trcyclic antidepressants (TCAs)
• Side effects:
• Sedation
• Dry mouth
• Urinary retention and constipation
• Hypothyroidism ?
• *Can be used in combination with BZ (Storm fobia etc.)
6. *Selective Serotonin Reuptake Inhibitor
• Fluoxetine, paroxetine, sertraline and fluvoxamine
• Highly selective blockage of the reuptake of 5-HT into presynaptic neurons
• As for the TCA, treatment must continue for a minimum of 6-8 weeks
• Why?
• Receptor conformation changes through the production of new proteins
• Treatment of profound aggression, separation anxiety, panic disorder and OCD
6. *Selective Serotonin Reuptake Inhibitor
• Fluoxetine;
• Dog: 0.5-1 mg/kg po
• Cat: 0.5-1 mg/kg po
• Side effect: Common side effects on GI system-
inapetence, anorexia, diarrhoe, nausea
7. *Monoamine oxidase inhibitors (MAOIs)
• Selegiline
• Act by blocking oxidative deamination of brain amines-increase these substances
• Dopamine mediated -increase in reward-motivated activity
• Increased cognitive ability
• Main use: Cognitive dysfunction
• Dog: 0.5 mg/kg
• Cat: 1 mg/kg
• *Selegiline is metabolized into amphetamine-animals without
cognitive impairment will not benefit from selegiline
7. *Monoamine oxidase inhibitors (MAOIs)
• Combination therapy should be avoided!
• Combination with TCA and SSRI can result in CNS toxicity and fatal condition «serotonin syndrom»!-treat with propranolol (β- blocker)
• Phenothiazines, opiate analgesics and alpha-2-agonists are contraindicated!
• Use of selegiline in pregnant or lactating females is prohibited!
8. Alpha-Adrenergic Agonists
• Clonidine
• Lowers heart rate and blood pressure
• Increase GABA activity
• Treatment of noise reactivity and panic disorder, hyperarousal and hyperactivity in dogs
• Dog: 0.01-0.05 mg/kg po q 12 h
• Should not be used with TCA’s!- antagonist effects
9. Beta blockers
• Propranolol, *pindolol
• Treatment of situation- if specific anxiety-tachycardia and tachypnoe are prevalant
• Should be given before the anticipated stimuli
• Pindolol:
• Dog: 0.125-0.25 mg/kg po q 12 h
• Propranolol:
• Dog: 0.5-3 mg/kg po q 12h
• Cat: 0.2-1.0 mg/kg q 8h
10. Antiepileptics
• Phenobarbitone, carbamazepine
• Treatment of rage syndrom or OCD in which lymbic/temporal lobe epilepsy has been implicated
• Phenobarbitone: behavioral consequences of limbic epilepsy
• Dog: 1-8 mg/kg q 12h
• Cat: 1-2.5 mg/kg q 12 h
• Carbamazepine: Tail chasing/spinning
• Dog: 4-8 mg/kg q 12h
• Cat: 25mg q 12 h
• *Contraindicated in cases of renal and hepatic impairment, cardiovascular, heamotological disease
