Tranquilizers, Sedatives & Stimulants Flashcards
What are tranquilizers/neuroleptics/sedatives?
medicine that calms the animal and promotes sleep (not necessarily induce it) —> analgesia, sedation, decreased sympathetic tone, euphoria
What is the mechanism of action of tranquilizers/sedatives?
affect the CNS at the basal ganglia, hypothalamus, limbic system, and brain stem to act as CNS depressants through dopamine, adrenergic, serotonin, opioid, and GABA receptors
What 4 common therapeutic uses are tranquilizers/sedatives used for?
- calm animals for easy handling
- pre-anesthetic medications
- anti-ementics
- anti-allergic
What pharmacological effects do tranquilizers/sedatives have on the cardiovascular, respiratory, and GI systems?
CARDIOVASCULAR: bradycardia, hypotension, tachycardia
RESPIRATORY: hypoventilation
GI: decreased motility
What are the 5 major tranquilizers/sedatives?
- phenothiazine derivatives
- benzodiazepines
- α2-adrenergic agonists
- butyrophenone derivatives
- opioids
How do phenothiazine derivatives work?
block dopamine action and reduce serotonin action
bind to dopamine receptors (D1-like, D2-like) to keep dopamine from binding and causing CNS activation
What are 4 common phenothiazine derivatives used as tranquilizers?
- Chlorpromazine
- Aceptromazine (ACE)
- Promazine
- Triflupromazine
How do phenothiazine derivatives cause their pharmacological effects? What is important to consider with the induced tranquilization?
depress brainstem and connections to the cerebral cortex, which decrease spontaneous motor activity, like grooming, rearing, and sniffing
NOT accompanied by analgesia
What was the first drug developed with specific antipsychotic or tranquilizer actions?
Chlorpromazine —> phenothiazine derivative
What pharmacological effects does Chlorpromazine have on the CNS and cardiovascular system?
CNS:
- sedation
- blocks release of FSH and LH, increases plasma prolactin
- inhibit other hormones
CARDIOVASCULAR:
- reduction of contractility of myocardium
- arrythmias
What effect does Chlorpromazine have on the CNS of dogs, but not cats?
antagonizing effect on apomorphine-induced emesis
What adverse effect is common in dogs and cats on Chlorpromazine? Horses?
DOGS/CATS: extrapyramidal effects (movement disorders)
HORSES: hyperesthesia (increased response to stimuli), marked excitement, penile prolapse
In what 4 situations is it contraindicated to used Chlorpromazine as a tranquilizer?
- patients with hypovolemia or shock
- use carefully in animals with hepatic dysfunction
- HORSES: may cause severe CNS excitation/depression, seizures,or death
- DOGS: bradycardia (use atropine combination)
How does Acepromazine (ACE) affect compare to Chlorpromazine?
10-20x more potent —> mild to moderate sedation of shorter duration, with a smaller concentration
Why is there a fair volume of distribution of Acepromazine in horses?
highly protein bound
What are 2 common situations where Acepromazine is used?
- tranquilizer-sedative for controlling intractable animals and immobilizing large animals
- used before surgery, examinations/procedures, or grooming sessions with nervous/excitable animals
How does Promazine compare to Chlorpromazine?
structurally related, but 10-13x less potent to produce mild to moderate sedation
When is Triflupromazine commonly used? What makes it unique compared to other phenothiazine derivatives?
sedation + antiemetic
higher risk of side effects
What is the mechanism of action of benzodiazepines (BZDs) as tranquilizers?
bind to GABA receptors to enhance the inhibitory effect of GABA —> hyperpolarization!
(GABA-agonist to activate GABA-gated Cl- channel)
What 5 common benzodiazepines (BZDs) are used as tranquilizers?
- Diazepam (Valium)
- Midazolam
- Clonazepam
- Zolazepam
- Alprazolam (Xanax)
What are the 2 major pharmacological effects of benzodiazepines (BDZs)? What system do they have minimal effects on?
- depressed respiration
- muscular relaxation due to effects in spinal cord
minimal cardiovascular effect
What are 3 major uses for benzodiazepines? How is the use of this drug different in other species?
- sedative, anti-anxiety, anti-panic
- anticonvulsant in all domestic species
- muscle relaxant when given with ketamine
- BZDs alone are satisfactory in sheep, goats, and neonatal foals
- NOT reliable in horses, dogs, or cats
What is Diazepam most commonly used for? What else can it be used for?
benzodiazepine derivative used as a tranquilizer to sedate, reduce anxiety and panic, promote behavioral changes, and induce muscle relaxation
- anticonvulsant
- pre-anesthetic
- increase appetite in cats
- IV + opioids/anesthetics for general anesthesia
What are 2 common adverse effects of Diazepam? 2 rare adverse effects?
- impaired coordination
- lethargy
- aggression and excitement
- hepatotoxicity in cats
How do Clonazepam, Midazolam, and Zolazepam compare to Diazepam?
Clonazepam: stronger, but shorterd half-life
Midazolam: used in combination with opioids in older dos as a neuroleptanalgesic
Zolazepam: used exclusively with Tiletamine for anesthesia
Why is Alprazolam (Xanax) not recommended for use in dogs?
strong liver and kidney effects and can be passed to offspring in milk/colostrum
What are 3 common catecholamines? Where are they produced? When are they released?
- dopamine
- norepinephrine
- epinephrine
brain, nervous tissue, adrenal glands
in response to emotional or physcial stress —> fight or flight response (emergency stress)
What do catecholamines do? What receptors do they bind to?
control metabolism, heart rate, blood pressure, and respiratory functions
G protein-coupled receptors: α- and β-adrenergic receptors
How do α2-adrenergic agonists work as tranquilizers?
stimulate α2-adrenoreceptors, which inhibit NE release
What are 5 common α2-adrenergic agonists used as tranquilizers?
- Xylazine (cats, dogs, horses, wild animals)
- Dexmedetomidine (Dexdomitor - most potent)
- Medetomidine
- Detomidine (horses)
- Clonidine
What are 6 common pharmacological effects of α2-adrenergic agonists as tranquilizers?
- powerful sedation
- powerful analgesia
- skeletal muscle relaxation due to CNS effects
- emesis (cats)
- reduced GI motility and secretion
- hypertension followed by hypotension and bradycardia
What are the 2 most common uses of α2-adrenergic agonists as tranquilizers? What combination should be avoided in geriatric, weak, and diseased animals?
- sedative, analgesic, immobilizing agent
- pre-anesthetic and anesthetic combination
Xylazine + Ketamine —> only use in young an healthy animals
What is the most potent and selective α2-adrenergic agonist available for use in veterinary medicine?
Dexmedetomidine (Dexdomitor)
Xylazine can be given IV in the jugular vein of horses. When do adverse effects happen?
immediate collapse, convulsions, and sudden death can occur is accidentally given in the carotid artery, which is very close to the jugular vein
How can Xylazine cause hyperglycemia? What are 4 other adverse effects it has?
inhibits insulin release in horses
- cardiac aberrations
- renal insufficiency
- hepatic damage
- epilepsy
(never give within the last month of pregnancy!)
How do butyrophenone derivatives work as tranquilizers?
block dopamine D2 receptors
What 2 butyrophenone derivatives are used as tranquilizers?
- Azaperone
- Droperidol
What effect does Azaperone have? What receptors does it act on? What animals is it commonly used on?
sedative and antiemetic
potent D2 antagonist with some α1-adrenergic, muscarinic-cholinergic, and histamine receptor activity
pigs/swine as a pre-anesthetic before general anesthesia and C-sections or as a behavior modifying agent
What receptors does Droperidol work on? How does it compare to the phenothiazine derivatives, Chlorpromazine and Promazine?
potent D2 antagonist with some histamine and serotonin antagonist activity
more potent in dogs
What drug should Droperidol never be used with? How can it be used to induce neuroleptanalgesia? What is it most commonly used for?
epinephrine
Droperidol + fentanyl (opioid)
chemical restraining agent in aggressive dogs
How do opioids work as tranquilizers? What 4 are commonly used?
stimulate opioid receptors (μ, κ, δ)
- Morphine - μ+++, κ+
- Oxymorphone - μ+++, κ+, δ+ (10x more potent)
- Fentanyl - μ+++ (100x more potent)
- Carfentanil - μ+++ (100,000x more potent)
What are CNS stimulants (Analeptics)? What is their mechanism of action?
medicines that stimulate the brain, speeding up both mental and physical processes, which increases energy and metabolism, improves attention and alertness, and elevates blood pressure, heart rate, body temperature, and respiratory rate
promotes neurotransmission —> Amphetamines enhance the release of dopamine and norepinephrine onto the synaptic gap by blocking reuptake and allowing accumulation
What are 3 common times CNS stimulants (Analeptics) are typically used? What are 3 possible adverse effects?
- in emergency situations during anesthesia
- decrease respiratory depressant effects of opiates and barbituates
- treat Attention Deficit Hyperactivity Disorder (ADHD) or hyperkinesis in dogs
- high doses may induce seizures
- hypertension, arrhythmias, hyperventilation
- hepatotoxicity
What is the most frequently used CNS stimulant in veterinary medicine? What is its mechanism of action?
Doxapram
stimulates respiration through direct stimulation of the medullary respiratory centers and activation of carotid and aortic chemoreceptors
What therapeutic use is Doxapram used for? When is it not usually effective?
to arouse animals from inhalant and parenteral anesthesia or anesthetic overdose
in severely depressed neonates
not a good substitute for ET intubation/ventilation
What are 2 common adverse effects of Doxapram?
- high doses may induce seizures
- hypertension, arrythmias, hyperventilatio, and seizures can lead to respiratory alkalosis (low level of CO2 in the blood)
What are 7 signs and symptoms of accidental ingestion and intoxication of CNS stimulants?
- agitation
- increased heart rate
- panting
- tremors
- increased body temperature
- vomiting, diarrhea
- seizures
How are CNS stimulants used in humans? What pharmacological effect do they have?
treats ADD and narcolepsy —> methylphenidate, atomoxetine, modafinil, armodafinil (amphetamines, ecstasy)
stimulant effects on mood and alertness, enhances energy, sociability, and sexual arousal
What are some common side effects on CNS stimulants in humans?
- headache
- insomnia
- irritability, elation, agitation, confusion
- palpitations, tachycardia
- nasal stuffiness
- decreased appetite
- liver injury
- addictive qualities
What are 2 common CNS stimulants abused by humans? How do they work?
- COCAINE: binds to dopamine transporter, blocking the removal of dopamine from the synapse, allowing it to accumulate and produce an amplified signal (also affects NE and serotonin neurotransmission)
- MDMA: indirect serotonin agonist, increased the amount of serotonin released into synapse
