Week 5 - Tranquilizers Flashcards
Tranquilizers, Neuroleptics, and Sedatives are Medicines that _____ the animals and promote _____ but do not necessarily ______ sleep, even in ____ doses. Cause (4)?
calm, sleep, induce, high
analgesia, sedation, decreased sympathetic tone, euphoria
Immobilization?
Mechanism of action: affect the CNS at the (4)
CNS depressants acting through ?
basal ganglia, hypothalamus, limbic system, and brain stem
dopamine, α1-adrenergic, serotonin, opioid and GABA receptors
Therapeutic Uses: CNS tranquilizers are used to calm the animals for easy handling
as pre-anesthetic medications (allowing less general anesthetic)
anti-emetics
anti-allergi
Adverse Effects: _____, depending on ______ condition
various, existing
Phenothiazine derivatives - MOA:
Block Dopamine (DA) action and reduce action of serotonin.
Butyrophenone derivatives - MOA:
Block Dopamine (DA) receptors
Benzodiazepines: MOA
Enhance inhibitory effect of GABA
α2-adrenergic agonists: MOA
Stimulate α2-adrenoreceptors, which inhibit Norepinephrine (NE)/Noradrenaline release
Opioids: MOA
Stimulate opioid receptors [mu (μ), kappa (κ), and delta (Δ)
Phenothiazine derivatives block _____ and/or ______ receptors
dopamine, serotonin
Dopamine and serotonin are “happy” hormones. Produce similar feelings of wellbeing - alert, focused, motivated. We need to block the action of receptors to induce calmness. Pre-synaptic releases dopamine into cleft and then binds to DA receptor (agonists do the same thing). BUT, Dopamine antagonists have a different shape and therefore block the action of the receptor. Stops NT from binding to each receptor and sending a signal so we get a sedative effect.
Tranquilizers: Class of Phenothiazine Derivatives
Chlorpromazine
Acepromazine (Ace)
Promazine
Triflupromazine
KNOW THESE DRUG NAMES
Emphasis on the azine
Pharmacological Effects of Phenothiazine Derivatives
Effects are due to _______ of brain ____ and connections to the _______ ______.
* All phenothiazines decrease ______ _____ activity (3)
* The induced tranquilization is not accompanied by ________.
depression, stem, cerebral cortex, spontaneous motor, grooming, rearing, sniffing
analgesia
Chlorpromazine was the first drug developed with specific ______ or ______ action (year?)
* Appearance: _____ to slightly ______, _____, tasting crystalline _____
* Administration: ___ or ___, well absorbed and distributed throughout the body
* Rapidly absorbed after ____, undergoes extensive metabolism in the ____ and _____
antipsychotic, tranquilizer, 1950, white, creamy, odorless, bitter, powder, IM, IV, PO, liver, kidney
Chlorpromazine causes ______. When given IV gives –> ___-___ min
Antagonizing effect on _______- induced ___ in dogs but not cats
Endocrine effects: blocking release of ____ and ___, in plasma ____
May ____ release of other hormones
sedation, 10-20 , apomorphine, emesis, FSH, LH, prolactin, inhibit
Chlorpromazine
Pharmacological effects - Cardiovascular
Effects on myocardium:
Reduction of contractility
Arrhythmias
Chlorpromazine Adverse Effects
Produces extrapyramidal signs in ___ and ___, such as ?
* May cause _______ and marked excitement in _____ and may cause _____ in the penis
cats, dogs, tremors, muscle contractions, hyperethesia, horses, prolapse
Chlorpromazine Contraindication (and other drugs in this class)
In patients with hypovolemia or shock, carefully used in animals with _____ dysfunction
* In horses, may cause ?
* In dogs, combination with atropine is recommended to overcome _______ effect
hepatic
severe CNS excitation/depression, seizures, death
bradycardia
Chlorpromazine
What is the color of Acepromazine (Ace)?
Does Ace have an odor? What does it taste like?
Yellow, odorless, bitter tasting water soluble powder
How can Ace be administered?
IM or IV
Ace is __-___ times more potent than chlorpromazine, produces ___ to ____ sedation of ____ duration.
10, 20, mild, moderate, shorter
Ace is highly ___ bound and has a __ volume of distribution in ___.
protein, fair, horses,
It is used as a _____- _____ for controlling intractable animals and to ______ large animals. It is also used before _____ or veterinary ______ and procedures or _____ sessions with ______/_______ animals
tranquilizer, sedative, immobilize, surgery, examinations, grooming, nervous, excitable
Acepromazine (Ace)
Promazine
* Structurally related to ________
* Administration: ____ and ____
* 10-13 times less ______ than chlorpromazine, produces mild to moderate _______
* Duration is ____-dependent and can vary within __-___ hr
chlorpromazine, IM, IV, potent, sedation, dose, 4-6
Promazine
Triflupromazine is used occasionally in animals for ______ and as an ______ agent. Has ______ risk of side effects than other _______ derivatives
sedation, antiemetic, higher, phenothiazine
Triflupromazine
Tranquilizers: Benzodiazepines (BZDs)
GABA NT binds to site of GABA-A receptor.
Ligand gated ion channels allow for hyper-polarization of the membrane and inhibition of action potential happens.
Gaba agonist does the same thing as GABA NT.
Tranquilizers: Benzodiazepine (BZD) derivatives
Diazepam (ValiumR)
Midazolam
Clonazepam
Zolazepam
Tranquilizers: Benzodiazepine (BZD) derivatives
Pharmacological Effects
Minimal cardiovascular effects = good
* Depressed respiratory effects
* Muscular relaxation due to effects in spinal cord
Tranquilizers: Benzodiazepine (BZD) derivatives Uses
As anticonvulsants in all the domestic species
* As muscle relaxant when given together with ketamine
* BZD alone: satisfactory in sheep, goats, neonatal foals
NOT reliable in horses, dogs, or cats
Diazepam (ValiumR)
* PK: highly ____ soluble, widely distributed throughout the body, crosses _______, ____ metabolism
* Used in Vet Med to ?
* Also used as an anticonvulsant (dogs and horses)
* Can be prescribed to what species?
* Use as ______ in horses
* Can be used ____ in combination with ______ or _____ for general anesthesia
* Administration: ?
lipid, BBB, liver
sedate, reduce anxiety, panic, promote behavioral changes, or induce muscle relaxation
dogs, cats, reptiles, sheep, horses, and goat scan
sedative, IV, opioids, anesthetics
oral, IV, or rectal
Diazepam (Valium) - Adverse Effects
Impaired coordination Alprazolam (Xanax)
* Lethargy
* Rare: aggression and excitement
* Rare: hepatotoxicity in cats
Clonazepam is stronger than _____ but has shorter ___ )
diazepam, t1/2
Midazolam is used in combination with an ____ in older dogs as a __________.
opioid, neuroleptanalgesic
Zolazepam is used exclusively with _____ for anesthesia.(approved for animal use)
Tiletamine
In pre-synaptic and post-synaptic and nerves
Focus more on pre-synaptic
alpha2 agonists in pre-synaptic nerve; negative feedback mechanism in place which suppresses releases adrenaline goes down.
Tranquilizers: α2- Adrenergic Agonists
Xylazine (cat, dog, horse, and wild animals)
Medetomidine
Detomidine (horses, IM and IV)
Dexmedetomidine (most potent and selective α2-agonist in Vet Med)
Clonidine
Xylazine can be used in what species?
Dogs, cats, horses, and wild animals.
Detomidine can be used in ______ and is administered ___ or ___.
Horses, IV, IM
Tranquilizers: α2- Adrenergic Agonists - Pharmacological Effects
Powerful ______
* Powerful _____ (she emphasized this)
* _____ muscle relaxation due to effects in the CNS
* ______ (cats, less in dogs)
* Reduced both ___ ____ and ____ (control of diarrhea)
* _______ followed by hypotension, ______
sedation
analgesia
Skeletal
Emesis
GI motility, secretion
Hypertension
bradycardia
Tranquilizers: α2- Adrenergic Agonists
Uses
As a sedative, analgesic, and immobilizing agent
* As a pre-anesthetic, and as a part of the anesthetic combination
* Xylazine-ketamine combo should be avoided in geriatric, weak, and diseased small animals
Xylazine can lead to what side effects in horses?
Contraindications:
* Cardiac aberrations, renal insufficiency, hepatic impairment
* Epilepsy
* Immediate collapse, convulsions, and sudden death can occur in horse given Xylazine into carotid artery
* Xylazine inhibits insulin release in horses leading to hyperglycemia
* Accidental? Jugular?
Xylazine with ketamine should be use only in _____ and _________ animals
young, healthy
Xylazine should not be given within the ____ month of pregnancy
last
Tranquilizers: Butyrophenone derivatives
Butyrophenone derivatives: Block central dopamine D2 receptor
Azaperone is a _______ ______ with ____ and _____ effects
* Potent ___ antagonist with some (3) receptors
* Used as a __-________ agent prior to general _____ or ______ section.
* Occasionally used as a _____ modifying agent
* Mainly used in ___ and ___
Block ______ pathway
Butyrophenone neuroleptic, sedative, antiemetic, D2, α1-adrenergic, muscarinic-cholinergic and histamine, pre-anesthetic, anesthesia, caesarean, behavior, pigs, swine,
dopamine
Droperidol is a potent ___ antagonist with some _____ and _____ antagonist activity
* More potent than _______ and ______ in dogs
* Should not be used with _____
* Used in combination with ____ (opioid) for induction of _______
* Chemical restraining agent in _______ ___
Block ______ pathway
D2, histamine, serotonin, chlorpromazine, promazine, epinephrine, fentanyl, neuroleptanalgesia, aggressive, dogs, dopamine
Opioids: MOA: Stimulate opioid receptors [mu (μ), kappa (κ), and delta (Δ)]
Name the common Opiods
Morphine
Oxymorphine
Fentanyl
Carfentanil
CNS Stimulants (_________) are medications that stimulate the brain, speeding up both _______ and ______ processes.
They increase ______, improve _______ and ________, and elevate _______ ________, _______ rate and ______ rate
Analeptics, mental, physical, energy, attention, alertness, blood pressure, heart, respiratory
Amphetamines enhance release of ___ and ____ onto the synaptic gap by blocking _____ and/or ___ reuptake
DA, NE, dopamine, NE
What is the MOA of CNS Stimulants (Analeptics)?
MOA: Promotion of neurotransmission
CNS Stimulants Analeptics - Pharmacological Effects
CNS stimulants are used primarily in _______ situations during anesthesia or to decrease the _______ _______ effects of opiates and barbiturates; to treat _____ or _______ in dogs
emergency, respiratory depressant, Attention Deficit Hyperactivity Disorder (ADHD), hyperkinesis
CNS Stimulants (Analeptics) - Doses
1-5 mg/kg, IV, in dogs and cats
0.5 -1 mg/kg. IV in adult horses
0.02-0.05 mg/kg/min, IV in young animal
CNS Stimulants (Analeptics) - Adverse Effects
Adverse Effects: High doses may induce seizures
Hypertension, arrhythmias, and hyperventilation
Hepatotoxicity
Doxapram: Is used most frequently in Veterinary Medicine as a _____ ______
CNS stimulant
Doxapram MOA:
MOA: stimulates ______ through ____ stimulation of the _______ ________ centers and activation of _____ and _____ chemoreceptors
respiration, direct, medullary, respiratory, carotid, aortic
Doxapram Therapeutic uses:
To arouse animals from _____ and ______ anesthesia or anesthetic ________. Not effective in severely depressed _______ and is not a good substitute for ________ intubation and ______.
inhalant, parenteral, overdose, neonate, endotracheal, ventilation
Doxapram Adverse Effects
High doses may induce _____
* (4) –> may lead to respiratory alkalosis [a?]
seizures, Hypertension, arrhythmias, hyperventilation, and seizures , low level of carbon dioxide (CO2) in the blood
Accidental Ingestion and Intoxication in Pets
Signs and symptoms of toxicity in dogs
Agitation
* Increased heart rate
* Panting
* Tremors
* Increased body T
* Vomiting, Drooling
* Seizures
Accidental Ingestion and Intoxication in Pets
What medications are used in humans to treat ADD?
Medical use in humans: ADD and narcolepsy.
modafinil (narcolepsy),
methylphenidate, atomoxetine (ADD)
What medications are used in humans to treat Narcolepsy?
modafinil
Armodafinil, amphetamines, ecstasy are CNS ?
Stimulants
The pharmacological effects of CNS Stimulants:
Stimulant effect ____ and _____, enhance ___, _____, and ______ arousal
mood, alertness, energy, sociability, sexual
What are the side effects of CNS Stimulant ingestion?
Side Effects:
* Headache, insomnia, irritability, elation, agitation, confusion, palpitations, tachycardia,
nasal stuffiness, and decreased appetite
* Liver injury
* Addictive qualities
Abused: Cocaine, MDMA: “ecstasy”
Cocaine binds to ____ transporter, _______ the removal of _____ from the synapse. ______ accumulates in the synapse to produce amplified signal. Affects also ____ and ______ neurotransmission
dopamine, blocking, dopamine, Dopamine, NE, serotonin
Abused: Cocaine, MDMA: “ecstasy”
MDMA
(MethyleneDioxyMetamphetAmine): is an indirect serotonin agonist,
increasing the amount of serotonin released into the synapse
What are the side effects and clinical signs of Cocaine/Crack users?
