Chapter 8 Nerouvs System (Analgesics, Tranquilizers, Sedatives, and Anesthetics) Flashcards
Analgesics
Drugs used to control pain - reducing the perception of pain without significant loss of other sensations
Pain Pathway
Takes place in the nervous system, involves the transmission of information from a stimulus to perception by the brain
Transduction
Painful stimulus is transformed into an electrical signal mediated by depolarization of a pain receptor
Nociceptor
Pain receptor
Transmission
Impulses from the nociceptors are transmitted to the spinal cord
Modulation (modification)
Sensory depolarization wave is transmitted from the spinal cord toward the brain. At the level of the spinal cord, this wave can be modified (suppressed or enhanced) This can decrease pain perception at the brain level.
Perception
Pain is perceived at the conscious level. GA prevents conscious perception of pain
Hyperalgesia
Occurs when pain receptors are more sensitive and responsive to painful stimuli. Increased sensitivity can result from the influence of inflammatory molecules
Wind-Up
After initial pain impulse dampening is reduced, the pain is more effectively transmitted up the spinal cord to the brain, increasing pain perception. (Increasing success in transmitting pain up the spinal cord)
Hyperesthesia
Increased sensitivity to any stimulus
Opioids
Chemically synthesized drugs with opiate characteristics (most potent analgesics in vet med)
Neuroleptanalgesics
Opioids combined with tranquilizers or sedatives to lessen opioids undesirable effects
Opiates
Extracts from poppy plants
Narcotics
Drugs that cause a state of narcosis
Narcosis
Unconsciousness or stupor
Known opioid receptors in mammals are:
mu (µ), kappa (κ), and delta (δ) receptors
sigma (σ) is sometimes referenced
True or False - Drugs specifically targeting Sigma receptors are often used in vet med
False - these drugs are not used in vet med
Mu (µ) receptors
Found in pain related nerves in the brain and spinal cord - Agonists to these receptors cause profound analgesic effects
Kappa (κ) receptors
Effects of these receptors are milder than Mu (µ) receptors. Some Kappa (κ) agonists are also Mu (µ) receptor agonists, providing a stronger analgesic effect.
Kappa (κ) receptor agonist drugs
Butorphanol, Levorphanol, Pentazocine
Full Mu (µ) Agonist drugs
Morphine, Hydromorphone, Fentanyl
Partial Mu (µ) agonist drugs
Buprenorphine, Butorphanol
Mu (µ)- mediated analgesia occurs when:
A decrease in the release of neurotransmitters such as acetylcholine, dopamine and serotonin. This blocks or reduces depolarization waves along the pain pathway
Mu (µ) Antagonist Drug
Naloxone - reversal drug for opioid analgesics
List the Schedule II Opioid Analgesics
Morphine Hydromorphone Oxymorphone Fentanyl Methadone Meperidine
List the Schedule III Opioid Analgesics
Buprenorphine
List the Schedule IV Opioid Analgesics
Butorphanol
Tramadol
Visceral Pain
Pain involving the internal organs
Somatic Pain
Pain involving skin and superficial tissues
Morphine
- Stimulates primarily Mu receptors with some action on Kappa receptors
- Effective for both Visceral and Somatic pain
- Low doses IM or SQ cause vomiting and salivation in dogs (Morphine reaches CRTZ before suppressing the mu receptors of the emetic center)
- Causes histamine induced vasodilation causing a decrease in arterial BP
Hydromorphone/Oxymorphone
- Mu Agonists with a higher potency than Morphine
- Similar efficacy to Morphine
- Causes less vomiting and histamine release
- May cause transient hyperthermia in cats
Fentanyl
- Mu Agonist with greater potency and shorter duration than Morphine
- Causes less vomiting
- Given as IV infusion (CRI), patch, or transdermal solution
- Patch takes several hours to be delivered by patch
Recuvyra
Transdermal Fentanyl solution applied 2-4 hours prior to surgery and supplies analgesia for up to 4 days post surgery
Methadone
- Mu receptor Agonist
- Also blocks N-Methyl-D-Asparate (NMDA) receptors
- Less likely to cause vomiting/histamine release compared to other Mu agonists
Meperidine (Demerol)
- Less potent than morphine
- Shorter duration
- Has more cardiovascular depressant effects than other opioids
- Not widely used in vet med
Buprenorphine
- Partial Mu Agonist and a Kappa antagonist
- Has a ceiling effect
- Longer duration of effect than Torb (6-8 hours)
Simbadol
SQ brand of Buprenorphine approved for cats
Ceiling Effect
Regardless of the dose given, the degree of Buprenorphine analgesia will never reach that of Morphine.
** Increased doses do NOT increase the degree of analgesia/sedation, it only extends/prolongs the duration of the drugs effect **
NMDA (N0methyl-D-aspartate) Receptor
Blocking this receptor depresses activity of parts of the brain, thus reducing some of the adverse opioid effects (hypersensitivity, or reactions to other sensory stimuli)
Butorphanol
- Weak partial Mu agonist and a strong Kappa agonist
- Often mixed with sedatives/other analgesics for a full anesthetic regimen
- Considered a partial agonist/antagonist because it can be used to reverse some of the respiratory depressant effects of hydromorphone while providing analgesic effects
- Strong antitussive properties - only FDA approved cough suppressant in small animals
Tramadol
- Must be converted to the active form, O-desmethyltramadol (M1) which is a Mu receptor agonist
- Inhibits serotonin and norepinephrine re-uptake, blocking muscarinic cholinergic and stimulating alpha2 receptors
- Cats receive stronger analgesia from Tramadol than dogs (they can produce more M1 metabolite)
- Should not be administered in animals taking behavioral tricyclic antidepressants (causes serotonin syndrome)
Serotonin Syndrome
Clinically significant high serotonin levels
Naloxone (Narcan)
Pure Mu and Kappa antagonist used to reverse the effects of opioid overdose
(More difficult to reverse the effects of Buprenorphine given how tightly it binds to the Mu receptors)
Tranquilizers
Have anxiety lowering effects/calms the patient
Sedatives
Cause drowsiness and sleepiness but does not reduce the patients anxiety or agitation
Anxiolytic Agents
Literally means “Breaks apart anxiety”
Narcosis
State of sleep from which the animal is not readily aroused
When working with tranquilized animals it is very important to remember:
Tranquilized animals in a relaxed state are still capable of feeling pain and responding quickly and viciously to manipulations that elicit pain
Acepromazine
- Phenothiazine derivative that works by blocking Dopamine, Alpha-1 Adrenergic, Muscarinic Cholinergic, and histamine receptors in the brain
- Has antiemetic effects (inhibits receptors on the CRTZ and emetic center)
- Commonly causes protrusion of the nictitating membrane
- Can cause temporary or permanent penile prolapse in horses
Benzodiazepines
- Gamma-Aminobutyric Acid (GABA) receptor agonists tat provide anxiolytic and muscle-relaxing effects
- Does not bind to the same site as the endogenous GABA molecule, instead binding to an allosteric site, leading to a tighter binding of GABA to the receptor
- Schedule IV controlled substances
Diazepam (Valium)
- Most common benzodiazepine in vet met
- Drug of choice to control active seizures, used in anesthetic protocols to reduce muscle rigidity, dysphoria and agitation
Tiletamine
- Dissociative anesthetic
- Drug combined with Zolazepam, known as the commercial drug Telazol
- Used for minor procedures lasting less than an hour in cats, and less than 30 minutes in dogs
- Provides stronger analgesia than Ketamine
Midazolam
- Most commonly used as a pre-anesthetic tranquilizer
- Has a greater potency than Diazepam
Clonazepam
Orally administered drug used long-term with Phenobarbital to control seizures in dogs
Alpha-2 Agonists
- Cause a decrease in norepinephrine release in the CNS, leading to sedation
- There is also an analgesic component based on decreased perception of pain
- These drugs also have a ceiling effect
- Induce effects on the cardiovascular system
- Can also have an affect on Alpha-1 receptors (causing vasoconstriction and hypertension)
- Newer Alpha-2 drugs have a higher selectivity for Alpha-2 receptors
Xylazine
- 1st alpha-2 agonist used in vet med
- Horses require a much smaller dose than the dog, cattle even less than the horse, and goats less than the cattle
- Swine are considered highly resistant to the dose (requiring a higher dose than the dog)
- Should not be used in dogs with a history or susceptibility for gastric dilation
- Cattle are susceptible to rumen stasis
Detomidine
- Alpha-2 Agonist
- Labeled for use only in horses
(Extra label uses in cattle and small ruminants)
Medetomidine
- Alpha-2 Agonist
- Labeled for use in dogs as a sedative when minor surgery doesn’t require muscle relaxation
(extra label uses in cats and horses)
Dexmedetomidine (Dexdomitor)
- Alpha- 2 Agonist
- Labeled for use in dogs and cats
- This is the dextrorotatory only form of medetomidine (has 1:1 “dextro” and “levo” forms)
- More potent than medetomidine but has the same ceiling effect
Romifidine
- Alpha-2 Agonist
- Labeled for use in horses to ease handling for examinations and minor procedures
Alpha-2 Antagonists
Drugs that reverse the effects of Alpha-2 Agonists
Yohimbine
- Alpha-2 Antagonist
- Still used to reverse the effects of Xylazine
Tolazoline
- Alpha-2 Antagonist
Atipamezole (Antisedan)
- Alpha-2 Antagonist
- Used the most in vet med because of its better selectivity for alpha-2 receptors
- Caution should be used when giving this drug IV
Anesthesia
Refers to a state of no sensation
Local Anesthesia
Reversible loss of local sensation of the region of the body without loss of consciousness
General Anesthetics
The reversible loss of sensation associated with unconsciousness
Barbiturates
Used for anesthetic induction and euthanasia. Drugs in this class work directly at the GABA site of GABA receptors
Pentobarbital
- Short acting barbiturate
- Used more for long term control of convulsions in dogs with epilepsy
- Used in vet med as an anesthetic agent for short procedures when gas anesthetics were unavailable
Propofol
- Injectable anesthetic agent unrelated chemically to barbiturates and other injectable anesthetics
- Used to induce anesthesia and for short-duration diagnostic procedures
- Effects also mediated via the GABA receptors, but also inhibit NMDA receptors
- Net effect = suppression of neuronal activity in the brain, resulting in sedation or anesthesia
- Causes apnea, especially after rapid administration
Apnea
Cessation of breathing
Ketamine
- Dissociative anesthetic - short acting
- NMDA antagonists, and can stimulate Mu and Kappa opioid receptors
- Effect caused is that of being disconnected from the body (cataleptic state)
- Not suited for use alone fr internal procedures (limited efficacy at blocking visceral pain)
Methohexital
- Ultrashort-acting Barbiturate
- Still available but has largely fallen out of use
Phenobarbital
- Long acting barbiturate
-
Phenobarbital
- Long acting barbiturate
- Previously used successfully for anesthesia
- Anticonvulsant drug of choice for long-term control of epilepsy in small animals
Cataleptic State
Characterized by an appearance of being awake but being unable to respond to external stimuli
Etomidate
- Short acting anesthetic agent
- Enhances GABA effects on GABA receptors
- Used primarily for induction of anesthesia, especially in patients with cardiovascular problems (has minimal negative effect on the heart)
- Has no significant analgesic effects
Alfaxalone (Alfaxan)
- Neurosteroid / Neuroactive steroid - meaning it is similar to endogenous hormone-like steroids synthesized in the brain that alter the neuronal activity within the brain
- Causes inhibition of the brain and CNS depression
- Still causes apnea like propofol
- Can cause cardiovascular
Dysphoria
Bad hallucination
Idiosyncratic Reaction
Unpredictable reactions that is not dose related and cannot be predicted by an identifiable risk factor
Inhalant Anesthetics
Anesthetic agents delivered as a gas via the lungs that is absorbed from the alveoli into the blood and distributes to the brain to produce unconsciousness - used for anesthetic maintenance
MAC (Minimum Alveolar Concentration)
The lowest concentration of gas anesthetic that must be achieved in the alveoli of the lungs to produce safe anesthesia.
Each type of gas anesthetic has a specific MAC
(The lower the MAC the more potent the drug and the less drug that is required to achieve proper anesthesia)
Isoflurane
- Inhalant anesthetic
- Smoother induction and recovery than Halothane
- Has cardiac stabilizing effects
- Can cause a decrease in arterial BP
- Known for its distinct odor
- Minimally metabolized by the liver
Sevoflurane
- Inhalant anesthetic
- Faster induction and recovery than Isoflurane
- Has good cardiac stabilizing effects
- Newer than Isoflurane
- Minimally metabolized by the liver
- Does react with the CO2 scavenger compounds (soda lime) and cause production of a chemical called Compound A
Desflurane
- Inhalant anesthetic
- least used of the 3 common anesthetic gases
- Low potency (requires a higher MAC)
- Odor similar to Isoflurane
- High cost
- Requires a special heated and pressurized vaporizer to turn the liquid into a vapor that can be inhaled
Compound A
Sevoflurane reacts with the CO2 scavenger compounds commonly used in anesthetic machines and causes production of this chemical compound. It is has been found to cause nephrotoxicity in rats - controlled studies in dogs did not have the same conclusions
Nitrous Oxide
- Inhalant anesthetic (cannot be used alone)
- Added to inhalant anesthetic regimens to reduce the amount of other anesthetics needed
- Contraindicated in animals with distended rumen, twisted necrotic intestinal tissue, gastric dilatation, and pneumothorax
- Once Nitrous Oxide has been d/c’d 100% O2 must be administered for several minutes to prevent diffusion hypoxia
Diffusion Hypoxia
“Second gas effect” When Nitrous Oxide is ceased, it rapidly diffuses out of tissues into the blood and then into the alveoli, where it dilutes the O2 concentration. If 100% O2 is no longer being delivered and the animal is receiving room air (containing 15-17% O2) the O2 concentration in the lungs can be diluted enough by the nitrous oxide to produce hypoxia
CNS Stimulants
Occasionally used to stimulate respiration in anesthetized animals or to reverse CNS depression cause by anesthetic or sedative agents
Caffeine and Theobromine belong to a broad group of drugs known as …
Methylxanthine compounds- which include respiratory bronchodilating drugs like Theophylline and Aminophylline
The active ingredient in chocolate is…
Theobromine
Doxapram (Dopram)
- CNS Stimulant
- Works primarily in the medulla of the brainstem to increase respiration in animals with apnea, bradypnea, or other conditions in which the respiratory rate and depth of ventilation need to be increased
- Use with caution in animals that are predisposed to seizures
Halothane
- Inhalant anesthetic
- Discontinued in US in 1995
Bradypnea
Slow breathing
True or False - Gas anesthetics provide analgesia
False. Gas anesthetics do not provide analgesia and the rapid recovery from gas anesthesia can produce delirium because of the transition from unconscious state to a sudden awareness, especially if the animal is in pain
Apneustic Breathing Pattern
Respiratory rhythm is often altered so that the animal takes a long, deep inspiration, holds the breath momentarily, and then quickly exhales, producing a respiratory pattern
γ-aminobutyric acid (GABA) receptor
One of the more important inhibitory neurotransmitters found in the CNS of mammals
GABAA receptor
Located on the excitatory neuron and causes the GABA inhibitory neurotransmitter to bind more tightly with its receptor, opening chloride channels that flood the neuron cell with chloride and decrease the neurons ability to depolarize when stimulated
Flumazenil
- Benzodiazepine antagonist
- In the unlikely overdose of a benzodiazepine, or if there is a need to shorten a prolonged recovery (especially in cats) this drug can be used to reverse them
Hyperthermia
Increased body temperature
Potency
The relationship between the therapeutic effect of a drug and the dose necessary to achieve that effect (higher potency = smaller dose)
Efficacy
Expressed as effect
Mydriasis
Pupil dilation
Myosis
Pupil constriction
Euphoria
Pleasant hallucinatory effect
Agonist
Drug exerts a notable effect on the receptor
Partial Agonist
Partial effect on the receptor - some intrinsic activity
Antagonist
No effect on the receptor
Mixed agonist/Antagonist Drugs
The drug combines with multiple types of opioid receptors
Redistribution
Represents relocating the drug to an area of the body that is less likely to produce adverse reactions (moves the drug from the brain to other tissues)
