Injectable and Dissociative Anesthetics Flashcards
What 4 things do animals experience under general anesthesia? What agents are most commonly used?
- unconsciousness
- hyporeflexia
- analgesia
- skeletal muscle relaxation
IV and inhaled agents that allow adequate surgical access to the operative site
What 4 classifications are anesthesias typically divided into?
- barbiturates (injectable)
- non-barbiturates (injectable)
- cyclohexylamines (dissociative)
- inhalants
What is the difference between anesthetic agonists and antagonists?
AGONIST: binds to and stimulates CNS (most anesthetics and adjuncts)
ANTAGONISTS: bind to and don’t stimulate CNS (reversal agents)
Why do we typically combine anesthetics?
no single agent provides all desirable properties both rapidly and safely
- maximizes benefits of each drug
- minimizes adverse effects (lower dose and concentration)
- allows anesthetist to produce CNS depression, immobilization, and pain relief appropriate for the patient and procedure
What are 2 major cautions that should be noted with combining anesthetics?
- don’t mix drugs in a single syringe unless they are compatible
- don’t administer a drug combination if a precipitate develops when the drugs are mixed
What is unique about the mechanism of action of injectable anesthetics?
exact mechanism is not known and no specific receptor has been identified
What argues against the existence of a single receptor for anesthetics?
chemically unrelated compounds are all able to produce anesthesia
What don’t anesthetics provide? How are they administered?
analgesia or muscle relaxation (pre-anesthetics!)
IV to effect based on patient (titration)
What are examples of barbiturates, non-barbiturates, and dissociative agents used as anesthetics?
BARBITURATES: Thiopental*, Methohexital, Pentobarbital, Phenobarbital
NON-BARBITURATES: Propofol, Etomidate, Alphaxalone
DISSOCIATIVE: Ketamine, Tiletamine
What are Barbiturates?
a group of sedative-hypnotic medications used for the treatment of seizures, preoperative anxiety, and inducing anesthesia (weak analgesic)
- controlled
- no reversal agent
What are the 3 classifications of Barbiturates based on duration of action? What are examples of each?
- ULTRA-SHORT: Thiopental, Methohexital - dogs cats, horses to induce general anesthesia
- SHORT: Pentobarbital - lab animals to induce general anesthesia and treat epilepsy
- LONG: Phenobarbital - anticonvulsant and sedative
What are the 2 classifications of Barbiturates based on chemical structure? How does the difference in structure affect each group?
- OXYBARBITURATES: Methohexital, Pentobarbital, Phenobarbital
- THIOBARBITURATES: Thiopental, Thiamylal
- thiobarbiturates are more lipid soluble
How does lipid solubility of Barbiturates affect their pharmacokinetics?
high lipid solubility = quickly enter the CNS and depress its function with quick redistribution into other tissues (skeletal muscle and adipose tissue)
What affect do Barbiturates typically have on the respiratory system?
- apnea
- coughing
- chest wall spasm
- laryngospasm
- bronchospasm
What is the mechanism of action of Barbiturates?
not fully understood - bind to GABA-gated Cl- channels resulting in hyperpolarization of neurons
- mimics inhibitory effects of GABA to cause CNS depression and loss of consciousness
When will the effects of Barbiturates terminate?
agents leave brain or are metabolized, excreted, or redistributed
Barbiturates are used for rapid anesthetic induction. What are 2 things do they allow for? How is thiopental and methohexital sustained during the procedure?
- intubation - thiopental and methohexital
- used alone for short procedures
- THIOPENTAL: with inhalation anesthetic
- METHOHEXITAL: with repeated doses or continuous infusion
What 4 properties affect the potency, onset, and duration of action of Barbiturates?
- IONIZATION - non-ionized form makes for easier absorption
- PROTEIN BINDING - only unbound drug free of plasma proteins are able to have an effect
- LIPID SOLUBILITY - tendency of the drug to dissolve in fats, lipids, and oils
- REDISTRIBUTION - ability of blood to carry drug to brain and other tissues
How do ultra-short-acting barbiturates compare to short-acting and long-acting ones with respect to lipid solubility?
ULTRA-SHORT = high solubility (rapid tissue distribution)
SHORT = moderately soluble
LONG = low solubility
Where are barbiturates most quickly distributed to? When will their effects begin/end?
vessel-rich tissues
- begin = when drug reaches target tissue (brain)
- end = drug leaves tissue when blood level drops, carrying drug to other tissues where it can be released and eliminated (animal recovers)
What are the 5 steps to barbiturate redistribution?
- ultra-short-acting drug is given IV and travels to the brain, where it is able to cross the BBB quickly due to its high lipid solubility
- animal loses consciousness
- once the levels in the brain are higher than in the blood, the molecules will move back down the concentration gradient and re-enter circulation
- molecules redistribute to muscle, fat, and other body tissues, allowing the patient to recover
5 drug is released from muscle and fat and eliminated from the body by liver metabolism and excretion in urine
What are the 2 major pharmacological effects of barbiturates in the CNS?
- mild sedation to unconsciousness
- possible excitement at low doses (prolonged Stage 2 of anesthesia)
What are the 3 major pharmacological effects of barbiturates in the cardiovascular system?
- cardiac depression
- increased cardiac sensitivity to epinephrine
- THIOPENTAL - cardiac arrhthymias
What are the 3 major pharmacological effects of barbiturates in the respiratory system?
- decreased respiratory rate and tidal volume
- THIOPENTAL - brief apnea
- PENTOBARBITAL - shallow breaths
- respiratory acidosis and poor tissue oxygenation
What are 3 other pharmacological effects of barbiturates on other body systems?
- initial decreased motility in the GI tract followed by later increased motility
- sneezing, coughing, laryngospasm
- incomplete muscle relaxation
What are common adverse effects of barbiturates in the cardiovascular and respiratory systems?
CV: cardiac arrhythmias (Thiopental), skipping a beat (bigeminy)
RESP: initial apnea, neonate respiratory depression in C-sections (dose- and administration-dependent)
In what animals should barbiturates be used cautiously?
- SIGHTHOUNDS (not enough muscle/fat for redistribution)
- critically ill
- hypoproteinemic
- acidotic
How can route of administration of barbiturates cause adverse effects?
- not IV = tissue irritation and sloughs
- intra-arterial = vasoconstriction, pain, tissue necrosis
In what 3 situations can excitement during induction of barbiturate anesthesia happen? How can it be overcome?
- perivascular injection
- very slow rate of administration
- stage II excitement as a result of insufficient concentrations in the brain to induce stage III
administer more drugs
What barbiturate can commonly cause excitement as the patient is recovering? What are common signs? How can this be overcome?
Pentobarbital
paddling and vocalization
administer IV Diazepam or pre-anesthetics
What are 3 common barbiturate-drug interactions?
- enhances muscle relaxants
- increases hepatic enzyme activity, causing shorter duration of activity of drugs metabolized in the liver (opioids, diazepam)
- administration with chloramphenicol enhances the effect of pentobarbital and phenobarbital
In what animals is Thiopental typically used? How should the dosage be adjusted in debilitated and heavily sedated animals?
small animals and horses
give to effect - dose reduction
Methohexital is very similar to Thiopental. What makes it different?
higher in lipid solubility, making it useful in unfasted animals and greyhounds/other sighthounds
In what animals is Pentobarbital most commonly used in? Why has usage decreased?
lab animals to treat status epilepticus (IV) and preform euthanasia
- narrow margin of safety
- replaced by propofol
What is the most commonly used anesthetic in vet med? How quickly is it able to act? In what cases is it best?
Propofol (non-barbiturate)
ultra-short acting (highly lipophilic)
outpatient cases —> onset is smooth and rapid
- small animals, small ruminants, exotic animals, neonates of all species
What is the mechanism of action of Propofol? What are some major benefits to its use over barbiturates?
activates GABAa receptors (similar to barbiturates)
- onset = 30-60 secs
- complete and quicker recovery
- safe to use in animals with head trauma or increased intracranial pressure
Why should Propofol be used cautiously in cats?
cats may not tolerate prolonged infusion well
Why does Propofol have poor storage characteristics?
available in an egg lectin, glycerin, soybean oil aqueous solution which can support bacterial growth, making aseptic technique necessary
- discard unused drug within 6 hr of opening
- 3 year shelf life if unopened
- more expensive than ketamine, diazepam, and thiopental
What are the pharmacological effects of Propofol on the CNS, cardiovascular system, and respiratory system?
CNS: dose-dependent depression, poor to no analgesia, euphoric feelings
CV: cardiac depressant, transient hypotension
RESP: depressant with possible apnea
What are 6 other pharmacological effects of Propofol?
- twitching during induction (dogs)
- muscle relaxation
- safe in animals with liver or kidney disease
- appetite stimulant as low doses
- antiemetic
- decreases intraocular and intracranial pressure
What are possible adverse effects of Propofol in the CNS, cardiovascular system, and respiratory system?
CNS: transient excitement and muscle tremors on induction, paddling, muscle twitching, nystagmus, opisthotonus (resembling seizures)
CV: hypotension
RESP: apnea with rapid injection of high doses
What are 2 other possible adverse effects of Propofol? Specifically in cats?
- seizure-like signs (treat with diazepam)
- pain with injection (no perivascular injection tissue damage)
with multiple doses: anemia, diarrhea, anorexia, blindness, aggression, prolonged recovery, death
What is Etomidate? When is it commonly used?
sedative, hypnotic non-barbiturate of ultra-short duration with a high margin of safety
as an alternative to thiopental and propofol, specifically in animals with preexisting cardia dysfunction, head trauma, or critical illness
What is the mechanism of action of Etomidate? What are 2 possible adverse effects?
binds to GABA receptor and allosterically enhances the affinity of GABA to its receptor
- pain and hemolysis on IV injection
- may inhibit myocardial contractility
What pharmacological effects does Etomidate have on the CNS, cardiovascular system, and respiratory system? What effect does it have on hormones?
CNS: decreases cerebral blood flow, metabolic rate, and oxygen consumption
CV and RESP: minimal depression
- inhibits adrenal steroidogenesis reducing the normal increase in plasma cortisol levels during anesthesia and surgery
What is Alphaxalone? What is it mechanism of action?
synthetic neuroactive steroid wih rapid, short-acting general anesthetic effects
GABAa receptor agonist
What are 3 common situations when Alphaxalone is used? What are 3 possible adverse effects?
- short procedures
- induction of anesthesia and transition to an inhalant
- used as a constituent of anesthetic drug mixtures
- dogs and cats
~ respiratory depression when given with other sedatives and anesthetics
~ apnea
~ animals tend to become irritated during recovery
