Pharmacology I- General Anesthetics – Flashcards
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General Anesthesia
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A state of unconsciousness with lowered sensitivity to external stimuli
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Balanced Anesthesia:
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combination of unconsciousness, analgesia, and muscle relaxation. Preferred method of balanced anesthesia is achieved through use of small doses of different drugs.
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Anesthetic Protocol:
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Premedication- sedative & analgesic Induction- injection anesthetic Maintenance- inhalation anesthetic & oxygen (muscle relaxant) Recovery: analgesic (antibiotics)
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Pros and Cons of Injectable Anesthetics
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Pros: rapid onset, rapid control of airway, IM injection, minimal equipment Cons: no control over waking, controlled substances
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Barbiturates-Drugs
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Thiobarbiturates (thiopental), Oxybarbiturates (phenobarbital, pentobarbital, methohexital)
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Barbiturates- Mechanism of Action
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potentiates GABAa receptors
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What two pharmacological effects of barbiturates are dose-dependent?
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CNS depression- sedation, hypnosis, anesthesia, coma, death Respiratory depression- transient apnea
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What are the cardiovascular effects of barbiturates?
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hypotension- decreased stroke volume and cardiac contractility, vasodilation, reflex tachycardia
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Why shouldn't barbiturates be used in pregnant animals?
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May cause abortion/premature labor. Depression of uterine contractions and depression of fetal respiration.
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Barbiturates are very lipid soluble drugs, what is the implication of this?
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Redistribution; fat is a drug depot.
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Why wouldn't we use barbiturates on a greyhound
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Greyhounds are deficient in oxidative enzymes and are unable to metabolize barbiturates fully.
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What is a possible drug interaction when combining barbiturates and aminoglycosides such as gentamicin?
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Muscle relaxant effect is synergistic leading to flaccid paralysis
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Chloramphenicol is an enzyme inhibitor. How would this effect the dose of barbiturates?
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Barbiturates are enzyme inducers, with an enzyme inhibitor like chloramphenicol we would need to reduce the dose b/c of the reduced number of enzymes to metabolize.
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What are 5 clinical uses?
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sedation, induction of general anesthesia, anticonvulsants, euthanasia.
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What are some advantages for using thiopental? Disadvantages?
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reliable and cheap can only be given IV otherwise tissue irradiation or necrosis, short shelf life, narrow therapeutic index- give lowest dose possible to avoid overdose
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What is the most common use of pentobarbital?
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Euthanasia but can also be used in sheep and goats as an injectible anesthetic.
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Why is the protocol for using propofol "single use"
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preparations of propfol contain egg lecithin and soybean oil which is ideal for bacterial growth.
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What are the pharmacological effects of propofol on the CNS?
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dose=dependent depression, decrease intracranial and ocular pressures, decreases metabolic odygen consumption. Maintains cerebral autoregulation.
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Why is propofol a good anesthetic drug for CNS disease patients?
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Maintains cerebral autoregulation
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What is a cardiovascular effects of propofol?
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hypotension because there is vasodilation without reflex tachycardia
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How might propofol lead to acidosis?
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dose-dependent respiratory depression- mild hypercapnia
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How does propofol differ from barbiturates like thiopental in terms of pharmacokinetics?
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Propofol is distributed to all tissues and is a very lipid soluble drug. It is redistributed to muscle and then fat while thiopental and other barbiturates are redistributed to fat. Greyhounds are sensitive to both.
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What are some adverse effects of propofol?
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local pain on injection, increased wound infection, front leg paddling, opisthotonus, Heinz body formation in cats- presence of degraded hemoglobin in RBCs--> decreases oxygen transport. Excitement at induction.
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Neurosteroid that is very lipid soluble
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Alphaxalone
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What is the mechanism of action of alphaxalone?
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potentiates GABAa receptor
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Which injectable anesthetics are good choices for CNS disease patients?
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Alphaxalone, Propofol. Maintains cerebral autoregulation
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Cardiovascular pharmacological effects of alphaxalone?
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hypotension- decreased stroke volume and cardiac contractility, vasodilation, reflex tachycarida, histamine release. Decreases epinephrine-induced arrhythmias
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Alphaxalone is a good anesthetic in dogs and cats
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Fast induction (~1 min) and recovery (5-8 min). Maintenance (no accumulation)- repeated bolus, CRI
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Dissociative Agents-Drugs
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Ketamine, Tiletamine
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Dissociative Agents- response
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unresponsive to pain, muscle contraction (hypertonicity), swallowing reflex intact, eyes remain open
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Dissociative Agents- mechanism of action
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NMDA receptor channel blockade
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Pharmacological effects of dissociative agents
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thalamoneocortical (sensory perceptions), catalepsy, pharyngeal and laryngeal reflexes are maintained, eyes open and pupils dilated, consciousness not lost completely, analgesia. Bronchodilation, increase tracheobronchial secretions
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When would it be wise to use dissociative agent during anesthesia for minor surgery
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cardiovascular unstable or asthmatic patients, relative wide safety margin (5), tiletamine-zolazepam has wider safety margin in cats than dogs.
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What are the adverse effects of dissociative agents?
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respiratory depression at high doses, muscle tremors and hypertonicity, CNS stimulation and convulsions, vomiting, hypersalivation, pain at the injection site (IM administration), prolonged recovery.
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Why wouldn't you give a dissociative agent to a patient suffering from head trauma?
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Increased intracranial and intraocular pressure. Glaucoma
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What is the mechanism of action of Etomidate?
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potentiate GABA A receptor
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What are some pharmacological effects on the CNS of etomidate?
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dose-dependent depression, decreases intracranil and intraocular pressures, decreases cerebral blood flow, decreases metabolic oxygen consumption, maintains cerebral autoregulation, increase activity at epileptogenic foci
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Why would it be a good choice to use etomidate as an anesthetic in cardiovascular instability?
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it preserves cardiovascular system
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Adverse effects of etomidate:
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adrenocortical suppression, hemolysis, pain at injection
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Precautions/Contraindications of Etomidate?
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generalized tonic-clonic seizures, hypoadrenocorticism, liver/kidney disease, competitive neuromuscular blockers
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In what part of the anesthetic protocol is inhalation anesthetics?
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maintenance
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What are the pros and cons of inhalation anesthetics?
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Pros: control of airway, control of ventilation, control of drug uptake and elimination Cons: specialized (expensive) equipment, equipment failure
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How are inhalation anesthetics eliminated?
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Taken up by lungs, excreted mostly unchanged by the lungs, alvelolar concentration= brain concentration.
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Saturated Vapor pressure
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ability of the anesthetic to evaporate, different for different drugs, match drug with vaporizer
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Rubber and plastic solubility
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less tubing, less risk of interference, concern with older agents
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brain/blood coefficient
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concern with older agents
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blood/gas coefficient (solubility)
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Larger the blood/gas coefficient the longer the induction time.
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Ventilation:
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no breathing=no drug uptake
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Cardiac Output:
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no heartbeat= no systemic drug uptake. Shock-->decreased cardiac output
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MAC [Minimum alveolar concentration]
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concentration of anesthetic at steady state which will prevent purposeful movement in response to supramaximal noxious stimulus in 50% of individuals. - gives a good starting point for ventilator rate - alpha-2 or other sedatives have a MAC sparing effect meaning you can give less gas anesthetic to achieve the same level of anesthesia - Different for different drugs and species - ~1.3 MAC for maintenance: animal's state of excitement/pain, pre-medication
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Pharmacological Effects of inhalation anesthesia:
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CNS- depression, amnesia, immobility in response to noxious stimulus, predisposition to seizure activity, vasodilation Respiratory: dose-dependent depression: increased PaCo2, bronchodilation, airway irritation Cardiovascular: dose-related decreases of myocardial contractility: stroke volume and cardiac output, hypotension, alteration fo blood flow to organs, sensitization of the heart of catecholamines. Halothane has most prominent effect
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Inhalation Anesthetics- Drugs
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Halothane, Isoflurane, Sevoflurane, Desflurane, Nitrous oxide
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Why is halothane not the best inhalation anesthetics?
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respiratory and cardiovascular depression, most potent cerebral vasodilator, most arrhythmogenic-sensitizes the heart to epinephrine, hepatitis- decreased blood flow, humans (not animals), metabolite-immune mediated reaction
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What is the agent of choice for critically ill patients and for neurosurgery?
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Isoflurane
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Why is isoflurane a better choice of inhalation anesthetic than halothane?
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does not undergo metabolism (0.2%), less cerebral vasodilation than halothane, cerebral circulation autoregulation maintained, less cardiac depression similar to halothane, respirtory depression similar to halothane, liver and muscle blood flow less affected than with halothane, more potent than halothane to enhance the effects of competitive NMB
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Desflurane has the lowest blood/gas coefficient what are the implications of this?
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fast induction, change in depth, and recovery
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Nitrous oxide
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analgesic effects, poor anesthetic
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Second gas effect
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large proportion of the volume of gas moves from higher to lower tension until equilibrium Nitrious oxide-more fresh gas (and aneesthetic) moves to the alveolus-faster induction
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Fine effect-diffusion hypoxia:
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opposite to second gas effect, nitrous oxide-from blood to alvelous displacing alveolar gas.
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Inhalation induction: situation in which inhalation anesthetics are used to induce anesthesia:
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nasty animals, animals with no veins, neonatal animals, c-section
