Exam 1: Injectable Anesthetics

How are injectable anesthetics generally defined

• a drug administered via parenteral route and produces a state of hypnosis or katalyepsy

• used or induction or maintenance of anethesia

• agents such as Propofol, Etomidate, Thiopental can only be administered IV

• others multiple routes

• intraperitoneal route is listed in literature but not reccomended

what are the properties of an ideal injectable anesthetic

• water solubel

• long shelf life

• stable when exposed to light

• small volume required for induction

• safe therapeutic ratio

• short duration of action

• metabolized to non-toxic metabolites

• absence of hisamine release and anaphylaxis

• minimal CV and resp effects b

• no cumulative effects

what factors of an injectable determine anesthetic effect

• blood flow to the brain

• amount of non-ionized drug that crosses BBB- affected by the pat acid base status

• degree of protein binding (want more unbound)

• lipid solubility of the drug

• redistribution to other tissues

• metabolism and elimation

what is the purpose of a solvent or additive

• making the drug bioavailable

• presever the drug

what injectibles are water based

thiopental sodium

what injectibles have solvent propylene glycol (making solution hyperosmolar risking thrombophlebitis)

• Diazepam

• etomidate

what injectible is lipid emulsion

propofol (contains egg and soy)

what injective is formulated with Cyclodextrin

alfaxalone

what are the major groups of GABA(a) agonists

• barbituates

• phenols

• Neurosteroids

• imidazole derivatives

• primary target leading to anesthetic effect of all IV anesthetics except Ketamine and Tiletamine

how is thiopental generally descried

• classified as ultra short barbituate

• duration of action 20 minutes

• distrubutes rapidly within the IV space to highly perfused tissues including the brain

• redistributes to muscle and fat

• when it is redistributing, metabolism starts

what are the pharmacokinetics of thiopental

• liver metabolism via cytochrome P-450 enxyme

• action of a single bolus is terminated primarily by redistribution to the muscle and fat

• adipose tissue provides a large reservoir for delayyed drug uptake with prolonged administration or repeated doses

what is the major MOA of thiopental and cardiovascular side effects

• GABA(a)

• peripheral vasodilation, decreased preload, myocardial contractility, CO and BP

• increased HR

• causes VPCs via ventricular bigeminy contractions

• potent central respiratory depressant

• decreases renal/hepatic blood flo

what are the effects of Thiopental on the CNS

• excellent anticonvulsant properties

• decrease CBF

• decrease cerebral metabolic oxygen requirements

• decreases ICP and IOP

what are the other effects of thiopental

• splenic engorgement

• rough recoveries when used alone

• highly protein bound

what are extremely thin pt and sighthounds prone to prolonged recovery with thiopental

• relatively deficient in hepatic microsomal enzymes for the drug metabolism

• lack body fat, so drug remains in circulation longer

what is the MOA of propofol

• potentiates GABA inhibitory effects in CNS

• potentiates glycine at GABA receptors

• inhibits NMDA receptors with no analgesic properties

how is propofol generally defined

• short acting phenol

• lipophilic compound

• one bolus has 5-10 minute duration of action

  • oil/water emulsion is excellent medium for microbial growth so avoid contamination

what are the pharmacokinetics of propofol

• rapid redistribution to highly perfused tissues, especially the brain

• immediate onset, highly protein bound

• hepatic and extrahepatic (lungs, ± blood and GI) metabolism

• clearance is NOT affected by hepatic or renal dysfunction

• poor cumulative properly and canaccumulate in the body after hours of infusion or if given to cats for 8+ hrs

what are the effects of propofol on CNS

• anticonvulsant properties

• decreases CBF, CMRO2, ICP

• significantly reduces cerebral perfusion pressure in patients with increased ICP

• provides quiet and very smooth recovery

• good muscle relaxant, may cause myoclonic movements/opisthotonos

• no analgesia

what are the effects of propofol on the CV

• decrease arterial blood pressure

• decreases systeic vascular resistance and cardiac filling

• minimal change in HR

• no arrhytmogenicity

what is the effect of propofol on the respiratory system

• potent respiratory depressant

• may cause apnea for 30-60 seconds following induction

• apnea depends on dose and speed

what are the other effects of propofol

• may cause pain on injection- small veins or extravascular

• successfully used in pregnant patients

• appetitie stimulants and antiemetic

• promotes “well being feeling” at recovery

how is propofol oil in water macroemulsion described

• propofol, soybean , glycerol, egg phosphatide

• highly lipid soluble

• milky white substance

• no preservative, 6hr shelf life after opened

what is the preservative used in propofol oil in water macroemulsions +preservative “propofol 28”

benzyl alcohol

shelf life 28 days

cats lack required liver metabolism

accumulation may lead to toxicity

not recommended for CRIs in cats

what general precautions should be taken with propofol

• caution with severely hypovolemic or those with hypotension

• caution with its use for sedation without tracheal intubation

• may produce heinz body anemia from prolonged infusions in cats

what is the MOA of alfaxalone

• agonist at GABA receptors

• can be used IV r IM off label

what are the pharmacokinetics of Alfaxalone

• short acting neurosteroid (progesterone like)

• lipophilic with rapid redistribution to highly perfused

• fast onset of action after IV administration,

• 5-10min onset after IM

• one IV bolus lasts 5-10 minutes

• hepatic metabolism

• elimation by hepatic/fecal/renal

what are the effects of alfaxalone on CNS

• decreases CBF, CMRO2, ICP

• good muscle relaxant, may cause muscle tremors and paddling during recovery when used in high doses or repeatedly or as only sedative

• inititially not recommended IM in dogs by itself, + Midazolam and opioids improves

• no analgesia

what are the cardiovascular effects of alfaxalone

• no effect on CO or BP at clinical doses

• doses >10mg/kg causes decrease in CO and BP, decrease in systemic vascular resistance

• no arrhythmogenicity

what are the respiratory effects of alfaxalone

• potent respiratory depressent like propofol

• ± apnea

• decreases RR, minute volume, PaO2 when used in high doses

what are the indications for using alfaxalone

• IV induction even for animals with cardiac dysfunction

• IV maintenence (TIVA)

• Im sedation and short anesthesia for cats

• used in canine C sections but propofol beter

• consider that its more expensive than propofol and ketamne

what is the common formulation of alfaxalone

• cyclodextrin

• 1% alfaxalone

• clear substance

• hyperosmolar

• multidose vial

what is the MOA of etomidate

• GABA receptor agonists

• facilitates inhibitory synaptic transmission at GABAergic synapses

• potentiates the neurotransmitter GABA

what are the pharmacokinetics of Etomidate

• Imidazole derivative

• insoluble in water

• high osmolality solution in 35% proppylene glycol- higher doses or CRI can cause hemolysis and thrombophlebitis

• rapid onset and redistribution

• DOA = 5 min

• wide therapeutic index

• liver metabolism

• elimation via urine, bile and feces

what are the effects of etomidate on the CNS

• causes central vasoconstriction decreasing CBF and CMRo2

• decreases IP and IIOP

• does not provide muscle relaxion, myoclonus or tremors may occur

• no analgesia

what are the effects of etomidate on the CV

• very CV stable

• non-arrhythmogenic

• recommended fr pt with CHF

what are the respiratory effects of etomidate

• minimal resp depression

what are the other effects of etomidate

• pain on injection

• no significant effects on hepatic or renal functions

• 75% bound to plasmatic albumin, caution with low total protein

• adrenal suppression, not for immunosuppressed

what are the contraindications for etomidate

• adrenal suppression lasts 6hrs in dogs and 5hrs inc ats, do not use in addisons pt

• do not use as CRI

• expensive compared to propofol

what is a dissociative injectible

• ketamine and tiletamine

• cataleptic like state of unresponsiveness due to dissociation between thalamocortical and limbic systems

• analgesia

• amnesia

• anesthesia

• hallucinations

what is the MOA of ketamine

• inhibition of excitatory synaptic transmission → NMDA receptor antagonist

• also acts as opioid, monoaminergic, and muscarinic receptors agonist

generally define ketamine

• phecyclidine derivative

• racemic mixture

• extremely lipophilic and rapidly crosses BB

• DOA= 10-15 min

• usually used in combination with muscle relaxant to offset muscle rigidity

what are the pharmacokinetics of ketamone

• hepatic metabolism and produces an active metabolite Norketamine with parent effects
  -further metabolism by glucuronidation in most species (not cats)

  • renal elimation → most inactive, cats active

what are the effects of ketamine on CNS

• increase cerebral blood flow and thus ICP, potent cerebral vasodilator

• causes muscle rigidity when used alone, may cause seizure like activity in dogs but does not decrease seizure threshold

• causes mydriasis and nystagmus

• excellent analgesia

what are the CV effects of ketamine

• increase sympathetic outflow due to release of catecholamines

• increases HR, maintaining or increasing blood pressure and CO

• catecholamines’ exhaustion causes direct depressent on myocardium

what are the respiratory effects of ketamine

• mild resp depression and apneustic breathing

• bronchodilation reducing airway resistance

• airway protective reflexes maintained, could not intubate on just this

• increases pulmonary secretions

what are the common uses of ketamine

• induction of healthy pt

• capture of wild animals

• used as CRI for chronic pain management

what conditions contraindicate ketamine

• glaucoma

• hypertrophic cardiomyopathy

• hepatic dysfunction

• renal dysfunction in cats

• C section, decreases neonatal vigor

• caution with increased ICP pt

how is telazol described

• 50-50 tiletamine and zolazepam

• similar kinetics to ketamine

what are the pharmacokinetics of telazol

• longer lasting 40 min

• increases SNS outflow, maintains HR, BP and CO

• decreases tidal volume, hypoxemia

• increases CBF, ICP and IOP

• rapid onset

• great muscle relaxation from zol

• may cause different quality of recovery

what are the recovery issues with telazol

• recovery may be prolonged in some animals after IM

• Tiletamine typically lasts shorter tan Zolazepam in horses, pigsma d dogs causing smooth recovery

• cats have rough recoveries due to Tiletamine lasting longer than zolazepam

what are the contraindications of telazol

• increased ICP

• convulsions and seizures

• severe hepatic or renal disease

• pt with pre-existant respiratory depression

• cardiac disease in which tachycardia is undesired

how is guaifenesin described

• central muscle relaxant, not classified as anesthetic

• does not cause hypnosis by itself, acts in internucial neurons of spinal cord and brainstem

• used as co-induction agent with ketamine in horses and rum

• used as part of TIVA triple drip in horses, double in farm (bovine more sensitive to xylazine