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83 Cards in this Set
- Front
- Back
Increasing lipid solubility of injectable agents results has what affect on duration of action?
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makes it shorter acting
(because redistributed very easily, e.g. readily leaves circulation enters tissue) |
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EFFECTOR SITE FOR INJECTABLE ANAESTHETICS IS ?
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the brain...this mean must cross BBB via circulatory system
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IDEAL INJECTABLE anaesthetic should hydrophilic or lipophilic?
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should be highly lipid solubility (cross membranes faster), but in water-soluble formation
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______ compounds cross blood brain barrier (BBB) faster
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smaller molecular weight
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Following IV administration, plasma concentration falls due to:
(2) |
1. Redistribution to….
vessel rich tissues muscle fat 2. Elimination metabolism excretion * recovery seems to be predominantly due to redistribution |
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distribution depends on what three things?
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organ perfusion
protein binding lipid solubility |
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Which route of administration usually yields more predictable effects, while allowing a lower dose to be used?
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Intravenous
* rapid onset * lower dose * predictable effect |
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Which route of administration used for:
- slower onset - higher dose in small volume - less predictable effect - no secure venous access - must be non-irritant |
Intramuscular
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propofol, alfaxalone are examples of?
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STEROIDS
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Name the BARBITURATES (2)
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* thiopental
* phenobarbital ~ Pentobarbitone and methohexitone are no longer available as injectable drugs, so discussion will be restricted to mostly thiopental |
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____ are almost insoluble in water and require complex vehicles to render them suitable for injection
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STEROIDS
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Name 2 DISSOCIATIVE AGENTS
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ketamine, tiletamine
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Name a IMIDAZOLE DERIVATIVE
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etomidate
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Long acting Barbiturate?
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Long duration of action -> PHENObarbital
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Ultra-short acting Barbiturate?
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THIOPENTAL
methohexitone~(no longer used as injectable) |
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Formulation of Thiopentone is acidic or alkaline? ~pH?
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solution is very alkaline pH 10.5...but drug itself is a weak organic acid
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actual drug is a weak organic acid but it is prepared as a sodium salt buffered by sodium bicarbonate, mixed with anhydrous sodium carbonate to 5% (large animals only) or 2.5% solutions.
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Thiopentone
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Which of following can only be administered via IV? Why?
PROPOFOL THIOPENTAL ALFAXALONE KETAMINE ETOMIDATE |
THIOPENTAL
PROPOFOL ETOMIDATE Because painful irritants? Ketamine is also painful injection but can be given IV, IM, SC,PO, maybe b/c has analgesic effects, very lipid soluble, and also partially water soluble |
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Why is the fact that thiopental is highly alkaline (pH 10.5) significant?
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* concentrations greater than 2.5% are highly irritant to tissues
* pH of blood is 7.4 (less ionized at this pH) * also PH MAKES IT BACTERCIDAL * immiscible with acidic drugs; precipitation occurs |
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Barbiturates interact with what receptor?
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GABA receptor; they are GABA'ergic....mimics GABA
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Which of following can be given IM?
PROPOFOL THIOPENTAL ALFAXALONE KETAMINE ETOMIDATE |
ALFAXALONE (IM or IV)
KETAMINE (IV, IM, SC,PO) |
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Are GABA nt's (and barbiturates) inhibitory or excitatory in nature?
How so? |
inhibitory neurotransmitter
open Cl- channel allowing it to rush and hyperpolarize membrane...inhibiting neuronal depolarization... |
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Which is more lipid soluble thiopental or ketamine?
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Ketamine 5X more lipid soluble than thiopental!
Ketamine is also partially water soluble so will have effect when administered IV, IM, PO |
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Is thiopental lipid soluble? how does this affect duration of action?
recovery of consciousness is primarily a function of? |
yes very lipid soluble, so short induction, also very short duration of action
recovery of consciousness is by redistribution (not elimination, b/c metabolized slowly) |
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is thiopental protein bound?
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yes
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How long can a freshly prepared bottle of thiopentone be stored?
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7 hours
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Is the ideal anesthetic agent long or short acting?
which barbiturate drug makes better injectable agent for surgery? |
short acting, can be readily adjusted by changing the administration rate
thiopental |
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Is the ideal anticonvulsant drug long or short acting? (common sense)
which barbiturate drug makes better anticonvulsant drug? |
long acting...stopping convulsions for 30 seconds isn't going to do a whole lot of good
phenobarbital |
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Cardiocasular effects of thiopentone?
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* vasodilation (mediated via depression of the medullary vasomotor centre)
* hypotension * decr. vasculation resistance * decr. CO |
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Is thiopentone an analgesic?
intracranial affects? |
NO
depresses cerebral oxygen consumption (CMRO2) and intracranial pressure (ICP) |
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Respiratory effects of thiopentone?
Due to reduced sensitivity of ____? |
• Respiratory depression - of both rate and tidal volume.
due to reduced sensitivity of the respiratory center to CO2 |
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Disadvantages of thiopentone?
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* CUMULATIVE – Accumulates after repeated doses; prolong recovery (so giving via CRI not good idea)
* hyperalgesic * tissue irritation and sloughing on perivascular injection * solutions don’t mix with other drugs (esp. acidic drugs) |
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Give me names of 2 Injectable Anesthetics-Steroids!
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Propofol
Alfaxalone (Alfaxan-CD)(Saffan is old formulation, w/different vehicle; no longer licensed) |
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Speed of onset of propofol=
Speed of onset of alfaxolone= |
60-90 seconds
• Relatively rapid onset of anaesthesia. Slower onset than propofol; advised to administer for +60 seconds, to optimize predictable uptake into target tissue (brain), and thus achieve general anaesthesia using the minimum dose. |
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Is alfaxalone considered ‘safer’ for hypoalbuminaemic patients than propofol?
Why? |
• 30-50% protein bound: ‘moderately’ protein bound so considered ‘safer’ for hypoalbuminaemic patients
* in contrast, propofol is 98% protein bound! |
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Don’t use _____ in sight hounds (Greyhounds, Whippets, and Afghans etc.)
Also slow recovery in ______. |
Don’t use thiopentone in sight hounds
genetic hepatic metabolic defect in first step of hepatic metabolism Also slow recovery in thin animals |
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Can alfaxolone be administered via CRI? If not, why?
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alfaxolone is relatively non- cumulative so can be administered as a controlled rate infusion
also TIVA, IV, IM (IM administration requires large volumes) |
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. Principal mechanism of recovery following induction of alfaxalone= ?
What else can you say about the recovery process? |
• Rapid recovery through redistribution and rapid metabolism
• -> recovery can sometimes psychomotor excitement w/hypersensitivity to stimuli, paddling and muscle tremors |
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Contraindications of Propofol
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Cats-deficiency in glucuronide synthetase enzyme; hypoalbuminemic patients (b/c 98% protein bound!!!)
Also cats have poor capacity for triglyceride metabolism in general VERY slow to recover, esp. from CRI |
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Contraindications of alfaxalone
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Contraindicated in cats
occasional anaphylactoid reactions in cats - swollen pads Also cats have poor capacity for triglyceride metabolism in general |
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Propofol and Alfaxalone are agonist of ____?
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GABA agonists
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What steroid is NMDA/glutamate/glycine antagonist??
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Propofol, but it's GABA agonist
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CNS effects of alfaxolone?
How does it act? Analgesic effects? |
• Alfaxalone is a neuroactive steroid; acts on chloride ion transport by binding to central GABA-A receptors.
• NO analgesic activity; use w/analgesic premed for surgical interventions. |
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Which of following causes LEAST respiratory depression?
A. thiopental B. alfaxolone C. propofol |
B. alfaxolone
less respiratory depression than thio/ propofol |
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Which of following is good muscle relaxant?
A. thiopental B. alfaxolone C. propofol |
B. alfaxolone
C. propofol |
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Name Imidazole derivative
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• Etomidate
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Mechanism of action of ETOMIDATE anesthesia? Similar to what?? Depressed what?
Agonist of? |
ETOMIDATE = GABA’ergic: mode of anaesthetic action is similar to PROPOFOL
also depresses RAS |
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Effects of Etomidate on CNS and cranium?
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* depresses RAS like propofol
* like all most injectables decreases intracranial pressure * reduces cerebral blood flow while maintaining mean arterial BP, so that cerebral perfusion pressure is maintained * Myoclonus (invol. muscle twitching) |
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Rarely if ever administered alone, Ketamine is commonly used in combination with _____?
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benzodiazepines, ACP and a2 agonists.
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True or false:
Both Propofol and Alfaxalone are characterized by rapid induction and rapid metabolism? |
• TRUE
FYI: But recovery from Alfaxalone can sometimes involve psychomotor excitement w/hypersensitivity to stimuli, paddling and muscle tremors |
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What are some adverse effects of etomidate in animals? Are these effects clinically significant?
Other adverse effects? |
Temporary suppression of ADRENOCORTICAL function
Significant inhibition of adrenal synthesis of cortisol, aldosterone, and corticosterone (But effects usually short-lived; only significant in animal with adrenal insufficiency) Like propoforol, causes pain on injection..can reduce this by injecting a low dose of dilute lidocaine immediately beforehand. |
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Which drug is recommended to use heavy sedation prior to induction, or co-administer with benzodiazepine or opioid and is generally reserved for use in high-risk patients?
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Etomidate
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1. What are cardiovascular effects of ETOMIDATE?
2. What are cardiovascular effects of propofol and thiopental? |
1. In contrast to other injectable agents, etomidate has minimal effects on cardiovascular ****
2. propofol and thiopental both cause vasodilation, decr. CO, decreased vascular resistance |
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When would Intraperitoneal agents be approriate?
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small furries with tiny veins
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Which Injectable agent does following refer?
* clearance of _____ exceeds hepatic blood flow - are additional extrahepatic metabolic pathways– pulm., renal, sm.intestine • Recovery smooth and rapid (excepting cats), w/in 5-8 min. • No ‘hangover’ after awaken |
PROPOFOL
* alters mood less (less negatively?) than thio and promotes feeling of well being by increasing dopamine levels * awaken contented and "amorous" |
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Aside from making patients feel contented, what are CNS effects of PROPOFOL?
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• enhances GABA activity (hypnosis)
• inhibits NMDA activity • NO effect on pain perception • Reduces cerebral metabolic oxygen requirement (CMRO2) • reduces pressure • strong anti-convulsant & anti-emetic effects |
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Where does name for dissociative drugs come from?
Are KETAMINE & TILETAMINE good muscle relaxants? |
Humans feel "dissociated", hypnotic/cataleptic (muscle rigidity) effects in animals
NO, ketamine incr. muscular tone, and tiletamine can cause spasms; that is why rarely used alone |
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Which Injectable agent does following refer?
Wide safety margin. Acute tolerance studies showed that with ventilatory support, dogs survived 10X clinically effective dose of ____, cats 5X clinically effective dose. |
Alfaxalone (alfaxan-CD)
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What drug has similar CNS, cardiovascular, and respiratory effects to ketamine and maintains good CV and respiratory function?
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Telazol (Tiletamine/Zolazepam)
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Which Injectable agent matches this description/indication?
Routes of administration of _____= effective when administered IV OR IM and so used for darting wild animals and IM induction of feral cats, aggressive dogs. • In wild animals and certain domestic species, it is typically administered IM without prior premedication |
TELAZOL: TILETAMINE/ZOLAZEPAM
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Onset of ETOMIDATE?
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• Very rapid onset – highly lipid soluble, large un-ionised fraction at pH 7.4
• Rapidly penetrates BBB, unconsciousness within one arm-brain time (60-90 sec), similar to propofol |
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Recovery of ETOMIDATE is predominantly due to ?
elimination half-life is long or short? what route of administration? |
redistribution
relatively short elimination half-life and rapid clearance...suitable for CRI or single injection |
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How does rate of biotransformation of etomidate compare to thiopental?
is metabolite active? Is etomidate protein bound? |
five times faster than thiopental; metabolite is not active
yes, highly protein bound |
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Is ketamine a good choice for anaesthesia for head trauma or neurosurgery patients?
Is ketamine a good choice for glaucoma patients? |
No, bad choice - because ketamine increases intracranial pressure
Do not use in glaucoma patients, increases intra-ocular pressure |
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Does ketamine need to be used in combination with another drug with muscle relaxant properties?
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Yes
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What dissociative agents primary site of "anesthetic" action is the thalamoneocortical projection system, increases salivation and has NMDA receptor antagonism and effects on non-NMDA glutamate receptors?
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Ketamine
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Which of following do NOT have rapid elimination?
PROPOFOL THIOPENTAL ALFAXALONE KETAMINE ETOMIDATE |
THIOPENTAL
KETAMINE: prolonged after multiple top-ups |
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Which injectable anasthetic agent forms active metabolite in liver?
What kind of metabolism? Name of metabolite? |
Ketamine is metabolized in the liver by demethylation (cytochrome p450 system) into nor-ketamine (active metabolite) !!!
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What are some of the cardiovascular effects of ketamine?
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Unlike other injectable - stimulates CVS, INCREASES BP, CO & HR
This Increases myocardial work; overrides myocardial depressant effects May put unwanted stress on a diseased CV system (Do not use in congestive heart failure or animals with severe hypertension) |
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What are some advantages of "S" ketamine?
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Less adverse side effects
4 times more potent |
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Why does 10% ketamine sting when injected?
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pH 3.5
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What are some contraindications of ketamine?
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Head trauma or neurosurgery patients
Increases intraocular pressure (glaucoma) Certain cardiovascular disease hepatic or renal disease o urinary obstruction Animals at risk of seizuring |
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Solvent in which alfaxalone supplied (as Alfaxan-CD)?
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• Alfaxalone is solubilised in CYCLODEXTRIN
(non-toxic polysaccharide solubilising agent which does not stimulate histamine release as predecessor 'Saffan' did) |
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Which Injectable agent does following refer?
The mixture standardly contains NO preservatives and thus is a perfect medium for bacterial growth. For this reason ____ must be discarded after 12 - 24 hours/ at the end of the day, CERTAINLY NOT stored at room temperature and re-used. |
PROPOFOL
prepared as a 1% or 2% emulsion in 10% soybean oil, 2.25% glycerol, 1.2% purified EGG phosphatide at pH 7 |
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____ is a chiral molecule; how so?
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ketamine;
standard commercial preparation is a racemic mixture of S (+) and R (-) ISOMERS |
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This drug causes "functional disorganization" of the thalamus and the limbic cortex
• also blocks transmission of impulses in the medial reticular formation, which transmits the affective emotional components of nociception from spinal cord to higher centres |
Ketamine
What other inj. agents affect RAS? |
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Zolazepam is a _____(enter drug class), contributing sedation, hypnosis, muscle relaxation, anxiolysis, and sedation
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benzodiazepine
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Behavioral effects common during recovery from TILETAMINE/ ZOLAZEPAM anaesthsia:
In dogs and cats? |
In dogs and cats, recoveries are typically prolonged and rough, with the possibility of convulsions.
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True or False: Telazol can cause these adverse effects?
• Causes salivation • Causes muscular spasms and poor muscle relaxation for surgery • Can vomiting • Causes unpleasant emergence reactions • Induces tachycardia and hypertension |
True
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Telazol/ Zoletil combined with an α2 agonist (typically xylazine) is an effective, potent and popular anaesthetic in ___.
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pigs
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Which drug wears off first in cats: TILETAMINE or ZOLAZEPAM?
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In cats, Zolazepam outlasts tiletamine.
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Which drug wears off first in dogs: TILETAMINE or ZOLAZEPAM?
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In dogs, TILETAMINE’s effects outlast zolazepam’s and so recovery is prolonged, violent, noisy, etc.
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Contraindications to Zoletil?
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> Identical to ketamine
• Associated with severe cardiac or respiratory decompensation in compromised animals • AVOID in animals with pancreatic deficiency, severe renal or hepatic dysfunction |