General aneasthetics Flashcards
The stages and signs of general anaesthesia:
Stage 1: Disordered consciousness - Induction (stadium alangesiae)
Stage 2: Excitement (Stadium excitationis)
Stage 3: Surgical anesthesia (stadium anaesthesiae chirurgicae)
- ie: unconsciousness, amnesia, immobolity, unresponsive to surgical stimulation.
- “good-sleep”
Stage 4: Overdose (stadium paralysis respirationis)
- can lead to death if there is no special antidoteds
- used in euthanasia
Injectable anaesthetics:
Barbiturates:
- Pentobarbital, Mehtohexital, Hexobarbital, Thiopental, Thiamylal, Venobarbital
Imidazole anaesthetics:
- Etomidate, Medomidate
Steroid anaesthetics:
- Alfadolone, Alfaxone (in fix combination). (Alfaxane)
NMDAr antagonists (dissociative anaesthetics):
- Ketamine, Tiletamine
Others:
- Propofol, Propanidid, MgSO4, Chloral hydrate
Inhalational anaesthtics:
- Halothane, Isoflrane, Sevoflurane, Dinitrogen mooxide, Desflurane, Mehtoxyflurane
Properties of ideal injectable anaesthetics:
- water and lipid soluble
- sufficiently potent (volume)
- it should possess good analgesic activity
- it should produce muscle relaxation
- non-irritant to tissue
- rapid and safe induction and recovery
- it should have limited effect on vital functions (respiration and circulation)
- it should have high TI
- it should not have a direct reno- and hepatotoxicity
- Rapid metabolism (non-cumulative)
- neither chemical nor pharmacological incompatibility should occur
- it should have pharmacological antagonist.
Barbiturates - Mechanism of effects:
Mechanism of effects combined:
- GABA-BDZ-barbiturate-receptor complex (GABAa) allosteric act.
- further supposed effects: decrease in Ca accumulation -> inhibition in release of transmitters
- stabilisation of membranes
General inhibition, but sensitivity of certain structures differs
- paradox phenomenon, some are suitable for general anaesthesia
Pharmacological effects:
- CNS, circulation, respiration
Kinetics:
- pKa, lipophylicity, lipoid/water partition
- redistribution, metabolism
Classification according to the duration of action here: short acting, ultra-short acting
Apllications: only IV, effective and harmless
Barbiturates (ultra-short acting):
- Pharmacological effect, Pharmacokinetics
Pharmacological effect:
- unconscinousness
- muscle relaxation - good (eg. before incubation of tracheal tube)
- analgesia = not appropriate!
Pharmacokinetics:
- duration: I.V 15-60 min (short) 5-8 min (ultra.short)
- distribution: fast - complete, blood-brain barrier. Placenta -> foetus - pronounced side effect
- Re-distribution -> fat, muscle. CNS leave -> wake up
- Accumulation in fat - Do not re-adminstrate!! (can lead to overdose because of the fat storage!)
Barbiturates (ultra-short acting)
- Indication, contra-indications, Side effects
Indication:
- Induction, general anaesthesia (combination) (NO analgesi!!)
- convulsive state, epilepsy (pentobarbital IV)
- Euthanasia
Contra-indication:
- ypunger age (under 2 months), diminshed cardiac output
Side-effect: small therapeutic index (SE life threatening)
- respiratory depression (pronounced) –> neonates
- cardiovascular depression (hypotension, tachycardia)
- tissue irritation (paravenous, IM etc. inj)
- pre/postnarcotic excitations
Greyhounds are oversensitive (no fat-tissue)
Barbiturates:
- Pentobarbital and Thiopental difference
Pentobarbital (short)
- IV (15-60min duration)
- Anaesthesia
- euthanasia
Thiopental (ultra-short)
- IV (5-9 min duration)
- accumulation, slow/long wake up
- NO re-administration
- prior to inhalational anaesthesia
Propofol
- pharmacological effects and Pharmacokinetics:
Pharmacological effects: GABAa
- unconsciousness
- muscle relaxation - good
- not pronounced alangesic, used in combination of opioids
Pharmacokinetics:
- Duration: IV 30-45sek up to 5-15 min (continous infusion, longer), quick/complete recovery (minutes)
- distribution: fast - complete, blood-brain barrier, placenta
- Quick hepatic + extra hepatic metabolism -> safe in liver failure
- Elimination (days) in urine in the form of metabolites: mainly as glucuronide conjugate or other inactive forms
Propofol:
- Indications, contra-indications, side-effects
Indications:
- induction and maintain general anaesthesia, TIVA with opioids (e.g fentanyl) and sedatohypnotics
- convulsions, epileptic eizures (rarely)
Contra-indications:
- cardiac, respiratory, renal, hepatic impairment
Side-effects:
- transient apnoea during induction (rapid application)
- cardiovascular depression (negative inotropic, hypotension)
- vomitting, excitation during recovery (rare)
- allergy, septicaemias
- increased ICP and ocular pressure
Imidazole-anaesthetics etomidate:
- Pharmacological effect and Pharmacokinetics
Pharmacological effect:
- unconsciousness
- muscle relaxation - good
- not pronounced analgesia –> give in combination with opioids
Pharmacokinetics:
- Duration: IV up to 10-20min (2x longer than Propofol)
- distribution: fast - complete, blood-brain barrier, placenta
- quick wake-up + excitation
Imidazole-anaesthetics Etomidate:
Indication, side effects:
Indication:
- induction, before inhalational anaesthesia
- combination (opioids) -> short procedure
Side effects: Broad therapeutic index
- severe tissue irritation (acidic pH) Only IV
- respiratory depression (mild)
- no cardivscular depression –> cardiovascular insufficiency
- Adrenocortical suppression (2-3 hr) –> bolus! (not continous infusion)
- Pre/postnarcotic excitation (frequent)
Imidazole-anaesthetics Metomidate:
- Methyl analouge of Etomidate
- more commonly used in pigs
- analgesic effect moderate (better in combination with Aeperone).
- highly acidic (pH 2.4), it can be injected only into large veins.
- frequent excitations (pre-and post anastehtic)
- cardio-presiratory depression is moderate
- the number of breats decreases, but the volume is higher.
- in horse: tremors, convulsions
Steroid anaesthetics:
- pharmacological effect, pharmacokinetids
(Alphaxalone+alfadole=”althesin”) = alfaxane
Pharmacological effect:
- unconsciousness
- muscle relaxation - good
- not pronounced analgesia –> used in combo. with opioids
Pharmacokinetics:
- onset: IV 30sek. IM 5-10 min –> duration: up to 10-20 min
- quick metabolism, no accumulation –> re-administration safe
- quick recovery
Steroid anaesthetics:
- Side effects:
Borad therapeutic index:
- cardiovascular depression –> hypotension, negative ionotropic
- histamine release -> allergy (eg ear). –> Necrosis! <- antihistamine!
- postnarcotic exitation (rare) –> stimulation during recovery (vocalization)
Licenced product:
- cremofor (saffan inj) -> Cat! (shock in dogs)
- cyclodectrine (Alfaxan inj) –> Dogs + cats
NMDA-r antagonists:
Ketamine (S2 CD!)
- Bioketan inj. (AUV)
- CP-ketamin inj (AUV)
- Narketan inj (AUV)
- Calypsol inj (human)
Tiletamine (no CD)
- zoletic inj 50/100 AUV
Ketamine
- Pharmacological effect and Pharmacokinetics:
Antagonist of the NMDA receptors in CNS
Pharmacological effect:
- Unconsciousness (species-depending) -> catalepsy
- Analgesia - pronounced! (modulation of opioid receptors)
- muscle relaxation no good –> muscle rigidity
Pharmacokinetics:
- onset: IV 1min, IM: 5-10 min
- relatively long duration of action - delayed recovery (hours)
- distribution: crosses placenta barrier
- metabolised in the liver (80%) into norketamine. Norketamine is then primarily hydroxylised via glucuronoconjugation and excreted in urine and bile
Ketamine:
- Indications, contra-indications, side-effects
Indications:
- Anasethesia (in combinations) induction and maintain
Contra-indications:
- sole use in horses and dogs, hepatic and/or liver imparment, late pregnancy
Side-effects:
- catalepsy-like condition
- increased sympathetic nervous system tone
- increased cardiac output, heart rate, blood pressure, arrhytmias
- mild respiratory depression, tidal volume slightly increased
- salivation
- pre-post anasthetic excitations, convulsions
- increased ICP/eye pressure
- Hallucinations - “bed dream” -> misus-dependency
Administration: IM (SC, IV) 5-10% injection.
- Dog and horses only in combinations (opioids, alpha2-agonists, benzodiazepines etc!)
Zoletil:
- 1ml of fix combination solution contains 50 or 100mg Tiletamine a dissociative agents and 50 or 100mg Zolazepam (benzodiazepine)
- freshly dissolved in water, saline or 5% dextrose (14 days if stored in refrigerator)
- dose: cats 10-15 mg/kg, Dogs: 5-10 mg/kg (lower dose,strong sedation only)
- very fast onset of unconsciousness (2-5min)
Side effects:
- increased sympathetic tone –> tachycardia, arrythmias, hyperthermia, increased ICP
- dose-dependent respiratory depression (no with Xylazin!)
- pain response when the drug is given IM or SC
Comparison of injectable anaesthetics:
Combined Anaesthesia:
- Balanced anaesthesia:
- combination of antimuscarinics, sedatives, opioids, anaesthetics and muscle relaxants
- goal: “good sleep”, safe and deep anaesthesia, pain control, less side effects, relaxed body, smooth recovery etc. - Total intravenous anasthesia (TIVA)
- combination of agents given exclusively by the intravenous route without the use of inhalation agents
- eg: propofol + fentanyl, fentanyl + lidocaine + ketamine “FLK” - Neuroleptanalgesia:
- tranquilizer + opioids - Ataranalgesia
- Benzodiazepine + ketamine –> Zoletil A.U.V
Useful combination intended for light plane anaesthesia:
What is Neuroleptanalgesia:
- a state of sedation combined with analgesia (Neuroleptic + analgesic)
- similar, but not equal to light plane anaesthesia
- the animal no longer respond to pain or to surrounding but not totally unconscious
Advantages:
- less amount of sedative (safer)
- prior anaesthesia: induction is safer, analgesia is more pornounced
Combinations used for neurolpetanalgesia: see picture
Comparison of physiological signs of neuroleptanalgesia:
organ/dog/horse
Groups of inhalational anaesthetics:
Criteria for the efficacy of inhalational anaesthetics:
Inhalled air –> alveolar air (good vaporisation) –> BLOOD (good blood : gas distribution) –> BRAIN (lipid solubility, good oil : gas distribution
What does MAC mean?
MAC = Minimum alveolar concentration
- as small its value is, as higher the potency (ED50) is
Halothane
Most efficacious
- but: Teratogenic, carcinogenic, hepatotoxic, arrhytmogenic!!
- sensitivity to catchecolamine increases
- ADH level increases
–> EU bands
Induction/arousal phases are long:
- excitement are frequent
- obese animal –> delayed awake
Induction: 4-5%, maintenance 1.5-2.5 %
Isoflurane, Sevoflurane:
Indications: induction and maintain general anaesthesia
Contra indications:
- younger age, pregnant, lactating animals
- susceptibility to malignant hyperthermia
Side effects:
- cardiovascular and respiratory depression
- cardiac arrhytmias
- malignatn hyperthermia (Iso)
Dose:
- Iso: induction 2-5%, maintance: 0.25-3%
- Sevo: induction: 5-7%, maintance: 3.3-3.8%
Desflurane:
Side effects: more common than the others
- respiratory tract irritation, tachycardia
Methoxyflurane:
- because of low gas-tension (max % < 4) and excitments more preferred to use for maintanence (0.5-3%)
- respiration inhibition is more pronounced
- it is contraindicated in reptiles, strong nehrotoxicity
