14. General anaesthetics: Injectable anaesthetics Flashcards
Analgesia
Lack of pain sensation
Anaesthesia
Lack of sensation, total loss of motoric activity (+pain?)
Give the stages of general anaesthesia
Stage:
- Disordered consciousness - Induction
- Excitement
- Surgical anaesthesia
- Overdose
Induction is by…
Injectable anaesthetics
Maintenance is by…
Inhalational anaesthetics
List the injectable anaesthetics
- Barbiturates
- Propofol
- Imidazole anaesthetics
- Steroid anaesthetics
- NMDAr antagonists (dissociative anaesthetics)
List the barbiturate anaesthetics
- Pentobarbital
- Methohexital
- Hexobarbital
- Thiopental
- Thiamylal
- Phenobarbital
List the steroid anaesthetics
- Alfadolone
- Alfaxolone (in fix combination)
Imidazole anaesthetics
- Etomidate
- Medomidate
NMDAr/Dissociative anaesthetics
- Ketamine
- Tiletamine
Other injectable anaesthetics
- Propofol
- Propanidid
- MgSO4
- Chloral hydrate
Properties of ideal injectable anaesthetics
- Water + Lipid soluble
- Sufficiently potent (volume)
- Good analgesic activity
- Should produce muscle relaxation
- Non-irritant to tissue
- Rapid + safe induction
- High TI
- It should have a pharmacological antagonist
Barbiturates: Mechanism of effects combined
- GABA-BDZ-Barbiturate-receptor complex (GABAA) allosteric action.
- Further supposed effects: Decrease in Ca2+ accumulation → inhibition in the release of transmitters
- Stabilisation of membranes
Barbiturates: paradox phenomenon
General inhibition
- But the sensitivity of certain structures differs
- Some are suitable for general anaesthesia
Barbiturates: Pharmacological effects
- CNS
- Circulation
- Respiration
- Unconsciousness
- Muscle relaxation
- Analgesia (but not appropriate)
Barbiturates: Kinetics
- pKa
- Lipophilicity
- Lipoid/water partition
- Redistribution
- Metabolism
Barbiturates are classified according to…
The duration of action:
- Short-acting
- Ultra-short acting
Administration of barbiturates
Only IV
- Effective & harmless
Barbiturates: Pharmacokinetics
- Duration (IV) :
- = 15-60min (short)
- = 5-8min (ultra-short)
- Distribution: Fast - Complete, BBB
- Placenta → Foetus (pronounced side effect)
- Redistribution → Fat, muscle → Leave CNS → Wake up
- Accumulation (fat) → Readministration Ø
Barbiturates: Indication
- Induction, general anaesthesia (combination)
- Convulsive state, epilepsy (pentobarbital I.v)
- Euthanasia
Barbiturates: Contra-indications
- Younger age (under 2 months)
- Diminished cardia output
Barbiturates: Side effect
Small therapeutic index (Life-threatening)
- Respiratory depression
- Cardiovascular depression
- Tissue irritation
- Prenarcotic excitation (Cats)
- Postnarcotic excitation (Horse, dog)
- Greyhounds are oversensitive
List the ultra-short acting barbiturates
- Thiopental
- Methohexital
- Hexobarbital
- Pentobarbital
- Thiamylal
Dosage: Methohexital
BRIETAL®
IV:
- Large animal = 5-10mg/kg
- Small animal = 25-30 mg/kg
Dosage: Thiopental
INTRAVAL®
IV:
- Large animal = 5-10mg/kg
- Small animal = 25-30 mg/kg
Dosage: Hexobarbital
NOVOPAN®
IV
- Horse = 10-20mg/kg
- Cat = 30-40mg/kg
- Lab. animals = 100mg/kg (IP)
Dosage: Pentobarbital
NEMBUTAL®
IV
- Cat & Dog = 25-35mg/kg
- Lab animals = 50-80mg/kg (IP)
Dosage: Thiamylal
SURITAL®
IV
- Horse = 4-6mg/kg
- Cattle = 8-12mg/kg
- Dog & Cat = 10-20mg/kg
Pentobarbital (short-acting) effect
- IV: 15-60min duration
- Anaesthesia
- Euthanasia
Thiopental (ultra-short) effect
- IV 5-8min duration
- Accumulation, slow/long wake-up
- Ø Readministration
- Prior to inhalational anaesthesia (rare) (side-effect)
Propofol: Pharmacological effect
GABAA
- Unconsciousness
- Muscle relaxation (good)
- Analgesia (not pronounced) → Combination (opioids)
Propofol: Pharmacokinetics
- Duration
- IV = 30-45sec → 5-15min
- Quick recovery (minutes)
- IV = 30-45sec → 5-15min
- Distribution: fast - Complete, BBB, placenta
- Quick hepatic + extrahepatic metabolism
- Can be administered during liver failure
- Elimination in the form of metabolites
- Glucuronide conjugate
Propofol: Indications
- Induction and maintain general anaesthesia
- TIVA (Total IV anaesthesia) with opioids and sedatohypnotics
- Convulsions, epileptic seizure (rare)
Propofol: Contraindications
- Cardiac impairment
- Respiratory impairment
- Renal impairment
- Hepatic impairment
Propofol: Side effects
- Transient apnoea during induction
- Cardiovascular depression
- Vomiting, excitation during recovery (rare)
- Allergy, septicaemias
- Increased ICP & occular pressure
Propofol: Proprietary products
- Narcofol inj.
- Vetofol 1.0%
- Fresofol® 1.0%
- Diprican inj./inf. (human)
Propofol: Dosage
IV
- Induction
- Mammals = 5-6mg/kg
- Reptiles & birds = 10mg/kg
- Maintenance
- 2.5-5mg/kg (double-bolus)
- or continuous infusion = 0.1/mg/kg/min
List the Imidazole anaesthetics
- Etomidate
- Metomidate
Etomidate: Pharmacological effect
GABAA receptor
- Unconsciousness
- Muscle Relaxation - Good
- Analgesia (not pronounced) → Combination (opioids)
Etomidate: Pharmacokinetics
- Duration: IV = up to 10-20min
- Distribution: Fast - Complete, BBB, placenta
- Quick wake-up & excitation
Etomidate: Indications
- Induction, before inhalational anaesthesia
- Combination (opioids)
- Short procedures
Etomidate: Side effects
Broad therapeutic index
- Severe tissue irritation - only IV
- Respiratory depression (mild)
- Cardiovascular depression Ø
- Adrenocortical suppression (2-3 hours)
- Pre-/postnarcortic excitation
Etomidate: Dosage
Mouse = 23-33mg/kg (IP)
Metomidate
Methyl analogue of etomidate used mainly in pigs
- Moderate analgesic effect
- Highly acidic
- Cardio-respiratory depression is moderate
- Resps. ↓ but volume ↑
- Horses: Tremors, convulsions
Metomidate: Dosage
- Dog = 10-15mg/kg IV
- Cat = 3-5mg/kg IV
- Pig 4-10mg/kg IV (with Azaperone)
- Reptiles = 10mg/kg IM
- Fish = 1-20mg/L water
Give a steroid anaesthetic
Alfaxalone/Alfadolone = Althesin®
Alphaxalone/alfadolone: Pharmacological effect
- Unconsciousness
- Muscle relaxation - Good
- Analgesia (not pronounced) → Combination (opioids)
Alphaxalone/alfadolone: Pharmacokinetics
- Onset:
- IV 30sec;
- IM 5-10min
- Duration = up to 10-30min
- Quick metabolism; Ø Accumulation
- Readministration
- Quick recovery
Alphaxalone/alfadolone: Side effect
Broad therapeutic index
- Cardiovascular depression
- Hypotension, negative ionotropic
- Histamine release → Allergy → Necrosis (rare)
- Postnarcotic excitation (rare)
- Stimulation during recovery (vocalisation)
Alphaxalone/alfadolone: Licensed product
- Cremofor → Cat
NMDA-r antagonists
- Ketamine
- Tiletamine
Ketamine: Proprietary names
- Bioketan® inj.
- CP-Ketamin® inj
- Narketan® inj.
- Calypsol® inj. (human)
Tiletamine: Proprietary name
Zoletil® inj. 50/100
Ketamine: Pharmacological effect
An antagonist of the NMDA receptors in the CNS
- Unconsciousness (species-dependent) → Catalepsy
- Analgesia - Pronounced (modulation of opioid receptors)
- Ø Muscle relaxation → Muscle rigidity
Ketamine: Pharmacokinetics
- Onset:
- IV: 1min
- IM: 5-10min
- A relatively long duration of action - Delayed recovery (hours)
- Distribution: Crosses placenta barrier
- Metabolised in the liver (80%) into norketamine
- Norketamine → Hydroxylised → Urine and bile
Ketamine: Indications
- Anaesthesia
- Induction
- Maintenance
Ketamine: Contra-indications
- Sole use in horses & dogs
- Hepatic & liver impairment
- Late-pregnancy
Ketamine: Side effects
- Catalepsy-like condition
- ↑ Sympathetic tone
- ↑ CO, HR, BP, arrhythmias
- Mild respiratory depression, ↑ tidal volume
- Salivation
- Pre-/postaesthetic excitations, convulsion
- ↑ ICP/eye pressure
Ketamine: Dosage
IM (SC, IV) 10% injection
- Dogs & horses → Used in combination ONLY
- α2-agonists
Ketamine: TI
Broad TI
Ketmaine: Metabolisation in cats and dogs
- Dog: Primary metabolized in liver
- Cat: Primarily excreted by kidneys
Neuroleptanalgesia
A state of sedation combined with analgesia
(neuroleptic + analgesic)
Give an example of a combination used for neuroleptanalgesia
Etorphine & Acepromazine
