General Anaesthetic Pharmacology - Pre-med, inhalation, intravenous, muscle relaxants, opioids, interactions Flashcards
OBJECTIVES OF PRE-MEDICATION
- reduction of sensory input
- improving emotional state (+amnesia)
- reduction of metabolic rate
- reduction of autonomic nervous system activity
EFFECTS OF ANXIETY
- psychological trauma
- activation of sympato-adrenal exis
- activation of pituitary-hypothalamic-adrenal cortical system
- increased gastric juice secretion
- increased gastric volume
- delayed gastric emptying
POPULATIONS TO BE CAREFUL OF WITH PRE-MEDICATION
- infants and the elderly
- debilitated patients
- altered LOC
- intracranial pathology
- upper airway obstruction
- respiratory distress
- severe obstructive/restrictive lung disease
- hypovolemia/shock
EFFECTS OF PARASYMPATHETIC SYSTEM BLOCKADE
- reduced vagal tone
- reduced secretions
- reduced gastric fluid volume and acidity
- reduced gastrointestinal tone and motility
- reduced nausea/vomiting
- reduced hypersensitivity
EFFECTS OF SYMPATHETIC SYSTEM BLOCKADE
- reduced catecholamine release
- reduced nausea
- depressed central noradrenergic outflow
EFFECTS OF OPIATES AS PRE-MED
- analgesia
- reduced IV induction dosage needed
- reduced inhaled MAC needed
- reduced surgical stress response
- blunted intubation reflexes
ADVANTAGES OF BENZODIAZEPINE AS PRE-MED
- anxiolysis
- sedation
- anterograde amnesia
DISADVANTAGES OF BENZODIAZEPINE AS PRE-MED
- respiratory depression
- declined cognitive function
- declined fine motor function
A BENZODIAZEPINE WITH SHORT HALF LIFE
midazolam
A BENZODIAZEPINE WITH LONG HALF LIFE
diazepam
A BENZODIAZEPINE WITH LITTLE MYOCARDIAL DEPRESSION
lorazepam
A BENZODIAZEPINE WITH PSYCHOMOTOR AGITATION AND CONFUSTION IN THE ELDERLY
lorazepam
DRUG USED TO COUNTER NAUSEA ASSOCIATED WITH OPIATES
phenothiazine
ANTICHOLINERGICS USED
- atropine
- scopolamine
- glycopyrrolate
ANTICHOLINERGIC THAT DOES NOT CROSS THE BBB
glycopyrrolate
REASONS FOR USING ANTICHOLINERGICS
- dry secretions
- reduce bronchomotor tone
- prevent bradycardia from laryngeal stimulation
SIDE EFFECTS OF ANTICHOLINERGICS
- central anticholinergic syndrome
- reduced tone of LES
- mydriasis
- raised body temp
- increased physiological dead space
SIGNS OF CENTRAL ANTICHOLINERGIC SYNDROME
- restlessness, drowsiness
- prolonged anaesthesia
- coma
TREATMENT: CENTRAL ANTICHOLINERGIC SYNDROME
IV physostigmine
HEALTH STATUS GRADINGS
- healthy patient
- mild systemic illness
- significant systemic illness but not incapacitated
- significant systemic illness, constant threat
- very ill, unlikely to survive 24 hours
SITES OF ACETYLCHOLINE
- neuromuscular junction, nicotinic receptors
- autonomic ganglia
- post-ganglionic parasympathetic nerve endings
- sympathetic nerve endings of sweat glands
- CNS
TWO FORMS OF CHOLINESTERASE
- acetylcholine esterase
2. pseudocholine esterase
SHORT, MEDIUM AND LONG-ACTING ANTICHOLINE ESTERASES
SHORT: edrophonium
MEDIUM: neostigmine, pyridostigmine, physostigmine
LONG: organophosphates
EFFECTS: MUSCARINIC AGONISTS
- smooth muscle contraction
- pupillary contraction
- decreased rate/force of heart
- glandular secreations (salivary, sweat, pancreas)
- gastric acid secretion
- vasodilation
- inhibit neurotransmitter release
EFFECTS: MUSCARINIC ANTAGONISTS
- inhibit secretions
- tachycardia
- pupillary dilatation
- relaxation of smooth muscles
- inhibition of gastric secretions
- antiemesis
- inhibit tremor
COMMON MUSCARINIC ANTAGONISTS
atropine hyoscine tropicamide cyclopentolate ipratropium benztropine pilocarpine
CLINICAL USES: ANTICHOLINESTERASES
- glaucoma treatment
- myasthenia gravis treatment
- reversal of non-depolarising neuromuscular blockers
- Alzheimer’s dementia
CLINICAL USES: ADRENERGIC AGONISTS
- cardiac arrest
- cardiac failure
- heart block
- anaphylaxis
- asthma
- nasal decongestion
- inhibition of premature labour
- prolong effects of local anaesthesia
BE CAREFUL IN THESE PATIENTS WITH BETA BLOCKERS
- asthma/ obstructive lung disease
- diabetics
- poor cardiac function
- cardiac conduction disturbances
- peripheral vascular disease
EFFECTS OF THIOPENTAL INDUCTION
- pleasant induction
- reduced cerebral blood flow
- reduced ICP
- anticonvulsant
- reduced nausea
SIDE-EFFECTS: THIOPENTAL INDUCTION
- urticarial rash
- anaphylactoid reactions
- coughing/hiccups/irregular respiration
- venodilation
- negative inotropy
CONTRAINDICTATIONS: THIOPENTAL INDUCTION
- porphyria
- cardiac tamponade
- hypovolaemia
- cardiac failure
- IHD
- condiction defects
PREVENTING ARTERIAL INJECTION OF THIOPENTAL
- dilute it to 2.5%
- use an established IV line
MX: ARTERIAL THIOPENTAL
- papaverine 40-80 mg
- lignocaine 25-50 mg
- diluted heparin
BENEFITS: ETOMIDATE
- high safety margin
- safe in epilepsy
- minimal circulatory effects
- no myocardial effects
- minimal acumulation
SIDE-EFFECTS: ETOMIDATE
- myoclonic movements
- respiratory depression
- histamine release
- post-op N&V
- thrombophlebitis
- depressed adreno-cortical fx
BENEFITS: PROPOFOL
- short awake/recovery time
- amnesia, anxiolysis, sedation
- safe in MH
- antiemetic
SIDE-EFFECTS: PROPOFOL
- grand mal seizures
- abuse potential
- respiratory depression
- bradycardia
- severe hypotension
- anaphylactoid reactions
- culture growth
- metabolic acidosis
- adverse neurological outcome
- pain on injection
CONTRA-INDICATIONS: PROPFOL
- sepsis
- hypotension
- hypovolaemia
BENEFITS: KETAMINE
- amnesia
- anticonvulsant
- bronchial smooth muscle dilatation
- sedation
- safe in MH
SIDE-EFFECTS: KETAMINE
- raised ICP
- increased salivation
- hypertension
- tachycardia
- raised cardiac output
CONTRA-INDICATIONS: KETAMINE
- porphyria
- raised ICP/IOP
- psych problems
INDICATIONS: KETAMINE
- lung disease
- hypovolaemia
- cardiac tamponade
DEFINE MAC
percentage of one atmosphere required to prevent purposeful response to noxious stimuli in 50% of patients
PROPERTIES: IDEAL INHALED ANAESTHETIC
- pleasant inhalation
- potent
- rapid emergence
- depth adjustable
- easily measured
- inexpensive
- stable outside body
- specific for CNS unconsciousness
- no CVS/respiratory side-effects
- post-operative analgesia
FACTORS AFFECTING MAC
- age
- body temperature
- pregancy
- physiological alterations
- anaesthetic adjuvants
SIDE-EFFECTS: HALOTHANE
- ventricular extrasystoles in response to adrenaline/hypercarbia
- mild hepatic reactions
- severe hepatic necrosis
SIDE-EFFECTS: DESFLURANE
- CVS stimulation, tachycardia
- increased airway resistance
- laryngospasm, coughing
- increased carbon monoxide poisoning
SIDE-EFFECTS: ISOFLURANE
- cross-sensitivity to halothane
2. increased carbon monoxide production
AGENTS THAT WORK ON NMDA RECEPTORS
ketamine
nitrous oxide
SIDE EFFECTS: NITROUS OXIDE
- raised systemic vascular resistance
- raised ICP
- post-op nausea, vomiting
- increased size of air-filled spaces
- oxidation of vitamin B12
CONTRA-INDICATIONS: NITROUS OXIDE
- raised ICP
- pneumothorax
- eustachian tube pathology
- bowel obstruction
- abnormalities of folate metabolism
WHAT IS COMPOUND A
a vinyl ether
degradation product of sevoflurane
COMPOUND A LIKELIKHOOD INCREASED BY
- sevoflurane
- carbon dioxide
- low fresh gas flow
- raised temperature
- dehydration
- potassium
- sodium hydroxide
CLASSIFY NEUROMUSCULAR BLOCKERS
a. depolarising (suxamethonium)
b. non-depolarising: benzylisoquinolines (-curium)
c. non-depolarising: steroidals (-curonium)
SUBJECTIVE TESTS FOR MUSCLE FUNCTION POST-RELAXATION
- head lift
- hand grip
PERCENTAGE BLOCKADE WITH FOURTH/THIRD/SECOND TWITCH ABSENT
FOURTH: 75%
THIRD: 80%
SECOND: 90%
BLOCKAGE REQUIRED FOR SURGERY
75-90%
TOF REQUIRED FOR RESPIRATORY MUSCLE FUNCTION
0.8
WHAT IS FADE AND WHAT DOES IT INDICATE
FADE: gradual dimunition of evoked response during prolonged/repeated nerve stimulation
INDICATES: non-depolarising block of at least 75%
CORRELATION BETWEEN TOF AND CLINICAL SIGNS
- unable to lift hand/arm
- 3s head lift, eyes open
- 5s head lift, cough, 60% grip
- normal vital capacity and inspiratory force
SIDE-EFFECTS: SUXAMETHONIUM
- malignant hyperthermia
- fasciculations, muscle pain
- hyperkalaemia (especially in burns)
- bradycardia
- raised IOP
- raised intra-gastric pressure and LES pressure
- raised ICP
- masseter muscle rigidity
- anaphylactic reactions
- scoline apnoea
LONG-ACTING NDMR
pancuronium
MUSCLE RELAXANT SUITABLE IN IHD
vecuronium
MUSCLE RELAXANT APPROPRIATE IN KIDNEY DISEASE
rocuronium
NDMR ALTERNATIVE TO SUX
rocuronium
rapacuronium
MUSCLE RELAXANTS WITH HISTAMINE RELEASE
- atracurium
- mivacurium
- suxamethonium
NDMR METABOLISED BY PLASMA CHOLINESTERASE
mivacurium
REVERSAL OF NDMR BLOCKADE
- cholinesterase inhibitors
2. anticholinergic agent e.g. atropine, glycopyrrolate
EFFECTS OF UP/DOWN REGULATION OF RECEPTORS ON MEDICINE CHOICES
UP REGULATION:
higher sux affinity
lower NDMR affinity
DOWN REGULATION:
lower sux affinity
higher NDMR affinity
CONDITIONS RESULTING IN UP-REGULATION OF ACH RECEPTORS
- UMN lesions
- LMN lesions
- muscle trauma
- burns
- immobilisation
- sepsis/infection
CONDITIONS RESULTING IN DOWN-REGULATION OF ACH RECEPTORS
- myasthenia gravis
- organoposphate poisoning
EXAMPLES: ENDOGENOUS OPIOIDS
enkephalins
endorphins
OPIOID RECEPTORS
mu
kappa (1-3)
delta
EFFECTS OF OPIOIDS
CENTRAL - analgesia (spinal, supraspinal, peripheral) - anaesthesia (reduce MAC/induction dose) - miosis - euphoria RESPIRATORY - resp depression - anti-tussive - blunted upper airway reflexes CVS - hypotension - bradycardia GIT - nausea & vomiting - constipation - increase tone of gut sphincters, also of Oddi HISTAMINE RELEASE
OPIOID ANTAGONISTS
naloxone
nalorphine
OPIATE POTENCIES, FROM WEAK TO STRONG
- codeine
- pethidine
- morphine
- alfentanil
- fentanyl
- sulfentanyl
OPIATE GIVING CHEST WALL RIGIDITY
fentanyl
OPIATE CROSSING BBB RAPIDLY
alfentanyl
OPIATE USEFUL IN CHOLINESTERASE DEFICIENCIES
remifentanyl
OPIATE WITH SIMILARITY TO ATROPINE
pethidine
ACTION OF TRAMADOL
- acts on opioid receptors
- inhibits noradrenaline uptake
- enhances serotonin release
OPIOID DESIGNED TO REDUCE ABUSE
pentazocine
DEFINE PHARMACEUTICAL INTERACTIONS AND GIVE GOOD/BAD EXAMPLES
reactions between two drug alters chemical properties such that they cannot be absorbed/utilised
GOOD: protamine reverses action of heparin
BAD: insulin adheres to glass/plastic containers
thiopentone and adrenalin cause a precipitate
DEFINE PHARMACOKINETIC INTERACTIONS AND GIVE GOOD/BAD EXAMPLES
a drug alters degree of absorption/distribution/clearance of another
GOOD: second gas effect
IV opioid reduce MAC/induction dose
BAD: Rifampicin with halothane = hepatitis
DEFINE PHARMACODYNAMIC INTERACTIONS AND GIVE GOOD/BAD EXAMPLES
interactions at effector site, often by means of receptor competition
GOOD: nitrous oxide added to halothane requires less halothane
BAD: NSAIDs increase warfarin free portion