Anaesthesiology - Pharmacology Flashcards
General Anesthesia
- Define induction agent
- Examples
- Length of action
Induction agent: A drug which induces loss of consciousness in one arm-brain circulation time when given at an appropriate dose
Examples: **Benzodiazepines, Etomidate, Propofol, Ketamine **
Length of action of an IV bolus: 3-5 mins effect due to drug redistribution, actual elimination half-life is several hours
Ketamin: 5-10 mins effect, onset time 30s
General Anesthesia
- Define Maintenance agent
- Examples
- Drug used to maintain anesthesia until end of procedure
Examples:
- Volatile anesthetic agents (inhaled halogenated ether compounds): Sevoflurane, desflurane, isoflurane
- Nitrous oxide (inhalation)
- IV injection/ infusion of any induction agents
General Anesthesia
- List general side effects
- Hypoxia
- Hypotension
- Sedation
- Confusion and agitation
- Nausea and vomiting
- Headache
- Shivering
Barbituates
- Mechanism
- PK
- Effects
- Uses
Mechanism
- Potentiate effect of GABA at GABAA inhibitory receptor
Pharmacokinetics
- Rapid brain uptake, rapid redistribution, hepatic elimination
- Slow metabolism & prolonged elimination
Effects
- CVS - ↓MAP, ↑HR, myocardial depression
- Respiratory - depression ventilator centre, retain some airway reflexes
- CNS - ↓CMRO2, CBF, ICP, anti-convulsant
Uses
- Obstetrics, RSI, epilepsy/ seizures, neurosurgical emergency
Etomidate
- Mechanism
- PK
- Effects
- Uses
Mechanism
- Potentiate effect of GABA at GABAA receptor
Pharmacokinetics
- Rapid onset of action & redistribution. Hydrolysed by plasma esterases & liver
Effects
- CVS - cardiovascular stability, no effect on contractility, SVR, HR
- Respiratory - minimal effect on respiration
- CNS - ↓CMRO2, CBF, ICP
- Other - inhibits 11-β hydroxylase → adrenocortical suppression
Uses
- Cardiac patients
- Haemodynamically unstable patients
Propofol
- Mechanism
- PK
- Effects
- Uses
Mechanism
- Potentiate effect of GABA at inhibitory GABAA receptor
Pharmacokinetics
- Rapid onset, rapid redistribution, metabolised in liver, high clearance
Effects
- CVS - ↓SVR, cardiac contractility, preload
- Respiratory - ↓resp depression, obtunds laryngeal reflexes
- CNS - ↓CMRO2, CBF, ICP, burst suppression
- Others - fast clear headed wake-up, anti-emetic, propofol infusion syndrome
Uses
- Most suitable for infusion of induction agents
- Used with ultra-short-acting opioid remifentanil- synergistic effect
Ketamine
- Mechanism
- PK
- Effects
- Uses
Mechanism
- Inhibits excitatory NT glutamate at NMDA receptors
Dissociative anaesthesia rather than hypnosis
Pharmacokinetics
- Rapid onset, slower redistribution, hepatic metabolism to norketamine
Effects
- CVS - ↑HR, SVR, CO by SNS activation
- Respiratory - little effect on rate, bronchodilator, salivation, reflexes preserved
- CNS - ↑CBF, ICP, CMRO2, hallucinations, amnesic
- Others - analgesic
Uses
- Shocked patients
- As analgesic
Volatile anesthetic agents
- Mechanism
- Effects
- Examples
- Effect: Mainstay of anaesthetic maintenance
- Examples: Sevoflurane, desflurane, isoflurane
Halogenated ether compounds- comes in liquid form - Mechanism:
A device called a vaporiser adds a known concentration of volatile agent to a gas mixture (usually N2O, O2 or air/O2) which patient inhales via a breathing circuit
Concentration can be adjusted to keep appropriate concentration of volatile in the lungs
When volatile is stopped, as the patient exhales it is eliminated. When the alveolar concentration drops to a critical level, patient wakes up
Nitrous Oxide
- Mechanism
- Effects
- Advantages and disadvantages
Nitrous oxide (inhalation)
- Mechanism: Given with O2 or air in a gas mixture to inhale
- Effect: Weak anaesthetic, need to breathe 104% to achieve anaesthesia
Advantages
* Good analgesia
* Reduces MAC
Disadvantages
* PONV
* Diffusion into gas filled spaces
* Effects on bone marrow
* Environmental issues
Induction agents
- Mechanism
- Disadvantages
- S/E
All induction agents are suitable to maintain anaesthesia if given as infusion or regular boluses
Disadvantages with maintenance with induction agent:
- Accumulation on repeated dosing
- Very prolonged duration of action
- Difficult dose timing
Side effects
* Etomidate: adrenocortical suppression
* High doses of propofol: propofol infusion syndrome
Explain why GA agents cause Hypoxia
Hypoventilation
* Airway obstruction- tongue, oedema, laryngospasm
* Respiratory depression
* Residual neuromuscular blockade
* Poor analgesia
VQ mismatch
* Reduced CO & FRC
Shunt
* Small airways closure, lung perfused but not ventilated
Diffusion hypoxia
- N2O more soluble than O2, when N2O stopped, it diffuses into alveoli from blood faster than N2 can diffuse in opposite direction. This concentrates N2O compared to other gases in alveoli and decreases FiO2.
Explain why GA agents cause sedation, confusion and agitation
Multiple causes from GA
- residual effect of anaesthetic/analgesic drugs
- hypoxia
- hypotension
- hypoglycaemia
- hypothermia
- electrolyte disturbance
- intracranial pathology
Local Anesthetics
- MoA
- Examples
- Dose calculations
MoA: Sodium channel blocker
- Local anaesthetics enter the nerve in the unionised lipid-soluble free base form
- Once inside the nerve, it ionises and the ionised form enters and blocks sodium channels.
- Once enough sodium channels are blocked, depolarisation is prevented and action potentials cannot be generated, leading to nerve blockade
Examples:
- Bupivacaine, Levo-bupivacaine, Ropivacaine
- Lignocaine, Lidocaine
- Cacaine
- EMLA: Lignocaine + Prilocaine
- Additive: Adrenaline (for slower LA absorption)
Anxiolytics
- MoA
- Examples
- Effects
- Uses
- S/E
- Antagonist
MoA: enhancing GABAA inhibitory neurotransmission, increase GABA affinity to GABA-receptros, increase Cl- influx, increase hyperpolarization
Examples: BDZs
- Short-acting: Triazolam, Midazolam
- Intermediate: Temazepam, Alprazolam, Lorazepam
- Long-acting: Diazepam, Clonazepam, Flurazepam
Examples: Barbituates
- Ultra-short acting: Thiopental/ Thiopentone
- Short-acting: Pentobarbital
- Long-acting: Phenobarbital
Effects: Anxiolytic, Hypnotic, Sedation/ muscle relaxation, Anti-convulsion (note: no analgesic or antipsychotic effect)
Uses:
- Sedation, anxiolysis, GA induction, Anti-convulsion
S/E:
- Drowsiness and confusion
- Poor motor control and ataxia
- Anterograde amnesia
- Respiratory depressionm, coma
- Barbituates: Severe withdrawal symptoms, CYP450 induction, Addiction
Antagonist: Flumazenil (competitive BDZ antagonist)
Antiemetics
- Examples
- MoA/ pathways
- Block neurotrasmission (5HT3, D2, H1, ACh, NK1) into chemoreceptor trigger zone (area postrema at floor of 4th ventricle outside of blood brain barrier)
- Block output to vomiting center and nucleus tractus solitarius (NTS)
Examples:
First line:
- Anti-serotonin: Ondansetron
- Steroids: Dexamethasone
Second line:
- Anti-cholinergics: Hyoscine
- Anti-histamines: Cyclizine
- Anti-dopaminergics: Metoclopramide, prochlorperazine
Post-operative nausea and vomiting (PONV)
- List patient factors, surgical factors and anesthetic factors
Patient factors
- Female, young, non-smoker, history of PONV, travel sickness
Surgical factors
- Surgery type: ENT, eye, abdominal, gynaecological
- Surgical technique: laparoscopic
- Surgical complication: swallowed blood
Anaesthetic factors
- Pharmacological: opioid, N2O, volatile agent
- Others: dehydration, poorly controlled pain, anxiety
- Failure to give prophylaxis in high-risk patient
Analgesics
- Classes and Examples
- Antagonist
Analgesic and anti-inflammatory drugs:
Paracetamol
NSAIDs:
* Salicylates: Aspirin, Dilflunisal
* Propionic acids: Naproxen, Ibuprofen
* Acetic acids: Indomethacin, Sulindac
* Oxicams: Prioxicam
* Fenamates: Meclofenamic acid
* Selective COX-2 inhibitors: Celecoxib, Etoricoxib, Rofecoxib
Narcotic analgesics/ Opioids
- Morphine derivatives: Morphine, Codeine, Heroin
- Phenylpiperidine: Pethidine, Fentanyl, Sufentanil, Alfentanil, Remifentanil
- Methadone
- Propoxyphene
- Tramadol
Antagonist: Naloxone
Paracetamol
- MoA
- Effects
- S/E
MoA: inhibition of central prostaglandn synthesis, possibly multi-receptor action - COX (but not COX1 or COX2), serotonergic, endocannabinoid
Effects: Analgesics, Antipyretic, NOT anti-inflammatory
S/E: Skin rash, minor allergy, Asthma for GSH-deficient), NAPQI hepatotoxic intermediate in overdose
Opioid
- MoA
- S/E
Opioids MoA: Bind to mu-receptors in CNS (mu-1R block for supraspinal and peripheral analgesia; mu-2R block for spinal analgesia)
(Tramadol blocks serotonin and catecholamine reuptake)
S/E:
Acute S/E: Sedation, N/V, Respiratory depression, Euphoria (esp. Pethidine, morphine), Miosis, hypotension and bradycardia
Prolonged use S/E: Constipation, tolerance, dependance, arrhythmia (esp. Propoxyphene), Convulsion/ Seizure (esp. Pethidine/ kidney failure), hormonal effects: ACTH, Prolactin suppression
- Respiratory depression
- Euphoria
- Sedation
- Nausea & vomiting
- Bradycardia & hypotension
- Constipation
- Histamine release
- Hormonal effects- suppression of ACTH, prolactin
- Tolerance & dependence
NSAIDs
- MoA
- Effects
- S/E
MoA: Inhibit COX 1 or 2, decrease prostaglandin and TXA2 production
Effects: Analgesic, anti-pyretic, anti-inflammatory
S/E:
- GI bleeding, gastric ulceration (decrease protective PG production)
- Bleeding: Block Thromboxane A2 synethesis for aggregation, adhesion and vasoconstriction
- GI disturbances: dyspepsia, Diarrhoea/ constipation, N/V
- Asthma induction: shunt arachidonic acids into leukotrienes for bronchospasm
- Analgesic- associated nephropathy: Decrease renal angiotensins, block renal blood flow, cause interstitial nephritis
- Ischemic heart disease: Block PGI2 production for vasodilation and anti-thrombosis + increase TXA2 production for vasoconstriction and pro-thrombosis
- Skin rash/ urticaria/ photosensitivity
Neuromuscular blockers
- Examples
- Classes
- MoA
Depolarising NMB
- Succinylcholine (aka Suxamethonium), Decamethonium
- MoA: Nicotinic AChR agonist, sustained membrane depolarization, closure of h-gate, inactivate V-gated cation channels
Non-depolarizing NMBs
- Short acting: Mivacurium
- Intermediate: Atracurium, Cis-atracurium
- Steroidal: Vecuronium, Rocuronium
- Long-acting: Pancuronium, Tubocurarine
- MoA: Nicotinic AChR antagonist, competitive blockage of ACh-gated cation channels, sustained ACh-gated and V-gated channel close
Neuromuscular blockers
- S/E
- Route of elimination
Depolarising NMB:
- Muscle pain by fasciculation
- Malignant hyperpyrexia
- Raised intra-ocular pressure and intra-gastric pressure
- Hyperkalemia: Arrhythmia
- Bradycardia (reduce with Atropine)
- Allergy/type 1 hypersensitivity and anaphylaxis to Quaternary Ammonium Compounds (QACs)
- Elimination by Pseudocholinesterases (PChE) at NMJ
Non-depolarising NMB:
- Bronchospasm (histamine release)
- Hypotension (Sympathetic block)
- Allergy to QACs
- Elimination: Hoffman elimination for atracurium; hepatic/ renal elimination for others
