Anesthetics (Waller) Flashcards
(32 cards)
Inhaled Anesthetics
drug list
Volatile Anesthetics: Desflurane Enflurane Halothane Isoflurane Sevoflurane
Gaseous Anesthetics:
Nitrous oxide
Intravenous Anesthetics drug list
Propofol (Diprivan) Fospropofol Barbiturates (thiopental, methohexital) Benzodiazepines (midazolam, lorazepam, diazepam) Etomidate Ketamine Dexmedetomidine (Precedex)
Drug List – Local Anesthetics
Esters Benzocaine Cocaine Procaine (Novocain) Tetracaine
Amides Articaine Bupivacaine Lidocaine (Xylocaine) Mepivacaine (Marcaine) Ropivacaine
General Anesthesia
Anesthesia – loss of “awareness”
Goal – maintenance of physiologic homeostasis
Five Primary Effects:
Unconsciousness–> complete or partial unawareness
Amnesia
Analgesia
Inhibition of autonomic reflexes
Skeletal muscle relaxation–> neuromuscular blockade
Balanced Anesthesia
Minor Superficial Surgery or Invasive Diagnostic Procedures
- Sedative (PO or IV) + local anesthetic
- Profound analgesia with retention of patent airway
Extensive Surgical Procedures
- Preoperative sedative + anesthesia induction (IV) + maintenance with combination inhaled or intravenous drugs
General Anesthetic Action
Neuron Level:
Presynaptic- Alter release of neurotransmitters
Postsynaptic- Change frequency or amplitude of impulse exiting the synapse
Organ Level:
Strengthen inhibition or diminish excitation within the CNS
Inhaled Anesthetics
Agents:
Volatile – halothane, enflurane, isoflurane, desflurane, sevoflurane
Gaseous – nitrous oxide
Important PK Determinants:
- Uptake – gas exchange in alveoli
- Distribution/partitioning into effect compartment
Alveolar Concentration –> Solubility –> Cardiac Output –> Alveolar-Venous Partial Pressure –> Elimination
Alveolar Concentration
–> Solubility –> Cardiac Output –> Alveolar-Venous Partial Pressure –> Elimination
Factors Determining Change in Alveolar Concentration:
- Inspired concentration or partial pressure
- Partial pressure expressed as ratio: FA/FI
- – FA - alveolar concentration
- – FI - inspired air concentration
- The faster FA/FI approaches 1, faster anesthesia will occur - Alveolar ventilation
Solubility
Blood:Gas Partition Coefficient
Describes relative affinity for blood compared to inspired gas
Inverse relationship between partition coefficient value & rate of anesthesia onset
Low blood solubility (nitrous oxide, desflurane) = fast onset of action. Blood:gas partition coefficient .47
High blood solubility (halothane) = slow onset of action- Blood: gas partition coefficient 2.3
Cardiac Output–> Alveolar-Venous partial Pressure
Cardiac Output ↑ pulmonary blood flow ↑ uptake of anesthetic ↓ rate of FA/FI rise ↓ rate of induction
Alveolar-Venous Partial Pressure
Depends on tissue uptake
If venous blood contains significantly less anesthetic than arterial blood
Requires more time to equilibrium
Elimination
Recovery:
Follows same principles in reverse
If relatively insoluble in blood and brain –> eliminated faster
Time to recovery depends on elimination from brain
Remember factors controlling speed of induction?
- Inspired concentration or partial pressure
- Alveolar ventilation
Duration of exposure may also impact recovery
Lungs – major route of elimination
- Extent of hepatic metabolism: halothane > enflurane > sevoflurane > isoflurane > desflurane > nitrous oxide (none)
Inhaled anesthetics: Pharmacodynamics – Organ System Effects: CNS
Minimum alveolar concentration
Describes anesthetic potency
1.0 MAC = partial pressure of inhaled anesthetic, 50% of population remain immobile at skin incision
Value expressed as volume %
Successful anesthesia = 0.5 – 2 MAC
MAC is additive: 0.5 MAC of x + 0.5 MAC of y = 1 MAC
Nitrous oxide: MAC
> 100%
so even if 100% of the air were NO, would not immobilize half the population
Central Nervous System
Anesthesia Stages
Stage I Analgesia
- Analgesia without amnesia; later will experience both
Stage II Excitement
- Delirious, completely amnesic; rapid respirations; HR and BP increase
Stage III Surgical Anesthesia
- Slowing RR and HR, extends to apnea; four planes described
Stage IV Medullary Depression
- Requires circulatory and respiratory support
Toxicity of inhaled anesthetics
Nausea & vomiting
Halothane – hepatitis (1:20,000-35,000)
Renal toxicity – fluoride ions
Malignant hyperthermia
Propofol
MOA:
Potentiation of Cl- current mediated through GABAA receptor complex
PK:
Poorly soluble in water; formulated as a lipid emulsion
Rapidly metabolized (liver), excreted through kidneys
Fast onset, fast clearance
Brief context-sensitive half-time
Organ System Effects:
CNS – no analgesia; EEG burst suppression
CV – hypotension
Respiratory – depressant (apnea)
Barbiturates
Agents: thiopental, methohexital
MOA:
Act on GABAA receptor to increase duration of channel opening
PK:
Highly lipophilic; hepatic metabolism
Organ System Effects:
- CNS – sedation; no analgesia
Decrease electrical activity on EEG (exception methohexital)
- Respiratory – depressant (apnea)
Benzodiazepines
Agents: midazolam, lorazepam, diazepam
MOA:
- Act on the GABAA receptor, increase receptor sensitivity to GABA (agonist), enhance inhibitory neurotransmission
PK:
- Highly lipid soluble; rapid onset of action
- Midazolam shortest context-sensitive half-time
Organ System Effects:
- CNS – potent anticonvulsants
- Respiratory – depression may occur when given with opioids
Etomidate
MOA:
GABA like effects, potentiation of GABAA mediated Cl- currents
PK:
Minimal effect on hemodynamics + short context-sensitive half-time = may give larger doses and repeat boluses
Organ System Effects:
- CNS – cerebral vasoconstrictor
- CV – minimal impact on hemodynamics
- Endocrine – adrenocortical suppression
Ketamine
MOA:
Inhibits NMDA receptor complex
PK:
- High lipid solubility; fast onset of action
- Similar in structure to phencyclidine (PCP)
Organ System Effects:
CNS – profound analgesia; cerebral vasodilator
** Emergence reactions; dissociative anesthesia
CV – *increase systemic BP, HR, CO; however, is a direct myocardial depressant
Dexmedetomidine
MOA:
Highly selective α2-adrenergic agonist
PK:
Water soluble; rapid hepatic elimination; high clearance
Short half-time; however, significantly prolonged after longer infusion times
Organ System Effects:
CNS – hypnosis, analgesia, activates endogenous sleep pathways
CV – decrease in HR and SVR
good way to transition off of mechanical ventilation
Local Anesthetics
Administration – drug is delivered directly to target organ
- Loss of sensation in limited region of the body
Disrupts afferent neural traffic
- May also cause muscle paralysis and suppression of somatic or visceral reflexes
Local anesthetics - Basic Pharmacology
Structure: Lipophilic group (e.g., aromatic ring) + intermediate chain via an ester or amide + ionizable group (e.g., tertiary amine)
PK:
Those agents that are more lipid soluble = generally more potent, longer duration of action, take longer to achieve clinical effect
Metabolized in liver (amides) or plasma (esters)
Excreted in urine
Neuronal Factors Affecting Anesthetic Block
Differential Block
- Block all nerve actions (not just loss of sensation)
Intrinsic Susceptibility of Nerve Fibers Fiber diameter -- Block smaller diameters first? -- Variable portion of large fibers -- Myelinated fibers blocked faster than unmyelinated
Firing frequency
– More significant at high firing frequency
Anatomic arrangement
– Anesthetize from proximal to distal
