Anesthetics (Waller) Flashcards
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
Routes of Administration
(anesthetics)
Topical: nasal mucosa, wound (incision site) margins
Injection:
Peripheral nerve endings (perineural infiltration) & major nerve trunks (blocks)
Epidural or subarachnoid spaces surrounding the spinal cord
Orderly evolution of anesthetic block:
Sympathetic transmission Temperature Pain Light touch Motor block
anesthetic Toxicity
Systemic Effects
Inadvertent intravascular injection or absorption from site of administration
- CNS – sedation, light headedness, visual and auditory disturbances, restlessness
- CV – arrhythmia and cardiac arrest
Neurotoxicity
- Local effects by direct contact with neural elements
A 21 y/o male is scheduled to undergo a laparoscopic hernia repair on an outpatient basis under general anesthesia. This is the first time he has undergone surgery and he is highly anxious in the preoperative area. Which benzodiazepine may be utilized in this situation to reduce his anxiety?
Benzocaine Fentanyl Midazolam Propofol Thiopental
Midazolam
A 19 y/o female is admitted to the ambulatory surgery center for strabismus surgery to correct misalignment of her extraocular muscles. She is otherwise healthy and all laboratory values are within normal limits. Which intravenous induction agent may be used that is rapid in both onset and recovery and has antiemetic actions?
Halothane Nitrous oxide Procaine Propofol Sevoflurane
Propofol
The chemical with which blood:gas partition coefficient will reach the highest concentration in the brain the fastest (assume brain:blood partition coefficients are equal)?
- 42
- 47
- 69
- 4
- 8
least soluble is best.
A: .42
The anesthesiologist prepares to administer several drugs to a patient as part of normal perioperative care. Which drug lacks the ability to cause generalized CNS depression, lacks the ability to reduce or impair the patient’s level of consciousness, or lacks the ability to prevent or reduce pain?
Midazolam
Pancuronium
Propofol
Thiopental
Pancuronium
neuromuscular blockade
Nitrous oxide is a common component in the technique of balanced anesthesia. It is used in conjunction with a volatile anesthetic. Which phrase best summarizes why nitrous oxide cannot be used alone for general anesthesia?
Almost total lack of analgesic activity, regardless of concentration
Great solubility in blood, effects take an extraordinarily long time to develop
Inspired conc. > 10% tend to have profound, negative cardiac inotropic effects
MAC (minimum alveolar concentration) is greater than 100%
Very high frequency of bronchospasm
MAC (minimum alveolar concentration) is greater than 100%
