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PHARM ORAL 2021 > Inhaled Anesthetics + Dantrolene > Flashcards

Inhaled Anesthetics + Dantrolene Flashcards

1
Q

Nitrous Oxide: Class, structure + properties

A
  • Class
    • only inorganic anesthetic gas
  • Structure
    • double bond b/t 2 N atoms
  • Properties
    • colorless
    • sweet smell - odorless
    • gas @ room temp
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2
Q

Nitrous oxide: MOA

A
  • MOA unknown
  • potential sites of action
    • pre synaptic voltage gated sodium channels
    • 2 pore potassium channels
      • TREK and TASK channels
    • Ionotropic and metabotropic receptors
      • GABAA and glycine
        • glycine: major inhibitory neurotransmitter in the spinal cord and may be the site of action of immobility effect
      • gluatamate (NMDA, AMPA, Kainate)
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3
Q

Nitrous oxide: PK

A
  • 34x more soluble than N2 (diffusion hypoxia risk)
  • B/G: 0.46 (low blood solubility: rapidly taken up into tissues, fast on/off)
  • Dose → MAC: 105% (low potency)
    • ​MACawake: 60% of MAC
  • VP: 38, 770 @ 20 C
  • Metablism
    • < .01% biotransformation in GI tract
  • Elimination
    • exhalation: mainly unchanged by exhalation
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4
Q

Nitrous oxide: SE

A
  • Neuro:
    • ↑ CBF, mild ↑ ICP, ↑ CMRO2
    • ​analgesic properties
    • may ↑ motor activity w/clonus & opisthotonus
    • ↓ hearing post op
  • CV:
    • SNS stimulant; direct myocardial depressant → but still less than other IA;
    • unchanged HR, BP, CO, SVR or slight ↑ if SNS stimulation;
    • ↑ PVR → ↑ RA pressure
  • Resp:
    • ↑RR ↓TV & hypoxic drive (markedly)
    • no change in resting PaCO2
    • speeds induction by 2nd gas effect & concentration effect
    • diffusion hypoxia
  • Hepatic/renal:
    • ↓RBF, GFR & UOP
    • ↓ HBF - mild
  • GI:
    • PONV
    • bowel distention
  • Immune:
    • prolonged exposure (>24 hrs) → BM depression (megaloblastic anemia), peripheral neuropathies, pernicious anemia
    • may alter immune response to infection
    • inactivates methionine synthase (B12-dependent enzyme required for DNA & myelin synthesis)
  • Neuromuscular:
    • _​_Relaxes skeletal muscle & potentiates NMBs
  • Other:
    • Miscarriage & impaired fetal development
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5
Q

Nitrous oxide: Contraindications/Cautions

A
  • Contraindications:
    • closed air spaces
      • pneumothorax
      • air embolism
      • tympanic membrane surgery
      • eustachian tube obstruction
      • eye surgery
      • intestinal obstruction/bowel surgery
      • intracranial air
    • pts with pulm HTN (inc PVR)
  • Caution
    • Hx PONV
    • pregnancy - inc risk of miscarriage
    • long cases - diffuses into ETT cuff
    • associated with higher incidence of epi induced dysrhythmias
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6
Q

Isoflurance: Class + structure + properties

A
  • Class
    • inhaled anesthetic
  • structure
    • halogenated methyl ethyl ether
    • isomer of Enflurane
  • properties
    • pungent odor (not good for peds induction)
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7
Q

Isoflurane: MOA

A
  • MOA unknown
  • potential sites of action
    • pre synaptic voltage gated sodium channels
    • 2 pore potassium channels
      • TREK and TASK channels
    • Ionotropic and metabotropic receptors
      • GABAA and glycine
        • glycine: major inhibitory neurotransmitter in the spinal cord and may be the site of action of immobility effect
      • gluatamate (NMDA, AMPA, Kainate)
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8
Q

Isoflurane: PK

A
  • Dose → MAC: 1.2% (high potency)
    • MACawake: ⅓ MAC
  • B/G: 1.4 (intermediate solubility)
    • has the highest blood solubility of the gases that we use = slowest onset/offset
  • VP: 240 mmHg at 20 ℃
  • Metabolism: 0.2%-2% by CYP450 to trifluroacetic acid
  • Elimination: exhalation
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9
Q

Isoflurance: SE

A
  • Neuro:
    • ↑ CBF, ICP @ > 1 MAC - effects reversed by hyperventilation
    • ↓ CMRO2
      • silent EEG at 2 MAC
    • ↑ CSF reabsorption
  • Neuromuscular:
    • Relaxes skeletal muscle & potentiates NMBs
  • CV:
    • mild dose dependent myocardial depression
    • CO maintained by ↑HR (partial preservation of baroreceptor reflex)
      • elderly/nenoates may see ↓HR
    • mild Beta stimulation: ↓BP via ↓SVR, ↓ LV SV 15-30%, ↑cutaneous and skeletal muscle blood flow,
    • transient ↑ HR/BP w/rapid ↑ [] (less than des)
    • ↑RAP/CVP
    • CA vasodilator: coronary steal (possible exacerbation of cardiac ischemia w/CAD);
    • Anesthetic pre conditioning - brief exposure can activate KATP channels - hyperpolarizing effect (negative inotropic/relax vascular smooth muscle) – protects the tissue to subsequent ischemic episode
  • Resp:
    • ↑ RR ↓TV, ↓MV
    • >1 MAC: tachypnea less pronounced compared w/ other agents
    • ↓ response to hypoxia & hypercarbia
    • resp irritant r/t noxious odor (risk of laryngospasm, coughing)
    • bronchodilator in maintenance phase
    • ↓ HPV at > 1 MAC (↑ hypoxia risk during one lung ventilation)
  • Hepatic/renal:
    • ↓ RBF, GFR & UOP
    • maintains HBF - vasodilates hepatic circulation
  • GI:
    • PONV
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10
Q

Isoflurance: Cautions/Contraindications

A
  • Contraindications
    • MH
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11
Q

Desflurane: Class + structure + properties

A
  • class
    • inhaled anesthetic
  • structure
    • fluorinated methy ethyl ether
    • similar structure to isoflurane
  • properties
    • pungent odor (not good for peds induction)
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12
Q

Desflurane: MOA

A
  • MOA unknown
  • potential sites of action
    • pre synaptic voltage gated sodium channels
    • 2 pore potassium channels
      • TREK and TASK channels
    • Ionotropic and metabotropic receptors
      • GABAA and glycine
        • glycine: major inhibitory neurotransmitter in the spinal cord and may be the site of action of immobility effect
      • glutamate (NMDA, AMPA, Kainate)
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13
Q

Desflurane: PK

A
  • Dose → MAC: 6% (low potency)
    • MACawake: ⅓ MAC
  • B/G: 0.42 (low blood solubility: rapidly taken up into tissues, fast on/off)
  • VP: 669 mmHg at 20 ℃ (Tec 6 vaporizer)
  • Metabolism: 0.02%
  • Elimination: exhalation
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14
Q

Desflurane: SE

A
  • Neuro:
    • ↑ CBF, ICP, ↓ CMRO2
      • effect not usually seen until > 1 MAC
      • can lower ICP with hyperventilation
    • high rate of emergence delirium in peds?
  • Neuromuscular:
    • Relaxes skeletal muscle & potentiates NMBs
  • CV:
    • mild dose dependent cardiac depressant
    • ↓ in SVR → ↓ ABP, ↓ LV SV 15-30%
    • CO remains unchanged or slightly depressed at 1 - 2 MAC → baroreceptor reflex intact → rise in HR
    • rapid ↑ in []: transient SNS stimulation: ↑HR, BP and catecholamine levels (greater than with iso)
    • ↑ RAP/CVP
  • Resp:
    • ↑ RR ↓ TV, overall ↓ MV
    • ↑PaCO2 - blunts hypercarbic and hypoxic response
    • profound apnea at 1.5 - 2.0 MAC
    • ↓ HPV at > 1 MAC
      • ↑ hypoxia risk during one lung ventilation
    • irritating to the AW→ can cause coughing, bucking, ↑ secretions, bronchospasm, & laryngospasm (don’t use for inhalational induction)
    • bronchodilation during maintenace phase
  • Hepatic/renal:
    • no change in HBF
    • similar ↓ in RBF, GFR, and U/O you see w/ other agents (r/t ↓ CO and BP)
  • GI:
    • ​PONV
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15
Q

Desflurane: Cautions/Contraindications

A
  • Cautions
    • pts where tachycarida would be harmful (transient SNS stim): CAD, pheochromocytoma, hyperthyroid
    • highest risk of CO formation from degradation by dried out CO2 absorbent
      • can result in critically high levels of carboxyhemoglobin in exposed patients
  • Contraindications
    • MH
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16
Q

Sevoflurane: Class + structure + properties

A
  • class
    • inhaled anesthetic
  • structure
    • fluroinated methy isolpropyl ether
  • properties
    • non pungent
    • sweet odor (ideal for peds inductions)
17
Q

Sevo: MOA

A
  • MOA unknown
  • potential sites of action
    • pre synaptic voltage gated sodium channels
    • 2 pore potassium channels
      • TREK and TASK channels
    • Ionotropic and metabotropic receptors
      • GABAA and glycine
        • glycine: major inhibitory neurotransmitter in the spinal cord and may be the site of action of immobility effect
      • gluatamate (NMDA, AMPA, Kainate)
18
Q

Sevo: PK

A
  • Dose → MAC: 2%
    • MACawake: ⅓ MAC
  • B/G: 0.65 (low blood solubility: rapidly taken up into tissues, fast on/off)
  • VP: 160 mmHg at 20 ℃
  • Metabolism:
    • 3-5% to inorganic fluoride ion by CYP450 (no reported nephrotoxicity)
    • no metabolism to trifluroacetylated liver proteins so NO risk of halothane hepatitis
  • Elimination: exhalation
19
Q

Sevo: SE

A
  • Neuro:
    • ↑ CBF (least)
    • ↓ CMRO2 (most)
    • ↑ ICP (effect usually not seen until > 1 MAC)
    • response to CO2 & autoregulation maintained @ 1.5 MAC
    • high rate of emergence delirium w/peds
  • Neuromuscular:
    • _​_Relaxes skeletal muscle & potentiates NMBs
  • CV:
    • mild dose-related CV depression
    • SVR and ABP ↓ slightly (less than iso and des) → little rise in HR (only sig ↑ at > 1.5 MAC) → CO not as well maintained compared to other IA
    • SV ↓ similar to iso and des (15 - 30%)
    • no change in CVP, no evidence of coronary steal
  • Resp:
    • ↑ RR ↓ TV, overall ↓ MV
    • ↑PaCO2 ↓ response to CO2
    • profound apnea at 1.5 - 2.0 MAC
    • bronchodilation, minimal a/w irritation (use w/peds)
    • ↓ HPV at > 1 MAC (↑ hypoxia risk during one lung ventilation)
  • Hepatic/renal:
    • ↓ RBF, GFR, UOP
    • HBF maintained (similar to iso)
  • GI:
    • PONV
20
Q

Sevo: Cautions/Contraindications

A
  • Cautions
    • sevo metabolized to free fluoride ions → potential for tubular injury and loss of concentrating ability → ARF ⇒ BUT, no clinical evidence to support
    • potential for nephrotoxicity: compound A with exposure > 2 MAC hours and low flows (keep FGF >2L)
    • renal insufficiency (relative contraindication)
    • pts with hypo/hypertension, elderly
  • Contraindications
    • MH
21
Q

Dantrolene: Class + Use

A
  • class
    • centrally acting muscle relaxant
  • uses
    • malignant hyperthermia
      • without dantrolene - 70% mortality
      • with dantrolene - 5% mortality
22
Q

Dantrolene: MOA

A
  • reduces muscle tone & metabolism → restores balance between release and uptake
    • prevents the ongoing release of Ca2+ from the SR
    • blocks external entry of calcium into sarcoplasm
    • hypothesized to inhibit calcium conductance through ryanodine channels
23
Q

Dantrolene: PK

A
  • Onset: <5min
  • DOA: 3 hrs
  • E 1/2 life: 10-15 hrs
24
Q

Dantrolene: SE

A
  • skeletal muscle weakness
    • but does not signifcantly potentiate effects of NDMR or interfere with reversal of muscle relaxants
  • phlebitis - often follows administration
25
Q

Dantrolene: Cautions/Contraindications

A
  • Cautions
    • may cause significant muscle weakness in patients with pre existing muscle disease - USE WITH EXTREME CAUTION
    • when used with calcium channel blockers - may produce life threatening hyperkalemia and myocardial depression
26
Q

Dantrolene: dose

A
  • bolus 2.5 mg/kg IV then 2 mg/kg IV Q5 min to a total of 10 mg/kg
  • then 1 mg/kg Q6 x 72 hrs
  • reconstitute each 20 mg vial with 60ml of bacteriostatic sterile water (need 36 vials and 2L H2O)
  • other formulation: ryandoex
    • 3 vials of 250 mg/vial

PHARM ORAL 2021 (9 decks)

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