Induction Drugs (Barbs & Propofol) (Exam II) Flashcards

Question

At a normal pH _____% of methohexital is non-ionized. At a normal pH ____% of sodium pentothal is non-ionized. What does this mean in regards to induction for comparing these drugs?

Answer 1

- 76% (more unionized molecules than pentothal) - 61% (still more lipid-soluble than brevital) - Methohexital **for induction** has a faster metabolism and recovery even though thiopental (pentothal) is more lipid soluble.

Answer 2

Methohexital ## Footnote M in metho for myoclonus and H in hexital for hiccups?

Answer 3

**Very lipid-soluble** so: - Drug **persists from infusion** but **clears quickly from induction** due to its rapid metabolism (faster than thiopental). ## Footnote Est 1/2 time of Thiopental > Methohexital Peds: generally shorter half-time d/t ↑ metabolism

Answer 4

- 1.5 mg/kg IV - 20 - 30 mg/kg PR

Answer 5

1. Continuous infusions induce post-op seizures in ⅓ of patients. 2. Seizures are induced in **patients undergoing temporal lobe** resection. 3. Seizure duration **REDUCED** 35-45% in ECT patients **vs** etomidate.

Answer 6

- Transient sBP **decrease** of 10-20mmHg - Transient HR **increase** of 15-20 bpm Decrease in BP is rapidly offset by increase in HR ## Footnote Caution with lack of baroreceptor response: Hypovolemia, CHF, Beta blockade ‣in shock (↓perfusion) ‣ elderly & women ( ↓ muscle mass)

Answer 7

- Hypovolemia, CHF, & β-blockade

Answer 8

anaphylactic ; histamine

Answer 9

Dose-dependent medullary & pontine respiratory depression. ## Footnote * Less sensitivity to CO₂ levels (may need CO2 increased to initiate spontaneous respiration) * Slow frequency and decreased Vt

Answer 10

- Immediate, limb-threatening vasoconstriction with pain radiating along the distribution of the artery. - Lidocaine or papaverine injection as well as any other vasodilatory method (must sustain adequate bloodflow!) ## Footnote Patient can have obscure distal arterial pulses, blanching of the extremity followed by cyanosis, and possible gangrene with permanent nerve damage

Answer 11

Barbs do not affect neuron transmission, thus, they **DON'T** effect SSEPs

Answer 12

- CYP450 induction can be seen if infusion persists for 2-7 days and can last up to 30 days after the infusion is D/C! - Enzyme induction when on prolonged gtt increases metabolism of: anticoagulants, phenytoin, TCA's, digoxin, corticosteroids, bile salts, vitmain K ## Footnote Special caution in coagulation. Induction of CYP450 can cause additional clotting in patients on warfarin (drug metabolized faster) and bleeding with plavix (more of prodrug is metabolized so more effective)

Answer 13

- Modest, but transient ↓RBF and ↓GFR ## Footnote Remember the transient decrease in BP?

Answer 14

1. **Induction** = 1.5 - 2.5 mg/kg IV 2. **Maintenance** = 100 - 300 μg/kg/min 3. **Conscious sedation** = 25 - 100 μg/kg/min ## Footnote Induction dose has to be higher for rapid onset (dose in mg/kg) and because we are giving a one-time IVP. Maintenance infusion can be lower (dose in μg/kg/min) to keep adequate blood concentration and conscious sedation must be even lower than maintenance so we don't snow or patients.

Answer 15

- 10mg/mL ## Footnote General rule for % concentration dictates you move the decimal to the right 1 place and that tells you how many grams/L you have. i.e. 0.9%NS=9g of salt/liter. 1.0% lido means 10g/L→10,000mg/L→10mg/mL

Answer 16

- 1.2% **Lecithin (from egg yolks)** can cause anaphylaxis with egg allergies. - 2.25% glycerol (causes pain on injection) - 10% soybean oil ## Footnote Both lecithin and soybean oil are factors that contribute to bacterial growth

Answer 17

- ↑ bacterial growth - ↑ plasma triglycerides with prolonged infusions - Pain on injection

Answer 18

- Ampofol - low-lipid, no preservative that burns on injection more often. - Aquavan - prodrug with less injection pain but causes unpleasant dysesthesias (especially in females). Slower onset, larger Vd, and high potency.

Answer 19

- GABA_A receptor modulator (Agonist) that increases Cl⁻ conductance. ## Footnote This causes hyperpolarization of the postsynaptic cell membrane and functional inhibition of the postsynaptic neuron

Answer 20

- Trick question. Immobility from propofol **is not** from drug-induced spinal cord depression.

Answer 21

* Plasma (pulmonary/lungs uptake) > hepatic blood flow (Note: Lungs do **NOT** metabolize the propofol, they temporarily remove some of it from systemic circulation) * Tissue uptake > Cytochrome P450 ## Footnote The elimination of propofol is primarily through hepatic metabolism, and excretion by the kidneys. However, about 30% of a propofol bolus is taken up by the lungs (lung first-pass) and is eventually (usually quickly) released back into circulation.

Answer 22

- 24-60% **CYP450** (in the liver) and 40-76% **UGT1A9** (liver, kidney, colon, esophagus, and small intestine)

Answer 23

- 30 - 90 minutes

Answer 24

- 40 minutes (for an 8 hours infusion) - Low CS ½ time.

Answer 25

1. E ½ time = 30 - 90 minutes 2. Vd = 3.5 - 4.5L 3. Clearance = 30 - 60 mL/kg/min

Answer 26

- Propofol: ↓BP (greater than Thiopental) & ↓HR (Direct SNS inhibition) - Thiopental: ↓BP & ↑HR (Both transient) ## Footnote Profound brady and asystole even in healthy patients!!! Consider pre-treatment with glyco (FDA Black box warning in Pedi<2yrs)

Answer 27

- Yes but is rapidly cleared from neonatal circulation. ## Footnote Although unlikely, still consider ion-trapping

Answer 28

No ## Footnote While primarily metabolized in liver, UGT1A9 that exists in the liver, kidney, colon, esophagus, and small intestine can pick up slack if liver is impaired.

Answer 29

Propofol ## Footnote Quick on, quick off, and can be metabolized in multiple tissues so it still works well in liver impairment

Answer 30

- Adults: 1.5-2.5 mg/kg IV - Pediatrics: higher doses due to larger central volume and clearance rate.

Answer 31

- 1 mg/kg IV (25 - 50% lower than regular adult) ## Footnote General concensus is that elderly are more sensitive to propofol, don't know why. Maybe aging organs reduce efficiency of CYP450 and UGT1A9?

Answer 32

- Unconscious: 2 - 6 μg/mL - Awake: 1 - 1.5 μg/mL

Answer 33

- 25 - 100 μg/kg/min

Answer 34

- Minimal analgesia but has anti-convulsive and amnestic properties. - Prompt recovery w/ low residual sedation - ↓ risk of PONV - Midazolam or opioids as adjuncts.

Answer 35

- Very anti-emetic (more effective than Zofran) - Depresses sub-cortical pathways and has a direct depressant effect on the vomiting center)

Answer 36

- 10 - 15 mg IV, followed by 10 mcg/kg/min

Answer 37

- 10 mg IV

Answer 38

- **Bronchodilation** - Anti-emetic (better than Zofran) - Anti-pruritic - Anti-convulsant - Analgesia at low doses - Potent Antioxidant - Does **not** trigger MH

Answer 39

- ↓ CMRO₂, CBF, and ICP (Coupled response)

Answer 40

myoclonus (This is normal) ## Footnote Note: Myclonus is involuntary, sudden, and brief muscle contractions that can affect one or multiple muscles. This can initially look like a seziure but is transient.

Answer 41

- Propofol

Answer 42

Propofol ## Footnote Thiopental is transient and is mitigated by a reflexive HR increase. Propofol has direct cardiac-suppressive effects!

Answer 43

- SNS inhibition causing ↓SVR and ↓ ICF Ca⁺⁺. - Hypovolemia, elderly, and LV compromise - ↓SBP>Thiopental ## Footnote Can cause profound brady and asystole even in healthy patients!!! Consider pre-treatment with glyco (FDA Black box warning in Pedi<2yrs)

Answer 44

- Intubation (from laryngeal stimulation). ## Footnote Cold blade=SNS Stimulation

Answer 45

- ↓SNS response & baroreceptor reflex depression. - Profound bradycardia & eventual asystole.

Answer 46

- Dose-dependent depression of respiratory drive. - Synergistic resp depression with opioids

Answer 47

- Hepatocellular injury or Propofol Infusion Syndrome.

Answer 48

- **Metabolic acidosis** thought to occur from poisoning of electron transport chain and impaired oxidation of fatty acids. - S/sx: Lactic acidosis, Brady-dysrhthmias, Rhabdo. ## Footnote PIS expected to occure in gtt's > 75 mcg/mg/min for > 24 hrs. Is reversible in early stages but may require ECMO if cardiogenic shock occurs.

Answer 49

**Green and cloudy urine** from phenols and uric acid crystals. *Neither alters renal function.*

Answer 50

- >75 μg/kg/min for longer than 24 hours

Answer 51

- Severe, refractory, fatal bradycardia - While we prefer not to give propofol to pedi, if you have to, heaviliy consider small dose of glyco before. Pediatric patients have to keep high HR to maintain CO! ## Footnote FDA blackbox to not use propofol in children but we still do because anesthesia knows best...seriously though, consider glyco or some other alternative to keep HR normal, especially in kids because nobody wants the smoke.

Answer 52

- Urine changes, lactic acidosis, brady-dysrhythmias, and rhabdomyolysis. - ABG & serum lactate concentrations.

Answer 53

- Injection pain (lido before) - ↓ IOP (great for galucom patients) - Plt aggregation inhibition (slight bleeding risk?) - Allergic reactions (lecithin) - Prolonged myoclonus - Abuse/misuse (MJ gone too soon)