IV induction meds

Question 1

Barbiturates MOA

Answer 1

depresses RAS in brainstem by binding GABAa receptor

• increases duration of Cl channel opening
• long-branched chain at C5 determines the potency and anticonvulsant property

Question 2

Distribution of Barbs

Answer 2

redistributes to skeletal muscle where it accumulates
- affected by low protein and volume contraction

*can get dose stacking due to this

Question 3

Biotransformation of Barbs

Answer 3

hepatic oxidation

Question 4

Effects of Barbs on Organs

Answer 4

CV: vasomotor medullary depression with vasodilation = pooling of blood and reflexive tachycardia
Resp: depresses ventilatory center and response to hypercarbia
CNS: constricts vasculature = reduced CBF and ICP
- increased cerebral perfusion, reduces CMRO2
Hepatic: Aminolevulinic Acid Synthetase –> porphyrin
Immune: thiobarbs evoke mast cell release and histamine

Question 5

Benzos MOA

Answer 5

binding to GABAa -> increase frequency of Cl channel opening

*Flumazenil = benzo receptor antagonist

Question 6

Burning of benzos with injection

Answer 6

IV forms are insoluble in water and therefore contain propylene glycol = burns with irritation

Question 7

Absorption of Benzos

Answer 7

diazepam and lorazepam around 1-2 hrs

Question 8

Distribution of Benzos

Answer 8

high lipid solubility –> rapid penetration of BBB

Question 9

Biotransformation of Benzos

Answer 9

hepatic glucuronidation

• diazepam has active metabolites
• midazolam has highest hepatic extraction

Question 10

Organ effects from benzos

Answer 10

CV: minimal
Resp: dose-dependent depression of response to CO2 (rare for apnea)
CNS:  decreases CMRO2, CBF, ICP
   - anterograde amnesia
   - good for breaking seizures

Question 11

Ketamine MOA

Answer 11

NMDA receptor antagonist - dissociates the thalamus from limbic system (no relay to the awareness)
*Structural analog of PCP

Question 12

Distribution of Ketamine

Answer 12

VERY LIPID SOLUBLE -> rapid brain uptake and entering into BBB

Question 13

Biotransformation of Ketamine

Answer 13

hepatic -> to norketamine

Extensive hepatic extraction = short elimination (2-3 hrs)

Question 14

Organs effects of Ketamine

Answer 14

CV: increase MAP, CO, HR
- central stimulation from SNS activation
- inhibition of NE uptake @ nerve terminals
*be careful in CHF/trauma patients with reduced cathecholamine reserves, can precipitate CV collapse due to the myocardial depression
Resp: minimal effect on respiratory drive
- bronchodilator, increased secretions
CNS: ok to use with high ICP as long as you hyperventilate
- increased CMRO2, ICP, CBF

Question 15

Etomidate MOA

Answer 15

depresses RAS and mimics the inhibitory effects of GABAa

- possible disinhibition for extrapyramidal motor cortex = leading to myoclonus

Question 16

Distribution of Etomidate

Answer 16

GREAT lipid solubility and non-ionized fraction = very rapid induction
- can be used for RSI

Question 17

Biotransformation of Etomidate

Answer 17

plasma esterases hydrolyze into inactive metabolites

Question 18

Organ effects of Etomidate

Answer 18

CV: minimal, reason to use in unstable patients
Resp: minimal
CNS: decreases CMRO2, CBF, ICP
- CPP is well maintained due to limited effect on CV system
Endocrine: transient inhibiton of 11-beta hydroxylase can leading to adrenocortical suppression (more with long infusions)

Question 19

Propofol MOA

Answer 19

allosterically increases binding affinity of GABA –> hyperpolarization of nerve terminals
*not soluble in water -> made with oil-water emulsion w/ soybean oil, glycerol and egg lecithin
Ok with egg allergies
- most allergies are from white albumin, propofol made with yolk

Question 20

Sterility and propofol

Answer 20

Propofol can support bacteria growth due to the way it is comprised = use sterile technique and administer within 6 hrs of opening
- it contains EDTA or bisulfate to retard bacteria growth

Question 21

Distribution of Propofol

Answer 21

RAPID ONSET - very lipid soluble

• initial short distribution t1/2
• reduced dose in elders given the lower volume of distribution
• less “hangover”

Question 22

Biotransformation of Propofol

Answer 22

clearance of propofol exceeds hepatic blood flow

• some clearance in kidneys and lungs
• inactive metabolites

Question 23

Propofol infusion syndrome

Answer 23

prolonged infusion - patients develop lipemia (high triglycerides), refractory acidemia leading to death

Question 24

Organ Effects of Propofol

Answer 24

CV: inhibition of SNS vasomotor response -> reduction in MAP, preload and contractility (direct myocardial suppression)
Resp: profound respiratory depressant leading to apnea
- inihibits hypoxic ventilatory response and blunts upper airway reflexes
CNS: decreased CBF, ICP, CMRO2
- can cause a critical reduction in CPP due to effects on MAP
- antipruritic, antiemetic, anticonvulsant

*CAN make urine green!