Volatile Anesthetics
You can reduce the formation of this potentially nephrotoxic compound formed by the reaction of this inhaled anesthetic and alkali CO2 absorbers by reducing fresh gas flow, reducing anesthetic delivery, preventing the CO2 absorber from overheating or becoming excessively dry, or using a Ca(OH)2 absorber. (two answers)
What is compound A and sevoflurane?
You might be concerned for this syndrome in a critically ill patient with unexplained severe metabolic acidosis, rhabdomyolysis, multisystem organ failure, and hypertriglyceridemia especially if they are on >4mg/kg/hr of this sedative hypnotic.
What is propofol infusion syndrome and propofol?
Opioid exert their effect in these three anatomic parts of the spinal cord, brainstem, and brain.
Dorsal horn of the spinal cord, substantia gelatinosa has high concentration of mu-opioid receptors; inhibition the release of substance P mitigating the transfer of painful/peripheral sensations to the brain.
Brainstem -- periaqueductal gray matter/medulla; modulates nociceptive transmission in the dorsal horn of the spinal cord through descending inhibitory pathway potentiation/activation
Brain -- direct action on cortical regions which are thought to change the pain processing centers and activation of central reward pathways to create calm/satisfied/euphoric sensation
Generally speaking, opioids act at spinal, brain, and peripheral u-receptors providing analgesia by attenuating nociceptive traffic from the periphery and also altering the affective response to noxious stimulation centrally. Thus, analgesia is likely the result of activity and multiple nervous system sites.
When calcium stimulates the release of acetylcholine into the neuromuscular junction at the motor neuron endplate it must bind to both of these subunits on this receptor to trigger an action potential.
What is both alpha subunits of the nicotinic acetylcholine receptor?
This PK/PD "space" refers to the immediate milieu where a drug acts upon the body.
What is the biophase.
Essentially refers to the immediate milieu where drug acts upon the body; more thoroughly described as the time required for drug to diffuse from plasma to the site of action + time required for drug to elicit an effect
John Dalton described a law related to this ideal gas property in 1802. Coincidentally, the property described is also responsible for achieving the steady state and effective dose of volatile anesthetics.
What is partial pressure?
All barbiturates, except for this drug commonly used to provide anesthesia for electroconvulsive therapy, increase the seizure threshold through their GABAergic effects.
What is methohexital?
This hydromorphone metabolite may cause this symptom when given in patients with renal failure.
Neuro-excitation (tremors, agitation, myoclonus, hyperalgesia)
Hydromorphone is hepatically metabolized via glucuronic acid conjugation to hydromorphone-3-glucuronide, which has no analgesic/opioid receptor property but is neurotoxic. May cause neuro-excitation and cognitive impairment especially in accumulation for patients with renal disease
Drugs in this structural class of non-depolarizing neuromuscular blocking agents are more likely to cause histamine release... it's a tongue twister.
What are Benzylisoquinoliniums?
e.g. cisatracurium, atracurium, mivacurium
The other class of NDNMBAs are aminosteroids. e.g. pancuronium, vecuronium, rocuronium.
This pharmacokinetic term refers to the delay between drug plasma concentration and peak effect site concentration following bolus administration.
Hysteresis
Explains the general principle that as we induce a patient with propofol, although plasma concentrations have peaked immediately, we DO NOT immediately intubate
This partition coefficient is related to inhaled anesthetic potency and inversely proportional to MAC while this partition coefficient is related to inhaled anesthetic solubility and related to the rate of induction and emergence from an inhaled anesthetic. (two answers)
What is the oil:gas partition coefficient and the blood:gas partition coefficient?
Despite reducing CBF, CMRO2, and ICP, an IV bolus induction dose of propofol may decrease this hemodynamic variable defined as MAP - ICP or CVP (whichever is higher) depending on the effects on systemic SVR.
What is cerebral perfusion pressure?
Acute opioid effects are mediated by agonism of this receptor and mediated by what two secondary messengers.
What is GPCR; inhibition of adenylyl cyclase & voltage-gated calcium channels?
GPCR activation has a primarily inhibitory effect leading to hyperpolarization of the cell reducing neuronal excitability.
You performing a preoperative assessment when a patient tells you they had a dibucaine test performed due to a complication from a previous surgery. They report a dibucaine number of 20%. Based on this, the patient is likely has this kind pseudocholinesterase deficiency.
What is homozygous pseudocholinesterase deficiency?
Dibucaine inhibits NORMAL pseudocholinesterase (plasma cholinesterase, butyrylcholinesterase). 80% inhibition suggests normal enzyme function, 50% suggests heterozygous mutation, 20% suggests homozygous mutation.
This elimination order kinetic describes a constant amount of drug removed per unit time while this elimination order kinetic describes a constant fraction of drug eliminated per unit time.
What is zero-order kinetics and first order kinetics.
Zero order kinetics describes a situation where the enzyme or enzymes involved in that particular drug’s metabolism are at maximum capacity or Vmax. In this situation, drug metabolism is independent of drug concentration because the enzymes are saturated. This means the rate of elimination is constant or linear; there is a constant amount (like mg) of medication removed per unit time
First order kinetics describes a situation where drug elimination is proportional to drug concentration. As more drug is introduced into the system, more enzymes are induced and metabolism increases proportionally. The rate of elimination is not constant nor linear; it is exponential. As time goes on, progressively less drug leaves the body per time constant. Liver blood flow dependent elimination is characteristic of first-order kinetics, not zero-order kinetics.
Either way, it is important to remember that drug metabolism is not an inherent property of a medication, but rather a way to describe mathematically how these drugs behave in vivo.
Compared to a healthy newborn, a newborn with tricuspid atresia undergoing an inhaled induction with isoflurane will have a (faster/slower/unchanged) rate of induction. This effect will be even (faster/slower/unchanged) if sevoflurane is used.
What is slower and slower?
Match the following sets of characteristics and drugs.
1. Ketamine
2. Propofol
3. Etomidate
4. Dexmedetomidine
A. inhibits 11-beta-hydroxylase, causes thrombophlebitis, induces myoclonus, can trigger porphyria attack
B. highly protein bound, lowers seizure threshold, high affinity for inhibitory auto-receptor, common adjunct in peripheral nerve blocks, lacks amnestic properties, does not cause respiratory depression
C. increases CBF, direct myocardial depressant, stimulates catecholamine release, preserves airway reflexes, causes nystagmus
D. can cause myoclonus, causes dose dependent respiratory depression, has anti-emetic properties, causes thrombophlebitis
1. C
2. D
3. A
4. B
Tramadol needs to be metabolized by what enzyme to what metabolite in order to be activated?
What is CYP2D6.
O-desmethyltramadol has a greater affinity for the mu-opioid receptor and exhibits a longer half-life. Becausae of this phenomena, there is variable effectiveness of tramadol due to variations in CYP2D6 activity; ultra-rapid metabolizers may be prone to opioid adverse effects (like respiratory arrest). Because of this, tramadol (and codeine for that matter) is usually avoided in children < 12 yo.
What is vecuronium?
Rocuronium - 70% hepatic metabolism, no active metabolites
Vecuronium - 50% hepatic metabolism, 3-OH metabolite has 80% activity and accumulates in renal failure
Cisatracurium - Hoffman degradation
Elderly patients have increased or decreased changes to the following pharmacokinetic principles:
Lean body mass
Body fat
Total Body water
Hepatic and renal clearance
Plasma proteins
Decrease lean body mass
Increased body fat --> larger Vd for fat soluble drugs
Decreased total body water --> smaller central compartment and Vd for water-soluble drugs
Decreased hepatic and renal clearance --> decreased metabolism
Decreased plasma proteins --> less protein binding causing changes to effective concentration and duration of action
To deliver 1 MAC of sevoflurane to a 40 year old adult on Mt. Everest (atmospheric pressure 235mmHg) you must deliver this percent concentration of anesthetic. For desflurane you must deliver this percent concentration of anesthetic.
What is 2% and 19%?
Place the following IV anesthetics in ascending order based on their context- sensitive half lives after prolonged infusions.
1. Dexmedetomidine
2. Ketamine
3. Propofol
3. Midazolam
4. Thiopental
5. Etomidate
6. Diazepam
1. Etomidate
2. Propofol
3. Ketamine
4. Dexmedetomidine
5. Midazolam
6. Diazepam
Place these opioids in descending order of potency:
Methadone
Remifentanil
Fentanyl
Hydromorphone
Morphine
Sufentanil
Drug (analgesic equivalent)
Sufentanil (5 mcg)
Remifentanil ~ Fentanyl (50 mcg)
Hydromorphone (0.75 mg)
Methadone (2.5 mg)
Morphine (5 mg)
Compared to succinylcholine, the fade noted on train of four monitoring for NDNMBAs is due to their ability to block this receptor.
What is presynaptic acetylcholine receptors?
The hydrolic three-compartment model of IV bolus'd medications has these three distinct phases.
Rapid-distribution and equilibration begins immediately after injection -- phase 1
Slow-distribution and equilibration alongside return of drug to plasma from rapidly equilibrating tissues -- phase 2
Terminal or elimination-phase as drug is eliminated from the body, however best characterized as plasma [drug] > tissue [drug] in which the relative proportion of [drug] in plasma AND tissue reamins constant (thus the nearly straight line) -- phase 3