PHARMACOLOGY | IV Anesthetics Part II Flashcards
Sedation of which following drugs most likely to resemble normal sleep?
A) Propofol
B) Midazolam
C) Dexmedetomidine
D) Ketamine
C) Dexmedetomidine
The α2 agonists produce their sedative-hypnotic effect by an
action on α2 receptors in the locus ceruleus and an analgesic action at α2 receptors within the locus ceruleus and within the spinal cord.
The sedative effect of dexmedetomidine acts through the endogenous sleep-promoting pathways, generating natural sleep patterns.
Least likely side effect of dexmedetomidine in healthy patient is?
A) Respiratory arrest
B) Bradycardia
C) Sinus arrest
D) Hypotension
A) Respiratory arrest
The most commonly reported hemodynamic adverse reactions associated with dexmedetomidine in a phase III trial in 401 patients were hypotension (30%), hypertension (12%), and bradycardia (9%).
Which of the following is NOT an adverse effect of Dexmedetomidine during a maintenance dose?
A. Bradycardia
B. Dry mouth
C. Nausea
D. Hypertension
E. Shift of CO2 response curve to the right
E. Shift of CO2 response curve to the right
The main adverse reactions of dexmedetomidine are hypotension, bradycardia, dry mouth, nausea, and hypertension.
Post anesthesia shivering can be treated w/ all of following except?
A) Naloxone
B) Physostigmine
C) Mg sulfate
D) Dexmedetomidine
A) Naloxone
TRUE or FALSE
Dexmedetomidine pharmacokinetics are not significantly different in patients with severe renal impairment
compared to healthy subjects
TRUE
Clinically, the use dexmedetomidine effect on MAC is:
A) No change
B) Increase
C) Decrease
D) Acute: increase; chronic: decrease
C) Decrease
- This probably due to he propensity of Dexmedetomidine to hypotension.
TRUE or FALSE
Dexmedetomidine decreases the incidence of emergence delirium.
TRUE
Compared to placebo, dexmedetomidine (0.5 to 1 mcg/kg)
decreases the incidence of emergence delirium from 47% to 2.8% with slightly prolonged emergence time
TRUE of Dexmedetomidine EXCEPT:
A. Biotransformation involves both direct glucuronidation as well as cytochrome P450– mediated metabolism.
B. It shows a high ratio of specificity for the α2-receptor (α2/α1 = 1600:1) compared with clonidine (α2/α1 = 220:1).
C. Polymorphism in CYP2A6 does not influence clinical dosing regimens
D. It has a very low protein binding
E. Renal dosing is necessary especially in renally challenged patients
D. It has a very low protein binding - FALSE
Dexmedetomidine belongs to the imidazole subclass of α2-receptor agonists, similar to clonidine, and its structure. It is freely soluble in water and available as a clear isotonic solution containing 100 μg per mL and 9 mg sodium chloride per mL of water.
- Highly protein bound - close to 95%
- Renal dosing is not necessary.
The pharmacokinetics of dexemedetomidine are not
influenced by renal impairment (creatinine clearance
<30 mL/min) or age
The plasma concentration of Dexmedetomidine which corresponds to “conscious sedation” significant yet rousable sedation:
A. 0.2 to 0.3 ng/mL
B. 0.1 to 0.5 ng/mL
C. 0.01 - 0.1 ng/mL
A. 0.2 to 0.3 ng/mL
- The plasma concentration at which significant yet rousable sedation is achieved is about 0.2 to 0.3 ng/mL.
- Unarousable deep sedation is thought to occur at plasma concentrations above 1.9 ng/mL.
1.9 ng/mL = UNAROUSEABLE DEEP SEDATION!
Miller | 9th edit
The analgesia effect of dexmedetomidine at least in the SPINAL level is primarily thru:
A. stimulation of the α2C and α2A receptor in the dorsal horn
B. stimulation of the α2C and α2A receptor in the ventral horn
The analgesic effect of the α2 agonists is mediated through
stimulation of the α2C and α2A receptor in the dorsal horn,
directly suppressing pain transmission by reducing the
release of pronociceptive transmitters, substance P and glutamate, and hyperpolarization of interneurons.
TRUE or FALSE
The significant CNS effect of Dexmedetomidine is decrease in CBF WITHOUT reduction in CRMO2.
TRUE
Miller | 9th edit
TRUE or FALSE
Dexmedetomidine significantly REDUCES minute ventilation and ventilatory response curve
In spontaneous breathing volunteers, dexmedetomidine
at concentrations producing significant sedation
reduces minute ventilation, but results in no change in
arterial oxygenation, pH, or the slope in the CO2 ventilatory response curve.
Miller | 9th edit
Clinical significance of omitting the loading dose of Dexmedetomidine:
A. Minimizes transient hypertension
B. Reduction of the incidence of bradycardia and hypotension
C. All are correct
All are correct statement!
The incidence of hypotension and bradycardia may be related to the administration of a large intravenous “loading” dose. Omitting the loading dose or not giving more than 0.4 μg/kg reduces the incidence of hypotension or makes it less pronounced.
The bradycardia associated with dexmedetomidine
typically occurs after a loading dose.
- Omitting the loading dose decreases the incidence of bradycardia
Giving the loading dose over 20 minutes also minimizes the
transient hypertension
TRUE or FALSE
Dexmedetomidine can be employed as an agent for the treatment of substance abuse addiction.
TRUE
Dexmedetomidine can be employed for addiction treatment;
it has been described for use in rapid opioid detoxification,
cocaine withdrawal, and iatrogenic-induced benzodiazepine and opioid tolerance after prolonged sedation.
The principal mechanism of action of the barbiturate
class of drugs is best described as:
(A) blockade of CNS sodium channels
(B) inhibition of NMDA receptors
(C) potentiation of GABA-mediated chloride currents
(D) stimulation of mu- and kappa-opioid receptors
(E) stimulation of alpha-2 adrenergic receptors
(C) potentiation of GABA-mediated chloride currents
In which of the following circumstances should the
induction dose of barbiturates be reduced?
(A) neonates
(B) plasma pH of 7.25
(C) plasma pH of 7.55
(D) nonpregnant female patients
(E) patients taking barbiturates regularly
(B) plasma pH of 7.25
Chronic use of barbiturates is known to induce the
same oxidative microsomal enzymes that are responsible
or metabolism. For this reason, patients that take
barbiturates often require a higher induction dose.
Barbiturates are weak acids, and both thiopental
(7.6) and methohexital (7.9) have a pKA slightly above
normal physiologic pH. Thiopental and methohexital
are approximately 40% and 25% ionized at physiologic
pH, respectively.
Acidosis will increase the nonionized fraction and favor transfer of these agents into the brain. In patients who are acidemic, a dose reduction of approximately 50% is often recommended in order to achieve an appropriate effect.
In contrast, patients who are alkalemic frequently require an increased dose.
Miller | 9th edit
TRUE or FALSE
Primary metabolism of both barbiturates classes is hepatic.
TRUE
Primary metabolism of both barbiturates classes is hepatic, yielding water soluble inactive metabolites that are subsequently eliminated in urine and bile.
TRUE or FALSE
Thiopental exhibits ZERO order kinetics
TRUE!
TRUE or FALSE
A low dose of Thiopental typically produces burst suppression
FALSE
- Low dose = Low amplitude and high frequency
- High dose = Burst suppression
In obese patients, the inducting dose of Thiopental should ideally be based on:
A. LBW
B. Actual body weight
C. Total body weight
A. LBW
Why is Thiopental not ideal for continuous IV infusion?
READ
TRUE or FALSE
Thiopental has HIGH HEPATIC EXTRACTION RATIO
FALSE
It’s one of the drugs that displays low extraction ratio.
For drugs with low intrinsic clearance:
Hepatic extraction ratio will drop more rapidly with increasing hepatic blood flow.
Hepatic clearance will not increase significantly with increasing blood flow.
For drugs with high intrinsic clearance:
Hepatic clearance will increase in a fairly linear fashion, in proportion to hepatic blood flow.
Increasing the intrinsic clearance will have diminishing effect on total hepatic clearance.
Which of the following medications have HIGH hepatic extraction ratio:
A. Diazepam
B. Rocuronium
C. Methadone
D. Ketamine
D. Ketamine
Cardiovascular effect of Barbiturates EXCEPT:
A. decreases in MAP
B. decrease in cardiac output.
C. peripheral pooling of venous blood, hence decrease in venous return
D. No change in MAP
D. No change in MAP
The most prominent cardiovascular changes after an induction dose of thiopental are decreases in both MAP and cardiac output.
The primary mechanism is reduction of venous vascular tone, followed by peripheral pooling of venous blood and a decrease in venous return.
