INTRAVENOUS ANESTHETICS

Question 1

Discuss the pharmacokinetics of propofol?

How does it induce anesthesia?

Answer 1

Most frequently used for the induction of anesthesia
Increase GABA mediated INHIBITORY tone in the CNS. Propofol decreases the rate of dissociation of the GABA from the receptor, thereby increasing the duration of the GABA-activated opening of the chloride channel with resulting hyperpolarization of cell membranes.

Question 2

2. What are its effects in the different organ systems?

CNS: ECG, CMRO2, CBF, and ICP

Answer 2

CNS: causes a dose-dependent decrease in cerebral function, culminating in unconsciousness
Propofol produces ECGchanges characteristic of general anesthesia with a decrease in global cerebral function and is accompanied by decreased cerebral metabolism, cerebral blood flow, and intracranial pressure.

Question 3

Propofol benefits

Answer 3

Rapid onset and offset
Low cost
minimal side effect

Question 4

Activation of GABA does what?

Answer 4

activation of the ligand-gated GABAA receptors increases chloride ion permeability and inhibits further action potential generation.

Question 5

IV propofol dose and onset of action

Answer 5

Injected intravenously as a bolus dose of 2 mg/kg, propofol induces unconsciousness in less than 1 min, a rate that is comparable to that of thiopental, etomidate, and methohexital.

Question 6

IV propofol dose and onset of action

Answer 6

Injected intravenously as a bolus dose of 2 mg/kg, propofol induces unconsciousness in less than 1 min, a rate that is comparable to that of thiopental, etomidate, and methohexital.

Question 7

IV propofol duration of action

Answer 7

3-5 minutes

Question 8

IV propofol duration of action

Answer 8

4-5 minutes

Question 9

Propofol on CV: BP, SVR,
At higher doses does what?
How to attenuate hypotension produced by Propofol

Answer 9

Propofol reliably causes a dose-dependent decrease in blood pressure.
Decrease in BP is mediated by decreased SVR though myocardial contractility decreases at higher doses, resulting in a fall in cardiac output. Propofol-induced hypotension can be attenuated by slow titration of bolus doses and/or the concomitant use of vasoactive medications such as phenylephrine.

Question 10

Propofol and the respiratory system?

Respiratory drive, apnea, Bronchodilation and HPV?

Answer 10

Propofol produces a dose-dependent depression of central respiratory drive that ultimately results in apnea.
Propofol can produce bronchodilation and has minimal effects on hypoxic pulmonary vasoconstriction

Question 11

Propofol effect on the respiratory response to CO2 and hypoxia? What can make the decrease response worse? How can you preserve spontaneous respiration ?

Answer 11

The ventilatory response to carbon dioxide and hypoxia is decreased, and the effect is compounded with the addition of other respiratory depressants (e.g., opioids, benzodiazepines).Carefully titrated boluses (or low-dose infusion) for sedation can preserve spontaneous respiration; however, the individual patient response is variable.

Question 12

Mostly propofol causes a

Answer 12

decrease effect on most organ systems

Question 13

Starting dose of propofol for conscious sedation is

Answer 13

50mcg per kg /min

COntinuous of 100-200mcg/kg/min

Question 14

rapid of offset of propofol is because of

Answer 14

The rapid offset time of propofol following an intravenously administered bolus dose is caused by redistribution, Half life 2-8 min

Question 15

Propofol excretion

Answer 15

Propofol is excreted as glucuronide and sulfate conjugates, primarily in the urine.

Question 16

Gold standard of IV anesthetics for protection of the brain is

Answer 16

Barbiturates are the historic “gold standard” for neuroprotection when they are administered before a focal ischemic event.

Question 17

Barbiturates on EEG

Answer 17

resulting in electroencephalographic isoelectricity. burst suppression are equally cerebroprotective, suggesting that additional protective mechanisms are in effect

Question 18

Unwanted effects of Barbiturates

Answer 18

Unwanted effects of high-dose barbiturates, such as cardiovascular instability and delays in awakening and neurologic assessment, must be considered when using this class of drug.

Question 19

The most significant aspect of the metabolism of barbiturates (e.g., phenobarbital, thiopental, methohexital) is their effect on the

Answer 19

hepatic microsomal enzyme system (cytochrome P450 (CYP) enzymes). Chronic use of barbiturates will cause upregulation, or induction, of the microsomal enzymes (CYPs 1A2, 2C9, 2C19, and 3A4), increasing the metabolism of drugs metabolized by these enzymes.

Question 20

Barbiturates and contraindications

Answer 20

contraindicated in patients with acute intermittent porphyria (AIP) or variegate porphyria because they may precipitate an attack,

Question 21

Barbiturates metabolized by ______excreted by

Answer 21

Liver; Kidneys

Question 22

Barbiturates MOA

Answer 22

Binds to GABA, at a different site than benzodiazepines

Question 23

Barbiturates and CV

Answer 23

Direct myocardial depression, (2) peripheral venous pooling with decreased left ventricular diastolic filling and stroke volume, and (3) decreased sympathetic nervous system outflow from the central nervous system.1

Question 24

What are the effects of benzodiazepines on the respiratory system and the central nervous system?

Answer 24

Respiratory depression

Question 25

9. What are the clinical uses of benzodiazepine?

Answer 25

Use for amnesia, anticonvulsants, sedatives

Question 26

Benzodiazepines, mediated through the promotion of

Answer 26

binding of γ-aminobutyric acid (GABA) to the GABAA receptor, with subsequent enhancement of the inhibitory effect of GABA on neuronal excitability.

Question 27

WHy did Benzos replace barbiturates?

Answer 27

All benzodiazepines possess sedative-hypnotic properties and have displaced barbiturates for this purpose, primarily because of their remarkably low capacity to produce fatal CNS depression.

Question 28

Midazolam on BP and HR

Answer 28

Peripheral vasodilation , decrease BP and increase in HR

Question 29

CBF; CMRO2, The administration of midazolam results in dose-related

Answer 29

decreases in cerebral blood flow and cerebral O2 consumption.

Question 30

Midazolam properties

Answer 30

sedative, anxiolytic, amnesic, and anticonvulsant properties.

Question 31

Water solubility of midazolam

Answer 31

Midazolam is water soluble, making the addition of propylene glycol unnecessary.

Question 32

What class of drugs does ketamine belong to?

Answer 32

Chemically related to PCP. It is a dissociative anesthetics,
Patient appears dissociated from the environment, WHILE OTHER REFLEXES remain intact, including corneal, papillary, and gag reflexes, laryngeal tone, and muscle tension. EEG showing that the thalamus is no longer synchronized with, or is “dissociated” from, the limbic system.

Question 33

What is the mechanism of action of ketamine?

Answer 33

Ketamine pharmacology is complex because it is not a particularly selective drug, with multiple sites of action, including those in the central and peripheral nervous systems.

Question 34

What is the mechanism of action of ketamine?

Answer 34

Ketamine pharmacology is complex because it is not a particularly selective drug, with multiple sites of action, including those in the central and peripheral nervous systems.
——–noncompetitive antagonism at N-methyl-d-aspartate (NMDA) receptors for glutamate.

Question 35

Ketamine and opioid receptor action?

Answer 35

Examples include agonistic activity at µ, δ, and κ opioid receptors, providing analgesia.

Question 36

Reversal of ketamine’s central anticholinergic effects?

Answer 36

Physostigmine, an anticholinesterase, can reverse the central anticholinergic and hypnotic effects of ketamine.

Question 37

Effect of Ketamine on CV

what about heart transplant pt

Answer 37

increase in HR
MIMICS SYMPATHETIC NS
Inhibits reuptake of NE
doses (20 mg/kg) or in the denervated or transplanted heart, there is a direct negative inotropic action effect by ketamine.

Question 38

Effect on ketamine on RESP

Answer 38

Airway reflexes well maintained with ketamine
BRONCHODILATIONS
INCREASE salivary and tracheobronchial secretions however; consider scopolamine or glycopyrrolate

Question 39

Effects of Ketamine on CNS: Vasodilation vs vasoconstriction ? CBF , ICP and CMRO2

Answer 39

Ketamine, a cerebral vasodilator, causes an increase in cerebral blood flow, cerebral oxygen consumption, and intracranial pressure in patients with space-occupying intracranial lesions. Elevation of intracranial pressure is minimal if ventilation is controlled.

Question 40

What are the effects of etomidate on the cardiovascular system?
CAUTION:

Answer 40

Known for its mild CV effects
Used for patient with hemodynamics instability , decrease EF, CAD or valvular disease.
May decrease coronary blood flow and the myocardial o2 requirements will also be decrease. Be cautious with patient with O2 supply/demand instability.

Question 41

What class of drugs does dexmedetomidine belong to?

Answer 41

Dexmedetomidine is an intravenously administered α2-agonist with sedative, analgesic, sympatholytic, and anxiolytic properties.preserve respiratory drive and airway reflexes.

Question 42

How does dexmedetomidine ( Precedex )exert its effects?

Answer 42

8 times affinity for the ALPHA 2 receptor

Alpha 2 to alpha 1 ratio is 1620: 1

Question 43

How does dexmedetomidine produces its effect Presynaptically?

Answer 43

Presynaptic α2-adrenoceptor activation, primarily in the spinal cord, inhibits release of norepinephrine, terminating the propagation of pain signals.

Question 44

How does dexmedetomidine produces its effect Postsynaptically?

Answer 44

Postsynaptic α2-adrenoceptor activation in the central nervous system, primarily the locus coeruleus, both inhibits sympathetic activity and modulates vigilance

Question 45

Dexmedetomidine: What are the effects on the cardiovascular and respiratory system?

Answer 45

No direct cardiac effects
A biphasic CV response can be seen
Initially (response last 5-10 mins) : A transient increase in blood pressure, with a decrease in baroreceptor-mediated reflex in heart rate, occurs initially; is explained by peripheral α2-adrenoceptor vasoconstriction and can be attenuated by infusing the bolus over 10 min or more.
FINAL Response is : The final result is that both the blood pressure and heart rate fall 10% to 20% below baseline values. These effects are caused by inhibition of central sympathetic outflow and activation of the presynaptic α2-adrenoceptor, leading to decreased release of norepinephrine and epinephrine.

Question 46

Dexmedetomidine: Avoided in those patients

Answer 46

Hypotension, bradycardia, and varying degrees of heart block may occur; therefore dexmedetomidine should be avoided in patients with hypovolemia, hypotension, bradycardia, fixed stroke volume, or advanced heart block.

Question 47

Clinical use of Dexmedetomidine:

Answer 47

As an adjunct To local, regional, and general anesthesia
In labor analgesia and cesarean delivery

• To facilitate awake fiberoptic intubation in patients with difficult airways
• In combination with propofol, to provide anesthesia for infants undergoing microlaryngeal surgery

To alleviate preoperative anxiety and emergence delirium in children*

To blunt the cardiovascular effects of cocaine intoxication

To treat drug and alcohol withdrawal syndromes

Question 48

In the following clinical scenarios, what IV anesthetics would you like to use and why?
• 70 y/o male with well controlled hypertension and CAD, presenting for elective colonectomy
• 25 y/o male, mentally challenged, agitated, no IV access for dental rehab
• 42 y/o previously healthy male in burn unit for lower extremity dressing change
• 30 y/o multigravid female for emergency C-section 2° to bleeding placenta previa, BP 80/40
• 27 y/o intoxicated male in ER, s/p MVA, combative, unable to obtain vital signs because of agitation

Answer 48

Reasone