Pharm - IV Anesthetics

Question 1

What is special about the mechanism of propofol?

Answer 1

• low conc- acts like barbituates & reinforces GABA
• high conc - instead of acting on GABA, it acts on NMDA glutametergic system that blocks excitation.

*it is independent of GABA being present

Question 2

What are the 2 ascending arousal pathways?

Answer 2

1. cholinergic activates thalamus

2. (monoamine), histaminergic, serotonergic, GABAergic activates cortex to process thalamic inputs

Question 3

What are adverse effects of cholinergic antagonists?

Answer 3

• block cholinergic activity = reduce lvl of consciousness
• the addition of a muscarinic anticholinergic drug to anesthetic premedication to decrease secretions and to prevent harmful vagal reflexes was mandatory in the era of ether anesthesia, but it is no longer necessary with modern inhalational agents.

Question 4

How do antihistamines produce sedation?

Answer 4

produce sedation via blockage of histaminergic system

Question 5

What is the NMDA glutametergic system?

Answer 5

NMDA receptor allows for transfer of electrical signals betw neurons in brain & spinal column.
- Receptor must be open for signals to go through—to be open, need to be binded to glycine or glutamate.

Question 6

What is special about the mechanism of Ketamine?

Answer 6

has no effect on GABA, but is a NMDA receptor antagonist.

Question 7

What do barbiturates do to GABA receptors? What about benzodiazepines? What do they both have in common?

Answer 7

• Barbiturates prolong binding of GABA to receptor (inc opening time–more profound effect than benzodiazepines)
• Benzodiazepines cause an allosteric change in receptor activity [activity of receptor is shifting to LEFT (smaller amounts of GABA produces a larger effect]

*BOTH require endogenous GABA for their action

Question 8

What is the difference in dosages of barbiturates & benzodiazepines?

Answer 8

• high lvls of barbiturates can be lethal
• benzodiazepines have a ceiling effect–no matter how much you inc dose it is plateau’d [shifts dose response curve of GABA left, but max effect doesn’t change]

Question 9

IV anesthetics redistribute basically throughout the body via the circulation. However, the majority of the initial drug bolus goes to the _____. The reason for this is because the drugs are highly _____.

Answer 9

brain (cerebral circulation); lipophilic

*drug will go to areas with more blood flow 1st & then later diffuse to tissue with lesser blood supply

Question 10

Although onset & distribution of IV anesthetics are rapid, the drugs’ ____ is much slower.

Answer 10

Elimination; this could take many hours…

*Why would they have a short duration of clinical action if they have such long elimination half-lives? This is bc they undergo rapid redistribution (bc highly lipid soluble) from their main site of action to non-active sites.

Question 11

After prolonged infusions, drug half lives and durations of action are dependent on complex interaction between what 3 factors?

Answer 11

drug redistribution, accumulation in fat, and drug metabolic rate

Question 12

If you want to have no effect on CV system, which IV anesthetic would you choose?

Answer 12

etomidate (useful for pts w/ underlying CV problems)

Question 13

What IV anesthetic could precipitate porphyria?

Answer 13

Thiopental can cause porphyria due to hepatic enzyme induction in susceptible pts.

Question 14

What does antiemetic mean, and what drug has this?

Answer 14

Antiemetic = inhibits nausea & vomiting; propofol

Question 15

What is propofol infusion syndrome?

Answer 15

• rare syndrome which affects patients undergoing long-term treatment with high doses of propofol.
• can lead to myocardial failure, rhabdomyolysis, metabolic acidosis, arrhythmias, hepatomegaly, and renal failure, and is often fatal.

Question 16

How do you treat propofol infusion syndrome?

Answer 16

stop drug, cardiocirculatory stabilization, correction of metabolic acidosis
• Hemodialysis

Question 17

Which drug inhibits steroidogenesis (by preventing cortisol activity)?

Answer 17

etomidate

Question 18

What is special about ketamine in comparison to other IV anesthetics?

Answer 18

can cause dissociated state = eyes open, but unconscious & pain-free

Question 19

What are some advantages/attributes of benzodiazepines

Answer 19

– Anticonvulsant, amnesia act on memory stabilization receptors
– Wide therapeutic safety margin
– Specific antagonist: flumazenil (Romazicon)
– Minimal CV, & respiratory depression if used alone
– useful where no analgesia is required

Question 20

If you needed to perform a short procedure, which benzodiazepine would you use? Which one would you not use?

Answer 20

• Midazolam = half-life of 10-20 hrs

- Diazepam = half-life of 20-40 hrs

Question 21

Advocates for opiods?

Answer 21

– absence of direct effects on heart
– maintenance of regional bloodflow autoregulation
– decreased airway reflexes (facilitates intubation)
– pain relieved but patient arousable
– non organotoxic: no malignant hyperthermia

Question 22

Critics for opiods?

Answer 22

• incomplete amnesia
• histamine-related reactions
• increased blood requirements
• prolonged respiratory depression in ICU
• cardiovascular instability
  • bradycardia, hypo- or hypertension
  • addition of N20 results in cardiovascular depression

Question 23

What do Fentanyl congeners do?

Answer 23

Act at opiate receptors (OP1-3) in spinal cord and CNS

*morphine also does this, but fentanyl induces analgesia more rapidly

Question 24

What is the overdose triad of opiods?

Answer 24

pinpoint pupils, dec respiration, coma.

Question 25

What are the effects of opiods?

Answer 25

1. dose-dependent respiratory depression
2. muscle rigidity: “wooden chest” syndrome
3. inc’d intracranial BF & pressure
4. nausea, vomiting, constipation, miosis
5. overdose triad

Question 26

What is the tx to reverse the effects of opiods?

Answer 26

naloxone (Narcan) nalmefene (Revex)

Question 27

What do anesthetics do in response to PaCO2?

Answer 27

Anesthetics reduce normal ventilation response to PaCO2–no reflex response. Baroreceptor attenuation.

Question 28

For long-lasting analgesia, what is the drug of choice?

Answer 28

morphine; peak relief 15-30 min

Question 29

What is the new opioid class that is very effective and is rapidly metabolized?

Answer 29

Remifentanil (Ultiva)

• rapid onset & peak effect
• short half-life
• non-cumulative
• recovery rapid when administration is discontinued (loss of analgesia).

Question 30

What is the “20 min drug for a 20 min procedure”?

Answer 30

Fetanyl
–  More lipid soluble
–  Onset in <30 seconds
–  Peak effect in 2-3 min
– nausea & vomiting = rare, unlike in morphine!


Question 31

What is the pharmacogenomic (autosomal dominant) disorder of the skeletal muscle? Briefly describe it.

Answer 31

MALIGNANT HYPERTHERMIA

• involves ryanodine receptor in SR (issue w/ sequestering Ca)
• uncontrolled loss/release of Ca that produces
  1. muscle rigidity/tension
  2. inc body temp (fever)
  3. inc metabolic activity (inc in lactate & CO2)

Question 32

What drug was malignant hyperthermia originally recognized in? What are other triggers of MH?

Answer 32

succinylcholine

other: desflurane, sevoflurane

Question 33

What is the tx for malignant hyperthermia?

Answer 33

Tx: DANTRIUM–causes repackaging of liberated Ca back into sarcoplasmic hypothermia

• stop giving trigger agent; hyperventilate w/ O2
• avoid Ca chnl blockers
• correct hyperkalemia & acidosis, cool core temp

Question 34

Why should Ca channel blockers not be given w/ dantrolene/dantrium?

Answer 34

When used with calcium channel blockers, dantrolene may produce life-threatening hyperkalemia and myocardial depression.