Flashcards in Pharm - IV Anesthetics Deck (34):
What is special about the mechanism of propofol?
- 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
What are the 2 ascending arousal pathways?
1. cholinergic activates thalamus
2. (monoamine), histaminergic, serotonergic, GABAergic activates cortex to process thalamic inputs
What are adverse effects of cholinergic antagonists?
- 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.
How do antihistamines produce sedation?
produce sedation via blockage of histaminergic system
What is the NMDA glutametergic system?
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.
What is special about the mechanism of Ketamine?
has no effect on GABA, but is a NMDA receptor antagonist.
What do barbiturates do to GABA receptors? What about benzodiazepines? What do they both have in common?
- 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
What is the difference in dosages of barbiturates & benzodiazepines?
- 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]
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 _____.
brain (cerebral circulation); lipophilic
*drug will go to areas with more blood flow 1st & then later diffuse to tissue with lesser blood supply
Although onset & distribution of IV anesthetics are rapid, the drugs' ____ is much slower.
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.
After prolonged infusions, drug half lives and durations of action are dependent on complex interaction between what 3 factors?
drug redistribution, accumulation in fat, and drug metabolic rate
If you want to have no effect on CV system, which IV anesthetic would you choose?
etomidate (useful for pts w/ underlying CV problems)
What IV anesthetic could precipitate porphyria?
Thiopental can cause porphyria due to hepatic enzyme induction in susceptible pts.
What does antiemetic mean, and what drug has this?
Antiemetic = inhibits nausea & vomiting; propofol
What is propofol infusion syndrome?
- 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.
How do you treat propofol infusion syndrome?
stop drug, cardiocirculatory stabilization, correction of metabolic acidosis
Which drug inhibits steroidogenesis (by preventing cortisol activity)?
What is special about ketamine in comparison to other IV anesthetics?
can cause dissociated state = eyes open, but unconscious & pain-free
What are some advantages/attributes of benzodiazepines
– 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
If you needed to perform a short procedure, which benzodiazepine would you use? Which one would you not use?
- Midazolam = half-life of 10-20 hrs
- Diazepam = half-life of 20-40 hrs
Advocates for opiods?
– 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
Critics for opiods?
- 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
What do Fentanyl congeners do?
Act at opiate receptors (OP1-3) in spinal cord and CNS
*morphine also does this, but fentanyl induces analgesia more rapidly
What is the overdose triad of opiods?
pinpoint pupils, dec respiration, coma.
What are the effects of opiods?
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
What is the tx to reverse the effects of opiods?
naloxone (Narcan) nalmefene (Revex)
What do anesthetics do in response to PaCO2?
￼Anesthetics reduce normal ventilation response to PaCO2--no reflex response. Baroreceptor attenuation.
For long-lasting analgesia, what is the drug of choice?
morphine; peak relief 15-30 min
What is the new opioid class that is very effective and is rapidly metabolized?
- rapid onset & peak effect
- short half-life
- recovery rapid when administration is discontinued (loss of analgesia).
What is the "20 min drug for a 20 min procedure"?
– More lipid soluble
– Onset in <30 seconds
– Peak effect in 2-3 min
– nausea & vomiting = rare, unlike in morphine!
What is the pharmacogenomic (autosomal dominant) disorder of the skeletal muscle? Briefly describe it.
- 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)
What drug was malignant hyperthermia originally recognized in? What are other triggers of MH?
other: desflurane, sevoflurane
What is the tx for malignant hyperthermia?
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