General anesthetics Flashcards
What is MAC?
This is the minimum alveolar conc. that prevents movement in response to surgical stimulation in 50% of subjects
- it is an indicator of gas potency
- indicated by how lipophillic it is as well as how fast the mechanism of action works in the brain
- Faster mechanism of action and high lipophillicy would have the lowest MAC and considered the most potent drug!
Would a smaller MAC be more lipophilic or less?
More lipophilic
What does 1.04 MAC mean?
It means you need 104% of the drug in the body to get it to knock you out. Thus you would need another drug to get you knocked out.
What are the 5 general effects of GA?
Amnesia
SKM relaxation
inhibition of autonomic reflexes
Analgesia
Unconsciousness
- none of the currently available GA’s can cause all 5 and only 5 alone.
- we rely on IV and inhaled drugs- a balance between to the two
What is an ideal drug?
rapid, smooth loss of consciousness, rapidly reversible upon discontinuation and a wide margin of safety (LARGE Therapeutic index)
What is conscious sedation?
Drug induced alleviation of anxiety and pain and….
smaller doses of sedative medication (altered level of consciousness)
- patient will maintain patent airway and is responsive to verbal commands
Name some common drugs that can cause conscious sedation?
Diazepam Midazolam Propofol Benzos and opioids - benefit is there are rapidly reversible
What drug would you use to reverse opioids?
Naloxone
What drug would you give to reverse benzos?
Flumazenil
What is deep sedation?
Similar to light state general anesthesia
- There is a gray medium between deep sedation and GA
- may be even indistinguishable from GA
What are two ways which GA works?
- Enhance inhibitory activity
2. inhibition of excitatory activity
How does GA target and act on enhancing inhibitory activity?
- Either through chloride channels
- pump Cl- into cell to make it stay at resting membrane potential
- do so through GABAa and glycine - or through K+ channels
- Postsynaptically it hyper-polarizes
- pre it hyperpolarizes and thus no NT’s are released
How does GA target and act on inhibition of excitatory activity?
- inhibits release of glutamate via AMPA and NMDA
- how ketamine and NO works - via Nicotinic and muscarinic receptors
- through ACh
- nicotine can modulate amnesia and analgesia
What are the volatile anesthetics?
Halothane, enflurane, isoflurane, desflurane and sevoflurane
- low VP and high BP
What are the gaseous anethetics?
NO
- high VP and low BP
What are the factors controlling uptake of inhaled anesthetics?
- Inspired conc and ventilation
- Solubility
- Alveolar-venous partial pressure difference
What 2 parameters determine how quickly the alveolar conc changes?
- inspired conc or partial pressure (how much is given)
2. Alveolar ventilation (how big the breath is)
What is the partial pressure alveoli ratio?
Alveolar conc (FA)/(FI) inspired conc. - significance being that the closer this number is the one the faster anesthesia will occur during inhaled induction
What is the partioning coefficient?
Blood:gas (Otsward coefficient)
- basically how fast the drug can pass from the gas of lungs to the blood
- the higher solubility in the blood would indicated a higher B:G ratio and would cross the blood/gas barrier easier.
How would you compare solubility to B:G to FA/FI?
The higher the solubility the faster it crosses the B:G barrier and the greater number of B:G
- This means it will take longer to reach FA/FI to reach equilibrium because so much is lost to the blood right away.
- So higher solubility means higher B:G and means longer time to reach high conc. in the blood and the anesthetic agent is the brain can rise no faster than it does in the blood.
- Lower B:G thus means faster onset of anesthetics
What does a B:G of 1.7 mean?
Means that at equilibrium there is 1.7x more drugs in the blood than in the gas. Since B:G is high its soluble and would take longer to have its effects.
What is henry’s law?
Number of gas molecules that enter a liquid equilibrium is reached is determined by the solubility of the gas in the liquid.
- as pressure decreases the amount of gas dissolved in a liquid decreases
What is the alveolar venous partial pressure difference?
Dependent mainly on the uptake of the anesthetic by the tissues, even non neuronal tissues
- influences by tissue:blood coefficients
How does tissue:blood coefficient affect induction of anesthesia?
The more soluble the drug is in tissues, the highly perfused tissues will take that drug and will have less venous partial pressure of the drug.
- thus the longer it will take to reach FA/FI
How would elimination of a drug be faster?
Have a smaller B:G and be less soluble. Exact opposite of onset.
- most inhaled anesthetics are exhaled through the lungs rather than excreted by the kidneys
- metabolized at a very small extent
What is the only way to speed recovery?
To hyper ventilate
At what levels of MAC is amnesia evident?
0.2-0.4
What are some of the cerebral effects of GA?
- decreased metabolic rate which decreases blood flow
- The net effect depends on conc of anesthetic because some GA’s are vasodilators which would increased cerebral blood flow
- at 0.5 MAC reduction of CMR is greater than vasodilation for example
- keep in mind an increased in cerebral blood flow is not desired for ICP pts
What are the 4 levels of CNS depression
- Analgesia
- Excitement (bad)
- Surgical anesthesia
- Medullary depression (bad)
How is volatility related to vapor pressure?
They are directly related
- the higher the vp and more volatile a drug is.
What are some highly volatile GA’s?
Desflurane> halothane>isoflurane>enflurane
What do inhaled anesthetics do the blood pressure?
They all decrease it
What GA’s preserve CO?
Isoflurane and desflurane and sevoflurane
- cause vasodilation but minmially effect CO
What drugs have minimal effect on arterial resistance?
Halothan and enflurane
What are some respiratory effects of GA’s?
All volatile drugs are respiratory depressants
- all drugs except NO cause dose dependent decrease in tidal volume and increased RR
What GA’s seem to be nephrotoxic?
Enflurane and sevoflurane due to fluoride iones
What is a rare but significant cause of anesthesia?
Malignant hyperthemia
- Muscle ragidity, tacy, hyperthermia, hyperkalemia, metabolic acidosis
- Caused mainly by succinylcholine
- treat with Dantrolene- released Ca from SR
what is the mechanism of action of Propofol?
- chloride channel current mediated through GABAa.
- Very poor solubility in water
- less of a hangover effect after due to high plasma clearance
Where is propofol metabolized?
The liver
How does propofol affect the CNS?
Hypnotic not a analgesic
- decreased CMR=Decreased Flow=Decreased ICP
what does propofol do the the CV and respiratory system?
CV: vasodilation and inhibits the baroreflex response that should come there after of hypotention
- thus inhibition from 10 and 9 stay the same so no compensatory increased in BP
Res: depressant
- also an antiemetic
- pain at injection is also common
what are some barbiturates?
Theopental and methohexital
which ct to activated GABAa which acts on chloride channels
- of not they have a high toxicity
What is the CNS effects of barbs?
Vasoconstrictors and thus decreased cerebral flow, then volume then ICP
- no analgesia
CV and respiratory effects of Barbs?
Vasodilation in the periphery and allows for compensatory increase in HR
- RR- depressant
- good for the induction of anesthesia
What are some benzos?
Midazolam, Loraxepam and diazepam
what is the mechanism of action of benzos?
Facilitates GABAa
highly lipid soluble and thus has a rapid CNS onset
What is the only benzo that is suitable for IV infusion and why?
Midazolam because of its short sensitive half time
aka Versed
What are the effects of Benzos on the CNS?
Decreased CMRo2 via decreased blood flow
- smaller extent than Prop and barbs
What are some of the CV and RR effects of Benzos?
CV: no CO change bu decreased in BP peripherally
RR: minimal depression
what is the mechanism of action of Etomidate?
GABAa mediated but often chosen for it minimal hemodynamic effects.
- example patient with blood loss
- very good for pts with myocardial contractibility compromise
what is the effect of etomidate on the CNS?
It is a potent cerebral vasoconstrictor
- decrease in blood flow and decrease in ICP
- CV stable
- RR depressant
What does etomidate do to the endocrine system?
It is a adrenocortical suppressant
- it inhibits the action of 11b- hydroxylate which is the enzyme needed to convert cholesterol to cortisol
what is the mechanism of action of Ketamine?
Inhibition of the NMDA receptor complex
- high lipid solubility
What are the effects of ketamine on the CNS?
Upleasant emergence reactions
cerebral vasodilatory that increases cerebral blood flow as well as CMRO2
-not given to people with ICP
- vivid dreams, out of body experiences and hallucinations
- fear and confusion
- no as many of these affects on kids
What are the effects of ketamine on Cv and RR?
increases BP, HR and CO by mediation of sympathetic stimulation
what can be added to opioids to cause GA?
benzos
- hemodynamic stabilty- good for pts with compromised myocardial functoin
