A: 23, 24 Flashcards
Inhaled anasthestics
DIS flower is so calming
Administered as gases , where partial pressure/tension in the inhaled air/in blood/ in tissues is a measure of their conc,
- Halogenated HC:
- Desflurane
- Isoflurane
- Sevoflurane
- halothane
- enflurane
- nitrous oxide (N2O)
inhaled anesthetic mechanism of action
- Facilitate GABA-mediated inhibition
- Block brain NMDA
- inhinit AchR (nicotinic) at medium/high conc.
Desflurane
Isoflurane
SE
- Pulmonary irritant, may cause bronchospasm (BOTH)
- Isoflurane:
- peripheral vasodialtion
- sensitizes myocardium to catecholamines > Arrhythmias
Sevoflurane SE
- Nephrotoxic ( with prolonger anesthesia)
Pharmacologic effects on inhaled anesthetics
- NO2
- Uterine contraction > spontanoues abortion
- drug of abuse “laughing gas”
- diffusional hypoxia
- Desflurane:
- Pulmonary irritant (bronchospasm)
- Peripheral vasodialation (decrease BP)
- Isoflurane
- Peripheral vasodialation (decrease BP
- sensitizes myocardium to arrhythmogenic effect of catecholamines
- pulmonary irritant (bronchospasm)
- Sevoflurane
- Nephrotoxicity (with prolonged anesthesia)
- Peripheral vasodialation (decrease BP
- Enflurane
- myocardial depressant
- Nephrotoxicity (with prolonged anesthesia)
- increased cerebral blood flow : high level of enflurane cause muscle twitch & spike-&-wave activity.
- myocardial depression (decrease CO): Enflurane , halothane (NO2 least likely)
- ALL decrease respiratory function
- Halothanne , isoflurane (less) : sensitize myocardium to arrythmogenic effect of catecholamines.
- lung irritation (desflurane, isoflurane)
Which has high Blood:gas partition coefficient?
Halothane
Sevoflurane
Sevo Stay in blood
Higher blood solubility > equilibrates with blood slower
Which has low Blood: gas partition coefficient?
Desflurane
N2O
Deso Dissolves in gas
equilibrates more rapidly with blood; drug passes into brain faster producing anesthesia
Most inhaled anesthetics inhibit —– at moderate-high conc.c
nictotinic AchR isoforms
Inspired gas partial pressure effect on inhaled anesthetics
- A high partial pressure of gas in the lungs results in —–
Rapid achievement of anesthesitic levels in blood
Done by administering higher gas conc. than required for maintencance of anesthesia.
The greater the ventilation rate the ……..
more rapid is the rise in alveolar and blood partial pressure of agent & onset of anesthesia
Potency of inhaled anesthetics is roughly proportional to their ——-
lipid solubility
pulmonary blood flow effect on inhaled anesthetics
- high pulmonary blood flow :
- gas partial pressures rises at slower rates; speed of onset of anesthesia in REDUCED.
- low pulmonary blood flow
- faster onset of anesthesia
In circulatory shock, this effect may accelerate rate of onset of anesthesia with agent of high blood solubility.
Elimination of inhaled anesthtic
- redistribution of drug from brain > blood> alveolar air> elimination by lung
CNS neurons in diff regions of the brain have different sensitivities to general anesthetics
what is inhibited first neurons involved in pain pathway VS neurons in midbrain reticular formation
neurons involved in pain pathway is inhibited first
rate of recovery from Low blood: partition coefficient VS high solubility drugs
- rate of recovery from Low blood: partition coefficien : FASTER
eg. desflurane, nO2 have low blood solubility ; shorter recovery time than older agents
Potency of inhaled anesthetic is best measured by ——
- MAC (minimum alveolar anesthetic conc.)= alveolar conc. required to eliminate response to standarized painful stimulus in 50% of patients
- each anesthetic has defined MAC, but value may vary among patients depending on
- age
- CV status
- use of adjuvant drugs
- NOTE: MAC for infants and elderly are lower than those for young adults
inhaled anesthetic pharmacokinetics
- Rate of onset and recovery vary by blood:gas partition coeffient
- drugs with low blood: gas coeff equilibrates more rapidly> faster anesthesic effect
- Recovery mainly due to redistribution from brain>blood> alveolar air> other tissues
If several inhaled anesthetic agents used simultaneously their MAC values are —–
Additive
eg. 0.5 MAC NO2 +
0. 5 MAC desflurane = 1MAC inhaled anesthetic
Toxicities of inhaled anesthetics
- Extensions of effects on
- brain:
- decreased brain metabolic activity
- increase cerebral blood flow; increased ICP
- high conc. enflurane cause spike-and-wave activity and mucle twitching
- heart/vessels
- decrease arterial BP (less likely with no2)
- isoflurance, desflurane, sevoflurane > peripheral vasodialation
- lungs:
- RR increase
- dose-dep decrease in TV, Minute ventilation> increased arterial CO2 tension
- most are bronchodilators
- brain:
- Drug interactions:
- additive CNS depression with opoids & sedative-hypnotics
prolonged exposure to no2 causes
megaloblastic anemia (due to decreased methionine synthase activity)
SE when using inhaled anesthetic together with Neuromuscular blockers (esp succinyl choline_
malignant hyperthermia (sign: masseter hypertonia)
due to mutations in gene loci of RYR1 and
skeletal muscle L-type Ca channel
uncontrolled release of Ca by SR of skeletal m leads to
- muscle spasm
- hyperthermia
- autonomic lability
Dantrolene indicated + supportive
What anesthetics Facilitate GABA-mediated inhibition
- Inhaled anesthetics
- Barbiturates: thiopental
- Benzodiazepine: midazolam
- etomidate
- propofol
y-aminobutyric acid
Stages of anesthesia
-
stage 1: analgesia
- Patient has decreased awareness of pain
- Amnesia (sometimes)
- conciousness impaired, BUT not lost
- stage 2 : Disinhibition
- patient is in delerious and excited
- amnesia occurs
- reflexes are enhanced
- irregular respiration
- retching and incontinence (lack of voluntary control over urination or defecation) may occur
-
stage 3: surgical anesthesia
- Unconcious
- no pain reflexes
- respiration is regular
- BP maintained
-
stage 4: Medullary depression
- Patient develops severe respiratory & CV depression
- requires mechanical and pharmacologic support to prevent death
general anesthetic VS conventional sedative-hypnotics
- general anesthetics are CNS depressants with actions that can be induced and terminated more rapidly
general anesthesia definition
- state of
- unconciousness
- analgesia
- amnesia
- skeletal muscle relaxation
- loss of reflexes
IV anasthestics
PEKMully? TFuu.פחמימות לוריד ישר
Propofol- GABA-A inhibition
Etomidate- GABA-A inhibition
Ketamine- NMDA inhib. (central glu R)
Midazolam(benzo)- GABA-A inhibition
Thiopental (barbiturate)- GABA-A
Fentanyl- opioid u-r agonist
Dexmedetomidine - ( centrally-acting alpha-2 agonist)
ketamine mechanism
- Antagonist of action of excitatory glutamic acid on the NMDA-r
Special SE of Ketamine
- Cardiovascular stimulant
- Intracranial hypertension
- disorientation, excitation, hallucination, delerium, vivid nightmare
D2-R antagonist sedative
Metoclopramide - antiemetic ( perioperative)
מתוק לו כשאין דופמין
כי דופמין מוריד פרולקטין וחלב זה מתוק אז כשאין דופמין יש חלב מתוק
Preoperative sedation
Midazolam
Perioperative agents
- anxiolytics: benzo (midazolam, lorazepam)
-
Analgesics :
- opioid ( fentanyl, morphine, hydromorphone)
- NSAIDS (ketorolac, diclofenac, meloxicam)
- Anti-emetic
- Metoclopramide (D2-r blocker) oral, parenteral
- droperidol
- GI protective agents
- H2 blockers : Cimetidine, famotidine, ranitidine, nizatidine
- PPI
- sucralfate
- Anti-muscurinics
- Atropine: (non-selective) -oral, parenteral : anti spasmodic , anti diarrhea, reversal of AV block, managing bradyarrythmias (IV)
- Antibiotic prophylaxis
- Ampicillin
- cefazolin
- cefuroxime
- Acid-supressing agents (ANTACID) - weak bases neutralise stomach acid
- NaHCO3
- Mg(OH)2
- AL(OH)3
Barbiturates drugs and mechanism of action
- Intravenous anesthetic
- Facilitates GABA-mediated inhibition at GABA-A receptor
- Thiopental
- thiamylal
- methohexital
Barbiturates pharmacologic effects and pharmacokinetics (onset, duration, termination, elimination)
- pharma effects:
- Circulatory and respiratory depression
- decrease intracranial pressure (ICP) - depress cerecral blood flow
-
High lipid solubility - which promotes rapid entry into the brain and results in surgical anesthesia in one circulation time (<1 min)
- fast onset
- short duration due to distribution
- The anesthetic effects of thiopental are terminated by redistribution from the brain to other highly perfused tissues
- but hepatic metabolism is required for elimination from the body
Barbiturates
Toxicities and interactions
- Extensions of CNS depressant actions
- Additive CNS depression with many drugs
Barbiturates drugs and indication
Thiopental
Metho-hexital
- induction of anesthesia
- for short surgical procedures.
Propofol mechanism of action, pharmacokinetics
- GABA-A inhibition
- I.V anesthetic
- Fast onset , Fast recovery due to inactivation
- propofol produces anesthesia as rapidly as I.V barbiturate but recovery is more rapid!
- Hepatic metabolism
Propofol pharmacologic effect, toxities
- Vasodialation and hypotension
- negative inotropy : decreased contractility force
- Anti-emetic effect
- Hypotension (during induction)
- CV depression
propofol indication
- General anesthesia
- Outpatient anesthesia
- Prolonged sedation in patients in Intensive care setting
- Anti-emetic activity
I.V
Etomidate mechanism of action and administraion, onset
- Imidazole derivative
- GABA-mediated inhibition at GABA-A receptors
- I.V
- Rapid onset and short duration of action due to distribution
Etomidate pharmacologic effects and toxicities
- This drug is not analgesic, its primary advantage is in anesthesia for patients with limited cardiac or respiratory reserve.
- because it has Minimal effects on cardio-vascular and respiratory function
- Pain on injection (may need opioid)
- myoclonus
- nausea and vomiting
- Prolonged administration may cause adrenal suppression.
Ketamine mechanism of action and administration, pharmacokinetics
- Blocks excitation by glutamate at NMDA receptors
- IV
- Hepatic metanolism
- moderate duration of action
ketamine indication and toxicities
- produces a state of “dissociative anesthesia” in which the patient
-
remains conscious but has marked
- catatonia
- analgesia
- and amnesia
-
remains conscious but has marked
- toxities:
- Increased intracranial P ( due to Cardio-vascular stimulanting effect!)
- emergence reactions (disorientation, excitation, and hallucinations) which occur during recovery from ketamine anesthesia, can be reduced by the preoperative use of benzodiazepines.
- toxities:
Dexmedetomidine mechanism and administration
- centrally acting α2-adrenergic agonist
- when used intravenously has: analgesic and hypnotic actions
- rapid clearance ; short elimination T1/2
Dexmedetomidine indiation
- mainly used for short-term sedation in an ICU setting.
- When used in adjunct to general anesthesia, the drug decreases dosage requirements for both inhaled and intravenous anesthetics
- achieves sedation with no respiratory depression
centrally acting alpha2 agonist has analgesic and hypnotic actions when used intravenously
Midazolam mechanism and administration, metabolism
- Benzodiazepine
- Facilitates GABA-mediated inhibition at GABA-A receptors
- I.V
- Hepatic metabolism
- post-operative respiratory depression reveresd by flumazenil
Benzodiazepine action can be terminated by
effect terminated by flumazenil (accelerates recovery)
flumazenil can terminate what drug action
does it work on ethanol or barbiturates?
- Flumazenil (anatginost at benzo site on GABA-A r) can be used to reverse the CNS depressant effects of benzodiazepines,(midazolam)
- but there is NO antidote for barbiturates or ethanol.
midazolam indication and SE
- Preoperative sedation
- Induction anesthesia
- outpatient anesthesia ( eg colonoscopy)
- SE:
- CV and respiratory depression
BENZO compared with barbiturates
- onset
- duratuin
- depressant
Benzos are
- less depressants than barbiturates
- slower onset
- longer duration than barbiturates
fentanyl mechanism . administration, metabolism
- Opoid receptors (u) agonist
- I.V
- Hepatic metabolism
fentanyl indication , SE
- used with other CNS depressants (NO2, BENZO) in anasthesia resgimens
- esp valuable in high-risk patients who might not survive ful general anesthesia
- SE:
- respiratory depression ( can be revesed postoperatively by naloxone)
