Pharm: General Anesthetics Buzzwords

enflurane

- inhaled anesthetic - less potent than halothane - equilibrates faster than halothane (less induction time, lower λ) AE: highly nephrotoxic, seizures

Meyer-Overton Rule (Oil/gas partition coefficient (λ oil/gas)

- solubility of anesthetic in oil - directly proportional to potency of anesthetic - higher λ oil/gas) = more potent = lower MAC unit = Lgas / (L tissue x atm)

Benzodiazepines withdrawal

Anxiety Confusion Agitation or Irritation Insomnia

BZDs when administered either with ethanol, tricyclic antidepressants, opioids or in combination

CNS depression and death in rare cases

BZD and sleep enhancement

Treat insomnia (Estazolam, Triazolam, Quazepam, Temazepam, Flurazepam, Z drugs) Help sleep onset and overall length of sleep ↑ length of Stage 2 NREM, ↓length of REM, ↓slow wave sleep

rare AE of benzodiazepines

sleep walking, driving, and eating

Stages of Anesthesia

stage IV can be fatal

how can you decide which anesthetic is more potent?

want one with low MAC

Diazepams and Alprazolam

- BZD - mitigate anxiety and anxiety from depression and schizophrenia AE: tolerance, addiction, dependence

Midazolam

- BZD used for anesthetic adjuvant (with general anesthetics) - prep for invasive procedures - rapid onset, short acting anxiolytic, sedative , amnestic effects

Z drugs

- BZD used for insomnia - GABA-A receptors (a1 subunit) - faster onset of sleep AE: amnesia, rebound insomnia (except zalepon)

diazepam

- BZD used for muscle relaxant - alleviate muscle spasm from physical trauma and muscle spasticity (MS)

Clonezepam and clobazam

- BZD with anti-epileptic effects

Phenobarbital

- Barbiturate - treat seizures and status epilepticus (has long duration, can last days)

propofol (,6-diisoprophylphenol)

- IV anesthetic - suitable for induction and maintenance - 1st choice for asthmatics - DONT use in pneumothorax AE: - does NOT cause nausea and vomiting - has pain at injection site MOA: - GABA > Cl >hyper polarization

What is anesthesia?

- amnesia (memory loss) - analgesia (reduced pain awareness) - unconscious - immobility in response to noxious stimulation - attenuation of autonomic responses to noxious stimuli

Minimal Alveolar Concentration (MAC)

- concentration (partial pressures) at which inhaled anesthetic abolishes a movement in response to surgical incision in 50% of patients - potency of anesthetic is inversely proportional to MAC (low MAC = high potency) unit = atm

sedative drug

- decrease activity - moderate excitement - calms recipient

hypnotic drug

- drowsiness - onset of sleep - maintains sleep - pt can be aroused easily

Triazolam

- fast onset BZD - sleep enhancement AE: rebound insomnia, does NOT cause carry over effect (Sedation)

Etomidate

- general IV anesthetic - pt with HYPOTENSION - NOT suitable for maintenance use in: Hemodynamic unstable, limited Res. reserve AE: - high injection site pain - myoclonic movements - repeated doses causes adrenal insufficiency and decreased cortisol and aldosterone MOA: - GABA > Cl > hyper polarization

ketamine

- general IV anesthetic - pediatric procedure - hypotension, limited Resp. Reserve (better than etomidate) AE: less effects, NO pain, can cause dissociate amnesia MOA: NMDA > glutamate > block Na/Ca conduction > block AP, NT

Benzodiazepines

- high affinity and high selectivity - binds to single site (Allosteric) on GABA-A receptors - highly hydrophobic, bound to plasma proteins - CI in acute hemodilution, liver issues (increases potency)

Sevoflurane

- inhaled anesthetic - Equilibrates nearly as fast as N2O ( Low λ blood/gas, Fast induction) - more potent than N2O (higher λ oil/gas) - used with NO used in peds since its sweet AE: exposed to carbon dioxide adsorbents in anesthetic machinery, it becomes unstable and degrades into olefinic compound → nephrotoxicity

Halothane

- inhaled anesthetic - Higher λ oil/gas → more potency - Higher λ blood/gas → more induction time → slow induction and recovery AE: hepatotoxicity, malignant hyperthermia (tx with dantrolene), ↑ Epinephrine sensitivity → tachycardia, Arrhythmia CI: liver conditions

desflurane

- inhaled anesthetic - Equilibrates faster than N2O Lower λ blood/gas Faster induction - more potent than NO, less than sevoflurane AE: - pungent - airway irritation → laryngospasm or cough

nitrous oxide

- inhaled anesthetic - equilibrates fastest (Lowest λ blood/gas ,Fastest induction) - low λ oil/gas → High MAC - need high [ ], and give with something else AE: - Expands close air compartments (example - pneumothorax in car accidents, retinal disease, etc.) - second gas effect and hypoxia

Flurazepam

- longest acting BZD - sleep enhancement AE: no rebound insomnia, long half life (78 hr) can cause carry over effect (Sedation) into day

isoflurane

- preferred over enflurane since NO seizures

BZD - sleep enhancement AE

- safe - unless, pulmonary or CVD, then can cause depression of pulmonary and CVD - can cause tolerance or rebound insomnia

clobazam

- seizure control - long acting

Blood/gas partition coefficient (λ blood/gas)

- solubility of inhaled anesthetic in blood - predicts induction time unit = Lgas / (L tissue x atm)

what factors contribute to adverse effects of barbiturates ?

- wide CNS depression - lower selectivity and high efficacy for enhancing GABA- receptors - low therapeutic index

A 32-year-old male is admitted to the hospital for a reduction of a dislocated shoulder. Sedation with midazolam is supplemented with a 70% concentration of nitrous oxide, 28% oxygen, and 2% isoflurane. Which of the following effects most likely occurred immediately after these drug administrations? A. Fast induction of anesthesia B. Profound bronchoconstriction C. Sharp increase in blood pressure D. Skeletal muscle relaxation E. Slow induction of anesthesia

A. Fast induction of anesthesia

A 21-year-old woman brought to the emergency department is diagnosed with status epilepticus. She is given an intravenous injection of a drug that binds to GABAA receptor complex. Which of the following drugs is most likely administered? A. Methohexital B. Midazolam C. Phenobarbital D. Zaleplon E. Zolpidem

C. Phenobarbital

symptoms of barbiturate withdrawal

CNS excitability, seizures, cardiac arrest, tremors, anxiety

Benzodiazepines withdrawal

Can be managed unless psych comorbidities or polydrug dependence Need to taper off dose and frequency to prevent

A 72-year-old female suffering from anxiety starts treatment with a drug that activates GABAA receptors both in the brain and in the spinal cord. The activation most likely prolonged the opening of which of the following ion channels? Ca2+ Cl- HCO3- K+ Na+

Cl

An 81-year-old female is rushed to an emergency department. She has suffered a severe brain injury and will need to undergo an immediate brain surgery. Your attending asks you to select the most potent anesthetics. Which of the following would you pick? Drug L M (MAC = 0.004 atm) Drug NO (MAC = 0.001 atm) Drug PQ (MAC = 1.201 atm) Drug RS (MAC = 1.307 atm) Drug TU (MAC = 0.514 atm)

Drug NO (MAC = 0.001 atm) (lowest MAC)

BZD that help sleep enhancement

Estazolam Triazolam Quazepam Temazepam Flurazepam Z-drugs:

MANAGEMENT OF BENZODIAZEPINE OVERDOSE

FLUMAZENIL - antidote for overdose - does NOT block effect of ethanol or barbiturates

A 28-year-old male is rushed to an emergency department. It is reported that he had a panic attack about one hour ago. His medical records show that he has been suffering from insomnia and anxiety for the last three months and has been prescribed Triazolam. His vital signs are declining. Which of the following drugs is most likely administered to treat this patient? Atropine Flumazenil Flunitrazepam Haloperidol Naloxone

Flumazenil

inhalation anesthetic MOA

Fluranes and Halothane → GABAA Receptor potentiators

A 48-year-old male suffering from primary insomnia is prescribed Zolpidem, but the drug is soon withdrawn because he develops conjunctivitis, apparently due to a hypersensitivity reaction to the drug. He is then prescribed behavioral therapy and a short course of Temazepam. Which of the following most likely an action of the drug on the patient's sleep architecture? Decreased duration of sleep Decreased NREM sleep Increased REM sleep Increased sleep onset Increased slow-wave sleep

Increased sleep onset

A 4-year old girl, who had been suffering from severe asthma for 6 months, was scheduled for a short suture procedure that was anticipated to take approximately 10 minutes. She was brought to the operating room by her parents and was in distress over parting from them and afraid of the doctors. Which of the following would be appropriate for providing sedation and analgesia for this girl?' Etomidate Haloperidol Ketamine Propofol Thiopental

Ketamine

A 55-year-old male undergoing a cardiac surgery is anesthetized by a drug that inhibits the excitatory glutamate sensitive AMPA receptors. Which of the following drugs is most likely administered? Diazepam Halothane Methohexital Metoprolol Propofol

Methohexital

A 43-year-old male gets into a car accident and is presented to the emergency department with severe neck pain. The physical examination and X-ray results indicate fracture of the atlas vertebra and requires surgery. The patient is anesthetized, and the surgeons begin the procedure. Ten minutes into the surgery, the patient begins to breath abnormally, and the surgeons realized that they missed a pneumothorax injury from the car accident which was not taken into consideration before administering anesthesia. Which of the following most likely contributed to the irregular breathing in this patient? Carbon dioxide Desflurane Etomidate Halothane Nitrous oxide

Nitrous oxide

What are the IV anesthetics?

Propofol Etomidate Ketamine

Tolerance for Barbiturates

Results from prolonged use which ↑activity of P450 Accelerating metabolism of barbiturates Inducing cross tolerance to benzodiazepines and ethanol Dependence leads to withdrawal

A 63-year old man underwent cholecystectomy (gallbladder removal). The patient was a heavy smoker and had been suffering from chronic obstructive pulmonary disease (COPD) for 20 years. General anesthesia was induced with propofol and maintained with isoflurane. Which of the following effects most likely occurred with propofol during surgery? Bronchoconstriction Bronchodilation Increased blood pressure Increased cardiac output Increased cerebral blood flow

bronchoconstriction

Benzodiazepines tolerance

chronic use can manifest as decreased efficacy and unable to function without Comes from ↓ expression of GABA - R (downregulation) and uncoupling of BZD binding site on the receptor

FLUMAZENIL MOA

competitive antagonist at GABA receptor

barbiturates used as

general anesthetics anti epileptics