CNS and Anesthesia Flashcards
Triptans
5HT agonists Prevent release of 'inflammatory soup' of prostaglandins, substance P and histamine Drugs: Sumatripan - most common Zolmitriptan Rizatriptan - no nasal spray Naratriptan - longer acting, for recurrence Use: - stop migraines
Dihydroergotamine
Rescue medication and for refractory migraines (with metoclopromide)
Barbiturates
IV anesthetics
Mechanism:
- binds to specific sites on GABA A receptors, enhances affinity of GABA, increases Cl influx
Drugs:
- thiopental
- methohexital
Uses:
- induction of anesthesia
- neuroprotection - treat raised ICP and focal cerebral ischemia
Effects:
CNS
- sedation, anesthesia, not analgesic (anti-analgesic), cerebral vasoconstriction, decrease CMRO2 (EEG can flatline)
- methohexital activates epileptic foci
CV
- peripheral vasodilation, decrease in BP
Respiratory
- respiratory depressant
- decrease ventilatory response to hypercapnea and hypoxia
- inadequate suppression of airway and laryngeal reflexes
Other
- precipitation when mixed with acidic drugs
- pain and tissue injury in paravenous tissue
- pain, vasoconstriction, gangrene if arterial injection cuz alkaline pH
- exacerbation of acute intermittent porphyria - stimulates D-ALA synthetase
Desflurane
Inhaled anesthetic
- immobility
- amnesia
- CNS depression - enhance GABA, block NMDA
- not analgesic
Needs highest concentration to achieve MAC
Least soluble - fast onset/offset
Use:
- gastric bypass, obese pts
- peds tonsillectomy
Pros:
- rapid onset/offset
Cons:
- pungent, expensive, tachycardia
Effects:
- decrease MAP due to decreased TPR - vasodilators
- increased HR
- increase RR, decrease tidal volume (maintain minute ventilation)
- decrease FRC, increase dead space
- increase PaCO2, less responsive to it, lead to apnea
- bronchodilation - good for asthma
- depression of pharyngeal and laryngeal reflexes - can intubate
- cerebral vasodilation - increased CBF and ICP
- decrease CMRO2
- dose dependent EEG depression
- dose related skeletal muscle relaxation
- decreased renal blood flow
- decreased hepatic blood flow
Side effects:
- airway irritant - don’t use for mask induction
- expensive
- may prolong QT
Sevoflurane
Inhaled anesthetic - immobility - amnesia - CNS depression - enhance GABA, block NMDA - not analgesic Most commonly used in OR Medium solublity, medium potency Not expensive Use: - inhaled induction in peds - least noxious and least irritating to airways - quicker adult cases - induction agent Pros: - rapid, pleasant Cons: - emergence delirium Effects: - decrease MAP due to decreased TPR - vasodilators - increased HR after 1 MAC - increase RR, decrease tidal volume (maintain minute ventilation) - decrease FRC, increase dead space - increase PaCO2, less responsive to it, lead to apnea - bronchodilation - good for asthma - depression of pharyngeal and laryngeal reflexes - can intubate - cerebral vasodilation - increased CBF and ICP - decrease CMRO2 - dose dependent EEG depression - dose related skeletal muscle relaxation - decreased renal blood flow - decreased hepatic blood flow Side effects: - nephrotoxic effects - keep flow higher - may prolong QT
Isoflurane
Inhaled anesthetic
- immobility
- amnesia
- CNS depression - enhance GABA, block NMDA
- not analgesic
Needs lowest concentration to achieve MAC - most potent
Most soluble - longer emergence
Most economical
Pros:
- inexpensive, hemodynamic stability
Cons:
- long acting
Use:
- longer cases, especially if pt doesn’t get extubated
Effects:
- decrease MAP due to decreased TPR - vasodilators
- increased HR
- increase RR, decrease tidal volume (maintain minute ventilation)
- decrease FRC, increase dead space
- increase PaCO2, less responsive to it, lead to apnea
- bronchodilation - good for asthma
- depression of pharyngeal and laryngeal reflexes - can intubate
- cerebral vasodilation - increased CBF and ICP
- decrease CMRO2
- dose dependent EEG depression
- dose related skeletal muscle relaxation
- decreased renal blood flow
- decreased hepatic blood flow
Side effects:
- may prolong QT
Nitrous Oxide N2O
Inhaled anesthetic
- immobility
- amnesia
- CNS depression - enhance GABA, block NMDA
- mild analgesic
Cannot achieve 1 MAC
Not expensive
Use:
- in combination with volatile anesthetics
- induction agent
- only use alone to calm kids down before inserting IV
- don’t use in surgeries with air cuz diffuses fast into air filled spaces
- labor analgesia
Pros:
- inexpensive, combined with VA, rapid
Cons:
- not used alone, caution with air spaces
Effects:
- little change in MAP or TPR
- bronchodilation - good for asthma
- depression of pharyngeal and laryngeal reflexes - can intubate
- cerebral vasodilation - increased CBF and ICP
- decrease CMRO2
- dose dependent EEG depression
- dose related skeletal muscle relaxation
- decreased renal blood flow
- decreased hepatic blood flow
Side effects:
- increases nausea/vomit
Benzodiazepines
Sedatives/anxiolytics Highly lipid soluble and protein bound, fast BBB penetration Mechanism: - enhance affinity of GABA receptor for GABA, increase Cl flux; BDZ site on GABA receptor Metabolism - midazolam inactive metabolites; diazepam active metabolites so longer duration and hangover effect Drugs: - Midazolam, Diazepam Uses: - pre-medication - sedate pt, anti-anxiety, amnesia - sedation for short procedures (midazolam) - suppression of seizure activity in status epilepticus Effects: CNS - sedation, hypnosis - anterograde amnesia - anticonvulsant - decrease CMRO2 and CBF - not neuroprotective Respiratory - minimal respiratory depression CV - decrease in TPR and BP - CO not affected, so CV stable Other - pain on injection with diazepam
Propofol
Isopropylphenol IV anesthetic - lecithin and soybean oil - need sterile technique Mechanism: - inhibition of neurotransmission via GABA potentiation - increase Cl current Not analgesic Wake up 8-10 mins after induction bolus due to redistribution Uses: - induction agent - maintenance of anesthesia - sedation - flexible use - neuro rooms, seizure, brain tumor, trauma Pros: - rapid onset, short acting - anti-emetic - bronchodilaion - use for asthmatics, smokers - amnesia - neuroprotective Cons: - pain on injection - hypotension - CV and resp depression - allergy to soy, eggs - propofol infusion syndrome - lactic acidosis - not analgesic Effects: CNS - hypnotic, anesthetic, amnesic - decreased CBF, decreased CMRO2, decreased ICP - anticonvulsant - neuroprotective during focal brain ischemia CV - vasodilation, decreased BP, inhibits baroreceptor reflex Respiratory - respiratory depressant - apnea after induction bolus - upper airway reflex suppressed - use for airway instrumentation like bronchoscopy Other - anti-emetic - reduces post op N/V
Etomidate
Imidazole, acidic IV anesthetic Mechanism: - binds GABA A receptor, enhances affinity of GABA for receptor, increases Cl influx Ionized, penetrates brain rapidly Uses: - induction agent for CV unstable Pros: - less respiratory depression/apnea - CV stability - cardiac dysfnx, shock, hypovolemia are good uses Cons: - adrenal suppression - pain on injection - myoclonus Effects: CV - cardiovascular stability after IV bolus - minimal change in BP, HR, TPR, myocardial contractility Respiratory - minimal depressant of ventilation - apnea after IV bolus CNS - cerebral vasoconstrictor, decreased CBF and CMRO2 - myoclonic activity so don't use in seizure disorders Endocrine - adrenocortical suppression - inhibits 11 beta hydroxylase so no cortisol so don't use in critically ill
Ketamine
Phencyclidine
IV anesthetic
Mechanism:
- NMDA receptor antagonist
- binds opioid receptors also
Stimulant and sedative
Highly lipid soluble - rapid onset and short duration of action
Uses:
- induction of anesthesia
- maintenance of anesthesia
- sedation - dressing changes or suturing
- dissociative amnesia
- analgesic affect, post-op pain
- cardiac tamponade
- kids
Pros:
- less respiratory depression
- bronchodilator
- analgesic
- vasoconstrictor
- dissociative state
Cons:
- increase HR and BP
- psychotropic side effects - emergence delirium
- direct cardiac depression in pts with high symp tone - hemorrhage
- increased ICP
- salivation/increased secretions
Effects:
CNS
- dissociative anesthesia
- analgesic
- cerebral vasodilation and increased CBF - increase ICP and CMRO2
- myoclonic and seizure activity so don’t use for neurosurg, brain tumors, seizures, trauma
CV
- symp stimulation centrally - increase HR, BP, CO, myocardial O2 consumption so don’t use in ischemic heart disease
- myocardial depression in pts who can’t raise symp nerve activity - don’t use in shock
Respiratory
- no significant resp depression; apnea if IV bolus
- bronchodilation - use in asthma
- increases salivary and tracheobronchial secretions so treat with glycopyrrolate
Other
- emergence reaction - nightmares, hallucinations, etc. so pretreat with midazolam
Opioids
Mechanism: - bind opioid receptors, decrease Ca influx presynaptically and increase K efflux postsynaptically Drugs: - fentanyl - CV stability, fast acting - alfentanyl - sufentanil - remifentanil - fastest onset, shortest duration - hydromorphone - morphine - methadone - meperidine Pros: - analgesia - minimal cardiac depression - reduces inhalational agents - versatile Cons: - respiratory depression - decrease RR - increase apneic threshold - blunts ventilatory response to hypoxia - bradycardia - skeletal muscle rigidity - nausea, vomit - constipation/ileus - pruritis Effects: - CNS - analagesia, sedation - respiratory system - depression via decreased brainstem ventilation, loss of CO2 responsiveness - antitussive - methorphan, codeine - muscle rigidity - miosis - excitation at E-W nucleus - CV - hypotension due to bradycardia from decreased central symp tone and incrased vagal activity, depressant on SA node, histamine release leads to decreased TPR - GI - decreased peristalsis and increased sphincter tone, constipation, increased biliary pressure from sphincter of Oddi narrowing; nausea and emesis are most common via chemoreceptor trigger zone - GU - urinary retnetion - skin - histamine release, urticaria, cutaneous vasodilation - placenta - neonatal respiratory depression and dependence
Neuromuscular blockade agents
Depolarizing - succinylcholine - rapid onset/short duration, rapid sequence induction Non-depolarizing - rocuronium - fastest onset - cisatracurium - Hoffman elimination - vecuronium - pancuronium - tachycardia - reverse via neostigmine and glycopyrrolate
Dexmedetomidine
Imidazole
IV anesthetic
Mechanism:
- stimulation of alpha 2 receptors in locus coeruleus, inhibits NE release
Uses:
- sedation short term, radiologic procedurs
- general anesthesia, needs loading dose
Pros:
- sedation and analgesia without respiratory depression
Cons:
- hypotension and bradycardia, with bolus
- longer onset and offset
Effects:
CNS
- sedation
- analgesia
- not much on CRMO2 or ICP so good for brain stuff, getting an MRI
CV
- cardiovascular depression - bradycardia, hypotension due to NE decrease
Respiratory
- minimal depressant effects on respiration, no effect on respiratory rate
- response to CO2 unchanged
- so use if no airway experts around
NSAIDs
Mechanism: - block COX - reduce PGE2 and other prostaglandin production Actions: - analgesia - antiinflammatory - anti-pyretic via inhibition of IL1 and IL6 production of prostaglandins in hypothalamus - synergistic with opioids Adverse events: - inhibit platelet aggregation - gastric ulceration - renal dysfnx - hepatocellular injury - allergic rxn - asthma - tinnitus - myocardial infarction
Salicylates
Irreversibly acetylates COX Actions: - analgesic - low intensity pain - anti-pyretic - anti-inflammatory - rapidly absorbed from small intestine - liver metabolism Side effects: - GI upset - dyspesia - bleeding - tinnitus - allergic rxn
Ibuprofen, naproxen
Propionic acid derivatives Actions: - analgesic - anti-pyretic - anti-inflammatory - less GI irritation, dyspepsia compared to aspirin Side effects: - renal toxicity in renal pts Naproxen - longer half-life
Acetaminophen
Actions: - analgesic - anti-pyretic - no interaction with platelets - no GI irritation Side effects: - NAPQI - hepatotoxic - treat with N-acetylcysteine
Ketorolac
Actions: - potent analgesic - moderate anti-inflammatory - potentiates opioid action - absence of ventilatory and cardiac depression Side effects: - inhibits platelet aggregation - bronchospasm in ASA sensitive pts - GI irritation - renal toxicity in renal pts - hepatic toxicity
Celecoxib
COX 2 selective inhibitor Actions: - analgesic - anti-inflammatory - crosses BBB - well absorbed from GI - lacks platelet aggregatoin - decreased GI side effects Uses: - arthritis and post-op pain
Morphine
Delayed onset and peak effect due to poor CNS penetration
- poor lipid solubility and mostly ionized and protein bound
Metabolism:
- most to M3G
- some to M6G - active, analagesia and respiratory depression
- removed in urine, worry about renal pts
Effects:
- analgesia, euphoria, sedation
- histamine release
Worry about renal pts and build up
Meperidine
Less potent than morphine Metabolism: - to normeperidine which can cause seizures and myoclonus - worry about renal pts cuz build up Uses: - post-op shivering Side effects: - decreased cardiac contractility - mydriasis, tachy - like atropine - seziures - histamine release
Fentanyl
Much more potent than morphine
More rapid and shorter duration than morphine - lipophilic
No myocardial depression or histamine release, no active metabolites
Sufentanil
More potent than fentanyl
Rapid onset/offset - lipophilic
Uses:
- big incision with lots of pain
Alfentanil
Less potent than fentanyl
Fastest equilibration and offset
- due to low pK
- readily crosses BBB
Hepatic metabolism, renal failure does not affect clearance
Uses:
- short lived stimuli like nerve block, before putting in big needle
Remifentanil
Similar potency to fentanyl
Very fast onset and offset like alfentanil
Metabolized by tissue plasma esterases so can use in kidney and liver failure
Methadone
Mu agonist and NMDA antagonist 2 half-lives, prolonged and unpredictable - pain is 4-8hrs - negative side effects is 20hrs Dose low and slow Uses: - pain and addiction
Hydromorphone
More potent than morphine - same side effects Safer in renal pts cuz no active metabolite build up Uses: - perioperative pain in renal pts
Buprenorphine, butorphanol
Agonist/antagonist mix Effects: - analgesia - minimal ventilatory depression - low physical dependence potential Uses: - pts who can't tolerate pure agonist, negative side effect profile reduced
Naloxone
Opioid antagonist
Mechanism:
- high affinity for opioid receptor, kicks out agonist
Potently and rapidly reverses agonist effects
Uses:
- treat opiate induced ventilatory depression, neonatal depression and overdose
Short duration
Side effects:
- CV stimulation, increased SNS activity, therefore increased pain perception, tachycardia, HTN, pulmonary edema and dysrhythmia
- can reverse pain/analgesia and lead to withdrawal (especially in neonates)
Phenytoin
Anti-epileptic Mechanism: - slows Na channel recovery rate - keep Na channel block in longer First line for partial/focal seizures 95% protein bound, so saturation kinetics - small dose increases can cause unpredictable changes in plasma concentration and adverse events Induces p450, increases its own metabolism Give IV for status epilepticus Adverse events: - Nystagmus - Ataxia - Lethargy - Gingival hyperplasia - Incoordination, confusion - Hirsutism - Facial coarsening - Systemic skin rash
Carbamazepine
Anti-epileptic Mechanism: - slows rate of Na channel recovery First line for partial/focal seizures - suppression of seizure foci and prevention of spread of activity Inactivated by liver metabolism; induces its own metabolism during first 3-6wks, need larger doses 10-11 epoxy metabolite may contribute to neurotoxicity Side effects: - sedation - drowsiness - headache - dizziness - blurred vision
