Kelly - Exam 3 Outline PDF

**[730 Exam 3: Cerebral Physiology, Monitoring in Neuro Anesthesia, States of Brain Activity and Anesthetic Effects]** Purple - it was on the quiz // Red - is had an asterisk next to it in the ppt **[Cerebral Physiology]** - this ppt was very repetitive so i may not type the entire ppt to try to c...

**[730 Exam 3: Cerebral Physiology, Monitoring in Neuro Anesthesia, States of Brain Activity and Anesthetic Effects]** Purple - it was on the quiz // Red - is had an asterisk next to it in the ppt **[Cerebral Physiology]** - this ppt was very repetitive so i may not type the entire ppt to try to condense a little - Monro-Kellie Doctrine / Hypothesis - Dynamic relationship exists between CSF, blood, and brain tissue - An increase in one component should cause a decrease in one or both of the other components - Implications for increased ICP and decreased CSF volumes - Supported by MRI abnormalities - "You have a rigid cranial vault, which doesn't allow for compensation for an increase in brain tissue / volume" - "A small volume increase isn't a big deal, but a large increase in volume is bad" -  - Cerebral Blood Flow - what is it? - Blood supply to the brain in a given time - Normal global CBF: 45-55 ml/100g brain tissue / min - "Some resources say 50-60 ml" - 750-900 ml/min - Cortical: 75-80 ml/100g brain tissue / min - Subcortical: 20 ml/100g brain tissue / min - "Supply, perfusion, and cerebral vascular resistance (CVR) all alter CBF" - Critical Thresholds for CBF - \~ 20ml/100g brain tissue / min → evidence of ischemia - \~ 15ml/100g brain tissue / min → complete cortical suppression - \< 15ml/100g brain tissue / min → membrane failure / cell death - Cerebral Blood Flow - Supplied by the central carotid (70%) and vertebral arteries (30%) - 50 ml/100 g brain tissue / min - \~ 14-15% of normal CO - Ohm's equation: Q = (Pa-Pv) / R - "Pressure difference divided by resistance" - CPP = MAP - ICP ("or CVP - whichever is higher") - The greater the ICP, the smaller the CPP with a stable MAP - CBP = CPP / CVR - CVR = MAP - ICP (CPP) / CBF - MAP = 2 (DBP) + SBP / 3 (nick so help me if you change this to your weird equation) - Normal global CBF = 50-65 ml/100 g brain tissue / min → 750-900 ml/min (adults) - Ohm's law → change in pressure / resistance - Poiseuille\'s law → Q = (P2 - P1) pi x r4 / 8 x viscosity and vessel length - CBF - Ohm's Law - Flow = inflow pressure - outflow pressure / resistance (ohm's) - Brain venous pressure = \~ 2-5 torr - "usually pretty low" - Directly influenced by ICP - Influenced by CVR (Poiseuille's law) - CBF - Poiseuille's Law - Vessel length - Blood viscosity - Radius of cerebral vessels - "since it's to the fourth power it has the most impact - think constriction and dilation" - Cerebral resistance (R) = (8 l n) / pi r\^4 - Flow = pi (constant) x (pressure gradient x vessel radius) r\^4 / 8 x blood viscosity and vessel length - Application of Poiseuille's Law in CBF - Flow rate is affected by the pressure difference, blood viscosity, length of the vessel, and the radius - Direct relationship to the pressure difference and the radius - "Radius is the most impactful - some volatiles and antihypertensives can increase CB through cerebral vasodilation" - Indirect relationship to blood viscosity and vessel length - Poiseuille's Law and Mean Flow Rates for IVFs - Increased radius → greatest effect on flow rate - Large bore peripheral IV \> flow rate than CVC - "Due to the PIV being shorter; cardiac surgery patients will get 14g or 16g - not even 18g" - "Exception to this is a 9fr trauma line" - Increased pressure gradient → gravity, pressure bags, infusion devices = increased flow rate - "Viscosity is inverse to the flow rate - LR has a lower viscosity than albumin, and cold blood is slower than warm blood because it's more viscous" - viscosity is inverse, because it\'s on the bottom of the equation - CMRO2: cerebral metabolic rate for O2 consumption - "highly coupled with CBF" - Describes how much oxygen the brain consumes / minute - Normal CMRO2 in adults: 3.0 - 3.5 - 3.8 ml O2 / 100g brain tissue / minute - "Older adults are even lower, which is why hyperbaric O2 chamber is correlated with decreased mentation in older adults" - Normal CMRO2 in peds: 5.2 ml O2 / 100g brain tissue / minute - Decreased by hypothermia ("due to to decreased metabolic rate"), and anesthetic drugs - Increased by hyperthermia, seizures, ketamine, N2O - "all increase metabolic rate" - Cerebral Metabolic Rate for Glucose - CMRg - glucose is consumed by the brain at a rate of 5-5.5 mg/100 g brain tissue / minute - More than 90% of glucose is metabolized aerobically through oxidative phosphorylation - Approximately 10% is converted anaerobically to lactic acid - Normal Values for Cerebral Substrates and Metabolism in Humans - - Global CBF - spinal cord blood flow - Global CBF in adults = 50 ml/100 g brain tissue / minute - Consists of flow from 2 different regions - gray matter (cortical) and white matter (subcortical) - Grey matter - neuronal cell bodies and synapses = higher metabolism → 75 ml/100 g brain tissue / minute - White matter - fiber tracts = lower metabolism → 20 ml/100 g brain tissue / minute - Global CBF in children = 95 ml/100 g brain tissue / minute - Global CBF in infants = 40 ml/100 g brain tissue / minute - Spinal cord blood flow; - Grey matter = 60 ml/100 g/minute - White matter = 20 ml/100 g/ minute - Cerebral and Spinal Cord Blood Flow - Rate of cerebral blood flow is largely determined by CMRO2 - "they're tightly coupled" - Coupling of blood flow and metabolism regionally - Global blood flow of the brain remains stable in a given physiologic state - "due to tight coupling" - Facts that Impact Cerebral and Spinal Cord Blood Flow - Anesthetics and hypothermia - Decreases in metabolism - Reduction in global CBF - 5 Main Factors Affecting CBF - Cerebral metabolic rate (CMR) - Autoregulation - CPP - 50-150 mmHg - Venous pressure - PaCO2 - CO2 reactivity - PaO2 - O2 reactivity - \*Autoregulation - MAP 50-150 mmHg - 60-160 in some texts - From Apex: - - Factors Affecting CBF - Hypothermia - CBF decreases 5% per degree (in celsius) drop in temperature - Increased body temperature = increase in CBF and metabolism - Blood viscosity, vessel diameter (also worded as the degree of vessel dilation) - cerebral perfusion pressure - Altitude - "those who live at high altitudes adjust, but when climbing you need to ascend slow / have supplemental O2" - Autoregulation and flow metabolism coupling - Blood gas content - Cardiac output - Chemical mediators - "CO2, H+" - Hypothermia - occurs when the body's core temperature drops below 95 F (35 C) - Risks vs Benefits - Decreased CBF - "don\'t want to decrease it too much" - Decreased cerebral metabolism - Decreased ICP - Cerebral vasoconstriction - Decreased CVR (increased makes more sense due to vasoconstriction, but her slide says decreased... good eye scott) - Decreased CMRO2 \> decreased CBF - Cognitive impairment - Excitotoxicity reduction - Decreased inflammation and edema - Decreased BBB disruption - Decreased oxidative stress - "Decreased temperature → body slows (decreased CMRO2) → decreased CBF - can be protective" - Altitude - CBF is elevated at high altitudes - High altitude headaches - Acute mountain sickness - High altitude cerebral edema - Compensation → increased hct/hgb = increased O2 carrying capacity - "Long term adaptation leads to polycythemia" - Cerebral autoregulation - What is it - homeostatic process → ability of the brain to regulate / maintain a constant CBF across wide range of blood pressures - Matched to cerebral metabolic demand - Ensure brain has a steady state of blood and nutrients - Involves myogenic, neurogenic, metabolic, and endothelial interactions - Physiologic, pathologic, and anesthetic conditions increase / decrease CBF - Protects the brain from hypo / hyper perfusion - CBF constant - MAP 50-150 torr or CPP 50-150 torr - Control and Regulation of CBF - Autoregulation - theories of autoregulation: - Myogenic - contraction or relaxation of smooth muscles around the arterial walls regulates changes in BP - Metabolic - metabolic substances regulate changes in the BP - Neurogenic - brainstem regulates changes in the BP - Endothelial - CBF controlled by numerous vasoactive mediators produced by the endothelium - NO - acts as a neurotransmitter and component in signaling pathways - ET1 - amino acid peptide → vasoconstriction - "Reality: it's probably a combination of all of these" - Regional flow metabolism coupling - Carbon dioxide reactivity - Hypoxemia - CBF Autoregulation Review - What is it? - "brain's ability to maintain constant flow with changes in the CPP" - Rapid response: 3-120 seconds - "if there's a drop in flow your body automatically reacts" - What is the purpose of cerebral autoregulation? - Constant CBF range for a MAP of 50/60 - 150/160 mmHg - Myogenic activity - Alteration of vessel diameter\* - Varying smooth muscle tone - Increased BP or MAP → vasoconstriction → decreased flow - Decreased BP or MAP → vasodilation → increased flow - Ensure a relatively stable blood flow and protects against swings in the blood pressure - CBF Autoregulation with MAP \> 150/160 mmHg - MAP \> 160 and \< 60 - CBF is directly proportional to MAP = linear relationship - What can happen at MAPs above 160? - Hyperemia - too much blood flow can raise the ICP causing compression and damage to the brain tissue - Disruption of BBB - Cerebral edema - CBF Autoregulation with MAP \ - Respiratory Clues in Coma - - Neurologic Assessment - Mental / Level of Consciousness Status - Glascow Coma Scale - Assess right and left symmetry of responses to stimuli - Look for any kind of posturing - Neurologic posturing can be caused by: - Conditions that lead to large increases in ICP - TBI - Stroke - Intracranial hemorrhage - Brain tumors - Encephalopathy - Malaria - Posturing due to stroke - usually occurs only on one side of the body → spastic hemiplegia - Decorticate posturing and decerebrate posturing - can indicate brain herniation - [Decorticate posturing]: decorticate response, decorticate rigidity, flexor posturing, "mummy baby" - Present with arms flexed, or bent inward on the chest, the hands are clenched into fists, and the legs extended and feet turned inward - Decorticate posturing in response to pain = 3 on GCS - Can indicate damage to: cerebral hemispheres, internal capsule, thalamus - may also indicate midbrain damage - This is an **ominous sign of severe brain damage, but decerebrate is usually indicative of more severe** damage - [Decerebrate posturing]: decerebrate response, decerebrate rigidity, extensor posturing - Present with head arched back, arms extended and rotated internally by the sides, elbows extended, legs extended and internally rotated - Patient is rigid with teeth clenched - Posting can be on both sides, one side, just arms, and also may be intermittent - Decerebrate posturing in response to pain = 2 on GCS - Indicates brain stem damage and is exhibited by people with lesions or compression in the midbrain and lesions in the cerebellum - common in Pontine strokes - Patients with decorticate posturing may begin to show decerebrate posturing, or may go from one form to the other - Progression from decorticate → decerebrate is often indicative of uncal (transtentorial) or tonsillar brain herniation - Patients displaying either type of posturing: - Have poor prognosis - Are at risk for cardiac arrhythmias, cardiac arrest, and respiratory failure - Normal and abnormal reflexes - Oculocephalic reflex - 'Doll's Eyes" - Oculovestibular reflex - 'Iced Caloric' - Neurologic Testing in Coma Patients - Normal and abnormal reflexes - Visual acuity can't be tested in a comatose patient - Pupillary response → CN 2 and 3 - Extraocular muscle testing → CN 3, 4, and 6 - Eye movement through reflex response - [Oculocephalic reflex / Doll's eyes reflex] → CN 3, 4, 5, 6, and 8 - Reflex is suppressed in an alert patient - Reflex eye movement that stabilizes images on the retina during head movement by producing an eye movement in the direction opposite to head of the bed - Produced by moving the patient's head passively from left to right or up and down - \+ reflex = eyes don't turn with the head when the head is turned or are asymmetric - Eyes should move in opposite direction to the head movement - Will normally lag behind head movement and then come back midline - Absence of asymmetry of this reflex indicated dysfunction somewhere in the reflex pathway - brain stem - Images on the center of the visual field are preserved - Avoid in suspected cervical spine injury - [Oculovestibular reflex] / cold calorics / caloric stimulation → CN 3, 4, 6, and 8 - Produced by placing the patient's upper body and head at 30 degrees of horizontal, and injecting 50-100 ml of cold water into their ear - Present in awake patients, but may produce vomiting - In a normal response, this reflex induces eye deviation and produces nystagmus in the direction of the non-injected ear - Eyes move slowly back to position - Warm H2O injected in the ear canal will produce nystagmus to the same side - COWS = cold opposite / warm same - Additional cranial nerve testing in comatose patients - CN III - response to light - CN V - corneal reflex test - CN VII - facial grimacing in response to noxious stimuli - CN IX and X - gag reflex **[Neuroanesthesia]** - impacts of Anesthesia Agents on CBF - Inhaled Anesthetics - Volatiles: isoflurane, desflurane, and sevoflurane - Gaseous anesthetics: nitrous oxide and xenon - N2O increases CMRO2 - N2O can increased CBF → increase in ICP - These effects are most likely due to activation of the SNS - These can be offset by combining N2O with volatile agents, IV anesthetics, and/or hyperventilation - Hyperventilation decreases CBF in patients with increased ICP - "Some people avoid N2O in sitting position - VAE risk" - Cerebral effects - Decrease metabolic activity of the brain and CMRO2 (dose dependent) - Intrinsic vasodilatory properties uncouple CMRO2 and CBF - Cerebral vasodilation - can increase CBF - Net effect on CBF (increase, decrease, or no change) → concentration of agent delivered (minimum alveolar concentration) - 1.0 MAC - what is this? - "partial pressure of inhalational anesthetic in the alveoli that causes 50% of patients to not move in response to skin incision" - Formation of both types of memory is reliably prevented at low MAC values of **0.2-0.4** - Implicit and explicit memory and awareness - **0.5 MAC** - the reduction in the cerebral metabolic rate \ the vasodilation caused by anesthetic → CBF is decreased - **1.0 MAC** - effects are balanced → unchanged CBF = baseline - **1.5 MAC** - vasodilation effects \ reduction in cerebral metabolic rate → CBF increased - "You could offset this with mild hyperventilation" - What does this mean for the patient with an increased ICP? - "These patients really don't need a further increase in ICP - be aware of concentrations, fresh gas flows, end-tidal measurements, etc. → you could use hyperventilation to attenuate the vasodilation" - Iso, des, and sevo produce initial activation of EEG at low doses, then slowing of electrical activity up to 1-1.5 MAC - At higher concentrations, EEG suppression increases to the point of electrical silence with isoflurane at 2.0-2.5 MAC - Isolated epileptic like patterns may be seen at concentrations between 1.0-2.0 MAC - especially with sevo - Clinical seizure activity ("true tonic-clonic movements") has been observed with enflurane - N2O used alone causes fast electrical oscillations in frontal cortex at doses associated with analgesia/depressed consciousness - Stages of inhalational anesthetics → "BIS can help us know our stages, and help us use less inhalational anesthestics" - Stage I - analgesia (both analgesia and amnesia in late stage I) - Stage II - excitement - State III - surgical anesthesia - Stage IV - medullary depression - Induction agents - Facilitate rapid induction of anesthesia - Provide sedation during monitored anesthesia care - Good option for maintenance of anesthesia - Cerebral vasoconstriction - decreased CMRO2 and CBF in parallel except for one ("ketamine") - IV non-opioid anesthetics - Propofol - most frequently used induction agent - Also used for maintenance phase of general anesthesia in continuous infusions or by boluses - Useful as sedation in monitored anesthesia care - Alkyl phenol with hypnotic properties - Is chemically distinct from other groups of IV anesthetics - Poor solubility in water - emulsion of 10% soybean oil, 2.25% glycerol, and 1.2% lecithin - How do these additives affect the patient? - Should be used ASAP, but must be used within 8 hours after drawing up medication - Sterile technique is required - Metabisulfite is added in some formulations - issues with sulfite allergy and can cause reactive airway disease - MOA → potentiation of the chloride current mediated through the GABA receptor complex - Short context sensitive half-time leads to relatively prompt recovery - CNS effects: - Hypnotic without analgesic properties - Induction - may cause excitatory effects which resemble seizure activity - Safe to use in patients with seizure disorders - some studies suggest anticonvulsant properties - CBF and CMRO2 decreased - Decreases in ICP and IOP - Comparable to thiopental - Potential for decreased CPP due to: - Decreased CBF - Decreased MAP due to peripheral vasodilation - Fospropofol - "may see when there are supply issues" - Water soluble prodrug of propofol - Rapidly metabolized by alkaline phosphatase - Propofol, phosphate, formaldehyde - Formaldehyde is metabolized by aldehyde dehydrogenase in the liver and in erythrocytes - Lusedra 35 mg/ml - No injection pain, but paresthesia in perianal region - Similar effects to propofol but with prolonged onset and recovery - Barbiturates - "not commonly used anymore" - Thiopental - no longer available in the US - Why don't we use it anymore - "We used it for capital punishment, so manufacturers didn't want to make it for that and now it's made in other countries that won't sell it to us because they don't believe in capital punishment" - Methohexital - ECT → "short-acting barbiturate" - Combination of inhibitory and inhibition of excitatory transmission - Activation of GABA receptors - Dose dependent CNS depression - Ranges from sedation to GA - No analgesia, possible hyperalgesia - Potent cerebral vasoconstrictors - Decreases CBF, CBV, ICP, and CMRO2 - Dose dependent suppression of EEG activity - Can be used as an anticonvulsant - except Methohexital - Methohexital - Activates epileptic foci - Useful in ECT - Surgery - Neuroprotective effects - Etomidate - Carboxylated imidazole derivative - Poorly water soluble - Hypnotic, but no analgesic effects - Minimal hemodynamic effects - Endocrine effects limit use as an continuous infusion - GABA like effects - CNS effects: - Potent cerebral vasoconstrictor - Decreases CBF, ICP, CMRO2 - **No neuroprotective effects** - **May activate seizure foci** - Myoclonic activity with seizure like activity on the EEG - Ketamine - Partially water soluble and highly lipid soluble phencyclidine derivative - Produces significant analgesia\* - Dissociative anesthesia - MOA - inhibition of the NMDA receptor complex - Highly lipid soluble - rapid onset - Metabolized in the liver - excreted in the urine - Produces norketamine - Low protein binding - CNS effects: - Cerebral vasodilator\* - Increases CBF and CMRO2 - These effects may be blunted by maintenance of normocapnia - Anticonvulsant properties - Potential to produce myoclonic activities\* - Used as treatment for status epilepticus when more conventional drugs are ineffective\* - Unpleasant emergence reactions - lower incidence and less severe in children - Vivid colorful dreams, hallucinations, out of body experiences - Increased and distorted visual, tactile, and auditory sensitivity - Euphora - high abuse potential - Other IV anesthetics - Dexmedetomidine - Highly selective, water soluble, alpha-2 adrenergic agonist - Effects can be antagonized with alpha-2 antagonist drugs - Metabolites are excreted in the urine and bile → short elimination half-time - Context sensitive half-time increases with longer infusions - Has the potential to lead the development of tolerance and dependence - CNS effects: - Selective alpha adrenergic effects through activation of CNS alpha-2 receptors - Hypnosis - stimulation of alpha-2 receptors - Analgesic effect originates at the level of the spinal cord - Sedative effects produced by dexmedetomidine resembles a physiologic sleep state through activation of endogenous sleep pathways → "still allows a patient to breath spontaneously - less risk for hypercapnia (increased CBF)" - Decrease in CBF without significant changes in ICP and CMRO2 - Opioids - phenylpiperidines - Produce analgesia without hypnotic effects - can be used in combination with benzodiazepines as an induction agent - Slight decrease in CMRO2 and CBF - Large doses of potent opioids such as fentanyl can induce chest wall and laryngeal rigidity - "especially when remi is pushed" - Opioid agonists interact fully with the opioid receptors - **Mu** - analgesia, euphoria, sedation, dependence, respiratory depression, miosis, marked constipation, urinary retention, bradycardia, pruritus, muscle rigidity, biliary spasm - **Kappa** - analgesia, dysphoria, sedation, miosis, anti-shivering - **Delta** - analgesia, dependence, mild constipation, urinary retention - Opioid receptors are a group of inhibitory G-protein coupled receptors - CNS effects of opioids - Analgesia - inhibit ascending transmission of nociceptive transmission from the spinal cord - Activate pain control pathways from the midbrain - Sedation and euphoria - receptor dependent, not an anesthetic (recall) - ICP - changes result from hypercarbia → "due to the depressed respiratory function" - Full Agonists - Fentanyl - 100x more potent than morphine - Produces profound dose dependent effects - Terminated by redistribution - Highly lipid soluble - rapid onset and short DOA - Undergoes significant 1st pass effect in the lungs - Continuous infusion or high bolus doses results in a change in termination of effect - Clearance dependent on liver blood flow - Inactive metabolites - Affected by redistribution unless given in high doses - Remifentanil - Rapid and ultra short acting - Has an ester group that allows for easy and rapid metabolism by blood and tissue esterases \*\* - Increased risk for muscle rigidity → limit bolus dosing - "will mostly see it as a drip in neuroanesthesia" - Concerns with post-op analgesia → "if patient needs post-op pain control - use a long-acting pain medication" - Should not be given epidurally or intrathecally - Not for use for post-op pain - Sufentanil - Most potent of all the phenylpiperidine - Highly lipophilic - Shorter half-life than fentanyl - Excreted unchanged in the urine - Profound respiratory depression - "not good for neuro patients / those with high ICP" - Alfentanil - More rapid onset and shorter DOA than fentanyl - Highly non-ionized - Great patient to patient variability - High potential for post-op nausea - Peak respiratory depression in less than 2 minutes - Partial Agonists - Buprenorphine - partial agonists - Synthetic opioid derivative - Very potent and slow to dissociate - Has a high affinity to the mu receptor (50x greater than morphine) - Exhibits a ceiling effect - Antagonistic effects related to its ability to displace opioid agonists from their receptors (kappa) - Nalbuphine - partial agonists and is related to the opioid antagonist naloxone - Agonist at the kappa receptor and weak antagonist at the mu receptor - Potent analgesic - Respiratory depression exhibits a ceiling effect - Can be used to treat post-op shivering (kappa) - Very slow to dissociate from the opioid receptor - "May be used for withdrawal effects" - Equal in analgesic potency to morphine - Less potent antagonists than naloxone - Does not impact CV system and may be more useful in populations with cardiovascular disease - Can cause dysphoria - \*\*If you give an agonist /antagonist as a primary analgesic, consider your options for rescue or further tx of pain - Opioid Antagonists - Naloxone - non-selective opioid antagonist at all receptors - Used to treat: - Opioid induced respiratory depression - Pruritus (regional block) - Suspected drug overdose - Shorter duration of action than most opioids (½ life is one hour) - Should be administered in low and incremental doses - Can cause pulmonary edema - Naltrexone - Not addictive - Similar actions to naloxone - Blocks euphoric and sedative effects of opioids ("heroin, morphine, codeine, fentanyl, etc.") - Reduces / suppresses opioid cravings - Exhibits a longer duration of action than naloxone - Often given as a part of a treatment protocol for those recovering from SUD - Vivitrol (extended release) - Nalmefene - Alcohol abuse treatment - similar to naltrexone but not the same drug - Improved opioid receptor binding, improved bioavailability, less hepatotoxicity - She skipped the rest of the slides, but I still think she'll test on them so I added them on here - Benzodiazepines - Anxiolysis and anterograde pre-op medications - Highly lipid soluble - rapidly enter the CNS - Rapid onset, redistribution to inactive tissue sites, and subsequent termination of effects - Acts on glycine and GABA receptors - Midazolam - Shortest context sensitive half time - Continuous infusion - Decreased CMRO2 and CBF - but less than propofol and barbiturates - Ceiling effect for decreased CMRO2 - Little to no change in ICP in patients with decreased intracranial compliance - Potent anticonvulsant - Can be terminated by flumazenil - Diazepam - Lorazepam - Neuromuscular Blocking Agents - Depolarizers - act on receptors at the motor end plate → make the end plate refractory to ACh - Succinylcholine - 2 molecules of acetylcholine; has a single linear structure - MOA - agonist at nicotinic receptors at the NMJ - DOA - \< 10 minutes - Considerations: - Fasciculations (can cause increased ICP, but transient / during the fasciculations) - Hyperkalemia in patients with burns (1-2 years after), nerve damage, neuromuscular disease, closed head injury, etc. - Increased IOP, IGP, muscle pain - Can cause bradycardia - Non depolarizers - compete for binding sites on the alpha subunits of nicotinic receptors - 2 types of semi-rigid rings - Isoquinolines - Atracurium - hoffman elimination; histamine release - rarely used - Cisatracurium - hoffman elimination; less histamine release - Steroid derivatives - Vecuronium - Rocuronium - Pancuronium - can cause moderate increase in HR - MOA - competitive antagonism at nACh receptors in NMJ - Larger muscles are more resistant to NMB → recover more rapidly than smaller muscles - Don't cross the BBB - All NMBDs resemble acetylcholine structurally - Acetylcholine → a neurotransmitter at the NMJ - Synapses in the ganglia of the visceral motor system and at a variety of sites within the CNS - Synthesized in nerve terminals from acetyl coA and choline - Actions of ACh in the CNS are not well understood - Reversal Agents - Cholinesterase inhibitors → antagonize neuromuscular blockade - Neostigmine - Pyridostigmine - Increase availability of ACh at the motor end plate - Inhibition of acetylcholinesterase - Edrophonium - Inhibits acetylcholinesterase - More rapid onset - Less effective with profound block - Sugammadex - Selective relaxant binding agent → first of its kind - Reversal of rocuronium - bind to roc in a 1:1 ratio - MOA - encapsulates the roc molecule which then inactivates it - Can reverse all levels of NMB by aminosteroid ND-NMB - No parasympathetic side effects so no coadministration of antimuscarinic needed - Vecuronium (idk why she has this under sugammadex?) - Muscarinic receptor blocking drugs - Antimuscarinic - subtype of anticholinergic drugs - Parasympatholytics - MOA - block the effects of parasympathetic autonomic discharge - Atropine and scopolamine - tertiary amines - Glycopyrrolate - quaternary amine → less CNS effects, do not cross BBB - Used in conjunction with cholinesterase inhibitors to offset parasympathetic effects