• characterized by marked atrophy of the cerebral cortex and loss of cortical and subcortical neurons
• deficiency of intact cholinergic neurons observed in these areas

• present in high concentrations in cholinergic synapses
• hydrolyzes acetylcholine (Ach) and terminates its actions

• aka pseudocholinesterase
• may play some role in degradation of Ach in normal and Alzheimer's disease brains
• Rivastigmine inhibits both AChE and BuChE

• excitatory n.t. in the brain
• implicated in ling term potentiation
• glutamate mediated toxicity may play a role in neruodegeneration in Alzheimer's disease

• global and reversible depression of CNS
• Anesthetic state includes loss of consciousness, amnesia, and immobility (lack of response to noxious stimuli), but not necessarily complete analgesia
• can be IV or Inhalational

• several inhaled and/or IV drugs are used in combination to produce the anesthetic state
• administration of a mixture of small amounts of several CNS depressants maximizes the advantages, but not the disadvantages of the individual components of the mixture

• extreme variability in structures of molecules capable of producing general anesthesia
• suggests not all general anesthetics interact with a single receptor site

• Stage 1: analgesia (includes amnesia and euphoria)
• Stage 2: Excitement  (delirium, combative behavior)
• Stage 3: Surgical anesthesia (unconsiousness, regular respiration, ↓ eye movement)
• Stage 4: Medullary depression (respiratory and cardiac arrest, no eye movement)

• Pass rapidly through stage 2
• surgery occurs during stage 3
• avoid stage 4
• goal is to go from 1-3, then 3-1 post surgery as quickly as possible

• GABA enhancing action of barbiturates is greater than that of benzodiazepines
• overdoses of benzodiazepines are deeply sedating but rarely dangerous, where as barbiturate overdose may produce profound hypnosis, coma, resp depression, and death if supportive therapy is not provided

• these agents have high lipid solubility and enter brain rapidly
• they are then redistributed to less highly perfused tissues. This produces a short duration of action after a single bolus
• these agents leave CNS quickly but can be redistributed back later. Explains why they are short acting but can cause lingering effects

distributed from very rich organ groups with low capacity to low blood flow organs with high capacity

Blood→ CNS & visceral organs ↔ muscle & skin ↔ fat

• slow elimination 
• large volume of distribution 
• leads to cumulative prolonged effects
• Methohexital has more rapid clearance and does not [ ] in fat deposits → fewer cumulatie effects, more rapid recovery

condition in which there is a lack of the enzymes that produce heme

• fatal attacks can be induced in these patients if given IV barbiturates

moves from blood→ CNS → peripheral compartment (very little goes back to CNS)

short duration of action due to high clearance and slow diffusion from peripheral to central compartment

• can be a source of infection, but this is rare
• provides a large caloric source, can be important in critically iill pts who receive prolonged propofol infusions (can ↑ TG levels, etc.)

• ↓ BP (if given too rapidly IV or if rate of infusion is rapidly ↑)
• blunts baroreceptor reflex (smaller ↑ in heart rate seen for any given drop in BP after doses of propofol) Do not give bolus

• inhibits adrenal synthesis of cortisol and decreases plasma [cortisol]
• adrenal suppression may result in hypotension, electrolyte imbalance, and oliguria
• can lead to adrenal insufficiency 

accompanied by nystagmus with pupillary dilation, salivation, lacrimation, and spontaneous limb movements with ↑ overall muscle tone

• does not interfere with anesthetics, just looks scary

• side effect of ketamine
• post op disorientation, illusions, and vivid dreams
• causes serious pt dissatisfaction and complicates post op management
• to reduce chance of this effect, limit the dose or use IV diazepam or midazolam before admin of ketamine

• agents used in surgical procedures and in the intensive care unit to produce muscle paralysis
• interfere with transmission at the neuromuscular end plate and lack CNS activity
• 2 groups: depolarizing and nondepolarizing(competitive)

• used primarily to treat chronic back pain and painful fibromyalgic conditions or to reduce spasticity in a variety of painful conditions

• produce an excess of depolarizing agonist
• succinylcholine

• prevent access of acetylcholine to its receptor and thereby prevent depolarization

• experienced by chronic drinkers when forced to ↓ or discontinue alcohol
• indicates the existence of physical dependence
• symptoms include: hyper-excitability (in mild cases), and seizures, toxic psychosis, and delirium (in severe cases)
• Due to GABA/glutamate imbalance

• facial flushing, dizziness, nausea/vomiting, tachycardia and headach

ethanol ↑ endogenous opioid peptides and subsequently leads to release of dopamine

• this effect thought to be blocked by Naltrexone (Revia)

induces a hyperglutamatergic state

• antagonized by acamprosate

• uses as part of organic solvents
• converted to toxic metabolites formaldehyde and formate by alcohol and aldehyde dehydrogenases
• drugs that inhibit alcohol dehydrogenase (ie ethanol and fomepizole) reduce formation of toxic metabolites

involves 3 interventions:

1. suppress methanol metabolism (Fomepizole or ethanol)
2. hemodialysis
3. alkalinization with sodium bicarbonate to avoid metabolic acidosis

(metabolite of methanol) 

causes retinal and optic nerve damage

• chemical used in antifreeze
• metabolized by alcohol dehydrogenase to glycolic acid

1. nicotine replacement therapies (which are slowly tapered off)
2. non-nicotine therapy
3. 2nd line therapies (miscellaneous agents including clonidine nortriptyline, topiramate)