Anticholinesterases

Acetylcholine is used in entire parasympathetic nervous system (parasympathetic ganglions and effector cells), parts of the sympathetic nervous system (sympathetic ganglions, adrenal medulla, and sweat glands), some neurons in the central nervous system, and somatic nerves innervating skeletal muscle

- anticholinesterases increase muscarinic stimulation, which is to be minimized by giving glycopyrrolate or atropine. Muscarinic stimulation causes SLUDGE syndrome to brady, bronchospasm, GI output

- Neostigmine onset 5 min, peak 10 min, lasts 70 min. Glycopyrrolate has similar onset compared to atropine which has faster onset. However, neostigmine crosses the placenta to cause fetal bradycardia so theoretical benefit in using atropine in preggers

- Edrophonium onset ins 1-2 min but shorter duration. Full dose should be given each time so that duration will be long enough. Use with atropine.


Anticholinergic drugs such as glycopyrrolate, atropine, scopolamine causes tachycardia, inhibits secretions, reduces GI secretions (but not enough to reduce aspiration), causes mydrasis and cycloplegia (inability to accomodate near vision), urinary retention.

Scopolamine causes reduction in motoin sickness (n/v), potent sialagogue (better than atropine), and drowsiness. Lipid solubility means it can be given via patch. Avoid in closed-angle glaucoma

Anticholinergic syndrome (alice in wonderland)

Nondepolarizing Muscle Relaxants

Metabolism/Excretion
- Liver metabolizes pancuro/vec. Biliary excretes vec/roc. Liver failure potentiates pancuro/roc> vec>>pipecuronium. Miva is metabolized by pseudocholinesterases, atra/cis metabolized by hoffman
- Kidney excretes pancuro/vec/pipe/doxa but not roc

Potentiation/Resistance
Potentiation:
- calcium channel blockers, beta blockers, magnesium, lithium, aminoglycosides, volatiles, local anesthetics
- Volatiles decrease nondepolarizer requirements by 15%. Des>Sevo>Iso>NO2 and pancuro>vec/atra
- Combining nondepolarizers of different classes (aminosteroid vs benzylisoquinoliniums) provide synergistic effects (greater than additive)
- Neuro disease potentiates N-NMBs except burn, CP, denervation, sepsis which causes resistance
- Newborns are more sensitive to NMB because of immature receptors but they also have greater extracellular space so no net effect in dosage. N-NMB have faster onset though. Vec is longer lasting.

Resistance:
- anticonvulsants (only aminosteroids?)
- Neuro disease potentiates N-NMBs except burn, CP, denervation, sepsis which causes resistance

Onset/Duration
- ED95 for NMB is the dose when 95% twitch suppression occurs in 50% of patients. Intubation dose is usually twice the ED95. Increasing the dose means faster relaxation but more side effects and prolonged block.
- Onset is 2.5 to 3 minutes except roc which works in 1.5 to 2 minutes
- Duration is 40-70 minutes except pancuronium which is 60-90 minutes
- histamine release by vec/atra can cause hypotension, vagolysis by pancuronium can cause tachycardia, older tubocurium and metocurium block sympathetics causing brady and hypotension
 -Dosage by Adjusted BW = 0.4(ABW - IBW)+ IBW. IBW = 50kg + 2.3kg*(each inch after 60)

Atracurium - histamine release (hypotension, tachycardia), bronchospasm (avoid in asthmatics, 2/2 histamine), laudanosine metabolite is degraded by liver (raises seizure threshold), hoffmann slowed by hypothermia and acidosis, anaphylaxis. Cisatracurium is 4x more potent and makes up 15% of atracurium but produces no histamine release and less laudanosine 2/2 potency.

Pancuronium - metabolized by liver with active metabolites, excreted by kidney and bile. Vagolytic and sympathetic effect. Vecuronium is similar. Prolonged infusion in ICU causes prolonged block for days.

Rocuronium - mainly excreted in liver/bile some in kidney.

Succinylcholine

Dose 1-1.5mg/kg
- higher in children who have more extracellular space
- use real weight (pseudocholinesterase increase with real weight)
- very weakly lipophilic

Duration 5-10 mins, Onset 30-60 secs

Metabolism by pseudocholinesterases
- dibucaine 80% normal, 20% homologous abnormal, 40-60% hetero; prolonged to 2-4 hours in homo, 20 min in hetero
- Medications that decrease pseduocholinesterases: phenelzine, neo, physo, edrothiophate, cyclophosphamide, metoclopromide, esmolol, OCPs
- metabolized to succinylmonocholine, which may sensitize SA node to 2nd dose of sux, causing brady

Interactions
- nondepolarizing blockers antagonize sux but prolongs phase II block
- cholinesterase blockers like neo, physo, organophosphate, echothiophate prolongs sux

CV
- brady and even asystole in children 2/2 muscarinic effects
- metabolized to succinylmonocholine, which may sensitize SA node to 2nd dose of sux, causing brady

Fasiculations and Mylagias
- possibly decreased by priming with non-depolarizing, but requires higher dose of sux 2/2 interactions

Hyperkalemia
- worst in day 7-10 after burn or trauma, minimal in 48 hours
- burns and traumas
- myopathies and GBS
- parkinsons, stroke, encephalitis, immobilization

aspergillosis

- colonizing

- ABPA requires hypersensitivity (anti-aspergillus abs, skin prick) + asthma
- Eosinophilia and elevated IgE
- CXR shows proximal bronchiectasis, fleeting infiltrates

Aspergilloma
- old bulla or cavity
- CXR shows dependent fungal ball
- no treatment

Chronic necrotizing aspergillosis
-

Invasive aspergillosis
- tissue biopsy
- surgery and anti-fungals