Cholinesterase Inhibitors 2-3

Question 1

Cholinesterase

Answer 1

-an enzyme that breaks down ACh (a neurotransmitter) into choline and acetic acid
–> allows neuron to return to resting state after activation
-can breakdown ACh in short period of time

Question 2

Cholinesterase inhibitors
(anticholinesterase agents)

Answer 2

-drugs that prevent breakdown of ACh by cholinesterase –> increase ACh at neuromuscular junction
-lack sensitivity: thus have limited therapeutic effects

Question 3

Alzheimers

Answer 3

-meds are targeted to slow loss of memory, cognition AND prolong independent function (help with ADLs)
(CANT stop disease progression, not even in early stage or treat core s/s or reduce cognitive impairment)

-ONLY has modest/little improvements in cognition –> NO significant delay progression
-GI side effects is common
-avoid antihistamines (and other drugs that block cholinergic receptors)
-DO improve neurons NOT damaged yet

-Rivastigmine patch needs to be changed daily, not reused same site in 14days, and has reduced side effects

Question 4

Myasthenia Gravis (MG)

Answer 4

-autoimmune/congenital neuromuscular disease –> fluctuating muscle weakness and muscle fatigue
(due to circulating antibodies that block ACh receptors)

-s/s: ptosis (eye droop), difficulty swallowing, skeletal muscles weakness, can cause difficulty breathing (weakness of diaphragm muscles upwards –> aspiration risk)

Question 5

Reversible cholinesterase inhibitors: Neostigmine (Prostigmin)

Answer 5

-reverse MG
-MOA: cholinesterase needs a long time to breakdown neostigmine –> keeps enzyme busy –> more ACh available to activate cholinergic receptors

==> all rapidly absorbed by all routes

other uses: reverse competitive NMB
-post op
-treat overdose of NMB (except Succinylcholine)
(be sure to bag/vent pt until recover bc resp depress)
==> effect of cholinesterase inhibitors at muscarinic receptors are opposite to Atropine

Question 6

Neostigmine pharmacokinetics

Answer 6

-duration: 2-4h
-no cross BBB
-take before dinner/meal: so it peaks at meal
-take 3-4 times a day
-take a supplementary dose before exercise

Question 7

Neostigmine pharmacodynamics

Answer 7

MUSCARINIC RESPONSES: wet (slug bam) (opposite of Atropine)
-prevent breakdown ACh: bradycardia, bronchial constriction, urinary urgency, increased GI motility (diarrhea), excess salivation and lacrimation, blurred vision (myosis: pupils constrict)

NEUROMUSCULAR EFFECTS
-dose dependent
-therapeutic dose: increase force of contraction (and mild CNS stimulation)
-toxic dose: decrease force of contraction and decrease CNS and respiratory (cholinergic crisis) –> reverse with Atropine (but resp depression CANNOT be reversed so give supportive therapy)

Question 8

Mysathenic crisis

Answer 8

-pt are inadequately medicated
-cause death from paralysis of respiratory muscles

==> antidote: Neostigmine

Question 9

Cholinergic crisis

Answer 9

-overdose of cholinesterase inhibitor (Neostigmine)
==> antidote: Atropine + respiratory support (code cart)

Question 10

differentiate between crises

Answer 10

diagnosis is made by administering Edrophonium (Tensilon)
-if s/s improves after administration: myasthenia crisis
-if s/s intensifies after administration: cholinergic crisis