Beruflich Dokumente
Kultur Dokumente
Drugs
Kelompok 3
Anisa Rahma
Arifin Yusup
Sri Ramadhani
Wahyu Rizaldi
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Anticholinesterase Drugs
Cholinesterase (ChE)
inhibitors comprise
another group drugs
mimicing ACh by
inhibiting the hydrolysis
of endogenous ACh.
Cholinoceptor
agonists bind to
and activate
cholinoceptors
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Mode of action of Anticholinesterase drugs
Anti-ChE agents produce
Drugs act primarily where
effects by inhibiting AChE,
ACh is physiologically
decreasing hydrolysis of
released
ACh, and and are amplifiers
increasing A
of hendogenous
. ACh.
ACh evoke an increased
responses.
Their primary effects are
Anticholinesterase Drugs
The action of ACh is terminated by destruction
of AChE which is present
in cholinergic synapses.
(1) simple
alcohol
bearing a
quaternary
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Larger doses are
required for oral
administration than
for injection.
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Distribution
Distribution into CNS is negligible.
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Phosphoramide-type AChE inhibitors are inactive.
The selective toxicity is due to the differences in
the biotransformations between insects and
mammals
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Pharmacodynamics
Mechanism of Action
agents undergo a
of quaternary alcohols
two-step
bind electrostatically and hydrolysis
sequence. However,
by hydrogen bonds to the
the covalent bond of
active site, preventing
the carbamoylated
access of ACh. Theenzyme is more
enzyme-inhibitor resistant
complexto the
is short-lived. second process.
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Mechanism of Action of AChE Inhibitors
Organo-phosphates
AChE also active site and are hydrolyzed
inhibitors bind to AChE
undergo initial binding
and hydrolysis by the Covalent bond Irreversible
Ch
enzyme, resulting
Electrostatically
Hydrogen bond Ch
in a Ch
bond
phosphorylated active
site. The covalent
phosphorus-enzyme bond
is extremely stable and
hydrolyzed in a very slow
rate.
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Mechanism of Action of AChE Inhibitors
After the initial binding-hydrolysis step,
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Cardiovascular System-
The ChE inhibitors can
increase activation in ganglia
supplying the heart.
In the heart, the effects on the parasympathetic
Glaucoma is
with increasing
intraocular pressure.
Cholinesterase inhibitors reduce intraocular
pressure by increasing ACh concentration,
contracting the ciliary body and facilitating
outflow of aqueous humor.
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Gastrointestinal and Urinary Tracts
Postoperative ileus and congenital
megacolon involve depression of smooth
muscle activity without obstruction.
Urinary retention may occur postoperative
or postpartum or secondary to spinal cord
injury.
Of the cholineaterase inhibitions,
neostigmine is the most widely used for
these applications.
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Myasthenia gravis is a disease affecting skeletal
muscle neuromuscular junction.
Frequent findings are
ptosis, difficulty in
speaking and
swallowing, and
extremity weakness.
Even respiratory
muscles.
An autoimmune
process produces
antibodies that
decrease the
number of N2
receptors. 27
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Myasthenia gravis is a disease affecting skeletal
muscle neuromuscular junction.
ChE inhibitors can
increase ACh
concentration,
excite N2 receptors,
which strengthen
contraction.
Patients are also
treated with
immunosuppressan
t drugs and some
with thymectomy.
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Heart
The short-acting
cholinesterase inhibitor
edrophonium had
been used to treat
supraventricular
tachycardia.
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Antimuscarinic Drug in Toxication
Atropine intoxication is potentially lethal in
children and may cause prolonged severe
behavioral disturbances in adults. The
tricyclicantidepressants in overdosage, also
cause severe muscarinic blockade.
Cholinesterase inhibitors can antagonize the
blockage of M receptors (atropine
overdosage). 30
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CNS: Alzheimers disease
Tacrine is a drug with anticholinesterase and other
cholinomimetic action that has been used for the
treatment Alzheimers disease.
Donepezil, galantamine, and rivastigmine are more
selective AChE inhibitors that appear to have the
same modest clinical benefic as tacrine in treatment
of cognitive dysfunction in Alzheimers patient.
Donepezil may be given once daily because of its
long half-life.
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Toxicity of Cholinesterase Inhibitors
The acute toxicity:
The initial signs are those of
M symptoms: miosis, salivation,
sweating, vomiting, diarrhea,
and bronchial constriction.
CNS involvement usually follow rapidly,
accompanied by peripheral N effects, especially
depolarizing N2 blockade.
Chronic exposure to organophosphate ChE inhibitor
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cause neuropathy with demyelination of axons
ChE Reactivators
Cholinesterase reactivation, capable of
regenerating active enzyme from the
organophosphosphorus-cholinesterase
complex, is available to treat
organophosphorus poisoning.
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glad to share my knowledge with you,
and want you to become a master
of the subject, pharmacology
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