Download 06 Cholinergic agents. Anticholinergic Agents

Cholinergic agonists and
antagonists
Synapses are specialized junctions
through which neurons signal to each
other and to non-neuronal cells such as
those in muscles or glands
Cholinergic nervous fibres are:
1)
preganglionic (sympoathetic and
parasypmathetic);
2)
all postgnglionic parasympathetic;
3)
postganglionic sympathetic which supply sweat
glands and vessels of skeletal muscles;
4)
somatic nerves;
5)
nerves which supply adrenal medulla and
carotic sinuses;
6)
neurons of CNS
Adrenergic nervous fibres are:
1)
postganglionic sympathetic, except those which
supply sweat glands and vessels of skeletal muscles;
2)
neurons of CNS
Cholinergic drugs
1) M-, N-cholinomimetics (acetylcholine, carbacholine);
2) Anticholinesterase drugs – cholinesterase inhibitors
(proserin, galanthamine hydrobromide, pirydostygmine
bromide, armine);
3) M-, N- cholinoblockers (amisyl, cyclodol);
4) M-cholinomimetics (pilocarpin, aceclidyn);
5) M-cholinoblockers (atropine sulphate, platyphyllin
hydrotartrate, scopolamine hydrobromide, metacinum);
6) N-cholinomimetics (cytyton, lobelin);
7)
N-cholinoblockers:
а)
ganglionblockers
(benzohexonium,
pentamin,
hygronium,
arphonade);
б) myorelaxants (tubocurarinum chloride, dytylinum,
melliktin)
Amizyl
Indications for administration
neurotic disorders, Parkinson disease and other
extrapyramidal disorders, for premedication before
narcosis, for diseases which are accompanied with spasm
of smooth muscles, for dilation of pupil in ophtalmology
The drug is administered orally 0,001-0,002 g
3-4 times per day,
as eye dropps - 1-2 % solution is used
Side effects : dryness of mucous membranes,
tachycardia, dilation of pupils, disturbances of
accomodation.
The drug is contraindicated in case of glaucoma!
Cyclodol
Anticholinergic drug, mainly blocks central Ncholinoreceptors and peripheral Mcholinoreceptors
Usage
Parkіnson disease,
medicamental parkinsonism
Anticholinesterase drugs
Proserinum,
Galanthamini hydrobromidum,
Armin,
Pirydostygmini bromidum
Proserinum
Proserin is an anticholinesterase drug of
reverse action, its effect lasts for 2,5-4 hours.
Indications for administration
• Impairment of nerve conduction
after polyomyelitis, paralysis,
neurities, traumas
• overdosing with M-cholinoblockers
Galanthamini
hydrobromidum
Duration of action of
Galanthamini hydrobromidum is
longer than of Proserinum, that’s
why it can be administered 1-2 times
during the day
Indications for administration
Impairment of nerve conduction
after polyomyelitis, paralyses,
neuritis, traumas, overdosing with
M-cholinoblockers
myastenia gravis
Anticholinesterase
drugs are
contraindicated
in cases of epilepsia,
hyperkinesias, bronchial
asthma, stenocardia,
bradycardia
Acute poisoning with anticholinesterase drugs
(POC)
nausea, vomiting, diarrhea, abdominal pain
quick contraction of pupils, disturbance of
visus (spasm of accomodation)
increasing of salivation and sweating
bronchospasm
tachy- or bradicardia
seizures, excitement, loss of consciousness,
coma
Death is caused by breath insufficiency,
bronchospasm and lungs edema
POC (phosfororganic compounds as
insecticides)
Treatment of acute poisoning
•
•
Treatment should be started immediately (WHO)
stomach lavage with solution of Sodium hydrocarbonate
salt laxatives, enterosorbents
siphon enema
•
the poison should be carefully washed away from the skin
•
forced diuresis, in complicated cases - hemosorbtion,
hemodialysis
Indication of antagonist is necessary!!! –
atropine
sulphate. It should be introduced intravenously repeatedly, 2-4
ml of 0,1 % solution with the interval of 5-10 minutes. Appearance
of tachycardia, dilation of pupils, dryness in the mouth are the
criteria of sufficiency of atropine sulfate dose.
Also reactivators of cholinesterase which renew activity of this
enzyme are administered – dipyroxym, alloxym, isonitrosyn
M-cholinomimetics
Рilocarpini hydrochloridum
Pharmacodinamics
Contraction of pupil, improvement of outflow of
intraocular liquid and relief intraocular pressure
Dilation of eye vessels
Usage
Treatment of glaucoma
Improvement of eye nutrition in a case of thrombosis of
retinal central vein, acute obstruction of retinal arteries,
optic nerve atrophy
Systemic (resorbtive) action of the drug is not used
because of its high toxicity. The most dangerous
manifestation of poisoning with pilocarpinum is edema
of lungs
Acute poisoning
with substances of M-cholinomimetic action
(overdosing of drugs, consumption of mushrooms of Inocibe
family)
Clinical signes
• diarrhea, stomachache
• contraction of pupils, disorders of accomodation
• increasing of salivation, vomiting
• disorders of breathing because of bronchial spasm
• confusion, consciousness, seizures, coma
Treatment
• measures for organism purifying form poison
• intravenous introduction of 0,1 % Atropine sulfate solution –
2 ml every 10 min. (until appearance of dryness in mouth and
dilation of pupils)
• symptomatic treatment
M-cholinoblockers
Atropine sulfate
Scopolamine hydrobromide
Platyphyllin hydrotartrate
Metacinum
Dry extract of Belladonna
Atropa Beladonna
Pharmacokinetics and usage of M-cholinoblockers
Influence on an eye
Dilation of a pupil (midriasis)
Increasing of intraocular pressure
Paralysis of accomodation (cycloplegia)
Midriasis and cycloplegia stay for: atropine – 7-11 days, gomatropine – 1-2
days, platyphyllin – 5-6 hours,
scopolamine – 4-5 days
Usage
Investigation of orbital fundum (posterior chamber of eye)
Prevention of synechia (comissures) in case of trauma and operations on
eye
Contraindication
glaucoma
Pharmacodynamics and usage of
M-cholinoblockers
Pharmacodynamics
• Decreasing of function of excretory glands, except mammal glands
• Decreasing of tonus and peristalsis of smooth muscles of digestive tract,
bronchi, urinary tracts
Usage
• Ulcer disease of stomach and duodenum (gastrocepin)
• Liver, renal, intestinal colics
• Dyskinesias of gastrointestinal tract, enteritis, colitis
• Cystitis
• Bronchial spasm (Ipratropii bromide - atrovent)
Other cases of M-cholinoblockers
administration
• Holding of atropine test in case of atrioventricular blockade
(atropine)
• In anesthesiologia for premedicatoin – for prevention of
bronchial and laryngeal spasm, syncope, limitation of salivary
and bronchial glands secretion (atropine, scopolamine,
metacinum)
• Poisoning with M-cholinomimetics and POC (atropine)
• Sea, air disease (scopolamine, aeronum)
Gastrozepin (Gastrocepinum)
Side effects of M-chlinoblockers
•
•
•
•
•
Dryness of mucous membranes, dysphagia, dysphonia
Tachycardia
Increasing of intraocular pressure, glaucoma attack
Constipation, retention of urine (ischuria)
Formation of bronchial plugs in patients with bronchial
asthma
• Overheating
M-cholinoblockers are absolutely contraindicated in
patients with glaucoma
Acute poisoning with substances of Mcholinoblocking action
Causes
• Overdosing with drugs of
Mcholinoblockers group
• Consumption of plants, which include
alcaloids of this group
Belladonna
Datura stramonium L
Symptoms of acute poisoning with Mcholinoblockers
• “Atropine
psychosis”:
delirium,
hallucinations,
disorientation,
psychomotor excitement
• Redness and dryness of skin, increasing of body temperature
• Dryness of mucous membranes causes disorders of swallowing
(dysphagia), speech (dysartria, raleness of voice)
• Thirst
• Quick dilation of pupils (midriasis)
• Photophobia
• Visus disorders (Paralysis of accomodation)
• Tachycardia
• Atony of intestines
• Retention of urine
Death is caused by paralysis of breath center
Hyoscyamus niger
TREATMENT OF ACUTE POISONING WITH
CHOLINOBLOCKERS
M-
• wash out of stomach with 0,5 % Tannin solution, laxative
agents, sorbents, forced diuresis
• Specific antagonists – anticholinesterase drugs: repeated
introduction of proserinum, galantaminum, hydrobromidum until
symptoms of disappearance of M-cholinoblockers blockade
• removal of psychomotor excitement - aminasinum, sybazon,
barbiturates
• removal of tachycardia – anapryline
• for relief of photophobia patient is transferred to a dark room
• for decreasing of body temperature ice-cube bottles are placed
around the patient
• In case of considerable depressing of breathing - artificial
ventilation with oxygen inhalation
N-cholinergic
drugs
Lobeline is a natural
alkaloid found in "Indian
tobacco" (Lobelia inflata)
Usage
Breath stop of reflex
origin
Lobeline has been used as a
smoking cessation aid, and may have
application in the treatment of other
drug addictions such as addiction to
amphetamines, cocaine or alcohol.
Acute poisoning with nicotine
Clinical picture
nausea, vomiting, salivation,
abdominal pain, diarrhea,
dizziness,
headache,
cold sweat, weakness,
loosing of consciousness,
tachy- or bradycardia,
cardiac arrhythmias,
seizures,
breathing depression
Death is caused by acute depression of respiratory
center and paralysis of breathing musculature
Chronic poisoning with nicotine
Chronic diseases of respiratory system,
Lung cancer,
Malignant tumors of other etiology,
Ischemic heart disease,
Obliterating endarteritis,
Gastric and duodenal ulcer disease
• Women
Depression of female sex hormones production, yellow face,
early wrinkles, damaging of teeth, harsh voice, sometimes
male type hair growth
• Men
Deep, irreversible changes of spermatozoids
N-cholinoblockers
Ganglionblockers
Benzohexonium, pentamin, hygronium,
arphonad
Myorelaxants
Tubocurarine chloride, dithylin,
mellictin