Transcript Засоби, які впливають на функцію органів дихання

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)
M-, N-cholinomimetics
Acetylcholine
Carbacholine
Carbacholine
0,5-1 % solutions of carbacholine eye drops for treatment of glaucoma
The drug is never used orally and with
injections because of its consideralbe toxicity !
M-, N-cholinoblockers
Amizyl
Cyclodol
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
Pirydostigmini bromide (calimin)
Usage
• myastenia gravis
• after traumas, neuritis, paralyses
• in a period of recovery after polyomyelitis,
encephalitis
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
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
Treatment of acute poisoning
Depending on severity of poisoning
dipyroxym is introduced once or a few
times. An average dose of the drug in
heavy cases is 3-4 ml of 15 % solution.
The total dose of alloxym is 0,4-1,6 g
(0,075 g every 1-3 hours). If necessary artificial ventilation should be performed
to a patient. And after symptomatic
treatment is carried on.
M-cholinergic
drugs
M-cholinomimetics
M-cholinoblockers
M-cholinomimetics
Pilocarpini hydrochloridum
Aceclidinum
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
Aceclidinum
Pharmacodinamics
• Miosis, decrease of intraocular pressure, spasm of
accomodation
• Increase of tonus and peristalsis of smooth muscles of
digestive tract organs, urinary bladder
• Increase of tonus of uterus and bronchial muscles
• treatment of glaucoma
Usage
• prophylaxis and treatment of postoperative atony of
stomach, intestines, urinary bladder
• stopping of post delivery uterus bleedings
The drug is contraindicated in case of bronchial
asthma, pregnancy, stenocardia
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
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
cholinoblockers
M-
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
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
N-cholinomimetics
Cytitone
Lobeline hydrochloride
Cytitone
Pharmacodynamics
• increases tone of respiratory center of medulla oblongata
reflectively
• increases arterial pressure due to reflective excitation of
vascular-motor center
Usage
• respiratory arrest due to inhalation of irritative substances,
• traumas, electro-shock, surgical operations
• morphine and CO poisoning
• shock and collapse conditions, depression of blood
circulation and breathing in patients with infectious diseases
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
Ganglionblockers
PHARMACODYNAMICS
• Dilation of peripheral vessels
• Decreasing of blood pressure
• Decreasing of smooth muscle tone of inner
organs (bronchi, GI tract, urinary and bile
tracts)
• Decreasing of gland secretion: bronchial,
gastric, salivary
Benzohexonium
Does nor penetrate through blood-brain barrier
Duration of action varies from 3 to 6 hours
Usage
Hypertensive crisis
Obliterating endarteritis
Spasm of peripheral vessels
Intestinal, hepatic, kidney colic
Gastric ulcer
Bronchial asthma, lung emphysema, lung edema
Pentaminum
Duration of action– 2-4 hours
Usage
Hypertensive crisis
Obliterating endarteritis
Spasm of peripheral vessels
Intestinal, hepatic, kidney colic
Gastric ulcer
Bronchial asthma, lung emphysema
Hygronium
Effect develops after 2-3 min, and lasts for
10-15 min after stopping of infusion
Usage
For controlled hypotonic
For treatment of nephropathy and eclampsia
For complex therapy of hypertensive crisis, brain
edema, lung edema
Pirilenum
Penetrates through blood-brain barrier and
blocks central N-cholinergic systems
Effect is observed after 1-2 hours and lasts
for 6-8 hours if administered orally
Usage
Heavy form of arterial hypertension
Trophic disorders
Side effects and complications
of ganglionblockers
Orthostatic collapse (postural hypotension)
Dryness of mucous membranes
Disturbance of accommodation
General weakness
Dizziness
Tachycardia
Atonia of urinary bladder, intestines (paralytic
ileus)
Myorelaxants
Antidepolarizing type of action
(pachicurare)
Tubocurarine chloride, anatruxonium,
pipecuronium bromide, mellictin
Depolarizing type of action
(leptocurare)
dithylinum
Skeletal muscles relax in such turn
Small muscles of fingers,toes, ears, eyes,
head, neck, muscles of extremities,
trunk,
Intercostals muscles and diaphragm
Restoring of tone is performed in reversed
sequence
2
3
5
4
4
7
6
1
4
1
4
Tubocurarine chloride
Relaxation begins after 1-1,5 min after introduction and
lasts for 25-40 min
Usage
• For prolonged relaxation of striped muscles during
surgical operations
• For relaxation of muscles while repositioning fractured
bones and complicated dislocations
• For prevention of traumatic injuries during seizure
therapy of schizophrenia, during epileptic status, seizures
of other etiology
PROSERINE is introduced
to overcome action of the drug
Dithylinum
(suxamethonium, succinilcholin, listenon)
Miorelaxation develops after 40-60 sec. Total
reviving of muscle tone comes after 5-10 min.
Usage
• before such manipulations as tracheal
intubation, broncho- and esophagoscopia,
cystoscopia
• for reposition of fractures bones, dislocations
Insufficiency of buthyrilcholinesterase
(genetic pathology)
In this pathology action of dithylinum can last
for several hours, and all this time the patient
should be connected to artificial respiration
device
TREATMENT
• Introduction of fresh-citrate blood
• Direct blood infusion from donnor
• Introduction of buthyrilcholinesterase
Mellictine
Usage
For disease and syndrome
postencephalitic parkinsonism,
spinal arachnoiditis,
arachnoencephalitis
of
Parkinson,
All myorelaxants are contraindicated for
patients with myasthenia