Download M-cholinoblockers

Anatomy-physiological
peculiarities of vegetative
nervous system.
Anticholinesterase drugs
Lector prof. Posokhova K.A.
Efferent
nervous fibres supply
skeletal muscles – somatic;
regulate funtions of internal organs vegetative
Synaps -
is a place of contact of long
fibre ending (axon) of one neuron with a
body of other one or cell of active organ
(effector cell)
Cholinergic synaps
Influence of parasympathetic and sympathetic nervous system on
function of organs
Eye
m. sphincter pupillae
m. dilatator pupillae
m. ciliaris
contraction (miosis)
absent innervation
contraction (close sight)
absent innervation
contraction (midriasis)
dilation (far sight)
Heart
Excitability
Conduction
Power of contractions
Frequency of contraction
dicreasing
slowing down
dicreasing
dicreasing
increasing
speeding up
increasing
increasing
absent innervation
- ’’ -
contraction
- ’’ –
dilation
- ’’ -
- ’’ –
- ’’ –
Bronchi
Circular muscles
Glandular secretion
contractoin
increasing
dilation
decreasing
Stomach, intestines
Perystaltics
Tonus of sphyncters
Glandular secretion
increasing
decreasing
increasing
decreasing
increasing
decresing
Urinary bladder
Detrusor
Sphyncter
contraction
dilation
dilation
contraction
Glands (secretion)
Salivary
Sweat
incresing (liquid
quantity)
Vessels
Skin, mucous membranes
Mesentraium, organs of abdominal
cavity
Skeletal muscles
Heart, brain
secret,
large
increasing (small quantity)
- ’’ -
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-, Ncholinomimetics
Acetylcholine
Carbacholine
Carbacholine
0,5-1
%
solutions
carbacholine - eye drops
treatment of glaucoma
of
for
The drug is never used orally
and with injections because of its
consideralbe toxicity !
M-, Ncholinoblockers
Amizyl
Cyclodol
Amizyl
Indications for administration
neurotic disorders, Parcinoson’s 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, preferably
blocks central N-cholinoreceptors
and peripheral M-cholinoreceptors
Usage
Parcіnson’s disease,
medicamentous parcinsonism
Anticholinesterase
drugs
Proserinum,
Galanthamini hydrobromidum,
Armin,
Pirydostygmini bromidum
Proserinum
Proserinum 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 Mcholinoblockers

Galanthamini
hydrobromidum
Duration of action of Galanthamini
hydrobromidum is longer than of
Proserinum, that’s why it can be
administered 1-2 times per 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, neuryties,
paralyses
in a period of recovery after
polyomyelitis, encephalitis
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

Usage of antagonist is necessary!!! – atropine
sulphate. It should be introduced intravenously
repeatedly, 2-4 ml of 0,1 % solution with the interval of 510 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
Mcholinomimetics
Mcholinoblockers
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
Pilocarpine causes constriction of
pupils (myosis)
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

Usage
treatment of glaucoma
 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,
ischemic heart disease
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

mushrooms of Inocybe family
M-cholinoblockers
Atropine sulfate
Scopolamine hydrobromide
Platyphyllin hydrotartrate
Metacinum
Dry extract of Belladonna
Pharmacokinetics and usage of Mcholinoblockers
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 peristaltic of smooth muscles of
digestive tract, bronchi, urinary tract
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)
Seasickness (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 M-cholinoblocking action
Causes
 Overdosing
with drugs of
M-cholinoblockers group
 Consumption of plants, which include
alcaloids of this group
Belladonna
Datura stramonium
Symptoms of acute poisoning with
M-cholinoblockers
“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
M-CHOLINOBLOCKERS
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 put 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
Cytiton
Lobelin hydrochloride
Cytiton
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

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 sharp depression of
respiratory center and paralysis of breathing
musculature
Chronic poisoning with nicotine
Chronic diseases of respiratory system,
Lung cancer and Malignant tumors of other
localisation,
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, nonreversible changes of spermatozoids
N-cholinoblockers
Ganglionblockers
Benzohexonium, pentamin,
hyhronium, pyrilen
Myorelaxants
Tubocurarine chloride, dithylin,
mellictin
Ganglionblockers
PHARMACODYNAMICS
Dilation of peripheral vessels
 Decreasing of blood pressure
 Decreasing of smooth musculature
tone of internal organs (bronchi, GI
tract, urinary and bile tracts)
 Decreasing of glandular secretion:
bronchial, gastric, salivary

Benzohexonium
Does nor penetrate through hematoencephalic (blood-brain) barrier.
Duration of action varies from 3 to 6 hours
Usage
Hypertensive crisis
Guided (controlled) hypotonia
Obliterating endarteritis
Spasm of peripheral vessels
Intestinal, hepatic, kidney colics
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, nephral 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 hypotonia
For treatment of nephropathy and
eclampsia
For complex therapy of hypertensive
crisis, brain edema, lung edema
Side effects and complications
of ganglioblockers’ administration
Orthostatic collapse
Dryness of mucous membranes
Disturbance of accomodation
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
Sequence of relaxation of
striped muscles
Small muscles of fingers,toes,
ears, eyes, head, neck, muscles
of extremities, trunc,
Intercostal muscles and
diaphragm
Reviving 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 combined dislocations
 For prevention of traumatic injuries during
seizure therapy of schizophrenia, during
epileptic status, seizures of other ethiology
(tetanus)
PROSERINE is introduced
to abolish action of the drug

Dithylinum
(suxamethonium, succinilcholin,
listenon)
Myorelaxation develops after 40-60 sec.
Total restoring of muscle tonus comes after
5-10 min.
Usage
 before such manipulations as
tracheal intubation, broncho- and
esophagoscopia, cystoscopia
 for reposition of bone fractures,
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
Mellictin
Usage
For disease and syndrome of Parkinson,
postencephalitic parkinsonism,
disease of Little,
spinal arachnoiditis,
arachnoencephalitis
All myorelaxants are
contraindicated for patients with
myastenia
ADRENERGIC
DRUGS
Adrenergic drugs
medical substances
which act in
adrenergic synapses
Adrenergic synaps
Typical localization of adrenal receptors and changes of functions observed during stimulation of these receptors
Smooth muscles of vessels:
skin
mucsous membranes
mesentery ,
organs of abdominal cavity
skeletal muscles
coronary
lungs
kidneys
veins
M dillatator pupillae
Ciliary muscle
Heart
Bronchial muscles
Bronchial glands
Smooth musculature of GI tract:
walls
- sphincters
Smooth musculature of urinary bladder:
walls
sphincters
Liver
1
1
1
1
2
1
2
1
2
1
Д1
1
1
2
1
Contraction of vessels
- ’’ - ’’ - ’’ - ’’ Dilation of vessles
Contraction of vessels
Dilation of vessles
Contraction of vessels
Dilation of vessles
Contraction of vessels
Dilation of vessles
Contraction of vessels
Midriasis (dilation of pupil)
Dilation (far vision)
Increasing of power and frequency of contraction, conductivity,
automatism
2
1,  2
Dilation of bronchi
Decreasing of secretion, increasing of secretion
2,  2
1
Decreasing of tone, peristaltic
Increasing of tone
2
1
2
Relaxation
Contraction
Decomposition of glycogen
Uterus
1
2
Contraction
Relaxation
(pregnant>not pregnant)
Salivary glands
1

Increasing of К+ , f amylase and Н2О
secretion
Sweat glands
1
Increasing of secretion
Insulin secretion
2

Decreasing
Increasing
Presynaptic formations of adrenergic neurons
2
1
Decreasing of releasing of nor-adrenalin into synaptic split
Stimulation of releasing of nor-adrenalin into synaptic split
Presynaptic formations of cholinergic neurons

Stimulation of releasing of acetyl-choline into synaptic split
Adrenomimetics
а) adrenomimetics of direct
action
б) adrenomimetics of indirect
action or sympathomimetics
Adrenoblockers
or adrenolytics
Sympatholytics
І. Adrenomimetics
1. - і -adrenomimetics (adrenalin hydrochloride,
noradrenalin hydrotartrate)
2. dopamine-, -, -adrenomimetics (dopamine)
3. -adrenomimetics (mesatone, naftizin, galazoline)
4.
-adrenomimetics
(isadrine,
salbutamol,
phenoterol, terbutalin, dobutamine)
ІІ. Sympathomimetics (ephedrine)
ІІІ. Adrenoblockers
1. -adrenoblockers (phentolamine, tropaphen,
prasosine, pyroxan)
2. -adrenoblockers (anaprilin, athenolol, talinolol,
acebutolol)
3. - і -adrenoblockers (labetalol)
ІІІ. Sympatholytics (reserpine, octadine)
Adrenomimetics
Adrenalin (epinephrine) is a
hormone of medulla of suprarenal glands which
is used in a form of a remedy
adrenaline hydrochloride
It is an adrenomimetic which stimulates
1,- 2- and 1,- 2-adrenoreceptors
Administration


Cardiac arrest, for example, during surgical
general anesthesia, electric trauma
shock (anaphylactic shock) and collapse of
different origine

bronchial spasm

hypoglycemic coma

treatment of open-angle glaucoma
Noradrenalin hydrotartrate
(norepinephrine)
Is an adrenomimetic of direct action which
stimulates 1-, 2- and 1-adrenal receptors
Administration
in cases of acute decreasing of blood
pressure
- shock and collapse conditions,
surgeries, traumas
The drug is absolutely contraindicated
for subcutaneous and intramuscular
introductions
Necrosis
Dopamine
Drug of a first
choice for treatment of
shock and collapse
of different aetiology, including
cardiogenic and hemorrhagic
Mesaton (phenylefrin)
Is a synthetic a1-adrenomimetic drug of direct
action
Administration
acute hypotensive conditions,
 prophylaxis
of decreasing of blood
pressure in case of infectious diseases,
poisonings,
 decreasing
of blood pressure during
narcosis with halothan and cyclopropan
 nose drops in case of rhinitis

Naphthysin
Xylometazolin
are a2-adrenomimetics of direct
action
Usage
for rhinitis in a form of nose drops
– 1-2 drops 2-3 times a day
It is not recommended for
chronic cold
NAPHAZOLIN
Isadrin (isoprenalin,
novodrin, euspiran)
– is a synthetic katecholamine, which is a strong
stimulant of β1- і β2-adrenoreceptors
Administration
bradycardia, atrio-ventricular blockade
 bronchial spasm
 complex therapy of some kinds of shock (if the
patient doesn’t have hypovolemia)

Side effects
nausea, hands tremor, dry mouth,
 in patients with ischemic heart disease – acute
ischemic attack,
 heavy cardiac tachyarrhythmias, even fibrillation
of ventricles

Salbutamol
(ventolin)
selective
b2-adrenomimetic
of direct action
Administration
 inhalations during attacks
of bronchial asthma and
bronchial spasms of other
etiology
premature child delivery,
rapid
(vigorous)
child
delivery

Terbutalin (brikanil) and
phenoterol (berotek, partusisten)
are stimulants of mostly 2-adrenal
receptors. They posses broncholytic and
tokolytic activity
Dobutamin
Is a synthetic 1adrenomimetic
Cardiotonic effects of
dobutamin is 5 times
stronger than action of
dopamine
Administration
some forms of acute and
chronic cardiac insufficiency
intravenous dropping
infusion with the speed of
2,5-10 mcg / (kg.min)
Sympathomimetics
Ephedrine hydrochloride (Ephedrini hydrochloridum)
It is an alkaloid of plants of Ephedra family, which
has indirect α-, β-adrenomimetic (sympathomimetic)
action
Administration
 collapse conditions, for prophylaxis of decreasing of
blood pressure before spinal anesthesia, infectious
diseases
 treatment of rhinitis (2 %, 3 % solution as nose
drops).
 prophylaxis and elimination of bronchial spasm
(inhalations 0,5 %-1 % solutions of drug)
SIDE EFFECTS
 agitation, excitement, tremor, inconsiderable euphoria,
insomnia, seizures
 drug addiction
 tachyphylaxy
Adrenoblockers
Alfaadrenoblockers
Phentolamine, tropaphen
are synthetic 1, 2-аdrenoblockers
administration
diagnostics and symptomatic
treatment of feochromocytoma
 disturbances
of
peripheral
blood
circulation in case of endarteriitis,
Reino’s disease, trophic ulcers, decubitus
 complex
treatment of hypertensive
crises, acute cardiac insufficiency
 complex therapy of hypovolemic and
cardiogenic shock

Prasosin
Selective  1- adrenoblocker
Administration

treatment of arterial hypertension
Side effects
“phenomenon of first dose”: sudden
decreasing of blood pressure and even
development of orthostatic collapse after
first administrations of the drug
Prophylaxis: administration of half-dose
before sleep
Betaadrenoblockers
Anaprilin
Is a β1- і β2-adrenoblocker
Administration
ischemic heart disease
 arterial hypertension
 cardiac tachyarrhythmias
 acute myocardium infarction

Talinolol or cordanum
is a cardioselective
β-adrenoblocker
Administration
disorders of cardiac rhythm
(extrasystolies,
paroxysmal
tachycardia,
fibrillation
and
scintillation of atria)
 ischemic heart disease
 arterial hypertension
.

Atenolol (tenormin)
cardioselelctive -adrenoblocker with long
duration of action
Indications for
administration
ischemic heart disease
 arterial hypertension
 cardiac arrhythmias
acute myocardium infarction


Acebutolol (sectral)
1-adrenoblocker with inner
sympathomimetic activity
Indications
disorders of cardiac
(tachyarrhythmias)
 hypertension
 ischemic heart disease

rhythm
Labetolol
-, -adrenoblocker. The drug blocks 1,
2, 1 and 2-adrenoreceptors
Administration

treatment of patients with arterial
hypertension
 hypertensive crisis
Contraindications
Atrio-ventricular blockade,
cardiac insufficiency
CARVEDILOL, NEBIVOLOL
increase the production of NO in
blood vessels
are used now for chronic cardiac
insufficiency (congestive heat
failure)
Sympatholytics
Reserpin
is a sum of Rauvolfia (plant) alkaloids. Maximal hypotensive action
develops after 5-7 days of regular administration of the drug. After the
treatment coarsed effect can still stay for two weeks.
Administration
treatment of different forms of essential hypertension
(drugs of a second row, second line)
(combined drugs trirezid, cristepin, adelfan, brinerdin)
Side effects
manifestations of parkinsonism
 fatigue, somnolence, depression,
 bradycardia
 increasing of motor and secretory activity of
gastro-intestinal tract,
 acute attacks of ulcer disease, diarrhea
 swelling
of nose mucous membrane with
complication of nose breathing

Octadin
Is a sympatholytic with strong hypotensive effect.
During administration of the drug decreasing of blood
pressure develops gradually, after 2-3 days. After
abolition of drug administration the effect still stays for
2 weeks.
Administration
heavy forms of arterial hypertension
Side effects
general weakness,
nausea, vomiting,
swelling of nose mucous membrane,
diarrhea,
liquid retention in the organism,
orthostatic collapse