1. Lector prof. Posokhova K.A.
Anatomy-physiological peculiarities of vegetative nervous system. Anticholinesterase drugs
Lector prof. Posokhova K.A.

2. 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)

3. Cholinergic synaps

5. 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)
contraction (midriasis)
dilation (far sight)
Heart
Excitability
Conduction
Power of contractions
Frequency of contraction
dicreasing
slowing down
increasing
speeding up
Vessels
Skin, mucous membranes
Mesentraium, organs of abdominal cavity
Skeletal muscles
Heart, brain
’’ -
dilation
- ’’ -
contraction
’’ –
- ’’ –
Bronchi
Circular muscles
Glandular secretion
contractoin
decreasing
Stomach, intestines
Perystaltics
Tonus of sphyncters
decresing
Urinary bladder
Detrusor
Sphyncter
Glands (secretion)
Salivary
Sweat
incresing (liquid secret, large quantity)
increasing (small quantity)

6. 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

7. 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)

8. M-, N-cholinomimetics
Acetylcholine
Carbacholine

9. 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 !

10. M-, N-cholinoblockers
Amizyl
Cyclodol

11. 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 % solution is used
Side effects : dryness of mucous membranes, tachycardia, dilation of pupils, disturbances of accomodation.
The drug is contraindicated in case of glaucoma!

12. medicamentous parcinsonism
Cyclodol
Anticholinergic drug, preferably blocks central N-cholinoreceptors and peripheral M-cholinoreceptors
Usage
Parcіnson’s disease,
medicamentous parcinsonism

13. Anticholinesterase drugs
Proserinum,
Galanthamini hydrobromidum,
Armin,
Pirydostygmini bromidum

14. Indications for administration overdosing with M-cholinoblockers
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 M-cholinoblockers

15. Galanthamini hydrobromidum Indications for administration
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

16. Pirydostigmini bromide (calimin)
Usage
myastenia gravis
after traumas, neuryties, paralyses
in a period of recovery after polyomyelitis, encephalitis

17. Anticholinesterase drugs are
contraindicated
in cases of epilepsia, hyperkinesias, bronchial asthma, stenocardia, bradycardia

18. 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

19. 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 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

20. 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.

21. M-cholinergic drugs

22. M-cholinomimetics
M-cholinoblockers

23. Pilocarpini hydrochloridum
M-cholinomimetics
Pilocarpini hydrochloridum
Aceclidinum

24. 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

25. Pilocarpine causes constriction of pupils (myosis)

26. Aceclidinum Pharmacodinamics Usage treatment of glaucoma
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

27. 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

28. mushrooms of Inocybe family

29. M-cholinoblockers Atropine sulfate Scopolamine hydrobromide
Platyphyllin hydrotartrate
Metacinum
Dry extract of Belladonna

30. 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

31. Pharmacodynamics and usage of M-cholinoblockers
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)

32. 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)

33. Gastrozepin (Gastrocepinum)

34. 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

35. 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

36. Belladonna

37. Datura stramonium

38. 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

39. 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

40. N-cholinergic drugs

41. N-cholinomimetics
Cytiton
Lobelin hydrochloride

42. Cytiton Pharmacodynamics Usage
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

43. 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

45. 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

46. N-cholinoblockers Ganglionblockers Myorelaxants
Benzohexonium, pentamin, hyhronium, pyrilen
Myorelaxants
Tubocurarine chloride, dithylin, mellictin

47. Ganglionblockers

48. 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

49. Benzohexonium Usage Hypertensive crisis Guided (controlled) hypotonia
Does nor penetrate through hemato-encephalic (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

50. Duration of action– 2-4 hours
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

51. Hygronium
Effect develops after 2-3 min, and lasts for 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

52. 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)

53. Myorelaxants

54. Tubocurarine chloride, anatruxonium, pipecuronium bromide, mellictin
Antidepolarizing type of action (pachicurare)
Tubocurarine chloride, anatruxonium, pipecuronium bromide, mellictin
Depolarizing type of action (leptocurare)
dithylinum

55. 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

56. 1 2 3 4 5 6 7

57. Tubocurarine chloride
Relaxation begins after 1-1,5 min after introduction and lasts for 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

58. (suxamethonium, succinilcholin, listenon)
Dithylinum
(suxamethonium, succinilcholin, listenon)
Myorelaxation develops after 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

59. 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

60. All myorelaxants are contraindicated for patients with myastenia
Mellictin
Usage
For disease and syndrome of Parkinson, postencephalitic parkinsonism,
disease of Little,
spinal arachnoiditis,
arachnoencephalitis
All myorelaxants are contraindicated for patients with myastenia

61. ADRENERGIC DRUGS

62. which act in adrenergic synapses
Adrenergic drugs
medical substances
which act in adrenergic synapses

63. Adrenergic synaps

65. 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 1 2 Д1
Contraction of vessels
- ’’ -
- ’’ -
Dilation of vessles
M dillatator pupillae
Ciliary muscle
Heart 1
Midriasis (dilation of pupil)
Dilation (far vision)
Increasing of power and frequency of contraction, conductivity, automatism
Bronchial muscles
Bronchial glands
1, 2
Dilation of bronchi
Decreasing of secretion, increasing of secretion
Smooth musculature of GI tract:
walls
- sphincters
2, 2
Decreasing of tone, peristaltic
Increasing of tone
Smooth musculature of urinary bladder:
sphincters
Relaxation
Contraction
Liver
Decomposition of glycogen
Uterus
(pregnant>not pregnant)
Salivary glands 
Increasing of К+ , f amylase and Н2О
secretion
Sweat glands
Increasing of secretion
Insulin secretion 2
Decreasing
Increasing
Presynaptic formations of adrenergic neurons
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

66. б) adrenomimetics of indirect action or sympathomimetics
а) adrenomimetics of direct action
б) adrenomimetics of indirect action or sympathomimetics
Adrenoblockers
or adrenolytics
Sympatholytics

67. ІІ. Sympathomimetics (ephedrine) ІІІ. Adrenoblockers
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)

68. Adrenomimetics

69. adrenaline hydrochloride
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

70. 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

71. Necrosis

72. Dopamine shock and collapse Drug of a first choice for treatment of
of different aetiology, including cardiogenic and hemorrhagic

73. 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

74. 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

75. NAPHAZOLIN

76. 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

77. 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

78. Terbutalin (brikanil) and phenoterol (berotek, partusisten)
are stimulants of mostly 2-adrenal receptors. They posses broncholytic and tokolytic activity

79. Dobutamin Is a synthetic 1-adrenomimetic
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)

80. Sympathomimetics

81. 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

82. Adrenoblockers

83. Alfa-adrenoblockers

84. 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

85. Selective  1- adrenoblocker
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

86. Beta-adrenoblockers

87. Anaprilin Administration arterial hypertension
Is a β1- і β2-adrenoblocker
Administration
ischemic heart disease
arterial hypertension
cardiac tachyarrhythmias
acute myocardium infarction

89. Talinolol or cordanum Administration is a cardioselective
β-adrenoblocker
Administration
disorders of cardiac rhythm (extrasystolies, paroxysmal tachycardia, fibrillation and scintillation of atria)
ischemic heart disease
arterial hypertension .

90. Atenolol (tenormin) arterial hypertension cardiac arrhythmias
cardioselelctive -adrenoblocker with long duration of action
Indications for administration
ischemic heart disease
arterial hypertension
cardiac arrhythmias
acute myocardium infarction

91. 1-adrenoblocker with inner sympathomimetic activity
Acebutolol (sectral)
1-adrenoblocker with inner sympathomimetic activity
Indications
disorders of cardiac rhythm (tachyarrhythmias)
hypertension
ischemic heart disease

92. Labetolol Contraindications
-, -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

93. increase the production of NO in blood vessels
CARVEDILOL, NEBIVOLOL
increase the production of NO in blood vessels
are used now for chronic cardiac insufficiency (congestive heat failure)

94. Sympatholytics

95. Reserpin Administration Side effects fatigue, somnolence, depression,
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

96. 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