Cholinergic agonists and antagonists

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Cholinergic agonists and antagonists
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• Synapses are specialized junctions through which
  neurons signal to each other and to non-neuronal
  cells such as those in muscles or glands

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• 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

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• 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 ?) ganglionblockers
  (benzohexonium, pentamin, hygronium, arphonade)
  ?) myorelaxants (tubocurarinum
  chloride, dytylinum, melliktin)

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M-, N-cholinomimetics

• Acetylcholine
• Carbacholine

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• 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 !

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M-, N-cholinoblockers

• Amizyl
• Cyclodol

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• 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!

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• Cyclodol
• Anticholinergic drug, mainly blocks central
  N-cholinoreceptors and peripheral
  M-cholinoreceptors
• Usage
• Park?nson disease,
• medicamental parkinsonism

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Anticholinesterase drugs

• Proserinum,
• Galanthamini hydrobromidum,
• Armin,
• Pirydostygmini bromidum

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• 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

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• Galanthamini hydrobromidum
• Duration of action of Galanthamini hydrobromidum
  is longer than of Proserinum, thats 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

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• Pirydostigmini bromide (calimin)
• Usage
• myastenia gravis
• after traumas, neuritis, paralyses
• in a period of recovery after polyomyelitis,
  encephalitis

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myastenia gravis
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• Anticholinesterase drugs are
• contraindicated
• in cases of epilepsia, hyperkinesias, bronchial
  asthma, stenocardia, bradycardia

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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

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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

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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.

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M-cholinergic drugs
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• M-cholinomimetics
• M-cholinoblockers

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• M-cholinomimetics
• Pilocarpini hydrochloridum
• Aceclidinum

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• ?ilocarpini 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

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• 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, stenocardia

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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

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

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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

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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)

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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)

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Gastrozepin (Gastrocepinum)
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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

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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

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Belladonna
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Datura stramonium L
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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

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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 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

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N-cholinergic drugs
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• N-cholinomimetics
• Cytitone
• Lobeline hydrochloride

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• 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

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• 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.

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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

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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

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• N-cholinoblockers
• Ganglionblockers
• Benzohexonium, pentamin, hygronium, arphonad
• Myorelaxants
• Tubocurarine chloride, dithylin, mellictin

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• Ganglionblockers

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• 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

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• 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

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• 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

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• 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

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• 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

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• 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)

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• Myorelaxants

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

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• 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

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• 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

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• 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

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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

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• Mellictine
• Usage
• For disease and syndrome of Parkinson,
  postencephalitic parkinsonism,
• spinal arachnoiditis,
• arachnoencephalitis
• All myorelaxants are contraindicated for
  patients with myasthenia