Cholinoblockers презентация

Anticholinergics block the cholinergic receptors, prevents their interaction with acetylcholine and disrupts the conduction of nerve impulses.
Cholinoblockers:
M-cholinoblockers
M,N-cholinoblockers
N-cholinoblockers
Ganglionblockers
Neuromuscular relaxants (curare-like drugs)

N1 – 1,3,5
N2 – 6
M – 2
AR – 4

M-cholinoblockers block the peripheral M-cholinoceptors of the effectors' cell membranes (on the terminals of postganglionic cholinergic fibers) and M-cholinoceptors in the CNS. Among these drugs there are:
1.Preparations of plant origin:
Herbal medicines:
Tincture of belladonna
Extract of belladonna (tablets “ Besalol”, suppositories “ Anusol”),

B. Alkaloids: Atropine, Scopolamine, Platyphilline
2.Semisynthetic derivatives: Homatropine, Tiotropium bromide, Ipratropium bromide
3. Synthetic drug: Tropicamide, Metocinium iodide,
Pirenzepine hydrochloride,
4. Antiparkinsonian: Trihexyphenidyl

Alkaloids are tertiary amines and pass well through the BBB, synthetic drugs (Quaternary ammonium compounds) pass poorly.
M-cholinoblockers block receptors differently.
Selective blocker of M1-cholinoceptors of stomach – pirenzepin
N, m blocker - Platyphylline
Non-selective blockers – all other drugs

CNS
Atropine stimulates many medullary centres —vagal, respiratory, vasomotor.
It depresses vestibular excitation and has antimotion sickness property. It suppresses tremor and rigidity of parkinsonism.
High doses cause cortical excitation, restlessness, disorientation, hallucinations and delirium followed by respiratory depression and coma.

EYE: 1. The dilatation of the pupil (mydriasis) is the effect of the block of the iris circular muscle M-CR.

2. The fluid outflow from the anterior chamber of the eye is decreased and intraocular pressure can increase (especially in glaucoma).
3. Blocking M-CR of the ciliary muscle leads to its relaxation, which results in an increase of the ciliary zonule (ligament of Zinn) tension and a reduction of lens curvative. Accommodation paralysis occurs and the eye become adjusted to the distant point of vision.

Normal condition
Atropine

Indications: for diagnostic purposes (to examine retina, prescribe glasses), in the treatment of iridocyclitis.
Side effects: increased intraocular pressure, photophobia, accommodation disorder.

Heart. The main effect is tachycardia. It is due to blockade of M2 receptors on the SA node through which vagal tone decreases HR. Atropine facilitates A-V conduction.
Smooth muscles. A. decreases muscular tone of the gastrointestinal tract, bile ducts, gallbladder, bronchi, bladder.

Exocrine glands. It inhibits glandular secretion: bronchial, nasopharyngeal, digestive (especially salivary), sweat and lacrimal. It leads to a dryness of oral mucous membrane (xerostomia), skin (xerodermia) and a change in the timbre of the voice. A decrease in sweating may leads to a rise in body temperature.

Indications:
Bradyarrhythmia, atrioventricular block;
Stomach and duodenal ulcer, hyperacid gastritis; acute pancreatitis;
Spastic pain or colic (intestinal, hepatic, renal);
Bronchial asthma, bronchospasm;
Hypersalivation (in Parkinsonism, poisoning with heavy metals salts);
Overdose of cholinomimetics, anticholinesterase drugs, cardiac glycosides

Wide use of atropine for premedication before surgical interventions is linked to its ability to inhibit secretion of salivary, nasopharyngeal and thracheobrochial glands. Moreover, blocking MCR of the heart (vagolytic action), A. prevents negative effects on the heart, including the possibility of its reflectory arrest (for example, in administration of inhalation anesthetics that irritate the upper respiratory tract).

Side effects of atropine:
Dryness of oral mucosa,
Accommodation disorder,
Tachycardia,
An increase in intraocular pressure,
Constipation,
Urination difficulty.

Symptoms of atropine poisoning (usually children):
Dryness of the mucous membranes of the mouth and nasopharynx, difficulty with swallowing and speech,
dry skin, rise of temperature,
dilated pupils, photophobia,
motor and verbal agitation, impairment of memory and orientation, hallucinations (acute psychosis).
Help: anticholinesterase drugs

Scopolamine more strongly affects the eyes and the secretion of a number of excretory glands. It causes calming, drowsiness, sleep. It inhibits the extrapyramidal system and transmission from pyramidal pathways to motorneurons.
It can be used for the prevention of seasickness and airsickness and for Parkinson treatment.

Platyphilline has moderate ganglioblocking and direct myotropic spasmolytic (papaverine-like) actions. It inhibits the vasomotor center.
It is used as a spasmolytic drug in spasm of the stomach, intestine, biliary ducts, gallbladder and uretes. It is administered to reduce pathologically increased tone of cerebral and coronary vessels.

Metocinium iodide passes poorly through the blood-brain-barrier. It does not affect the CNS and eye. It has more prominent broncholytic effect.
It is used as broncholytic in bronchial asthma, biliary colic, for premedication in anesthesiology (reduces secretion of the bronchial glands, blocks transmission from the vagus nerve to the heart and bronchi).

Ipratropium, Tiotropium, Troventolum
They are administered via inhalation.
They dilate the bronchi and are used for the treatment of bronchial asthma.

Pirenzepine blocks M1-CR of the enterochromaffin cells and parasympathetic ganglia of the stomach. It suppresses basal and induced secretion of hydrochloric acid and pepsinogen, causes a decrease in gastrin release in response to food.
It increases the resistance of gastric mucosal sells to injury (gastroprotective effect).
P. causes a slight decrease in salivary glands secretion.
It is used for the treatment of gastric and duodenal ulcers.

Ganglionic blockers block sympathetic and parasympathetic ganglia, N-CR of the adrenal medulla and carotid body.
Classification
Bis-Quaternary ammonium salts do not penetrate the BBB
1. Short-acting drugs (5-20 minutes): Trepirium iodide
2. Average duration (3-4 hours): Azametonium bromide, Hexamethonium benzolsulfonate
3. Long-acting (tertiary amines): Pachycarpine (6-8 hours)

They dilate arterial and venous vessels, decrease blood pressure, reduce preload and postload of the heart, improve blood circulation in organs (lower limbs), improve tissue trophism .
They reduce smooth muscle tone (intestine, bronchi, except myometrium), secretion of exocrine glands (salivary, gastric). But they can increase tone of uterine and stimulate labor.

Indications for the use:
Obliterating endarteritis, pulmonary edema, arterial embolism, hypertensive crisis.
Short-acting drugs can be used for controlled hypotension during operation. They are administered IV drip, dilate vessels, decrease arterial pressure and reduce hemorrhage during thyroidectomy and mastectomy. In neurosurgery they reduce the possibility of the development of brain edema.
Spastic pain (colic), bronchospasm, gastric and duodenal ulcer.

Side effects:
Orthostatic collapse develops after an abrupt change of the body’s position in space. Marked and rapid decrease in the arterial pressure develops after transition from horizontal to vertical position.
Syncope.
Constipation, urinary retention.
Accommodation disorder, mydriasis.
Dysarthria, dysphagia.

Drugs blocking neuromuscular transmission (neuromuscular relaxants, peripheral muscles relaxants)
They inhibit neuromuscular transmission on the level of postsynaptic membrane, interacting with N-cholinoceptors of the endplates.
Curare was the first muscle relaxant. Its extract was obtained from plants in South America and used as an arrow poisoning.

N1 – 1,3,5
N2 – 6
M – 2
AR – 4

Classification
Antidepolarizing (nondepolarizing) drugs: Tubocurarine, Pancuronium, Pipecuronium bromide,
Atracurium besilate,
Mivacurium chloride
Depolarizing drug – Suxamethonium iodide

Duration of action:
Short-acting:
Mivacurium chloride (15 min), Suxamethonium iodide (5-8 min)
Average duration:
Atracurium besilate(15-35 min)
Long-acting:
Pipecuronium bromide (50-120 min)

Antidepolarizing drugs block N-ChR and prevent depolarizing effect of acetylcholine. They act competitive. If the concentration of acetylcholine in the area of block is increased significantly this will lead to restoration of the neuromuscular transmission.
Depolarizing drug excite N-ChR and causes steady depolarization of the postsynaptic membrane. In the beginning, depolarization development is manifested by muscular fasciculations. Soon after a myoparalytic effect develops.

Muscles are relaxed in a certain sequence:
Muscles of the face and neck;
The lower and upper limbs;
Muscles of the trunk;
Respiratory muscles;
The diaphragm.
Myoparalytic action range: the range between doses in which drugs paralyze more sensitive muscles, and doses that cause respiratory arrest.
Artificial ventilation of the lungs is required when using muscle relaxants

The sequence shutdown of skeletal muscle during intravenous curare-like drugs

Antagonists:
Antagonists of the antidepolarizing drugs are anticholinesterase drugs (Neostigmine, Galanthamine).
The action of depolarizing drug (suxamethonium) can be reversed by the administration of fresh citrated blood, containing plasma cholinesterase, which hydrolyzes suxamethonium.

Indications for the use:
In anaesthesiology during the performance of most operations on the organs of the thoracic and abdominal cavities, on the upper and lower limbs;
Tracheal intubation, bronchoscopy, reduction and reposition of bone fracture fragments;
The treatment of tetanus and epilepsy.

Side effects:
Tachycardia (pancuronium), fluctuations in blood pressure,
Allergic reactions,
Arrhythmia, increase in intraocular pressure, muscular pains, long-term apnoea (suxamethonium).