Ticket 41.

1. Principles of drug discovery. Ways of synthesis of pharmacological substances. Obtaining preparations from plant and animal raw materials.

The creation of drugs has developed in the following areas:

1) chemical synthesis of drugs;

2) receiving drugs from raw drugs and isolating the individual in-in (alive, growing, miner of origin);

3) isolation-e-in - products of life-giving fungi (penicillin) and microbes (interferon, interleukins, enzymes), biotechnology (use in the industry of biosystems and processes).

Chemical synthesis of drugs is carried out in 2 directions: directed synthesis and empirical path.

Directed synthesis:

Reproduction of biogenic substances - this is how adrenaline is synthesized;

creation of antimetabolites - by changing the structure of the molecule of the island, you can get its antagonist;

Modification of molecules of compounds with known biological activity

the study of the structure of the substrate with which the drug interacts - X-ray structural analysis, nuclear magnetic resonance allows you to establish a 3-dimensional structure of the island in the solution;

a combination of 2 connections with the necessary saints - genetic engineering;

synthesis based on the study of chemical transformation in org-me (prodrugs; creation of drugs that change the activity of enzymes).

The empirical path is random finds, "screening" is a laborious and ineffective path.

Many medicines (galenic, novogalene, alkaloids, glycosides) were obtained from medicinal raw materials. Biotechnology - biosynthesis of antibiotics (penicillin), the development of hybridoma technology (cell engineering), the method of recombinant DNA (genetic engineering). The industry uses biosystems and processes.

2. The history of the discovery of non-inhalation anesthesia (NI Pirogov, NP Kravkov, SP Fedorov). Classification of drugs for anesthesia. Requirements for non-inhalation anesthetic drugs. Advantages and disadvantages of non-inhalation anesthesia versus inhalation. Comparative characteristics of non-inhalation anesthetic drugs.

1846 - the discovery of anesthesia. Morton (1819-69) was an American dentist who first introduced ether anesthesia into a surgeon's practice. Pirogov (1810-81) - Russian surgeon and anatomist, the main field of military surgery. For the first time he performed an operation under anesthesia on the battlefield (1847).

Classification of drugs for anesthesia.

Inhalation : volatile liquids: ether, fluorothane, sevoflurane, isoflurane, methoxyflurane

Gaseous substances: nitrous oxide, cyclopropane, xenon.

Non-navigational : derivatives of barbituric and thiobarbituric acids: thiopental sodium, thiobutal, hexenal

Steroids: Predion.

GHB salts: sodium oxybutyrate.

Others: propofol, propanidide, ketamine.

Anesthesia is a condition characterized by the shutdown of consciousness, suppression of sensitivity, reflex reactions, and decreased tone of skeletal muscles.

The actions of anesthetic drugs are associated with the fact that they inhibit the interneuronal transmission of excitation in the central nervous system. Dysfunction of the membrane. One of the manifestations of the interaction of drugs for anesthesia with the postsynaptic neuronal membrane is a change in the permeability for ion channels (for example, for K ions), which disrupts the process of depolarization, and, consequently, interneuronal impulse transmission.

Receptor component of the action of drugs for anesthesia. All inhalation (volatile) and non-inhalation drugs (except for ketamine) in narcotic concentrations interact with GABA receptors, potentiating their action. Nitrous oxide does not affect gamk. Ketamine is an NMDA receptor antagonist. These receptors are blocked by xenon.

Ftorotane became widespread. It is characterized by high drug activity, a short stage of arousal. anesthesia is easily controlled, after the patient stops inhaling fluorothane, awakening will occur in 3-5 minutes. In terms of fire, it is safe. Has no irritating effect on the mucous membrane of the respiratory tract (unlike ether)

Respiratory side effects of fluorothane: moderately inhibits the respiratory center.

CCC: weakens myocardial contractility, reduces stroke volume, lowers blood pressure. The mechanism of hypotension is associated with inhibition of the vasomotor center and impaired transmission of vasoconstrictor impulses in the ganglia and the endings of sympathetic nerves., Cardiac arrhythmias are possible.

Kidneys: fluorothane reduces renal blood flow, SKF, diuresis, respectively.

Liver: with a healthy liver does not cause significant changes, is contraindicated in persons with liver disease.

Ether. It has a pronounced narcotic activity, sufficient arcotic breadth, relatively low toxicity. Less manageable. Irritates mucous membranes, causes a pronounced stage of arousal, explosive. Side effects: profuse secretion of the salivary and bronchial glands (the result of irritation of the mucous membranes), aspiration with vomit, which interferes with airway patency, bradycardia and even cardiac arrest due to reflex excitement of the vagus nerve. Ether is administered only against the background of premixing. Ether promotes the release of catecholamines from the adrenal medulla. This can lead to an increase in glycogenolysis, hyperglycemia (therefore, contraindicated in diabetes mellitus)

On the CVS: increased stroke and minute volume of the heart, increased heart rate, moderate narrowing of the peripheral vasculature.

Liver: hepatotoxic (but less than fluorothane),

Kidneys: decreased renal blood flow, skf, urine output.

Metabolism: a pronounced change in metabolism due to hyperglycemia, increased lactic acid, pyruvic acidosis.

In the postoperative period, vomiting is noted.

Nitrous oxide.

Immediate onset of anesthesia, without arousal stage. This is the effect of low plasma solubility. Because of this, a rapid awakening of the patient occurs. Penetrates quickly into the central nervous system. Used for pain relief in myocardial infarction, severe trauma, childbirth, etc. the main disadvantage: low drug activity. Therefore, it is necessary to combine with other anesthetic drugs. Should not be used for long-term analgesia.

In the postoperative period, nausea and vomiting may occur.

Respiration: does not irritate mucous membranes.

CVS: not accompanied by changes in heart function.

Liver: does not cause

Kidney: a transient decrease in urine output is due to constriction of the renal arteries, an increase in the production of ADH.

Metabolism: does not cause

Blood system: use of nitrous oxide for a long time may cause thrombocytopenia, agranulocytosis, megaloblastic anemia.