1. Neurotoxic - damage to 8 pairs of cranial nerves, neuromuscular block.
2. Nephrotoxic; 3. Inhibition of hematopoiesis; 4. Irritation of the gastrointestinal tract; 5. Teratogenic action; 6. Dysbacteriosis, candidomycosis; 7. Allergic reactions - skin, anaphylactic shock, serum sickness, agranulocytosis; 8. Reduction of the therapeutic effect - with the indiscriminate use of antibiotics, non-compliance with dosages, frequency of use, course doses.
The success of antibiotic therapy depends on the fulfillment of the following basic conditions:
- it is necessary not only to choose the right antibiotic, but also to cancel it in a timely manner;
- when finishing antibiotic therapy, the drug is canceled immediately, and not gradually;
- the duration of the course of antibiotic treatment should be at least 6 - 8 (sometimes 10) days;
- with combined treatment with antibiotics with glucocorticoids, the antibiotic is canceled 3 to 5 days after the end of the course of hormone therapy;
- uncontrolled prescription of antibiotics leads to allergization of patients and an increase in the number of antibiotic-resistant microorganisms;
- the method of administration of antibiotics is selected depending on the localization of the infection, must be individual and quickly create the optimal concentration of the drug in the focus of infection;
- the frequency of antibiotic administration is determined by the duration of the bacteriostatic or bactericidal concentration of the drug in the blood;
- the maximum effectiveness of antibiotics is achieved when combined with other antimicrobial, antihistamines and vitamin preparations.
Question 1. Absorption of medicinal substances from the injection site. Transport of drugs across cell membranes.
Question 2. H-cholinomimetic substances. Classification. Mechanism of action. Indications for use. Side effects. Contraindications Comparative evaluation of drugs.
Question 3. Stimulants of respiration. Classification. Mechanism of action. Indications for use. Side effects. Contraindications Comparative evaluation of drugs.
Question 4. Antibiotics of the group of carbapenems and monobactams. Classification. Mechanism of action. The nature of the action. Spectrum of action. Indications for use. Side effects. Contraindications Comparative evaluation of drugs.
1. Absorption of medicinal substances from the injection site. Transport of drugs across cell membranes.1. Peroral route. The medicine taken by mouth first meets the acidic environment of the stomach and may lose its effectiveness. In addition, some foods slow down the process of digestion and evacuation from the stomach. Therefore, drugs must be taken either 30 minutes before meals, or 1 hour after. Solutions and powders are absorbed faster than tablets and capsules. Medicines designed for intestinal absorption (protected by a membrane from the effects of acid and pepsin) are resorbed in a weakly alkaline medium (pH 8.0 - 8.5). Fat-soluble drugs are also absorbed from oil solutions (for example, vitamins D, E, A, etc.), but only after the oil is emulsified with bile acids. After absorption in the stomach and intestines, medicinal substances enter the liver through the portal vein system, where they are partially bound and rendered harmless. Only after passing through the liver,
Sublingual path. Due to the rich vascularization of the oral cavity, the absorption of the preparations occurs quickly. They are not affected by proteolytic enzymes and hydrochloric acid. Such prepats are in the process of emergency assistance (antianginal). They enter the superior portal vein system and further into the general bloodstream, bypassing the liver.
Rectal pathway. The rectal route is used when it is impossible to use drugs inside (vomiting, unconsciousness). From the rectum, 50% of the dose is absorbed into the inferior vena cava system, bypassing the liver, 50% enters the portal vein and is partially inactivated in the liver.
Subcutaneous route. The drugs should not have an irritating effect (subcutaneous fatty tissue is rich in nerve endings) and cause vasospasm. The pharmacological effect occurs 15 to 20 minutes after injection. When solutions of the irritating substance calcium chloride and the strong vasoconstrictor noradrenaline are injected under the skin, necrosis occurs. This route of administration is commonly used in emergency response at the scene of a disaster for injections of pain relievers, vasoconstrictors, psychosedatives, tetanus toxoid, etc. This is the usual route of administration of insulin.
Intramuscular route. The introduction by this method is less painful than the introduction into the subcutaneous tissue. The most rapidly resorption comes from the deltoid muscle of the shoulder, more often in practice it is done in the outer upper quadrant of the gluteus muscle (it is more voluminous, which is important with multiple injections). When injecting oil solutions or suspensions, you must first make sure that the needle does not get into the vessel. Otherwise, vascular embolism with serious consequences is possible. Absorption can be accelerated by applying a heating pad or, alternatively, slowed down with an ice pack.
Intravenous route. Here, in a short time, the maximum (peak) concentrations of the substance in the heart are reached, high - in the central nervous system, only then its distribution in the body occurs. Some drugs may experience sensitization (that is, they have become allergens for the patient) or genetically determined hypersensitivity (idiosyncrasy). refusal of some drugs is required (novoca-ina, penicillins, etc.). Idiosyncrasy causes lightning-fast development of toxic reactions, which are impossible to predict. Therefore, injections of substances that are especially dangerous in this regard (iodine-reducing X-ray contrast drugs, quinine, etc.) are made in two stages: first,
a test dose (no more than 1/10 of the total) and, after making sure that the drug is sufficiently tolerated, the rest is injected after 3 - 5 minutes. Some substances irritate the vein wall. They should first be strongly diluted in an infusion solution (saline, glucose) and administered drip.
Intra-arterial pathway. The introduction of drugs into an artery is resorted to for special purposes, when it is necessary to create a large concentration of a drug (for example, an antibiotic, an antitumor agent, etc.) in the tissue or organ supplied by it.
It should be borne in mind that the walls of the arteries, in contrast to the venous ones, contain a significant amount of bound catecholamines (norepinephrine, adrenaline), which, when a substance with irritating properties is injected, can be released and cause a persistent spasm of the vessel with necrosis of the supplied tissue.
Intraosseous pathway. In terms of the rate of distribution of matter in the body, this path approaches the intravenous route. Applied only for extensive burns or situations that do not allow to enter otherwise.
Intracardiac path. This method of administering drugs (usually adrenaline) is practiced only in one case - during emergency therapy for cardiac arrest. The injection is made into the cavity of the left ventricle and accompanied by cardiac massage.
Subarachnoid path. It is used to inject local anesthetics or morphine-like analgesics (spinal anesthesia) into the spinal canal with a puncture of the membranes of the brain, as well as for chemotherapy of meningitis - infections that nest in the meninges and are difficult to access for drugs (penicillins, aminoglycosides, etc. etc.) introduced in other ways. Injections are usually done at the level of the lower thoracic - upper lumbar vertebrae. and. For punctures, it is advisable to use thin needles, since the hole in the dura mater is poorly tightened and the cerebrospinal fluid oozes through it into the tissue. This causes changes in intracranial pressure and severe headaches.
Biological barriers: mucous membrane of the stomach, intestines, oral cavity, nasopharynx, skin, geb, placental, mammary epithelium, renal.
Diffuse transport. The bottom line is that lipid-soluble substances easily dissolve in the membrane and move inside the cell by diffusion until the concentration outside and inside becomes the same. Moreover, they can accumulate in the membrane. (alcohols, ethers, etc.). Pinocytosis. The substance comes into contact with the membrane and this area bends inward, the edges close, a bubble is formed. It is transferred inside the cell. Some proteins are polypeptide hormones.
2. H-cholinomimetic substances. Classification. Mechanism of action. Indications for use. Side effects. Contraindications Compare the markup of drugs.
- Cititon (ampoules for i / v)
- Lobelin
They work for 5-10 minutes and are available in the form of ampoules for intravenous administration.
Mechanism of action: they have an effect on n-cholinergic receptors in two phases - the stage of excitation is replaced by the stage of oppression. They speed up breathing, constrict blood vessels, increase blood pressure.
Indications: respiratory depression, the threat of stopping it (carbon monoxide poisoning, mechanical asphyxia, drowning), newborn asphyxia, shock, collapse, are part of Lobelin and Tabex tablets, which are used for smoking cessation.
Side effects: nausea, vomiting, weakness, dizziness.
Contraindications: atherosclerosis, high blood pressure, bleeding from large vessels, pulmonary edema.
Lobelin and tsititon are respiratory analeptics of reflex action. In phase I, receptors are excited, the glomeruli of the carotid sinuses are most sensitive - the respiratory center is excited. Excitation of the chromaffin substance of the adrenal glands - an increase in blood pressure (lobelin lowers blood pressure).
Breathing is regulated by the respiratory center (DC) located in the medulla oblongata. DC activity depends on the content of carbon dioxide (CO2) in the blood. With an increase in CO2 level, DC is directly activated; in addition, DC is activated by CO2 reflexively due to stimulation of the chemoreceptors of the carotid glomeruli of the carotid sinus zone (SCZ).
Classification of respiratory stimulants according to the mechanism of action 1. Means that directly activate DC: BEMEGRID, CAFFEINE, ETHIMIZOL 2. Means that stimulate reflexive breathing (H-cholinomimetics): CITIZINE (cytiton), LOBELINA HYDROCHLORIDE 3. Means of mixed action type: , CARBON ACID *, CAMPHORA (camphor) Mechanisms of action: Under the influence of respiratory stimulants, the volume of respiratory movements and their frequency increase. BEMEGRID, CAFFEINE, ETHIMIZOL have a direct stimulating effect on DC. ETIMIZOL activates the subcortical formations of the brain and the centers of the medulla oblongata and differs from typical analeptics in that it has a depressing effect on the cerebral cortex, which justifies its use also in psychiatry; has a stimulating effect on the adrenocorticotropic function of the pituitary gland, what is the reason for its anti-inflammatory effect. In CORDIAMINE, CARBON ACID and CAMPHORA, the central effect is complemented by a stimulating effect on the chemoreceptors of the carotid glomerulus. N-cholinomimetics - CITITONE and LOBELINA HYDROCHLORIDE stimulate DC reflexively. The mechanism of their action lies in the fact that they excite the H-cholinergic receptors of the SCZ, from where afferent impulses enter the medulla oblongata, and increase the activity of the DC. These drugs are ineffective for respiratory depression with hypnotics or anesthetics. hypnotics and anesthetic drugs violate the reflex excitability of DC. H-cholinomimetics act for a short time (5 - 10 min.), The nature of breathing is jerky. If we compare the action of LOBELIN and CITITON, then the advantage is given to CITITON, because in the action of LOBELIN, there are 2 phases: Phase 1 - respiratory depression (due to stimulation of n. Vagus); Phase 2 - stimulation of respiration (due to the stimulation of H-cholinergic receptors). When taking CITITONE, there is no inhibition phase and DC stimulation occurs immediately.
Indications for use. ∙ respiratory depression associated with mild intoxication with opioid analgesics, carbon monoxide, hypnotics drugs of a narcotic type of action;
∙ asphyxia of newborns; ∙ in order to restore the required level of pulmonary ventilation in the post-anesthetic period.
Additional effects: ETIMIZOL has found application in psychiatry as a sedative in conditions accompanied by anxiety; it is used as an anti-inflammatory and anti-allergic agent for arthritis, polyarthritis and some forms of asthma. CORDIAMINE and CAMFORA are used for cardiovascular insufficiency, collapse. CITITONE, LOBELIN and CARBON ACID are also indicated for shock and collapse.
Side effects: ∙ BEMEGRID: nausea, vomiting, muscle twitching, convulsions; ∙ CAFFEINE: state of agitation, insomnia, arrhythmias, increased blood pressure (BP); ∙ ETHIMIZOL: nausea, dyspeptic symptoms, dizziness, anxiety, sleep disturbance, tremors; ∙ CORDIAMINE: convulsions, allergic reactions, pain at the injection site; ∙ CARBON ACID: in high concentrations causes severe acidosis, convulsions and DC paralysis; ∙ CAMPHORA: in rare cases, after the administration of the drug, the formation of an infiltrate (oleoma) is noted, sometimes allergic reactions are possible; ∙ CITITON and LOBELIN: nausea, vomiting, bradycardia, convulsions. Contraindications: ∙ increased mental excitability, epilepsy, convulsive syndrome and / or hyperkinesis in history; ∙ arterial hypertension (AH), essential hypertension (HD), organic diseases of the cardiovascular system (CVS) (including atherosclerosis); ∙ pulmonary edema, bleeding from large vessels (for H-cholinomimetics); ∙ analeptics are contraindicated in case of poisoning with substances that depress the central nervous system, since drugs of this group do not restore breathing and at the same time increase the need for brain tissue for O2.
4. Antibiotics of the group of carbapenems and monobactams. Classification. Mechanism of action. The nature of the action. Spectrum of action. Indications for use. Side effects. Contraindications Comparative evaluation of drugs.
Classification: belong to beta-lactam antibiotics:
1. Carbapenems - imipenem, meropenem, ethapenem.
2. Monobactams - aztreones.
Mechanism: inhibit the synthesis of the cell wall.
Mode of action: bactericidal.
Spectrum of action: Carbapenems - G + and G-, anaerobes. Monobactams: G-
Indications:
CARBAPENEM MONOBACTAMS
hospital pneumonia with exacerbation of chronic bronchitis, community-acquired and hospital pneumonia; pulmonary sepsis with cystic fibrosis, intra-abdominal and gynecological infections; complicated urinary tract infections; urinary tract infections; community-acquired and hospital intra-abdominal infections; infections of the skin, soft tissues, bones and joints; gynecological and obstetric sepsis infections; infections of the skin, soft tissues, bones and joints; diabetic foot; neutropenic fever; endocarditis, sepsis; meningitis and brain abscess; prevention of infectious complications of anesthesia and perioperative infections
Side effects:
o nausea, vomiting, diarrhea, allergic reactions, tremors, convulsions (carbapenems)
o abdominal pain, nausea, vomiting, diarrhea, phlebitis, pain and swelling at the site of intramuscular injection, rare allergic reactions (monobactams)
Contraindications:
o hypersensitivity to β-lactam antibiotics, pregnancy, infants under 3 months of age, breastfeeding (carbapenems)
o hypersensitivity, pregnancy, infants, breastfeeding, with renal failure and cirrhosis, reduce the dose of antibiotic (monobactams)
Imipenem, thienam - resistant to beta-lactamases, is destroyed in the renal tubules.
Meropenem is resistant to beta-lactamases, does not break down in the renal tubules, lasts 8 hours. Aztreonam - resistant to beta-lactamases, does not work on gram (+), in case of urinary tract infections.