3... Antihypertensive drugs that affect the renin-angiotensin system. Classification. Mechanism of action. Side effects. Contraindications Comparative evaluation of drugs.

Classification:

1. Inhibitors of angiotensin II synthesis (angiotensin-converting enzyme inhibitors)

Captopril, Enalapril

Mechanism of action of angiotensin 2 synthesis inhibitors: under the influence of the renin enzyme, angiotensin-I is formed from angiotensin, then the angiotensin-converting enzyme acts on it and angiotensin-2 is formed, which causes narrowing of the arterioles. ACE inhibitors block angiotensin-converting enzyme.

Side effects: allergies, tachycardia, impaired taste

Contraindications: pregnancy, cases of Quincke's edema, hypersensitivity.

2. Angiotensive receptor blockers

Losartan

Mechanism of action of angiotensive receptor blockers: are competitive antagonists of type A1 angiotensive receptors, eliminate the pressor effect of angiotensin A2.

Side effects: allergy, headache

Contraindications: pregnancy, lactation, individual intolerance.

Compare characteristics:

Captopril the action develops after 30-60 minutes for 4-8 hours, is an ambulance drug. Captopril - for hypertensive crises, the rest of the drugs - for the systematic treatment of hypertension.

Enalapril -more active than captopril and longer (day). Fewer side effects.

Losartan -Acts quickly within 2 hours, does not penetrate the BBB ..

4. Antiviral agents. Classification. Mechanism of action. The nature of the action. Indications for use. Side effects. Contraindications Comparative characteristics of drugs.

Antiviral drugs are a group of drugs used for the prevention and treatment of viral infections.

Classification:

- antiherpetic - acyclovir, valacyclovir, penciclovir and famciclovir

- anti-cytomegalovirus - ganciclovir, valganciclovir, foscarnet and cidofovir.

- anti-influenza - amantadine, rimantadine - and viral neuroaminidase inhibitors - zanamivir, oseltamivir

- extended spectrum drugs - ribavirin, lamivudine.

- antiretroviral (for the prevention and treatment of HIV infection) - 1. Nucleoside inhibitors of HIV reverse transcriptase.

2. Non-nucleoside inhibitors of HIV reverse transcriptase.

3. Inhibitors of HIV protease.

Mechanism of action: Antiherpetic chemotherapy

Acyclovir is the ancestor of antiherpetic drugs - blockers of viral DNA synthesis. The active metabolite of acyclovir, acyclovir triphosphate, has an antiviral effect. By inhibiting viral DNA polymerase, acyclovir triphosphate blocks viral DNA synthesis.

Penciclovir in human cells affected by the virus is activated, turning into penciclovir triphosphate, which disrupts the synthesis of viral DNA.

Foscarnet forms inactive complexes with DNA polymerase of herpes viruses and cytomegaloviruses.

Anti-cytomegalovirus: Ganciclovir.

In cells affected by cytomegalovirus, ganciclovir is converted to its active form - ganciclovir triphosphate, which inhibits viral DNA polymerase.

Anti-influenza:

The antiviral effect of amantadine and remantadine is realized by blocking special ion channels of the M2-channels of the influenza A virus, and therefore its ability to penetrate cells and release ribonucleoprotein is impaired. Thus, the most important stage of viral replication is inhibited.

Extended spectrum drugs: RIBAVIRIN.

The mechanism of antiviral action has not yet been clarified. It is assumed that ribavirin causes a decrease in the intracellular pool of guanosine triphosphate and, thus, indirectly decreases the synthesis of viral nucleic acids.

Lamivudine.

In cells affected by the virus, it is activated, turning into lavimvudine triphosphate, which inhibits hepatitis B virus DNA polymerase and HIV reverse transcriptase.

Antiretrovirals: The structure of all nucleic reverse transcriptase inhibitors is based on one of the analogs of the natural nucleoside (thymidine, adenine, cytidine or guanine), which determines the general properties of the metabolites of each drug to block HIV reverse transcriptase and selectively inhibit viral DNA replication. Under the action of appropriate enzymes, drugs are metabolized to form triphosphates, which exhibit pharmacological activity. The ability of drugs in this group to inhibit HIV reverse transcriptase is hundreds of times higher than the ability to inhibit human DNA polymerase. Nucleoside reverse transcriptase inhibitors are active in HIV-infected T cells and macrophages, inhibiting the early stages of the virus life cycle.

Nature and spectrum of action: Antiherpetic: Acyclovir - Spectrum of action: Herpes symplex types 1 and 2, Varicella-zoster, cytomegalovirus (470 times less sensitive to acyclovir than HSV type 1). Mode of action: virucidal.

Anti-cytomegalovirus

Ganciclovir

Spectrum of activity: cytomegalovirus (activity is 10-50 times higher than that of acyclovir), herpes viruses. Character: virucidal

Anti-influenza drugs

Remantadine

Spectrum of action - type A influenza virus. Nature: virucidal.

Extended-spectrum antivirals

Ribavirin

Structurally similar to the guanosine nucleotide. Possesses a wide spectrum of activity against many DNA and RNA viruses. Highly toxic. Character: virucidal.

INDICATIONS:

Antiherpetic: Valacyclovir:

- infections of the skin and mucous membranes;

- ophthalmic herpes (only acyclovir);

- genital herpes;

- herpetic encephalitis;

- neonatal herpes.

Anti-cytomegalovirus: cytomegalovirus infection

Anti-influenza: Amantadine and rimantadine- Treatment of influenza caused by virus A.

Prevention of influenza (if the epidemic is caused by the A virus). Efficiency - 70 - 90%.

Extended spectrum drugs: Ribavirin - Respiratory syncytial virus infections (only serologically confirmed): severe bronchiolitis and pneumonia in infants and young children at risk of death (congenital heart disease, immunodeficiency, bronchopulmonary dysplasia), in the background severe cystic fibrosis or pulmonary hypertension.

Antiretrovirals:

Non-nucleoside reverse inhibitors

HIV transcriptase

Combination therapy for HIV-1 infection (nevirapine, efavirenz).

Prevention of mother-to-newborn transmission of HIV-1 infection (nevirapine).

Chemoprophylaxis of parenteral HIV infection (efavirenz).

Side effects:

Antiherpetic: Acyclovir: Local:

- burning sensation when applied to mucous membranes, especially when applied vaginally;

- phlebitis when administered intravenously.

Systemic:

Gastrointestinal tract: pain or discomfort in the abdomen, nausea, vomiting, diarrhea;

Anti-cytomegalovirus: Ganciclovir: Hematological reactions (up to 40%): neutropenia, anemia, thrombocytopenia. Cases of severe persistent neutropenia complicated by fatal infection have been reported. Risk factor: AIDS.

Gastrointestinal tract: diarrhea (44%), anorexia, vomiting.

Anti-influenza:

Gastrointestinal tract: abdominal pain, impaired appetite, nausea.

CNS: when using amantadine - in 14% of patients, remantadine - in 3 - 6%: drowsiness, insomnia, headache, dizziness, visual disturbances, irritability, paresthesia, tremors, convulsions.

Extended spectrum drugs: Ribavirin: Hematological reactions: anemia, hemolytic anemia, leukopenia, neutropenia, granulocytopenia, trombocytopenia. Control methods: clinical blood test every 2 weeks.

CNS: asthenic syndrome, headache, insomnia, fatigue, irritability.

Antiretrovirals:

• Diarrhea

• Fatigue

• Headache

• Liver problems

• Upset stomach (nausea), stomach pain, vomiting, decreased appetite

Contraindications: Antiherpetic: Valacyclovir: Allergic reactions, hypersensitivity to the drug.

Anti-cytomegalovirus: Undesirable side effects in 1/3 of patients are the reason for drug withdrawal

Anti-influenza: Arbidol.

Allergic reaction to arbidol.

Age up to 2 years (in children from 2 to 6 years, it is used only for the treatment of influenza).

Extended spectrum drugs: Ribavirin: Hypersensitivity to ribavirin.

Severe hepatic and / or renal impairment.

Anemia

Hemoglobinopathy.

Severe heart failure.

Pregnancy.

Antiretrovirals: STAVUDIN (D4T).

- hypersensitivity to stavudine;

- peripheral neuropathy;

- lactation;

- age up to 3 months;

- liver failure;

- severe renal failure