1. Mechanism and spectrum of action, side effects, contraindications and indications for prescribing carbapenems and monobactams. Interaction ?. Mechanism and spectrum of action, side effects, contraindications and indications for prescribing inhalational glucocorticosteroids. Interaction.

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I. Carbapenems and Monobactams

CARBAPENEMS

Drugs in Class

Imipenem/cilastatin (Primaxin)
Meropenem (Merrem)
Ertapenem (Invanz)
(Doripenem — no longer available in the USA)

Mechanism of Action

Carbapenems are β-lactam antibiotics that act by binding to penicillin-binding proteins (PBPs), thereby inhibiting transpeptidation — the final cross-linking step in bacterial cell wall (peptidoglycan) synthesis. This results in a weakened, osmotically unstable cell wall and bactericidal cell lysis.

They are resistant to most β-lactamases (including extended-spectrum β-lactamases, ESBLs) due to the unique 1-β-methyl group on the carbapenem ring — but are destroyed by serine carbapenemases and metallo-β-lactamases.

Imipenem is inactivated by renal tubular dehydropeptidase-I; therefore it is always co-administered with cilastatin (a dehydropeptidase inhibitor) to prevent renal degradation. Meropenem and ertapenem are not significantly degraded by this enzyme.

— Katzung's Basic and Clinical Pharmacology, 16th Ed.; Lippincott Illustrated Reviews: Pharmacology

Spectrum of Action

Agent	Spectrum
Imipenem / Meropenem	Broadest: aerobic gram-positive cocci (including pneumococci), gram-negative rods (including P. aeruginosa, Enterobacterales, Acinetobacter), and anaerobes
Ertapenem	Similar broad spectrum but lacks activity against P. aeruginosa and Acinetobacter spp. — once-daily dosing

Intrinsically resistant organisms (to all carbapenems):

Enterococcus faecium
MRSA (methicillin-resistant S. aureus)
Clostridioides difficile
Burkholderia cepacia
Stenotrophomonas maltophilia

Carbapenem-resistant Enterobacterales (CRE) — treated with combination products such as meropenem-vaborbactam or imipenem-relebactam.

— Katzung's Basic and Clinical Pharmacology, 16th Ed.

Pharmacokinetics

All carbapenems must be given parenterally (IV or IM)
Penetrate body tissues and fluids well, including CSF — except ertapenem has poor CSF penetration
All are renally cleared; dose must be reduced in renal insufficiency
Half-lives: imipenem ~1 h, meropenem ~1 h, ertapenem ~4 h (once-daily dosing)

Indications

Serious polymicrobial infections (mixed aerobic/anaerobic) — e.g., intra-abdominal, pelvic
ESBL-producing gram-negative organisms — treatment of choice
Enterobacter infections (resistant to destruction by AmpC β-lactamases of these organisms)
Febrile neutropenia (imipenem or meropenem ± aminoglycoside)
Hospital-acquired pneumonia / VAP with multidrug-resistant (MDR) gram-negatives including P. aeruginosa
Nosocomial sepsis caused by organisms resistant to other available drugs
Ertapenem is used for community-acquired intra-abdominal infections, complicated UTIs, and gynecological infections where P. aeruginosa is not a concern

— Katzung's Basic and Clinical Pharmacology, 16th Ed.; The Washington Manual of Medical Therapeutics

Side Effects / Adverse Effects

Effect	Notes
Nausea, vomiting, diarrhea	Most common GI effects
Seizures	Risk is highest with imipenem (especially at high doses or in renal failure); meropenem and ertapenem carry much lower seizure risk
Hypersensitivity reactions	Skin rashes, fever, anaphylaxis (class-wide β-lactam risk)
Thrombophlebitis	At IV infusion site
Elevated liver enzymes (transaminases)	Transient
Superinfection	C. difficile-associated diarrhea, candidiasis

Excessive imipenem levels in renal failure may trigger seizures. Meropenem and ertapenem are far less likely to cause this.

— Katzung's Basic and Clinical Pharmacology, 16th Ed.

Contraindications

Known hypersensitivity to carbapenems
Cross-reactivity with penicillins: occurs in a small fraction (~1%) of penicillin-allergic patients — use with caution; avoid in those with confirmed penicillin anaphylaxis
Imipenem in seizure-prone patients or those with CNS disorders — use meropenem instead
Dose adjustment required in renal insufficiency (not a contraindication per se, but failure to adjust risks seizures)

Drug Interactions

Interaction	Effect
Valproic acid	Carbapenems — especially imipenem — dramatically reduce valproate serum levels (by up to 60-100%), leading to seizure breakthrough. This is a critical and well-documented interaction. Avoid combination.
Probenecid	Reduces renal tubular secretion of meropenem, increasing its plasma levels
Aminoglycosides	Additive/synergistic activity against gram-negative rods (used in febrile neutropenia) — but mix in same IV line with caution due to chemical incompatibility
Other nephrotoxic agents	Additive renal toxicity risk

MONOBACTAMS

Drug in Class

Aztreonam (Azactam) — the only commercially available monobactam

Mechanism of Action

Aztreonam is a monocyclic β-lactam that binds selectively to PBP-3 of gram-negative bacteria, inhibiting bacterial cell wall synthesis and producing bactericidal elongated filamentous bacteria that then lyse. Its monocyclic ring structure renders it stable to many β-lactamases.

— Katzung's Basic and Clinical Pharmacology, 16th Ed.; Current Surgical Therapy, 14th Ed.

Spectrum of Action

Active exclusively against aerobic gram-negative bacteria — including P. aeruginosa, and most Enterobacterales
No activity against gram-positive organisms
No activity against anaerobes
Gram-negative spectrum is similar to third-generation cephalosporins (structural similarity to ceftazidime)
Inactivated by AmpC β-lactamases, ESBLs, and carbapenemases

— Katzung's Basic and Clinical Pharmacology, 16th Ed.; Harrison's Principles of Internal Medicine, 22nd Ed.

Pharmacokinetics

Administered IV or IM; given every 8 hours at 1–2 g
Half-life: 1–2 hours; prolonged in renal failure — dose must be reduced
Penetrates well into CSF
Excreted primarily by the kidneys

Indications

Serious gram-negative infections (pneumonia, meningitis, sepsis, UTI, intra-abdominal infections) when caused by susceptible organisms
Patients with documented severe penicillin allergy — aztreonam does not cross-react with penicillins and can be used safely in most penicillin-allergic patients
Combination therapy in hospital-acquired pneumonia as a second-line agent when no other β-lactams are appropriate
P. aeruginosa infections in patients who cannot receive other antibiotics

— Harrison's Principles of Internal Medicine, 22nd Ed.; The Washington Manual of Medical Therapeutics

Side Effects

Generally well tolerated
Skin rashes
Transient elevations of serum aminotransferases
Phlebitis at IV site
Major toxicity is uncommon

Contraindications

Known hypersensitivity to aztreonam
Caution with ceftazidime allergy: Due to structural similarity to ceftazidime, cross-reactivity is possible in patients with documented severe ceftazidime allergy — unique among β-lactam cross-reactivities
Dose adjustment required in renal insufficiency

Drug Interactions

No significant cross-reactivity with penicillins (can be used in penicillin-allergic patients)
Pharmacokinetic interactions are minimal
May be combined with other β-lactam antibiotics when necessary for broader coverage in HAP

II. Inhaled Glucocorticosteroids (ICS)

Drugs in Class

Beclomethasone dipropionate (BDP)
Budesonide
Fluticasone propionate / fluticasone furoate
Mometasone furoate
Ciclesonide (prodrug)
Flunisolide

Mechanism of Action

ICS act via glucocorticoid receptors (GRs) — cytosolic nuclear receptors that, upon ligand binding, translocate to the nucleus where they exert effects through two main pathways:

Trans-repression (main anti-inflammatory effect):
- Inflammatory stimuli (IL-1β, TNF-α) activate IKKβ → NF-κB nuclear translocation → binding to coactivators (CBP) with histone acetyltransferase (HAT) activity → acetylation of histones → increased transcription of inflammatory genes
- Corticosteroid-GR complexes recruit HDAC2 (histone deacetylase 2), which reverses histone acetylation and suppresses activated inflammatory gene transcription (e.g., cytokines, adhesion molecules, inflammatory enzymes)
Trans-activation (some anti-inflammatory + systemic side effects):
- GR dimers bind to glucocorticoid response elements (GREs) in gene promoters, increasing transcription of anti-inflammatory proteins (e.g., lipocortin-1, IL-10, IκBα)

Results:

Reduced eosinophil, mast cell, lymphocyte, and macrophage activity in airways
Decreased production of cytokines (IL-4, IL-5, IL-13), chemokines, and arachidonic acid metabolites
Reduced mucus secretion and airway hyperresponsiveness
Structural benefits: reduction in submucosal edema and airway remodeling (long-term)

Interaction with β₂ receptors: Steroids potentiate β₂-agonist effects by increasing β₂-receptor gene transcription and preventing receptor downregulation/desensitization. Conversely, β₂ agonists enhance glucocorticoid receptor nuclear translocation — creating mutual synergy (the pharmacological basis for ICS + LABA combination inhalers).

— Goodman & Gilman's The Pharmacological Basis of Therapeutics; Fishman's Pulmonary Diseases and Disorders

Pharmacokinetics

Inhaled fraction acts locally on airway mucosa
A portion is absorbed from the airway/alveolar surface → enters systemic circulation
Fraction deposited in the oropharynx is swallowed → absorbed from gut → undergoes first-pass hepatic metabolism (high first-pass extraction reduces systemic bioavailability)
Spacer chambers reduce oropharyngeal deposition and therefore systemic absorption and local side effects
Beclomethasone and ciclesonide are prodrugs activated by esterases in the lung
Budesonide and fluticasone have high first-pass metabolism after oral absorption (~99% for fluticasone), minimizing systemic effects

— Goodman & Gilman's The Pharmacological Basis of Therapeutics

Indications

Persistent asthma (mild, moderate, severe) — first-line long-term controller therapy; should be initiated whenever a patient needs short-acting β₂ agonist for symptom control more than twice weekly
COPD — reduce exacerbation frequency in patients with ≥2 severe exacerbations/year AND blood eosinophils >300 cells/μL; used in triple combination (ICS + LABA + LAMA)
Croup (nebulized budesonide)
Allergic rhinitis (intranasal formulations)
Eosinophilic conditions (eosinophilic esophagitis — budesonide)
During pregnancy: budesonide, beclomethasone, and fluticasone are acceptable first-line agents

— Goodman & Gilman's The Pharmacological Basis of Therapeutics; Goldman-Cecil Medicine; Creasy & Resnik's Maternal-Fetal Medicine

Side Effects

Local (oropharyngeal)

Effect	Notes
Oropharyngeal candidiasis (thrush)	Most common local side effect; reduced by rinsing mouth after use and using a spacer
Dysphonia (hoarseness)	Due to myopathy of laryngeal muscles
Cough / throat irritation	Especially with MDI

Systemic (dose-dependent, with high doses)

Effect	Notes
Hypothalamic-pituitary-adrenal (HPA) axis suppression	At high doses (>1000 μg/day BDP equivalent); risk of adrenal insufficiency
Growth retardation in children	At doses >400 μg/day — not seen at standard doses
Osteoporosis	With prolonged high-dose use
Skin thinning / easy bruising	Systemic steroid effect
Cataracts / glaucoma	With chronic high-dose ICS
Metabolic effects	Blood glucose elevation, minimal at usual doses

ICS + ritonavir (HIV protease inhibitor): fluticasone and budesonide levels can be dramatically elevated (CYP3A4 inhibition by ritonavir), leading to iatrogenic Cushing's syndrome and adrenal suppression. Beclomethasone is the ICS of choice in patients on ritonavir/PIs.

Contraindications

Acute severe bronchospasm / status asthmaticus — ICS have no bronchodilator effect and are not indicated as rescue therapy; systemic steroids are required
Active pulmonary tuberculosis or untreated respiratory infections — relative contraindication (may worsen)
Hypersensitivity to the specific agent
Cystic fibrosis and bronchiectasis — largely ineffective (neutrophilic inflammation is steroid-resistant)
ICS do not modify COPD disease progression and should not be used solely for that purpose

Drug Interactions

Interaction	Mechanism	Clinical Significance
Ritonavir / HIV protease inhibitors	Strong CYP3A4 inhibition raises ICS (fluticasone, budesonide) plasma levels	Iatrogenic Cushing's syndrome, adrenal suppression; use beclomethasone instead
Ketoconazole / itraconazole	CYP3A4 inhibition increases ICS systemic exposure	Increased systemic side effects
β₂ agonists (LABA/SABA)	Mutual pharmacodynamic synergy	Enhanced bronchodilation and anti-inflammatory effect; basis of combination inhalers
Anticholinergics (LAMA)	Additive bronchodilation	Used in triple therapy for COPD
Oral corticosteroids	Additive systemic effects	Increased HPA suppression, metabolic side effects

— Goldman-Cecil Medicine; Goodman & Gilman's The Pharmacological Basis of Therapeutics

Quick Reference Summary

Feature	Carbapenems	Monobactams (Aztreonam)	ICS
Mechanism	PBP inhibition → cell wall synthesis block	PBP-3 inhibition → gram-negative cell wall synthesis block	GR activation → HDAC2 recruitment → suppression of inflammatory genes
Spectrum	Broadest: G+, G−, anaerobes (ertapenem: no Pseudomonas)	Gram-negative aerobes only	N/A (anti-inflammatory)
Key use	Severe/MDR infections, ESBL, polymicrobial, febrile neutropenia	Gram-negative infections in β-lactam-allergic patients	Persistent asthma, COPD exacerbations
Key SE	Seizures (imipenem), valproate interaction	Minimal; ceftazidime cross-reactivity	Oral candidiasis, dysphonia; systemic effects at high doses
Key interaction	Valproic acid (carbapenems ↓ levels → seizures)	Minimal	Ritonavir/CYP3A4 inhibitors ↑ systemic ICS exposure → Cushing's

In short but informative

Carbapenems & Monobactams

Carbapenems (imipenem/cilastatin, meropenem, ertapenem)

Mechanism: Bind PBPs → inhibit peptidoglycan cross-linking → bactericidal cell wall lysis. Resistant to most β-lactamases. Imipenem is degraded by renal dehydropeptidase-I → must be co-given with cilastatin.

Spectrum: Broadest of all β-lactams — gram-positive cocci, gram-negative rods (incl. P. aeruginosa), anaerobes. Ertapenem excludes P. aeruginosa and Acinetobacter. All fail against MRSA, E. faecium, C. difficile, Stenotrophomonas.

Indications: MDR/ESBL infections, polymicrobial (aerobic + anaerobic) infections, febrile neutropenia, hospital-acquired pneumonia, Enterobacter infections.

Side effects: Nausea/vomiting, seizures (imipenem >> meropenem/ertapenem — especially in renal failure), hypersensitivity, transaminase elevation, C. difficile colitis.

Contraindications: Allergy to carbapenems; caution in penicillin anaphylaxis; avoid imipenem in seizure-prone patients.

Key interaction: Valproic acid — carbapenems reduce valproate levels by up to 100% → seizure breakthrough. Avoid combination.

Monobactams (aztreonam only)

Mechanism: Monocyclic β-lactam; binds PBP-3 of gram-negative bacteria → bactericidal. Stable to many β-lactamases.

Spectrum: Gram-negative aerobes only (Enterobacterales, P. aeruginosa). No gram-positive, no anaerobic activity.

Indications: Gram-negative infections (pneumonia, sepsis, meningitis, UTI) — especially valuable in severe penicillin-allergic patients (no cross-reactivity with penicillins).

Side effects: Minimal — skin rash, transient transaminase elevation.

Contraindications: Allergy to aztreonam; caution with ceftazidime allergy (structural similarity → possible cross-reactivity).

Key interaction: No significant pharmacokinetic interactions; can be combined with other β-lactams for broader coverage in HAP.

Inhaled Glucocorticosteroids (ICS)

(beclomethasone, budesonide, fluticasone, mometasone, ciclesonide)

Mechanism: Bind cytosolic glucocorticoid receptors → translocate to nucleus → recruit HDAC2 → reverse histone acetylation → suppress NF-κB-driven inflammatory gene transcription (cytokines, adhesion molecules). Also upregulate β₂-receptor expression, enhancing bronchodilator response. Beclomethasone and ciclesonide are prodrugs activated in the lung.

Spectrum of action: Reduce eosinophilic airway inflammation, mucus secretion, airway hyperresponsiveness, and submucosal edema. No immediate bronchodilator effect.

Indications: Persistent asthma (first-line controller), COPD with frequent exacerbations + eosinophilia (>300/μL), croup (nebulized budesonide). Safe in pregnancy (budesonide, beclomethasone, fluticasone preferred).

Side effects:

Local: oral candidiasis, dysphonia, throat irritation (reduced by spacer + mouth rinsing)
Systemic (high doses): HPA suppression, growth retardation in children, osteoporosis, cataracts, skin thinning

Contraindications: Acute severe bronchospasm (no rescue role), active untreated TB, cystic fibrosis/bronchiectasis (steroid-resistant neutrophilic inflammation), known hypersensitivity.

Key interactions:

Ritonavir / CYP3A4 inhibitors (ketoconazole) → ↑ fluticasone/budesonide plasma levels → iatrogenic Cushing's + adrenal suppression. Use beclomethasone instead in patients on HIV protease inhibitors.
LABAs — mutual synergy: ICS upregulates β₂ receptors; LABAs enhance GR nuclear translocation. Basis of combination inhalers.

Priscription for these drug how? By Kazakhstan style

Рецепты по казахстанскому стандарту (форма 107/у)

Бланк рецепта — форма 107/у

Республика Казахстан
Наименование МО: ГКБ №1 г. Алматы
Дата: 15.01.2025                    № рецепта: _______

ФИО пациента: Иванов Иван Иванович
Дата рождения: 01.01.1985          Возраст: 39 лет
Номер амбулаторной карты: 12345

ФИО врача: Сейткалиев А.М.
Специальность: Терапевт

Rp.:

1. КАРБАПЕНЕМЫ

Имипенем/Циластатин

Rp.: Imipenem + Cilastatinum 500 mg/500 mg
     pulv. pro inject. d.t.d. № 10 in flac.
S.: Содержимое флакона растворить в 100 мл
    физ. раствора. Вводить в/в капельно
    каждые 6–8 часов. Курс — по назначению врача.

Врач: _____________    Личная печать: [М.П.]

Меропенем

Rp.: Meropenemum 1,0 g
     pulv. pro inject. d.t.d. № 10 in flac.
S.: Растворить в 100 мл 0,9% NaCl.
    Вводить в/в капельно по 1,0 г каждые 8 часов.
    Длительность инфузии — 30 мин.

Врач: _____________    Личная печать: [М.П.]

Эртапенем

Rp.: Ertapenemum 1,0 g
     pulv. pro inject. d.t.d. № 7 in flac.
S.: Растворить в 50 мл 0,9% NaCl.
    Вводить в/в капельно по 1,0 г 1 раз в сутки.
    Длительность инфузии — 30 мин.

Врач: _____________    Личная печать: [М.П.]

2. МОНОБАКТАМЫ

Азтреонам

Rp.: Aztreonamum 1,0 g
     pulv. pro inject. d.t.d. № 10 in flac.
S.: Растворить в 100 мл 0,9% NaCl.
    Вводить в/в капельно по 1,0–2,0 г
    каждые 8 часов.

Врач: _____________    Личная печать: [М.П.]

3. ИНГАЛЯЦИОННЫЕ ГЛЮКОКОРТИКОСТЕРОИДЫ

Беклометазон (лёгкая-средняя степень астмы)

Rp.: Beclometasoni dipropionas 250 mcg/dose
     aerosol. inhal. 200 dos. — 1 flac.
D.t.d. № 1
S.: Ингалировать по 1–2 вдоха (250–500 мкг)
    2 раза в сутки. После ингаляции
    прополоскать рот водой.

Врач: _____________    Личная печать: [М.П.]

Будесонид (взрослые / дети)

Rp.: Budesonidum 200 mcg/dose
     aerosol. inhal. 200 dos. — 1 flac.
D.t.d. № 1
S.: Ингалировать по 1–2 вдоха (200–400 мкг)
    2 раза в сутки. Рот прополаскивать после
    каждого применения.

Врач: _____________    Личная печать: [М.П.]

Для детей — небулайзерная форма:

Rp.: Budesonidum 0,25 mg/ml — 2 ml
     susp. pro inhal. d.t.d. № 20 in amp.
S.: Ингалировать через небулайзер по 0,5–1 мг
    1–2 раза в сутки.

Флутиказон

Rp.: Fluticasoni propionas 125 mcg/dose
     aerosol. inhal. 120 dos. — 1 flac.
D.t.d. № 1
S.: По 1–2 вдоха (125–250 мкг) 2 раза в сутки.
    После ингаляции прополоскать рот.

Врач: _____________    Личная печать: [М.П.]

Флутиказон/Салметерол (комбинация ИГК + ДДБА)

Rp.: Fluticasoni propionas + Salmeterolum
     250 mcg/50 mcg/dose
     aerosol. inhal. 60 dos. — 1 flac.
D.t.d. № 1
S.: По 1 вдоху 2 раза в сутки (утром и вечером).
    Рот прополаскивать после применения.

Врач: _____________    Личная печать: [М.П.]

Ключевые правила оформления рецепта по РК

Элемент	Требование
Бланк	Форма 107/у (амбулатория) или 148/у (льготный)
Язык	Латынь для Rp., русский/казахский для S.
Подпись врача	Обязательна + личная печать врача
Печать МО	Треугольная печать учреждения
Срок действия	10 дней (обычный), 1 месяц (хронические)
Антибиотики	Выписываются на отдельном бланке
ИГК	Рецептурный отпуск (Рецептурная форма А)

Карбапенемы и азтреонам — исключительно стационарные препараты, назначаются листом назначений в истории болезни, не амбулаторным рецептом.

No only style that but everything in english

Prescriptions — Kazakhstan Format (Form 107/u), English

1. CARBAPENEMS

Imipenem/Cilastatin

Republic of Kazakhstan
Medical Organization: City Clinical Hospital No.1, Almaty
Date: 15.01.2025                        Prescription No.: ___

Patient: John Smith
DOB: 01.01.1985                         Age: 39
Outpatient Card No.: 12345

Physician: A.M. Seitkaliev
Specialty: Internist

Rp.: Imipenem + Cilastatinum 500 mg/500 mg
     pulv. pro inject. d.t.d. No. 10 in flac.
S.:  Dissolve vial contents in 100 ml of 0.9% NaCl.
     Administer IV drip every 6–8 hours.
     Duration: as directed by physician.

Physician signature: __________   Personal stamp: [seal]
Institution stamp:   [triangular seal]

Meropenem

Republic of Kazakhstan
Medical Organization: City Clinical Hospital No.1, Almaty
Date: 15.01.2025                        Prescription No.: ___

Patient: John Smith
DOB: 01.01.1985                         Age: 39
Outpatient Card No.: 12345

Physician: A.M. Seitkaliev
Specialty: Internist

Rp.: Meropenemum 1.0 g
     pulv. pro inject. d.t.d. No. 10 in flac.
S.:  Dissolve in 100 ml of 0.9% NaCl.
     Administer IV drip 1.0 g every 8 hours.
     Infusion duration: 30 minutes.

Physician signature: __________   Personal stamp: [seal]
Institution stamp:   [triangular seal]

Ertapenem

Republic of Kazakhstan
Medical Organization: City Clinical Hospital No.1, Almaty
Date: 15.01.2025                        Prescription No.: ___

Patient: John Smith
DOB: 01.01.1985                         Age: 39
Outpatient Card No.: 12345

Physician: A.M. Seitkaliev
Specialty: Internist

Rp.: Ertapenemum 1.0 g
     pulv. pro inject. d.t.d. No. 7 in flac.
S.:  Dissolve in 50 ml of 0.9% NaCl.
     Administer IV drip 1.0 g once daily.
     Infusion duration: 30 minutes.

Physician signature: __________   Personal stamp: [seal]
Institution stamp:   [triangular seal]

2. MONOBACTAMS

Aztreonam

Republic of Kazakhstan
Medical Organization: City Clinical Hospital No.1, Almaty
Date: 15.01.2025                        Prescription No.: ___

Patient: John Smith
DOB: 01.01.1985                         Age: 39
Outpatient Card No.: 12345

Physician: A.M. Seitkaliev
Specialty: Internist

Rp.: Aztreonamum 1.0 g
     pulv. pro inject. d.t.d. No. 10 in flac.
S.:  Dissolve in 100 ml of 0.9% NaCl.
     Administer IV drip 1.0–2.0 g every 8 hours.
     Infusion duration: 30 minutes.

Physician signature: __________   Personal stamp: [seal]
Institution stamp:   [triangular seal]

3. INHALED GLUCOCORTICOSTEROIDS

Beclomethasone (mild–moderate asthma)

Republic of Kazakhstan
Medical Organization: Polyclinic No.3, Almaty
Date: 15.01.2025                        Prescription No.: ___

Patient: John Smith
DOB: 01.01.1985                         Age: 39
Outpatient Card No.: 12345

Physician: A.M. Seitkaliev
Specialty: Pulmonologist

Rp.: Beclometasoni dipropionas 250 mcg/dose
     aerosol. inhal. 200 doses — 1 inhaler
D.t.d. No. 1
S.:  Inhale 1–2 puffs (250–500 mcg) twice daily.
     Rinse mouth with water after each use.
     Use a spacer to reduce oropharyngeal side effects.

Physician signature: __________   Personal stamp: [seal]
Institution stamp:   [triangular seal]

Budesonide — Adults

Republic of Kazakhstan
Medical Organization: Polyclinic No.3, Almaty
Date: 15.01.2025                        Prescription No.: ___

Patient: John Smith
DOB: 01.01.1985                         Age: 39
Outpatient Card No.: 12345

Physician: A.M. Seitkaliev
Specialty: Pulmonologist

Rp.: Budesonidum 200 mcg/dose
     aerosol. inhal. 200 doses — 1 inhaler
D.t.d. No. 1
S.:  Inhale 1–2 puffs (200–400 mcg) twice daily.
     Rinse mouth with water after each use.

Physician signature: __________   Personal stamp: [seal]
Institution stamp:   [triangular seal]

Budesonide — Children (nebulizer)

Rp.: Budesonidum 0.25 mg/ml — 2 ml
     susp. pro inhal. d.t.d. No. 20 in amp.
S.:  Inhale 0.5–1 mg via nebulizer
     once or twice daily.
     Rinse mouth after use.

Fluticasone Propionate

Republic of Kazakhstan
Medical Organization: Polyclinic No.3, Almaty
Date: 15.01.2025                        Prescription No.: ___

Patient: John Smith
DOB: 01.01.1985                         Age: 39
Outpatient Card No.: 12345

Physician: A.M. Seitkaliev
Specialty: Pulmonologist

Rp.: Fluticasoni propionas 125 mcg/dose
     aerosol. inhal. 120 doses — 1 inhaler
D.t.d. No. 1
S.:  Inhale 1–2 puffs (125–250 mcg) twice daily.
     Rinse mouth with water after each use.

Physician signature: __________   Personal stamp: [seal]
Institution stamp:   [triangular seal]

Fluticasone/Salmeterol (ICS + LABA combination)

Republic of Kazakhstan
Medical Organization: Polyclinic No.3, Almaty
Date: 15.01.2025                        Prescription No.: ___

Patient: John Smith
DOB: 01.01.1985                         Age: 39
Outpatient Card No.: 12345

Physician: A.M. Seitkaliev
Specialty: Pulmonologist

Rp.: Fluticasoni propionas + Salmeterolum
     250 mcg/50 mcg per dose
     aerosol. inhal. 60 doses — 1 inhaler
D.t.d. No. 1
S.:  Inhale 1 puff twice daily (morning and evening).
     Rinse mouth after each use.
     Do NOT use as rescue inhaler.

Physician signature: __________   Personal stamp: [seal]
Institution stamp:   [triangular seal]

Prescription Rules — Kazakhstan Standard

Element	Requirement
Form	107/u (outpatient) or 148/u (subsidized/льготный)
Latin	Used for Rp. (drug name, form, dose, quantity)
S. (Signa)	Instructions in English/Kazakh/Russian
Physician stamp	Personal stamp + signature mandatory
Institution stamp	Triangular stamp of medical organization
Validity	10 days (standard); 1 month (chronic conditions)
Antibiotics	Written on a separate prescription form
ICS	Prescription-only (Form A)
Carbapenems / Aztreonam	Inpatient use only — prescribed via inpatient medication order sheet, not outpatient prescription

Case 3: Patient M., 57 years old, complains of moderate pain in the right knee joint, which increases with exertion, slight morning stiffness, increased pain by the end of the day. There is a slight increase in CRP in the laboratory data. In the anamnesis: a year ago she was treated for a stomach ulcer. Station 1 1. Identify the problem (diagnosis : 2. Choose your P-medication for this condition: 3. Dosage form 4. Dosage Station 2 5. Pharmacokinetics of the drug 6. Mechanism of action 7. Write a prescription Station 3 8. Duration of treatment 9. Side effects 10. Contraindications In very short

Case 3 — Patient M., 57 y.o.

Station 1

1. Diagnosis: Osteoarthritis (OA) of the right knee joint, moderate severity (pain with exertion, end-of-day worsening, brief morning stiffness <30 min, slightly elevated CRP — no signs of RA)

2. P-drug of choice: Celecoxib (selective COX-2 inhibitor)

Rationale: Patient has a history of peptic ulcer — non-selective NSAIDs (ibuprofen, diclofenac) are contraindicated. Celecoxib spares COX-1 → gastric mucosa protected.

3. Dosage form: Capsules (oral)

4. Dosage: 200 mg once daily or 100 mg twice daily

Station 2

5. Pharmacokinetics:

Parameter	Detail
Absorption	Well absorbed orally; Tmax ~3 h
Bioavailability	~40% (food increases absorption)
Protein binding	~97% (albumin)
Metabolism	Liver via CYP2C9
Half-life	~11 hours
Excretion	Feces (~57%), urine (~27%)

6. Mechanism of Action: Selectively inhibits COX-2 → blocks conversion of arachidonic acid to prostaglandins (PGE₂) → reduces inflammation, pain, and fever. Spares COX-1 → does not inhibit thromboxane A₂ in platelets → less GI mucosal damage than non-selective NSAIDs.

7. Prescription:

Republic of Kazakhstan
Medical Organization: Polyclinic No.1, Almaty
Date: 15.01.2025              Prescription No.: ___

Patient: M., 57 years old
Outpatient Card No.: _____

Physician: ____________
Specialty: Rheumatologist / GP

Rp.: Celecoxibum 200 mg
     caps. d.t.d. No. 30
S.:  Take 1 capsule (200 mg) once daily
     with food. Duration — 4 weeks.

Physician signature: ______   Personal stamp: [seal]
Institution stamp: [triangular seal]

Station 3

8. Duration of treatment: 4–6 weeks per course (symptomatic relief). For chronic OA — intermittent courses; use minimum effective dose for shortest necessary time. Reassess regularly.

9. Side effects:

System	Effect
GI	Less ulcerogenic than non-selective NSAIDs; still possible — nausea, dyspepsia
Cardiovascular	↑ risk of MI, stroke, hypertension (main concern with long-term use)
Renal	Fluid retention, edema, ↑ creatinine
Hepatic	Transaminase elevation (rare)
Skin	Rash; rare — Stevens-Johnson syndrome

10. Contraindications:

Active cardiovascular disease (post-MI, stroke, severe heart failure)
Sulfonamide allergy (celecoxib contains sulfonamide moiety)
Severe hepatic impairment
Severe renal insufficiency (GFR <30)
Pregnancy (3rd trimester)
Active GI bleeding (relative — though safer than non-selective NSAIDs)
Children <18 years

Station 2 and 3 more short

Station 2

5. Pharmacokinetics: Oral, well absorbed (Tmax ~3h), protein binding 97%, metabolized by CYP2C9 in liver, t½ ~11h, excreted in feces/urine.

6. Mechanism: Selective COX-2 inhibitor → blocks PGE₂ synthesis → ↓ pain & inflammation. Spares COX-1 → gastric mucosa protected.

7. Prescription:

Rp.: Celecoxibum 200 mg
     caps. d.t.d. No. 30
S.:  1 capsule once daily with food.

Station 3

8. Duration: 4–6 weeks per course; minimum effective dose, reassess regularly.

9. Side effects:

CV: ↑ MI/stroke risk (main concern)
GI: dyspepsia, nausea (less ulcerogenic than NSAIDs)
Renal: edema, fluid retention
Rare: rash, transaminase elevation

10. Contraindications:

Severe cardiovascular disease (post-MI, stroke, heart failure)
Sulfonamide allergy
Severe hepatic/renal impairment
Pregnancy (3rd trimester)

Now explain but not too much all station

Case 3 — Full Explanation

Station 1

1. Diagnosis — Osteoarthritis (OA), right knee

The clues are: age 57, mechanical pain (worse with exertion and by end of day), brief morning stiffness (OA stiffness is <30 min, unlike RA which is >1 hour), and only mildly elevated CRP. This points to degenerative joint disease, not inflammatory arthritis.

2. P-drug — Celecoxib

NSAIDs are the first choice for OA pain. However, this patient had a peptic ulcer one year ago — non-selective NSAIDs (ibuprofen, diclofenac, naproxen) block both COX-1 and COX-2, and COX-1 inhibition destroys the gastric mucosal protective barrier, risking ulcer recurrence. Celecoxib selectively blocks only COX-2, leaving COX-1 intact, so it is the safest NSAID option for this patient.

3. Dosage form — Oral capsules

Convenient for outpatient use, consistent absorption, suitable for chronic intermittent therapy.

4. Dosage — 200 mg once daily

This is the standard approved dose for OA. Can be split to 100 mg twice daily if once-daily causes GI discomfort.

Station 2

5. Pharmacokinetics

After oral intake, celecoxib is well absorbed with peak levels at ~3 hours. Food (especially fatty meals) increases absorption. It is heavily bound to plasma albumin (97%), meaning little free drug circulates. It is metabolized in the liver by the CYP2C9 enzyme — important because drugs that inhibit CYP2C9 (e.g., fluconazole) can raise celecoxib levels. Its half-life is ~11 hours, allowing once-daily dosing. It is excreted mainly through feces, with some via urine.

6. Mechanism of Action

Arachidonic acid is converted by COX enzymes into prostaglandins, which sensitize pain receptors and cause local inflammation, swelling, and fever.

COX-1 is always active ("housekeeping") — protects gastric mucosa, supports platelet aggregation, maintains renal blood flow
COX-2 is induced during inflammation — drives prostaglandin-mediated pain and swelling

Celecoxib selectively blocks COX-2 only → reduces prostaglandin production at the inflamed joint → less pain and swelling, without disrupting the gastric protective COX-1 pathway.

7. Prescription

Republic of Kazakhstan
Medical Organization: Polyclinic No.1, Almaty
Date: 15.01.2025

Patient: M., 57 y.o.

Rp.: Celecoxibum 200 mg
     caps. d.t.d. No. 30
S.:  Take 1 capsule (200 mg) once daily with food.
     Duration — 4 weeks.

Physician signature: ______    Personal stamp: [seal]
Institution stamp: [triangular seal]

Station 3

8. Duration of Treatment

OA is a chronic disease, but NSAIDs should not be used continuously long-term due to cardiovascular and renal risks. The approach is 4–6 week symptomatic courses, with regular reassessment. Use the lowest effective dose. On pain-free days, the drug can be skipped. Non-pharmacological measures (weight loss, physiotherapy, knee support) should accompany treatment.

9. Side Effects

The most important concern with celecoxib is cardiovascular — long-term COX-2 inhibition shifts the prostacyclin/thromboxane balance toward prothrombotic state, increasing the risk of myocardial infarction and stroke. This is why it is used at the lowest dose for the shortest duration.

GI side effects (nausea, dyspepsia) still occur but are significantly less than with non-selective NSAIDs. It does not cause the classic NSAID gastric ulcer but is not entirely risk-free, especially at high doses.

Renal effects include fluid retention and edema due to reduced prostaglandin-mediated renal vasodilation — monitor in elderly patients.

Skin rash is possible; rarely Stevens-Johnson syndrome.

10. Contraindications

Established cardiovascular disease (recent MI, stroke, significant heart failure) — COX-2 inhibitors increase thrombotic risk
Sulfonamide allergy — celecoxib has a sulfonamide side chain; cross-reactivity is possible
Severe liver disease — CYP2C9 metabolism is impaired, drug accumulates
Severe renal impairment (GFR <30) — risk of acute kidney injury
Pregnancy, 3rd trimester — prostaglandins are needed for fetal ductus arteriosus patency; COX-2 inhibition can cause premature closure
Active GI bleeding — although safer than non-selective NSAIDs, still relatively contraindicated

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