RESPIRATORY AND ANTI-TB DRUGS

Characterization of Asthma

Airway inflammation and episodic reversible bronchospasm

Cause of Bronchoconstriction

Release of several mediators from IgE-sensitized mast cells. This attracts inflammatory cells leading to inflammation

Present in airway inflammation

Airway edema (fluid)

Contributes to airflow obstruction and bronchial reactivity

Mucus secretion

Factors to Airflow Inflammation

• Degree of mononuclear cell and eosinophil infiltration

• Mucus hypersecretion

• Desquamation of the epithelium

• Smooth muscle hyperplasia

  • Airway remodeling

Factors in Airflow Obstruction

• Acute bronchoconstriction

• Airway edema

• Chronic mucous plug formation

• Airway remodeling

Cause of Acute bronchoconstriction

Consequence of IgE-Dependent mediator release due to exposure to aeroallergens

Acute bronchoconstriction is considered as a

Primary component of an early asthmatic response

Airway edema occurs for this long following allergen challenge

6-24 hours

Airway edema is known as a

Late asthmatic response

Chrnoic mucous plug consists of

exudate of serum proteins and cell debris taking weeks to resolve

Airway remodeling is due to the

Long stranding inflammation affecting reversibility of obstruction

Components of strategies of asthma therapy

Relievers and Controllers

Relievers role in Asthma Treatment

Acute Attacks - Bronchospasms

Controllers role in Asthma Therapy

Long term- Prophylaxis

Drugs under Relievers

• Bronchodilators

• Short-acting beta-2 agonists

• Muscarinic antagonists

• Methylxanthines

  • IV corticosteroids

Drugs under Controllers

• Antiinflmmatory druugs

• Corticosteroids

• Long-acting beta-2 agonists

• Mast cell stabilizers

• Anti IgE, IL5, IL5R, IL4tR antibodies

  • Leukotrienes

Compound promoting bronchodilation

cAMP

Explain the role of cAMP in bronchodilation

cAMP is increased by beta-adrenoceptor agonists whinch increases the rate of synthesis by adenylyl cyclase or by phosphodiesterase inhibitors

apart from cAMP, Bronchoconstriction can be inhibited by

Muscarinic antagonists and adenosine antagonists

beta-2 selective agonists (short acting) drugs

Salbutamol (Albuterol), Terbutaline, Metaproterenol

Uses for short acting beta-2 agonists

DOC for acute asthma attack

Long acting beta-2 agonists drugs

Salmeterol, Formoterol, Bambuterol, Clenbuterol

Use of long acting beta-2 agonists

Asthma prophylaxis (with inhaled corticosteroid)

MOA of beta-2 agonists

Activates beta-2 receptors in bronchial smooth muscle causing bronchodilation. Potentiation with corticosetorid

Adverse effects of beta-2 agonists

• Tachycardia

• Tremors

• Nervousness

• Restlessness

• Arrythmia

Muscarinic Receptor Antagonist Drugs

Ipratorpium, Tiotropium, Umecllidinium, Glycopyrronium

MOA of Muscarinic Receptor Antagonists

Blocks muscarinic receptors. Prevents vagal-stimulated bronchoconstriction

Uses for Muscarinic Receptor Antagonists

Acute Asthma and COPD

Uses for Glycopyrronium

Monotherapy for COPD and antispasmodic and reduce salivation with some anesthetics

Adverse Effects of Muscarinic Receptor Antagonists

Dry mouth, blurred vision

Methylxanthines drugs

Theophylline, Aminophylline, Pentoxifylline, Doxofylline

MOA of methylxanthines

Phosphodiesterase inhibiton and Adenosime receptor antagonists for bronchodilation

Uses for methylxanthines

• Asthma (prophylactic against nocturnal attacks)

Uses for Pentoxifylline

Intermittend claudication

Adverse Effects of Methylxanthines

• CN stimulation (insomnia,, seizure, anorexia)

• Cardiac stimulation

• Tremors

Mast Cell Stabilizers Drugs

Cromolyn, Nedocromil, Loxoxamide

MOA or Mast Cell Stabilizers

Prevents calcium influx and stabilizes mast cell to prevent degranulation nad release of hhistamine, leykotrients and other mediators

Uses for Mast Cell Stabilizers

Asthma prophylaxis, Allergies (opthalmic, nosopharyngeal, gastrointestinal)

Adverse effects of mast cell stabilizers

Cough, airwar irritation

Corticossteroids Drugs

Fluticasone, Beclomethasone, Budesonide, Ciclesonide, Flunisolide

MOA of corticosteroids

Inhibits synthesis of arachidonic acid by inhibiton of phopholipase A.

Reduuces expression of COX and LT

Increases responsiveness of beta receptors

Uses of corticosteroids

• DOC for asthma prophylaxis

• COPD

• Allergic rhinitis

  • 1st line of treatment for severe bronchial assthma

Adverse effects of corticosteroids

Oropharyngeal candidiasis, minimal systemic steroid toxicity

Leukotriene Synthesis Inhibitor

Zileuton

Leukotriene Synthesis inhibitor MOA

Inhibits 5-lipoxygenase. Reduuces synthesis of leukotrienes preventing airway inflammation and bronchoconstriciton

Uses for Leukotriene Synthesis Inhibitor

• Asthma prophylaxis

• Exercise- Antigen- and Aspirin-induced bronchospasm

Adverse effects of Leukotriene synthesis inhibitor

• Flulike syndrome

• Headache

• Drowsiness

• Dyspepsia

  • Hepatitis

Anti IgE Antibodies Drugs

Omalizumad

MOA of Anti IgE Antibodies

Binds to igE antibodies on sensitized mast cells. Reduces reaction to inhaled antigen and precents activation of asthma triggers

Uses of Anti IgE Antibodies

Prophylaxis of severe refractory asthma

Adverse effects of Anti IgE Antibodies

• Fever

• Angioedea

• Anaphylactic reactin

• Idiopathic severe thrombocytopenia

• Nasopharyngitis

  • Upper absominal pain

Explain GINA Asthma Management 2025

A reflex protecting airway and lungs against irritant

Courgh

How far does a cough propel air and particles

50 mph

Role of Cough

Clears throat of germs, mucus, and dust

Causes of Cough

• Allergies

• Asthma and COPD

• Common colds

• Glu

• Viral infection, lung infection

• Sinusitis

• GERD

Explain the mechanism of cough

1. Stimulation of mechano- or chemoreceptors

2. Afferent impulses to cough center

3. Efferent impulses via parasympathetic and motor nerves to the diaphragm, intercostal muscles, and lungs

4. Increased contraction of diaphragmatic, abdominal and intercostal muscle

5. Cough

Mucolytics Drugs

N-Acetylcysteine, Carbocisteine, Ambroxol, Bromhexine, Erdosteine

Mucolytics MOA

Decreased septym activity, derivatives is cyteine; reduces disulfide bridges that binds glycoprotein to other protein. Acts as antioxidants and reduces airway inflammation

Uses of Mycolytics

Cough

Adverse Effects of Mucolytics

• Chest tightness

• Drowsiness

• Fever

• Hemoptysis

• Increased volume of bronchial secretion

• Irritation of tracheal or bronchial tract

• Nausea

• Rhinorrhea

  • Vomiting

Uses of N-acetylcysteine

Management of acetaminophen toxicity preventil fulminant hepatitis

Expectorant Drugs

Guaifenesin

Expectorant MOA

Act as irritant to gastric vagal receptors and recruit efferent parasympathetic reflexes causing glandular exocytosis of a less viscous mucus mixture

Uses for Expectorants

Cough

Adverse Effect of Expectorrant

• Drowsiness

• Incomplete or Infrequent Bowel Movements

• Inducing of a Relaxed State

• Stomach Cramps

• Dizziness or Headache

• Rash

• Nausea

• Vomittine

• Stomach Upset

Central acting opioids Drugs

Dextromethorphan and Codeine

Central acting opioids MOA

Decreased sensitivity of the medullary/CNS cough centers to peripheral stimuli and decrease mucosal secretion

Uses of Centrally acting opioid

Cough

Adverse Effects of Centrally acting opioid

• Decreased secretions in the bronchioles

• Thicken septum and inhibited ciliary activity

• Reduced clearanced or thickened septum

• Constipation

Central acting non opioid Drug

Butamirate Citrate

Central acting non-opioid Drug

Butamirate citrate

Central acting non-opioid MOA

Act through receptors in the brainstem to inhibit cough

Uses of Central acting non opioid

Cough

Adverse Effects of Central acting non-opioid

• Somnolence

• Nausea

• Vomiting

• Dirrhea

• Dizziness

• Hypotension

Peripheral acting drugs

Levodropropizine

MOA of Peripheral acting drugs

Inhibits the afferent pathways that generate the cough reflex (modulate C-fibers activity)

Cough center of the brain

Medulla

Uses of Peripheral acting drugs

Cough

Adverse effects of Peripheral acting drugs

• Nausea

• Vomiting

• Heartburn

• Diarrhea

• Fatigue

• Weakness

• Drowsiness

• Dizziness

• Headache

• Palpitations

Tuberculosis agen

Mycobacterium tuberculosis

Characteristics of Mycobacterium tuberculosis

Rod-shape, non-spore-forming, thin aerobic bacterium

Mycobacterium tuberculosis in gram stain

Neutral

Mycobacterium tuberculosis in Acid alcohol

Not decolorized - Acid-fast

Pathogenesis of Tuberculosis

1. Introduction of bacteria via droplet propelled in the air by infected patient

2. Inactivated alveolar macrophage phagocytose the bacilli

3. Adhesion to macrophage result to binding of the cell wall to a variety of macrophage cell molecules

4. Phagocytosis is enhanced by complement activation, leading to opsonization of bacilli

Explain the survival mechanisms of Mycobacterium tuberculosis

• Depends on the reduced acidification dur to lack of assembly of a complete vascular proton-ATP

  • Blocking autophagy

Nicotinic acid derivatives drugs

Isoniazid

Nicotinic acid derivative MOA

Inhibits mycolitic acid synthesis

Nicotinic acid derivative type of antibiotic

Bactericidal

Uses of Nicotinic acid derivative

Tuberculosis (active, latent, prophylaxis)

Adverse effects of Nicotinic acid derivative

• Hepatitis

• Neurotoxicity

• Drug induced Lupus

Rifamycins drugs

Rifampicin, Rifabutin, Rifapentine, Rifamixin

Rifamycin MOA

Inhibits DNA-dependent RNA polymerase inhibiting RNA production

Type of antibiotic Rifamycin

Bactericidal

Rifamycin Uses

• Tuberculosis (Active, latent, prophylaxis)

• Leprosy

• Atypical mycobacterium

  • Prophylaxis of meningococcal

Adverse effects of Rifamycins

• Red-orange body fluids

• Light chain proteinuria

• Skin rash

• Thrombocytopenia

Pyrazine derivatives Drugs

Pyrazinamide

Pyrazinamide MOA

Convert active pyrazionic acid under acidic condition

Pyrazinoic acid distupt mycobacterial cell membrane metabolism and transport function

Uses of Pyrazinamide

Active Tuberculosis