1 drugs affecting respiratory system. 2 asthma chronic inflammatory airway disease excessive...
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ASTHMAASTHMAchronic inflammatory airway disease excessive tracheobronchial reactivity
SYMPTOMSwheezing, chest tightness, restlessnesscough, dyspnea Mostly in night / early morning
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ASTHMA ASTHMA –– 5% POPULATION 5% POPULATION
ALLERGIC FAMILY HISTORY HYPERSENSITIVITY Ig E MEDIATED RESP INFECTIONS DRUGS CHEMICAL
IRRITANTS
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TRIGGERING FACTORSTRIGGERING FACTORS RESPIRATORY INFECTIONS Cold Air Fog Wood smoke; tobacco smoke Emotions Stress Laughter Anxiety Exercise (dry, cold weather especially ) OCCUPATION
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INTERACTIONSINTERACTIONS
Airway inflammatory cells,
Inflammatory mediators,
Cytokines,
Surface epithelium.
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CELLS INVOLVEDCELLS INVOLVED Mast cells, Eosinophils,
T-lymphocytes,
Macrophages,
Neutrophils,
Epithelial cells
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CHEMICAL MEDIATORSCHEMICAL MEDIATORS
HISTAMINE
LEUKOTRIENE
BRADYKININ
PLATELET ACTIVATING FACTOR
PROSTAGLANDIN E2, F2, D2
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Rationale for Pharmacological Rationale for Pharmacological Intervention Intervention
Reduction of mast cell degranulation
– Sympathomimetic agents
– Cromolyn / Nedocromil
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Rationale for Pharmacological Rationale for Pharmacological Intervention Intervention
Reduction of cholinergic influence from vagal motor nerves – Antimuscarinic agents
Direct relaxation of airway smooth muscle – Sympathomimetic drugs – Theophylline
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Agents acting on Beta Adrenergic Agents acting on Beta Adrenergic ReceptorsReceptors
Albuterol Bitolterol Pirbuterol Salmeterol Terbutaline Ephedrine Epinephrine Ethylnorepinephrine Isoetherine Isoproterenol Metaproterenol
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Sympathomimetic DrugsSympathomimetic Drugs ACTIONS ACTIONS
Relax airway smooth muscle
May Inhibit release of some mast cell bronchoconstrictive mediators
May inhibit microvascular leakage
May increase mucociliary transport
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ßß2 receptor activation2 receptor activation
Relaxation of airway smooth muscle
Skeletal muscle tremor (toxicity)
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Beta 2 agonistsBeta 2 agonists
Short acting Albuterol, Pirbuterol, Epinephrine,
Terbutaline. Route : Inhalational Uses : Acute conditions & Symptomatic
treatment of asthma No anti inflammatory action Never used as sole agent Side effects : Tachycardia, Hyperglycemia,
tremors.
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Beta 2 agonistsBeta 2 agonists
Long acting : SALMETEROL
SLOW ONSET OF ACTIONLONG DURATION OF ACTION : 12 hrs
NOT FOR ACUTE ASTHMATIC ATTACKUSED for Maintainance
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Anticholinergic Agent
– Ipratropium bromide– Competitive blocker of muscarinic receptors –
prevents bronchoconstriction.
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IpratropiumIpratropium
DOC for beta-blocker-induced bronchospasm
USEFUL FOR Pt. INTOLERANT TO BETA 2 AGONISTS
MORE USEFUL IN ELDERLY
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MAST CELL STABILIZERSMAST CELL STABILIZERS
CROMOLYN , NEDOCROMIL
Chloride-mediated channel effects: Inhibition of cough Inhibition of early response to antigens
(mast cells) Inhibition of late response to antigens
(eosinophils)
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CROMOLYN, NEDOCROMILCROMOLYN, NEDOCROMIL
PROPHYLACTIC ANTI INFLAMMATORY
NO DIRECT ACTION ON AIRWAYS
NOT USEFUL IN ACUTE. ASTHMATIC ATTACK
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USES : PROPHYLACTIC AGENT FOR– EXERCISE INDUCED ASTHMA– ALLERGEN INDUCED ASTHMA
SIDE EFFECTS : THROAT IRRITATION , COUGH
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METHYLXANTHINESMETHYLXANTHINES
THEOPHYLLINE ( AMINOPHYLLINE )
ACTION : DIRECT BROCHODILATORMech :??
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Central Nervous System Central Nervous System EffectsEffects
Increased alertness; reduced fatigue
In more sensitive individuals: nervousness/insomnia
Very high methylxanthine doses: medullary stimulation, convulsions
Primary side effect in patients requiring aminophylline (large doses) for control of asthma: nervousness & tremor
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Cardiovascular Effects: – direct positive chronotropic – direct enhanced myocardial contractility
GIT Effects: – enhanced secretion of gastric acid and digestive
enzymes
Renal Effects: – weak diuretics-- not therapeutically important
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THEOPHYLLINE - USETHEOPHYLLINE - USE
Relieves airway obstruction:
– In acute asthma
– Reduces symptoms severity
– In chronic asthma
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THEOPHYLLINE THEOPHYLLINE –– SIDE SIDE EFFECTSEFFECTS
Nausea, Headache, Insomnia, Nervousness
Seizures, Neuromuscular irritability, Tremor,
Arrhythmias, hypokalemia, hyperglycemia, vomiting
IV push - seizures/cardiac arrhythmias
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Corticosteroids Corticosteroids NO DIRECT ACTION OVER AIRWAYS
INHIBIT INFLAMMATIONDECREASE ACTIVITY OF CELLSDECREASES RELEASE OF
MEDIATORSDECREASE HYPERRESPONSIVENESS
OF AIR WAYSDECREASES MUCOSAL EDEMA
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CORTICOSTEROIDS - USESCORTICOSTEROIDS - USESStatus asthmaticus (Combination with Beta 2
agonists)
For management of acutely ill patients
Patients not adequately maintained with bronchodilators
Patients whose symptoms are worsening, despite reasonable maintenance treatment
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ADVERSE EFFECTSADVERSE EFFECTSInhaled topical corticosteroids: oropharyngeal
candidiasis Hoarseness: local effect -- vocal cords Suppression of hypothalamic-pituitary-adrenal
axis Decreased bone density , delayed pubertyCataract formation High doses:
– dermal thinning – glaucoma
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Other drugsOther drugsInterruption of leukotriene Interruption of leukotriene
pathwayspathways
Inhibition of 5-lipoxygenase-- Zileuton
Rationale: Prevents leukotriene synthesis Effective for maintenance treatment of
asthma Requires monitoring for hepatic toxicity
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Inhibition of leukotriene D4 Inhibition of leukotriene D4 receptor bindingreceptor binding
Zafirlukast Montelukast
Less effective than steroids
SIDE EFFECT : BLEEDING COMPLICATIONS
Monitor hepatic function
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Drugs to Treat CoughDrugs to Treat Cough What causes a cough?
– Irritation of mucosal surfaceInflammation, hypersecretion
Solutions:– Decrease sensitivity of CNS cough center,
decrease secretionsCodeine, Hydrocodone, HydromorphoneDextromethorphan
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Drugs for Allergic RhinitisDrugs for Allergic Rhinitis The Problem:– Inflammation of mucous membranes– IgE-mediated– Mast cell degranulation
The solution:– Antihistamines (eg:
Diphenhydramine)– α-adrenergic agents (eg:
Phenylephrine)– Steroids (eg: Beclomethasone)– Cromolyn
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Presents mainly with sneezing, nasal itching, watery rhinorrhea and congestion.
H/O – allergen will be there
Rx - Oral antihistamines + decongestants.
In the form of intranasal spray.
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ANTIHISTAMINESANTIHISTAMINES
H1 receptor blockerDiphenhydramineClorpheniramineLoratidineTerfenadineAstemizoleCetirizine
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Alpha adrenergic agonistsAlpha adrenergic agonists
PhenylephrineOxymetazolineEphedrinePhenylpropanolamineTetrahydrozolineNaphazolineXylometazoline
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Drugs to Treat COPD Drugs to Treat COPD The Problem:
– Chronic, irreversible airflow obstruction
– Variety of causes The Solutions:
– β2 agonists
– Theophylline– Glucocorticoids– Ipratropium