Post on 26-Jun-2015
description
DRUGS AFFECTING
RESPIRATORY SYSTEM
AsthmaA disease of the airways
characterized by :hyper-responsiveness of the tracheo-bronchial tree to a multiplicity of stimuli
Manifested physiologically by :widespread reversible narrowing of the air passages clinically by :paroxysm of coughing, dyspnea, and wheezes
Drugs Affecting AsthmaCromolyn & Nedocromil
Beta-Agonists
Methylxanthine
Corticosteroids
Cromolyn Sodium & Nedocromil
-MOA: alteration in the function of delayed chloride channels in
-the cell membrane, inhibiting cell activation
-Inhibiting parasympathetic and cough reflexes
-Inhibition of the early response to Ag challenge
-Inhibition of the inflammatory response
-inhibiting mediator release from bronchial mast cells
-Taken prophylactically-Used as aerosol
Cromolyn Sodium & Nedocromil
- Effectively inhibit both antigen- and exercise-induced asthma & reducing symptoms of allergic rhinoconjunctivitis
Side Effect: - throat irritation, cough, mouth dryness,
- chest tightness and wheezing,
- reversible dermatitis, - myositis, - gastroenteritis, - pulmonary infiltration with eosinophils and anaphylaxis
METHYLXANTHINE DRUGS
Caffeine (1,3,7-trimethyxanthine)Theobromide (3,7-dimethylxanthene)Theophylline (1,3-dimethylxanthine)
Most commonly used
Derivatives: Aminophylline Dyphylline oxtriptylline
Mechanism of action:
inhibit cyclic nucleotide phosphodiesterases → high
Concentration of IC cAMP & cGMP → smooth muscle relaxation
Inhibition of cell surface receptors for
adenosine
= Enprofylline: xanthine derivative devoid of adenosine antagonism
anti-inflammatory effect : inhibit synthesis & secretion of inflammatory mediators from mast cells & basophils
• Pharmacodynamics:
– CNS :
• mild cortical arousal w/ increased alertness & deferral of fatigue
• nervousness; insomnia
– CVS:
• have positive inotropic and chronotropic effects• sinus tachycardia and increased cardiac output• rises the PVR and BP slightly• decrease blood viscosity and may improve
blood flow
• Pharmacodymanics:
– GIT: • stimulate secretion of gastric acid and digestive
enzymes
– Kidneys: • weak diuretics
– Skeletal muscles: • have potent effects in improving contractility and in
reversing fatigue of diaphragm in patient with COPD
– Smooth muscle: • inhibit antigen-induced release of histamine from
lung tissue
• Pharmacokinetics:
– Absorbed readily & completely
– Food slows the absorption of theophylline
– 40% protein bound
– Distributed into all body compartments
– Cross the placenta & pass into breast milk
– Metabolism: liver by CYP 1A2 enzyme
– 10% excreted unchanged
– Half-life: 3.5 hrs – children; 8 or 9 hrs – adult
– Usual dose: 3-4 mg/kg every 6 hours
• Drug Interactions:
– Erythromycin, cimetidine, cirrhosis, CHF, acute pulmonary edema - half-life
– Phenytoin, barbiturates, cigarette smoking, rifampicin, oral contraceptives - clearance
b. Non-selective Beta-Agonists:Non-selective Beta –R agonist
- Epinephrine- Rapid acting- Injected SC or inhalation- Onset: 15 minutes- DOA: 60-90 minutes- SE: tachycardia, arrhythmias, worsening
of the angina pectoris
- Ephedrine- Longer duration of action - Orally/parenterally administered- Lower potency- More pronounced central effects
Beta-R agonist
Beta-2 Selective Agonists
• Short-acting: – Used only for symptomatic relief of asthma
– Terbutaline, albuterol, levalbuterol, metaproterenol, pirbuterol
• inhaled drugs: – onset of action: 1-5 min., – Peak effects: 15-30 min., – Duration of action: 2 – 6 hours
Salmeterol (SEREVENT®)
Salmeterol is a selective, long-acting b2-adrenergic agonist
Longer chain 10,000 times more lipid soluble
ATPAC
cAMP
Relaxation
Corticosteroids- Improving all indices of asthma: severity of
symptoms, tests of airway caliber, bronchial reactivity, frequency of exacerbation and quality of life
- Inhibiting airway inflammation: - modulation of cytokine & chemokine production, - (-) of eicosanoid synthesis, - (-) of accumulation of basophils, eosinophils & other
leukocytes in lung tissue, - decrease vascular permeability
Corticosteroids- Preparations: a. oral: prednisone b. IV: methylprednisolone c. aerosol: beclomethasone, flunisolide,
budesonide, triamcinolone, fluticasone, mometasone
- SE:- oral candidiasis, hoarseness,
slow the rate of growth in children, decrease bone mineral density, cataract, mood disturbances, appetite, & impaired glucose control in diabetics
-
Fluticasone propionate(Flixotide, Flovent)
Is a synthetic, trifluorinated corticosteroid with potent anti-inflammatory activity
A human glucocorticoid receptor agonistwith an affinity 18 times greater than dexamethasone, almost twice that of beclomethasone-17-monopropionate
Pharmacokinetics
The oral systemic bioavailability of Fluticasone propionate is negligible (<1%),
Vd: 4.2 L/kgProtein bound: 91%Elimination half-life: 7.8 hr in urine
Drugs affecting COPD
Major factor :CIGARETTE
Beta-AgonistsCorticosteroids Ipratropium bromide) a
quarternary ammonium derivative of atropine(
Drugs Affecting Rhinit Allergic
Rhenit:Inflamatory of the nasal mucus membrane
Symptom:Sneezing-Runny nose Itchy nose-congestion
MOA ?
Treatment of the Rhinit Antihistamines+DecongestantsFirst therapeutic line
Diphenhydramide,chlorpheniramine Loratadine, Terfenadine, Astemizole
Treatment of the Rhinit
Alpha-R agonistsphenylephrine: DecongestantLong-acting agent :Oxymethazoline
Corticosteroids Like :Beclomethazone,Triamcinolone Nasal spry Cromolyn sodium (Nasal)
Antitussives1. Narcotic antitussives:
codeine2. Non-narcotic
antitussive: DextromethorphanClobutinol Expectorant Mucolytic Agents
Guaifenesin
Bromhexine
Any Question ?
Special Tnx:
Dr borushki(PRO of pharmacology)
And
Tnx for your attention
Be Happy