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