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Respiratory Pharmacology

Respiratory Pharmacology. ‘ Tis the Season for Sneezin’ and Wheezin’. Human Nervous System. Central Nervous System Brain Spinal Cord Peripheral Nervous System Arising from the vertebrae Autonomic Nervous System controlled through hormonal mediator release. Autonomic Nervous System.

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Respiratory Pharmacology

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  1. Respiratory Pharmacology ‘ Tis the Season for Sneezin’ and Wheezin’

  2. Human Nervous System • Central Nervous System • Brain • Spinal Cord • Peripheral Nervous System • Arising from the vertebrae • Autonomic Nervous System • controlled through hormonal mediator release

  3. Autonomic Nervous System • Parasympathetic • neural transmitter substance • acetylcholine • cholinergic response • responsibility • maintaining calm operations • smooth muscle constriction • bronchoconstriction • pulmonary vasoconstriction

  4. Autonomic Nervous System • Sympathetic • neural transmitter substance • nor-epinephrine [adrenaline] • adrenergic response • responsibility • ‘Fight or Flight’ • smooth muscle relaxation • bronchodilation • pulmonary vasodilation

  5. The Role of Cyclic AMP • Smooth Muscle Relaxation • Promotes bronchodilation • Pulmonary Vasodilation • Beta 2 Effect

  6. What Does It Look Like?

  7. A Closer Look

  8. How Does It Work?

  9. 2nd Messenger SystemsGeneral Function

  10. 2nd Messenger Systems • For a second messenger to work effectively it must have the following characteristics: • Amplification – when a few hormone molecules signal the cell, it needs to respond with a signal that is strong enough to get a job done without repeated high levels of stimulation. • Control --- eventually a response must be shut down, and there are instances when its necessary to respond a little or a lot – so control is needed. • Specificity – when a hormone is released, a given cell should respond in a specific way. Not all cells will respond to this hormone. The hormone may not have the same effect in all the cells tat do not respond.

  11. Receptors and Effectors

  12. Receptor Function • As you can imagine the challenge of pharmacology is to find agonists (+) and antagonists (-) for specific receptors. For instance, beta stimulation increases the heart rate and dilates the smooth muscle leading to the bronchi. If a beta blocker is used to slow the heart rate, it could have a very undesirable effect of cutting off oxygen. However B1 receptors primarily affect the heart and B2 receptors the constriction of the airways

  13. Chronic Obstructive Airway Diseases • Cystic Fibrosis • Bronchitis [acute - chronic] • Asthma • Bronchiectasis • Emphysema

  14. Manifestations of An Asthma Attack • Bronchospasm • Irritable [twitchy] Airways • Inflammation • Increased Mucous Production

  15. Classes of Respiratory Drugs • Sympathomimetic Amines • Parasympatholytics • Methyl Xanthines • Mediator Antagonists • Inhaled Steroids • Mucolytics • Anti-Infectives • Exogenous Surfactants

  16. Sympathomimetic Amines • Also Called • Beta agonists • Beta adrenergic bronchodilators • Catecholemines • Alpha agonists • decongestant • vasopressor • vasoconstrictor • Examples • albuterol sulfate (Proventil] • metaproteranol (Alupent} • epinephrine

  17. Sympathomimetic Amines • Effects • Short Term • acute rescue use • immediate response • albuterol (Proventil) • Long Term • maintenance • prophylaxis • salmeterol (Serevent)

  18. Sympathomimetic Amines • Major Action • Stimulate production of cyclic AMP • Smooth muscle relaxation • Bronchodilation • Pulmonary vasodilation • Routes • inhaled via nebulizer or MDI • PO, GI • sub-Q ( terbutaline ]

  19. Sympathomimetic Amines • Side Effects • Cardiovascular (B1) • tachycardia • hypertension • Somatic tremor • Nausea • Insomnia

  20. Parasympatholytics • Also Called • Anticholinergics • Examples • atropine sulfate • ipratropium bromide ( Atrovent ] • Major Action • inhibits acetylcholine release • limits bronchoconstriction

  21. Parasympatholytics • Routes • inhalation via nebulizer and MDI • Side Effects • cardiovascular • tremors • peripheral pooling • atropine flush • nausea • allergic reactions (Atrovent) • drying of secretions

  22. Methyl Xanthines • Also Called • Xanthines • Phosphodiesterase Inhibitors • PDI;s • Examples • theophylline • Aminophylline • Theodur • Luflyn

  23. Methyl Xanthines • Major Action • Inhibits the breakdown of cyclic AMP into 5 AMP • maximizes cyclic AMP • Routes • IV • PO • Cannot aerosolize **

  24. Methyl Xanthines • Side Effects • nausea (titrate) • tachycardia • CNS stimulation • insomnia • caffeine-like effects • bad taste in mouth • Therapeutic Serum Levels • 10 to 20 mcg/m/L

  25. Mediator Antagonists • Also Called • Prophylactic bronchodilators • Examples • cromolyn sodium (Intal) • nedocromil (Tilade) • leukotrine inhibitors • montelukast (Singulaire) • zafirlukast (Accolate) • zileuton (Zyflo)

  26. Mediator Antagonists • Major Action • mast cell inhibition • cromolyn sodium (Intal) • nedocromil (Tilade) • leukotrine inhibition • montelukast (Singulaire) • zafirlukast (Accolate) • zileuton (Zyflo)

  27. Mediator Antagonists • Routes • cromolyn sodium (Intal) • MDI, DPI, SVN (ampoule) • Intranasal spray • nedocromil (Tilade) • MDI • zafirlukast, montelukast zileuton • oral tablets

  28. Mediator Antagonists • Side Effects • Inappropriate usage • Not for use in acute episodes • May cause bronchospasm via mechanical irritation

  29. Inhaled Corticosteroids • Examples • Dexamethasone sodium phosphate [Decadron, Respirahaler] • Beclomethasone dipropionate [Beclovent, Vanceril,] • Triamcinolone acetonide [Azmacort] • Flunisolide [Aerobid] • Fluticasone propionate [Flovent] • Budesonide [Pulmicort]

  30. Inhaled Corticosteroids • Major Actions • anti-inflammatory • modification of cell transcription • peak action or effectiveness from hours to days depending on the cellular metabolism • not for acute relief • dosages vary • initially used to cause ‘bursts’ for airway clearance

  31. Inhaled Corticosteroids • Routes • MDI • 2 puffs • 5 to 10 second breath hold • 1 minute rest between puff • rinse mouth after treatment • if Bronchodilator via SVN is given, give steroid 10 minutes following SVN treatment • SVN (2000) • Pulmocort • [0.5 ml undiluted]

  32. Inhaled Corticosteroids • Side Effects • Short-Term • anaphylaxis [beclomethoasone] • yeast infections • trouble breathing • wheezing • a tight feeling in the chest • a change in behavior • feeling depressed • feeling restless or nervous • dry mouth

  33. Inhaled Corticosteroids • Side Effects • Long-Term • moon face (Cushingoid) • fluid retention • weight gain • increase in fat pad [dowager’s hump] • osteoporosis • pathologic fractures • glomerulonephritis

  34. Mucokinetic Agents • Also Called • Mucolytics • Mucoactive agents • Mucous controlling agents • Examples • Mucomyst [n-acetylcysteine] • Pulmozyme [dornase alfa] • Bland aerosol therapy • 2% sodium bicarbonate

  35. Mucokinetic Agents • Major Actions[s] • Mucomyst breaks down di-sulfide bonds • Pulmozyme is a proteolytic used primarily for the treatment of cystic fibrosis patients • Bland aerosols mechanically hydrate and loosen secretions • 2% sodium bicarbonate may hydrate or affect mucous bonding

  36. Mucokinetic Agents • Routes of Administration • primarily via SVN • bland aerosols may be administered via large volume nebulizers • may be instilled into endotracheal tubes during bronchoscopy • Mucomyst [n-acetylcysteine] may be administered via ingestion for acetominophen [Tylenol] overdose

  37. Mucokinetic Agents • Side Effects • n-acetylcysteine [Mucomyst] • may precipitate wheezing; a bronchodilator should be added to the aerosol • airway obstruction due to liquefaction of secretions • nausea and rhinorrhea • odor [hydrogen sulfide] • increased drug concentration at the end of treatment • incompatibility with anti-infectives

  38. Mucokinetics • dornase alfa [Pulmozyme] • pharyngitis, laryngitis • rash • chest pain • conjunctivitis • respiratory problems such as cough up to pneumothorax • weight loss • GI syndrome

  39. Mucokinetics • Bland Aerosols • swelling of dried secretions • fluid overload • bronchospasm due to mechanical irritation • mucosal drying • 2% sodium bicarbonate • mechanical irritation • metabolic alkalosis

  40. Anti Infectives • Also Called • Antimicrobials, Antibiotics • Examples • Pentamidine isethionate (Pentam, NebuPent] • Ribavirin - virazole

  41. Anti Infectives • Aerosolized antibiotics • gentamicin • carbenicillin • colomycin • ceftazidime • gentamicin • tobramycin • garamycin

  42. Anti Infectives • Major Action • Pentamidine - treatment of pneumocystis carinii pneumonia [PCP] - a protozoan. • Ribavirin - treatment of respiratory syncytial virus [RSV] • Aerosolized antibiotics - bacterial organism specific

  43. Anti Infectives • Routes of Administration • Pentamidine - oral or aerosolized every two weeks • Ribavirin - aerosolized via small particle aerosol generator [SPAG] • Aerosolized antibiotics - SVN

  44. Anti Infectives • Side Effects • Pentamidine • cough, bronchial irritation, bronchospasm and wheezing, shortness of breath, fatigue, bad or metallic taste, pharyngitis, conjunctivitis, rash and chest pain. • Decreased appetite, dizziness, rash, nausea, night sweats, chills, spontaneous pneumothorax, neutropenia, pancreatitis, renal insufficiency and hypoglycemia. • Side effects v. the disease ????

  45. Anti Infectives • Side Effects • Ribavirin • skin rash, eyelid erythema and conjunctivitis. • When used in conjunction with mechanical ventilators may cause sticking of exhalation valve and other sensors. • Pulmonary function may deteriorate

  46. Anti Infectives • Side Effects • Aerosolized Antibiotics • bronchospasm • anaphylaxis • need for higher flow rates • right drug - right job

  47. Exogenous Surfactants • Examples • Survanta [beractant] - natural bovine extract • Exosurf [colfosceril palmitate with cetyl alcohol and tyloxapol] - -a synthetic mixture

  48. Exogenous Surfactants • Major Action • Replacement therapy for low L:S ratios • Rescue for RDS infants • Prophylactic in infants less than 1350 grams or who larger infants who show signs of respirator distress

  49. Exogenous Surfactants • Routes of Administration • Instilled directly into endotracheal tubes • Side Effects • Procedural • Physiological

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