Lesson 6 Drugs for the Respiratory System PDF

Drugs Affecting the Respiratory System Antihistamines, Decongestants, Antitussives and Expectorants Common Cold Most colds are caused by viral infections: Rhinovirus Influenza Common Cold Virus invades the mucosa of the upper respiratory tract, nose, phary...

Drugs Affecting the Respiratory System Antihistamines, Decongestants, Antitussives and Expectorants Common Cold Most colds are caused by viral infections: Rhinovirus Influenza Common Cold Virus invades the mucosa of the upper respiratory tract, nose, pharynx and larynx Signs and symptoms: excessive mucous production leads to sore throat, coughing & upset stomach Treatment: reduce symptoms Note: antibiotics do not help viral infections  Histamine Histamine: an organic compound that triggers the inflammatory response and local immune responses Histamine receptors H1 through H4 are found on smooth muscle, endothelium, and central nervous system tissue Stimulation of histamine receptors causes;  vasodilation  bronchoconstriction  smooth muscle activation and separation of endothelial cells (responsible for hives)  pain and itching due to insect stings Histamine Histamine 10% to 20% of general population is sensitive to various environmental allergies Histamine-mediated disorders: Allergic rhinitis (hay fever, mold and dust allergies) Anaphylaxis Angioneurotic edema Drug fevers Insect bite reactions Urticaria (itching) Antihistamines Action: acts directly on histamine receptor sites Antihistamines have several properties: Antihistaminic Anticholinergic Sedative Antihistamines Block the action of histamine at the H1 receptor sites Compete with histamine for binding at unoccupied receptors Cannot push histamine off the receptor if already bound More effective in preventing the actions of histamine rather than reversing them Should be given early in treatment, before all the histamine binds to the receptors Antihistamines The binding of H1 blockers to the histamine receptors prevents the adverse consequences of histamine stimulation: Vasodilation Increased GI and respiratory secretions Increased capillary permeability Antihistamines 1. Antihistamines associated with sedation 2. Non-sedating antihistamines Antihistamines Antihistamines: sedating Classification: H1 antihistamine diphenhydramine (Benadryl®) Antihistamines: diphenhydramine Generic name: diphenhydramine Trade name: Benadryl® One of the oldest anti-histamines Concentration: 50mg/ml Pharmacodynamics: Antagonizes the effects of histamine at the H1 receptor sites. Antagonism is achieved through blocking the effect of histamine more than blocking its production and release. Inhibits most responses of smooth muscle to histamine and acts as a vasoconstrictor by inhibiting the vasodilator effects of histamine Also has some antiemetic effects and significant sedative side effects Antihistamines: diphenhydramine Pharmacokinetics: Absorption:  Onset: IV 5-10min, IM: 30-60min PO: within 60min  Peak: IV 1 to 4 hours  Duration: IV 3 to 6hours, PO: 4 to 6hours  Half-Life: 4 to 6 hours Metabolism: liver Distribution: widely distributed throughout body, including CNS. Distributed by protein binding and bound to plasma proteins. Bioavailability: 100% when given IM or IV (any first-pass effect?) Elimination: ultimately eliminated by the kidneys slowly, mainly as inactive metabolites via urine. Antihistamines: diphenhydramine Precautions: has an atropine-like action and therefore, should be used with caution in patients with: a history of bronchial asthma increased intraocular pressure hyperthyroidism cardiovascular disease Hypertension Lower respiratory disease Adverse Effects: Significant CNS depressant: drowsiness, dizziness, hypotension, dry mouth, nausea and nervousness may occur. Antihistamines: diphenhydramine Indications: Exposure to probable allergen; AND S & S of a moderate to severe allergic reaction Conditions: Weight > 25kg Contraindications: Allergy or sensitivity to diphenhydramine  Diphenhydramine (Benadryl ®) Treatment: Weight Weight >25kg to 50kg Route Route Route Route IV IV IM IM Dose 25 mg 50mg 25mg 50mg Max. Single Dose 25 mg 50mg 25mg 50mg Dosing Interval N/A N/A N/A N/A Clinical considerations Max. # of doses 1 1 Epinephrine should 1 1 be the 1 medication st administered in anaphylaxis Documenting diphenhydramine (Benadryl) Epinephrine Epinephrine for Anaphylaxis Classification: sympathomimetic Generic Name: epinephrine Trade Name: Epi-Pen, Adrenaclick, Adrenalin Pharmacodynamics: alpha 1 effects: vasoconstriction Beta 1 effects: increased H.R., increased force of cardiac contraction Beta 2 effects (moderate): bronchodilation inhibits histamine release +ve chronotropic, +ve dromotropic and +ve inotropic effects Epinephrine for Anaphylaxis Pharmacokinetics: Absorption:  Onset: IV- 24 hours Antihistamine: Non-sedating Generic name: cetirizine Trade name: Zyrtec® Therapeutic classification: allergy, cold, and cough remedies, antihistamine Action: Antagonizes the effects of histamine at H1 receptor sites; anticholinergic effects are minimal Onset: 30 minutes Peak: 4-8 hours Duration: 24 hours Decongestants Nasal congestion is due to excessive nasal secretions and inflamed and swollen nasal mucosa Three types of decongestants: adrenergic anticholinergic corticosteroids Decongestants Routes of Administration: Oral: produces a systemic effect Inhaled: administered directly into the lungs with some systemic effects Nasal: administered locally with some systemic effects Decongestants Intranasal Adrenergic: Nasally applied directly into the nares which provides a very potent decongestive effect Main side effect: rebound effect (after a few days of use if discontinued can have rebound congestion) Example: Dristan® Decongestant Nasal Mist Decongestants Oral Adrenergic Decongestants: Examples: Sinutab® Dristan® Tylenol Cold® Sudafed® Decongestants Intranasal Corticosteroids: Often used prophylactically to prevent nasal congestion in patients with chronic upper respiratory tract infections Action: aimed at the anti-inflammatory response Trade names: Nasacort® Flonase® Nasalide® Drugs to Treat Coughs 2 main classifications and can be combined Antitussives: Opioid Non-opioid Expectorants Antitussive Drugs All opioid drugs have some antitussive effects Codeine® is the only opioid used as a cough suppressant Action: suppresses the cough reflex through direct action on the cough center in the CNS (medulla) Adverse effects: CNS and respiratory depression with addictive potential Antitussive Drugs Non-opioid Generic name: dextromethorphan Trade names: Vicks Formula 44® Robitussin DM® Safe, non-addicting and does not cause CNS or respiratory depression Used only for nonproductive coughs Expectorants Aid in coughing up excess mucous that has accumulated in the respiratory tract by breaking down and thinning secretions Action: Loosening and thinning respiratory tract secretions Direct stimulation of secretory glands of the respiratory tract Expectorants guaifenesin is the only drug currently available Trade names: Robitussin Mucinex Therapeutic effect: relief of respiratory congestion and cough suppression Bronchodilators and Other Respiratory Drugs Respiratory System System Alveoli Have a very thin membrane that allows rapid diffusion of oxygen and carbon dioxide between capillary blood and alveolar air spaces. Lined with surfactant to prevent alveolar collapse What is diffusion? Alveoli Surfactant Essential fluid that lines the alveoli and smallest bronchioles Reduces surface tension of the lung allowing the oxygen and carbon dioxide across the membrane Diseases of Respiratory System Upper respiratory tract: colds rhinitis hay fever Lower respiratory tract: asthma emphysema chronic bronchitis All involve obstruction of airflow through the airways Bronchial Asthma Recurrent and reversible shortness of breath that occurs when the bronchi and bronchioles become narrow as a result; bronchospasm Inflammation edema of the bronchial mucosa, and the production of viscid (sticky) mucous Bronchial Asthma Allergic Asthma Caused by hypersensitivity to allergens in the environment Allergen: a substance that elicits an allergic reaction Antigen: a substance (usually a protein) that causes the formation of an antibody and reacts with the antibody Antibody: Immunoglobulins (IgE) produced by lymphocytes in response to bacteria, viruses or other antigen substances Stepwise Therapy for Management of Asthma Step 1: mild, intermittent symptoms Quick relief: Short-acting inhaled B 2 agonists salbutamol (Ventolin ®) Salbutamol (Ventolin) MDI & Nebulized  Salbutamol (Ventolin ®) Classification: bronchodilator Pharmacodynamics: selective beta 2 adrenergic receptor stimulation which are predominant receptors in bronchial smooth muscle this promotes bronchodilation by relaxing the muscle fibers some beta 1 effect – especially with repeated doses little or no alpha stimulation beta 1 and beta 2 agonist effects; we expect an: Increase in blood pressure. Increased heart rate. Increased cardiac contractility. Pharmacokinetics: MDI & Nebulized Absorption: Systemic absorption is rapid following aerosol administration Metabolism: not metabolized in the lung but is converted in the liver to the 4’-o-sulphate Distribution: n/a Elimination: Approx. 72% of the inhaled dose is excreted in urine within 24 hours, 28% as unchanged drug and 44% as metabolite. ONSET : 5-15min PEAK : 60-90min HALF-LIFE : 2.7 and 5 hrs DURATION : 3-6 hrs  Salbutamol (Ventolin ®) Indications: Respiratory distress; AND Suspected bronchoconstriction Conditions: NONE Contraindications: Allergy or sensitivity to salbutamol or in nebulization case patients with known or suspected fever or in the setting of a declared febrile respiratory illness outbreak  Salbutamol (Ventolin ®) Treatment: Weight Weight 25kg Route Route Route Route MDI* MDI* NEB NEB Dose Up to 600mcg Up to 800mcg 2.5mg 5mg (6puffs) (8 puffs) Max. Single Dose 600mcg 800mcg 2.5mg 5mg Dosing interval 5-15min PRN for both 5-15min PRN for both Max. # of doses 3 3 *1 puff = ? Documenting Salbutamol (Ventolin) Beta Adrenergic Drugs Nonselective adrenergics: Stimulate alpha, beta1 (cardiac) and beta2 (respiratory) receptors Example: epinephrine Nonselective beta-adrenergics: Stimulate both beta1 and beta2 receptors Example: isoproterenol Selective beta2 drugs: Stimulate only beta2 receptors Example: salbutamol Anticholinergic Drugs Acetylcholine (ACh) causes bronchial constriction and narrowing of the airways Anticholinergics bind to the ACh receptors, preventing ACh from binding Result: bronchoconstriction is prevented, airways dilate NOT used for acute asthma exacerbations Combivent® (salbutamol/ipratroprium) Atrovent® (ipratropium bromide) is the only anticholinergic used for respiratory disease Stepwise Therapy for Management of Asthma Step 2: mild, persistent asthma Short acting inhaled Beta2 agonist prn: salbutamol (Ventolin®) Low dose inhaled corticosteroids: budesonide (Pulmicort®) fluticasone (Flovent®) Inhaled Corticosteroids Generic name: fluticasone Trade name: Flovent® Action: potent locally acting anti-inflammatory and immune modifier Therapeutic effects: Decrease frequency of asthma attacks Prevention of pulmonary damage associated with chronic asthma Inhaled Corticosteroids Adverse reactions and side effects: EENT: hoarseness, oropharyngeal fungal infections Dry mouth, esophageal/oral candidia (thrush) Stepwise Therapy for Management of Asthma Step 3: moderate, persistent asthma Inhaled corticosteroids Long-acting bronchodilator: salmeterol Add anti-leukotriene drug: Singulair® Antileukotriene Drugs Trade name: Singulair® Accolate® New class of asthma drugs called leukotriene receptor antagonists Action: works on the immune system at the cellular level Onset: 30 minutes Peak: 3-4 hours Duration: 24 hours Stepwise Therapy for Management of Asthma Step 4: severe, persistent asthma High dose inhaled corticosteroids PO prednisone prednisolone (Pediapred®) prednisone (Deltasone®) ® If severe, IV corticosteroids (Solu-Medrol )** Common Corticosteroids beclomathasone betamethasone budesonide cortisone Dexamethasone hydrocortisone methylprednisolone (Solu-Medrol) prednisolone and prednisone Exercise Induced Asthma Prevention: Short acting B2 agonist Take 15 to 20 minutes before activity Increase fluid intake Stay indoors when air quality is poor Epinephrine for Asthma Exacerbation Treatment: Route IM Concentration 1mg/ml = 1:1,000 Dose 0.01mg/kg Max. Single Dose 0.5mg Dosing interval N/A Max. # of doses 1  Epinephrine dose may be rounded to the nearest 0.05mg.  Dexamethasone (Decadron) Classification: corticosteroid Pharmacodynamics: binds to the glucocorticoid receptor this inhibits pro-inflammatory signals and promotes anti-inflammatory signals lower doses provide anti-inflammatory effects, while higher doses are immunosuppressive helps with mucus & edema Pharmacokinetics: Absorption: no set time for absorption, IV fast onset compared to IM, we give it PO (preferred method) Distribution: protein binding in plasma Metabolism: by liver Eliminated: mostly via urine  Common PO or Parenteral Steroids Beclamethasone Betamethasone Budesonide Cortisone Dexamethasone Hydrocortisone Methylprednisolone Prednisolone Prednisone COPD COPD Chronic Bronchitis Continuous inflammation of the bronchial tubes One of the most common causes is smoking Predisposing factors of pulmonary infections during childhood Emphysema The tissues necessary to support the physical shape and function of the alveoli are destroyed Elasticity is impaired, exhalation is difficult Treatment of COPD Atrovent®: long acting bronchodilator Classification: anticholinergic Uses: bronchodilator in maintenance therapy of airway obstruction due to COPD Action: inhibits cholinergic receptors in bronchial smooth muscle allowing for brochodilation Dosing: 2 puffs q.i.d Salmeterol Brand name: Serevent® Classification Pharmacologic: adrenergic Classification Therapeutic: bronchodilator Action: Produces accumulation of cyclic adenosine monophosphate (cAMP) at the beta 2-adrenergic receptors xanthine Trade name: Theophyline®, Slo-bid® Action: increases level of cAMP (adenosine monophosphate) which aids in dilation of bronchioles Indication: long term control of COPD Adverse reactions: tachycardia, arrhythmias, seizures, nausea and vomiting How given: PO or IV Solumedrol (methylprednisolone) Action: reduces SOB by decreasing inflammation in the bronchial tubes. Indication: Adverse reactions: Routes: PO or IV  Oxygen Classification: naturally occurring atmospheric gas Pharmacodynamics: Increases SpO2 and PaO2 reverses hypoxemia oxidizes glucose to produce ATP (energy source) Pharmacokinetics: Immediate ONSET: < 1 minute PEAK: unknown HALF-LIFE: < 2 minute  Oxygen Indications: prevent/treat hypoxemia respiratory distress decreased hemoglobin/oxygen carrying capacity treatment/prophylaxis for decrease in atmospheric pressure (decreased PO2) for air transport depressed LOC Contraindications: no absolute contraindication use with caution in COPD – watch for signs of hypoventilation Use with caution for the cardiac patient Oxygen Precautions: COPD with CO2 retention – Consider limiting FiO2 neonates: prolonged exposure to high PO2 may cause blindness NEVER withhold O2 from a patient in respiratory distress/failure Oxygen Adverse Effects: none with short-term use Dosage: generally titrated to maintain SpO2 92-95% For COPD titrate to maintain SpO2 of 88-92% high FiO2 for patients with signs and symptoms of respiratory distress, respiratory failure or decreased O2 carrying capacity consider lower FiO2 in the newborn and the head injured patient Pediatric: · same as adult Oxygen Special Notes: Oxygen may increase infarct size in normoxic STEMI patients Secondary brain injury occurs largely as a result of oxygen free radicals, hence the rational for the current trend to limit the fraction of inspired oxygen (FiO2) in the head injured patient Rule out hyperventilation as a cause of respiratory distress Oxygen The FiO2 is generally determined by the size of the reservoir: i.e. with nasal prongs the O2 reservoir would be the nose and mouth and therefore the FiO2 would be low. With a simple mask the reservoir would be the nose, mouth and mask and therefore the FiO2 would be higher. With a partial-rebreather mask the reservoir would be the mouth, nose mask and reservoir bag and therefore the FiO2 would be higher still. Oxygen Concentrations Method Flow Rate FiO2 (L/min) (comparison between the oxygen level in the blood and the oxygen concentration that is breathed.) Nasal Prongs 1-6 24-44 Nebulizing Mask 6-8 40 Venturi Mask 4-12 25-50 Simple Mask 6-10 40-60 Non-rebreather 10-15 60-90 Mask Continuous Positive Airway Pressure (CPAP)  CPAP Indications: Severe respiratory distress AND S/S of acute pulmonary edema or COPD Conditions: AGE: > 18 years RR : tachypnea SBP: normotension Other: SpO2 6months to