Pharm Other BD (Side Door) Flashcards
-Methylxanthines (Side Door)
-Referred to simply as xanthines, xanthine derivatives, or as methylxanthines
-These are phosphodiesterase inhibitors which indirectly increase the amount of cyclic AMP within smooth muscle causing bronchodilation
-Xanthines used therapeutically include:
-Caffeine
found in the seeds of a coffee plant
-Xanthines used therapeutically include:
-Theophylline
found in tea leaves (mostly oral medications Theo-Dur
-Clinical uses of theophylline include the management of:
-Asthma
-Sustained release theophylline is indicated as an alternative for maintenance therapy of mild, persistent asthma and higher in patients older than 5 years of age
-Listed as an alternative for patients older than 5 years of age in combination with ICS -Side effects and narrow therapeutic index may make it a poor choice vs. others agents
-Clinical uses of theophylline include the management of:
-Chronic obstructive pulmonary disease(COPD)
-The global initiative for chronic obstructive lung disease (gold) states that inhaled bronchodilators are preferred when available
-Theophylline: recommended by GOLD as alternative to B2 agonist and anticholinergics -Not used in acute exacerbation
-Apnea of prematurity in neonates
-Methylxanthines are considered the first line agents of choice as treatment
-Theophylline was most extensively used in the past, but caffeine citrate may be a better choice (as it is safer, higher therapeutic index)
All xanthine’s have the following effects
-CNS stimulation
-Skeletal muscle stimulation -Cardiac stimulation -Bronchodilaton -Pulmonary vasodilation -Smooth muscle relaxation -Theophylline is generally classified as a bronchodilator -Peripheral and coronary vasodilation -Diuresis -Cerebral vasoconstriction -Used in headache remedies
-The basic effects of xanthine’s on the lung are:
-Decreased airway resistance (result of Bronchodilation
-Decreased pulmonary vascular resistance (result of pulmonary vasodilation) -Stimulated ventilation (CNS)
optimum serum theophylline level
-There is variability in individual metabolic rates among patients, which makes it difficult to control therapeutic dosages
-To optimum serum theophylline level for maximal bronchodilation in adults is between 10n and 20 mcg/ml. And 5-10 mcg/mL in neonates and children
-Blood levels are important to monitor in patients receiving methylxanthine drugs as toxicity is serious!
-Side effects or lack of therapeutic effects are associated with the following serum levels:
-Theophylline
-< 5 micrograms/ ml- no effects seen
-10-20 micrograms/ ml therapeutic range - > 20 micrograms/ ml Nausea - 40-45 micrograms/ ml seizures -Asthma management - 5 to 15 ug/ ML ug means micrograms -COPD management -5 to 10 ug/ ml
-Theophylline Theraputic index
-It is stressed that the ranges given for toxic effects are approximate
-It is possible for an individual to bypass the nausea phase of toxicity and begin having seizures immediately -In practice and initial loading dose is given following by a maintenance dosage adjusted to obtain therapeutic plasma levels
aminophylline
-It should be noted that aminophylline is a double salt of theophylline compound to give aqueous solubility
-This enables one to give the drug IV
-Adverse Reaction with Theophylline
-Central nervous system
-Headaches
-Anxiety -Restlessness -Insomnia -Tremor Convulsions
-Adverse Reaction with Theophylline
-Gastrointestinal
-Nasua
-Vomiting -Anorexia -Abdominal pain -Diarrhea -Gastroesophageal reflux
-Adverse Reaction with Theophylline
-Respiratory
-Tachypnea
-Adverse Reaction with Theophylline
-Cardiovascular
-Palpitations
-Ventricular arrhythmias -HYpotension
-Adverse Reaction with Theophylline
-Renal
-Diuresis
contraindications of xanthines
-Because of side effects in the gastrointestinal system, xanthines are contraindicated in subjects with active peptic ulcers or acute gastritis
-Ingestion of large amounts of caffeine from other sources such as tea or coffee may precipitate side effects when taking theophylline
-Mucolytic
Mucolytic refers to an agent that breaks down or liquifies thick mucus to a watery state
Mucoactive
refers to any agent that has an effect on mucus secretion (mucolytic, expectorant, mucokinetic, etc.)
Mucus and Biofilm
-Mucus lubricates, waterproofs, and it protects
-The normal mucus barrier can entrap microorganisms, inhibiting chronic bacterial infection and biofilm formation
-Biofilm , an aggregate of microorganisms in which cells adhere to each other on a surface (ex, dental plaque is a biofilm on the surface of the teeth)
mucoactive therapy
-The general indication for mucoactive therapy is to reduce the accumulation of airway secretions, with improvement in pulmonary function ans gas exchange and the prevention of repeated infection and airway damage
-Disease in which mucoactive therapy is indicated are those with hypertension or poor clearance of airway secretions such as
-Cystic Fibrosis
-Acute and chronic bronchitis -Pneumonia -Asthma -Bronchiectasis -Diffuse panbronchiolitis (DPB) -Primary ciliary dyskinesia
-Three drugs are available that have been used for administration as an aerosol, to treat abnormal pulmonary secretions
-N-acetylcysteine (NAC) aka mucomyst
-Dornase alfa aka Pulmozyme -Hypertonic saline
-The therapeutic options for controlling mucus hypersecretion are outlined as follows
-Remove causative factors where possible
-Treat infections -Stop smoking -Avoid pollution and allergens - -Optimize tracheobronchial clearance -Use bronchodilators as prescribed -administer bronchial hygiene measures -Improve airflow by exercise and nutrition rehabilitation -Use mucoactive agent when indicated
-Acetylcysteine
-Generic name: N-Acetylcysteine, Acetylcysteine, or NAC
-TRade name: Mucomyst, mucosil -Mechanism of action: Lyses disulfide bonds holding mucoproteins together, thus increasing fluidity of mucoid sputum -Concentration: 20% W/V solution or 10% W/V solution -Dosage: SVN 3-5 ml of 10% or 20% W/V
-Acetylcysteine -Indication for use
-Treatment of conditions associated with viscous secretions
-Also used for Acetaminophen overdose -Contraindications: Hypersensitivity
-Acetylcysteine
Side Effects and other Traits
-Side effects
-Bronchospasm -Excessive liquefaction of dried, retained secretions -Hypersensitivity -Nausea -Rhinorrhea -Highly recommended that the drug be administered in conjunction with a bronchodilator -Should be refrigerated after opening, use within 96 hrs -Foul smelling -Supplied in 4ml, 10ml, and 30 ml vials
-Dornase Alfa
-Generic name: Dornase Alfa
-Trade name: Pulmozyme
-Dornase Alfa
-Inication:
-Inication: For the management of cystic fibrosis, to reduce the frequency of respiratory infections requiring parenteral antibiotics and to improve or preserve pulmonary function
-Dornase Alfa
-Mode of action:
-Mode of action: Reduce the viscosity and adhesivity if infected respiratory secretion when given by aerosol, accomplished with a decrease in the size of the DNA in the sputum
-Dornase Alfa
-Dosage:
-Dosage: Single unit dose ampule given SVN 2.5 mg drug in 2.5 ml of solution daily. The solution should be refrigerated and protected from light. Delivered by a tested and approved nebulizer.
-Optimal delivery of the enzyme requires a neb system capable of producing appropriate sized particles and quantity of aerosol. Important when goven expensive drugs or medication with a narrow TI -Hudson RCI UP-DRAFT OPTI_NEB -ACRON 2 NEB -PARI LC PLUS neb -Mesh neb
-Dornase Alfa
-Adverse effects
-Adverse effects: Common side effects with the use of the drug have included voice alteration, pharyngitis, laryngitis, rash, chest pain, and conjunctivitis
-Contraindication: Hypersensitivity -Dornase alfa is design as an orphan drug -A drug or biological product for the diagnosis or treatment of a rare disease
-Expectorants
-Expectorants are medications meant to increase the volume or hydration of airway secretion for clearance
-Cough suppressants should never be given to a patient with thick retained secretions
-Expectorants
-Sodium bicarbonate
-Inflammation caused by bicarbonate is thought to draw water into secretions
-Has not been clinically demonstrated to improve airway mucus clearance -However in CF there is loss of airway bicarbonate transport with acidification of secretions, so.. -Aerosolized bicarbonate is now being studied as a potential therapy for CF
-Expectorants
-Guaifenesin (Mucinex)
-Guaifenesin (Mucinex)
-Usually considered an expectorant -CAn be ciliotoxic when applied directly to respiratory epithelium -Thought that expectorant action is mediated by stimulation of the GI tract -Guaifenesin has been approved as an expectorant by the FDA in a bilayer extended-release tablet Mucinex
-Cough and Cold agents
-Antihistamines
-Antihistamines- drugs that reduce the effects mediated by histamine, a chemical released by the body during allergic reactions.
-Antihistamines are often administered to reduce secretions (e.g., runny nose and sneezing), but they can cause drowsiness and impaired responses -Note: Drying of secretion, whether caused by antimuscarinic or antihistamine action, may suprepress a needed defense reaction of the airways. Nocturnal use is indicated more than around the clock use
-Cough and Cold agents
-Antitussives
-Antitussives- drugs that suppress the cough reflex
-Note productive coughs should not be suppressed
-Four classes of agents can be distinguished in cold remedies, used individually or in combination
-Sympathomimetics: For decongestion
-Pseudoephedrine (sudafed) -Antihistamines: To reduce (dry) secretions -Diphenhydramine HCI (benadryl) cetirizine (zyrtec), Loratadine (claritin) -Expectorants: To increase mucus clearance -Guaifenesin (Mucinex) -Robitussin DM -Antitussives: To suppress the cough reflex -Codeine, dextromethorphan, (Delsym, Trocal, Robitussin Maximum Strength Cough)
