Exam 1: Respiratory Drugs Flashcards

Question

bronchodilators: Methylxanthines - phosphodiesterase inhibitors (PDE-5 inhib's) (2 brands) MOA, considerations for 3rd world countries, SEs

Answer 1

* MOA * nonspecific inhibition of Phosphodiesterase isoenzymes (Types III and IV) which prevents cAMP degradation in airway smooth muscle as well as in inflammatory cells → airway relaxation and bronchodilation * Clinical Applications: COPD, Asthma * Theophylline, Aminophylline → LOTS of SEs, and have to monitor blood levels bc you can have toxicity quickly * Because PDI have multiple mechanisms of actions and are nonselective they have multiple side effects and a narrow therapeutic index * Theophylline * Therapeutic plasma level of 10-20mcg/ml * Toxic at \>20mcg/ml * Caution with Halothane (3^rd world anesthesia/mission trip – might see either theophylline or halothane) * Sensitize the myocardium to EPI – might see arrhythmias * Susceptible to drug-drug interactions due to metabolism by cytochrome P450 * such as cimetidine and antifungals (cytochrome P450 inhibitors) * Metabolized in the liver and excreted in kidney * Side Effects * Headache * Nausea/vomiting * Irritability/restlessness * Insomnia * Cardiac arrhythmias * Seizures * Stevens Johnson Syndrome

Answer 2

* Inhaled Corticosteroids * Cromolyns * Leukotriene Inhibitors * Anti-IgE Antibodies

Answer 3

* Brands * triamcinolone * fluticasone * beclamethasone * budesonide * "TF, BB? You have asthma - you should be on an inhaled corticosteroid!" * Major preventive treatment for patients with asthma * MOA- **Alter genetic transcription** * Increases transcription of genes for b2 receptor and anti-inflammatory proteins * Decreases transcription of genes for pro-inflammatory proteins * Induce apoptosis in inflammatory cells (eosinophils, TH2 lymphocytes) * Indirect inhibition of mast cells over time * Reverses many features of asthma * Used as Suppressive therapy, _not a cure_ * Inhaled corticosteroids * Reduce the number of inflammatory cells in the airways and the damage to airway epithelium * Vascular permeability is reduced which decreases airway edema * Overall reduction in airway hyper-responsiveness * Inhaled Corticosteroids considered the most important drug in management of asthma * Inhaled Corticosteroids * Beclomethasone * Triamcinolone * Fluticasone * Budesonide * May consider the use of corticosteroid administration 1-2 hours pre-op * They prolong the response of beta agonists * May consider 5-day course of combined corticosteroid and albuterol to minimize the risk of intubation evoked bronchospasm * Only 25% of inhaled corticosteroids reaches airway * 80-90 % of the inhaled dose reaches oropharynx and is swallowed (unless mouth is rinsed after using the inhaler) * Higher airway concentration than same dose given PO * Systemic effects are decreased thru inhalation * Side Effects: * Oropharyngeal candidiasis * osteopenia/osteoporosis, * delayed growth in children, * hoarseness, * hyperglycemia * *rinse mouth after using the inhaler to try to prevent this*

Answer 4

"Cromo-lyn, hista-min(e), sev-en (days before effects start)" * Not used often - usually used as a suppressive therapy if other things aren't working! * Stabilize mast cells * MOA * Inhibits antigen-induced release of histamine * including the release of inflammatory mediators from eosinophils, neutrophils, monocytes, macrophages, lymphocytes and leukotrienes from pulmonary mast cells * Inhibits immediate allergic response to an antigen **but not the allergic response once it has been activated** * Administered via inhalation 8-10% enters the systemic circulation * Take 4 times daily * Principle use: Prophylactic therapy of bronchial asthma * Does not relieve an allergic response after initiation – only works as a preventative med!! * Must be used for 7 days before you start to see an effect * Not used as a rescue inhaler * Side effects are rare * Infrequent but serious side effects include: * laryngeal edema * angioedema, * urticaria, * anaphylaxis

Answer 5

"In Zi-LIEU of arachidonic acid converting to leukotriene, causes hepatotoxicity" "Monte-sits on the-Cysteinyl lukotriene 1 receptor, prevents binding. Make sure it's the Single (Singulair) agent, bc if you add Warfarin → ↑ PT" * Inhibitors of leukotriene pathway are useful drugs for bronchial asthma * Leukotreines are synthesized from arachidonic acid when inflammatory cells are activated * Not effective in the treatment of ACUTE Asthma attacks * Few extrapulmonary effects * Drug prototypes * Zileuton * Montelukast * Zileuton * Lipoxygenase inhibitor which blocks the biosynthesis of leukotrienes from arachidonic acid – blocks biosynthesis * Produces bronchodilation, improves asthma symptoms, and has shown long-term improvement in PFT * Low bioavailability, low potency, and significant adverse effects * **Hepatotoxic – 2% in people have hepatitis from this** * Not widely used * Montelukast-Singulair * Leukotriene receptor antagonists block the mechanism of bronchoconstriction and smooth muscle effects. – blocks receptor from accepting the leukotriene * This drug blocks the ability of leukotrienes to bind to Cysteinyl-Leukotriene 1 receptor * Improve bronchial tone, pulmonary function, and asthma symptoms * Caution with co- administration with warfarin which could result in prolonged PT

Answer 6

* Asthma * Prominence of IgE mediated allergenic responses * Removal of IgE antibodies from circulation would mitigate the acute response of the inhaled allergen * Omalizumab—monoclonal antibody derived from DNA \*\*the brand you’ll see * Given in the early and late phase of asthmatic response, LAST DITCH * Given SQ for 2-4 weeks/parenterally infused (comes IV or subcutaneous) * High cost and inconvenience * Omalizumab * Humanized mouse monoclonal antibody * Binds to IgE * Decreases quantity of circulating IgE * Prevents binding of IgE to mast cells * Down-regulation of receptors * In response to the lower levels of circulating IgE; receptors on the mast cells, basophils and dendritic cells are down-regulated. * Rare Adverse Effect: triggering of an immune response ## Footnote *Down-regulation of receptors is the opposite of what I would've thought. SO think of it like this: mast cells notice decreased IgE floating around, thinks "they don't need me right now" and down-regulates receptors. But if IgE does hit one of the receptors → triggers immune response!*

Answer 7

* Respiratory Airway/Treatment Bronchospasm Summary * Bronchodilation * B2 adrenergic agonists; Sympathomimetics- 3,5 cAMP production → bronchodilation * Methylxanthines/PDE Inhibitors- Inhibit breakdown of 3,5 cAMP (not usually used anymore) * Anticholinergics → competitive inhibition of cholinergic receptors with acetylcholine → block constriction * Usually used for COPD * Inflammation and mucous * Steroids-decrease mucosal edema (mainstay tx for asthma) * Cromolyn-Mast cell stabilization * Leukotriene inhibitors –block the synthesis or action (blocks synthesis or blocks the receptors) * IgE (last ditch)

Exam 1: Respiratory Drugs Flashcards

(31 cards)