21-Drugs for Pulmonary Disorders Flashcards
Bronchiolar smooth muscle input
controlled by ANS, sympathetic stimulates beta-2 adrenergic receptors (bronchodilation)
Major features of asthma (3)
- variable airway obstruction
- airway inflammation
- airway irritability
methacholine and histamine are responsible for __________ and increased ___________
airway inflammation
fall in FEV (forced expired volume)
common causes of asthma (5)
- air pollutants
- allergens
- chemicals and food
- resp infections
- stress
what are the 2 goals of therapy for asthma?
- reduce the intensity and frequency of asthma symptoms
2. decrease the risk of adverse effects associated w asthma
reducing the intensity and frequency of asthma symptoms means:
reducing symptoms, need for short acting beta-agonist (<=2x/w), reduce night time awakening, optimize lung function, participate in formal activities
decreasing risk of adverse effects includes
preventing recurrent exacerbations and need for emergency/hospital c are, preventing poor lung development in children and loss of function in adults, optimizing pharmacotherapy w little to no adverse effects
2 strategies for pharmacological management of asthma and their drug classes:
- relievers
- SA beta-adrenergic agonists
- muscarinic antagonists - controllers
- glucocorticoids
- LA beta-adrenergic agonists
- leukotriene antagonists and lipoxygenase inhibitors
- methylxanthines (PDE inhibitors)
- IgE antibodies
Mast cell stabilizers
briefly, how is histamine produced during asthmatic response
Allergen binds to IgE receptor, Gq receptor releases 2nd messenger, IP3 (cleaved by PIP2) and increases Ca, mast cell degranulation, and histamine release = bronchoconstriction
briefly, how are Leukotrienes produced during asthmatic response
Allergen binds to IgE receptor, Gq releases 2nd messenger IP3, cleaved by PIP2, releaseing Ca activating phospholipase A2
phospholipase A2 converts arachadonyl ester into AA, AA converts into leukotrienes via 5-lipoxygenase (and PGs through COX1 and 2)
when leukotrienes and histamine act on the receptors (Gq) of SM on bronchioles what occurs
bronchoconstriction
Beta 2 adrenergic agonists: action, routes, adverse
1st line therapy:
bronchodilator (SABA or LABA)
- binds to Gs proteins on SM of bronchioles to release cAMP and sequester Ca in endoplasmic reticulum (BONUS! hyperpolarize cell w K+ eflux)
PO (LABA), inh(SABA/LABA), neb (severe attack)
Adverse: tremor tachycardia (sympathetic syimulaiton)
Anticholinergic drugs: action, routes, adverse
- muscuarining antagonists 2nd line therapy: (only works for 2/3 pt.s, good for COPD, chronic bronchitis) - use w pt. w cardiovascular concern - few adverse can combine w SABA
Airway inflammation in asthma, main mediators
inflammatory cytokines from transcription factors produce eosinophils (increases production, recruitment, and survival and secretes cytotoxic, inflammatory, and bronchoconstrict)
glucocorticoids: action, use, adverse
- suppress inflammation (inhibit COX2), hyper-responsiveness, obstruction, and prevent attacks
- does NOT dilate bronchioles
- ## works at cell membrane and DNA t bring to GCSr and GRE to downregulate gene producing mediators OR inactivate transcription factors
Leukotrienes Receptor Antagonists (LTRA): action,
competitive antagonist, induces bronchodilator and immunomodulatory effects
- can sue in combo w glucocorticoids, weaker than beta-2 adrenergic antagonists
PO, chewable form adverse: nausea, headache
Mast cell stabilizers: use
- prevent allergen-induces A metabolization (decrease leukortienes) and prevents mast cell degranulation (decrease histamine and bronchoconstrictors)
- no bronchodilatory effect, prevent constriction in response (take before exposure to antigen)
- Martha’s damn cat
lipoxygenase inhibitor: action, adverse
- inhibit formation of leukotrienes
- minimal adverse, contraindication: liver disease
Methylxanthines: action, use, adverse
- inhbit PDE (phosphodiesterase - degrades cAPM - no mast cell degranulaiton or IP3)
- slow release, for nocturnal
adverse: GI distress, irritability, insomnia, headache, nausea, vomiting
IgE antibodies: use, considerations, adverse
subcut q2-4w for allergic asthma (reduces production of IgE, downregulates receptors, significant mast cell stabilizing effects)
- v expensive, lots of tests, administered by HCP
adverse: pain (arms, legs, ears), dizziness, fatigue, skin rash, anaphylaxis
T/F: Drugs for asthma can be topically applied?
true
What is the gold standard for relieving asthma attack?
beta adrenergic agonists
What is used and is known as gold standard for prevention of attacks?
- glucocorticoids
How are glucocorticoids administered?
inhaled or orally
COX enzymes convert arachidonic to
prostaglandins
Lipoxygenase convert arachidonic to
leukotrienes
Where are leuktrienes and histamines receptors found?
smooth muscle of lung
t/f: with increase in Ca levels; contraction occurs
true
Which are the most effective and rapid acting bronchodilator?
beta 2 adrenergic agonists
Short and rapid acting beta 2 adrenergic agonists are known as
Salbutatomal and are relievers
Long and slow acting forms of beta 2 adrenergic agonists are known as
salmeterol; LABA which is controller
Routes of administration for beta 2 adrenergic agonists; which is short and long acting?
inhaler- short and long acting
oral- long acting
Between inhaler or oral which one has the greatest increase of adverse effects
oral
Adverse effects of B2 adrenergic agonists
- tremor
- tachycardia
Which types of patients are muscarinic relievers good for?
those with COPD and chronic bronchitis
Function of muscarinic antagonists
- blocks muscarinic receptors in smooth muscle of the bronchi
Adverse effects of muscarinic antagonists
- dry mouth
- sedation
- inappropriate inhalation
Adverse effects for high and low dose glucocorticoid controllers
- Low: throat irritation, oral candidiasis
- high: adrenal insufficiency, osteoporosis…
Glucocorticoid controllers: route of admin for severe asthma
IV and PO
Glucocorticoid controllers: route of admin for moderate to severe asthma
inhaled
Which is a second line therapy for controllers; leukotriene or glucocorticoids
leukotrienes
function of leukotriene receptor antagonists
- competively bind to leukotriene receptors in bronchial smooth muscle
- induce bronchodilation
How are leukotrienes administered? and how often
- orally; one daily
Adverse effects of leukotriene receptor antagonists
Nausea and headache
