Exam I - Asthma and COPD Flashcards
Drug List
Systemic
Methylprednisolone
Drug List
Aerosol Corticosteroids
Fluticasone
Drug List
SABA
Albuterol
Drug List
LABA
Salmeterol
Drug List
SA Muscarinic Antags
Ipratropium
Drug List
LA Muscarinic Antags
Tiotropium
Drug List
Phosphodiesterase Inhibitors
Non-selective
Theophylline
Drug List
Leukotriene Inhibitors
Montelukast
IgE Inhibitors
Omalizumab
Acute Asthma
Stimuli
- Allergens
- Viral Inxns
- Pollutants
- Cold Air
- Exercise
- Stress
Asthma
Immunopathogenesis
Early Phase
- sharp decline FEV1
- IgE/mast cell/histamine mediated
- T-cell participation
- Also: Tryptase, PGD, LTC, PAF
- bronchodilator drugs
Asthma
Immunopathogenesis
Late Phase
- Eosinophil -> ECP, MBP
- Neutrophil -> Proteases, PAF
- anti-inflammatory drugs
Maintenance Drugs
- ICS
- anti-inflammatory
Maintenance Drugs
Effect
-airway responsiveness
Quick Relief
Drugs
- SABA
- IV/oral CS
Quick Relief
Effect
-airway resistance
Therapeutic Index
Equation
TD50/ED50
Asthma Inhaler
Types
- MDI w/ or w/o Spacer (+mask PRN)
- DPI (really effective and easy for kids!)
- Nebulizer w/ face mask
Deposition of
Inhaled Drugs
- 10-20% inhaled
- 80-90% swallowed + first pass
- side effects from circulation
Attack Prevention
Drug Targets
- Immune cells: CS, leukotrienes, IgE
- Muscarinic cholinergic antagonists
- B2 adrenergic agonists
Most Effective Tx
-inhaled glucocorticoids (ICS)
ICS
mechanism
-Suppress inflammation
(inflamm gene transcr.)
-direct inhibition of CBP/HAT gene transcr.
(acetylation of enzyme)
-indirect inhibition of HDAC2 gen transcr.
(deacetylation of DNA)
ICS
Effects on Inflamm Cells
- incr. B2 receptors on smooth musc
- decr. Eosins, macs, dendritics
- decr. cytokines on T cells
- decr. T cell activation of mast/eosin
ICS
Not mechanism
- effect on mediator release
- effect on early response
ICS
TX Timeline
-weeks/mos/long-term
ICS
Not working well enough?
What to do?
-Add LABA before increasing ICS
ICS
Adverse
-oral candidiasis, dysphonia
-suppress hypothal/pit axis
(bone resporption, skin thinning,
growth retardation)
ICS
COPD indications
-only if FEV1<50%
Systemic Glucocorticoids
Indications
- acute asthma exacerbation
- may need to use IV
- 3-10 day short-course
- replace with ICS upon conclusion
Systemic Glucocorticoids
Adverse
-Same as ICS
SABA/LABA
mechanism
- Relax smooth muscle/bronchodilator
- pos reg of adenylate cyclase-> cAMP
- inhibits methylxanthines
- Inhibit mast cells
- inhibit vasc leakage
- stimulate glucocorticoid receptor translocation
- incr. mucociliary transport
SABA
Indication
Duration/Impact
- Rescue
- effects in 3-5 min
- peak 30-60 min
- duration 3-6 hours
LABA
Indication
Duration/Impact
- adjunct to ICS
- duration > 12h
- COPD monotherapy
SABA/LABA
Adverse
-muscle tremor, tachycardia, hypokalemia
-no LABA w/o concurrent ICS
(use combo inhaler)
Muscarinic Cholingergic Antags
Mechanism
- block vagus ACh on M3
- inhib sm musc contraction
- additive effect w/ B2 agonists
- no anti-inflammatory action
Muscarinic Cholingergic Antags
Indication
- B2 agonist intolerance
- more effective in COPD
Muscarinic Antags
Durations
- Ipratropium: SA, 15 min to 4 hours
- Tiotropium: LA, >24 hrs
Muscarinic Antags
Adverse
- few systemic (poor absorption)
- dry mouth
Methylxanthines
Mechanism
-oral!
-inhibs cAMP phosphodiesterase
(incr cAMP)
-blocks adenosine receptors on sm musc, mast cells
(reduce constriction, reduce histamine)
-deactylates histones
-decr. cytokine release
Methylxanthines
and COPD
- increases diaphragm contractility
- may increase ICS effects
Methylxanthines
Adverse
- Nausea/vomit
- CNS stim: anxiety, tremor, convulsions
- CV: tachycardia, arrhythmias, vasodilation
- narrow tx window!
Leukotriene Pathway Inhibs
Mechanism
-Oral
-inhibit bronchoconstriction
(blocks receptor for cysteinyl leukotrienes in COX)
Leukotriene Pathway Inhibs
Indications
- aspirin-sensitive asthmatics
- additive for poorly controlled mild/mod asthma
- NO ROLE IN COPD
Leukotriene Pathway Inhibs
Adverse
- rare hepatic dysfx’n
- reversible on discontinuation
Anti-IgE
Mechanism
- injected Ab
- binds Fc portion of IgE
- prevents IgE from binding
Anti-IgE
Adverse
- $$$$$$$$$$$
- rare anaphylaxis
- rare increase in malignancies
COPD
best cure
stop smoking, beez
Asthmatic Sx following URI
TX
- no official recommendations
- can use SABA or SA anti-chol or LABA
