Drugs for asthma and COPD Oct18 M2 Flashcards
side effects origin
action of the drug on unwanted targets
asthma 2 components
bronchoconstriction
inflammation
intermittent asthma (least severe, episodic crises) treatment
SABA (rescue inhaler)
Mild, persistent asthma treatment
SABA + low dose ICS
Moderate, persistent asthma treatment
SABA + low dose ICS + LABA
Severe persistent asthma treatment
SABA + medium/high dose ICS + LABA
alternative treatments with persistent, refractory (doesn’t respond to treatment) disease
leukotriene modifiers, theophylline, muscaranic antagonists (anti cholinergics), IgE Ab
important principle about asthma treatment
flexibility to treatment at all severities
remain uncontrolled: treatment
oral CS: prednisone (systemic effects bc by mouth)
specific receptors beta agonists and antimuscarinic agents act on
B2 adrenergic receptor on SM of bronchioles
M3 muscarinic receptor on SM of bronchioles
B2 adrenergic receptor type of protein
7 transmembrane, G protein coupled receptor (GS coupled)
B2 adrenergic receptor: what happens after substrate binds it
conformational change activates beta alpha subunit which changes GDP to GTP and frees alpha subunit
B2 adrenergic receptor: what happens when alpha subunit-GTP is free
binds adenylyl cyclase: activates it to produce cAMP
B2 adrenergic receptor: what cAMP does
binds protein kinase A (cyclin dependent prot kinase). Shape change to separate 2 regulatory and 2 catalytic subunits
B2 adrenergic receptor: what activated protein kinase A does
2 catalytic subunits go phosphorylate an enzyme
M1/M3 musc receptor type of protein
7 transmembrane protein, Gq (G alpha q or G alpha 11 coupled)
M1/M3 musc receptor: what happens when ligand binds it
activation of beta-gamma/alpha q protein, which converts GDP to GTP, releasing alpha q-GTP protein
M1/M3 musc receptor : what alpha q-GTP does
activates phospholipase C
M1/M3 musc receptor: what activated phospholipase C does
Cleaves PIP2 into DAG and IP3
M1/M3 musc receptor: what IP3 does
soluble so goes to bind sarco reticulum in SM to release stored Ca in cytoplasm.
M1/M3 musc receptor: what free Ca in smootj muscle does
activates processes leading to SM contraction (e.g. activates Ca dependent prot kinase)
what regulates balance in M3 and beta2 receptor signals
Ultimate signaling to myosin light chain kinase (MLCK)
what MLCK does
phosphorylates myosin light chain to activate it and let it couple to actin
how MLCK activate
when unphosphorylated. if phosphorylated by PKA, is inactive
how beta2 receptor modulates MLCK
Protein kinase A phosphorylates MLCK to inhibit it (no SM contraction)
how M3 receptor modulates MLCK
increased IC calcium, Ca binds calmodulin. Calmodulin-Ca activates MLCK
what theophylline does
acts on phosphodiesterase (PDE) to stop if from changing cAMP to AMP.
ultimate effect of blocking PDE
more cAMP in cell, more PKA activated, more MLCK inactivated
SABA molecule name and drug name
albuterol/salbutamol (Ventolin), isoproteranol, terbutaline
SABA mode of action
similar molecules to epinephrine, bind at its site to activate the B2 receptor (orthosteric binding)
What is drug tolerance
desensitization of receptor. More occupancy of receptor downregulates its activity or amount of this receptor on membrane
inhaled drug delivery: most common inhaler + 2 others
metered dose inhaler (with or withotu spacer)
dry powder inhalers
nebulizers
trick for beta agonist names
end in ol
CS molecular ‘‘shape’’
ressemble shape of cortisol (4 cycles)
CS why slow onset of activity
act on gene transcription
CS: 2 names
fluticasone, budesonide
ICS mode of action in general
regulate airway inflammation. act on many processes that influence that
ICS 3 examples of effects
- promote eosinophils apoptosis
- decrease cytokine (IL,inflam mediator) release
- increase beta 2 R number on SM
ICS why synergistic effect with beta agonist
increases number of B2R which will then receive beta agonist
4 adverse effects of ICS
oral candidiasis (thrush)/yeast in mouth bc ICS has immunosuppressive action and some of it goes to mouth
- HPA axis suppression
- Growth inhibition
- Decreased bone density
LABAs: 2 important things to note
1) not for acute bronchospasm
2) never taken alone, always with ICS
2 drugs name where LABA contained and name of molecules inside
Advair: salmaterol/fulticasone
Symbicort: Formoterol/budesonide
important molecule from which PG and leukotrienes come from
arachidonic acid
what NSAIDs (ibuprofen, aspirin) do
inhibit cyclooxygenase 1 and COX2 production of PG from AA
why leukotrienes important in asthma (4)
- SM contraction
- bronchovascular leakage
- mucous gland secretion
- leukocyte infiltration
how leukotriens produce
Lipooxygenases convert AA to leukotrienes
2 ways to inhibit leukotriene effect
- inhibit lipooxygenases
- inhibit leukotriene receptors
most common way of inhibiting leukotriene effect and 2 drugs
inhibit leukotriene receptor
Montelukast
Zafirlukast
(end with kast)
leukotriene modifying agents vs ICS what’s best
are less effective than ICS
2 classes of muscarinic antagonists
short acting (ipratropium) and long acting (triotropium)
PSS spine origins + important one in bronchial tree
cranial nerves (not cervical!) (vagus in resp) and sacral
main diff between asthma and COPD and consequence
COPD less inflammatory so ICS used in later stages only
order of drug implementation in COPD
SABA, SAMA, LABA or LAMA or both.
ICS+LABA/ICS+LAMA, ICS+LABA+LAMA
SABA vs SAMA (ipratropium)
SAMA has slower onset and acts longer than SABA
