asthma Flashcards
whats asthma?
chronic inflammatory disease of the airway
what are the 2 phases of asthma?
immediate phase –> hypersensitivity due to irritant
Delayed phase –> chemotaxis are been released by the inflammatory cells to attract more immune cells
what happens to the bronchial wall in asthma due to irritations and inflammation?
1- Smooth muscle hyperproliferation
2- increased gland secretions
why asthma is not considered COPD?
Because asthma can be reversed by drugs
what are the two types of asthma??
chronic asthma —–> stable
acute asthma —> Severe and unstable
how do you administer drugs in chronic asthma?
orally
how do you administer drugs in acute asthma?
Inhaled
IV
whats extrinsic asthma?
the irritant comes from outside the body
whats intrinsic asthma?
the irritant comes from inside the body
whats the triad of asthma?
wheezing
cough
shortness of breath
what drugs are contraindicated in asthma?
1- beta blockers
2- morphine
3- PGI
4- cholinomimetics
5- drugs that causes histamine release
cold weather
exercise
cough during crying
all of these cause bronchoconstriction so worsens the situation
whats are the 2 potent bronchoconstrictors ?
leukotrien b4
adenosine receptor
whats the pathophsiology of asthma?
the irritation will cause inflammation then immune cells come and start producing cytokines and worsen the problems
what are some examples of cytokines that can be released in asthma by immune cells?
1- histamine
2- serotonin
3- PGD
4-leukotriens ( B4)
5- platelet activating factors
6- interlukeins
7-adenosine
what are the 2 primary treatments used in asthma?
1- Bronchodilators ( beta2 agonists )
2- Antiinflammatory
3- adjuvent treatments ( used as proph)
can you use NSAIDS?
no because it will block cox pathway and then all the archnoid acid will be converted to leukotriens and ths will worsen the situations
what are some examples of bronchodilators?
1- beta agonists
2- muscarinic blockers ( muscrinic causes constriction so blockers do opposite )
3- methlyxanthine الشاي و القهوه
what are some examples of selective beta agonists?
TEROLS —> end with terol
salbutamol –> albuterol
terbutaline
salmeterol
formoterol
metaproterenol
pirbuterol
which ones are SABA?
short acting beta agonists work only for 3-4 hours
Salbutamol ( albuterol )
terbutaline
metaproterenol
pirbuterol
which ones are LABA?
long acting beta agonists –> work for 12 hours
salmeterol
formoterol
whats the mechanism of beta agonists?
they go and activate beta 2 receptors in the bronchi and increase CAMP and this will lead relaxations of muscles
CAMP always lead to smooth muscle relaxations EVERYWHERE
except in the heart and the brain
why? CAMP when increased it will activate protein kinase A ( PKA ) which will inhibit myosin light chain kinase which is responsible for contraction
whats none selective beta agonists?
adrenaline
isoprenaline
not used anymore
how are beta agonists administered ?
inhalation or IV in acute severe asthma
how are short acting beta agonists excreted?
excreted unchanged
when are short acting beta agonists used?
first line drug for the immediate phase and acute attack
NOT EFFECTIVE IN DELAYED PHASE because delayed phase is mainly due to cytokines
what are the adverse effects of beta agonists?
T—> tachycardia because direct effect and vasodilation –> reflex tachy
T —>Tremors because increased sensitivity of muscles
T—> tolerance they get downregulated يزعل منك
H—> hypokalemia –> beta 2 will take potassium from the blood and send it to muscle
revise the effects beta receptors
how are the LABA excreted?
metabolized in liver by p450 and lost in faeces
when are laba used?
used as prophylaxis before exercises and in night before sleep
it is not used for acute attacks but used in regulation with corticosteroids
what are ultra long acting beta agonists?
indacaterol
olodaterol
vilanterol
bambuterol
when are ultra long beta agonists used?
in asthma but in combination with corticosteroids NEVER ALONE
alone in COPD only
what are the 2 types of methylxanthine drugs?
natural
semi synthetic
whats an example natural methylxanthine drugs?
caffeine
theophylline
theobromine
whats an example of semi synthetic methylxanthine drugs?
aminophylline its js modified theophylline
whats the function of Adenosine receptor? ( A1)
bronchi —> bronchoconstriction
bronchi —> increase gland secretions
CNS –> depression of CNS
Heart –> inhibit conduction ( negative dromotropic effect)
whats the function of PDE enzyme?
breaks down CAMP and GAMP
CAMP, GAMP –> 123
CAMP –> 4 7 8
GAMP –> 5 6 9
which versions of PDE are mainly inhibited by pde inhibitors?
3
4
whats the function of methylxanthine drugs?
1- they block Adenosine receptor 1 which lead too :
- bronchodilation
-decreased gland secretion
-increases CNS activity
-increase heart conduction ( positive dromotropic effect)
2- Inhibit PDE enzyme which lead increased CAMP
what happens when theres an increase in CAMP?
CAMP ALWAYS LEAD TO RELAXATION IN SMOOTH MUSCLES
EXCEPT FOR THE HEART IT LEADS TO INCREASED CONTRACTILITY and THE BRAIN
different effect in heart because its the MLCK enzyme is different in the heart compared to smooth muscles
for example in kidneys anything that increase CAMP will lead to dilation and uresis
what are the uses of methyl xanthine ?
bronchial asthma (IV , OR ORAL) ( 2ND LINNEEE, right after SABA)
IV as aminophylline and orally as theophylline
Increase cns activity ( why we drink coffee and caffiene )
Migraines ( cuz of vasoconstriction
Delayed physical fatigue and increased performance
neonatal apnea syndrome ( baby doesnt cry after birth which is due to cns depression
how can we administer methylxanthine?
IV and oral BUT NO INHALERS
what are the adverse effects of methylxanthine?
1- excessive CNS stimulation ——-seizures
2- CVS tachycardia + Arrhythmia ( tachycarida due to increased conduction and vasodilation –> reflex tachy )
3-Increase HCL ( GIT disturbance )
when is methlyxanthine contraindicated?
peptic ulcer
hepatic failure
renal failure
what you dont add to methylxanthine?
anything that inhibit metabolism you have to decrease the dose (CYP 450)
what do you do in smokers?
smoking and drinkers increases metabolism so you have to increase the dose
whats the clinical uses of methylxanthine?
second line drug for chronic asthma
aminophylline is used as IV for severe acute asthma
which methylxanthine can be given orally?
theophylline
theobromine
caffeine
which methylxanthine can be given IV?
aminophylline and its used in acute asthma
whats roflumilast?
ORAL, selective PDE 4 inhibitor that decreases the risk exacerbations in patients with COPD
why we dont have methylxanthines in inhalation format?
because there is not a significant bronchodilation effect and risk of adverse effect is severe
whats the relation between methylxanthines and beta agonists?
they should not be given together because the methylxanthine will not enhance the effect of beta agonist and it will js cause side effects
But beta agonists and muscranic blockers good combo
what should be monitored when give methylxanthine?
plasma level of the drug because its easily affected by any drug that affects the metabolism
whats the pathway of arachidonic acid after its formed?
2 pathways
COX 2 PATHWAY : FORMATION OF PGE2 AND PGI 2 –> INFLAMMATION AND PAIN : vasodilation, vascular permeability, cytokine release, leukocyte migration , pain
LOX pathway : formation of leukotriens LTC4, LTD4, etc —-> inflammation and bronchoconstriction : b.c , mucus secretion , edema, eosinophil migration
which group of drugs inhibit the cox 2 pathway ?
NSAIDS
which group of drugs inhibit the lox pathway?
leukotriene pathway inhibitors
whats an example of lox enzyme inhibitor?
zileuton
whats the function of zileuton?
inhibit lox enzyme and lead to anti inflammatory effect and bronchodilation
whats the other type leukotriene inhibitors ?
Leukotriene receptor blocker/antagonist (LTRA)
zafirlukast
montelukast
whats the clinical use of leukotrienes inhibitors ?
third line drug for asthma
Aspirin induced asthma ( aspirin will inhibit the cox 2 pathway so it will be directed to lox pathway luekotrienes inhibitors can block the lox pathway)
can be used instead of corticosteroids when they are contraindicated
easy for children to take
in children do you use leukotrienes inhibitors or coritcosteroids?
corticosteroid aare bad for children because soo many severe adverse effects
so you give leukotrienes inhibitors
whats the relationship between leukotriene inhibitors and methylxanthine?
leukotriene inhibitors inhibit metabolism and CYP450 so it increases the concentration of methylxanthine
must decrease the dose of methylxanthine
examples of antimuscarinc agents?
atropine —> not used anymore because not selective and many side effects
ipratropium
tiotropium bromide
glycopyrronoium bromide
umeclidinium bromide
whats the function muscarnic blockers?
they block m3 which is responsible for constriction once its blocked it wont cause constriction and it will give beta 2 receptors the upper hand تفضي المعلب
which muscarinic blockers are short acting ?
ipratropium bromide last for 3-5 hours
which muscarinic blockers are long acting?
tiotropium bromide
glycopyrronium bromide
umeclidinium bromide
last for 12-24 hours
when are the long acting muscarinic blockers used?
choice for COPD
asthma in addition to LABA AND inhaled corticosteroids
what are the adverse effects of muscarinic blockers?
urinary retention
dry mouth
constipation
pharyngitis
whats the best combination in inhalers that is used now a days?
Short acting beta agonists ( albuterol for example )
short acting muscarinic blockers ( ipratropium )
or LAMA + LABA
why did we develope additive combinations?
because using 2 different types drugs has proved to show better results than just increasing the dose
whats another reason why did we develope the laba/lama combinations ?
they show better results when used combined that using them individually
a lama may block the tightening of smooth muscles around your neck to help keep the airways open
whats the main anti inflammatory drug used in asthma?
corticosteroids
whats the function of corticosteroid?
1- inhibit the PLA2 enzyme stops production of archnoid acid القصه من اولها
2- inhibit immune cells ( B lymphocytes, T lymphocytes, Macrophages, mast cells
3- upregulate B receptors
how do corticosteroids inhibit the immune system?
they bind to GRS ( glucocorticoid receptor) and then it will result in repression of transcription factors for example : Nuclear factor kappa D (NF-KB)
what are some examples of inhaled corticosteroids ?
all have son
triamcinolone
budesonide
ciclesonide
flunisolide
mometasone
fluticasone
on which phase do corticosteroids work mainly?
they work on the delayed inflammatory phase only
no effect on the immediate phase
what do you combine the inhaled corticosteroids with?
LABA/LAMA or both
which corticosteroid is given iv?
hydrocortisone its given in acute severe asthma
when are corticosteroids used?
added to bronchiodilators incase they dont work alone and in emergencies as iV as in status asthamticus
what are the adverse effects of corticosteroids ?
hoarse voice –> oral candidiasis ( thrush ) due to severe immune system inhibition
adrenal suppression
what are some examples of targeted monoclonal antibody therapy?
end with mab
omalizumab
mepolizumab
whats the function of the antibodies?
they bind to igE stopping them from binding to mast cells and release of histamine and what not
on which phases do the antibodies work on?
both phases immediate and delayed
how are the antibodies administered?
subcutaneously at 2-4 weeks
require expert administration
whats the clinical uses of the antibodies?
persistent allergic asthma that is not controlled by laba or corticosteroids
what are the adverse effects of the antibodies?
hypersensitivity reactions
what does omalizumab bind to?
igE
what does dupilumab bind to?
IL4 and IL3 receptors ( antagonist )
what does reslizumab bind to?
bind to IL-5 directly
what does mepolizumab bind to?
similar to reslizumab, binds to IL-5
what does benralizumab bind to?
IL-5 receptor
what are the uses of IL-5 inhibitors?
reslizumab and mepolizumab and benralizumab
they are used in refractory eosinophilic asthma
what are the adverse effects of IL-5 inhibitors?
headache
injection site reactions
back pain
myalgia
what are examples of mast cell inhibitors ?
cromolyn
nedocromil
whats the function of cromolyn / nedocromil ?
they stabilize the mast cells and prevent their degranulation
how are cromolyn/nedocromil administered?
powder inhalation
when are the mast cell inhibitors used?
prophylaxis of asthma mainly in older children to reduce symptoms of allergic rhinitis
what are the adverse effects of mast cell inhibitors?
irritation of throat by powder
whats the best initial drug choice in acute bronchospasm?
Selective SABA –> albuterol
terbutaline
metaproterenol
pirbuterol
whats the most useful drug in long term management of COPD?
SAMA –> ipratropium
but its ineffective in acute bronchospasm but it aids the beta agonists تفضي الملعب
whats the 2nd line drug in COPD?
theophylline ( methylxanthine )
orally
which drugs are used prophylactically ?
cromolyn and nedocromil
which anti inflammatory drug is given in acute episodes of bronchoconstrictions?
corticosteroid –> orally or IV
whats the common regimen for moderate asthma?
inhaled corticosteroid + SABA
whats the common regimen for severe asthma?
inhaled corticosteroid + SABA + LABA
leukotriene inhibitor can be added if needed
whats the common regimen for severe asthma in children?
leukotriene inhibitor + saba and laba
leukotriene inhibitor replaced corticosteroids
whats the advantage of multi regimens than single regimen?
you will give smaller doses of multiple drugs than js large doses of single drugs
whats combivent?
albuterol ( saba ) + ipratropium ( sama ) combination in inhaler
whats advair?
salmeterol ( laba ) + fluticasone ( corticosteroid ) in combined inhaler
