Asthma basics of therapeutics and pharmacological treatments Flashcards
Epidemiology
study of distribution and determinants of health related states and events in specified populations
Extrinsic asthma
allergic - more in children ( 1/11 affected in Uk)
intrinsic asthma
non-allergic - no detectable
how many people have asthma in the uk
5.4million
Episodic
seasonal
Pets Stress Exercise Pollen Pollution Smoke Dust Cold air Fungus spores Bug Chemical fumes
all triggers of asthma
what antibody mediates asthma
IgE - formed in response to allergen
frist exposure drives sensitization and memory
preexposure - allergen binds to specific IgE molecule on the mast cell surface
what ion moving into the mast cell drives degranulation ?
what does the mast cell release
calcium
histamines and prostoglandins
Mechanism of airway narrowing in asthma
takes around 20mins to hours
Airway narrowing
Open airway - smooth muscle layer goes into spasm , narrowing the airway ,
lining of the lung becomes inflamed and then mucus production is increased blocking the airway even more than usual - in some part of the airway mucus can from plush that nearly or completely block the airway
Imagine airway picture as a circle
In the early phase of an asthma attack what happens
Allergen or non specific stimulus binds to the mast cell releasing spasmogens leading to bronchospasm.
Chemotaxins and chemokines are released by the mast cells
this leads into the late phase - what happens here
Infiltration of Th2 cells -activation of inflammatory cells such as eosinophils
These release cysLTs and other mediators
This leads to airway inflammation and airway hyperreactivity leading to bronchospasm and wheezing
What to eosinophils release that contribute to airway hyperactivity and damage epithelial lining
EMBP
ECP
common signs and symptoms of asthma
Coughing - worse at night or first in morning
Wheezing or whistling noise in the chest heard on expiration - tight airway pressure to exhale
SOB
Tightness in the chest ( dyspnoea)
dyspnoea
shortness of breath
In asthma how does FVC and FEV1 and the ratio change - on spirometry
FVC dose not change
FEV1 reduces
So ratio falls and PEFR drops
comparing moderate , acute/severe and life threatening asthma change
PEF SpO2 speech Respiration Pulse
PEF >50-70% , 33-50 , under 33
SpO2 >92 , “ , below 92
speech normal, can’t complete sentences , silent chest cyanosis or poor respiratory effort
Respiration <25/m , over 25 then hypotenison and arrhythmia
Pulse <110 then above then altered consciouness
in self management of asthma what can you do
Avoidance of triggers Desensitisation to specific allergen House dust mite control measures Smoking cessation Weight reduction
what are the 3 relievers
Relievers Beta 2 agonists
antimuscarinics
methylxanthines
what are the preventers
corticosteroids
leukotriene receptor antagonists
cromones
long acting beta agonists
examples of Short acting beta 2 agonists
and how does it work
via what second messenger
Salbutamol, terbutaline
Stimulation of B2 receptor on airway smooth muscle - cAMP
adverse effects of short acting beta 2 agonists
fine tremors of the hands , nervous tension , headaches and tachycardia
Hypokalemia at high doses
how do Methylxanthines eg theophylline work
how are they given
Inhibits phosphodiesterase - break down cAMP
Given orally ( usually s/r) or by very slow i/v infusion Hepatically metabolised ( CYP1A2- half lives of drugs)
what type of receptor is a Beta 2 adrenoreceptor
how does it work
G alpha s receptor
Beta 2 Galpha S coupled - adenyl cyclase coverts ATP to cAMP
cAMP inhibit MLCK so stops interaction and leads to broncho dilation and relaxation of the smooth muscle
aminophylline otherwise known as PDE - breaks down what
PDE
what dos a narrow therapeutic range mean
therapeutic window of a certain drug reflects the conc range that provides efficacy without unacceptable toxicity
Antimuscarinics eg ipratropium
work how
Main target is M3 subtype- block it - onset is slower than that of beta 2 agonists
inhaled
atropine I a antimuscarinics - why is it not used
not used in an airway disorder as increase mucus viscosity and reduces clearance
when should you be careful when using antimuscarinics
prostatic hyperplasia, bladder outflow obstruction , angle closure glaucoma
examples of corticosteroids
beclomethasone
fluticasone
budesonide
side effects of corticosteroids
transcription of proteins
Hoarse voice ( dysphonia) , reflex cough following inhalation Oral candidiasis
what do you give as an IV injection in emergency treatment of a severe acute asthma attack
Hydrocortisone
Leukotriene - receptor antagonists eg montelukast and zafirlukast
effective in late phase asthmas response - inhaled with corticosteroid
how does it work
Block effects of cysteinyl leukotriene in airways - anti-inflammatory reaction
cromones is a prophylactic drug
would it have value in an acute asthma attack
no
What are limitations of croons
Must be withdrawn gradually over 1 week - side effects - throat irritation and untolerable for some patients , sudden withdrawal rebound sensitivity
Long acting Beta 2 agonists salmeterol and formoterol
used when
long term control of chronic asthma
How to monoclonal antibodies work
selectively bind to IgE forming a complex ( mast cell not activated reducing mediated response)
over 12
what does well controlled asthma look like
Well controlled asthma look like
No daytime symptoms
No night time awakening due to atham
No need for rescue medication ( reliever ones)
No limitation on activity including exercise
Normal lung function with minimal side effects
FEV1 and/or PEF >80% predicted or best
ICS
inhaled corticosteroids
. A patient comes into hospital after falling through thin ice on a frozen lake. He is hypothermic.
i). Which direction will the oxygen dissociation curve shift in response to this patient’s change in temperature?
Ii). Does this environment favour the loading or unloading of oxygen?
i). Left, (½ mark).
Ii). Loading, (½ mark).
Reduced temperature is a factor which shifts the oxygen dissociation curve to the left, favouring the binding or loading of oxygen to haemoglobin. This naturally occurs in the alveoli which have a reduced temperature compared to other parts of the body, encouraging the loading of oxygen to red blood cells in the lungs in order to be delivered to the rest of the body. In hypothermia, the entire body temperature is reduced, this means oxygen isn’t unloaded as readily in it’s target locations around the body.
other factors that shift it left are
Any two of: Alkalosis/Increased blood pH/less acid; Decreased CO2/metabolites; Decreased 2, 3 DPG; CO poisoning; foetal haemoglobin. (½ mark each). This environment is found naturally in alveolar cells to encourage loading of oxygen. However it can also occur during pathological processes in areas of the body where the unloading of oxygen is needed such as CO poisoning.
Sx of asthma
a whistling sound when breathing (wheezing). Breathlessness. a tight chest, which may feel like a band is tightening around it.Coughing, hyperresonant chest on percussion
The cold produces histamine , fluid evaporates faster than it can be replaced so dry airways - produce histamine - allergic
what is occurring immunological with asthma
Allergen inhaled to bronchioles, consumed by dendritic cells activating them they release chemokines - TH2 cells bought in or recognised by columnar epithelium released by TSLP increases mre chemokine
TH2 activate plasma cells to release IgE using Il-13,4
Mast cell but Il-9
Eosinophil production and bone marrow
Ige binds on to mast cell to bind to complex and release prostaglandins causing bronchoconstriction , all inflammation creates mucus build up
Endothelial - main mast cells to area - release stem cell factors
Long term asthma control medication that is taken regularly to control chronic symptoms and prevent asthma attacks — the most important type of treatment for most people with asthma
Inhaled corticosteroids Leukotriene modifiers Long-acting beta agonists (LABAs) Theophylline Combination inhalers that contain both a corticosteroid and a LABA
quick relief medications ( rescue medications) -Taken as needed for rapid, short-term relief of symptoms — used to prevent or treat an asthma attack
Short-acting beta agonists such as albuterol
Ipratropium (Atrovent)
Oral and intravenous corticosteroids (for serious asthma attacks)
Medications for allergy-induced asthma- Taken regularly or as needed to reduce your body’s sensitivity to a particular allergy-causing substance (allergen)
Allergy shots (immunotherapy) Allergy medications
