Asthma Series 1: AsthmaMeds

Hello everyone. Let's revise on how asthma happens and what are the medications available.

Pathogenesis of asthma 
(The basis to understanding all the medications used below, so please spend time understanding the concise version of pathogenesis. Feel free to drop a comment if there is any part that is not clear or you would like to provide us with extra info)


Reference:
Robbins Pathology, 8th Edition

Asthma medications are divided into 2:
1. Reliever (Relief of bronchoconstriction)
2. Controller (Reduction of symptoms and prevention of attacks)

RELIEVERS
Beta-2 agonist (eg: salbutamol and terbutaline)
Pharmacology:
Rapid onset (15-30 mins)
Peak: 30-60mins
Duration of action: 4-6hours


Mechanism of Action: 

Beta adrenergic receptors are coupled to a stimulatory G protein, Gs, of adenyl cyclase (AC). AC will then catalyze the production of second messanger cyclic adenosine monophosphate (cAMP).

In the lungs, cAMP reduces calcium concentrations within cells and activates protein kinase A, leading to inactivation of myosin light-chain kinase (MLCK) and activation of myosin light-chain phosphatase (MLCP).

Beta-2-agonists also open up Ca2+-activated K+ channel, thus causing hyperpolarization of airway smooth muscle cells.

Low intracellular calcium + Increased membrane K+ conductance + Decreased myosin light chain kinase activity --> Smooth muscle relaxation and bronchodilation

Pearls of Beta 2 agonist
1. MOA: Relax airway smooth muscle, 
inhibit release of bronchocontricting mediators from mast cells
inhibit microvascular leakage and
 increase mucociliary transport by increasing ciliary activity

2. Best mode is by INHALATION
- greatest local effect on airway smooth muscle 
- least systemic toxicity

3. Best deposition of aerosol particles when it size is 2-5mm, SLOW INHALATION of a nearly full breath and by more than 5 seconds of BREATH HOLDING at the end of inspiration

4. Particles generated by nebulizer are bigger than those from metered-dose inhaler, much higher dose must be given but are no more effective. Thus, is reserved for patients unable to coordinate inhalation from MDI.

5. Tablet form is of no advantage over inhaled treatment, thus rarrely prescribed

Low-dose ICS/formoterol
eg: beclomethasone/formoterol or budesonide/formoterol
(for patients on maintenance and reliever medications, reduce risk of exacerbation)

NOTE: Long acting beta 2 agonist(salmeterol/formoterol) does not provide any anti inflammatory action, thus cannot be used as monotherapy BUT appear to interact with inhaled corticosteroids to improve asthma control

Short-Acting Anticholinergics
eg: Ipratropium bromide
- used during asthma exacerbation
- less effective than SABA but can reduce hospital admission if used with SABA
- MOA: Competitively inhibit the effect of acetylcholine at muscarinic receptors --> block the contraction of airway smooth muscle and the increase of mucus secretion


CONTROLLER

1. Corticosteroids
MOA: Reduce bronchial reactivity and reduce frequency of asthma exacerbations if taken regularly.
Most important is the inhibition of of infiltration of asthmatic airways by lymphocytes, eosinophils, and mast cells.

Route of administration: 
a) Oral and parenteral (reserved for urgent treatments ie: not responsive to bronchodilators or worsening symptoms despite maintenance therapy)
eg: Prednisolone, hydrocortisone
- short term treatment (5-7 days --> tackle the late phase reaction of asthma..refer to pathogenesis above)
- long term oral treatment in selected patients with severe asthma, after considering its side effect
b) Inhaled (usually prescribed with long acting beta 2 agonist to improve asthma control)

When to give:
a) Early in the morning (to reduce the effect of adrenal suppression as endogenous adrenocorticotropic hormone has peaked due to diurnal variation)
b) Late afternoon (for prevention of nocturnal asthma)

Side effects:
i) Inhaled corticosteroids
a) Oropharyngeal candidiasis 
- can be reduced by gargling water and spit after each inhalation
b) Hoarseness
- due to local effect of corticosteroids on vocal cords
c) Slow growth rate by about 1 cm over the FIRST YEAR of treatment in children and not the rate afterwards. So the effect is minimal in adults. 

ii) Systemic corticosteroids
a) Short term: Sleep disturbances, reflux, appetite increase, hyperglycemia, mood changes
b) Long term: cataract, glaucoma, osteoporosis, adrenal suppression, Cushing syndrome, high blood pressure, diabetes

2. Leukotriene Pathway Inhibitors
Improve asthma control and reduce the frequency of asthma exacerbation in outpatients

a) 5-lipooxygenase inhibitor
eg: zileuton
- it is the least prescribed due to liver toxicity

b) Leukotriene receptor antagonist (LTD4-receptor antagonists)
eg: zafirlukast and montelukast (tablet/granules form) - 10mg for adults / 4mg for children (once daily) - most prescribed (why? once daily, can be taken without regard to meals)

3. Cromolyn and Nedocromil
They effectively inhibit both antigen and exercise-induced asthma, and chronic use (4x daily) slightly reduced the overall level of bronchial reactivity (good as a prophylaxis)

Side effects:
Minor and localized (due to its poor absorption)
a) Common:Throat irritation, cough, and mouth dryness 
b) Rare: chest tightness, and wheezing

Serious 
a) Reversible dermatitis, myositis, or gastroenteritis (2%)
b) Very rare: Pulmonary infiltration with eosinophilia and anaphylaxiis

4. Long acting anticholinergic
eg: Tiotropium
Add on therapy to Step 4/5 by mist inhaler for 12 years old and above with history of exacerbation despite ICS+LABA

Side effects:
Dry mouth (uncommon)

5. Anti IgE Monoclonal Antibodies
eg: SC Omalizumab
Inhibits the binding of IgE to mast cells but does not activate IgE already bound to these cells, hence does not provoke mast degranulation
- Reduction of the frequency and severity of asthma exacerbations by ~88%
- Reduction in the need of corticosteroid

Add on therapy for patients with severe allergic asthma, who are 6 years and above in Step 4 (high dose ICS/LABA)

Side effects: Reactions at site of injection, Anaphylaxis is rare.

6. Anti Interleukin 5
eg: SC mepolizumab, IV reslizumab

Add on therapy for patients with severe allergic asthma, who are 12 years and above in Step 4 (high dose ICS/LABA)

Side effects:
Headache, reactions at injection site (common but minor)

Others:

Magnesium sulfate 
It is used in some exacerbation cases when patient is not improving despite treatment

MOA:
  • inhibit smooth muscle contraction
  • reduces histamine release from mast cells
  • inhibit acetylcholine release 

References:
1. GINA 2017 Pocket Book
2. Principles of Pharmacology: The Pathophysiologic Basis of Drug Therapy
    https://goo.gl/wgdeDl
3. Basic and Clinical Pharmacology, 12th edition


Comments

  1. Anneke Sergio28 August 2019 at 14:56

    Here is a great herbal doctor who cured me of Hepatitis B. his name is Dr. Imoloa. I suffered Hepatitis B for 11 years, I was very weak with pains all over my body my stomach was swollen and I could hardly eat. And one day my brother came with a herbal medicine from doctor Imoloa and asked me to drink and I drank hence there was no hope, and behold after 2 week of taking the medicine, I started feeling relief, my swollen stomach started shrinking down and the pains was gone. I became normal after the completion of the medication, I went to the hospital and I was tested negative which means I’m cured. He can also cure the following diseases with his herbal medicine...lupus, hay fever, measles, dry cough, diabetics hepatitis A.B.C, mouth ulcer, mouth cancer, bile salt disease, fol ate deficinecy, diarrhoea, liver/kidney inflammatory, eye cancer, skin cancer disease, malaria, chronic kidney disease, high blood pressure, food poisoning, parkinson disease, bowel cancer, bone cancer, brain tumours, asthma, arthritis, epilepsy, cystic fibrosis, lyme disease, muscle aches, fatigue, muscle aches, shortness of breath, alzhemer's disease, acute myeloid leukaemia, acute pancreatitis, chronic inflammatory joint disease, Addison's disease back acne, breast cancer, allergic bronchitis, Celia disease, bulimia, congenital heart disease, cirrhosis, constipation, fungal nail infection, fabromyalgia, (love spell) and many more. he is a great herbalist man. Contact him on email; drimolaherbalmademedicine@gmail.com. You can also reach him on whatssap- +2347081986098.

    ReplyDelete
  2. Joyce Hillary2 October 2019 at 15:04

    All thanks to this great herbal doctor who cured me from (LUPUS DISEASE) his name is dr imoloa.  I suffered lupus disease for over 8 years with pains like: joints, Skin rash,  Pain in the chest,  swollen joints and many more.  The anti-inflammatory drugs couldn’t cure me, until I read about his recommendation. 2 months ago, I contacted him through his email address. drimolaherbalmademedicine@gmail.com . and he sent me the herbal treatment through DHL courier service and he instructed me on how to drink it for good two weeks. after then,  And I was confirmed cured and free at the hospital after taken his powerful herbal medications You too can be cured with it if interested, he also uses his powerful herbal healing medicine to cure disease like:parkison disease, vaginal cancer, epilepsy,  Anxiety Disorders, Autoimmune Disease,  Back Pain,  Back Sprain,   Bipolar Disorder,  Brain Tumour,  Malignant,  Bruxism, Bulimia,  Cervical Disk Disease, cardiovascular disease, Neoplasms,  chronic respiratory disease,  mental and behavioural disorder,  Cystic  Fibrosis,  Hypertension, Diabetes, asthma,  Inflammatory autoimmune-mediated arthritis.  chronic kidney disease, inflammatory joint disease, back pain,  impotence,  feta  alcohol spectrum,  Dysthymic Disorder,   Eczema, skin cancer,  tuberculosis,  Chronic Fatigue Syndrome, constipation, inflammatory bowel  disease, bone cancer, lungs cancer,  mouth ulcer,  mouth cancer, body pain, fever, hepatitis A.B.C.,   syphilis,  diarrhea,  HIV/AIDS,  Huntington's Disease,  back acne,  Chronic renal failure,   addison disease,  Chronic Pain,   Crohn's  Disease,   Cystic Fibrosis,  Fibromyalgia,   Inflammatory Bowel Disease,  fungal  nail disease, Lyme Disease, Celia disease, Lymphoma, Major  Depression,  Malignant Melanoma,   Mania,  Melorheostosis,   Meniere's  Disease,  Mucopolysaccharidosis , Multiple Sclerosis,  Muscular  Dystrophy,  Rheumatoid Arthritis, Alzheimer's Disease      Contacts him today  and get permanently cure. contact him via... email- drimolaherbalmademedicine@gmail.com  /whatssapp-+2347081986098.

    ReplyDelete

Post a Comment

Popular posts from this blog

Ortho Fracture Series 1: Proximal Humerus Fracture

Image
The new Ortho Fracture Series will cover the most important type of fractures. It is a compilation of info from various websites and textbook. In our very first series, we will look into proximal humerus fracture. It comprise of 4-6% of all fractures and the third most common fracture in elderly with females having higher incidence (2:1 ratio). Increasing age is also a risk factor for women. Understanding anatomy The 5 most important parts of proximal humerus: Greater tuberosity Lesser tuberosity Humeral head Anatomical neck (the epiphyseal plate) - located distal to the head of the humerus, at an oblique angle to the shaft of the humerus (fracture here,although rare, may lead to avascular necrosis) Surgical neck -  most frequently fractured  site of the proximal humerus (so surgeon operate here more often, hence the name, surgical neck), putting the  axillary nerve  and  posterior circumflex humeral branch  of the axillary artery at risk. Muscle around proxi
Read more

Baby gerak ok? (Approach to Reduced Fetal Movement)

Image
Very often reduced fetal movement causes anxiety to mothers. They are often worried something might have gone wrong to their child. Let's us dive into this topic to understand more about it and hopefully may help future mothers to alleviate their anxiousness. So, how do we define fetal movement? Fetal movement, defined as any discrete kick, flutter, swish or roll, is very subjective. It is usually based on maternal perception and varies according to individual. Most mothers will be able to feel the movement by 20 weeks of gestation (primiparous:18-20 weeks or later than 20 weeks, multiparous: ~16 weeks onward). These movements would increase until 32nd week and will then be plateau. During afternoon and evening periods, the fetal movement is at its peak. After moving much, there will of course be a sleeping period, which could last for 20-40 minutes, rarely exceeding 90 minutes, and occur throughout day and night. Presence of fetal movement symbolises the maturity of central ne
Read more

Cold Sweat Series 1: Oxygen Desaturation

Image
Nurse A: Dr, Dr! Patient desat.... New Dr : >< ohhh..desat..desat...what to do? God, please help me save this patient Below is the overview of the approach in this case Treatment: 1. Identify underlying cause 2. Supplementary oxygen maintain Pa02 at 60-80mmHg / SPO2 of 92-100%  to avoid oxygen toxicity as PaO2 of >80% is not proven to improve oxygen delivery and hence unnecessary Oxygen toxicity is concentration and time-dependent Lowest FiO2 should be used as FiO2 >60% leads to inflammatory changes, alveoli infiltration and then pulmonary fibrosis Nasal cannulae: 1-6L/min of oxygen (because 6L/min is adequate to fill the nasopharynx) - Fi02<40% Fi02>40% is delivered via oxygen mask with a reservoir Remember the oxygen dissociation curve? In the context of anesthesiologists, there are a few important points in the curve. They are ICU point, mixed venous point, arterial point, and P50. Definition of each term is as follows: ICU point
Read more