Pharmacology of Asthma

Question 1

Chronic asthma - what is it? what symptoms does it cause?
acute asthma - what is it? what is it marked by?

a list of treatments (4/6)

Answer 1

chronic- chronic inflam. associated with hyper-responiveness + variable airflow obstruction causing wheeze, chest tightness, breathlessness

acute- progressive worsening of inflam. symptoms and acute exacerbation marked by decrease in baseline assessment, dec. in FEV1 and Peak flow

treatments:

• SABA
• LABA
• LTRA (Leukotriene receptor agonist)
• inhaled corticosteroid
• Oral corticosteroids
• biologics

Question 2

Pathophysiology

Immediate Phase aka KEY WORD
what key thing is happening?
why? (2)

Late Phase aka
whats happening (3)
why? (mediators)

Answer 2

Immediate Phase aka Bronchospasm
-reversible airway obstruction
- smth. mscle in bronchioles contract
why?
genetic predisposition -> hypersensitive immune system
environmental trigger -> allergen, pollution, smoking

Late Phase aka inflammation 
- reveersible airflow obstruction
- inc. exudate, mucous, odema
why? Th cells, eosinophils, L-4 and IL-13 -> Th2
IL-3 and IL-5 -> Eosinophilic

Question 3

1,2, 3 steps of sensitisation
4,5,6,7, steps second exposure and EARLY PHASE
8,9,10 LATE PHASE

Answer 3

1) allergen picked up by APC
2) taken to lymph node, presented to T cell, activates B cell -> IgE produced
3) IgE from plasma cells binds to Mast cells via the Fc£RI receptor and they circulate

second exposure

4) allergen presents again
5) binds to IgE on mast cells circulating
6) cross-linking of multiple IgE on mast cell greatly inc. signalling inside mast cell
7) huge overproduction of granule contents and enzymes (histamine) leading to hypersensitivity

8) mast cell activates vagal afferent, activates parasympathetic stim. of smooth muscle on bronchi via adrenaline
9) inc. vascular permeability
10) exudation formed from eosinophils, neutrophils, Th2

Question 4

Budesonide
Class
Type 
Primary Target 
Activity 
Physiology

Answer 4

Class- ICS (inhaled corticosteroid)
Type- small mol.
Primary Target- Glucocorticoid Receptor
Activity- Agonist
Physiology:
Transrepression-> dec. pro-inflams mediators eg. TNFa, IL-6, COX-2, PGE2
Transactivation -> inc. anti-inflams, Eg IL-10, Anexin A1

Question 5

Salbutamol
Class- 
Type-
Primary Target -
Activity -
Physiology -
classic GCPR
extra->
overdose can cause ->

Answer 5

Class- SABA (Shot Acting B2 Agonist)
Type- small mol
Primary Target - B2 adregernic receptor 
Activity - agonist 
Physiology -
Gs -> adenyly cylase -> cAMP -> pKA -> s.m relaxation -> BRONCHODILATION 

extra: inc. cAMP can degranulate mast cells
overdose can cause binding to B1 in heart and heart palpitations (+ve inotropic effect)

Question 6

Montelaukast
Class- 
Type-
Primary Target -
Activity -
Physiology -

be careful with aspirin and asthma!

Answer 6

Class- LTRA (antagonist)
Type- small mol
Primary Target - Cys LT receptor
Activity - antagonist
Physiology -
LTs are inflam. medaitors derived from arachodonic acid
cause smth. muscle contraction, vasodilation, bronchoconstriction

aspirin will inhibt COX, LOX favoured and then casues brinchonstriction!

Question 7

Theophylline 
Class- 
Type-
Primary Target -
Activity -
Physiology -
clinical

Answer 7

Class- methyloxthine
Type- small mol.
Primary Target - Adenosine rec (non-selective)
Activity - comp. antagonist
Physiology -
GPCR: A2, GaS, inc. cAMP, pKA, bronchodilate
clincal (also a duirectic)

Question 8

Tiotropium 
Class- 
Type-
Primary Target -
Activity -
Physiology -

Answer 8

Class- LAMA (musiniric anatgonist)
Type- small mol
Primary Target - M3 rec
Activity - comp. anatagonsit
Physiology
INHIBITS: Ach + M3, GaQ, [Ca2+], contraction, inc. mucous.
therefore causes bronchodilation and dec. mucous

Question 9

differences between asthma and COPD (4)

Answer 9

astma is episodicand intermittent, COPD progressive
asthma night cough, COPD morning cough
asthma atopic/ genetic related, COPD smoking related
asthma younger, COPD older

Question 10

Biologics - monoclonal antibodies 
Benralizumab 
Mepolizumab 
Resilizumab
Omalizumab

Answer 10

Benralizumab- Binds to IL-5R on baso and eisinophils, FCyR3 becomes target for NK cells, dec baso and eosinophil levels.
Mepolizumab- binds to IL-5 dec, growth, act, recruit, eosinophils
Resilizumab ‘’
Omalizumab- Binds to IgE, dec IgE + Mast cell, dec. crosslinking and hypersensitivity