F11i / 19B08 / 16B04 / 14B11: Tx Asthma

19B08: Exam Report

Outline the pharmacology of drugs used to treat asthma.

29% of candidates passed this question.

Answers should have included the most important aspects of the pharmacology of the most commonly used drugs e.g. class, mechanism of action, pharmacodynamics and important adverse reactions. More information on beta-agonists and corticosteroids (mainstays of management) was expected than drugs like magnesium, ketamine and other adjunctive
treatments.

16B04: Exam Report

Categorise the drugs used in the treatment of asthma, give examples and outline their mechanisms of action.

71% of candidates passed this question.

Asthma drugs are typically categorised according to mechanism of action. A reasonable alternative is to categorise by clinical use, e.g. short acting, long acting, preventer, rescue etc.

A lot of emphasis in marking was placed on an understanding of the beta-adrenergic pathway, its secondary messenger system and how this medicates smooth muscle relaxation. Candidates whose answers had structure as well those who described the wide range of drugs used to treat asthma scored well.

14B11: Exam Report

Describe the mechanisms of action of drugs used to treat acute severe asthma and give examples.

54% of candidates passed this question.

Asthma involves reversible bronchospasm, inflammation, and airway hyper-responsiveness to inhaled stimuli. The main classes of drugs for acute therapy include sympathomimetics, antimuscarinic agents, corticosteroids, methylxanthines and magnesium. Candidates should have a detailed knowledge of the mode of action of these mainstream drugs. Information about drugs used for prevention  and for chronic asthma was not asked for and answers which provided details about long term inhaled steroids or leukotriene antagonists did not gain extra marks.

This question was well covered by some candidates in a semi-table format. A structured approach worked well with details about drug class, mechanism of action and example(s).

F11i / 19B08 / 16B04 / 14B11: Categorise the drugs used in the treatment of asthma, give examples, outline their mechanism of action (70%)

Define

  • Asthma is a chronic airway disease, characterized by airway hyper-responsiveness

Mechanism of Asthma

Early

Genetic predisposition

Allergen exposure

IgE Ab production

IgE Ab bind to MCs of bronchial mucosa

Re-exposure to allergen

MC degranulation

Histamine, Tryptase, Leukotrienes, PGIs → sm m contraction & vascular leakage

Late

Influx inflam cells to bronchial mucosa

Release cytokines +++

­bronchial reactiveness

Class

Drug

B2 agonist

Salbutamol

Sympathomimetic

Adrenaline

Steroid

Hydrocortisone

Methylxanthine

Theophylline

Antimuscarinic

Ipratropium

Oxygen

Oxygen

Other

Class

Drug

MoA

B2 agonist

Salbutamol

B2 agonist

­↑AC

­↑cAMP

­↑Pr Kinase A

Inhibits phosphorelation of myosin

↓Ca intrac

=

1)sm m relaxn

2)inhibits MC degranulation

3)Inhibits microvascular leakage

4)↑mucociliary clearance

Sympathomimetic

Adrenaline

Agonist at b1, b2, a receptors

­↑AC

­↑cAMP

­↑Pr Kinase A

Inhibits phosphorelation of myosin

↓Ca intrac

=

1)sm m relaxn

2)inhibits MC degranulation

3)Inhibits microvascular leakage

4)↑mucociliary clearance

Steroid

Hydrocortisone

Binds steroid receptors

Alters DNA protein transcription

Inhibits Phospholipase A2

↓Arach Acid

↓PG, leukotriene, interleukin production

↓inflam cascade, oedema, cap leakiness

↓airway hyperresponsive

ness w time

Methylxanthine

Theophylline

1)PDE Type 3&4 inhibitor

↓cAMP breakdown

­↑cAMP

↓Ca incrac

sm m relaxn

2)Adenosine Rec Blockade

inhibits Adenosine-mediated sm m constriction

= bronchodilation

Antimuscarinic

Ipratropium

Quaternary – does not cross BBB

 

Inhibits mACHR (M3) on bronchial sm m

GPCR

↓Phospholipase C

↓DAG, IP3

↓Ca

↓vagal mediated bronchoconstr

& secretions

Oxygen

Oxygen

Rapidly diffuses Blood Gas Barrier

Enables aerobic metab

Other

Heliox – low density gas

­↑laminar flow

↓turbulent flow

Propofol

mAChR antagonism = bronchodil

Ketamine

Intrinsic catechol release

mAChR antag

= broncholdl

Volatiles (sevo) = ↓sm m tone

Mg++ = blocks Ca ch = sm m relax

Omalizumab

Anti-IgE-Ab

Prevents degranulation

Class

Drug

SE

B2 agonist

Salbutamol

B2

Tremor

Sweating

B1

Palpitations

tachycardia

Sympathomimetic

Adrenaline

A1

Periph VC

B1

Tachy, arryth

Nausea, abdm pain, hyperglycaemia

Steroid

Hydrocortisone

Adrenal suppression

Hyperglyc

Osteoporosis

↓plat aggr  = bleeding

Methylxanthine

Theophylline

GI – ­↑gastric acid production

CNS – stimulant, ­↑seiz risk, ↓CBF

RESP – inhibits HPVC

CVS +ve inotropy, arythmogenic, ↓SVR

Antimuscarinic

Ipratropium

Unpleasant taste

Oxygen

Oxygen

Oxygen

Toxicity

RESP

CNS

RETINAL

AE

Other