Asthma Drug Treatment

Question 1

Two types of drug treatment for asthma?

Answer 1

Relievers and Controllers.

Question 2

Difference between a reliever and a controller?

Answer 2

Relievers are fast acting and treat an acute attack whereas controllers have no effect during an acute attack and require long term usage.

Question 3

4 types of relievers.

Answer 3

Slow Acting Beta2-adrenoceptor agonist (SABA)

Long acting beta2-adrenoceptors agonist (LABA)

Ultrs-LABA

CyLT1 receptor antagonists.

Question 4

SABA drugs in treatment of asthma?

Answer 4

Salbutamol and Terbutaline.

Question 5

Other name for Salbutamol?

Answer 5

Albuterol.

Question 6

LABA drugs in treatment for asthma?

Answer 6

Salmeterol and Formoterol.

Question 7

Why is salmeterol not used in acute attacks?

Answer 7

Slow acting.

Question 8

What are LABAs usefor for treating?

Answer 8

Nocturnal asthma as they act for about 8 hours.

Question 9

Most important things about LABAs?

Answer 9

CANNOT be administered alone.

Question 10

What must LABAs be co-administered with?

Answer 10

Glucocorticoids. e.g. beclametosone

Question 11

Effects of SABAs?

Answer 11

Relax bronchial smooth muscles.

Increase mucus clearance.

Decrease mediator release from mast cells and monocytes.

Question 12

What are methylxanthines sometimes used as?

Answer 12

Both relievers and controllers.

Question 13

Purpose of controllers?

Answer 13

With long term usage they reduce the frequency and severity of asthma attacks.

Question 14

Examples of controllers?

Answer 14

Glucocorticoids,
Cromoglicate,
Humanised monoclonal IgE antibody (Expensive).

Question 15

Beta2-adrenoceptor agonists act as…

Answer 15

Physiological antagonists for all spasmogens.

Question 16

Why are non-selective beta-adrenoceptor agonists redundant in asthmatics?

Answer 16

Risk of bronchospasm.

Question 17

What is the name of CysLT1 receptor antagonist and what does it act as?

Answer 17

Cysteinyl leukotriene receptor antagonists.

Bronchodilator.

Question 18

How does CysLT1 receptor antagonist act as a reliever?

Answer 18

CysLT1 act competitively on CysLT1 receptor. Competing with LTC4, LTD4 and LTE4 which are derived from mast cells and infiltrating inflammatory cells causing smooth muscle contraction, mucus secretion and oedema.

Question 19

What occurs if CysLT1 receptor antagonists do not bind to CysLT1 receptor?

Answer 19

CysLTs (LTC4, LTD4, LTE4) bind to receptor instead activating it and causing early phase bronchoconstriction followed by delayed phase inflammation.

Question 20

Examples of CysLT1 receptor antagonists?

Administration route?

Primary treatment or add on?

Answer 20

Montelukast, Zafirlukast.

Oral.

Suitable as an add on to treat bronchospasm.

Question 21

Why is CysLT1 receptor antagonists not recommended for relief of acute severe asthma?

Any side effects?

Answer 21

Not as effective as a SABA such as salbutamol.

Generally well tolerated but headaches and gastrointestinal upset reported.

Question 22

Methylxanthines molecular mechanism?

Answer 22

Unknown but thought to inhibit isoforms of phosphodiesterases (PDE3 & 4) which inactivate cAMP preventing binding to PKA and advancement to MLCK which results in relaxation of ASM.

Question 23

Effects of methylxanthines?

Primary or add on treatment?

Administration route?

Side effects?

Answer 23

Bronchodilator (high doses) and anti-inflammatory. Increased mucous clearance, increased diaphragmatic contractibility

Add on used in combination with Beta-2-adrenoceptor agonists and glucocorticoids.

Oral.

Very narrow therapeutic window, nausea, headache, vomiting reported and above TPW can cause seizures and hypotension.

Question 24

What could potentiate anti-inflammatory action of glucocorticoids?

Answer 24

Theophylline activates histone deacetylase.

Question 25

What are the 2 classes of steroid hormone? Where are they synthesised? Pre stored?

Answer 25

Glucocorticoids, Mineralocorticoids. Adrenal cortex. No, synthesised and released on demand.

Question 26

Main hormone in glucocorticoids? Effects?

Answer 26

Cortisol (hydrocortisone). < inflammatory response < immunological response

Question 27

Main mineralocorticoid? Effect?

Answer 27

Aldosterone. Regulates sat and water retention by the kidneys.

Question 28

Why are glucocorticoids ineffective in an acute attack? Administration route?

Answer 28

They have no direct bronchodilator action and therefore cannot relieve bronchospasm. Usually inhaled to minimise adverse effects.

Question 29

What is an endogenous steroids?

Answer 29

Gluco and mineralocorticoid actions but the latter is unwanted in treatment of inflammatory conditions.

Question 30

Glucocorticoid molecular mechanism of action?

Answer 30

Signal via nuclear receptors (GRalpha). Glucocorticoids are lipophilic and diffuse into cell across PM. In cytoplasm they combine with GRa producing dissociation of HSPs. The activated receptor translocates to the nucleus via importins. Here the monomers assemble to homodimers and bind to Glucocorticoid response element (GRE). Transcription of specific genes is switched on (transactivated) or switched off (transrepressed) to alter mRNA levels and rate of synthesis of mediator proteins.

Question 31

How do glucocorticoids affect translation of inflammatory and ant-inflammatory genes?

Answer 31

Decrease inflammatory. Increase anti-inflammatory.

Question 32

Why do glucocorticoids recruit HDACs?

Answer 32

To switch off transcription.

Question 33

What does expression of inflammatory genes involve?

Answer 33

Acetylation of histones by histone acetyltrasferases (HATs).

Question 34

What does acetylation of histones cause?

Answer 34

Unwinding of DNA from histones allowing transcription.

Question 35

Effect of HDAc and HAT on transcription?

Answer 35

HDAC = No transcription HAT = Transcription.

Question 36

Effect of glucocorticoids on TH2 cytokines?

Answer 36

Decrease formation of eg IL4 IL5 and cause apoptosis.

Question 37

How are glucocorticoids usually administered?

Answer 37

By inhalation from a metered dose inhaler (to minimise adverse effects such as oropharyngeal candidiasis).

Question 38

What are cromones?

Answer 38

Drugs that supress histamine release from mast cells.

Question 39

What is the effect of cromones on bronchial smooth muscle?

Answer 39

None.

Question 40

What is sodium cromoglicate?

Answer 40

Specific cromone agent, delivered by inhalation and more effective in young people.

Question 41

Example of a monoclonal antibody directed on IgE? Mechanism of action?

Answer 41

Omalizumab. Requires IV administration.