Respiratory Pharmacology

Question 1

Whereas BTS guidelines suggest adding a LABA after low dose ICS, NICE suggests trying a LTRA before moving to a LABA.

Why?

Answer 1

LTRAs are cheaper (but most end up on LABAs anyway

Question 2

Beclometasone, Budesonide and Fluticasone are members of what class of drugs?

When are these prescribed?

Answer 2

Inhaled Corticosteroids (ICS)

First line management of Asthma, used as preventers

Question 3

How do ICS drugs work?

Answer 3

• Pass through plasma membrane, activate cytoplasmic receptor-> Modified transcription
• Reduce mucosal inflammation, widen airways and reduce mucus
• Reduce Arachidonic acid production-> reduced production of Leukotrienes and Prostaglandins

Question 4

List ADRs, Contraindications and DDIs of ICS therapies

Answer 4

ADRs;
- Local Immunosuppression (Candidiasis, hoarse voice)

Contraindications;
- Risk of pneumonia in COPD, if taken at high doses

DDIs;
- Very few if taken correctly

Question 5

ICS therapies have a poor oral bioavailability and high affinity for glucocorticoid receptors.

At high doses, which ICS therapies can cause systemic effects?

Answer 5

All of them

Question 6

List 2 Short Acting Beta Agonists (SABAs)

Compare the LABAs, Salmeterol and Formoterol

Answer 6

• Salbutamol
• Terbutaline
• Salmeterol: Slow onset of action
• Formoterol: Fast onset of action

Question 7

Compare SABA and LABA use

Answer 7

SABA: Symptom relief, used only when required

LABA: Used as add-on therapy to ICS, SABAs still used when required

Question 8

How do Beta agonists work to alleviate asthma symptoms

Answer 8

• Major action on airway smooth muscle
• Increase mucus clearance by cilia action

(SABAs can be used to prevent constriction prior to exercise)
(Regular SABA use can lead to poor asthma control/ tolerance?)

Question 9

List 7 ADRs of Beta agonists

Answer 9

• Tachycardia
• Palpitations
• Anxiety
• Tremor
• Increased renin
• Increased glycogenolysis
• Possible SVT

Question 10

List 2 contraindications of Beta agonists

Answer 10

• LABAs should ONLY be prescribed alongside ICS (often as a combined inhaler)
• CVD (tachycardia may cause angina)

(LABAs alone can mask airway inflammation and fatal/ near-fatal attacks

Question 11

List DDIs of Beta agonists

Answer 11

Beta blockers may reduce effectiveness of Beta agonists

Question 12

What kind of drug is Montelukast?

(These drugs are used as additional controller therapies in asthma)

How does it work?

Answer 12

Leukotriene Receptor Antagonist (LTRA)

Prevents Leukotrienes (from Mast cells/ Eosinophils) binding to CysLT1 (a GPCR) therefore reducing;

• Bronchoconstriction
• Mucus production
• Oedema

Question 13

List 4 ADRs of LTRAs

What are the DDIs of LTRAs?

Answer 13

Headache, Hyperactivity
GI disturbance, Dry mouth

• No major DDIs reported

Question 14

What kind of drug is Tiotropium?
What are 2 uses for these drugs?

How do they work?

Answer 14

• Long Acting Muscarinic Antagonist (LAMA)
• Severe asthma and COPD
• Block Vagal mediated contraction of airway smooth muscle

Question 15

Compare LAMAs to SAMAs in terms of receptor selectivity

Answer 15

LAMAs are more selective for M3 receptors

Question 16

List 3 ADRs for LAMAs

Answer 16

Infrequent Anticholinergic effects;

• Dry mouth
• Urinary retention
• Dry eyes

Question 17

What kind of drug is Theophylline?
How do these work?

(Theophylline is taken orally for poorly controlled asthma)

Answer 17

• Methylxantine

- Adenosine receptor antagonist = Less bronchoconstriction

Question 18

Suggest an ADR for Theophylline

Answer 18

Has a narrow therapeutic index so can-> Arrhythmia (SVT)

Can also cause seizures

Question 19

Suggest a DDI for Theophylline

Answer 19

If taken with CYP450 inhibitors, higher dose needed

Question 20

Describe the treatment of acute severe/ life threatening asthma

Answer 20

• Get O2 sats to 94-98%
• High dose Beta agonist
• Oral steroids for 5 days minimum, alongside ICS
• Nebulised SAMA alongside Beta agonist, if response is poor
• Consider IV Aminophylline if no success with above and life threatening (caution if also on Theophylline)

Question 21

Name an oral steroid and a SAMA that can be used in treating life threatening asthma

Answer 21

Oral steroid: Prednisolone (Hydrocortisone in emergency)

SAMA: Ipratropium

Question 22

What are the 5 ‘tasks’ of managing COPD

Answer 22

1. Confirm diagnosis
2. Smoking cessation
3. Breathlessness/ MRC Dyspnea score (+ lifestyle advice)
4. Vaccination (flu, pneumococcal)
5. Medication

Question 23

How would you treat an acute exacerbation of COPD?

What if patient is hypercapnic/ acidotic?

Answer 23

• Nebulised Salubutamol or Ipratropium
• Drive nebuliser by air not O2
• Antibiotics (narrow or broad)
• Oral steroids (can be less effective than in eosinophilic asthma, due to reduced action on neutrophils)

Question 24

Compare 3 broad categories of inhalers

Inhalers often prescribed by brand

Answer 24

pressured Metered Dose Inhalers (pMDI);

• Inhalation and actuation of device
• Slow breath in and hold
• Can be used with a spacer to improve delivery

Breath-actuated pMDI;
- Automatic actuation upon inspiration

Dry Powder Inhalers (DPI);

• Micro ionised drug + carrier powder
• Fast deep inhalation

Question 25

State the major site of drug deposition, using an inhaler if Inspiratory Flow is;

• Too fast
• Too slow
• Optimal

Answer 25

Fast: Throat

Slow: Mouth

Optimal: Lungs