Bronchodilators

Question 1

What do bronchodilators do?

Answer 1

• Reverse bromchospasm
• Rapid relief

Question 2

What are B2-adrenoceptor agonists?

Answer 2

• E.g. Salbutamol
• Agents of 1st choice
• Inc FEV1
• Act on B2 adrenoceptors–>bronchodilation
• Given by inhalation
• Longer acting agents (e.g. salmeterol) given for long term prevention

Question 3

How does salbutamol work?

Answer 3

• Binds to B2-adrenoceptor, casuing the release of adenylyl cyclase inside the cell
• This converts ATP to cAMP, this activates protein kinase A
• Protein Kinase A causes K+ to leave cell, causing Hyperpolarisation
• Causes the calcium channels to close, resulting in a decrease in Ca infulx
• Leading to relaxation of airway tone

Question 4

Where else are B-adrenoceptors found?

Answer 4

• Found on mast cells
• Inc in cAMP prevents release of histamine etc.
• Also effects on mucous secretion

Question 5

What is Desensitisation?

Answer 5

• Long term use of B-adrenoceptor agonists leads to tolerance/desensitisation
• Due to internalisation
• Prevented by steroids

Question 6

What happens in short-term activation of a receptor?

Answer 6

• Phosphorylation of receptor and uncoupling of signalling

Question 7

What happens in long-term activation of a receptor?

Answer 7

• Internalisation of receptor
• Reversible
• Internalisation into endosomes-receptor processed and returned to membrane

Question 8

What happens with chronic activation?

Answer 8

(tens of mins to hours)
* Internalisation of receptor
* Degredation of receptor in lysosomes
* Irreversible
* Downregulation of receptor

Question 9

What are some examples of B-adrenoceptor agonists?

Answer 9

1. Salmeterol
2. Formoterol(2xDay)
3. Indacaterol(1xDay)
4. Salbutamol(4xDay)

Question 10

What are some adverse effects of B2 adrenoceptor agonists?

Answer 10

• Tremor
• Palpitations
• Hypokalaemia (hugh doses e.g nebulisers)

Question 11

What do PDEs do? (phosphodiesterase)

Answer 11

• Regulated cAMP by metabolising it to 5’AMP

Question 12

What are some PDE inhibitors?

Answer 12

• Roflumilast (PDE4) inhibitor (DAXAS)
• COPD
• Red inflammation
• Pot for enhancing B-AR effects
• Roflumilast for treating chronic obstructive pulmonary disease

Question 13

What do Muscarininc M-receptor antagonists do?

Answer 13

• Block parasympathetic bronchoconstriction
• E.g. ipratropium
• Given by inhalation-fewer systemic side effects
• Also inhibits mucous secretion
• Titotropium-long acting, due to slow dissociation from receptor
• Based on Atropine

Question 14

What are the Muscarinic receptor subtypes?

Answer 14

• M1 CNS-Salivary glands, gastric glands
• M2Heart-rate of contraction, GI smooth muscle contraction, CNS
• M3 Salivary glands, smooth muscle (GI, Airways)
• M4 CNS
• M5 CNS

Question 15

Explain how Adrenaline and noradrenaline work on the airways?

Answer 15

Question 16

What are side effects of Muscarinic M-receptor antagonists?

Answer 16

• Non-selective therefore block muscarininc receptors around body (NB inhaled vs Oral):
• Dry mouth (salivation)
• Nausea/Headache (CNS)
• Atrial fibrillation & tachycardia & palpitation (Cardiac)
• Constipation (GI)
• Blurred vision (accomodation)

Question 17

What are Xanthines?

Answer 17

• e.g theophylline (Doxofylline)
• Bronchodilators
• Oral (or i.v. amonophylline in emergrncy)
• Historically- Phosphodiesterase inhibitors- Inc cAMP but not at clinically relevant concs
• Adenosine rec antagonist
• Anti-inflam effects

Question 18

What is Aminophylline?

Answer 18

• Mix of theophylline and ethylenendiamine (2:1)
• Improves solubility
• Used for emergencies

Question 19

What are the side effects of Aminophylline?

Answer 19

• Tremor, palpitations, Nausea
• CNS stimulation (sleep disturbance, “overactivity”)
• Drug interactions:
  1. Inhibition of metabolism inc risk of toxicity
  2. Induction of metabolism red plasma levels