Respiratory Pharmacology

Question 1

Smooth muscle contraction

Answer 1

• Ca2+ increase extracellular & sarcoplasmic reticulum
• Ca2+ binds to calmodulin
• Ca2+ and calmodulin complex activates myosin light chain kinase which phosphorylates myosin complex
• Myosin head can bind to actin
• Fibres contract by power stroke always smll level of contraction

Question 2

Parasympathetic innervation

Answer 2

• Parasmpathetic dominant by vagal nerve
• M1, M2 and (M3 which is most important)
• M3 produce most stimulatory effects from neurotransmitter acetylcholine
• Gq protien bind to M3 inosital phosphate pathway (increase IP3)
• Gland secreation calcium and smooth muscle of airways contraction

Question 3

Sympathetic NS Innervation

Answer 3

• Sympathetic innervate blood vessels and gland in trachea and blood vessel
• B2 adenoreceptors couple with apha subunit Gs smooth airway muscles and alveoli
• Increase in cAMP and PKA
• Inactivates myosin light chain kinase so myosin is not phosphorylated
• Respond to circling agonist - relax bronchial smooth muscle
• Activate potassium channel leaves hyperpolarise less likely to form AP

Question 4

Beta-adenoreceptors

Answer 4

• Mast cells inhibit mediator release
• Epithelium enhance muco-cilliary clearance
• Decrease in calcium
• Stimulation effects the heart, lungs, skeletal muscle and blood vessels

Question 5

Other forms of innervation

Answer 5

• Airways supplied with excitatory and inhibitory non-adrenergic non-cholinergic (NANC)

Question 6

What substance is secreted during broncoconstriction?

Answer 6

• Acytylcholine and substance P

Question 7

What substance is secreated during bronchodialation?

Answer 7

• Nitric oxide by the endothelial cells

Question 8

Receptors on bronchial smooth muscle

Answer 8

• Histamine for bronchoconstriction
• Leukotreines which are inflammatrory mediators for bronchoconstriction

Question 9

Aim of Bronchodialators

Answer 9

• Relief and rescuing patient from bronchospasm

Question 10

Aim of anti-inflammatories

Answer 10

• Prophylaxis by reducing frequency of attack
• Reduced severity of attacks
• Limit structure remodelling

Question 11

Bronchodialator classes

Answer 11

• Beta adenoceptor agonist
• Xanthines
• Muscarinic receptor agonist
• Leukotriene receptor antagonists
• Histamine receptor antagonists

Question 12

Anti-inflammatory receptor classes

Answer 12

• Glucocorticoids
• Cromoglicate and nedocromil
• Anti-IgE immunotherapy
• Phosphodiesterase (PDE) inhibitors

Question 13

Beta-adrenoceptor agonist mechanism

Answer 13

• Beta receptor stimulation via G protien activating adenylyl cyclase
• Increasing levels of cAMP activating protien kinase A which phosphorylates targets and leads to bronchodialation
• MLCK activity decrease less contract
• Activate K+ channel leads to hyperpolarisation decrease Ca2+ channel open less entry to intracellular so less contract

Question 14

Beta-adenoreceptor agonist

Answer 14

• Bronchodilation
• Inhibition of mediator release from mast cells
• Enhanced mucocilliary clearance
• Little effect on bronchochiral hyperactivity

Question 15

Delivery of Beta-adenoreceptor agonist

Answer 15

• Inhalation of aerosol powder or nebulised solution
• Lower dose required via airways fast onset of action with inhaled brochodialators than systemic

Question 16

The optimum penitration of airways

Answer 16

• 5-10 microns - the lower airways bronchioles and alveoli
• 10-15 microns for particles in the upper airway 100% deposition

Question 17

SABA: Short acting beta adenotreceptors agonist

Answer 17

• Salbutamol, terbutaline
• Hydrophilic in nature
• Short duration of action (4-6hrs)
• Take as required

Question 18

Long lasting beta adenoreceptor agonist

Answer 18

-