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Respiratory > Drugs Affecting Airway Structure & Function > Flashcards

Drugs Affecting Airway Structure & Function Flashcards

1
Q

What are some of the cellular processes underlying asthma?

A

Mucus hypersecretion, vasodilation, oedema, epithelial shedding, nerve activation, subepithelial fibrosis, bronchoconstriction

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2
Q

What contributes to airway constriction in asthma?

A

bronchoconstriction, mucus plug, oedema

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3
Q

Which part of airway constriction do preventer drugs help?

A

bronchoconstriction, mucus plug and oedema

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4
Q

Which part of airway constriction to relievers and controllers help?

A

Just bronchoconstriction

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5
Q

What holds airways open?

A

Smooth muscle, cartilage, attachments to parenchymal tissue, deep inspiration

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6
Q

What determines how fast and how much shortening of smooth muscle occurs?

A

The load on the muscle

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7
Q

What is the contractile mechanism of airway smooth muscle?

A

Increase in intracellular calcium, calcium binds to calmodulin, calmodulin activates myosin light chain kinase, myosin light chain phosphorylated, actomyosin ATPase activated, cross bridges between actin and myosin break and reform, results in cell shortening

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8
Q

What cause the increase in intracellular calcium?

A

voltage operated calcium channels and phospholipase C and inositol triphosphate releasing calcium from intracellular stores

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9
Q

What causes a decrease in intracellular calcium?

A

plasma calcium ATPases and sarcoplasmic reticulum calcium ATPases

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10
Q

What is the mechanism of regulation airway smooth muscle?

A

protein kinase A activates myosin light chain phosphatase. MLC phosphatase dephosphorylates myosin light chain. This prevents actin and myosin sliding and prevents contraction.

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11
Q

What is the action of PKC and Rho kinase?

A

Inhibit MLC phosphatase - this results in the smooth muscle being more sensitive to calcium and thus more able to contract

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12
Q

Which mediators result in smooth muscle contraction?

A

acetylcholine, histamine, leukotriene C4 and D4

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13
Q

Which mediators result in smooth muscle relaxation?

A

prostaglandin E2 and I2, adrenaline

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14
Q

What causes basement membrane thickening in asthma?

A

chronic epithelial cell damage where the repair process is not proportionate to degree of injury which leads to residual scarring

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15
Q

What are reliever drugs for asthma?

A

Short acting beta agonists

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16
Q

What are salbutamol and terbutaline?

A

Short acting beta agonists

17
Q

Which receptors to SABAs work on?

A

selective for beta-2 adrenoceptors

18
Q

What are the adverse effects of SABAs?

A

tachycardia, tremor, hypokalemia and regular use may have a link to morbidity and mortality

19
Q

What feature of SABAs helps to avoid tolerance?

A

They are all partial agonists

20
Q

What determines the duration of action of SABAs?

A

Rate of perfusion of bronchial tissue

21
Q

What is the mechanism of action of SABAs?

A

Binds to beta 2 adrenoceptor which couples to Gs which activates adenyl cyclase which makes cAMP and PKA. PKA increases activity of the sarcoplasmic reticulum calcium ATPase to decrease intracellular calcium. PKA also inhibits IP3R to reduce calcium release from the sarcoplasmic reticulum. This results in decreased intracellular calcium and so reduces activity of MLC kinase. PKA also activates myosin light chain phosphatase so dephosphorylate myosin light chain. Overall this prevents smooth muscle contraction and leads to smooth muscle relaxation.

22
Q

What are the controller drugs for asthma?

A

Long acting beta agonists

23
Q

What are salmeterol and formoterol?

A

Long acting beta agonists given twice daily

24
Q

What is indacaterol?

A

A long acting beta agonist given once daily

25
Q

What is the purpose of LABAs?

A

To provide a background of bronchodilator tone to reduce likelihood of bronchoconstriction

26
Q

How are LABAs given?

A

In a combined therapy with glucocorticoids

27
Q

What is the difference between SABAs and LABAs?

A

No difference in the way they interact with the receptor but LABAs dissolve in the lipid membrane so are more persistent

28
Q

Can SABAs be used on top of LABAs?

A

Yes

29
Q

How are beta 2 adrenoceptors regulated?

A

Within seconds by phosphorylation by PKA, within minutes by being internalised, and within hours by being down regulated

30
Q

How are muscarinic receptor antagonists used in asthma?

A

By blocking the action of acetylcholine from parasympathetic nerves on smooth muscle and preventing contraction - used in combination with LABAs

31
Q

What is ipratropium bromide?

A

a short acting muscarinic receptor antagonists (SAMA) - non selective

32
Q

What is iotropium bromide?

A

A long acting muscarinic receptor antagonist (LAMA) - M3 selective

33
Q

Which causes more bronchodilation in asthma, beta adrenoceptor agonists or muscarinic receptor antagonists?

A

beta adrenoceptor agonists

Respiratory (31 decks)

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