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RESP > 15. Pulmonary Pharmacology > Flashcards

15. Pulmonary Pharmacology Flashcards

1
Q

What are the inflammatory mediators involved in the initial phase of asthma?

A

Mast cell IgE
Histamine
Prostaglandins

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2
Q

What effect do the mediators in the initial phase of asthma have?

A

Bronchoconstriction

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3
Q

What are the inflammatory mediators involved in the intermediate phase of asthma?

A

IL-4,5,13

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4
Q

What effect do the mediators in the intermediate phase of asthma have?

A

Leukocyte release

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5
Q

What is the pathophysiology of the late phase of asthma?

A

Influx of Th2 cells> activate neutrophils and eosinophils> release proteins that damage the lung epithelium

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6
Q

Name a protein that damaged the lung epithelium in asthma

A

Eosinophil cationic protein

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7
Q

What is the parasympathic control of asthma?

A

M3 receptors and ACh cause bronchoconstriction

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8
Q

What is the sympathetic control of asthma?

A

B2 adrenoceptors and adrenaline inhibit bronchoconstriction

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9
Q

Name 3 types of bronchoconstrictors

A

B2 adrenoceptor agonists
Muscarinic antagonists
Xanthines

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10
Q

What is the MOA of B2 adrenoceptor agonists?

A

Increase cAMP by GPCR-linked activation of adenylate cyclase, causing relaxation of bronchial smooth muscle
Inhibit mediator release from mast cells
Increase mucociliary clearance

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11
Q

Name a short acting and long acting B2 adrenoceptor agonist

A

Short: salbutamol and terbutaline
Long: Salmeterol

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12
Q

What are the side effects of B2 agonists?

A

Tremor
Arrhythmias
Hypokalaemia
Muscle cramps

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13
Q

Name 2 muscarinic antagonists

A

Ipatropium

Titropium

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14
Q

What is the MOA of ipatropium?

A

Inhibits action of ACh and M1,2,3

Causes bronchodilation and decreased mucous production

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15
Q

Which acts quicker: B2 agonists or muscarinic antagonists?

A

B2 agonists

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16
Q

What is the MOA of titropium?

A

Selective inhibition of M1 and M3

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17
Q

What are the side effects of muscarinic antagonists?

A

Very well tolerated: dry mouth and urinary retention

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18
Q

What is the MOA of xanthines?

A

Inhibit phosphodiesterase> increases cAMP and cGMP, causing bronchodilation
Also anti-inflammatory so inhibits the late phase

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19
Q

Give 2 examples of xanthines

A

Theophylline (PO)

Aminophylline (IV)

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20
Q

What are the side effects of xanthines?

A

Have a narrow therapeutic range so side effects common
Nausea, anorexia
Arrhythmias, nervousness, tremors, seizures

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21
Q

What isoenzyme of CYP450 breaks down theophylline?

A

CYP1A2

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22
Q

What substances can affect the break down of theophylline?

A

Rifampicin increases CYP450 so increases clearance
Macrolides inhibit clearance, so increase toxicity
Smoking and caffeine can alter blood levels of theophylline

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23
Q

Name 3 classes of anti-inflammatories that are used in asthma

A

Glucocorticoids
Cromones
Leukotriene synthesis inhibitors and receptor antagonists

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24
Q

What is the MOA of corticosteroids?

A

Bind to intracellular glucocorticoid receptor
Transactivate responsive genes via glucocorticoid response elements
Transrepress pro-inflammatory TFs

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25
Q

Name a glucocorticoid response element

A

Lipocortin 1: activation results in decreased prostaglandins

26
Q

Name 2 pro-inflammatory transcription factors

A

AP-1

NFkappaB

27
Q

Name 3 inhaled corticosteroids

A

Beclomethasone
Budesonide
Fluticasone

28
Q

Name a PO corticosteroid

A

Prednisolone

29
Q

Name an IV corticosteroid

A

Hydrocortisone

30
Q

Name 2 cromones

A

Sodium cromoglycate

Nedocromil

31
Q

What route are cromones given?

A

Inhaled

32
Q

What is the MOA of cromones?

A

Mast cell stabilisation (decrease degranulation and mediator release)
Inhibit sensory neurons
Inhibit eosinophil accumulation in lungs

33
Q

What are the side effects associated with cromones?

A

Cough and wheeze transiently after administrating

34
Q

Which are more effective: steroids or cromones?

A

Steroids

35
Q

What side effects are associated with PO steroids?

A 
Adrenal suppression
Infection
Effects of mineralocorticoids
Structural effects
Glucose intolerance
36
Q

What structural effects can steroids have?

A

Osteoporosis
Myopathy
Growth retardation
Obesity

37
Q

What are the side effects associated with inhaled corticosteroids?

A

Oral candidiasis

Dysphonia (myopathy of laryngeal muscles)

38
Q

What enzyme converts arachiodonic acid to leucotrienes?

A

LOX

39
Q

What drug inhibits LOX?

A

Zileuton

40
Q

What drugs inhibit the leucotriene receptor?

A

Zafirlukast

Montelukast

41
Q

What are the effects of leucotriene receptor antagonists?

A

Reduce mucosal inflammation, oedema, mucous and bronchoconstriction

42
Q

How are leucotriene receptor antagonists administered?

A

PO

43
Q

When are leucotriene receptor antagonists useful?

A

Exercise, cold, aspirin and NSAID induced asthma

Not in acute attacks

44
Q

What are the side effects of leucotriene receptor antagonists?

A

Headaches
GI upset
EGPA rarely

45
Q

Where is the mutation for A1ATD found?

A

SERPINA-1 gene, chromosome 14

46
Q

What other diseases does A1ATD increase the risk for?

A

Liver disorders
Vasculitis
Skin disease

47
Q

What is the treatment for A1ATD?

A

Augmentation therapy: infused pooled A1AT

48
Q

What is type 1 respiratory failure?

A

PO2 is low but PCO2 normal

Due to a V/Q mismatch

49
Q

What conditions can cause type 1 respiratory failure?

A

PE

High altitude

50
Q

What is type 2 respiratory failure?

A

Low PO2 and high PCO2

Hypoventilation throughout lung

51
Q

What conditions can cause type 2 respiratory failure?

A

COPD
Asthma
Sedation overdose

52
Q

What is the treatment for type 2 respiratory failure?

A

Low dose O2 (24%) while monitoring ABG
Through a NIPPV (pressurised face mask)
Mechanical ventilation only for acute cases

53
Q

Explain class 1-5 CF mutations

A
  1. no functional CFTR
  2. misfolded CFTR that doesn’t reach surface
  3. non-functional CFTR
  4. Faulty opening of CFTR
  5. Not enough
54
Q

Name a class 2 mutation

A

delta F508

55
Q

Name a class 3 mutation

A

G551D

56
Q

Name a class 4 mutation

A

R117H

57
Q

Name a CF potentiator

A

Ivacaftor

58
Q

What is the function of potentiators?

A

Help the CFTR transport Cl- across the cell surface

Used in G551D

59
Q

What is the function of correctors?

A

Bind to CFTR and help it fold into the right shape so more gets to membrane

60
Q

Name a CF corrector

A

Lumacaftor

61
Q

What name is given to the triple combo CF treatment?

A

TRIKAFTA

RESP (17 decks)

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