Asthma Flashcards

1
Q

Characteristics of category 1 asthma (4)

A

Intermittent
Daytime symptoms <2 /week
Nocturnal <2 per month
PEFR >80%

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2
Q

Characteristics of category 2 asthma (4)

A

Mild persistent
Daytime symptoms 3-4 / week
Nocturnal 2-4 / month
PEFR >80%

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3
Q

Characteristics of category 3 asthma (4)

A

Moderate persistent
Daytime symptoms >4 / week
Nocturnal > 4 / month
PEFR 60-80%

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4
Q

Characteristics category 4 asthma (4)

A

Persistent severe
Daytime symptoms continuous
Nocturnal frequent
PEFR <60%

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5
Q

Name 3 examples of short acting B2 agonists.

A

Salbutamol!
Fenoterol
Terbutaline

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6
Q

Half life of salbutamol

A

4-6 hours

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7
Q

MOA B2 adrenoreceptor agonists (7-2 direct,4 indirect )

A

Increase cAMP by stimulating adenylyl cyclase via stimulatory G proteins. cAMP phosphorylates a cascade of enzymes which results in:
• Relaxation smooth muscle
• bronchodilation (direct effect-functional antagonists to reverse bronchoconstriction)
• inhibit release of inflammatory mediators (mast cells,TNF-alpha from monocytes ) (indirect)
• increased mucociliary clearance
• prevent microvascular leakage, therefore limit mucosal oedema
• reduce presynaptic acetylcholine release, preventing reflex cholinergic bronchoconstriction

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8
Q

Route of admin of ß2 agonists

A

Inhale mostly.
Oral: only children and people unable to use inhalers
Salbutamol can be given as nebuliser, also iv if life threatening.

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9
Q

3 main classes of bronchodilators

A
  • B2 adrenergic agonists (sympathomimetics)
  • Anticholinergics (muscarinic receptor antagonists)
  • Methylxanthines and PDE4 inhibitors
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10
Q

Indications inhaled ß2 adrenoreceptor agonists

A

Drug of choice in management acute bronchoconstriction or spasm. Principle management of asthma and COPD.

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11
Q

Contraindications to B2 agonists (3)

A

Hyperthyroidism
Cardiovascular disease
Arrhythmia
(Caution)

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12
Q

Adverse effects B2 agonists (3)

A
  • Fine tremor
  • Tachycardia and palpitations
  • Hypokalaemia
  • Nervousness, headache (vasodilation), dizzy. ‘
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13
Q

Drug interactions B2 agonists (2)

A

Corticosteroids - increase R hypok and hyperglycemia

Digoxin and diuretics- increase risk cardiac arrhythmia

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14
Q

Name 2 examples of long acting B2 agonists

A

Salmeterol!

Formoterol

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15
Q

Half life of salmetorol

A

12 hours

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16
Q

Name 2 examples of methylxanthines

A

-Phylline.
Aminophylline!
Theophylline
Bronchodilators

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17
Q

MOA xanthines

A

Inhibit enzyme phosphodiesterase, which catalyse hydralysis of CAMP to AMP
Therefore increased CAMP - relax smooth muscle → bronchodilation
Also antagonise adenosine at A2 receptors (a potent broncoconstrictor) and has anti-inflammatory activity on t cells by decrease release platelet activating factor (PAF)

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18
Q

Route administration Xanthines

A

Oral (theophylline)

Aminophylline IV for severe attacks.

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19
Q

Indications methylxanthines

A
  • Second line treatment for acute, severe and chronic persistent asthma !
  • Also in children unable to use inhalers
  • IV in status asthmaticus (aminophylline)
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20
Q

Contraindications xanthines (3)

A

Cardiac disease
HT
Hepatic impairment (metabolised by liver)

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21
Q

Adverse effects methylxanthine. 2 GIT, 5 CV, 3 CNS

A

GIT: nausea, vomit,
Cardiovascular: tachycardia, dysrythmias. Headache, flushing, hypotension (dilate smooth muscle)
CNS: insomnia, tremor, anxiety

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22
Q

What is the therapeutic index of Xanthines?

A

Very narrow! 10-20 mcg/ml

This causes adverse effects more easily and small increases above therapeutic dose can be toxic and even fatal.

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23
Q

When do methylxanthines become most effective?

A

6 days after starting

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24
Q

Drug interaction Xanthines

A

Macrolides. Macrolidies occupy the enzymes involved in theophylline breakdown, increasing the plasma conc. Small increases above therapeutic dose toxic/fatal.

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25
MOA glucocorticoids in treatment asthma (4 nb, 8 total)
INHIBIT INFLAMMATORY CASCADE • Induce formation lipocortin -1!, which inhibits phospholipase A2. This reduces free arachidonic acid and therefore decreased LEUKOTRIENE • reduced mucosal oedema and mucous production • inhibit generation PROSTAGLANDIN E2 and PGI2 by inhibit COX2 • decrease formation CYTOKINES (esp th2), eosinophils, macrophages, T cells, mast cell infiltration • B2 - adreno receptor upregulation • decrease permeability capillaries • decrease hyper responsiveness to sensitive stimuli eg cold, allergens
26
Indications glucocorticosteroids in asthma (3)
* Most effective controller therapy! * For asthma (prevent progression), usually in combination with B2 agonists, or severe frequent exacerbations COPD * rescue course in rapidly deteriorating conditions * iv for acute exacerbations
27
Contraindications glucocorticoids (2)
Caution in growing children, systemic and local resp/ear, nose, throat infections
28
Adverse effects glucocorticosteroids (4)
Oral candidiasis (rinse mouth) Irritation, hoarseness voice, dysphonia Suppression hypothalamic-pituitary-adrenal axis: Cushings, HT, diabetes Headache, skin reactions and bruises, psych, paradoxical bronchoconstriction, hypersensitivity
29
Name 2 examples of Leukotriene R antagonists
Montelukast! | Zafirlukast
30
Leukotriene R antagonists MOA
Selective reversible inhibitors of cysteinyl leukotriene -1 R, thus blocking the effects of leukotrienes LTC4, LTD 4, LTE 4 Causing bronchodilation
31
Indications leukotriene r antag
Prophylaxis and PREVENTOR asthma to decrease response to allergens. Children Allergic rhinitis Not effective in COPD
32
Contraindications leukotriene R antagonists (4)
Not useful in COPD or severe asthma Elderly Pregnancy Churg - Strauss syndrome
33
Adverse effects Leukotriene R antagonists (4)
GIT disturbance Headache Eosinophilia, Vasculitis ( churg Strauss Syndrome) Rash, dry mouth, anaphylaxis, liver dysfunction (very rare)
34
Drug interactions Leukotriene R antagonists. (4)
Warfarin (enhance anticoag effect) Erythromycin, terfenadine (zafirlukast levels reduced) Theophylline (zafirlukast levels reduced) (Zafirlukast extensively metabolised by liver. Inhibit cyp 3a4 and Cyp 2c9) NSAIDs: may narrow the airway when interact with LRA
35
Anticholinergics examples (2)
``` Ipratropium bromide (short acting) Tiotropium (long acting) ```
36
Muscarinic receptor antags MOA
* Competitive agonists of ach on m3 receptors. This blocks effect of ach, block direct constrictor effect on bronchial smooth muscle mediated by PLC-IP3-Ca path, block ach mediated tracheobronchial constriction * bronchodilation by inhibit parasymp vagal fibres
37
Indications antimuscarinics in obstructive airway diseases (4)
* Adjuncts to B 2 agonists to treat obstructive airway diseases (synergistic) * More useful in COPD - long term maintenance elderly * Pts that can't tolerate adverse effects B 2 agonists, especially elderly * Cystic Fibrosis
38
Contraindications muscarinic anticholinergics (3)
Glaucoma! Prostatic hypertrophy (urinary retention) Pregnancy
39
Adverse effects muscarinic receptor antagonists (2)
* May precipitate glaucoma in elderly (direct contact)! * Dry mouth * Paradoxical bronchoconstriction , rebound airway hyperresponsiveness when abruptly stopped (rare), constipation rare
40
Name 3 pathophysiological causes of asthma symptoms
* broncoConstriction muscle * oedema mucosal lining of small bronchi * plugging bronchial lumen with viscous mucus and inflammatory cells
41
Name 2 classes asthma preventers with examples
Anti-inflammatory to prevent attacks • inhaled corticosteroids: beclomethasone, budesonide, ciclesonide, fluticasone • oral corticosteroids:prednisone (Cromylons, sodium cromoglycate)
42
Name 3 classes asthma controllers with examples
Sustained bronchodilator action but weak/unproven anti inflammatory effect • Long acting beta 2 agonists eg salmeterol • methylxanthines eg theophylline • leukotriene receptor antagonists eg montelukast, zafirlukast
43
Name 3 classes asthma relievers with examples
* Short acting beta 2 agonists eg salbutamol * anticholinergics eg ipratropium, tiotropium * short acting theophylline (xanthine)
44
Name 2 iv corticosteroids for asthma
* Methylprednisolone | * hydrocortisone
45
Name 2 mast cell stabilisers
* sodium chromoglycate * ketotifen ( second gen h1 r antag ) * Nedocromil (chromones)
46
What is the treatment of choice for acute bronchoconstriction?
Beta 2 agonists
47
Moa anticholinergics for asthma?
* Parasympathetic vagal fibres provide broncoconstrictor tone to smooth muscle of airway. They are activated by reflex on stimulation of sensory (irritant) receptors in airway walls. * antimuscarinics block muscarinic r, especially m3
48
Name 3 inhaled corticosteroids for asthma controller
• Beclomethasone . Budesonide • fluticasone
49
Name 4 systemic corticosteroids for asthma controller
* Prednisone * methylprednisolone * betamethasone * dexamethasone, hydrocortisone
50
Name 3 classes mediator antagonists in treatment asthma and examples. (Adjunctive therapy)
* Antihistamines eg chlorphenIramine (allergex) (H1), * anti-leukotrienes eg montelukast, zafirlukast * mast cell stabilisers eg sodium cromoglycate
51
Name 4 first generation traditional (sedative) h1 antihistamines
* Chlorphenamine (allergex) * promethazine * cyclizine (valoid) * hydroxizine (aterax)
52
Difference in pharmacokinetics for first and second generation h1 receptor antagonists? (4)
* Nonselective vs selective for h1 * cross BBB vs minimal penetration * t1/2 shorter (4-8h) vs longer (10 h) (thus daily dosing) * metabolised by liver vs minimally metabolised, excreted by kidney unchanged
53
Name 5 indications for first generation h1 receptor antagonists?
* allergic conditions eg chronic urticaria * acute urticaria, acute anaphylaxis * angioedema * motion sickness, nausea, vomiting * common cold and rhinorrhea!
54
Name indications for second generation h1 receptor antagonists?
• Allergic conditions symptomatic treatment: allergic rhinitis, chronic urticaria, atopic dermatitis Not effective against common colds like first gen because not anticholinergic!
55
Name 5 second generation h1 antihistamines (non-sedative)
* Cetirizine * loratadine * ebastine * fexofenadine * ketotifen (mast cell stabiliser)
56
Indications ketotifen?
Adjunct to bronchodilator therapy in highly allergic children <3 who have atopic eczema or hay fever in addition to asthma
57
Moa Chromones mast cell stabilisers?
Stabilise antigen-sensitised mast cells by reduce calcium influx and subsequent release of inflammatory mediators.
58
Name 3 indications mast cell stabilisers (chromones)
* Prophylactic anti-inflammatory to reduce bronchial hyperactivity ( not acute attacks) * allergic rhinitis spray * allergic conjunctivitis drops
59
Name a phosphodiesterase 4 inhibitor for copd/asthma
Roflumilast
60
Indication roflumilast?
Antiinflammatory adjunct only in severe COPD and asthma with frequent exacerbations (severe git side effects)
61
When are immunosuppressants used in asthma?
Last resort
62
Name 3 immunosuppressants that may be used as last resort in asthma or COPD
* Methotrexate * cyclosporine * iv immunoglobulins
63
Which monoclonal antibody may be considered for use in asthma?
Omalizumab. | Block IgE
64
Name 3 indirect acting adrenergics causing release of ne from storage vesicles
• Amphetamine • cocaine • ephedrine Used in cold and flu preparations.
65
Name 3 direct acting adrenergics that are agonists on alpha 1 receptors
``` .Pseudoephedrine (oral) •Phenylpropanolamine (oral). • phenylephrine (oral and topical ) • oxymetazoline (topical) • naphazoline (topical) • xylometazoline (topical) ```
66
Name indications direct agonists postsynaptic alpha 1 receptors respiratory
• Systemic and topical nasal decongestants
67
Name 3 antitussives
``` Opium alkaloids (opioids) • codeine • pholcodeine • dextromethorphan • methadone ```
68
Moa opium alkaloids as antitussives?
* Opiate receptor agonists on mu receptors | * lower doses needed for pain relief, only suppress medullary cough centre brainstem.
69
Name 3 adverse effects opioids as antitussives
• Constipation, git disturbances, dizzy • inhibit mucociliary clearance, decrease bronchial secretions (thicken sputum) • respiratory depression . Confusion, sedation
70
Name 3 mucolytics
• Carbocisteine • acetylcysteine (acc) . Bromhexine Clear excess bronchial secretions.
71
Moa mucolytics?
Cleave disulphide bonds cross-linking mucus glycoprotein molecules, loosening sputum and reducing viscosity and facilitate expectoration by coughing.
72
Name 3 expectorants and what do they do?
``` Increase volume mucus to decrease viscosity and enhance coughing, enhance ciliary movement. Can also be used as emetic because irritate gi mucous membrane • guaifenesin • ammonium chloride • chloroform • Menthol ```
73
Name 5 drugs that may trigger asthma attack
* Sympatholytics: beta blockers * parasympathomimetics: cholinergic agonists (ach, bethanechol)., anticoline esterase's (neostigmine) * NSAIDs * hypersensitivity reactions: penicillins, tubocurarine, pancuronium morphine * irritants: tartrazine, carbamazepine, Iron dextran complex, preservatives