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Pharmacology > Asthma > Flashcards

Asthma Flashcards

1
Q 
Pathogenesis of asthma
Inflammatory cells
Structural cells
Mediators
Effects
A 
Inflammatory cells
- mast cells
- eosinophils
- Th2 cells
- basophils
- neutrophils
- platelets
Structural cells
- epithelial cells
- smooth mm cells
- endothelial cells
- fibroblasts
- nerves

Mediators

  • histamines
  • leukotrienes
  • prostanoids
  • PAF
  • kinins
  • adenosine
  • endothelins
  • nitric oxide
  • cytokines
  • chemokines
  • growth factors

Effects

  • bronchospasm
  • plasma exudation
  • mucus secretion
  • AHR
  • structural changes
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2
Q

Guideline goals for successful asthma management

A 
Current control 
- control of symptoms
- maintain normal activity levels
- maintain pulmonary function
Future risk
- avoid adverse treatment effects
- prevent asthma exacerbation
- prevent asthma mortality
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3
Q

M3 receptor under stimulation by the agonist Ach mimics what effect?

A

Bronchoconstriction
Increased bronchial gland secretions
Increased mediator release

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4
Q

Beta 2 receptor under stimulation by the agonist NA mimics what effect?

A

Bronchodilatation
Mast cell stabilization
Increased mucocilliary clearance
Decreased microvascular permeability

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5
Q

Alpha 1, Alpha 2 receptor under stimulation by the agonist NA mimics what effect?

A

Bronchoconstriction

Decreased gland secretions

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6
Q

H1 receptor under stimulation by the agonist histamine mimics what effect?

A

Bronchoconstriction

Inflammatory reaction

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7
Q

5-HT3 receptor under stimulation by the agonist serotonin mimics what effect?

A

Bronchoconstriction

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8
Q

Beta 2 receptor under stimulation by the agonist bradykinin mimics what effect?

A

Bronchoconstriction

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9
Q

Pharmaceutical options for asthma treatment

A 
Corticosteroids
Leukotriene antagonists
Mast cell stabilizers
Anticholinergic drugs
Theophylline
Selective beta 2 adrenergic agonists
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10
Q

Which drug class of asthma pharmacotherapy results in reduced bronchial hyper-reactivity?

A

Mast cell stabilizers

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11
Q 
Which drug class of asthma pharmacotherapy results in 
decreased response to allergens?
A

Leukotriene antagonists

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12
Q

Which drug class of asthma pharmacotherapy results aids in prevention of progression of chronic asthma, rescue course in rapidly deteriorating conditions and IV for acute exacerbations?

A

Corticosteroids

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13
Q

Which drug class of asthma pharmacotherapy results in relief of acute exacerbation and control/prevention of chronic asthma?

A

Anticholinergic drugs
Theophylline
Selective beta 2 adrenergic agonists

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14
Q

Definition of severe asthma

A

Asthma that requires treatment w/ high dose inhaled corticosteroids + a second controller and/or systemic corticosteroids to prevent it from becoming uncontrolled or that remains uncontrolled despite this therapy

To qualify:
Asthma diagnosis should be confirmed
Comorbidities should be address

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15
Q

Definition of uncontrolled asthma

A

At least 1 of the following

  • poor symptom control (ACQ consistently >1.5, ACT<20)
  • frequent severe exacerbations (>2 burts of systemic corticosteroids in the prev year)
  • serious exacerbations (> hospitalization or ICU stay in prev year)
  • airflow limitation (FEV1 <80% predicted after withholding bronchodilators
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16
Q

What should you check for in uncontrolled asthma before changing the treatment?

A 
Incorrect diagnosis
Significant comorbidities
Poor compliance
Poor inhaler technique
Environmental factors (allergen exposure, occupation, smoking)
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17
Q

Management of refractory asthma

A

Life-threatening
Most commonly precipitated by URTIs

Hydrocortisone 100 – 200 mg 4 – 8hourly infusion
Nebulised salbutamol 2.5 – 5mg with ipratropium bromide 0.5 mg driven by O2
High flow humidified O2
Intubation & mechanical ventilation prn
Antibiotic treatment of respiratory tract infection
Correct dehydrationand acidosis
Saline + sodium bicarbonate infusion

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18
Q

Inhaled + local corticosteroid options

A

Beclometasone (Beclate)
Budesonide (Pulmicort)
Ciclesonide (Alvesco)
Fluticasone (Flixotide)

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19
Q

Systemic (oral/IV) corticosteroid options

A 
Prednisone (Meticorten)
Methylprednisolone (Medrol)
Betamethasone (Celestone)
Dexamethasone (Decasone)
Hydrocortisone (Solucortef)
Triamcinolone (Kenalog)
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20
Q

Indication for corticosteroid use in asthma treatment?

A

Most effective controller therapy available for asthma

ICS not systemic (severe S/E)

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21
Q

Mechanism of action of corticosteroids in asthma treatment

A
  1. Decrease formation of cytokines (esp Th2), eosinophils, macrophages and T lymphocytes - Th2 recruit and activate eosinophils and are responsible for promoting the production of IgE and the expression of IgE receptors)
  2. Reversing mucosal oedema
  3. Inhibit the generation of PGE2 and PGI2 by inhibiting induction of COX-2
  4. Decreases down-regulation of B-receptors
  5. Decrease permeability of capillaries
  6. Decrease release of leukotrienes and histamine which cause bronchoconstriction
  7. Decrease hyperresponsiveness of airway smooth muscle to
    sensitive stimuli such as cold, irritants, allergens etc
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22
Q

What is the pathophysiology of cysteinyl leukotrienes in asthma?

A 
Constriction of bronchiolar smooth muscle
Airway hyperresponsiveness
Plasma exudation
Eosinophilic inflammation
Increased endothelial permeability
Promotion of mucous secretion
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23
Q

Mechanism of action of anti-leukotrienes in asthma treatment?

A

Selective reversible inhibitors of cysteinyl
leukotrine-1 receptor, thus blocking the effects of cysteinyl leukotrines (LTC4, LTD4, LTE4) (Montelukast, Zafirlukast)
Inhibitor of 5-lipoxygenase pathway (Zileuton)

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24
Q

Anti-leukotriene options for asthma treatment?

A

Montelukast (Singulair)
Zafirlukast (Accolate)
Zileuton (not available in SA)

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25
Q

Pharmacokinetics of anti-leukotrienes in asthma treatment?

A

Good oral absorption
90% plasma protein bound
Undergo biliary excretion
Pharmacological response within 24hrs

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26
Q

What are adverse effects of anti-leukotrienes?

A 
Abdominal pain
Headache
Rash
Anaphylaxis
Eosinophilia, vasculitis (Churg Strauss Syndrome)
Liver dysfunction (rare)
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27
Q

Drug interactions of anti-leukotriene options?

A

Zafirlukast extensively metabolized by liver (inhibitor of CYP3A4 and
CYP2C9)
Enhances anticoagulant effect of warfarin
Erythromycin + terfenadine combination reduces zafirlukast levels
Theophylline reduces zafirlukast levels

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28
Q

Name options in the short acting beta 2 agonist drug class

A 
Salbutamol (Ventolin)
Fenoterol (Berotec)
Terbutaline (Bricanyl)
Hexoprenaline (Ipradol)
Orsiprenaline /Metaproterenol
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29
Q

Name options in the long acting beta 2 agonist drug class

A

Salmeterol (Serevent)
Formoterol (Foradil)
Indacaterol (Onbrez)

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30
Q

Adverse effects of beta 2 agonists?

A 
Muscle tremors
Palpitations
Restlessness
Nervousness
Throat irritation
Ankle oedema
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31
Q

Name anti-cholinergic options for asthma treatment and their half life

A

M3 receptor antagonists
- Ipratropium bromide (t1/2 = 4 - 6 hours)
- Tiotropium bromide (t1/2 = 24 hours)
Slower response than beta 2 agonists

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32
Q

Adverse effects of anticholinergics

A 
Mostly elderly affected
Sedation
Confusion
Hallucination
Mydriasis + blurred vision
Sinus tachycardia
Urinary retention
Constipation
Dry mouth
Parotitis
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33
Q

Name methylxanthine options for asthma treatment

A

Theophylline
Aminophylline
Caffeine
Oxtryphyline

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34
Q

Mechanism of action of methylxanthines?

A

Multiple mechanisms responsible, but most important respiratory effects due to inhibition of PDE (phosphodiesterase) which is responsible for intracellular metabolism of cAMP

35
Q

Pharmacokinetics of methylxanthines

A

Variable t½ (3-12hrs)
Good oral absorption
Metabolized by liver (substrate for CYP1A2 and CYP3A4)
NB – Very narrow therapeutic index (10 20mcg/ml)
Therapeutic drug monitoring recommended

36
Q

Adverse effects of methylxanthines

A

Adverse effects are related to plasma concentration (if >15mg/L) + may be reduced by gradually increasing the dose until therapeutic concentrations are achieved

Most common side effects: headache, nausea, vomiting and increased acid secretion (due to inhibition of PDE4)
CNS irritability tremor, nervousness, convulsions
Tachycardia, arrhythmias (fatal) (due to inhibition of cardiac PDE3
Transient urinary frequency (due to inhibition of adenosine A1 receptors)

37
Q

Name options of mast cell stabilizers?

A

Cromolyn (Vividrin)

Nedocromil

38
Q

Mast cell stabilizers have no effect when?

A

If already bronchoconstricted

39
Q

Mechanism of action of mast cell stabilizers

A

Block calcium channels essential for mast cell degranulation, stabilizing the
cell and thereby preventing the release of histamine and related mediators -> without intracellular calcium, the
histamine vesicles cannot fuse to the cell membrane and degranulate

40
Q

Indications for mast cell stabilizers

A

Effective prophylactic anti-inflammatory agents - not for use in acute asthmatic attacks
Useful in allergic rhinitis (nasal sprays)
Allergic conjunctivitis (eye drops)

41
Q

Pharmacokinetics of mast cell stabilizers

A

Efficacy only determined after 4-6 weeks

Short duration of action – tds, qid dosing

42
Q

Another name for the drug class of mast cell stabilizers?

43
Q

Adverse effects of mast cell stabilizers?

A 
Minimal adverse effects
Mainly transient e.g
- pharyngeal irritation
- chest tightness
- coughing + nasal congestion
- mouth dryness
44
Q

Immunomodulatory therapy in asthma treatment

A

Immunosupressive therapy could be considered when ALL other treatments are unsuccessful

Anti-IgE receptor therapy (monoclonal antibodies)

  • consider omalizumab
  • blocks IgE binding to receptors
45
Q

Immunomodulatory treatment is routine in the treatment of asthma
True or false

A

False
Less effective and more side effects than oral corticosteroids therefore
NOT recommended for routine therapy

46
Q

Give examples of medications that fall under the antitussive drug group

A

Cough suppressants (opium alkaloids)

Dextromethorphan
Noscapine
Pholcodine
Codeine
Dihydrocodeine
Methadone
47
Q

Mechanism of action of opium alkaloid cough suppressants

A

Suppress medullary cough centre in brain by acting on μ opioid receptors in lower doses than needed for pain relief

48
Q

Side effects of of opium alkaloid cough suppressants

A 
Decreases bronchial secretions (thickens sputum)
Inhibits ciliary activity
Constipation
GI disturbances
Dizziness
Respiratory depression
Confusion and sedation
49
Q

Drug interactions with opium alkaloid cough suppressants

A 
CNS depressants
Potentially fatal
- amiodarone
- fluoxetine
- MAOI
50
Q

Give examples of medications that fall under the mucolytic drug group

A

Acetylcysteine (ACC)
Carbocisteine (Mucospect)
Bromhexine (Bisolvon)
Sodium-2-mercapto-ethane sulphonate (Mesna/Mistabron)

51
Q

Give examples of medications that fall under the expectorant drug group

A 
Guaifenesin (Benylin)
Tinct ipecacuanha
Ammonium chloride
Chloroform
Sodium citrate
Menthol
52
Q

Definition of allergic rhinitis

A

A symptomatic disorder of the nose, induced after
allergen exposure, by an IgE- mediated inflammation of the nasal membranes
“Hay fever”

53
Q

Clinical presentation of allergic rhinitis

A 
Rhinorrhoea,
Nasal congestion/blockage
Nasal itching
Sneezing
Postnasal drip
54
Q

Least effective drugs for alleviating nasal itching in allergic rhinitis?

Intranasal corticosteroids
Antihistamines
Intranasal cromones
Intranasal decongestants
Anticholinergics
LTRA
A

Intranasal decongestants
Anticholinergics
LTRA

55
Q

Most effective drugs for alleviating nasal itching in allergic rhinitis?

Intranasal corticosteroids
Antihistamines
Intranasal cromones
Intranasal decongestants
Anticholinergics
LTRA
A

Antihistamines

56
Q

Least effective drugs for alleviating sneezing in allergic rhinitis?

Intranasal corticosteroids
Antihistamines
Intranasal cromones
Intranasal decongestants
Anticholinergics
LTRA
A

Intranasal decongestants
Anticholinergics
LTRA

57
Q

Most effective drugs for alleviating sneezing in allergic rhinitis?

Intranasal corticosteroids
Antihistamines
Intranasal cromones
Intranasal decongestants
Anticholinergics
LTRA
A

Antihistamines

58
Q

Least effective drugs for alleviating rhinorrhoea in allergic rhinitis?

Intranasal corticosteroids
Antihistamines
Intranasal cromones
Intranasal decongestants
Anticholinergics
LTRA
A

Intranasal decongestants

59
Q

Most effective drugs for alleviating rhinorrhoea in allergic rhinitis?

Intranasal corticosteroids
Antihistamines
Intranasal cromones
Intranasal decongestants
Anticholinergics
LTRA
A

Intranasal corticosteroids
Antihistamines
(but anticholinergics only work for rhinorrhoea symptoms)

60
Q

Least effective drugs for alleviating nasal obstruction in allergic rhinitis?

Intranasal corticosteroids
Antihistamines
Intranasal cromones
Intranasal decongestants
Anticholinergics
LTRA
A

Intranasal decongestants

61
Q

Most effective drugs for alleviating nasal obstruction in allergic rhinitis?

Intranasal corticosteroids
Antihistamines
Intranasal cromones
Intranasal decongestants
Anticholinergics
LTRA
A

Anticholinergics

62
Q

Nasal irrigation in the treatment of allergic rhinitis

A

Nasal irrigation is a simple and inexpensive non- pharmacological form of therapy for AR that has been shown to improve symptoms and QOL scores and reduce medication requirements

63
Q

Give examples of direct acting agonists in the treatment of allergic rhinitis

A 
Oral (tablets, syrups)
- pseudoephedrine
- phenylephrine
- phenylpropanolamine
Topical (nasal spray, drops)
- oxymetazoline
- naphazoline
- xylometazoline
- phenylephrine
64
Q

Mechanism of action of direct acting agonists in the treatment of allergic rhinitis

A

Direct agonists on postsynaptic alpha 1 receptors -> constricts dilated arterioles in nasal mucosa and reduce airway resistance

65
Q

Indications for the use of direct acting agonists in the treatment of allergic rhinitis

A 
Systemic and topical nasal
decongestants
Only direct acting agents used - indirect agents are illicit in cold/flu preparations
Usually in combination with
antihistamines
66
Q

Contraindications to use of direct acting agonists in the treatment of allergic rhinitis

A

Severe hypertension

MAOI

67
Q

Precautions in the use of direct acting agonists in the treatment of allergic rhinitis

A 
Rhinitis medicamentosa (>7 days use)
Cardiovascular disease
Hyperthyroidism
Diabetes
Prostatic hypertrophy
Renal impairment
Hepatic impairment
68
Q

Adverse effects of the use of direct acting agonists in the treatment of allergic rhinitis

A 
CNS stimulation (anxiety, restlessness, tremors, headache)
Reduced appetitie
N+V
Hypertension
Cerebral haemorrhage
Pulmonary oedema
69
Q

Give examples of 1st generation antihistamines used in the treatment of allergic rhinitis

A 
Promethazine (Phenergan)
Chlorpheniramine (Allergex)
Cyclizine (Valoid)
Cyproheptadine (Periactin)
Hydroxizine (Aterax)
Diphenhydramine (DPH)
70
Q

Indications for use of of 1st generation antihistamines used in the treatment of allergic rhinitis

A 
Allergic conditions
Urticaria
Angioedema
Acute anaphylaxis
Motion sickness
Nausea
Vomiting
Common cold
Rhinorrhoea
71
Q

Pharmacokinetics of 1st generation antihistamines used in the treatment of allergic rhinitis

A

Non selective
Crosses BBB
Good absorption + metabolised by liver
t1/2 between 2-8hrs

72
Q

Adverse effects of 1st generation antihistamines used in the treatment of allergic rhinitis

A

Sedation
Hallucinations
Seizure precipitation (epileptics)
Anticholinergic effects (useful in drying up secretions during cold/flu)

73
Q

Drug interactions with 1st generation antihistamines used in the treatment of allergic rhinitis

A

Potentiates effects of CNS depressants
Potentiates effects of anticholinergic agents
Antidepressants

74
Q

Give examples of 2nd generation antihistamines used in the treatment of allergic rhinitis

A 
Cetirizine (Zyrtec)
Desloratadine (Deselex)
Levocetirizine (Xyzal)
Loratadine (Clarityne)
Ebastine (Kestine)
Fexofenadine (Telfast)
Mizolastine (Mizollen)
Ketotifen (Zaditen)
75
Q

Indications for use of of 2nd generation antihistamines used in the treatment of allergic rhinitis

A

Non sedative
Symptomatic treatment for allergic conditions
Not very effective in common colds due to lack of anticholinergic
effects

76
Q

Pharmacokinetics of 2nd generation antihistamines used in the treatment of allergic rhinitis

A

Selective for H1 receptors t½ 10h (thus daily dosing )
Minimal BBB penetration
Minimal metabolism - excreted unchanged by kidney

77
Q

Adverse effects of 2nd generation antihistamines used in the treatment of allergic rhinitis

A 
Sedation (uncommon)
Headache
Dizziness
GI disturbances
Hypersensitivity reactions
Potential for cardiac arrhythmias (QT prolongation)
78
Q

Drug interactions with 2nd generation antihistamines used in the treatment of allergic rhinitis

A 
CNS depressants
Drugs with arrhythmogenic
potential 
- ketoconazole
- erythromycin
- protease inhibitors
- quinine
79
Q

Mechanism of action of ketotifen as a mast cell stabilizer in the treatment of allergic rhinitis

A

2nd generation antihistamine with mast cell stabilizing effects

  • Histamine antagonist
  • Functional leukotriene antagonist
  • Phosphodiesterase inhibitor
80
Q

Indications for us of ketotifen as a mast cell stabilizer in the treatment of allergic rhinitis

A

Useful adjunct to bronchodilator therapy in highly allergic children <3 years who have atopic eczema or hay-fever in addition to asthma

81
Q

Drug interactions with of ketotifen as a mast cell stabilizer in the treatment of allergic rhinitis

A 
Oral antidiabetic preparations enhances the risk of reversible thrombocytopenia.
Potentiates the effect of
- sedatives
- hypnotics
- antihistamines 
- alcohol
82
Q

Adverse reactions with use of ketotifen as a mast cell stabilizer in the treatment of allergic rhinitis

A 
Somnolence (reversible)
Zerostomia (reversible)
Mild dizziness (reversible)
Fatigue (reversible)
Weight gain
Increased appetite
Hypersensitivity in
immunocompromized patients
83
Q

Management of anaphylaxis

A

Severe systemic IgE mediated hypersensitivity reaction
Drug of choice = adrenaline
Other options
- glucocorticoids
- antihistamines
- supportive therapy (positioning, inotropes, vasopressors)

Pharmacology (32 decks)

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