Asthma Drugs

Question 1

Albuterol (Proventil)

Answer 1

Class: Beta2 Adrenoceptor Agonist; Short Acting

Mechanism of action:

• G-coupled receptor
• Ligand binding moves receptor to active state
• G protein disassociates into Gα and β/γ dimer
• Gα activates adenylate cyclase
• ↑ cAMP in cell
• cAMP activates protein kinase A (PKA)
• PKA phosphorylates substrates that control Calcium in cell
• ↓ calcium concentration in cell
• Myosin light chain is unable to sustain contraction

Indication:
-Acute relief of bronchospasm

Pharmacological effects:

• Bronchodilation
• ↓ inflammatory cytokine production
• ↓ responsiveness
• ↓ plasma exudation

How this drug might effect dental treatment of patient
oAdverse effects you have to consider: 
-Seen with long term use
•↑ asthma exacerbations 
•Loss of bronchoprotection
oIf you use Salmeterol for long enough, the beta2 short acting agonist in Albuterol is not going to work anymore
-Receptor desensitization
•Causes?
oReceptor down-regulation
oGenetic polymorphisms of beta receptor
oIsomer effects: Levalbuterol (Xopenex)
People who have hard to control asthma will be on this drug (another clue as to what stage of asthma they are in)

oContraindicated drugs:

oContraindications:

oWhich analgesic can the patient take:

Question 2

Salmeterol (Advair)

Answer 2

Class: Beta2 Adrenoceptor Agonist; Long Acting

Mechanism of action:

• G-coupled receptor
• Ligand binding moves receptor to active state
• G protein disassociates into Gα and β/γ dimer
• Gα activates adenylate cyclase
• ↑ cAMP in cell
• cAMP activates protein kinase A (PKA)
• PKA phosphorylates substrates that control Calcium in cell
• ↓ calcium concentration in cell
• Myosin light chain is unable to sustain contraction

Indication:
-Controller for asthma

Pharmacological effects:

• Bronchodilation
• ↓ inflammatory cytokine production
• ↓ responsiveness
• ↓ plasma exudation

How this drug might effect dental treatment of patient
oAdverse effects you have to consider: 
-Seen with long term use
•↑ asthma exacerbations 
•Loss of bronchoprotection
oIf you use Salmeterol for long enough, the beta2 short acting agonist in Albuterol is not going to work anymore
-Receptor desensitization
•Causes?
oReceptor down-regulation
oGenetic polymorphisms of beta receptor
oIsomer effects: Levalbuterol (Xopenex)
People who have hard to control asthma will be on this drug (another clue as to what stage of asthma they are in)

oContraindicated drugs:

oContraindications:

oWhich analgesic can the patient take:

Question 3

Steroids

Answer 3

Class: Steroids

Mechanism of action:

Indication:
-Asthma or COPD

Pharmacological effects:

• Decrease airway responsiveness, severity, and decrease frequency of exacerbations
• Decrease rate of decline in COPD

How this drug might effect dental treatment of patient
oAdverse effects you have to consider:
-Inhaled steroids (not as bad as oral steroids)
Oropharyngeal candidiasis
Dysphonia
Lead to decrease adherence and quality of life

oContraindicated drugs:

oContraindications:

oWhich analgesic can the patient take:

Question 4

Interaction between steroids and beta agonists

Answer 4

oSynergistic effect (which is why we have Advair)
oβ2 receptor gene has GRE sites (Beta 2 receptor has steroid sites)
Offset one of the mechanisms for desensitization
oLong acting β2 agonists
Promote translocation of glucocorticoid receptor into the nucleus with no ligand present
Accelerate the rate of translocation when ligand is present

Question 5

Montelukast (Singulair)

Answer 5

Class: Leukotriene Receptor Inhibitor

Mechanism of action:
-Competitive antagonist of the cysteinyl leukotriene receptor

Indication:
-Asthma and seasonal allergic rhinitis

Pharmacological effects:

How this drug might effect dental treatment of patient
oAdverse effects you have to consider:

oContraindicated drugs:
-Avoid ASA and NSAIDs: these drugs can lead to more leukotriene production

oContraindications:

oWhich analgesic can the patient take:

Question 6

Sileuton (Zyflo)

Answer 6

Class: Leukotriene Formation Inhibitor

Mechanism of action:
-Inhibits 5-lipooxygenase

Indication:
-Prophylaxis and chronic treatment of asthma

Pharmacological effects:

How this drug might effect dental treatment of patient
oAdverse effects you have to consider:
-Can cause liver problems
-Liver enzymes must be monitored during therapy

oContraindicated drugs:

oContraindications:

oWhich analgesic can the patient take:

Question 7

Omalizumab (Xolair)

Answer 7

Class: Murine Anti-Human Monoclonal Antibody

Mechanism of action:

• Directed against the fragment on the IgE that binds to the IgE receptor
• Only binds to free IgE
• ↓ free IgE by 99 %
• Down regulates receptor expression on basophils
• ↓ IgE mediated inflammation

Indication:

• Nasopharyngitis
• Upper respiratory tract infections
• Headache

Pharmacological effects:

How this drug might effect dental treatment of patient
oAdverse effects you have to consider:
-0.1 % anaphylaxis in 2-24 hours after administration; need to stay in the hospital for a few days or sent home with anaphylaxis kit
-Black box warning

oContraindicated drugs:

oContraindications:

oWhich analgesic can the patient take:

Question 8

Ipratropium (Atrovent)

Answer 8

Class: Anticholinergics (inhibit bronchoconstriction)

Mechanism of action:
-Competitive antagonism of acetylcholine at M3 receptors in the lung

Indication:
-COPD

Pharmacological effects:
-Ipratropium (Atrovent) t½ = 0.3 hour
-Tiotropium (Spiriva) t½ = 35 hours
Used in once a day dosing in COPD

How this drug might effect dental treatment of patient
oAdverse effects you have to consider:
-Dry mouth
-Altered taste and coughing after administration

oContraindicated drugs:

oContraindications:

oWhich analgesic can the patient take: