PMCII- Exam1

Asthma meds

Norepinephrine contains a hydrogen group (α and β agonist) 

Epinephrine (adrenaline) contains a methyl group (less α and more β agonist) 

Isoproterenol contains a isopropyl group (β agonist) 

Metaproterenol (Alupent, Metaprel) - SABA

• Resistant to degradation by COMT due to lack of adjacent hydroxyl group 

• Resistant to degradation by MAO due to bulky side groups 

• Meta conformation of isoproterenol due to the positioning of the hydroxyl group 

• Available in tablet, syrup,, and inhalation 

• Good oral bioavailability with onset 30 minutes or 5 minutes if inhaled 

• DOA is 4 hours 

• Adverse effects are similar to epinephrine such as palpitations, tachycardia, nausea, vomiting, dizziness, tremor, and headache 

Terbutaline Sulfate (Brethine, Brethaire) - SABA

• Similar to metaproterenol but has a tert-butyl group instead 

• Resistant to COMT and MAO 

• Three times greater β2 receptor selectivity than metaproterenol 

• Available in tablet, injection, and inhalation 

Bitolterol mesylate (Tornalate)  - SABA

• Contains toluene groups to make esters 

• Prodrug activated by esterases in the lungs to become colterol (active metabolite) 

• Localized in the lungs due to lipophilicity of esters 

• 0.2% nebulized solution only 

• Onset inhaled is 3 minutes and DOA is 8 hours 

Albuterol (Proventil, Ventolin)  - SABA

• Contains a hydroxymethyl group that is meta to the side chain 

• Drug of choice for acute bronchospasm 

• Available in aerosol, solution, tablet and syrup 

• Inhalation onset is 5 minutes and DOA is 6 hours 

• Racemic mixture of R and S enantiomers 

Salmeterol xinafoate (Serevent Diskus) - LABA

• Contains a hydroxymethyl group that is meta to long lipophilic side chain 

• High receptor affinity due to lipid anchor 

• Aerosol and inhalant powder 

• Onset is 20 minutes and DOA is 12 hours 

R- isomer

Levalbuterol (Xopenex) - SABA

• The R isomer of albuterol 

• Available in aerosol and solution 

Formoterol fumarate (Foradil Aerosolizer)  - LABA

• Contains a formamide group 

• More water soluble than salmeterol 

• Racemic mixture 

• Inhalant powder only 

• Onset less than 20 minutes and DOA of 12 hours 

• Patients cautioned not to take the capsule orally 

R-R enantiomer

Arformoterol  - LABA

• R,R enantiomer of formoterol 

• Approved for COPD only through nebulizer and has a similar duration of action to formoterol, providing bronchodilation.

Indacaterol  - Ultra-Long-Acting Beta 2 Agonists

• Derivative of formoterol 

• Inhalation allows once daily dosing 

• DOA is 18 hours

Olodaterol - Ultra-Long-Acting Beta 2 Agonists

• Derivative of formoterol 

• Inhalation allows once daily dosing 

• DOA is 18 hours 

Atropine 

• Tropine chirality is insignificant 

• Acid chirality with R enantiomer is 100 times more active than S enantiomer in terms of antagonism 

• Phenyl stereochemistry disrupts carbonyl binding to tyrosine if not in R absolute configuration

Ipratropium bromide (Atrovent) - antimuscarinics 

• Tropine group contains an isopropyl group 

• Generally used for COPD but not asthma 

• Quaternary amine is not orally available due to it being too hydrophilic 

• 17% bioavailability after inhalation and it is localized to the lungs 

• 83% is swallowed and not absorbed 

• Aerosol or powder 

• Onset inhaled is 15 minutes and DOA is less than 4 hours 

• Adverse effects are blurred vision, dry mouth, tachycardia, urinary difficulty, and headache 

• Severe adverse effects are dilation of the eyes that can exacerbate narrow-angle glaucoma 

Tiotropium bromide (Spiriva) - antimuscarinics 

• Contains thiophene groups 

• Primarily use for COPD 

• Available in inhaled solution or powder 

• Onset inhaled is 30 minutes and DOA is 24 hours 

• Same adverse effects as ipratropium 

• Do not swallow the capsule

Cromolyn Sodium(Intal, Nasalcrom, Gastrocrom)- Mast Cell Stabilizers

• Stabilizers are only of use prophylactically. No use once degranulation has occurred.

• Derived from the chemical khellin, which is found in the plant Ammi visnaga (in the carrot family).

• Poor GI absorption. Must be inhaled as powder or aerosol into the lungs.

• Thought to act by blocking chloride channels.

• Specific to mast cells (No effect on basophils)

• Specific to lung and NOT to skin cells.

Nedocromil Sodium (Tilade)- Mast Cell Stabilizers

• Thought to have the same mechanism as cromolyn.

• Stabilizes mast cells.

• Blocks airway nerves (it inhibits cough).

• Stabilizes eosinophils, inhibiting inflammation.

Zileutin (Zyflo)- Leukotriene biosynthesis inhibitors 

• Blocks 5-lipoxygenase

• N-hydroxyurea is essential for activity.

• 90% of the oral dose is bioavailable.

• Metabolized by glucuronidation in liver.

• 95% excreted via urine. Half-life 2½ hours.

Montelukast (Singulair)- Leukotriene pathway inhibitors

B) Leukotriene Receptor Antagonists

• Rapidly absorbed orally (so better patient compliance than inhaled).

• 64% bioavailable, metabolized in the liver, 86% excreted in bile.

• Adverse affects same as placebo

• Metabolism by cytochromes causes drug interactions with CYP 450-inducing drugs such as phenobarbitol (anti-seizure), rifampin (bactericidal antibiotic), and phenytoin (anti-seizure).

Zafirlukast (Accolate)- Leukotriene pathway inhibitors

• Food reduces oral absorption by up to 40%.

• 90% of metabolites are excreted in feces.

• Zafirlukast is metabolized by CYP3A4 and CYP2C9 competing with other substrates.

• This will increase the level of warfarin, phenytoin (anti-seizure), carbamazepine (antiseizure), cyclosporin (immunosuppressant), and dihydropyridine (calcium channel blocker to reduce blood pressure).

Omalizumab (Xolair)

Anti-IgE monoclonal antibody

• This is an antibody designed to attach to an antibody.

• It does not bind to IgE already bound to mast cells.

• Subcutaneous injection yeilds 62% bioavailable.

• Metabolism is unknown

Theophylline- Methylxanthines

• Purported to act by inhibiting phosphodiesterase causing increased cAMP. (relaxes bronchial smooth muscle).

• Theophylline metabolism via C8 oxidation and N-demethylation.

• Methyluric acids do not exacerbate gout, and 1,3-dimethyluric acid is the major urinary metabolite 

• Narrow therapeutic window (10 to 20mg/L) since overdose can cause the quick onset of ventricular arrhythmias, convulsions, and death 

• Drug interactions, such as quinolones, macrolide antibiotics, and oral contraceptives, can increase theophylline concentration.

Dyphylline- N7 dihydroxylpropyl theophylline

• Less effective than theophylline, but also less side effects.

• Comes in elixer and tablet.

Histamine

Histidine