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Athsma Ii Notes

Pharmacology Notes > Drug Development (BIOL10822) Notes

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Anti-Asthma Drugs II - (Lecture 21)

Used in addition to beta-2 agonists, glucocorticoids if symptoms not controlled.

THE ALKYLXANTHINE BRONCHODILATOR - THEOPHYLLINE:Some of the oldest treatments for asthma are based around a group of drugs related to caffeine: the alkylxanthines.
Whilst caffeine itself has some anti-asthma effects, the main drug used today is theophylline. This is the main alkylxanthine in tea. INHIBITION OF CYCLIC NUCLEOTIDE PHOSPHODIESTERASE - THE MECHANISM
- The mechanism of the alkylxanthines if far from clear.
- They have two main pharmacological effects:
they inhibit the enzymes responsible for the breakdown of cAMP -
- This might impact on both the inflammatory processes and the bronchoconstriction seen in asthma.However, theophylline is also an antagonist of adenosine receptors and this is also likely to contribute to its mechanism of action.

AMINOPHYLLINE: A water soluble complex of theophylline and ethylenediamineTheophylline is not used as frequently now as it used to be, but it can be given either as an oral formulation (sustained release) or as an IV infusion. It is often complexed with ethylenediamine and is known as aminophylline.

THEOPHYLLINE:Use - orally (sustained-release capsules) as add-on therapy, i.v. for status asthmaticus (severe asthma attack - life threatening)
Therapeutic window is narrow - (toxic dose is only around 2x therapeutic dose)
Half-life affected by cardiac/liver disease, smoking, and many drugs
Monitoring a plasma or saliva assay can help to determine dosage regimen

METABOLISM OF THEOPHYLLINE:CYP1A2 - antidepressants, antipsychotic drugs, paracetamol, verapamil,
Inhibited by: verapamil, caffeine, amiodarone, grapefruit juice, many herbal teas
Induced by: tobacco, broccoli, cauliflower, grilled meat!

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