1. What are the therapeutic effects of theophylline in the treatment of bronchial asthma?

- prophylactic effects

- COPD use

- reduces shortness of breath, chest tightness and low oxygen in COPD patients

- relaxes and opens airways, easier to breath

2. What are the primary mechanisms according to which the therapeutic effects are evoked? What is the mechanistic connection with b₂-agonists and antimuscarinic drugs? How would you describe the interaction with the b₂-agonists molecular-pharmacologically? 

Mechanisms - smooth muscle relaxation

                        - suppression of response of airway to stimuli 

Mechanism connection - b₂-agonists acts as functional antagonist of all mediators of bronchial constriction, and antimuscarinic drugs are competing antagonists.

 b₂-agonists - relax airway smooth muscles and open airways

                      - stimulate beta-2-adrenergic receptors

                      - increases cyclic AMP

                      - antagonizes mechanism of bronchoconstriction

 

3.  On which other systems in the body do the methylxanthines have an effect?  Where do you see the potential for undesirable side-effects and possibly also for other therapeutic applications of these side-effects?  Place special emphasis on the central and skeletal muscle effects.

- Renal - glomerular filtration rate increases, frequent urination

- Central nervous system - insomnia(sleeplessness)

                                              - very alert

                                              -therapeutic : can give energy when feeling tired

-Gastrointestinal tract - increased secretion of digestive enzymes

- Skeletal muscles - diaphragm skeletal muscles contract stronger 

 COPD patients benefit due to increased ventilation(higher O2 levels).                                             

4. What can you say about serious toxicities and the therapeutic index of theophylline?  How can the plasma levels of theophylline be influenced by pharmacokinetic drug interactions?  With which drugs can it be clinically important and why?

Theophylline has small therapeutic index. Do not exceed 20 µg/ml, can lead to nausea, vomiting, headache, insomnia. Serious toxicities exceed 40 µg/ml, which leads to heart dysrhythmia and convulsions.

Drugs such as erythromycin, propranolol, isoproterenol, cimetidine and oral contraceptives can increase theophylline levels and should therefore be administered in a smaller dose if taken with these named medications.

5. How is theophylline administered?  What are the advantages of the slow-release forms? 

-IV

-orally

-inhalation

- slow release forms will supress symptoms of bronchial asthma for a longer period of time

6. You have a patient who uses theophylline for the treatment of chronic asthma.  Your patient, however, develops a cold leading to a worsening of asthma.  After a week your patient develops a secondary bacterial infection and the doctor prescribes a penicillin antibiotic.  You are an alert pharmacist and quickly detect that your patient is allergic to penicillin.  You phone the doctor who suggests that you must rather give erythromycin antibiotic.  Do you think it is a good idea?  Assume your patient has developed a genitor-urinary tract infection, do you think it is a good idea to use ciprofloxacin?  And if she has a problem with heartburn, are there drugs that you should be careful to recommend?  Make use of your SAMF in considering the case.

Erythromycin and Ciprofloxacin inhibits liver enzymes. These enzymes are used to metabolize theophylline. Theophylline levels will rise in the body and lead to toxic effects.