Classification:
Natural: there are three pharmacologically important xanthines:
- Caffeine; present in tea, coffee, cacao and cola drink.
- Theophylline.
- Theobromine. Synthetic: aminophylline
Mechanism of action:
-
They block cell surface receptor for adenosine (Adenosine causes contraction of airway smooth muscle, enhances histamine release from cells present in the lung).
-
They inhibit the enzyme phosphodiestrase (PDE) leading to an increase in the intracellular cAMP level which lead to relaxation of airway muscles and inhibition of release of the bronchoconstrictor substances from the mast cells.
-
They stimulate the release of catecholamines from adrenal medulla and inhibit COMT enzyme leading to bronchodilatation.
-
Theophylline Improves diaphragmatic contraction and reduces respiratory muscle fatigue.
Therapeutic Uses:
(A) Respiratory uses:
-
Management of asthma: Symptomatic relief of acute attack: aminophylline (250 mg) is given by slow ((may stop heart if fast == cardiac arrest)) I.V infusion (at least over 15 minutes) followed by maintenance I.V infusion of 0.7 mg/Kg/h. also used in all types of asthma.
-
Treatment of bronchospasm due to chronic bronchitis or emphysema.
(B) CNS uses:
- Headache (Caffeine + Aspirin)
- Migraine (Caffeine + Ergot)
(C) Cardiac uses: Refractory cases of congestive heart failure (positive inotropic)
(D) Gastrointestinal uses: acute biliary colic
Pharmacological effects:
Respiratory effects: thophphylline and aminophylline are potent direct bronchodilators and has some anti-inflammatory action in the air way
CNS effects:
- Caffeine and theophylline produce psychomotor stimulant effects.
- Reduced fatigue, improved mental performance, increased alertness and power of concentration without euphoria. large doses may produce restlessness, insomnia, headache and convulsions.
CVS effects:
- All xanthines, possess an inotropic action. Large and toxic dose may cause extrasystoles. The heart rate is usually increased .
- Xanthines cause constriction of the cerebral vessels (mainly caffeine).
- And causes peripheral dilatation of the blood vessels. Peripheral dilatation of blood vessels dominates the cerebral vasoconstrictor effect resulting in hypotension.
Smooth muscles: xanthines, particularly theophylline and aminophylline, are direct smooth muscle relaxants, the most prominent effect is on the bronchi = Bronchodilation
Skeletal muscles: xanthines, particularly caffeine, cause direct stimulation of the skeletal muscles, this together with the central stimulant action delays fatigue and improves muscle work.
Diuretic action: xanthines cause weak diuresis, this is partly due to increased renal blood flow and partly due to inhibition of sodium reabsorption.
Miscellaneous: Stimulation of gastric secretion (mainly caffeine).
Adverse effects:
GIT: nausea, vomiting, anorexia, reactivation of peptic ulcer.
CVS: palpitations, tachycardia, precordial pain, and arrhythmias. Rapid I.V.injection can cause hypotension, syncope and cardiac arrest.
CNS: irritability, insomnia, nervousness & convulsions.
Respiratory: tachypnea and respiratory arrest at large dose.