It has a very high volume of distribution, as it diffuses into the bodys adipose tissue.Accumulation of the drug may result in deposits that can lead to blurred vision and blindness. It and related quinines have been associated with cases of retinal toxicity, particularly when provided at higher doses for longer times. With long-term doses, routine visits to an ophthalmologist are recommended.Chloroquine is also a lysosomotropic agent, meaning it accumulates preferentially in the lysosomes of cells in the body. The pKa for the quinoline nitrogen of chloroquine is 8.5, meaning it is about 10% deprotonated at physiological pH (per the Henderson-Hasselbalch equation). This decreases to about 0.2% at a lysosomal pH of 4.6. Because the deprotonated form is more membrane-permeable than the protonated form, a quantitative "trapping" of the compound in lysosomes results. Mechanism of action
Malaria
The lysosomotropic character of chloroquine is believed to account for much of its antimalarial activity; the drug concentrates in the acidic food vacuole of the parasite and interferes with essential processes. Its lysosomotropic properties further allow for its use for in vitro experiments pertaining to intracellular lipid related diseases, autophagy, and apoptosis.Inside red blood cells, the malarial parasite, which is then in its asexual lifecycle stage, must degrade hemoglobin to acquire essential amino acids, which the parasite requires to construct its own protein and for energy metabolism. Digestion is carried out in a vacuole of the parasitic cell.Hemoglobin is composed of a protein unit (digested by the parasite) and a heme unit (not used by the parasite).
In patients with labial fusion, a flat plane of tissue with a dense central line of tissue is usually seen when the labia majora are retracted, while an anterior opening is usually present below the clitoris. Treatment
Treatment is not usually necessary in asymptomatic cases, since most fusions will separate naturally over time, but may be required when symptoms are present. The standard method of treatment for labial fusion is the application of topical estrogen cream onto the areas of adhesion, which is effective in 90% of patients. In severe cases where the labia minora are entirely fused, causing urinary outflow obstruction or vaginal obstruction, the labia should be separated surgically. Recurrence after treatment is common but is thought to be prevented by good hygiene practices. One study has shown that betamethasone may be more effective than estrogen cream in preventing recurrence, with fewer side effects. Epidemiology
Labial fusion is not uncommon in infants and young girls. It is most common in infants between the ages of 13 and 23 months, and has an incidence of 3.3% in this age group. It is estimated that labial fusion occurs in 1.8% of all prepubertal girls. It is rare in adult women, particularly in reproductive age, but is occasionally found in postpartum and postmenopausal women. References
External links
Labial adhesions at Medscape