External therapy: Minoxidil
MINOXIDIL: Minoxidil was approved in 1988 by the American FDA for use in males in a 2% solution, and in 1991 for use in women at the same concentration.  Subsequently, in 1997 it was approved for use in men in a 5% solution.  In the USA both concentrations are available commercially in foam or lotion format while in Spain only the lotion format is commercially available. The 5% solution has not yet been approved for use in women although it has been used globally by many dermatologists in made to order prescriptions. Mechanism of Action Minoxidil is a potent vasodilator and is administered orally for the treatment of arterial hypertension. A side effect of hypertricosis was observed in patients who were taking the medicine for more than one year. The exact mechanism of action at the level of the hair is still not exactly understood. It doesn’t appear to have any hormonal or immune-suppressor effects, but it has demonstrated a direct stimulating effect on the epidermis cells and developing hair bulbs. It has been shown that it prolongs the survival of the keratinocytes. And lastly, it is known that it acts by stimulating the opening of potassium channels, which provokes hyperpolarisation at the cell membranes. These conditions cause a decrease in the chance that other ionic channels would open, such as sodium, chloride or calcium channels. Calcium channels are suspected in playing a part in the inhibition of hair growth. Contrary to popular belief, local vasodilatation would appear to not have an important role in hair growth. Treatment with minoxidil leads to a thickening of the hair is affected zones, beginning with down hair and growth being observed in terminal hairs in a period up to 12 months, in masculine alopecia as well as female. A better result is seen in those patients who don’t have total hair loss in the affected zone as the increase in density is mainly due to miniaturized hairs becoming terminal hairs rather than the growth of new hair. This occurs in a period of no less than 4 months after first starting to use this product, and continuing its progress until reaching definitive results after one year. At the beginning (after approximately 20 days) there may be a slightly more hair loss than usual which is normal and expected and should not be a motive for suspending treatment. This happens as a result when minoxidil “assembles” a large number of follicular units which enter into a rest or telogen phase which after 3 – 4 months begin to generate new hairs all at the same time. The hair loss then stabilizes after the initial period of re-growth. The application of minoxidil should continue as long as the hair loss is a problem for the patient, since the suspending treatment leads to a loss in effectiveness and a possible return to the initial state of the alopecia in around 4 months. Treatment consists of external applications made twice daily during the entire time that the product is being used. Those patients who begin to apply the product only once a day may notice a reduction in their hair count after 12 months. Minoxidil should be tried for one whole year before evaluating its therapeutic effectiveness. This is evaluated by the patients satisfaction and comparison of photos by the doctor. Only a certain improvement is obtained during treatment. Minoxidil, external solution of 2% and 5%, is used for the treatment of masculine alopecia in the front-parietal and parietal-occipital regions and for diffuse feminine alopecia, both of androgenic origin. It is effective, especially on the crown area, where it preserves if not reduces the horizontal diameter of the alopecia. Although confirmative statistics don’t yet exist, the combined use of minoxidil and finasteride in men has a synergic affect which increases the benefits of that either can provide on their own. Dosage: The patient should use 1 millilitre of minoxidil solution two times a day. The drops should be applied directly onto the dry scalp and be spread around with the fingers (massage or friction not required). The dosage should be applied equally independently of the extent of hair loss, as the amount applied is absorbed and acts on the whole scalp. The maximum recommended daily dosage is 2 ml. The best way to apply it is to place 1 ml of the solution in a small syringe (the kind used for insulin) and perform three runs along the scalp from the crown to the front hairline or vice versa and then spread it around the whole area. A spray atomizer is not recommended as a large part of the solution will be applied to the hairs, where minoxidil is ineffective and is thus wasted. Minoxidil can be formulated with 0.025% retinoic acid to augment the effectiveness as this increases the anagen phase and favours the penetration of the minoxidil. When retinoic acid is added to minoxidil, however, the probability of local irritation increases and isn’t always tolerable. Side effects: Minoxidil is very tolerable and the side effects are mainly dermatological in nature. The most frequent unwanted effect is irritable contact dermatitis characterized by intense itching, redness and intense flaking of the skin. In the majority of cases this is caused by the carrier responsible for the absorption of minoxidil into the skin which is the ethanol’s (alcohols): propylene glycol (PPG), polyethylene glycol (PEG) or ethylene glycol (EG). Any of the aforementioned symptoms are sufficient motive to suspend the medication and consult a specialist. The contact dermatitis produced can be bad enough to cause a 40% increase in hair loss, a reaction called Chemical Telogen Effluvium, which as unpleasant as it is, is usually temporary and clears up in 3 – 4 months. The frequency of irritation in the scalp is approximately 7% for the 2% solution users and may be slightly higher with the 5% solution simply because the concentrations of the solvents are higher in these solutions. Bibliographic studies indicate that to date around 20% of the population is sensitive to these solvents without knowing it. Occasionally the active ingredient of minoxidil may cause allergic contact dermatitis but the percentage of these cases is less than 10%.  If patients experience contact dermatitis with the 5% solution, they should stop treatment until all symptoms have cleared up and they should also stop using any products that have the initials PPG, PEG and EG. Minoxidil solution shouldn’t be used again without consulting a doctor as it’s very unlikely that tolerance to this side effect can be developed. In these cases the use of minoxidil may never be a productive measure. Although less frequently, other effects may be observed such as acne, increased hair loss and facial swelling. Facial hypertricosis (growth of undesired hair) in the eyebrow, cheek or jaw regions may be observed in 3 – 5% of women but doesn’t seem to be a problem in men. An explanation for hypertricosis has not yet been found, although it is possibly due to a systemic effect of the inadvertent application of the medication to these other areas. Hypertricosis is completely reversible after the suspension of the treatment. It is important that patients wash their hands after application and that care is taken so that not a single drop falls outside of the scalp area. In the case that any of these reactions occur, the patient should stop using minoxidil and consult their specialist. Contact with any mucous surface should be avoided, mainly the eyes, as this would cause irritation and burning. If this occurs the eyes should be rinsed well with cold running water. The effects of minoxidil during pregnancy and lactation are unknown, so its use is not recommended without first consulting a doctor. Up to now there have been no human trials carried out, although alterations have been seen in rats and rabbits. Minoxidil taken orally is secreted in human mother’s milk. The accidental ingestion of minoxidil may incur significant side effects (each millilitre of 5% solution contains 0.05g of minoxidil); in these cases the patient should quickly go to the hospital emergency services.  
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