• Apomorphine (and Bromocriptide)
• A D₂ agonist used in the treatment of parkinsons
• It acts on the D₂ receptor in the CTZ to cause vomiting
• Morphine
• In excess amounts, also acts on D₂ receptors
• Syrup of Ibericat
• Irritates the gut, causing activation of 5HT₃ receptors
• Cisplatin
• Anti cancer drug which causes release of serotonin in the gut, which then acts on 5HT₃ receptors

• The main area in the brain responsible for vomiting is the vomiting center
• This area is located in the lateral reticular formation of the medulla
• It receives input from many areas:
• Chemoreceptor trigger zone
• Located in the floor of the 4th ventricle in the area postrema
• It picks up circulating chemical in the blood
• It is important because it lies outside the BBB, therefore, circulating toxins (e.g.bacterial food poisoning toxins, chemotherapy) can cause vomiting, even though they do not pass through the BBB

• Vestibular apparatus
• Tractus solitarius
• vagal afferents from the gut, heart and testes
• Direct input from gut (reflex)

• On the CTZ:
• 5HT3
• D2
• On the vagal afferents:
• 5HT3
• In the vomiting center
• Muscarinic
• H1 receptors

Several treatment schemes are possible.

• 1st choice: Intravenous or oral trimethoprim/sulphamethoxazole (= cotrimoxazole, Bactrim®, Eusaprim®) 4 x 3 ampoules IV per day or 6-8 Bactrim forte® tablets per day. If there is no pronounced dyspnoea, the treatment can be given all orally. Side-effects of the medicaments occur frequently (allergic reactions with cutaneous abnormalities).

• 2nd choice: Oral dapsone/trimethoprim (Dapson® 100 mg/day + Wellcoprim® 20 mg/kg/day divided over 4 doses). With less serious PCP 100 mg dapsone is administered together with TMP (trimethoprim) 3 x 300 mg/day.

• 3rd choice: Pentamidine (Pentacarinat®) IV. The guide dose is 4 mg/kg in one administration over 8 hours in a 5% glucose infusion.

• 4th choice: Pentacarinat® in 300 mg aerosol in 6 ml sterile water. It is advised to give salbutamol puffs beforehand.

• Alternatives: other medicaments are clindamycin + primaquine, atovaquone and trimetrexate (Neutrexin®). The duration of the treatment is 21 days.

In case of severe hypoxia intravenous steroids (methylprednisolone) should be given. The patient may exhibit a hypersensitivity reaction due to the release of large quantities of antigenic material from the organisms. At later stages, corticosteroids are no longer effective.

A relapse frequently occurs after discontinuing a "curative" treatment. Prophylaxis is therefore given after the initial treatment. The same medicaments but in lower dose (Bactrim forte® 1 per day; or dapsone 100 mg/day) PO or 300 mg pentamidine-aerosol once a month can be used. Fansidar® 1 tablet per week can also be given. Cotrimoxazole acts simultaneously as a prophylactic agent for toxoplasmosis. Dapsone can be tried when cotrimoxazole is not tolerated.

Candida albicans

in the mouth, throat and oesophagus causes difficulty in swallowing. This fungal infection can be treated with gentian violet or nystatin tablets, ketoconazole (Nizoral®), topical miconazole (Daktarin®), systemic itraconazole (Sporanox®) or fluconazole (Diflucan®). Gentian violet (1.5 ml 0.5 % aqueous solution, 2 x per day) is cheap, but stains the mouth purple. Gentian violet does not help in oesophageal candidiasis. Itraconazole and fluconazole are very expensive. Buccal tablets containing miconazole in a prolonged release formulation can be placed under the upper lip for local (topical) treatment of oropharyngeal candidiasis. Voriconazole, a new triazole, is very promising but at the moment there is very little data on it. It is also active against Candida kruseii, a yeast that is inherently resistant to fluconazole. It penetrates the blood-brain barrier and can be used in cases resistant to amphotericin B. Caspofungin (Cancidas®) belongs to the new class of echinocandins, and is active against divers Candida species (C. albicans and several C. non-albicans, including C. krusei). The normal dose is 70 mg as a single start-dose, followed by 50 mg/day IV. For patients heavier than 80 kg, a daily dose of 70 mg/day is advised. In case of medium liver failure (Child-Pughscore 7-9) 35 mg/day as maintenance dose is advised. There is no need for dose-adjustment in case of renal failure.

Blastomyces dermatitidis causes blastomycosis (USA and Middle East). The disease often resembles tuberculosis or a carcinoma. It can be treated with itraconazole (200-400 mg/day for a minimum of 6 months). Amphotericin B is used when the infection is resistant to itraconazole or when the brain is affected. There is still insufficient experience with echinocandine.

Herpes simplex can cause skin lesions and can also affect the gastrointestinal system. An oral antiviral treatment for 5 days can be considered in cases of a first episode of herpes genitalis. The antiviral agents aciclovir (Zovirax®), famciclovir (Famvir®) and valaciclovir (Zelitrex®) are all equally effective. However, the risk of recurrences is not diminished by these. Treatment must be started as soon as possible. Topical antiviral agents are not very effective. IV administration is no better than oral treatment. Local analgesics help to diminish the pain of miction or defaecation.

Treatment of recurrences

Episodic antiviral treatment or a prolonged prophylactic treatment can be considered in addition to the symptomatic treatment.

• Episodic antiviral therapy must be started upon appearance of the first symptoms. The duration of the symptoms is diminished by only 1 to 2 days.

• Prophylactic therapy lasting 6 months to one year is indicated for patients who have more than 6 to 8 relapses per year. A formal diagnosis (culture, PCR) is advisable before starting it. The patient's physical and mental well being can be considerably improved with prophylactic therapy.

• In patients in an advanced stage of immunodepression, herpes infections are often very serious. The possibility of the existence of these should be clinically considered when persistent, painful antibiotic-resistant genital or perianal ulcers are present. In Belgium the prevalence of strains resistant to aciclovir is 5 to 10%. In this case foscarnet can be used as an alternative.

Treatment of herpes genitalis during pregnancy.

The purpose of the treatment is both to alleviate the symptoms of the mother and to diminish the risk of neonatal herpes. Approximately 85% of neonatal herpes cases are attributable to perinatal transmission of the virus during vaginal childbirth. The risk is particularly high when the woman develops a primo-infection during the third trimester of pregnancy. If herpetic lesions first appear during the first trimester of pregnancy treatment with aciclovir can be considered. However, aciclovir is not registered for use during pregnancy, though the available data show no increase in the number of deformities in the children. A Caesarean section is recommended when there are active lesions at the time of childbirth. In cases where a first episode of herpes genitalis appears during the third trimester the birth must likewise be carried out by Caesarean section. Treatment with aciclovir, orally for the mother and intravenously for the child, should be started if the birth has to take place via the vaginal route.

Herpes zoster lesions occur in the region of a skin nerve (dermatoma). After healing a white band-shaped zone (depigmentation) or hyperpigmentation often remains. When the ophthalmic nerve is affected the eye can be damaged and blindness may occur. Many patients will develop herpes zoster, sometimes with several episodes and sometimes covering more than 1 dermatoma at the same time. If it is localised on the face, the eyes can be affected and blindness can occur. If the tip of the nose shows a lesion, the nasociliary branch of the ophthalmic nerve is involved. This makes corneal lesions very likely. Aciclovir (800 mg, 5 times per day), valaciclovir 1000 mg, 3 times per day or famciclovir (the prodrug of penciclovir) 500 mg, 3 times per day are used in the treatment. Post-herpetic neuralgia is difficult to treat. When customary analgesics or topical lidocaine have insufficient effect, the antidepressants nortriptyline, amitriptyline (Redomex®) or desipramine (Pertofran®) can be tried. Anticonvulsants such as carbamazepine or gabapentine can sometimes alleviate the pain. Opioids such as oxycodone can bring relief in some patients. A peripheral nerve blockade is an emergency solution. When analgesics bring no improvement, methylprednisolone may be administered intrathecally (the neuralgia has an inflammatory component).

Brivudin, an antiviral agent used in treating herpes zoster, is significantly more efficacious than standard aciclovir. Data also showed that brivudin is as effective as famciclovir in alleviating acute signs and symptoms of herpes zoster. Furthermore, brivudin, which is given orally at a dose of 125 mg once daily for seven days, improves patient compliance.

This virus of the herpes group can cause retinitis, pneumonitis, encephalitis and colitis. Ganciclovir (Cymevene®), foscarnet (Foscavir®), valganciclovir (Valcyte®) and cidofovir (Vistide®) are used in the treatment. These products are too expensive for use in developing countries. Ganciclovir is a nucleoside analogue [nucleoside = base + saccharide] and must be coupled intracellularly to 3 phosphate groups in order to be activated. The first phosphate is coupled by a viral kinase. The next two phosphate groups are attached by a cellular enzyme. The kinase of the virus can mutate and hence resistance can occur. Cidofovir is a nucleotide analogue [nucleotide = base + saccharide + phosphate] and must be coupled to 2 phosphate groups by cellular enzymes in order to be activated. Ganciclovir can be administered IV, PO or intraocularly. Its side-effects are haemato- and nephrotoxicity. When kidney function is reduced ganciclovir® is given in a dosage of 2 x 5 mg/kg/day (infusion over 1 hour). Maintenance therapy is 5 mg/kg/day for 7 days per week or 6 mg/kg/day for 5 days per week. In the West, maintenance therapy is often given via a Port-a-cath. Vitrasert is a minuscule shield impregnated with ganciclovir that can be surgically inserted into an eye, producing high concentrations in loco. Preventive oral ganciclovir therapy for CMV leads to resistance in 23% after one year. When kidney function is normal, treatment with foscarnet -a pyrophosphate analogue-, 180-200 mg/kg/day (normally 2 x 250 ml for an average adult, diluted for peripheral infusion) can be given as an alternative. The dose for maintenance therapy is 120 mg/kg/day. The principal side-effect of foscarnet is nephrotoxicity. Fomivirsen is an experimental anti-CMV product that is still being evaluated. Monthly maintenance eye injections of fomivirsen (Vitravene) are evaluated for resistant CMV retinitis. Lobucavir and adefovir (bis-POM-PMEA) are still in an experimental stage.