Teratogenesis Health Dictionary

A common skin condition starting after puberty, and which may persist for many years. It involves plugged pores (blackheads and whiteheads), pimples and deeper nodules on the face, neck, trunk and even the upper arms. It arises from pilosebaceous glands (relating to hair follicles and associated SEBACEOUS GLANDS). SEBUM production is increased and bacterial proliferation causes in?ammation with PAPULE and PUSTULE formation. Plugs of sebum and epidermal cells form blackheads (comedones); the colour is not due to dirt but to dried oil and shed skin cells in the hair-follicle openings.

Treatment Twice-daily washing with a salicylic-acid cleanser can help remove the pore-blocking debris, as can daily shampooing. Use only oil-free cosmetics and hide blackheads with a ?esh-tinted acne lotion containing benzoyl peroxide, acid or sulphur. Never squeeze blackheads, however tempting; ask a skin specialist how to do this properly. Other treatments include microdermabrasion, and the antibiotic lotions erythromycin and clindamycin may be e?ective. Tretinoin and adapilene can be used on the skin but are not permitted in pregnancy and may cause problems such as hypersensitivity to sunlight, so medical advice is essential. In resistant cases, long-term suppressive oral therapy with one of the TETRACYCLINES or with ERYTHROMYCIN may be necessary. In females a combined oestrogenantiandrogen ‘pill’ is an alternative. Severe resistant acne can be cleared by a 16- to 24week course of oral isotretinoin, but this drug is teratogenic (see TERATOGENESIS) and can cause many side-effects including depression, so its use requires specialist supervision.

See www.skincarephysicians.com/acnenet/... acne

When a new drug is introduced, it has usually been studied only in relatively few patients – typically 1,500. If n patients have been studied, and no serious effects observed, there is still a chance of a serious adverse e?ect occurring in the general population as frequently as 3/n (1:500).

Adverse effects can be divided into types. First, those which are closely related to the concentration of the drug and accord with what is known of its PHARMACOLOGY. These so-called type A (augmented pharmacological) effects are distinguished from type B (bizarre) effects which are unpredictable, usually rare, and often severe. ANAPHYLAXIS is the most obvious of these; other examples include bone-marrow suppression with CO-TRIMOXAZOLE; hepatic failure (see HEPATITIS) with SODIUM VALPROATE; and PULMONARY FIBROSIS with AMIODARONE. A more comprehensive classi?cation includes reactions type C (chronic effects), D (delayed effects – such as teratogenesis or carcinogenesis) and E (end-of-dose effects – withdrawal effects). Examples of adverse reactions include nausea, skin eruptions, jaundice, sleepiness and headaches.

While most reported adverse reactions are minor and require no treatment, patients should remind their doctors of any drug allergy or adverse e?ect they have suffered in the past. Medical warning bracelets are easily obtained. Doctors should report adverse effects to the authorities – in the case of Britain, to the Committee on Safety of Medicines (CSM), using the yellow-card reporting machinery.... adverse reactions to drugs

Alkylating agents are so named because they alkylate or chemically react with certain biochemical entities, particularly those concerned with the synthesis of NUCLEIC ACID. Alkylation is the substitution of an organic grouping in place of another grouping in a molecule.

Alkylating agents are important because they interfere with the growth and reproduction of cells, disrupting their replication. This CYTOTOXIC property is used to retard the division and growth of cancer cells, and alkylating drugs are widely used in the chemotherapy of malignant tumours – often in conjunction with surgery and sometimes with radiotherapy. Unfortunately, troublesome side-effects occur, such as: damage to veins when the drug is given intravenously, with resultant leakage into adjacent tissues; impaired kidney function due to the formation of URIC ACID crystals; nausea and vomiting; ALOPECIA (hair loss); suppression of BONE MARROW activity (production of blood cells); and adverse effects on reproductive function, including TERATOGENESIS. Indeed, cytotoxic drugs must not be given in pregnancy, especially during the ?rst three months. Prolonged use of alkylating drugs, especially when accompanying radiotherapy, is also associated with a sign?cant rise in the incidence of acute non-lymphocytic LEUKAEMIA. Among the dozen or so alkylating drugs in use are CYCLOPHOSPHAMIDE, CHLORAMBUCIL, MELPHALAN, BUSULFAN and THIOTEPA. (See also CHEMOTHERAPY.)... alkylating agents

This consists of defects in the distal part of the extremities: for example, the absence of a forearm or hand. Hemimelia is a congenital defect; large numbers of cases resulted from the administration of THALIDOMIDE during pregnancy (see also PHOCOMELIA; TERATOGENESIS).... hemimelia

A sedative and hypnotic drug long withdrawn from the market because it causes TERATOGENESIS. If taken during the ?rst trimester of pregnancy it may cause an unusual limb deformity in the fetus known as phocomelia (‘seal’ or ‘?ipper’ extremities).... thalidomide

n. a drug, related to *thalidomide, that affects the immune response and has activity against tumour cell formation and *angiogenesis. It is used to treat multiple myeloma and certain types of *myelodysplastic syndromes. The most serious side-effects are deep vein thrombosis and neutropenia, and there is a risk of *teratogenesis (women capable of bearing children must practise contraception during treatment and for a month before and after it).... lenalidomide

Cytotoxic means destructive to living cells. Cytotoxic drugs possess anti-cancer properties but also have the potential to damage normal tissue. Their use is twofold: to eliminate a cancer and so prolong life; or to alleviate distressing symptoms, especially in patients whose prospects of a cure are poor. In many cases CHEMOTHERAPY with cytotoxic drugs is combined with surgery, RADIOTHERAPY or both. Chemotherapy may be used initially to reduce the size of the primary TUMOUR (a process called neoadjuvant therapy) before using radiotherapy or surgery to eliminate it. Cytotoxic drugs may also be used as adjuvant treatment to prevent or destroy secondary spread of the primary tumour that has either been removed by surgery or treated with radiotherapy. All chemotherapy causes side-effects: the ONCOLOGIST – a specialist in cancer treatment – has to strike a balance between hoped-for bene?ts and acceptable (for the patient) toxic effects, which include nausea and vomiting, BONE MARROW suppression, ALOPECIA (hair loss) and teratogenic effects (see TERATOGENESIS).

Cytotoxic drugs are used either singly or in combination, when an enhanced response is the aim. Chemotherapy of cancer is a complex process and should be supervised by an oncologist in co-operation with physicians, surgeons, radiotherapists and radiologists as appropriate.

The cytotoxic drugs include:

(1) The alkylating agents which act by damaging DNA, thus interfering with cell reproduction. Cyclophosphamide, ifosfamide, chlorambucil, kelphalan, busulphan, thiotepa and mustine are examples of alkylating agents.

(2) There are a number of cytotoxic antibiotics used in the treatment of cancer – doxorubicin, bleomycin, dactinomycin, mithramycin and amsacrine are examples. They are used primarily in the treatment of acute leukaemia and lymphomas.

(3) Antimetabolites – these drugs combine irreversibly with vital enzyme systems of the cell and hence prevent normal cell division. Methotrexate, cytarabine, ?uorouracil, mercaptopurine and azathioprine are examples.

(4) Another group of cytotoxic drugs are the vinca alkaloids such as vincristine, vinblastine and vindesima.

(5) Platinum compounds such as carboplatin, cisplatin and oxaliplatin are e?ective. All of them are given intravenously, but the latter two tend to have more unpleasant side-effects. Carboplatin and cisplatin are useful in the treatment of solid tumours. Carboplatin, a derivative of cisplatin, is given intravenously in ovarian cancer and in small-cell lung cancer. Better tolerated than cisplatin, the drug causes less nausea and vomiting, nephrotoxicity, neurotoxicity and ototoxicity. Where platinum-containing therapy has failed, intravenous treatment with paclitaxel may be tried. With only a limited success rate, it is relatively toxic and should be carefully supervised; responses, however, are sometimes prolonged.

Also of increasing importance in treating cancer are interferons. These are naturally occurring proteins with complex effects on immunity and cell function. Although toxic, with numerous adverse effects, they have shown some anti-tumour e?ect against certain lymphomas and solid tumours.... cytotoxic

Unnecessary drugs during pregnancy should be avoided because of the adverse e?ect of some drugs on the fetus which have no harmful e?ect on the mother. Drugs may pass through the PLACENTA and damage the fetus because their pharmacological effects are enhanced as the enzyme systems responsible for their degradation are undeveloped in the fetus. Thus, if the drug can pass through the placenta, the pharmacological e?ect on the fetus may be great whilst that on the mother is minimal. WARFARIN may thus induce fetal and placental haemorrhage and the administration of THIAZIDES may produce THROMBOCYTOPENIA in the newborn. Many progestogens have androgenic side-effects and their administration to a mother for the purpose of preventing recurrent abortion may produce VIRILISATION of the female fetus. Tetracycline administered during the last trimester commonly stains the deciduous teeth of the child yellow.

The other dangers of administering drugs in pregnancy are the teratogenic effects (see TERATOGENESIS). It is understandable that a drug may interfere with a mechanism essential for growth and result in arrested or distorted development of the fetus and yet cause no disturbance in the adult, in whom these di?erentiation and organisation processes have ceased to be relevant. Thus the e?ect of a drug upon a fetus may di?er qualitatively as well as quantitatively from its e?ect on the mother. The susceptibility of the embryo will depend on the stage of development it has reached when the drug is given. The stage of early di?erentiation – that is, from the beginning of the third week to the end of the tenth week of pregnancy – is the time of greatest susceptibility. After this time the risk of congenital malformation from drug treatment is less, although the death of the fetus can occur at any time.... drugs in pregnancy

An infectious skin disease caused usually by Staphylococcus aureus and less often by Streptococcus pyogenes. The itching rash is seen especially on the face but may spread widely. Vesicles and pustules erupt and dry to form yellow-brown scabs. Untreated, the condition may last for weeks. In very young infants, large blisters may form (bullous impetigo).

Treatment Crusts should be gently removed with SALINE. Mild cases respond to frequent application of mupiricin or NEOMYCIN/BACITRACIN ointment; more severe cases should be treated orally or, sometimes, intravenously with FLUCLOXACILLIN or one of the CEPHALOSPORINS. If the patient is allergic to penicillin, ERYTHROMYCIN can be used.

For severe, intractable cases, an oral retinoid drug called isotretinoin (commercially produced as Roaccutane®) can be used. It is given systemically but treatment must be supervised by a consultant dermatologist as serious side-effects, including possible psychiatric disturbance, can occur. The drug is also teratogenic (see TERATOGENESIS), so women who are, or who may become, pregnant must not take isotretinoin. It acts mainly by suppressing SEBUM production in the sebaceous glands and can be very e?ective. Recurrent bouts of impetigo should raise suspicion of underlying SCABIES or head lice. Bactericidal soaps and instilling an antibiotic into the nostrils may also help.... impetigo