[Medicaments and oral healthcare. Medicaments potentially inducing angioedema and/or urticaria]. / Serie: Medicamenten en mondzorg. Medicamenten die angio-oedeem en/of urticaria kunnen induceren.

Angioedema stems from increased vasodilation and vascular permeability, resulting in extravasation of fluid. Hereditary and acquired types of angioedema can be distinguished, with 3 and 4 subtypes, respectively. Groups of medicaments potentially inducing angioedema are, among others: ACE inhibitors, angiotensin II receptor blockers, dipeptidyl peptidase-4 inhibitors, thrombocyte aggregation inhibitors and immunosuppressive agents. Urticaria is characterised by red, slightly raised swellings, usually associated with a strong itching sensation and can be subdivided in an acute and a chronic type. Mast cells in the uppermost layer of the skin or the mucous membranes release a lot of histamine, increasing the dilation and permeability of blood capillaries, resulting in extravasation of fluid. Medicaments potentially inducing urticaria are, among others, the following groups: analgesics, anaesthetics, antibiotics, antidepressants, antihistamines, antihypertensives, antifungals, corticosteroids, H2 blockers, cancer medicaments, muscle relaxants, thrombocyte aggregation inhibitors and vaccines. Medical history and being alert when administering and prescribing anaesthetics, analgesics and antibiotics are very important in the prevention or treatment of angioedema and/or urticaria.

[Facial angioedema following pharmacotherapy with an ACE inhibitor]. / Angio-oedeem in het aangezicht na medicatie met een ACE-remmer.

A 56-year-old women suddenly had a swelling on her right cheek and on the right side of her upper lip, for which she decided to first visit her family physician and subsequently her family dentist. During the past two years, she was treated for an ovarian carcinoma by an oncologist. Recently, she was using the antihypertensive ACE inhibitor enalapril, prescribed by her family physician. Consultation between her family dentist, family physician and oncologist led to the diagnosis angioedema as an adverse effect of enalapril. The family physician replaced enalapril by the angiotensin II receptor blocker losartan. Subsequently, the swelling disappeared within two days. This angioedema type occurs most frequently in the head and neck area. Oropharyngeal, tongue and laryngeal oedema are very dangerous because they may cause airway obstruction. Today, a live-threatening or fatal condition is mostly prevented as a result of better vigilance of dentists and physicians. Nevertheless, such a condition will still occur occasionally.

[Medicaments and oral healthcare. Hyperpigmentation of oral soft tissues due to afamelanotide]. / Serie: Medicamenten en mondzorg. Hyperpigmentatie van de orale slijmvliezen door afamelanotide.

The medicament afamelanotide is an analogue of endogenous ?-melanocyte-stimulating hormone. It promotes cutaneous pigmentation, providing protection from sunlight. In dermatology, afamelanotide seems to establish therapeutic results for polymorphic light eruption, solar urticaria, erythropoietic protoporphyria, Hailey-Hailey disease, vitiligo and acne vulgaris. Afamelanotide is available for non-medical use to realise quick and easy skin tanning. Adverse effects of afamelanotide mentioned in the scientific literature are development and aggravation of melanocytic naevi, degeneration of melanocytic naevi to melanomas, melanonychia, systemic toxicity, rhabdomyolysis, posterior reversible encephalopathy syndrome, priapism and hyperpigmentation of oral soft tissues. Furthermore, numerous adverse effects of afamelanotide have been reported to the Netherlands pharmacovigilance centre LAREB as well as numerous adverse effects due to overdosage of afamelanotide to the National Poisons Information Centre. Dentists should be alert to hyperpigmentation of oral soft tissues due to afamelanotide.

[Series: Medicaments and oral healthcare. Medicaments and addictive substances, potentially inducing or ameliorating bruxism]. / Serie: Medicamenten en mondzorg. Medicamenten en verslavende middelen die potentieel bruxisme induceren of dempen.

Bruxism is described as a repetitive jaw-muscle activity characterised by clenching or grinding of the teeth and/or by bracing or thrusting of the mandible. This article provides an inventory of medications registered in the Netherlands and of addictive substances reported to potentially induce or aggravate bruxism as an adverse effect, and of medications registered in the Netherlands reported to potentially ameliorate existing bruxism. Groups of medications known as having the potential adverse effect of bruxism are amphetamines, anticonvulsants and selective serotonin reuptake inhibitors. Separate medicaments found in the scientific literature, having this potential are aripiprazole, atomoxetine, duloxetine, flecainide, ketotifen and methadone. Addictive substances with bruxism as potential adverse effect are alcohol, heroin, methamphetamine, methylenedioxymethamphetamine, nicotine and piperazines. Medications with the potential to ameliorate existing bruxism are botulinum toxin A, bromocriptine, buspirone, clonazepam, clonidine, gabapentin and levodopa.

[Medicaments and oral healthcare. Proliferation of the gingiva]. / Serie: Medicamenten en mondzorg. Proliferatie van de gingiva.

Adverse effects of medications and self care products on the gingiva can be divided into inflammation, intrinsic discolouration, irritation, trauma, cytotoxicity, lichenoid reaction, and proliferation. This article deals with the last-mentioned type of adverse effects; the other 6 have been discussed in a previous article. Proliferation of the gingiva as an adverse effect of medications has been reported for anticonvulsants, calcineurin inhibitors, calcium channel blockers and isotretinoin. With regard to the anticonvulsants that have been registered in the Netherlands, proliferation of the gingiva is predominantly induced by phenytoin, but also by carbamazepine, ethosuximide, phenobarbital, gabapentin, levetiracetam, primidone and valproic acid. All calcineurin inhibitors registered in the Netherlands may induce the adverse effect. This is also the case for nearly all calcium channel blockers, but particularly for dihydropyridines. Presumably, proliferation of the gingiva may be prevented or reduced in a number of ways. The most important one is good oral hygiene. Furthermore, proteins and cells that play an important role [in the process of gingival proliferation] have been discovered and there are medications that have the potential to eliminate these proteins and cells.

[Medicaments and oral healthcare. Adverse effects of medicines and self care products on the gingiva]. / Serie: Medicamenten en mondzorg. Bijwerkingen van medicamenten en zelfzorgmiddelen op de gingiva.

Medications and self care products may have adverse effects on the gingiva. These adverse effects can be divided into inflammation, intrinsic discolouration, irritation, trauma, cytotoxicity, lichenoid reaction, and proliferation. This article deals with the first 6 types of adverse effects mentioned: a subsequent article will deal with the last type mentioned. Since contraceptives were introduced, there have been indications that they cause or promote gingivitis, but with the current contraceptives this adverse effect is rarely seen. Intrinsic discolouration of the gingiva has been reported when using Staloral®, minocycline, contraceptives and hydroxychloroquine. Irritation and trauma of the gingiva are seen when self care products containing carbamide peroxide or hydrogen peroxide are used for external tooth whitening, or which have analgesic potential, such as acetylsalicylic acid and hydrogen peroxide or oral rinses containing alcohol. Several cytostatics may induce apoptosis of keratinocytes in the gingiva. Oral rinses with antibacterial ingredients have cytotoxic potential. Lichenoid reactions have been reported due to the use of several (groups of) medications.

[Medicaments and oral healthcare 5. Adverse effects of -medications and over-the-counter drugs on teeth]. / Serie: Medicamenten en mondzorg 5. Bijwerkingen van medicamenten en zelfzorg­middelen op gebitselementen.

Intrinsic tooth discoloration may occur as an adverse effect of fluoride and tetracyclines. Extrinsic tooth discoloration may occur as superficial staining or as discoloration of the superficial pellicle and/or biofilm due to chlorhexidine, liquid iron salts, essential oils, some antibiotics and stannous fluoride. Inhibition of orthodontic tooth movement has been reported due to the use of prostaglandin synthetase inhibitors. If medications or over-the-counter drugs induce hyposalivation or contain much sucrose, caries may develop. Erosion may occur if the acidity of medications or over-the-counter drugs is excessive. Attrition is a well-known adverse effect of serotonin reuptake inhibitors, antiparkinson agents, and antipsychotics. Congenital dysplasia is observed following childhood treatment with cytostatic drugs. External cervical root resorption is an adverse effect of internal teeth-whitening products. Prenatal exposure to antiepileptic drugs and childhood treatment with cytostatic drugs may cause dental agenesis. Antiseptic drugs applied for external teeth-whitening and toothpastes with additional ingredients to prevent extrinsic discoloration and creation of calculus, may cause tooth hypersensitivity.

Causality methods in cosmetovigilance: comparison of Colipa and PLM versus global introspection.

The European Cosmetics Regulation requires a post-marketing system for detection of undesirable effects on human health of cosmetic products. Colipa, the European Cosmetic, toiletry and perfumery association, provided guidelines for causality assessment of these effects. In addition another causality method originally designed for causality rating in Post Launch Monitoring (PLM) of novel foods has been employed to assess causality of cosmetic products. In this study these two causality schemes for consumer cosmetic products were validated against clinical assessment, using the method of global introspection (GI) in 100 reported cases. Causality assessments were performed by three experienced assessors in pharmacovigilance. In the event of discordance between the assessors, an adapted Delphi method was used. The overall Spearman correlation coefficient was 0.74 for comparison of Colipa versus GI, whereas this was 0.50 for PLM versus GI. According to current guidelines, the sensitivity was 0.95 for both the Colipa and PLM method, specificity was 0.84 for Colipa and 0.40 for PLM. From these results it can be concluded the performance of the Colipa causality method yielded better correlation to GI than PLM causality method. The factor identified from comparison of these two schemes as having greatest impact was the course of the reaction.

[Recurrent attacks of angioedema ascribed to the use of estrogen preparations and a pregnancy (hereditary angioedema type 3)]. / Recidiverende aanvallen van angio-oedeem toegeschreven aan het gebruik van oestrogeenpreparaten en aan zwangerschap (hereditair angio-oedeem type 3).

A woman experienced recurrent attacks of angioedema from the age of 17 to 21 years and these appeared to be associated with the use of oestrogens. After stopping the medication her complaints disappeared, but they returned during her first pregnancy. Angioedema is a serious condition, which can lead to acute abdominal symptoms, oedema of the upper respiratory tract and death by asphyxiation. The most well-known cause is hereditary angioedema, an autosomal dominant disorder that is characterized by deficiency of C1 esterase inhibitor (C1-INH). Recently, a new type of hereditary angioedema (type 3) has been reported that occurs exclusively in women and is characterised by oestrogen dependency (both endogenous and exogenous), normal C1-INH concentrations and severe attacks of angioedema, which are clinically indistinguishable from the classic form.