Anthony Wong

36º Congresso da SBMF
Hotel Maksoud Plaza – São Paulo
27 e 28 de outubro 2011
Anthony Wong
CEATOX – Instituto da Criança
Hospital das Clinicas – FMUSP
IBEMAX - Instituto Bras. de Estudos e Avaliação
Toxicológica
CASO CLÍNICO
 Paciente masculino de 34 anos, casado, raça branca
 Histórico: Antecedentes de gota há mais de 2½
anos, fora prescrito etoricoxibe 100mg durante 4
dias. A artralgia resolveu, porém no 3º dia notou
uma ulceração de bordas irregulares no dorso da
glande peniana, hiperemia local, com dor e
prurido intenso, e secreção amarelada. Ele aplicou
uma pomada com antifúngico-cortisona com
melhora.
 N.B.- Não estava outros medicamentos nem
mudança de hábitos.
 Quatro meses mais tarde, apresentou novo
episódio de dor articular e voltou ao
reumatologista, que prescreveu novamente a
mesma dose de etoricoxibe por 4 dias. Ele
desenvolveu a mesma lesão, porém maior,
afetando 60% da glande. Foram feitos exames para
HIV, DST e infecções bacterianas e fúngicas, com
todos os resultados negativos. O médico tratou
como DST, com antibióticos e pomadas e as lesões
resolveram após 15 dias.
 Após mais 4 meses, as dores articulares recorreram e o mesmo
profissional prescreveu novamente etoricoxibe. As lesões
foram mais intensas com sangramento, secreção amarelada e
dor intensa. Desta vez, ligou ao CEATOX e foi informado que
poderia ser RAM. O médico não aceitou esta hipótese e
repetiu todos os exames. Prescreveu todos os medicamentos
para DST.
 Duas semanas antes da reunião do OMS, telefonei-lhe para
atualizar e confirmar suas informações. Disse-me que teve
novo episódio de dor articular e recebeu etoricoxibe por 4 dias
com as lesões recorrentes cobrindo quase 80% da glande.
 Ele disse que agora estava convencido de que era um RAM e
trocou de médico.
Caso Clínico
 Menina de 9 anos
 Há 2-3 meses, quadro progressivo de ataxia,
confusão mental, sonolência constante, hipotonia
generalizada, impossibilidade de ficar de pé e de
deambular, dificuldade de fixar a visão,
incapacidade de articular palavras e anorexia.
 Intolerância a alimentos, disfagia, vômitos e
irritabilidade.
 HD – neuropatia degenerativa, psicose aguda
A Wong - IBET/CEATOX
A Wong - IBET-CEATOX
“Medicamento Natural”
 Clorbenzorex 
anfetamina
hummm...não seria afrodisíaco?
Natu-DietMR
- PPA
- diazepinico
- T4
Fentanil
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Precautions
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abuse potential, high risk of addiction, misuse or diversion
concomitant cytochrome P450 3A4 inhibitors; may result in an increase in fentanyl plasma concentrations, and potentially fatal respiratory depression
different bioavailabilities among products and manufacturers; converting patients from other oral fentanyl products, including oral transmucosal
fentanyl citrate (OTFC and Actiq(R)), to Fentora(TM) cannot be substituted on on a microgram per microgram basis
hypoventilation; may occur at any dose
abrupt discontinuation; may result in withdrawal symptoms
bradyarrhythmias; potentiation of bradycardia
chronic obstructive pulmonary disease; risk of further decreased respiratory function
concomitant administration of opioid antagonists; may precipitate withdrawal symptoms
concomitant use of alcohol, other opioids, or other respiratory depressants; increased central nervous system depressant effect
concurrent consumption of grapefruit or grapefruit juice; risk of drug toxicity
debilitated patients; higher risk of respiratory depression
head injury, increased intracranial pressure, or impaired consciousness; carbon dioxide retention may exacerbate sedating effects of opioids and
increase risk of fatal overdose
hepatic disease, severe; repeated dosing or high single doses may result in diminished clearance
MAOI therapy within 14 days; severe and unpredictable potentiation of opioids by MAOI inhibitors
renal disease, severe; repeated dosing or high single doses may result in diminished clearance
respiratory depression; carbon dioxide retention may exacerbate sedating effects of opioids and increase risk of fatal overdose
respiratory disorders, underlying; increased risk of respiratory depression
Adverse Effects
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COMMON
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Cardiovascular: Peripheral edema (5% to 32% .)
Endocrine metabolic: Dehydration (0% to 21% .), Weight loss (3% to 11% .)
Gastrointestinal: Abdominal pain (3% to 15% .), Application site reaction (10% .), Constipation (8% to 26% .), Diarrhea (0% to 16% .), Loss of appetite (5% to 11% .), Nausea (9% to 42%
.), Vomiting (0% to 37% .)
Musculoskeletal: Backache (0% to 11% .)
Neurologic: Asthenia (5% to 16% .), Confusion (3% to 16% .), Dizziness (6% to 32% .), Headache (2% to 15% .), Sedated (0% to 15% .)
Renal: Urinary retention
Psychiatric: Fatigue (2% to 20% .), Insomnia (3% to 11% .)
Respiratory: Cough (3% to 9% .)
SERIOUS
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Cardiovascular: Tachyarrhythmia (1% or greater .)
Hematologic: Neutropenia (0% to 8% .)
Respiratory: Apnea (3-10%), Dyspnea (0% to 19% .)
A Wong - IBET/CEATOX
A Wong - IBET-CEATOX
Ciprofloxacina
 Adverse Effects
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Ciprofloxacin is generally well tolerated. The range of adverse effects associated with ciprofloxacin and the
other fluoroquinolones is broadly similar to that of earlier quinolones such as nalidixic acid. They most often
involve the gastrointestinal tract, CNS, or skin.
Gastrointestinal disturbances include nausea, vomiting, diarrhoea, abdominal pain, and dyspepsia and are
the most frequent adverse effects. Pseudomembranous colitis, pancreatitis, and dysphagia have been
reported rarely.
Headache, dizziness, confusion, insomnia, and restlessness are among the commonest effects on the CNS.
Others include tremor, drowsiness, nightmares, visual and other sensory disturbances, hallucinations,
psychotic reactions, depression, convulsions, and intracranial hypertension. Paraesthesia and peripheral
neuropathy have also been reported.
In addition to rash and pruritus, hypersensitivity-type reactions affecting the skin have included, rarely,
vasculitis, erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis.
Photosensitivity has occurred, although it may be more frequent with some other fluoroquinolones such as
lomefloxacin and sparfloxacin. Anaphylaxis has been associated with ciprofloxacin and some other
quinolones. As with other quinolones, reversible arthralgia or myalgia has sometimes occurred and joint
erosions have been documented in immature animals. Tendon damage has also been reported.
Other adverse effects reported with ciprofloxacin include crystalluria, transient increases in serum creatinine
or blood urea nitrogen and, rarely, acute renal failure secondary to interstitial nephritis. Elevated liver
enzyme values, jaundice, and hepatitis have occurred, as have haematological disturbances including
eosinophilia, leucopenia, thrombocytopenia and, very rarely, pancytopenia, haemolytic anaemia or
agranulocytosis. Cardiovascular adverse effects include tachycardia, hypotension, oedema, syncope, hot
flushes, and sweating. Some fluoroquinolones may rarely cause prolongation of the QT interval and
ventricular arrhythmias, including torsade de pointes.
As with other antibacterials, superinfection with organisms not very susceptible to ciprofloxacin is possible.
Such organisms include Candida, Clostridium difficile, and Streptococcus pneumoniae. There is some
evidence that fluoroquinolone use may be associated with an increased risk of colonisation by MRSA.
A Wong - IBET/CEATOX
A Wong - IBET-CEATOX
Ciprofloxacina - Interações
Fluoroquinolones, including ciprofloxacin, are known to inhibit the cytochrome P450 isoenzyme CYP1A2 and may increase plasma concentrations of drugs, such as
theophylline and tizanidine, that are metabolised by this isoenzyme. Use of ciprofloxacin with tizanidine is contra-indicated, although theophylline may be used providing
its dose is reduced and concentrations monitored.
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Ciprofloxacin is reported to enhance the effect of oral anticoagulants such as warfarin and the oral antidiabetic glibenclamide. Severe hypoglycaemia, sometimes
fatal, has occurred in patients also taking glibenclamide. Renal tubular secretion of methotrexate may be inhibited by ciprofloxacin, potentially increasing its
toxicity.
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The excretion of ciprofloxacin or related drugs is reduced and plasma concentrations may be increased by probenecid. Cations such as aluminium, calcium,
magnesium, or iron reduce the absorption of oral ciprofloxacin or related drugs when given together. Changes in the pharmacokinetics of fluoroquinolones have
been reported when given with histamine H(2) antagonists, possibly due to changes in gastric pH, but do not seem to be of much clinical significance.
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Transient increases in serum creatinine have occurred when ciprofloxacin is given with ciclosporin; monitoring of serum creatinine concentrations is recommended.
Altered serum concentrations of phenytoin have been reported in patients also receiving ciprofloxacin.
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Some fluoroquinolones have the potential to prolong the QT interval and should be avoided in patients also receiving class Ia antiarrhythmic drugs (such as
quinidine and procainamide) or class III antiarrhythmics (such as amiodarone and sotalol). In addition, caution should be exercised when they are used with other
drugs known to have this effect (such as the antihistamines astemizole and terfenadine, cisapride, erythromycin, pentamidine, phenothiazines, or tricyclic
antidepressants). ..
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Analgesics.
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Use of fenbufen with fluoroquinolones may increase the incidence of fluoroquinolone CNS adverse effects. Adverse neurological effects have also been reported in a
patient receiving naproxen and chloroquine when ciprofloxacin was given, which abated when the antirheumatic drugs were stopped. (4)
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Ciprofloxacin also interacts with opioid analgesics; peak serum concentrations of ciprofloxacin given by mouth pre-operatively were significantly reduced when
intramuscular papaveretum was injected.
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Antacids and metal ions. .
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Antibacterials. The simultaneous use of parenteral ciprofloxacin and azlocillin has resulted in higher and more prolonged serum concentrations of
ciprofloxacin. (1)
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Anticoagulants.
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Antidiabetics.
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Antiepileptics. phenytoin..
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Antifungals. Both fluconazole and levofloxacin can prolong the QT interval. The simultaneous use of intravenous levofloxacin and fluconazole resulted in an
episode of torsade de pointes in a patient on haemodialysis.
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Antimigraine drugs.
Antineoplastics.
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Absorption of oral ciprofloxacin appears to be reduced after cytotoxic chemotherapy. (1)
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Antivirals.
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Both ciprofloxacin and foscarnet can cause convulsions and 2 patients developed generalised tonic-clonic seizures while receiving the drugs together.
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Immunosuppressants.
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Muscle relaxants.
Xanthines. Ciprofloxacin and other fluoroquinolones (to a greater or lesser extent) decrease the clearance of theophylline (Ref.) and caffeine (Ref.) from the body. Seizures have
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occurred in patients given ciprofloxacin and theophylline and in one such report (1) serum-theophylline concentrations were normal.
A Wong - IBET/CEATOX
A Wong - IBET-CEATOX
Hidrato de Cloral
 Precautions
 history of gastritis, esophagitis, or gastric or duodenal ulcers
 mentally depressed patients or those with suicidal tendencies
 severe cardiac disease
 Adverse Effects
 COMMON
Cardiovascular: Lightheadedness
 Gastrointestinal: Abdominal pain, Diarrhea, Nausea, Vomiting
 Neurologic: Clumsiness, Dizziness, Hangover, Somnolence,
Unsteadiness present
 SERIOUS
 Dermatologic: Cutaneous hypersensitivity (rare)
 Neurologic: Confusion, Excitement, Unusual (rare)
 Psychiatric: Hallucinations
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A Wong - IBET/CEATOX
A Wong - IBET-CEATOX
Hidrato de Cloral – Interações
Acecainide (major, theoretical)
Adinazolam (major, theoretical)
Ajmaline (major, theoretical)
Alfentanil (major, theoretical)
Alprazolam (major, theoretical)
Amiodarone (major, theoretical)
Amisulpride (major, theoretical)
Amitriptyline (major, theoretical)
Amobarbital (major, theoretical)
Amoxapine (major, theoretical)
Anileridine (major, theoretical)
Aprindine (major, theoretical)
Aprobarbital (major, theoretical)
Arsenic Trioxide (major, theoretical)
Astemizole (major, theoretical)
Azimilide (major, theoretical)
Bepridil (contraindicated, theoretical)
Bretylium (major, theoretical)
Bromazepam (major, theoretical)
Brotizolam (major, theoretical)
Butabarbital (major, theoretical)
Butalbital (major, theoretical)
Carisoprodol (major, theoretical)
Chlordiazepoxide (major, theoretical)
Chloroquine (major, theoretical)
Chlorpromazine (major, theoretical)
Chlorzoxazone (major, theoretical)
Cisapride (contraindicated, theoretical)
Clarithromycin (major, theoretical)
Clobazam (major, theoretical)
Clonazepam (major, theoretical)
A Wong - IBET/CEATOX
Clorazepate (major, theoretical)
Codeine (major, theoretical)
Dantrolene (major, theoretical)
Desipramine (major, theoretical)
Diazepam (major, theoretical)
Dibenzepin (major, theoretical)
Disopyramide (major, theoretical)
Dofetilide (major, theoretical)
Dolasetron (major, theoretical)
Droperidol (major, theoretical)
Enflurane (major, theoretical)
Erythromycin (major, theoretical)
Estazolam (major, theoretical)
Fentanyl (major, theoretical)
Flecainide (major, theoretical)
Fluconazole (major, theoretical)
Flunitrazepam (major, theoretical)
Fluoxetine (major, theoretical)
Flurazepam (major, theoretical)
Foscarnet (major, theoretical)
Gemifloxacin (major, probable)
Halazepam (major, theoretical)
Halofantrine (major, theoretical)
Haloperidol (major, theoretical)
Halothane (major, theoretical)
Hydrocodone (major, theoretical)
Hydromorphone (major, theoretical)
Hydroquinidine (major, theoretical)
Ibutilide (major, theoretical)
Imipramine (major, theoretical)
Isoflurane (major, theoretical)
Isradipine (major, theoretical)
Ketazolam (major, theoretical)
Levomethadyl (contraindicated, theoretical)
Levorphanol (major, theoretical)
Lidoflazine (major, theoretical)
Lorazepam (major, theoretical)
Lorcainide (major, theoretical)
Lormetazepam (major, theoretical)
Medazepam (major, theoretical)
Mefloquine (major, theoretical)
Meperidine (major, theoretical)
Mephenesin (major, theoretical)
Mephobarbital (major, theoretical)
Meprobamate (major, theoretical)
Mesoridazine (contraindicated, theoretical)
Metaxalone (major, theoretical)
Methocarbamol (major, theoretical)
Methohexital (major, theoretical)
Midazolam (major, theoretical)
Morphine (major, theoretical)
Morphine Sulfate Liposome (major, theoretical)
Nitrazepam (major, theoretical)
Nordazepam (major, theoretical)
Nortriptyline (major, theoretical)
Octreotide (major, theoretical)
Oxazepam (major, theoretical)
Oxycodone (major, theoretical)
Oxymorphone (major, theoretical)
Pentamidine (major, theoretical)
Pentobarbital (major, theoretical)
Phenobarbital (major, theoretical)
Pimozide (contraindicated, theoretical)
Pirmenol (major, theoretical)
Prajmaline (major, theoretical)
Prazepam (major, theoretical)
Primidone (major, theoretical)
A Wong - IBET-CEATOX
Probucol (major, theoretical)
Procainamide (major, theoretical)
Prochlorperazine (major, theoretical)
Propafenone (major, theoretical)
Propoxyphene (major, theoretical)
Quazepam (major, theoretical)
Quetiapine (major, theoretical)
Quinidine (major, theoretical)
Remifentanil (major, theoretical)
Risperidone (major, theoretical)
Secobarbital (major, theoretical)
Sematilide (major, theoretical)
Sertindole (major, theoretical)
Sotalol (major, theoretical)
Spiramycin (major, theoretical)
Sufentanil (major, theoretical)
Sulfamethoxazole (major, theoretical)
Sultopride (major, theoretical)
Tedisamil (major, theoretical)
Telithromycin (major, theoretical)
Temazepam (major, theoretical)
Terfenadine (major, theoretical)
Thiopental (major, theoretical)
Thioridazine (contraindicated, theoretical)
Triazolam (major, theoretical)
Trifluoperazine (major, theoretical)
Trimethoprim (major, theoretical)
Trimipramine (major, theoretical)
Vasopressin (major, theoretical)
Warfarin (moderate, probable)
Ziprasidone (contraindicated, theoretical)
Zotepine (major, theoretical)
Problemas Preveníveis – Efeitos Adversos por
Medicamentos
A Wong - IBET/CEATOX
A Wong - IBET-CEATOX
Riscos e Benefícios
Doença
Segurança ao Paciente!
Benefício do
Tratamento
Risco do
Tratamento
Detectar e antecipar o impacto de vários
produtos na segurança dos pacientes
Produtos avaliados
Farmacovigilancia
Produtos para a Saúde:
Farmacos
Vacinas
Fitoterápicos
Teratovigilancia
Erros de Medicação
Cosmetovigilancia
Vigilancia de materiais médicos
Centros de Intoxicação
Produtos para a Saúde
Plantas tóxicas
Substancias químicas
Metais
Animais em geral
Contaminação de alimentos e água ….
17
Pharmacovigilance Terminology
Evento Adverso
Avaliação de
Causalidade
Reação Adversa ao
Medicamento
Metodos/avaliação
Qualquer evento médico
não-esperado
temporalmente associado ao
uso do produto medicinal,
mas não necessariamente
tendo relação causal
Efeito deletério não intencional
resultante do uso autorizado do
produto em doses ou condições
recomendadas, mas tambem de
erros de medicação e do uso for a da
indicação e autorização oficial,
incluindo abuso e mal uso do produto.
de prevenção?
SIM
NÃO
RAM prevenível RAM não prevenível
Erros de
Medicação 9 March 2011
DECLARAÇÃO DE ERICE 2008
Background
 Coletar os dados de erros de medicação faz parte da rotina dos Centros
de Farmacovigilância (CFs);
 Nem todos os Centros de Farmacovigilância estão cientes de que as
Reações Adversas ao Medicamento (RAMs) podem estar relacionadas ao
Erro de Medicação;
 Os Centros de Farmacovigilância estão permanentemente
comprometidos no sentido de minimizar Reações Adversas ao
Medicamento e os Erros de Medicação, aumentando a Segurança do
Paciente (Patient Safety).
Vantagens de se vincular um Centro Toxicológico a um
Centro de Farmacovigilância
 Compartilhar recursos físicos e humanos;
 Competência dos profissionais são coincidentes;
 Desenvolvimento e fluxo de atividades semelhantes;
 Ambos são centros de referência para a avaliação do impacto dos produtos
comerciais na saúde e no ambiente.
Reporting of Adverse Drug Reactions by Poison
Control Centers in the US
- Pete A. Chyka e Steven W. McCommon (Drug Safety 2000)
 Em 1996, MedWatch tabulou
159.504 casos de EAM, sendo
91% da industria
 De 2.241082 relatos aos PCC’s
 32.601 eram de EAM
 Dos 65 PCC americanos:
 56 responderam ao questionario
 30 não reportaram EAM
 22 reportaram < 10/ano
 4 reportaram total de 47/ano
 Porque não relatam?
CONCLUSÕES
 As bases de uma Farmacovigilância está no
preparo do profissional médico e farmacêutico na
identificação e no diagnóstico de EAs.
 O universo de “notificadores” deve ser ampliado,
preparado e estimulado.
 A notificação de um Evento Adverso deve merecer
a mesma importância de uma doença de
notificação compulsória.
 É necessário investir na cultura do “uso seguro” no
lugar de “indicações terapêuticas”.