WHO Collaborating Centre for International Drug Monitoring Dr

WHO Collaborating Centre for International Drug Monitoring Dr. Mohamed Farah the Uppsala Monitoring Centre 1

WHO Drug Monitoring Programme Founding Members 1968 Australia Canada Denmark Germany Ireland Netherlands New Zealand United Kingdom United States of America Sweden 2

WHO Programme for International Drug Monitoring 3

WHO Collaborating Centre the Uppsala Monitoring Centre • • established as a foundation 1978 based on agreement Sweden – WHO international administrative board WHO Headquarters responsible for policy 4

Signalling Procedure What should be achieved? • Signals should not be missed • Signals should be found early • ‘False’ signals should be kept to a minimum 5

Process for joining WHO Programme 1. Ministry of Health (or equivalent) designates National Centre Ministry of Health 2 5 2. Ministry of Health sends formal application to WHOHQ, Geneva National Centre 3 3. National Centre sends sample reports to the UMC WHO-HQ Geneva 4. UMC notifies WHO-HQ that reports are compatible 5. WHO-HQ advises Ministry of Health of admittance to the Programme 1 6 4

Africa -WHO Official member South Africa (1992) Morocco (1992) Tunisia (1993) Tanzania (1993) Zimbabwe (1998) Egypt (2001) Ghana (2001) Nigeria (2004) Associate member Democratic Republic of Congo Madagascar Sierra leone Botswana Eritrea Ethiopia Uganda Zambia Algeria Mozambique (2005) 7

Nomina si nescis, perit et cognitio rerum. (Carl von Linné, Critica botanica) If you do not know the names, the knowledge about the things vanishes as well. 8

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Isibhaha Warburgia salutaris (Bertol. f. ) Chiov. Syn: Warburgia breyeri Pott. ; Warburgia ugandensis Sprague; Chibaca salutaris Bertl. f. Common names: Pepper bark tree, Pepperbasboom (Afr. ), Shibaha (Tsonga), Amazwecehlabayo (Zulu), Isibaha (Z, V), Manaka (Venda), Sebaha (Sotho) Muthiga (Kikuyu), Sogdom (Amharic), Msokonoi (Swahili) Uses: Expectorant, Chest infections, Sinusitis, Malaria, Venereal diseases, Stomach ulcers, Toothache and Dermatological disorders Chemistry warburganal muzigadial polygodial 11 mukaadial

Artemisia annua L. leaf 12

Artemisia annuua L. The plant can grown in many places but it may not contain artemisinin. For example: Visitors of the ancient palaces in the forbidden city in beijing can find nice artemisia annua plants pushing left and right as weeds, but these plants do not contain artemisinin 13

Artemisia annua L. The average artemisinin concentration in plants of European origin range from 0. 03 to 0. 22 % (dry leaves weight basis) artemisinin, but a clone from China could contain up to 1. 1 % artemisinin 14

Artemisia annua L. 1, 8 -Cineole: leaf pesticide, insectifuge, herbicide Alpha-Pinene: leaf herbicide, insecticide, pesticide, insectifuge, insectiphile Artemisic-acid: plant: pesticide Artemisinin: flower leaf antimalarial, pesticide, schizonticide, herbicide Beta-Pinene: plant: herbicide, insectifuge, pesticide Beta-Sitosterol: plant: pesticide, antifeedant Borneol: plant: herbicide, insectifuge, pesticide, insect-repellent Camphene: plant: insectifuge, pesticide Camphor: leaf antifeedant herbicide, insect-repellent, insectifuge, pesticide Caryophyllene-oxide: plant: antifeedant, insecticide, pesticide Cuminaldehyde: leaf: larvicide, pesticide Delta-Cadinene: plant: pesticide Deoxyartemisinin: plant: pesticide Menthol: plant: pesticide, termiticide Ocimene: plant: insecticide P-Cymene: plant: herbicide, insectifuge, pesticide Scopoletin: plant: herbicide, pesticide 15 Terpinen-4 -ol: plant: herbicide, insectifuge, pesticide

Artemisia annua L. , flower, leaf ARTEMISININ Antimalarial Antitumor Antiviral Calcium-Antagonist Cytotoxic Herbicide Immunomodulator Neurotoxic Pesticide Plasmodicide Schizonticide Teratogenic 16

Artemisia annua L. leaf Artemisinin 青蒿素 Dihydroartemisinin Artemether Arteether 17 Artesunate

Artemisinin Synthesis 18

Artemisinin can be synthesized, but synthetic compound is unlikely to be economically competitive with the naturally produced compound 19

Case report WHO Record number: Country: Type of report: Age: 54 Years Adverse Reaction(s): Outcome: Suspected Drug: Drug administration data: Indication: Concomitant Drug(s): Rechallenge action: Rechallenge outcome: Ghana Spontaneous report/Hospital Sex: Female Face oedema; Oedema periorbital Not recovered Artesunate 200 Milligram Oral Total MALARIA Nifedipine 20 Milligram Oral per Day Rechallenge Reaction recurred Nifedipine: 17 Face oedema 20 29 Oedema periorbital

Artemether Total number of reports 44 Agitation 6 Anorexia Headache 9 Hypoplasia cerebellar Paroniria Stomatitis Ataxia cerebellar Fra Insomnia Sweating increased 2 Confusion Jaundice Urine abnormal 2 Confusion Fra Nausea 2 Vision abnorma Dizziness 9 Neurosis Eye malformation Zaf Vomiting 2 21

Artesunate Reports 22260 Anxiety 8 Alopecia 8 Agitation 341 Face oedema, Gha Abdominal pain 11 Ataxia 2 Cheilitis 29 Anorexia 513 Fever tha, Vnm Allergic reaction Zaf Delirium Coughing 2 Asthenia Gha Gingival bleeding 2 Dizziness Gha, 1439 Th Dyspnoea Nausea 990 Bullous eruption Hallucination 20 0 anaemia Epistaxis 3 Confusion 195 Hyperventilation Oedema periorbital Gha Insomnia 6 Flatulence Depression 53 Hypotension Gha Paranoid reaction 6 Naevus Haematuria Diarrhoea 207 Palpitation 241 Paroniria 52, Gha 1 Rash 2 Jaundice 61 Headache 1161 Spasm generalized Rash maculo-papular 6 Pallor 85 Melaena Stomatitis 40 Urine abnormal 2 Rash erythematous 24 Purpura Pharyngitis vomiting 720 Urticaria 3, 1 Vnm Sweating increased Pruritus 47 Tachycardia Anaemiah aemolytic 2 Thrombocytopenia 2 Tinnitus 3 22 Vision abnormal 168 Hypoaesthesia Tza

Artemisinin and derivatives There is a fear that improper use of artemisinin and its derivatives will spur the malaria parasite to evolve to resist treatment with the compounds, something that has happened to all previous malaria therapies Spread of chloroquine 23 resistance of Plasmodium falciparum

Natural Mosquito Repellents Agastache cana (Hook. ) Woot. & Standl. Azadirachta indica Juss f. Cymbopogon nardus (L. ) Rendle Melissa officinalis L. Pelargonium citrosum Vanleenii Pelargonium graveolens L'Her. ex Ait. Nepeta cataria L. * 24 *It is ten times more effective than DEET at repelling mosquitoes