Spring Intro 2023

22/03/2023

Toxicity: – It’s All Relative!

Agent

Lethal Dose 50 mg/kg

Ethyl alcohol

10,000

Sodium Chloride Ferrous sulphate Morphine sulphate

4,000 1,500

900 150

Phenobarbitone sodium

Sodium cyanide

5 1

Nicotine

d -tubocurarine

0.5 0.1

Tetrodotoxin

Dioxin (TCDD)

0.001

Botulinum toxin

0.00001

Polonium 210

0.00002

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60 Years of Drug Safety Disasters

1. 1961 Thalidomide. 1000s Foetal malformation. 2. 1975 Diethylstilboestrol vaginal tumours in daughters of mothers who took drug in pregnancy 100’s 3. 1983 Phenacetin analgesic. Urinary tract cancer - Death 4. 1992 Fialuridine, antiviral. Liver failure -Death 5. 1994 Pancreatic Enzymes. Fibrosing colonopath in children with cystic fibrosis 6. 1997 Terfenadine antihistamine, heart arrhythmias - Death 7. 1997/2000 Troglitazone, anti-diabetic. Liver failure - Death 8. 1998 Mibefradil (posicor) drug:drug interactions. 9. 2001 Cerivastatin (baycol) cholesterol lowering, Muscle damage, Kidney failure 10.2006 TGN1412 antibody clinical trial. Cytokine release syndrome. 6/6 healthy volunteers in intensive care, loss of fingertips 12.2009 Benfluorex, appetite suppressant. Heart Valve Damage Death 13.2016 Bial Clinical Trial, FAAH Inhibitor. Neurotoxicity. Healthy volunteers:1/6 Dead, 4/6 with brain damage

14.2018 Hydrochlorothiazide, Heart drug – causes skin & lip cancer 15.2020 Lorcaserin, Appetite suppressant - increased cancer risk

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