Lecture 19 Flashcards
What is the timeline of drug development?
Discovery and basic research takes approx 2 years
Preclinical studies takes 5 years and is followed by a regulatory review
Clinical testing takes five years and goes through 3 phases
There is another regulatory review
at this time the drug will be able to enter the market so prelaunch activities and the launch occurs
post marketing studies are then required to identify more adverse effects or drug drug interactions
What are some recent examples of drugs being withdrawn from the market because of drg-drug interactions?
Sorivudine which was an antiviral but inhibited the metabolism of 5-Fluorouracil leading to 15 fatalities in Japan
Terfendine which was an antihistamine which lead to cardiotoxicitiy if coadministered with ketoconazole
What are recent examples of drugs pulled from the market due to unexpected toxicity?
Troglitazone which was used for non-insulin dependant diabetes but lead to severe hepaptotoxicity
Rofecoxib selective cox-2 inhibitor which was with drawn as it increased the chances of strokes and heart attacks
How have pharmaceuticals become regulated?
The apothecary ware, drugs and stuffs act in the UK 1540
Then after thalidomide caused many to have severe adverse effects there began to be the establishment of regulatory authorities including the FDA, European Medicines evaluation agency, Therapeutic goods administration, Medicines advisory and assessment committe
What is the passage of a newly developed drug through the regulatory procedures?
The regulatory authority produces regulatory guidelines which are then reviewed in comparison to the drug data, the chemistry, pharmacology, toxicology and pharmacokinetics of the drug are examined in vivo and clinical trials
There is a decision to grant or refuse a licence if this step is passed then marketing of the drug can begin
What are the 6 methods through which new drugs are discovered?
Development from herbal or traditional remedies Empirical approach Rational drug design Pro drugs/analogues/metabolites Serendipity Genomics
What are examples of drugs that have been made from herbal remedies?
Morphine is made from the opium poppy
Digitoxin was made from foxglove
Salicyclic acid was made from willow bark
How is the empirical approach used to develop new drugs?
There is development of models felt to be predictive of activity, then a there is screening of a large number of compounds this is commonly used to find anti cancer agents and cyclosporin which is an immunosuppressant
How is rational drug design used to develop new drugs?
Through understanding the cellular or molecular basis of the disease and use of technology which can allow us to determine the 3D structure of the receptor so an appropriate agonist or antagonist can be designed
e.g. Propranolol and cimetidine
How are prodrugs/analogs and metabolites used to develop new drugs?
Taken from already existing drugs
e.g. aspirin and paracetamol
What drugs have been discovered through serendipity?
Penicillin, valproate, sildenafil (viagra)
How can genomics be used to develop drugs?
Information on the genes is used to identify drug targets, leads to gene therapy and siRNA
What is tested for in preclinical studies?
The principal pharmacological action and secondary properties of a drug (like if it is addictive)
The pharmacokinetic parameters of the drug
If there is acute or chronic toxicology and if it can act with mutagenicity which can lead to it being carcinogenic and well as checking if it is teratogenicity
What are the phases in clinical trials during drug development?
Phase 1 a small number of healthy volunteers or patients are used to determine the tolerated dose range as well as pharmacokinetics and dynamics
Phase 2 where there are several hundred patients with a specific disease and the therapeutic effectiveness of the drug is tested, the sort term safety and dosage strategy is also determined for phase 3
Phase 3 several thousand patients are used to check the clinical safety and efficacy of the drug to refine the dose, concentration and response and to gain qualitative and quantitative assessments of any adverse effects
Phase 4 post marketing surveillance and adverse reaction reporting
