Pharmacology L2 Flashcards
Stages of drug discovery& development
- drug discovery
- preclinical development
- clinical development
Drug discovery
Identification of candidate molecules based on their pharmacological, biochemical and physiochemical properties
Preclinical development
Non-human studies to determine basic pharmacokinetics, potential toxic side effects and formulation. These can take a long time
Clinical development
Evaluation of drug safety, side effects, efficacy and optimum dosage in volunteers and patients
Stages of drug development
- chemical or biochemical synthesis of novel compound
- isolation of active ingredient from natural source
- production and isolation of biologicals
- preclinical testing 1/2/3
- phase 0/1/2/3
- approval
Chemical or biochemical synthesis of a compound involves what?
Screening of the compound
Pre-clinical testing 1b involves?
Effects of drug on cellular function. How does it affect biological response? Is it an agonist, antagonist, modifier?
Pre-clinical testing 2 involves?
Mechanism of drug action. Is it blocking a pathway or is there a reaction
Pre-clinical testing 3 involves?
Toxicity testing ( in vivo, in vitro & ex vivo)
Phase 0 is what?
Human microdosing
What does phase 0 entail
Small amount of volunteers use non-pharmacological doses to see if there are any effects on cellular function, drug action and toxic side effects
What does phase 1 entail
Does the drug have any effects on body function, drug safety, unexpected side effects
What is phase 1
Clinical trial on healthy subjects (very small no;10-80)
What is phase 2
Clinical trial on small number of selected patients (100-300)
What does phase 2 entail
Effect on pathophysiology of the disease, therapeutic dosage.
What is phase 3
Clinical trial on diverse large group of patients (>1000)
Approval of drug development is usually carried out by?
Licensing by National regulatory agency
Regulatory agency in US and Europe
US- FDA (world standard)
EMA- European Medicines Agency
What is phase 4?
Post-licensing phase
Clinical trial: long-term benefit-risk evaluation
Large and extremely diverse patients
What does phase 4 entail?
Pharmacovigilance; determination of therapeutic value of novel drug or delivery system. Adverse effects in previously untested patient groups
What does phase 3 entail?
Comparison to other therapies and placebos
When do medical and ethical approval occur?
Before clinical development
When does regulatory approval occur?
Before post-licensing surveillance
Most drug targets are proteins like?
- receptors
- transporters
- enzymes
Target selection is often based on biomedical knowledge on
- disease mechanisms
- biochemical pathways
- cellular signalling
Pre-clinical testing is usually carried out on?
- animal(mice, rats, rabbits)
- animal models of human disorders
- isolated organs
- cell cultures (in vitro assay systems)
Preclinical testing in animals involves?
- determination of median effective dose ED50
- assessment of toxicity
- assessment of subacute toxicity (once lethal dose has been determined)
- estimation of human dose
- assessment of chronic toxicity
What are clinical trials
A set of tests prior to the approval of a new health intervention
Health interventions that require diff degrees of testing are
- pharmaceutical targets
- novel drug derivatives
- new drug combinations
- diagnostics
- medical devices
- therapy protocols
Preclinical and clinical trials are organized to?
Determine essential data sets on the safety and efficacy of novel health interventions
Initial requirement prior to start of extensive clinical trials
- provision of satisfactory information on the quality of non clinical safety to National Health Authority
- ethical approval by an independent National Ethics Committee
Authorization to conduct a clinical trial js carried out by
- pharmaceutical company
- medical institution
- academic institution
- specialist clinical research company
After expiration of patent product, what is produced?
A generic drug under a different brand name which has to be tested again
Generic drugs can lead to?
- analogue drugs
- new drug combinations
Analogue drugs
Imitation of chemical structure due to slight, but biochemically irrelevant, modifications of established drug molecule.
May have diff properties, may not be active
New drug combinations
Essential active substance plus low-dose indifferent second substance. Has to be tested again
