Basics of Drug Pharmacology Flashcards
What is a drug?
Any substance intended for use in diagnosis, cure, mitigation, treatment or prevention of disease
What is a drug substance?
Material exerting pharmacological action with excipients used to formulate medicinal product
What is a drug product?
One or more drug substances that contains excipients
What are the general properties of drugs?
Therapeutic effect
Side effects
Drug interaction with other drugs
What is therapeutic effect?
Desirable drug action
What are side effects?
Undesirable or harmful drug actions
What can drug interactions with other drugs produce?
Unpredictable effects
What is the sequence of drug discovery?
Target selection Lead discovery Medicinal chemistry In vitro studies In vivo studies Clinical trials
What is hit identification?
Once you have a target, you need to synthesise compound
Molecules identified have affinity for target
What test systems are required for hit identification?
Recombinant protein expressed artificially in cells grown in lab
Isolated enzyme assay
Biochemical assay
How to identify suitable bioassay?
Test should be simple, quick + relevant
Describe in vitro identification of suitable bioassay
Cheap
Easier
Less controversial
Describe in vivo identification of suitable bioassay
Needed to check drug interaction with target
What are in vitro pharmacology assays?
Isolated tissues, cells or enzymes
What are enzyme inhibitors tested on?
In vitro pharmacology assays
Pure enzyme in solution
What are receptor agonist/antagonists tested on?
In vitro pharmacology assays
Isolated tissue/cells
How are antibacterial drugs tested?
By measuring how effectively they kill in culture
What is affinity?
Strength of chemical interactions responsible for drug-target interaction
What is potency?
Degree of functional change imported to receptor upon binding of drug
What if efficacy?
Extent of biological effect as result of drug-induced modulation of receptor activity
Describe lead identification
Validated hits would be tested to determine factors such as: Selectivity vs panel of other receptors Physiochemical characteristics Drug-like properties Metabolic properties (half life)
Describe optimisation
Molecules fulfilling lead identification criteria can go on to molecular finishing school
What happens in optimisation?
Extensive SARs to improve potency + selectivity
What is optimisation an opportunity for?
To improve physiochemical + drug-like properties
What happens in preclinical studies?
Identify pharmacological properties PD (mode of action) PK (metabolism) Toxicology Safe initial dose
What are the 3 R’s strategy?
Reduce no. of animals to min
Refine way experiment carried out = animals suffer as little as possible
Replace animal experiments with non-animal techniques
How long does regulatory affairs take?
8-15 years
What do regulatory affairs look at?
Attention to early development = reduce no. of development failures
What happens if there is compliance to regulatory affairs?
Development success
What is a hazard?
Potential for damaging effect
What is a risk?
Includes likelihood that hazard would occur
How can risks be reduced?
Patient evaluation prior to use for “once a day”
Restrict patient population to those with greatest need
Lower dose
Develop safer analogues
When is a drug considered safe?
Expected therapeutic gain justifies risk
What is pharmacovigilance?
Science + activities relating to detection assessment, understand + prevention of adverse effects
What is an adverse event?
Any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product, which does not necessarily have casual link with treatment
What is an adverse reaction?
Any untoward + unintended response to an investigational medicinal product related to any drug administered
What is an unexpected adverse reaction?
An adverse reaction, the nature or severity of which is not consistent with the product info
What is a serious adverse event/reaction?
Any AE/AR/UAR that results in: Death Life threatening Hospitalisation Persistent disability Birth defect
