Pharmacokinetics and Dynamics Flashcards
(86 cards)
Principles of drug regulation
Safety - Relative absence of harm, there is never a guarantee of absolute safety
Efficacy - Has to be shown to have a positive effect, does it work QoL
Quality - Contains active ingredients and everything it states
Drug licensing
Purely risk benefit analysis. No element of cost. Must be proven evidence of safety and efficacy at certain doses. Relevant to target population and SE profile
Off license drugs
Drugs can be used off license but the doctor is then liable
To license a drug in the UK
Centralised procedure by the EMA obligatory for all HIV/AIDS, cancer, AI, diabetes, neurodegenerative. Also new technology including gene therapy and genetic engineering
National bodies - MHRA
Drug marketing
Direct to consumer advertising is banned in the EU and UK. Money is spent on healthcare professional advertising. MHRA must license a drug before this occurs
Attached to the license is a summary of product characteristics and a patient information leaflet
NICE
Crucial to determine cost effectiveness. They appraise new technologies and treatments, produce guidelines for treatment and care and recommend interventional procedures
Decide whether funding for specific drugs are available on the NHS. If green light added to formulary
No NICE approval
Apply to exceptional cases fund
Patents
Drugs are granted exclusivity for 20 yrs (+/-5) Typically development takes 10-15yrs so a drug only has a 8-10yr clinical lifespan. Commercial success if crucial
Local formularies
Subset of the BNF stating medications preferable in their locality. Aren’t legally binding just guidelines. Generic presricibing in encouraged to save money. Individual factors must be controlled
Preclinical development
1 - Establishing pharmacological action usually on enzymes, cell culture, perfused organs, bacteria or intact animals
2a - Safety assessment in animals. Toxicity - acute and chronic (4wks - lifetime), mutagenicity, teratogenicity, fertility and reproductive performance
2b - Species variation. 2 animals, 1 non rodent, 2 routes of administration
Required before 1st in man studies
Drug substance characterisation impurities, large scale compound synthesis,
Toxicology in 2 preclinical species, identification of major organ function effects, target organs for toxicity, assessment of monitoring toxic effects.
Drug metabolism and distribution
Lead optimisation
Potency, safety optimisation, cellular optimisation
Phase 1
First use in humans - often healthy volunteers, used to confirm pharmacology established from animal studies
- Pharmacokinetics (absorption, metabolism, elimination and distribution)
- Pharmacological actions
Detailed monitoring, dose ranging usually in 20-50 people over a year
Phase 2 requirements
Safe and well tolerated with single and multiple dosing
Characterisation of drug interactions and effects of food
Phase 2
Establishes therapeutic value and dose range
Explore common ADR
Assess pharmacokinetic actions in special pt groups
50-300 over 2-5yrs
Phase 3
Large multi centre often international comparisons with placebo or existing treatments.
RCT to prove efficacy and SE profile
Cost minimisation
Simple technique assumes equal efficacy between treatments, assumes all other factors i.e. SE are equal
Therefore cheapest option
Cost effectiveness
Cost A - Cost B
Efficay A - Efficacy B
20,000 pounds per life saved is the usual limit
Cost utility
Quantifies benefit using QALY.
QALY = survival years x QoL during those years
Cost benefit
Rarely used aims to value all inputs and outputs in monetary terms. Final result expressed as net monetary gain or loss / cost:benefit
Medication error
Any preventable event that may cause or lead to inappropriate medication use or harm while under control of health professional
ADR
Response to a drug either noxious or unintended occurs at normal doses for prophylaxis or therapy
Causes of medication error
Poor communication, lack of knowledge of drug, wrong patient, calculation errors, poor history skills - not eliciting allergies, poor handwriting, carelessness.
Avoiding errors
Systems and policies to prevent error. Checking pt identity Education Electronic records - no handwriting, Involvement of pt and family Good documentation and control of high risk drugs
