Pharmacodynamics

• Drug action in humans
• Drug acts on receptor or physiological mechanisms
• Leads to measurable change in body
• Different drug response in individuals

Sites

• Receptors - number available, configuration and binding of drug, physiological processes triggered by drug binding
• Enzymes - intrinsic activity of enzyme, drug binding
• Ion channels - number, conformation of channel

Agonist - Drug and receptor, Activation, Cellular response
Antagonist - Drug and receptor, Binding, No response

Pharmacokinetics (drug movement)

• Drug enter body and travels to site of action
• Factors affecting drug concentration: Bioavailability (absorption from stomach), First-pass metabolism (breakdown by liver enzymes), Clearance (metabolism and elimination through urine)

Bioavailability

• Proportion of drug that gets into systemic circulation
• Oral: How much can be absorbed, First-pass metabolism
• Calculated by comparing amount after oral dose and amount after iv dose

Half life

• Time taken for drug concentration to halve
• Determinant of dosing regimen (how much and how often)
• How long the drug is in body

Importance

• Drugs need to be administered in an acceptable and feasible way (oral, injection, rectal, topical)
• Substance has to traverse the body, active compound has to reach target site, remain at target for enough time at an appropriate concentration and eliminated from body in a consistent and predictable way.
• Target drug concentration delivers good efficacy but not toxicity.

Licensing approval

• Satisfactory Physico-chemical properties
• Good manufacturing practice
• Stability
• Pharmacokinetics/pharmacodynamics
• Clinical trials - efficacy and toxicity
• Acceptable packaging/marketing and patient information
• Monitoring presciption

Categories

• Prescription Only Medicines (POM) - Sold/supplied only on a prescription
• Pharmacy medicines (P) - Sold/supplied only from pharmacist
• General Sales List (GSL) - Sold/supplied direct to public unopened from lockable premises

Unlicensed prescribing

• Drug not licensed for patient group or disease
• Exercise duty of care
• Indication is not licensed
• Determine efficacy/safety is proven elsewhere
• Explain license status to patient
• CONSENT!
• Responsibility lies on clinician

Licensing

• Safe
• Effective
• Adequate quality control
• $\ne$ drug is better (only superior over placebo or no worse than established agent)
• Prescriber still needs to prioritise choices within treatment pathways.

Benefit harm balance

• Right drug, right dose at right time for the right patient
• Clinical trials - 'average effect'
• Some patients benefit sometimes
• Sometimes harm, varying severity
• Conditions can now have prediction calculators/prognostic scoring
• Choose drugs with higher chance of benefit
• Avoid high risk of harm drugs

Adverse reactions

• Dose - greater risk as dose increases due to pharmacokinetic/pharmacodynamic relationship
• Time/duration - cumulative dose over months or frequency of use
• Individual susceptibility factors - age, physiological impairment, genetic susceptibility
• Reduce harm - evidence-based choice of relevant drug for patient, avoid high risk drugs, adjust dose/duration, monitor to detect problems (hypersensitivity/allergies difficult to predict with early doses)