Drug regimes Flashcards
What are the key determinants of a dosage regimen?
Activity/toxicity (therapeutic window, side effects, dose-response relationships)
Clinical factors (state of patient, compliance, convenience)
Pharmacokinetics (dose, onset, loading dose, maintenance dose, time to steady-state)
Other factors (dosage form, route of administration, drug interactions).
Define dosage
The administration of medicine in prescribed amounts over time
What factors influence the onset of drug action
Route of administration
Bioavailability and first-pass metabolism
Clinical situations (pathologies, blood perfusion, changes in pH, etc.)
Chemical structure and formulation.
Describe the main routes of drug administration & elimination
What pharmacokinetic factors influence drug regimens?
Dose: potency and efficacy
Onset: Absorption & distribution
Loading dose: Vd
Maintenance dose: clearance
Time to steady-state: half-life
What drug factors affect the dosage of a drug given?
potency
absorption
Bioavailability and 1st pass metabolism
Distribution
What factors influence the onset of action of a drug?
Route of administration
Chemical structure and formulation (slow or fast release)
Clinical situations (pH change, shock, tissue blood perfusion)
If a drug is given orally what factors affect onset of action?
Polypharmacy (other drugs)
Gut content
Splanchnic blood flow
What is loading dose and how is it calculated
An initial higher dose to enable therapeutic concentrations sooner
Dose = Vd x plasma conc
What is a maintenance dose? How is it calculated?
The dose given to maintain drug conc at therapeutic conc
= clearance (CL) x steady state conc (Css)
How can steady state concentrations be maintained?
Constant IV infusion (impractical)
Increased dose frequency (beware of owner compliance)
What is saturation kinetics?
At high doses, increases in drug concentration result in disproportionate rises in steady-state levels due to enzyme saturation (e.g., phenytoin).
How does βnormalβ kinetics differ from saturation kinetics?
In normal kinetics, plasma concentrations increase proportionally with dose
What is plasma protein binding?
Only free drugs are active, distributed, metabolized, or excreted
Drugs bind to plasma albumin (acidic drugs) or Ξ²-globulin (basic drugs)
Extensive binding slows drug elimination.
What happens in cases of saturable binding?
At high drug concentrations, binding sites may saturate, leading to non-linear drug concentration increases.
What drug-related factors affect absorption?
High absorption for lipid-soluble drugs.
Low absorption for drugs with molecular weight > 1000 Da or high ionization.
Formulation can improve absorption
What body-related factors affect absorption?
Increased absorption with larger absorptive surface area.
Altered by pH, GI motility, absorptive surface integrity, and diseases
What drug-related factors affect distribution? (what kind of drugs have high/low distribution)
High for lipid-soluble and weak base drugs.
Low for water-soluble and weak acid drugs
What body-related factors affect distribution?
Higher body fat increases ππ for lipid-soluble drugs.
Higher body water increases ππ for water-soluble drugs.
Low for drugs highly bound to plasma proteins.
What drug-related factors affect metabolism?
High metabolism for lipid-soluble drugs.
Protective chemical groups (e.g., F, CN) can reduce metabolism.
CYP inhibition reduces clearance, and CYP induction increases clearance
What body-related factors affect metabolism?
Enzyme quantity (e.g., P450 enzymes).
Polymorphisms in metabolizing enzymes.
Decreased blood flow to metabolizing organs reduces clearance.
Diseases
What drug-related factors affect excretion?
High for water-soluble and ionizable drugs
Low for lipid-soluble drugs.
Inhibitory drug-drug interactions reduce excretion
Drug with low plasma protein binding have increased clearance
What body-related factors affect excretion?
Drug transporter quantity.
Blood flow and GFR in kidneys.
Diseases affecting excretory organs
How does absorption in neonates differ from adults?
