Drug Regime Fundamentals

Question 1

What factors determine a dosage regimen?

Answer 1

Activity/toxicity
○ Therapeutic window
○ Side effects
○ Dose-response relationships
Clinical factors
○ State of patient
○ Convenience of regimen
○ Compliance of patient
Pharmacokinetics
Other
○ Dosage forms
○ Route of administration
○ Drug interactions

Question 2

What pharmacokinetic factors determine a dosage regimen?

Answer 2

○ Dose
Potency and efficacy
○ Onset
Absorption and distribution
○ Loading dose
Vd
○ Maintenance dose
Clearance
○ Time to steady-state
Half-life

Question 3

Potency

Answer 3

Amount of the drug required to produce a defined effect

Question 4

Efficacy

Answer 4

Maximal effect that a drug produces irrespective of concentration

Question 5

How does potency affect dosage?

Answer 5

Full vs partial agonists
Full agonists elicit a full response at a lower concentration than a partial agonist
Ideally want a higher potency as it requires less drug

Question 6

What factors determine dosage?

Answer 6

Potency
Absorption
Bioavailability and first pass metabolism
Distribution

Question 7

How does absorbancy affect dosage?

Answer 7

Drugs need to be absorbed
* Need to cross plasma membrane
* Need to be lipophilic, uncharged and small
Additional transport molecules can aid absorption

Question 8

How does bioavailability affect dosage?

Answer 8

If it has low bioavailability more drug will be required

Question 9

Bioavailability

Answer 9

Amount by which drug is absorbed and reaches circulation

Question 10

How does distribution affect dosage?

Answer 10

Some drugs are tightly bound within plasma - stay in circulation
Drugs that need to be distributed throughout the body will have greater affinity for tissue proteins than plasma
* Determined by the volume distribution (Vd)

Question 11

Tmax

Answer 11

Time that maximum concentration occurs

Question 12

What factors affect onset of action (Tmax)

Answer 12

Route of administration
Chemical structure and function
Clinical situations

Question 13

How does route of administration affect onset of action?

Answer 13

Oral administration is affected by:
* Polypharmacy
* Gut contents
* Splanchnic blood flow
If IV much faster onset of action (immediate)

Question 14

How does chemical structure and function affect onset of action?

Answer 14

Drugs that can freely cross plasma membranes will be absorbed quicker and therefore have an earlier set of action
Protective coating can slow this down
Rapid action but won’t last as long - eliminated quicker

Question 15

How does clinical situations affect onset of action?

Answer 15

Pathologies
Tissue blood perfusion
Changes in pH
States of shock (absorption reduced - sympathetic pathway)

Question 16

Loading dose

Answer 16

Initial higher dose of drug to enable therapeutic concentration to be achieved sooner
Principally determines by Vd
DOSE = Vd x plasma conc

Question 17

Maintenance dose

Answer 17

Required to keep drug at therapeutic concentration
Maintenance rate of drug administration equal to rate of elimination at steady state
Steady state is normally achieved within 5 half-lives

Question 18

Multiple dosing and Frequency

Answer 18

To maintain steady state concentration
○ Ideally, constant (IV) infusion - not practically possible
○ Administer drug multiple times to maintain constant level
○ Increasing frequency of doses reduces peaks and troughs and approaches Css
○ However, reduced owner and patient compliance with multiple daily dosing
○ Thus, need for a balanced approach and considerations if dose is missed

Question 19

Multiple dosing and Saturation

Answer 19

1. “Normal” kinetics
   ○ Plasma concentrations (at Css) increase proportionally with dose
   ○ If dose doubles, plasma concentration doubles
   ○ Linear relationship - predictable
2. Saturation kinetics
   ○ If dose is increased, then disproportionate increase in steady state concentrations
   ○ Double dose could more than double plasma concentration
   Necessitates smaller dose increments