Lecture 19 Flashcards
(18 cards)
What four questions are to be asked when prescribing a drug?
Is drug getting into patient
Is drug getting to site of action
Is drug producing desired effect
Is this desired effect translating to a therapeutic effect
What is parenteral administration?
Those other than mouth and alimentary canal
What are the four main pharmacokinetic processes?
Absorption
Distribution
Metabolism
Elimination
What are the two broad sites of administration of drugs?
Focal- directly to target site eg eye skin inhaled etc
Systemic- enteral ( mouth and intestine) and parenteral (other routes)
Methods of drug absorption at molecular level?
Passive diffusion
Facilitated diffusion eg ping pong
Primary and secondary active transport
Pinocytosis
Passive diffusion at molecular level?
Ph determines amount of drug ionised or unionised. Unionised will diffuse and equilibrium shift will cause ionised drug to unionise
Facilitated diffusion?
Uses SLC or solute carrier molecules. They can be organic anion transporters or organic cation transporters.
What factors affect drug absorption?
Physicochemical factors- GI surface area, drug lipophilicity and SLC expression density
GI physiology- blood flow (increased post meal reduced fight or flight), GI motility slow post meal rapid severe diarrhoea, food and pH
First pass metabolism
What is first pass metabolism?
Phase 1- cytochrome p450
Phase 2- conjugating enzymes
Reduces availability of drug reaching systemic circulation
Some drugs activated through first pass metabolism
How do you avoid first pas metabolism?
Parenteral
Rectal
Sublingual
What is oral bioavailability?
Fraction of a dose of drug given orally (or any other route other than IV) that reaches the circulation unchanged.
Measured as amount reaching systemic circulation divided by total drug given as an IV dose
What factors affect drug distribution?
Drug hydrophilicity or lipophilicity
Degree of drug binding to plasma and tissue proteins
How does plasma and tissue protein binding influence drug actions?
If bound cannot interact with receptors
What is the therapeutic ratio?
Tolerated dose divided by minimum effective dose. Defined as LD50 or ED50
What is volume of distribution Vd?
Theoretical volume into which drug would distribute if this happened instantaneously.
Measured as total amount of drug in body over plasma concentration
Give an example of where volume of distribution can be clinically relevant?
In hypoalbuminimea- less rotein binding and so higher Vd- must be taken into account when dosing
When is protein drug binding important?
When highly bound to albumin (over 90%)
Has a small Vd
Has a low therapeutic ratio
What type of protein binding is there for drugs?
Class 1 drug (object drug)- used at lower dose than albumin binding site and so doesn’t saturate, little free drug
Class 2 drug (precipitant)- used at Doses greater than number of binding sites and so displaces class 1 drug, much free drug
Class 2 displaces class 1 and so can overdose on class 1 drug
Eg warfarin object and aspirin precipitant
