Routes of Administration: Pharmacokinetics Flashcards
Define Pharmacokinetics
Movement of drugs around the body
Pharmakon = medicine/drug
Kinetikos = “of motion”
ADME acronym
A - absorption
D - Distribution
M - Metabolism
E - Excretion
A - absorption
Movement of a drug from the site of administration to the bloodstream
D - Distribution
Movement of drug around different tissues in the body
M - Metabolism
Change of drugs into compounds which are easier to eliminate
E - Excretion
Irreversible loss of (unchanged) drug from the body
Blood is not being metobilised
Metabolism + Excretion =
“Elimination”
Metabolism + Excretion =
“Elimination”
Metabolism + Excretion =
“Elimination”
Is blood considered a tissue?
Yes, as it is a collection of cells
ADME – schematic representation (Aulton’s book)
- IV injection
- Drug at site of administration = absorption
- drug e.g. unbound drug = distribution
- Elimination > unchanged drug excreted +
metabolises excreted
Unbound drug / bound drug:
Unbound drug are the ones that can cause pharmacokinetics because the drug is unbound to proteins
Drug can be either _____ or _____
bound or unbound
at equilibrium = degree of where it lies depends of types of drug
One drug can distribute the other one
Unbound drug - distribution to =
1) drug at site of action
2) Tissues and fluids of distribution
Drug plasma concentrations
(See curve on graph - slide 7)
- Step increase (onset) and reach
- Peak concentration
- Then descend to minimum effective concentration
Therapeutic range:
This range is the target window for the drugs to be effective
What happens if the concentration exceeds a high point?
May be side-effects
Define Bioavailability;
The proportion of a drug or other substance which enters the circulation when introduced into the body and so is able to have an active effect
IV administration (100% biolavailibility)
IV administration means the entire dose reaches the systemic circulation
Bioavailability will be lower via other routes
Bioavailability can depend upon….
Permeability of the biological membrane, drug properties,and other route-dependent factors, e.g. stomach contents for oral route
Fraction of Bioavailability =
F = fraction of administered dose of drug which
reaches system circulation (intact)
First-pass (presystematic) metabolismWhere are drugs absorbed?
Drugs absorbed from the stomach, small
intestines and upper colon pass into the hepatic portal system —> liver
Some drugs are metabolised extensively through their “first-pass” through the liver
What contributes to bioavailability?
Presynaptic metabolism is one factor
Naloxone:
Used to combat opiate overdose
Rapid onset required
Undergoes first pass metabolism
Stomach > liver
oral availability
0.9% to 2%
Metabolism
the chemical processes that occur within a living organism in order to maintain life
The body has a number of processes for metabolising drugs
Metabolism can be affected (induced or inhibited) by other drugs
Where does metabolism predominantly take place?
The liver but can happen in e.g. skin, plasma, kidney
Metabolism - 2 phases:
Phase I - Simple changes
Phase II - Conjugation
Phase I - Metabolism
Simple chemical changes, e.g. oxidation, reduction, hydrolysis
Cytochrome P450 isoenzyme particularly important
Products are likely to be inactive and more water-soluble
Phase II - Metabolism
Involves the conjugation (or addition) of groups to the drug to increase its solubility
Conjugates include glucuronates and sulphates
Oral administration
The most common route of drug administration
Solid (tablets, capsules) or liquid (suspensions, solutions) dosage forms
Dosage form travels to the main sites ofabsorption – stomach and small intestines
Drug must cross lipophilic barriers to be absorbed
Amount of drug which enters the systemic circulation depends upon the bioavailability
Oral route is often confused with -
BUCCAL and SUBLINGUAL route
do not mix up!!!
Parenteral route
(injection)
Parenteral formulations include:
Injections (intravenous, intramuscular, subcutaneous…)
Infusions
Sterile dosage forms
Advantages of Partental dosage forms:
Useful if drug labile in GI tract
Fast-acting
Prolonged effect possible with IM
Localised effect, e.g. intra-articular
Drugs can be administered to unconscious patients
100% bioavailability for IV
Case Study – Diazemuls®
> Diazepam is a lipophilic drug, i.e. it could be described “oil-loving”
> Earlier IV diazepam formulations used solvents such as propylene glycol and ethanol to aid the dissolution of the drug
> These solvents led to pain on injection
An alternative approach was to use an oily vehicle or an emulsion
> Diazemuls® consists of an oil-in-water emulsion which provides an “oily phase” in which the drug dissolves
> Plasma concentration-time curve enables us to confirm that the emulsion formulation is equivalent
Inhalation route - where?
Drug is delivered directly to the lungs typically via an inhaler or a nebuliser
What is inhalation route usually used for?
Typically used for a local effect, e.g. in asthma treatment but can also be used for systemic delivery
Pharmacokinetic advantages of the inhalation route:
Smaller doses can be used (salbutamol oral dose = 4 mg; inhaled dose 0.2 mg)
Reduces the chance of unwanted systemic (side) effects
Fast onset because drug delivered to the site of action
Avoids first pass metabolism
Transdermal route
Involves the application of a drug to the skin surface with the intention of achieving a systemic effect
Pharmacokinetic advantages of the transdermal route:
Avoids first pass metabolism
Controlled rate of drug delivery (avoids the peaks and troughs found with oral delivery)
Reduces dosage frequency which can increase compliance
Transdermal routes –»> pharmacokinetics
After delivery = repeated oral delivery so the therapeutic range is met (drug effective)
Rectal route:
Avoids first pass metabolism
Controlled rate of drug delivery (avoids the peaks and troughs found with oral delivery)
Reduces dosage frequency which can increase compliance
[Issues with pharmacokinetics ad cultural acceptability]
Advantages of rectal route for systemic delivery:
- Suitable if patient cannot easily swallow a solid oral dosage form, e.g. unconscious, child
- Drug not suited for oral delivery
Suppository meaning?
a solid medical preparation in a roughly conical or cylindrical shape, designed to be inserted into the rectum or vagina to dissolve
Why is drug incorporated into a soppusitory?
So it dissolves or melts within the rectum
Foam formulations will ______ to fill the rectum (also available)
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