Download Phil Rowe Reader in pharmaceutical computing School of

Phil Rowe
Reader in pharmaceutical computing
School of Pharmacy & Chemistry
All these presentations can be downloaded from:
http://www.staff.livjm.ac.uk/phaprowe/
then follow 'Nurse prescribing'
Lecture 2
Routes and patterns of drug
administration
Part 1
Routes of
administration
Routes to be covered:
• Intravenous
• Oral
• Buccal & Rectal
• Intramuscular
• Subcutaneous
• Topical
Intravenous
Advantages:
• No absorption stage - immediate effect without delay
• Guaranteed 100% bioavailability - no variation
between patients
Disadvantages:
• Person administering dose needs careful training
• Sterility essential
• Possible extravasation
Oral
Advantages:
• Simplicity
Disadvantages:
• Low and unpredictable bioavailability for some drugs
• Rate of absorption - slow and unpredictable
– Release from the tablet/capsule etc
– Gastric emptying
Gastric emptying
Stomach
Small
intestine
Drugs absorbed
very slowly
Drugs absorbed
much more quickly
Drug absorption from oral
route
Absorption may be delayed by:
• Disintegration of dosage form (Tablet capsule etc)
– Capsules (Soft gelatin) Few minutes
– Capsules (Hard gelatin) Few minutes to an hour or more
– Tablets Very variable Several hours for controlled release
• Gastric emptying into intestine.
– Liquid 50% in about 30 mins
– Solids 50% in about 2 hours
Buccal & Rectal
Rectal may be useful if patient is vomiting.
Rectal not terribly popular with British!
Both may be useful in increasing bioavailability.
Blood drainage from G.I.T.
Mouth
General
circulation
Stomach
Small
intestine
Large
intestine
Rectum
Liver
General
circulation
Buccal & Rectal
Both the buccal and the rectal route have the potential to
increase bioavailability by allowing drugs to bye-pass the
liver.
Main advantage is that the dose that will reach the body is
more predictable.
Buccal route works well. e.g. Buccastem (Buccal
prochlorperazine - antiemetic) delivers higher and more
predictable dose than oral route.
Rectal is less reliable. Effectiveness depends on the
individual patient and the exact placing of the dose.
Intramuscular
Oil or water
Drug
Blood
Rate of absorption of drug may be limited either by rate of
release from injection vehicle or the ability of the blood to
carry the drug away.
Intramuscular
• Oil based dosage form:
Rate limiting step is release from vehicle. Slow (Many
hours to a few weeks) but predictable.
• Water based dosage form:
Rate limiting step generally removal of released drug by
blood flow. Quite quick, but very variable - exercise or
rubbing the injection site will increase rate of dispersal
into body.
Subcutaneous
Drug has to carried away from the injection site by blood
or lymph. Both blood and lymph flows to the
subcutaneous tissue are poor. Release therefore rather
slow.
If slow release is wanted, probably better to use a slow
release formulation (Oil or plastic).
Can be painful.
Topical
With topical application, intention is generally to achieve
a local effect. However, in many cases, drug will be
absorbed into the general circulation.
Examples:
• Inhaled steroids intended to act in the lungs, but are
absorbed and can cause some adrenal suppression.
• Beta-blockers in eye-drops reach measurable
concentrations in blood.
Part 2
Patterns of
administration
Patterns to be covered:
• Single dose
• Intravenous infusion
• Multiple dose
Single dose
Rapid release - Useful for a
"Quick hit". e.g. pain killers.
Slow release - Useful where
we want a prolonged steady
exposure to the drug
Intravenous infusion
Css
Steady state
Intravenous infusion
Rate of infusion
Concentration at
=
steady state (Css)
Clearance
Use of
a
loading
dose
Immediately effective treatment
Therapeutically effective range
With loading dose
No loading dose
Multiple
dose
Accumulation
with and without accumulation
Much of
of previous
previousdose
dosestill
stillpresent
present
Previous dose
fully
eliminated
Previous
dosealmost
almost
fully
eliminated
Concentrations at
Steady State
Peak
Average
Trough
Multiple dosing
Bioavailability x Dose size
Average
=
Conc
Clearance x Dosage interval
Divided doses
2 x 300 mg
3 x 200 mg
6 x 100 mg
Divided doses
Dose division should be great enough
to ensure that peaks and troughs are
not excessively high/low. But, always
keep number of doses per day as low
as possible to maximise compliance.