1 Routes of Administration Flashcards
Define Pharmacokinetics
what the body does to the drug
Define Pharmacodynamics
what the drug does to the body
What are the classes of Routes of administration
• Enteral
– via the gastro-intestinal tract
• Parenteral
– via a non-GI route that allows delivery into the systemic circulation
• Topical
– local administration: no requirement for drug to enter the circulation
Define route
– the site through which the drug is administered
– should allow access to the desired site of action!
Overview of circulation diagram
Draw
How is the route chosen?
• Goal – deliver the drug to site of action and achieve the desired therapeutic outcome while avoiding adverse events.
• Therapeutic considerations
– Eg rapid delivery (eg glycerol trinate) or sustained delivery (eg nicotine patch)
• Effect of disease on route
– Eg medicating a vomiting patient p.o.
• Drug properties
– Eg the drug may not be absorbed from the GI tract
– Eg drug may not be stable in gastric acid
• Adverse events
– Eg Drug may be toxic if systemically bioavailable eg Nystatin (treats fungal infection in GI tract)
• Patient preference
– paracetamol: p.r. or p.o. ?
What is topical administration
• Direct application to site of action
• Isn’t going to lead to large conc of drug present in plasma (Limited systemic exposure)
– relatively small dose absorbed, as its absorbed at site of active
• Note that some anatomical sites can be used for both topical and systemic administration
– Epicutaneous vs Percutaneous
topical administration - define epicutaneous
Epicutaneous (applied to the surface of the skin)
Eg. local anaesthesia, eczema medications
topical administration - define percutaneous
Percutaneous (through the skin)
Eg. subcutaneous, IV, IM
Examples of topical administration
• Epicutaneous – e.g. local anaesthesia, eczema medications • Inhalation – e.g. asthma medications • Ocular (eye drops) • Auricular (ear drops) • Intranasal (nose drops) • Rectal – e.g. laxatives • Vaginal – e.g. anti-infectives • Intrathecal
Properties of topical administration
• Fast
• Local
– Allows high local doses to be achieved with relatively small quantities
– Avoids systemic side-effects
• BUT:
– Skill required to administer inhalers & drops – Absorption may be affected by disease
Where is most of the drug absorbed
Small intestine
Enteral administration - advantages and disadvantages
By the gastrointestinal (GI) tract
• Oral (p.o.)
– several advantages: convenient; patient compliance good; usually consistent absorption
–BUT:
– drug must survive gastric acid (solubility may be affected)
– absorbed from small intestine
– delays in stomach emptying delay drug reaching small intestine
– absorption relatively slow (fastest with empty stomach)
– drug must be sufficiently lipophilic or taken up by transporter
– first pass effect – drug passes through liver before entering systemic circulation
What is first pass metabolism
- Reduces bioavailability p.o. •Drug specific
- Saturable
- Affected by liver disease
draw diagram
Enterohepatic recycling
draw diagram
Enteral administration routes
• Sublingual
– under the tongue, absorbed through mucosal membranes
– no first pass effect – enters systemic circulation before liver
– BUT: some drugs aren’t absorbed by his route; some drugs cause irritation.
• Buccal
– absorbed through mucosal membrane of cheek
– no first pass effect – enters systemic circulation before liver
• Rectal (p.r.)
– useful if patient unconscious, vomiting, or if drug has unacceptable taste
– no first pass effect – absorbed into internal prudenal veins to inferior vena cava (except upper part)
– BUT: absorption may be irregular and irritation of rectal mucosa can occur
Parenteral and examples
• Systemic administration through a route not involving the GI tract
– Injection » Intravenous (i.v.) » Intramuscular (i.m.) » Subcutaneous (s.c.) » Intradermal (i.d.) » Intrathecal (i.t.) » Epidural
– Transdermal (t.d.)
» e.g. nicotine, hormones
– Transmucosal
» Nasal
» Insufflation (“snorting”)
– Inhalation
» e.g. general anaesthetics
Properties of parenteral
- Fast (except t.d. and depot formulations)
- slow infusion (>20 min) allows “titration” of drug levels •i.m. injection allows “depot”
•BUT
injection: inconvenient; requires asepsis; requires training s.c. – only with non-irritating drugs
Drugs in plasma bind to ..
Serum Albumin,
Alpha 1 glycoprotein
may bind to drugs and limit their distribution into the tissues
ADME
• Absorption
– distinguish systemic absorption from intestinal absorption
– systemic absorption drug enters circulation and potentially can move to tissues
• Distribution - different tissues
• Metabolism - converted to metabolites (chemical transformation)
• Excretion via kidneys
Elimination by..
by metabolism and excretion
Disposition
– what happens to the drug after systemic absorption
– distribution and elimination
Whole blood
– uncoaggulated and containing red & white blood cells
Plasma
blood cells removed, uncoaggulated
Serum
devoic of cells, coaggulated
Comparison of kinetics following i.v and p.o. drug administration
draw graph
• Following i.v. administration, the drug is “instantaneously” bioavailable
• Following p.o admin, time is required for absorption and not all the drug may be absorbed (bioavailability <100%)
• Cmax – maximum concentration is achieved at time Tmax
• Cmax achieved earlier following i.v. admin. than p.o. admin.
Cmax
max conc
- the rate absorbed = rate eliminated
Tmax
time at which max conc is achieved
