W8 Routines of Administration- Pharmacokinetics Flashcards
What is pharmacokinetics?
The study and characterisation of the time course of drug ADME (adsorption, distribution, metabolism and excretion)
What is Absorption?
Movement of a drug from the site of administration to the bloodstream.
What is Distribution? (ADME)
Movement of drug around different tissues in the body.
What is Metabolism? (ADME)
Change of drugs into compounds which are easier to eliminate.
What is Excretion? (ADME)
Irreversible loss of (unchanged) drug from the body.
ADME-Schematic representation
Drug at site of administration (IV injection)
Absorption
Blood plasma: Bound- unbound drug
Distribution at site of action
Elimination:
- Unchanged drug excreted
- Metabolites excreted
If a drug concentration is too high/low what happens?
Too high= Drug is unsafe, may be side effects
Too low= Drug is ineffective
Bioavailability:
What is the bioavailability of IV?
- IV administration means the entire dose reaches the systemic circulation, i.e. 100% bioavailability (F)
What factors can bioavailability depend on? (3)
- Permeability of the biological membrane
- Drug properties
- Other route-dependent factors e.g. stomach contents for oral route
e.g. stomach contents for oral route
What does F stand for in bioavailability?
F= fraction of administered dose of drug which reaches system circulation (intact)
What is the First-pass (presystematic) metabolism?
- Drugs absorbed from the stomach, small intestines and upper colon pass into the hepatic portal system to the liver.
- Some drugs are metabolised extensively through their “first-pass” through the liver
- Pre systematic metabolism is one factor which contributes to bioavailability.
Oral administration:
(for info)
- The most common route of drug administration
- Solid (tablets, capsules) or liquid (suspensions, solutions) dosage forms
- Dosage form travels to the main sites of
absorption – stomach and small intestines - Drug must cross lipophilic barriers to
be absorbed - Amount of drug which enters the systemic circulation depends upon the bioavailability
What is the main site of absorption?
Small Intestines
What is an example of a drug that undergoes first pass metabolism?
Naloxone:
* Used to combat opiate overdose
* Rapid onset required
* Undergoes 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
Why are things applied transdermally rather than
topically?
Absorbed by blood vessels in the dermis
Where does metabolism occur?
- Metabolism predominantly takes place in the liver but can also happen elsewhere, e.g. skin, plasma, kidneys.
- Metabolism can be affected (induced or inhibited) by other drugs
What is 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
What happens in Phase II metabolism?
- Involves the conjugation (or addition) of groups to the drug to increase its solubility
- Conjugates include glucuronates and sulphates
What should the oral route not be confused with?
The buccal or sublingual route.
What do parenteral formulations include?
̶ Injections (intravenous, intramuscular,
subcutaneous…)
̶ Infusions
What is the parenteral route?
- Sterile dosage forms given through injections or infusions
What are the advantages of the parenteral route?
̶ 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
What are some examples of meds given by
Oral administration?
Parenteral route?
Transdermal route?
Inhalation route?
Oral- Paracetamol, omeprazole, amoxicillin
Parenteral- Insulin, Adrenaline, Benzylpenicillin Na
Transdermal- Estradiol, Fentanyl, Nicotine
Inhalation- Salbutamol, Beclometasone
What are Diazemuls?
Diazemuls® consists of an oil-in-water emulsion which provides an “oily phase” in which the drug dissolves (diazepam)
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
Plasma concentration-time curve enables us to confirm that the emulsion formulation is equivalent
What is the Inhalation route?
Drug is delivered DIRECTLY to the lungs typically via an inhaler or a nebuliser
* Typically used for a local effect, e.g. in asthma treatment but can also be used for systemic delivery
What are the 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
What is the Transdermal route?
- Involves the application of a drug to the skin surface with the intention of achieving a systemic effect
What are the 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
What is the Rectal route?
What formulations? (2)
- Typically used for the local delivery of drugs to the rectum, e.g. haemorrhoids, but can also be used for systemic delivery
- Drug usually incorporated into a suppository which dissolves or melts within the rectum
- Foam formulations which expand to fill the
rectum are also available - Issues with pharmacokinetics and cultural
acceptability
What are the Advantages of the 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
