W8 Routines of Administration- Pharmacokinetics

Question 1

What is pharmacokinetics?

Answer 1

The study and characterisation of the time course of drug ADME (adsorption, distribution, metabolism and excretion)

Question 2

What is Absorption?

Answer 2

Movement of a drug from the site of administration to the bloodstream.

Question 3

What is Distribution? (ADME)

Answer 3

Movement of drug around different tissues in the body.

Question 4

What is Metabolism? (ADME)

Answer 4

Change of drugs into compounds which are easier to eliminate.

Question 5

What is Excretion? (ADME)

Answer 5

Irreversible loss of (unchanged) drug from the body.

Question 6

ADME-Schematic representation

Answer 6

Drug at site of administration (IV injection)
Absorption
Blood plasma: Bound- unbound drug
Distribution at site of action
Elimination:
- Unchanged drug excreted
- Metabolites excreted

Question 7

If a drug concentration is too high/low what happens?

Answer 7

Too high= Drug is unsafe, may be side effects
Too low= Drug is ineffective

Question 8

Bioavailability:
What is the bioavailability of IV?

Answer 8

• IV administration means the entire dose reaches the systemic circulation, i.e. 100% bioavailability (F)

Question 9

What factors can bioavailability depend on? (3)

Answer 9

1. Permeability of the biological membrane
2. Drug properties
3. Other route-dependent factors e.g. stomach contents for oral route
   e.g. stomach contents for oral route

Question 10

What does F stand for in bioavailability?

Answer 10

F= fraction of administered dose of drug which reaches system circulation (intact)

Question 11

What is the First-pass (presystematic) metabolism?

Answer 11

• 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.

Question 12

Oral administration:
(for info)

Answer 12

• 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

Question 13

What is the main site of absorption?

Answer 13

Small Intestines

Question 14

What is an example of a drug that undergoes first pass metabolism?

Answer 14

Naloxone:
* Used to combat opiate overdose
* Rapid onset required
* Undergoes first pass metabolism

Question 15

Transdermal route:

Answer 15

• 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

Question 16

Why are things applied transdermally rather than
topically?

Answer 16

Absorbed by blood vessels in the dermis

Question 17

Where does metabolism occur?

Answer 17

• 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

Question 18

What is Phase I metabolism?

Answer 18

Simple chemical changes, e.g.
oxidation, reduction, hydrolysis
* Cytochrome P450 isoenzyme particularly important
* Products are likely to be inactive and more water-soluble

Question 19

What happens in Phase II metabolism?

Answer 19

• Involves the conjugation (or addition) of groups to the drug to increase its solubility
• Conjugates include glucuronates and sulphates

Question 20

What should the oral route not be confused with?

Answer 20

The buccal or sublingual route.

Question 21

What do parenteral formulations include?

Answer 21

̶ Injections (intravenous, intramuscular,
subcutaneous…)
̶ Infusions

Question 22

What is the parenteral route?

Answer 22

• Sterile dosage forms given through injections or infusions

Question 23

What are the advantages of the parenteral route?

Answer 23

̶ 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

Question 24

What are some examples of meds given by
Oral administration?
Parenteral route?
Transdermal route?
Inhalation route?

Answer 24

Oral- Paracetamol, omeprazole, amoxicillin
Parenteral- Insulin, Adrenaline, Benzylpenicillin Na
Transdermal- Estradiol, Fentanyl, Nicotine
Inhalation- Salbutamol, Beclometasone

Question 25

What are Diazemuls?

Answer 25

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

Question 26

What is the Inhalation route?

Answer 26

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

Question 27

What are the Pharmacokinetic advantages of the inhalation route?

Answer 27

̶ 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

Question 28

What is the Transdermal route?

Answer 28

• Involves the application of a drug to the skin surface with the intention of achieving a systemic effect

Question 29

What are the Pharmacokinetic advantages of the transdermal route?

Answer 29

• 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

Question 30

What is the Rectal route?

What formulations? (2)

Answer 30

• 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

Question 31

What are the Advantages of the rectal route for systemic delivery?

Answer 31

̶ Suitable if patient cannot easily swallow a solid oral dosage form, e.g. unconscious, child
̶ Drug not suited for oral delivery