Lecture 8: Pharmacokinetics II Drug disposition

Question 1

ADME processes of pharmacokinetics

Answer 1

-> Absorption from the site of administration
-routes of administration.
-> Distribution within the body
- special drug delivery systems
-> Metabolism
- Involves enzymatic conversion of one chemical entity to another within body (L9)
-> Excretion
- consists of elimination from the body of drug, or drug metabolites (L9)

Question 2

Absorption vs. Administration

Answer 2

Absorption: the passage of a drug from its site of administration into the plasma.
-Important for all routes BUT intravenous injection.
-Inhalation of a bronchodilator aerosol doesn’t require absorption as defined above for the drug to act.
-Drug must enter the plasma before reaching its site of action in most cases.

Question 3

Common routes of drug administration

Answer 3

1. Oral
2. Sublingual
3. Rectal
4. Application to other epithelial surfaces (skin, cornea, vagina, and nasal mucosa)
5. Inhalation
6. Injection (subcutaneous, intramuscular, intravenous, intrathecal, intravitreal)

Question 4

Oral (enteral) administration

Answer 4

-Most small molecules taken by mouth and swallowed.
- Little absorption occurs until the small intestine.
-SA are poorly absorbed

Pros: simple, cheap, convenient, painless
Cons: exposed to harsh GI environment, first-pass metabolism, slow delivery

Question 5

Sublingual Administration

Answer 5

• Absorption directly from oral cavity.
  -Anti-anxiety drugs

Pros: Rapid response
Cons: drug have bad taste

Question 6

Rectal administration

Answer 6

• Similar to sublingual
• local effect or systemic effects.

Pros: Good for vomiting
Cons: not reliable, inconvenient

Question 7

Cutaneous administration

Answer 7

-local effect.
-Absorbed very poorly through unbroken skin.

-Transdermal contraceptive patch (delivers hormones)
- Hormone replacement therapy (estrogen)

Question 8

Nasal spray administration

Answer 8

-Drug that binds to blood vessels
-Absorption through mucosa (high blood supply)
-Sniffing drugs can perforate or destroy the nasal septa.

Question 9

Eye drops administration

Answer 9

-locally into the eye
- absorption through the epithelium of the conjunctival sac
-can be done w/o systemic side effects.
-Bronchospasm in asthma patients (people w/ asthma it would exaggerated it)

Question 10

Administration by inhalation

Answer 10

-systemic administration of anesthetics.
-the lung route of both administration & elimination.

Question 11

transdermal administration

Answer 11

PROS: simple & convenient, slow absorbed (longer effects)
CONS: Drugs have to be lipophilic

Question 12

Subcutaneous administration

Answer 12

PROS: slow onset
CONS: Done in small volumes

Question 13

Intramuscular administration (vaccine)

Answer 13

PROS: immediate onset
CONS: painful

Question 14

Intravenous administration (IV)

Answer 14

PROS: Rapid, controlled easily
CONS: Overdose if long use

Question 15

Intrathecal injection

Answer 15

-> regional anaesthesia (labour, child delivery)
-> Implantable pumps

Pros: cross BBB
Cons: high infection risk

Question 16

Factors affecting gastrointestinal absorption

Answer 16

1. gut content (fed versus fasted) -> influence of feeding
2. gut motility -> a drug taken after a meal is slowly absorbed.
3. splanchnic blood flow
4. particle size and formulation -> Capsules designed to remain intact for hours after ingestion in order to delay absorption.
   -> some drugs designed to not be absorbed.
5. physicochemical factors (ex. drug interactions) -> chemical drug interactions that affect drug absorption.
6. genetic polymorphinsms in transporters
7. drug-drug competition for transporter

Question 17

Bioavailability

Answer 17

Used to indicate the fraction of an orally administered dose that reaches the systemic circulation as intact drug.

Bioavailability= Quantity of drug reaching systemic circulation/ Quantity of drug administered

Question 18

Distribution of drugs in the body:
Different Body compartments

Answer 18

1. Total body water: Small water-soluble molecules (ethanol)
2. Extracellular water: Larger water-soluble molecules (mannitol)
3. Blood plasma: highly plasma protein-bound molecules, very large molecules, highly charged molecules (heparin)
4. Fat: Highly lipid-soluble molecules (diazepam)
5. Bone and teeth: certain ions (fluoride, strontium)

Question 19

Distribution of drugs in the body:
Body fluid compartments

Answer 19

• 50 to 70%, less in women than in men.
  1. Extracellular fluid comprises:
  -the blood plasma (4.5%)
  -interstitial fluid (16%)
  -lymph (1.2%)
  2. Intracellular fluid (30-40%)
  -sum of all fluids of cell in body.
  3.Transcellular fluid (2.5%)
  -cerebrospinal, intraocular, peritoneal, pleura; and synovial fluids , and digestive secretions.

Question 20

Volume of distribution of a drug (Vd):
Dependence on solubility of various drug

Answer 20

Vd -> the volume of plasma that would contain the total body content of the drug at a concentration equal to that in the plasma
Vd= Dose/[Drug]plasma

• Higher for lipid soluble.

Question 21

Volume of distribution of a drug (Vd):
Define “Loading dose”

Answer 21

If a drug takes a long time to reach therapeutic levels, then higher dose (loading dose) may be given initially before dropping down to a lower maintenance dose. (to get to correct concentration of drug)

Question 22

Principles of evidence-based medicine

Answer 22

To compare the contraceptive effectiveness, cycle control, adherence (compliance), and safety of the skin patch or the vaginal ring vs. combination oral contraceptives (COCs)?

Question 23

Characterise the blood-brain barrier

Answer 23

• endothelial cells joined by tight junctions and pericytes.
  -brain is consequently inaccessible to many drugs.
  -Inflammation can disrupt the integrity of the BBB allowing normal impermeant substances to enter the brain.
  -Most antibiotics wont get into brain unless the BBB is disturbed.

Question 24

Examples of special drug delivery:

Answer 24

-prodrugs
-antibody-drug conjugates
-packing in liposomes
-coated implantable devices