Pharmacokinetics: ADME and Routes of Administration

Study Notes

Pharmacokinetics

Deals with the effect of the body on the drug, focusing on getting enough drug to its target site to produce a sustained therapeutic effect.
Has 4 main domains: Absorption, Distribution, Metabolism, and Excretion (ADME).

Routes of Administration

Oral
IV
Rectal
IM
ID
Subcutaneous
Sublingual
Buccal
Inhalation
Topical

Absorption

Movement of drug from site of administration to circulation.
Passive diffusion: used for small hydrophobic medications.
Facilitated diffusion: used for large hydrophilic medications.
Active Transport: used for large hydrophilic medications, moving against their concentration gradient.
Endocytosis: used for extremely large medications.

Factors Affecting Absorption

Surface area: intestine is a prime area for absorption due to its large surface area, which can be affected by IBD and gastroenteritis.
Enteric coat: some medications are sensitive to stomach acid and need a protective covering to avoid getting damaged.
Gastric emptying: certain medications or health conditions can slow down the emptying of the stomach, delaying the passage of the drug into the intestine.
Food: food can affect the absorption of medications, as seen in a study with the antibiotic cloxacillin.

First Pass Metabolism

The drug absorbed in the intestine will be transported to the liver via the hepatic portal vein before entering the systemic circulation.
Hepatic enzymes break down most medications into inactive metabolites and convert prodrugs into active metabolites.

Bioavailability

The fraction of administered medication that reaches systemic circulation in its unchanged form.

Distribution

Movement of medication from circulation to body tissues.
Dependent on factors such as:
- Blood supply: more rapidly distributed to tissues with high blood supply, e.g. brain, kidney.
- Barriers: blood brain barrier allows small fat soluble medications compared to large water soluble medications.
- Ion Trapping: dependent on the weak base property of a medication and the acidic pH of the brain, making it impermeable to the blood brain barrier.
- Placental barrier: lipid soluble medications readily pass through the placenta and enter the fetal circulation, whereas water soluble drugs cannot.
- Protein Binding: affects the distribution of medications, with partly unbound medications being free to diffuse into the tissue and partly bound medications remaining limited to the plasma.

Protein Binding

Partly unbound to plasma protein (or free): free to diffuse into the tissue.
Partly bound to plasma protein: remain limited to plasma and act as a reservoir.
Medications with low protein binding are readily distributed, while medications with high protein binding take longer to free themselves to diffuse, resulting in a longer duration of action.
Binding to specific proteins: different medications have preferences for binding to specific blood proteins based on their chemical properties, with acidic drugs binding to albumin and basic drugs mainly binding to a1-acid glycoprotein.

Metabolism

Process of converting a medication into a less or more active form.
Carried out in the liver (hepatocytes).
Phase 1: CYP450 (hepatic enzyme) deactivates the drug to produce a primary metabolite.

Description

This quiz covers the basics of pharmacokinetics, including the four main domains: absorption, distribution, metabolism, and excretion (ADME). It also explores the various routes of drug administration, such as oral, IV, and topical.