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Pharmaco kinetics W3, PART I: ADME
Absorption, distribution, metabolism,…
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PART I: ADME
Absorption, distribution, metabolism, excretion
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Drug administration: Various routes of drug delivery
Oral,mucus membrane, rectal, topical (skin), inhalation, injection, implants
Pathway for oral administrered drug:
Mouth -> stomach -> upper intestine -> blood supply -> liver -> blood supply -> target site
What happens at each stage?
A – Absorption
Definition: Drug entry into bloodstream.Site: Mostly small intestine (oral drugs).Factors affecting:
- Solubility & formulation
- pH & pKa
- Blood flow at absorption site
- GI motility
- Presence of food
- First-pass metabolism
D – Distribution
Definition: Drug movement into tissues.Factors Affecting:
- Blood bflow to organs
- Plasma protein binding (e.g. albumin)
- Tissue binding
- Lipid solutbility
- Cappilary permeability
E - Excretion
Definitiuon: Removal of drug/metabolites
Routes
- Renal (urine) - most common
- Bilary/fecal
- Pulmonary (exhaled gases)
- Sweat, saliva, breast milk
Factors affecting:
- Renal function
- Drug polarity (more poolar = better excretion)
- pH of urine (affects ionization and reabsorption (in the renal tubules, before reaching the bladder))
M - Metabolism
Definition: Biochemical modfication of the drug
Primary site: Liver (Via enzymes like CyP450.Phases:
- P1: Functionalization ( oxidation reductiom hydrolysis)
- P2: Conjugation (glucuronidation, sulfation)
Outcomes
- Inactvation
- Activation (prodrugs)
- Detoxifcation or generation of toxic metabolites
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