Pharmacology L2: Pharmacokinetics- ADME Flashcards
How does the body deal with drugs that are taken?
- Absorption : how a drug gets into the body
- Into bloodstream
- Distribution: how a drug moves around the body
- Through blood stream
- Metabolism: how a drug is changed in the body
- Excretion: how a drug is removed from the body
What happens with ADME?
______ is a major challenge of drugs. What is a factor?
Crossing membranes
Size is a factor, as smaller compounds can more easily cross the cell membrane.
Lipophillicity (uncharged nonpolar) is an advantage.
Charge is not.
What is Uncharged molecules cross membranes?
pH may affect this… Most drugs are weak acids or weak bases.
Body pH = 7.4-7.4
Stomach pH = 2-3
What is the route of administration?
Routes are optimised for delivery of required concentrations of drug, taking solubility and chemical factors, as well as adverse effects into account.
Enteral: absorption through the GI tract Oral, rectal
Parenteral: all other routes Injections, sublingual, inhalation, topical
What is Metabolism by liver hepatocytes?
- Drugs that are absorbed from the gut reach the liver via the hepatic portal vein before entering the systemic circulation.
- Some drugs may have low bioavailability/distribution due to this first-pass effect.
- Some drugs can be given as pro-drugs, relying on the body’s metabolic processes to make an active metabolite.
- Some metabolites are active, most are inactive.
Drugs that are absorbed from the gut reach the liver via the hepatic portal vein before entering the systemic circulation. Some drugs may have low _______/______ due to this first-pass effect. What does that look like?
bioavailability/distribution
What is the first-pass effect and bioavailability?
To avoid first pass metabolism, what are 5 types of parenteral administration for injections?
- Intravenous (i.v)
- Intramuscular (i.m)
- Subcutaneous (s.c)
- Intraperitoneal (i.p)
- Intrathecal (i.t)
What are 3 advantages of parenteral administration to avoid first pass metabolism?
What are 3 disadvantages of parenteral administration to avoid first pass metabolism?
What are 6 characteristics of intravenous (i.v) injection?
What are 2 characteristics of subcutaneous (s.c) injection?
What are 3 characteristics of intramuscular (i.m) injection?
What are 2 types of intramuscular?
What are 3 characteristics of dissolving tablet under the tongue (sublingual)?
- Good vascularisation
- Rapid absorption into bloodstream
- No “first-pass” metabolism in the liver
What are 2 characteristics of sublingual medication?
a
What are 2 characteristics of topical medication?
What are the 3 sites of absorption?
What are 3 membranes that drugs need to cross?
- GI tract
- Blood-brain barrier
- Cell membrane
What are the 2 absorption transport across membranes?
Passive diffusion- passage along concentration gradient Facilitated transport- involves carrier or transport
What is passive diffusion?
Passive diffusion is the movement of substances across cell membranes without any energy needed. Sufficient concentration and time are needed if the drug molecules can pass through the membrane.
What are 3 principles of the distribution of drugs requiring the crossing of barrier?
- Free or unbound drugs can move into tissues (receive the most blood)
- Brain, heart (receives most blood –> affected by blood most)
- Drugs are delivered from site of injection/absorption to site of action via the blood
- Drugs generally diffuse into peripheral tissue depending on their physiocochemical characteristics
- Only free (unbound) drug can diffuse out of the blood circulation into peripheral tissue
- Tissues which receive the greatest amount of blood may receive the greatest amount of drug over time.
What is metabolism in term soft drugs as foreign compound?
What are 2 purposes of metabolism of xenobiotics?
- Increase the rate of excretion
- Decrease likely toxicity
How does drugs turn into a metabolite by enzyme?
Drug
- Xenobiotic
- Toxic
Metabolites
- More polar
- More rapidly excreted
- Less pharmacological activity
- Less toxicity