Pharmacology Part 3 Flashcards
Define absorption
The process by which a drug enters the body from its site of administration and enters the circulation
Define distribution
The transport of the drug by the general circulation. Drugs often leave the blood and enter perfused tissues. Once within a tissue further, reversible, distribution dictated by a concentration gradient may occur by diffusion or carrier mediated transport
Define metabolism
The process by which tissue enzyme (principally in the liver) catalyse the chemical conversion of a frequently lipid soluble drug to an often less active and more polar form that is more readily excreted
Define excretion
The processes that remove the drug, or its metabolites from the body (principally the kidneys)
What are the linked processes of metabolism and excretion referred to as?
Elimination
Where does absorption of a drug occur
Stomach (limited)
Intestines (most)
Where does the drug move to after the liver?
Vascular compartment
Where does the drug move to following the vascular compartment?
Interstitial water or kidneys
Which physiochemical factors control drug absorption?
- Solubility
- Chemical Stability
- Lipid to water partition coefficient
- degree of ionisation
Describe drug solubility?
Drug must dissolve (dissolution) in an aqueous environment in order to be absorbed
Describe chemical stability of a drug?
- some dugs are destroyed by acid in the stomach, or enzymes in the Gi tract
- in a few instances a compound is modified within the gut to release the active drug
Describe the lipid to water partition coefficient in drug absorption?
the partition coefficient is the ratio of the drug concentration in the membrane and concentration in water at equilibrium
Describe the degree of ionisation of a drug?
Many drugs exist as weak acids or weak bases in ionised and unionised forms.
Only unionised forms can readily diffuse across the lipid bilayer
What does degree of ionisation depend upon?
pKa of the drug and local pH
What is pKa?
pH at which 50% of the drug is ionised and 50% is unionised
How can pKa be calculated?
Henderson-hasselbalch
Where are drugs as bases absorbed?
Small intestine
Where are acidic drugs absorbed?
Dacilitated by the pH of the stomach lumen
Where does the majority of absorption occur?
In the small intestine (even for weak acids)
What is the role of pH in absorption?
Weak acids and weak bases are well absorbed, strong acids (pKa < 3) and strong bases (pKa > 10) are poorly absorbed
acidic drugs become less ionised in an acid environment; basic drugs become less ionised in a basic environment
What is gastrointestinal motility?
The rate of stomach emptying and movement through the intestines
What modifies GI motility?
Drugs, disease, food
What factors affect GI absorption?
GI motility
pH at absorption site
Blood flow (increased by food)
Tables manufacture (the time it takes to release)
Physiochemical interactions (modified by calcium rich foods)
Presence of transporters in the membrane of epithelial cells
What is oral availability?
fraction of drug that reaches the systemic circulation after oral ingestion
What is systemic availability?
fraction that reaches the systemic circulation after absorption
How can PO drugs avoid first pass metabolism?
once absorbed, can be inactivated by enzymes in the gut wall and liver (first-pass or presystemic metabolism) before reaching the systemic circulation and body tissues in general
What are the common routes of drug administration?
Oral Inhalational Buccal/sublingual Transdermal/subcutaenous IV Rectal Intramuscluar
What compartments can drugs be distributed to?
Plasma water Interstitial water fat Intracellular water transcellular water
Which drugs can move from plasma water to interstitial water?
Ionised and unionised drugs that are not bound to protein
Which drugs can move between
- fat and interstitial water
- intwstitial and intercellular water
- intracellular and transcellular
Only unionised drugs
Wha tis the apparent volume in which a drug is dissolved?
Volume of distribution (Vd)
What does the Vd of an IV administered drug equate to?
Dose/Plasma concentration
What does Vd of <10 L imply?
Drug is retained din vascular compartment
What does Vd between 10 and 30L suggest?
restricted to extracellular water
What does Vd >30 L suggest?
Distributed throughout total body water, maybe accumulation?
