Basics of PK Flashcards
1
Q
What is Absorption?
A
- The transfer of a drug from its site of administration to the bloodstream
- rate and efficiency of absorption depend on the route of administration
2
Q
What is Distribution?
A
- The reversible transfer of drug from one location to another within the body
- once a drug enters the systemic circulation by absorption or direct administration, it must be distributed into interstitial and intracellular fluids
3
Q
What is Metabolism?
A
- The metabolism of drugs into more hydrophilic metabolites is essential for the elimination of these compounds from the body and termination of their biological activity
- the objective of drug metabolism is to create hydrophilic products for kidney excretion
4
Q
What is Elimination?
A
Irreversible loss of drug from the body by excretion of metabolism
5
Q
Factors Affecting Drug Absorption: Drug
A
- Molecular size
- Particle size
- Degree of Ionisation
- Lipid/water solubility
- Physical structure
- Chemical structure
- Dosage forms
- Formulation/concentration
6
Q
Factors Affecting Drug Absorption: Body
A
- Surface area
- Vascularity
- pH
- Presence of food
- Gastric emptying rate
- Integrity of absorptive surface
- Disease
- Secreted substances
7
Q
What are the three ways drugs use to cross cell barriers?
A
- Direct penetration of lipid membrane
- Diffusion through aqueous channels
- Transporters (influx & efflux)
8
Q
What is the importance of BBB?
A
- Specific characteristics of blood vessels within the brain
- Protects brain from molecules that are potentially harmful and are in the blood
- BBB has specific processes that takes up important molecules from the blood
9
Q
What are the processes drugs use to pass BBB?
A
- Move freely if drug is water soluble with small molecular weight
- Lipophilic pathway is easiest, because drugs move straight through
- Specific transport proteins
- Complex proteins
- Very large proteins such as albumin use absorptive transcytosis
*if drugs cannot pass BBB, then they cannot be used to treat the CNS
10
Q
What processes are involved in drug distribution?
A
- Excretion
- Metabolism
- Tissue
- Tissue and receptor sites
11
Q
What is the process of drug binding to plasma proteins?
A
- Once a drug has been absorbed into the circulation it may bind to plasma proteins
- rapidly reversible and non-specific
- Once the drug is bound to plasma proteins, it is not active
- the only drug that is active is the free drug because only then can it bind to the receptors
12
Q
What are the main characteristics of liver drug metabolism?
A
- Oral medication is transported to GI which dissolves and gets absorbed
- Transported to portal vein
- Metabolism in the liver starts immediately
- continues into systemic circulation via hepatic vein
- comes back via hepatic artery
- Goes back to second entry to the liver (second pass), then third etc. causing exponential decay of drug level in the blood
- each pass causes metabolism of the same % of original drug amount
13
Q
What are the Phases of Liver Drug Metabolism?
A
Phase 1 and 2
14
Q
Describe Phase I: functionalisation reactions (CYP)
A
- Convert a parant drug to more polar metabolite by oxidation introducing or unmasking a functional group
- results in loss of pharmalogical activity
- may be equally or more active than parent
15
Q
Describe Phase II: conjugation reactions
A
- Subsequent reaction in which a covalent linkage is formed between a functional group on the parent compound of Phase I metabolite and endogenous substrate
- Highly polar, usually inactive
