Basics of PK Flashcards
What is Absorption?
- The transfer of a drug from its site of administration to the bloodstream
- rate and efficiency of absorption depend on the route of administration
What is Distribution?
- 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
What is Metabolism?
- 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
What is Elimination?
Irreversible loss of drug from the body by excretion of metabolism
Factors Affecting Drug Absorption: Drug
- Molecular size
- Particle size
- Degree of Ionisation
- Lipid/water solubility
- Physical structure
- Chemical structure
- Dosage forms
- Formulation/concentration
Factors Affecting Drug Absorption: Body
- Surface area
- Vascularity
- pH
- Presence of food
- Gastric emptying rate
- Integrity of absorptive surface
- Disease
- Secreted substances
What are the three ways drugs use to cross cell barriers?
- Direct penetration of lipid membrane
- Diffusion through aqueous channels
- Transporters (influx & efflux)
What is the importance of BBB?
- 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
What are the processes drugs use to pass BBB?
- 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
What processes are involved in drug distribution?
- Excretion
- Metabolism
- Tissue
- Tissue and receptor sites
What is the process of drug binding to plasma proteins?
- 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
What are the main characteristics of liver drug metabolism?
- 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
What are the Phases of Liver Drug Metabolism?
Phase 1 and 2
Describe Phase I: functionalisation reactions (CYP)
- 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
Describe Phase II: conjugation reactions
- 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
What are endogenous substrates used in Phase II metabolism?
- Glucuronic acid
- Sulfate
- Acetate
- Amino acids
What are the characteristics of drug elimination by kidneys?
- Filtration
- Secretion
- Reabsorption
Characteristics of drug elimination by kidneys: Filtration
- Drugs are transported by the capillaries to the tubule by glomerular filtration at the renal corpuscle
- allowing small drugs and those not bound to plasma protein to filter from the blood into the Bowman’s Capsule
Characteristics of drug elimination by kidneys: Secretion
- Majority of drugs enter kidneys by tubule secretion (active process)
- involves two carrier systems
- basic carriers: transport basic drugs
- acidic carriers: transport acidic
- involves two carrier systems
Characteristics of drug elimination by kidneys: Reabsorption
- Some drugs and metabolites may be reabsorbed back into the blood stream
- Passive diffusion
What is a prodrug?
Originally pharmacologically inactive, has to be metabolised by the liver first in order to be activated
Define Drug Half-Life
The time necessary for blood levels to drop from Cmax to 50% of Cmax
Define Therapeutic Range
- Useful range of concentration over which a drug is therapeutically beneficial
- narrow therapeutic windows require smaller and more frequent doses/or a different method of administration
- drugs with slow elimination rates may rapidly accumulate to toxic levels
What is the Inhibition of Drug Metabolism?
Drugs and other substances can inhibit the metabolism of other drugs
What are the consequences of Inhibition of Drug Metabolism?
- Increase in plasma concentration of parent drug
- Reduction in metabolite concentration
- Exaggerated and prolonged pharmalogical effects
- Increased likelihood of drug-induced toxicity
Induction of Drug Metabolism
Induces its own metabolism or the metabolism of other drugs
What are the consequences of Induction of Drug Metabolism?
- Increased metabolism rate
- Decrease in drug plasma concentration
- Enhanced oral first pass metabolism
- If metabolite is more active than drug, increased drug effects or toxicity
