Drug Absorption, Distribution, Elimination Flashcards
Two types of drug that can be transported passively
- small!!!!! hydrophilic drugs
2. Hydrophobic drugs
Weak acid vs. weak base (to figure out pKA) and drug distribution:
Acid: HA –> (H+) + (A -)
Base: BH+ –> H+ + B
Only uncharged drugs can move across biological membranes!!
Physiological factors governing Drug absorption?
- Blood flow
- Surface Area
- Contact time
- Food
Factors that decrease Oral Bioavailability of a drug?
- First-pass Hepatic Transformation (metabolism)
- portal system brings blood to liver before it reaches systemic circulation.
- many drugs are altered : inactivation (usually) - Hydrophilicity
- too hydrophilic= never gain access to the body - Metabolic and pH instability
- labile drugs (drugs destroyed by GI juices) - Physical properties of drug preparation
- bioinequivalent – different based on preparation NOT on active ingredient.
- affect dissolution in aqueous luminal contents.
Problems arising from switching to a generic brand?
- bioinequivalent
2. low therapeutic index
What are the 4 main reasons for using IV administration?
- hydrophilic drug (not well absorbed in GI)
- metabolically labile
- increased speed of action
- maximal control of plasma concentrations
What are some drug physical properties that affect its distribution?
- High molecular weight drugs
- trapped in plasma because too big to go through endothelial slits
- Low molecular weight drugs
- can squeeze in-between endothelial slits
- hydrophilic drugs can only get to Interstitial Fluid NOT intracellular fluids - hydrophobic drugs can go EVERYWHERE
- can squeeze in-between endothelial slits
- Binding to plasma proteins
- drug-protein complexes cannot penetrate endothelial slits/ junctions.
What type of drugs bind to Albumin?
Anionic hydrophobia drugs (aka WEAK ACIDS).
Hydrophilic drugs DO NOT BIND TO ALBUMIN
120g of albumin in 3L of plasma volume
Factors affecting total body water and distribution
- AGE
- gender
- Body composition : % lipid
Volume of distribution? ( and assumptions)
apparent volume of distribution of a drug
Vd= Ab/ Cpl
(Amount in body / Amount in plasma)
- indicative of a drug’s tendency to distribute in non-water tissues beyond the vascular space.
Assumptions:
1. body is a singe compartment into which drug distributes uniformly
- drug concentration in that compartment is the same as the plasma concentration.
Factors that affect Vd?
- Body composition
- % lipid
- Pathological hemodynameics (blood flow)
- increase perfusion = increase [Drug] - Polypharmacy
- use of several drugs may induce competition at same binding site
Renal Elimination
1. Glomerular filtration
~125mL/min rate
- only FREE drug can be filtered (hydrophilic
and hydrophobic)
- Passive = non saturable process
- Tubular Secretion
– active transport ~ ATP consumption
–two separate carrier mediated systems
-1 for acids (anions), 1 for bases (cations)
–Saturable
–BOTH free and protein-bound drugs can be
secreted - Tubular reabsorption
- [drug] is high = gradient is made
- only FREE, UNIONIZED drug diffuses back.
Clearance
Rate of drug elimination by all routes normalized to the drug concentration in fluid.
Follows first order kinetics– drug plasma concentration is a function of time
- constant: factional rate of drug loss form the body.
Clearance follows first-order kinetics. What is the first-order rate constant?
Kd = fractional rate of drug loss from the body
Kd = Clearance (body) / Vd
Clearance of an organ
used for modeling the impact of a DISEASE to a given organ on clearance!
CL (organ) = Organ Plasma Flow x Extraction Ratio
