DRUG DISPOSITION AND FATE OF DRUGS 1 Flashcards
Drugs MUST have some ability to dissolve______ to move around (be absorbed, reach sites of action.)
WATER
drugs must also have a
certain degree of_____, to (leave and enter capillaries,
enter and leave cells.)
LIPID SOLUBILITY
is a preference not an absolut?
SOLUBILITY
drug concentration are measured in what?
SERUM or PLASMA
Drug dissolve in?
BODY FLUID
Drugs enter the circulatory system as fluid enters the?
CIRCULATORY SYSTEM
Drugs must enter the________ before they can distributed to sites of
action.
CIRCULATORY SYSTEM
drugs are not IN the body until they are IN the?
BLOOD STREAM
Advanatges of oral administration:
- CONVENIENT
- CHEAP
- NO NEED FOR STERILIZATION
- VARIETY OF DOSE FORM
Disadvantages pf oral administartion:
- Variability due to physiology, feeding, disease, etc.
- Intractable patients
- First-pass effect
- Efficiently metabolized drugs eliminated by the liver before they reach the systematic circulation.
The bolus remains relatively spherical. Mixing and
dissolution in tissue fluid occurs from surface of bolus, so entry of drug into
circulatory system limited by rate of drug “dissolution”
LIPID SOLUBLE VEHICLE
Can be given by the owner (small patients); also
Vasoconstrictor can be added to prolong effect at site of interest
SUBCUTANEOUS ADMINISTRATION
disadvantage of subcutanous administartion:
- VARIABILITY
2 types of TOPICAL ADVANTAGES :
- IF systemic therapy – easy painless application
- IF skin therapy – reduced systemic effects/enhanced skin effects
-Larger absorptive surface are than IM / Subcutaneous
-drugs & vehicles may cause peritonitis
-restricted to labortory animals
intraperitoneal
Direct delivery to site of action. High concentrations can be produces in the joint.
intra-actular
Direct delivery to site of action, via an injection into the spinal canal, or into the subarachnoid space so that it reaches the cerebrospinal fluid (CSF)
intrathecal
Absorption from the site to systemic is variable but often quite fast.
intra-actular
Produce extremely high concentrations “pointed at” (the tissue of interest. Used primarily for anti-tumor therapy and infectious disease therapy when blood supply is questionable.
intra-arterial
Animals may not willingly retain the drug, it has an advantages of Access to GI absorption in unconscious or vomiting patients
per rectum
Includes plasma, plasma water, and red blood cells. Equilibria occur between water and various plasma proteins, ionized and unionized drug, and plasma and cells. Distribution occurs within 10 to 30 minutes due to mixing
vascular spaces
Represents 7% of body weight. Equilibria occur between ionized and unionized drugs, and between plasma and cells. Distribution occurs within 10 to 30 minutes due to mixing.
tissue space
Special barriers exist between plasma and tissue fluids, such as cerebrospinal fluid (CSF), aqueous humor, and prostatic fluid. Distribution occurs in minutes to never, indicating limited or no permeability in some cases.
reserved spaces
Exists in both vascular and tissue spaces, constituting 35-45% of body weight. Equilibria occur between ionized and unionized drugs. Intracellular pH is lower than extracellular pH. Distribution takes 30 minutes to over 12 hours.
intracellular spaces
Occurs through transcytosis, endothelial junctions (in inflammation), and diffusion across endothelial cell membranes.
Vascular to tissue space
Includes extracellular fluid in both vascular and tissue spaces, constituting 15-20% of body weight. Equilibria occur between water and proteins, and ionized and unionized drugs. Distribution takes 30 minutes to 1.5 hours.
extracellular spaces
Involves diffusion through the lipid bilayer of cells.
Drugs can move from vascular extracellular space to vascular intracellular space, with the possibility of active acquisition by white blood cells.
Extracellular to Intracellular Space
Brain and liver concentration rise faster than muscle or fat
true
Diffusion can be rapid and is controlled by the rate of drug delivery to the tissue, determined by blood flow per gram of tissu
Blood Flow Limited Distribution
Diffusion is relatively slow compared to mixing within the vascular system.
diffusion limited to distrubution
This process leads to lower drug elimination rates and a higher volume of drug distribution.
Enterohepatic Circulation
This process is crucial in treating mammary gland infections and ensuring that nursing animals are not exposed to toxic drug levels in milk.
Mammary Excretion:
normal milk pH
6.6 (slightly acidic versus blood)
Drug in saliva passes into GI tract,
Ruminants can recycle certain drugs (similar to enterohepatic circulation) and trap drugs in the rumen based on pH, affecting elimination.
Salivary excretion
chemical mechanism involves in biotransformation:
- oxidation
- hydroxylation
- hydrolysis
- reduction
- conjugation
converts drugs into metabolites, often inactivating them but sometimes activating them
BIOTRANSFORMATION
Involves drugs with molecular weights > 300, usually conjugates of the original drug.
ACTIVE SECRETION
Involves drugs with molecular weights < 300, with biliary concentrations similar to plasma water.
PASSIVE SECRETION
passive elimination of drug dissolved in plasma water.
Glomerular excretions
energy dependent excretion by proximal kidney tubule
Tubular secretions
drug movement from renel tubule back to blood stream
passive reabsorption
renal elimination of aspirin can go from?
2% to 30% of total elimination
