Drugs Disposition and Fate of Drugs Flashcards
Drugs MUST have some ability to dissolve in ________ to move around.
WATER (be absorbed, reach sites of action.)
In almost all cases, drugs must also have a certain degree of ________ to move around (leave and enter capillaries, enter and leave cells.)
LIPID SOLUBILITY
is a preference not an absolute.
SOLUBILITY “water soluble”, “lipid soluble”
Drug effects are USUALLY __________________ to drug concentration at the site of action
PROPORTIONAL (though not always linear)
Drug concentrations in the ___________________ are USUALLY proportional (and usually linear) to drug concentrations
at the site of action.
BLOOD STREAM (measured in either serum or plasma)
TRUE OR FALSE
Drug concentration in the blood stream is ALMOST ALWAYS an excellent predictor of drug action (either efficacy or toxicity) even though they may not
be identical to the concentration in the target tissue.
TRUE
are the consequence of physiologic process (that may or
may not be altered by disease.)
pharmacokinetics
Drug dissolve in ______________.
Body Fluid (Water)
Drugs enter the _____________as __________ enters the circulatory system
circulatory system
fluid
Therefore, drugs are not IN the body until they are IN the _____________
bloodstream
_____________ must enter the circulatory system before they can distributed to sites of action.
Drugs
Advantages in Oral Administration
✓Convenient
✓cheap
✓ no need for sterilization
✓variety of dose forms
(fast release tablets, capsules, enteric coated layered tablets, slow release,
suspensions, mixtures)
✓You can get the dose back of you move fast enough.
Disadvantages in Oral Administration
✓ 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.
Patient and Pharmaceutical Factors in Oral Administration
✓ Pill compression, coatings, suspending agents, etc.
✓ GI transit time (too slow or too fast), inflammation, malabsorption, syndromes
Regional Differences
in Oral Administration
✓ stomach
✓ mechanical preparation
✓ “flat” absorptive surface
✓ pH extreme
✓ Rumenoreticulum
✓ stratified squamous epithelium
✓ pH varies with diet
✓ metabolism by bacterial flora
✓ significant volume of fluid compared to body water
✓ Small Intestine
✓ large absorptive functions
✓ relatively neutral pH
✓ Colon/Rectum
✓ accessible
✓ large absorptive surface
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” (Movement from the “bolus” to the tissue fluid).
liquid soluble vehicle
Advantages in Subcutaneous Injection
✓ Can be given by the owner (small patients)
✓ Vasoconstrictor can be added to prolong effect at site of interest
Disadvantage in Subcutaneous Injection
variability
Process in Subcutaneous Injection
Much like intramuscular
Patient and Pharmaceutical Factors in Subcutaneous Injection
✓ More autonomic control over blood flow (than muscle)
✓ dehydration
✓ heat
✓ cold
✓ stress
Advantages of Topical
✓ IF systemic therapy – easy painless application (e.g. mass medication of
cattle)
✓ IF skin therapy – reduced systemic effects/enhanced skin effects
Disadvantages of Topical
✓ Patients groom themselves
✓ Toxic skin reactions
✓ Variable blood flow to skin
COMPLEX relationship between drug, vehicle , skin physiology
Process of Topical
✓ Diffusion through stratified epithelium
✓ “Passage” through adnexal structures
Patient and Pharmaceutical Factors in Topical
✓ Lipid solubility and molecule size
✓ Skin hydration and abrasion
✓ Area of application
✓ Ambient an patient temperature
advantages in intraperitoneal
✓ Larger absorptive surface are than IM / Subcutaneous
Disadvantages of intraperitoneal
✓ Drugs or vehicles may cause peritonitis
✓ Damage to organs by needles
Injection into organs
Process of intraperitoneal
✓ Similar to subcutaneous
✓ Greater blood flow
✓ Less flow regulation
Patient and Pharmaceutical Factors
of intraperitoneal
Generally restricted to laboratory animals
advantages in Intrathecal
✓ Direct delivery to site of action
disadvantages of intrathecal
✓ Difficult dose calculation
✓ CSF volume is not proportional to body weight
✓ Toxicity likely, and toxicity may be unusual
✓ Introduce infection into a VERY bad location
process of intrathecal
✓ Absorption is usually by diffusion and very slow
advantages of intra-actular
✓ Direct delivery to site of action
✓ High concentrations can be produces in the joint.
Disadvantages of intra-actular
✓ It may be difficult to hit the joint space
✓ Difficult dose calculation
✓ Joint space volume depends on disease
Process of intra-actular
Absorption from the site to systemic is variable but often quite fast
advantages of Intra-arterial
✓ Produce extremely high concentrations
Disadvantages of intra-arterial
✓ Dose calculation is best guess
✓ Intra-arterial lines difficult to insert/maintain.
✓ Dosing is still really systemic.
✓ Limited number of efficacy studies
process of intra-arterial
Produce AND SUSTAIN high blood-to-tissue gradient to increase tissue concentrations of drug.
advantages of per rectum
✓ Access to GI absorption in unconscious or vomiting patients
✓ Drug can be recovered before absorption is complete
disadvantages of per rectum
✓ Animals may not willingly retain the drug
process of per rectum
✓ As for oral without mechanical preparation by stomach
