Basic Principles of Pharm III Flashcards
passive transport processes
follow a concentration gradient or hydrostatic pressure, don’t require metabolic energy
What variables affect simple diffusion?
lipid solubility, size (smaller is better), degree of ionization (nonionized is best)
Facilitated diffusion
uses a carrier protein
- masks characteristics that may impede simple diffusion
- selective, can be inhibited, can be saturated
filtration
driven by hydrostatic pressure
- drug dissolved in the moving fluid is transported through pores in a membrane or channels between cells
- drug molecule size is limiting
Active transport processes
Use metabolic energy in the form of high energy phosphates such as ATP or electrochemical gradients
- transport against a concentration gradient
- rapid, selective, can be inhibited, can be saturated
Active transport
uses a carrier
Micropinocytosis
Drug is transported in pinched off packets of single layer membrane
Weak electrolyte drugs
- nonionized forms can diffuse, ionized cannot
- weak acids give up a proton, weak bases accept a proton
Henderson Hasselbach Equation
pH = pKa + log A-/HA OR
log A-/HA = pH - pKa
Enteral advantages/ disadvantages
- use a portion of GI tract
Advantages: ease, safety, self-admin, cheap, prolonged absorption –> prolonged effect
Disadvantages: absorption can be too slow, often variable and unpredictable, can be too irritating, drug can be destroyed by gastric acid, enzymes, can be completely metabolized on first pass thru liver, not available for comatose or vomiting pts
Rectal advantages/disadvantages
Advantages: useful for infants, comatose, vomiting pts
- good for smelly or bad tasting drugs
- good for drugs destroyed in upper GI tract
- avoids immediate liver metabolism
- for local action in rectum
Disadvantages: nuisance –> poor compliance, absorption may be erratic or incomplete, possibly irritating to rectum
Sublingual advantages/disadvantages
Advantages: bypasses liver when first absorbed
- rapid absorption
Disadvantages: must be soluble in saliva, not too bad tasting, have appropriate pKa for rapid absorption. must be small tablets.
Intravenous pro/con
Pros: rapid effect, can watch response and titrate dose, all of dose enters circulation, can use when oral route unavailable, for drugs too irritating when given IM or SC, for drugs in large volumes of fluid, infusion and continuous monitoring, parenteral administration of hypertonic solutions is possible
Cons: cost, skill in administering, danger of infxn, possible anaphylaxis, danger of embolus formation, danger of adverse cardiovascular effects with too fast administration, pain
Intraarterial pro/con
Pros: administration of radio-opaque material for visualization of circulatory tree
- high concentration of drug going to local area when desirable
Disadvantages: same as for IV
Intramuscular pro/con
Pro: when oral route unavailable, absorption less variable than with oral route, may be less painful than SC, possibility of slowing absorption to prolong effect
Cons: pain, sterile technique, possible local necrosis, lag period before effect onset, accidental IV injection possible, not to be used after anticoagulant admin
Subcutaneous injection pro/con
Pro: absorption usually slower than IM, effect more prolonged
- Same general pros as IM
Con: same as IM
Intrathecal pro/con
Pro: when local effect on CNS is required and other routes are unsatisfactory
Cons: skill, danger of spinal cord injury
Topical pro/con
Pro: for local action on or under skin, for local action on or under membrane, non-invasive
Con: difficulty of absorption thru skin, danger of excessive absorption thru membranes and systemic toxicity
Inhalation pro/con
Pro: rapid absorption for systemic action, high concentration for local effect, self-admin possible
Con: possible excessive absorption and systemic toxicity, poor regulation of dosage, irritation of pulmonary
Bioavailability
The fraction of dose available for biologic action
- usually pertains to oral drug admin where variable absorption or “first pass” effects will decrease the amount of drug that reaches circulation
= AUC oral/ AUC injected x 100
Plasma concentration equation
(F x dose) = Cp x Vd
where F = fraction absorbed, Cp = plasma conc, Vd = volume of distribution
Factors that effect absorption
Enteral: form of drug, food in stomach, illness, blood flow
Solution>suspension>capsule>tablet>timed release
Parenteral: blood flow, heat, cold, illness, form of drug (wafer, rods, injection in oil, transcutaneous patch)
