Principles of Pharm- Quiz 1 Flashcards
What is Pharmacokinetics?
What the body does to a drug
What 4 things determine the onset, intensity, and duration of action of a drug?
- Absorption
- Distribution
- Metabolism
- Elimination
What is the pKa value?
A method used to indicate the strength of an acid.
A lower pKa value indicates a STRONGER acid.
The LOWER value indicates the acid more FULLY DISSOCIATES in WATER.
Absorption
From the moment of administration, absorption allows entry of the drug [either
directly or indirectly] into the plasma
Distribution
Next, the drug
may reversibly
leave the
bloodstream
and distribute
into the
interstitial and
intracellular
fluids
Metabolism (drug)
3rdstep—
metabolism
cause the drug to
be biotransformed
through metabolism by the liver or other organs
Elimination
The drug and
its metabolites are then
eliminated from the body—and excreted via
the urine bile or feces
Enteral Routes of Administration
Pharmacological Implications
Oral
Buccal
Sublingual
-Most common, convenient and economical method
-Toxicities and/or overdose of oral drugs may be overcome with antidotes like activated charcoal
-low gastric pH inactivates some drugs
-Enteric-coated drugs
-Extended release drugs
Routes of Parenteral Administration
Pharmacological Implications
IV
IM
SQ
Intradermal
-Route is irreversible
-Provides the most control over the dose delivered
-Since this way introduces the drug directly into systemic circulation it is used for drugs poorly absorbed from the GI tract, patients unable to take PO meds, and when you need a rapid onset of action
Other routes of administration (Other than Enteral or parenteral)
-Oral Inhalation
-Nasal Inhalation
—Rapid delivery to large amounts of mucus membrane of lung
—Drugs that are gasses or aerosols
—Convenient with respiratory disorders as it is delivered directly to the location of action
-Intrathecal or Intraventricular
—Bypasses the BBB delivering drugs directly into the CSF and therefore the CNS
—Used if local or rapid effects are needed, or if needed drug is unable to cross BBB
-Topical
—Used when a local effect is needed
-Transdermal
—systemic effects when applied to skin
—absorption can VARY SIGNIFICANTLY
-Rectal
—Biotransformation of drug by liver is minimal (bypasses 1st pass), prevents GI destruction of drug.
—Useful if can’t take PO, vomiting
—Absorption is erratic and incomplete, many drugs irritate the rectal tissues
What is Absorption
-Transfer of a drug from the site of where it is
given into the bloodstream
-Rate of absorption depends on environment
where drug is absorbed, chemical
characteristics of the drug and route
What are the 4 mechanisms of Absorption from the GI tract?
- Passive Diffusion
- Facilitated Diffusion
- Active Transport
- Endocytosis/Exocytosis
What is Passive Diffusion?
-Driving force for passive diffusion of a drug is the concentration gradient across a membrane—the drug moves from an area of high concentration to one of lower concentration
-Does not involve a carrier, in not saturable and shows low structural specificity
-VAST MAJORITY OF DRUGS ARE ABSORBED BY THIS MECHANISM
-Water-soluble drugs penetrate the cell
membrane through aqueous channels [pores]
-Lipid soluble drugs readily move across most
biologic membranes due to solubility in the
membrane lipid bilayers
What is Facilitated Diffusion?
-Drug enters the cell through specialized transmembrane
carrier proteins that facilitate the passage of large molecules
-Dose not require energy
-Can be saturated
-May be inhibited by
compounds that compete for
the carrier
What is Active Transport?
-Specific carrier proteins that span
the membrane
-Is energy dependent, driven by
hydrolysis of ATP
-Capable of moving drugs against a concentration gradient, from a region of low drug concentration
to an area of higher concentration
-Process is saturable
-Selective and may be inhibited by
other co-transported substances
What is Endo/Exocytosis
-Used to transport drugs that are very large across cell membranes
-Endocytosis involves engulfing a drug by the membrane and transporting it into the cell by pinching off the drug filled vesicle
-Exocytosis is the opposite, cells secrete substances out of the cell through a similar process of vesicle formation
What factors influence absorption?
-pH
-Blood flow: intestines receive more blood flow than the stomach, so absorption of the intestines is preferred over the stomach
-Total surface area available: when a surface is rich in brush boarders containing microvilli the intestine has a surface areas 1000x than the stomach
-Contact time: if a drug moves through the GI tract quickly, it is NOT well absorbed. Anything that delays the transport of the drug from the stomach to the intestine delays the rate of absorption
-Expression of P-glycoprotein
What kind of drugs pass more readily?
UNCHARGED
Why is drug pH a significant factor for absorption?
-Most drugs are either weak acids or weak bases
–acid drugs release a proton becoming
a charged form
–while bases are usually charged and when they lose a proton, they
become an uncharged base
—Drugs pass through membranes more readily
if it is UNCHARGED
How is pH related to pKa?
-Effective concentration of the permeable form of each drug at the absorption site is determined by the relative concentrations of the charged and uncharged forms
-Ratio between the 2 forms is determined by the pH at the site of
absorption and by the strength of the weak acid or weak base—which
is represented by the ionized constant pKa
-The lower the pKa of a drug, the more acidic it is
-The higher the pKa of a drug—the more basic it is
What is distribution equilibrium?
Distribution equilibrium occurs when the permeable form of a drug reaches an equal amount in all body water spaces
What is P-glycoprotein?
Where is it found?
What does it do?
-P-glycoprotein is a transmembrane transporter protein responsible
for transporting various molecules and drugs across cell membranes
-It is in liver, kidneys, placenta, intestines, brain capillaries
-Involved in transportation of drugs from tissues to blood
- “it pumps” drugs out of cells
-In areas of high expression—P-glycoprotein reduces drug absorption
- P-glycoprotein is also associated with multidrug resistance
What is Bioavailability?
-Rate and extent to which a given drug reaches the systemic circulation
-if 50mg of a drug is given PO, and 25mg is absorbed unchanged, then the bioavailability of the drug is 0.5 or 50%
-This is important for calculating dosages for non-intravenous routes
How is bioavailability determined?
-Compare plasma levels of a drug after a particular route of
administration with levels achieved by IV route
-Plotting concentrations of the drug vs. time, the area under the curve [AUC] can be measured
-Bioavailability is AUC of oral dose ÷AUC of IV dose multiplied by 100%
What factors influence bioavailability?
-First pass
-Solubility of the drug
-Chemical instability
-Nature of the drug
formulation
*IV drugs have a 100% bioavailability
**With oral agents-drugs undergo 1stpass metabolism, in addition, chemical and physical properties determine rate and extent to which the drug reaches the
systemic circulation
How does first pass work?
Why is this important to know?
-Drug absorbed from GI tract—enters the portal circulation before entering systemic circulation
- If drug is rapidly metabolized in liver or gut wall during this
passage, the amount of unchanged drug entering the systemic circulation is decreased
**—-This is 1stpass metabolism
-1stpass metabolism by the intestine or liver limits efficacy of many PO meds
-Drugs with high 1stpass metabolism must be given in doses sufficient to ensure that enough active drug reaches the desired site of action
How does solubility of a drug affect bioavailability?
-Very hydrophilic drugs are poorly absorbed
-Drugs that are extremely lipophilic are also poorly absorbed, because they are insoluble in aqueous body fluids and as such cannot get into the surface of the cells
-For a drug to be readily absorbed, it MUST BE LARGELY LIPOPHILIC, yet have some SOLUBILITY in AQUEOUS solution—this is one reason why many drugs are either weak acids are weak bases
How does chemical stability affect bioavailability?
-Some drugs are
unstable in pH of
gastric contents
[PCN G]
-Others are destroyed
in the GU tract by
degradative
enzymes [insulin]
How does drug formulation affect bioavailability?
Drug absorption can
be altered by factors unrelated to the chemistry of the drug—particle size, salt form, crystal polymorphism, enteric coatings, presence of binders and/or dispensing agents
What is bioequivalence?
What is pharmaceutical equivalence?
What is therapeutic equivalence?
-Drugs are bioequivalent if they show comparable bioavailability and similar times to achieve peak blood levels
-Drugs are therapeutically equivalent if they are pharmaceutically equivalent—with similar clinical and safety profiles
-Therapeutic Equivalence requires that drug products are bioequivalent and pharmaceutically equivalent
What is drug distribution?
-Process where a drug reversibly leaves the bloodstream and enters extracellular fluids and tissues
-For drugs given IV—absorption is not a factor, distribution begins immediately, where the drug leaves the circulation and enters the tissues
-Distribution depends on CO, local blood flow, capillary permeability, tissue volume, degree of binding of the drug to plasma and tissue proteins and relative lipophilicity of the drug
How does blood flow to different types of tissue affect distribution?
-Blood flow to brain, liver, and kidney is > than skeletal muscle
-Adipose tissue, skin and viscera have even lower rates of blood flow.
-High blood flow + high lipophilicity = rapid distribution to CNS
–slower distribution to skeletal muscle and adipose tissue
How does capillary permeability affect the movement of drugs into the CNS?
-Permeability determined by capillary structure and chemical nature of drug
-To get to the brain, drugs must pass thought the endothelial cells of the CNS capillaries or undergo active transport
-Lipid soluble drugs readily penetrate the CNS because they dissolve in the endothelial membrane
-Ionized or polar drugs usually fail to enter the CNS because they can’t get through the endothelial cells. This endothelium has no slits and are juxtaposed, having tight junctions that create the BBB.
What protein can serve as a drug reservoir?
Albumin
