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56 Cards in this Set

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Pharmacokinetics
refers to the absorption, distribution, biotransformation and excretion of drugs in the intact organism.
fundamental hypothesis of pharmacokinetics
relationship exists between the pharmacological or toxic response of a drug and the plasma drug concentration
In most cases, the plasma concentration of drug will be related to the concentration of drug at ________
its sites of action
The ultimate drug concentration at the site of action depends on _________(6)
the dose administered, the extent and rate of its absorption, distribution, binding in tissues, biotransformation, and excretion
Permeation
Passage of drugs across cell membranes
Most common mode of drug transfer
Passive transfer:
Passive diffusion
Movement of a drug molecule down its concentration gradient by virtues of its solubility in the lipid membrane
Passive diffusion is directly proportional to ___________ (2)
1)concentration gradient across the membrane 2) the lipid: water partition coefficient of the drug.
Bulk flow
Movement of drug molecules through membrane channels or pores, e.g., capillary endothelial membranes
Active transport
requires energy(ATP) and can move drug molecule across membranes against its concentration gradient.
Facilitated diffusion
requires no energy.
Endocytosis and exocytosis
e.g., VITAMIN B12, IRON
Factors affecting the diffusion of drugs across lipid membrane barriers:
e.g. lipid solubility; charge; size; etc.
Lipid: water partition coefficient
It is defined as the ratio of the concentration of the drug in water and a nonpolar organic solvent (e.g. oil, ether,chloroform, etc.)
-Lipophilic vs. hydrophilic.
Drugs with large lipid: water partition coefficients tend to readily undergo ________ diffusion
passive
Degree of ionization: inversely affects ________
lipid solubility
Most drugs are either _________
weak acids or bases
Ionized molecules have low lipid solubility. Such drugs are often dispensed as _____
salts
______ of drug's aqueous enviornment determines ratio of charged to uncharges species.
pH
Henderson Hasselbach equasion
pH = pKa + log A-/HA
Acid pH (e.g. stomach)
favors absorption of ______
weak acids
Basic pH (e.g. intestine)favors absorption of _______
weak bases
Drugs administered in ______ solution are more rapidly absorbed than drugs administered in ______ solution.
aqueous / oily
For drugs given in solid form, the __________ may be the limiting factor in absorption.
rate of dissolution
Factors that affect rate of absorption:
1)Solubility
2)Concentration (C1-C2)
3)Area of the absorbing surface (A)

4) Thickness of membrane (T)
5) Blood circulation to the absorptive site
6)Route of administration
Enteral
Oral route
Most drugs taken orally are absorbed by passive diffusion through GI mucosa -- absorption is favored when the drug is in the __________.
ionized and lipophilic form
In orally taken drugs the _______ is usually the major site of absorption, NOT the ________
upper small intestine/ stomach
Any factor that decreases gastric emptying time tends to _______ the rate of absorption, while any factor that increases gastric emptying time tends to ______ rate of absorption
increase/ decrease
Factors affecting rate of GI absorption
1) ionized vs. nonionized form
2)Gastric emptying time (GET)
3) Intestinal transit time (ITT)
4)Food decreases drug absorption by forming complexes with drugs
First-Pass Effect”
orally administered drugs are unusually susceptible to destruction by enzymes in the liver
Oral cavity: sublingual; buccal
Advantages & Disadvantages
1) Advantages: avoids the first-pass effect and gastric acid.
(2) Disadvantages: taste; irritation; only small amounts can be administered.
Rectal administration: suppositories; retention enema.
Advantages & Disadvantages
(1) Advantages: useful during vomiting or unconsciousness; voids first-pass effect and gastric acid.
(2) Disadvantages: irritation to mucosa, absorption is irregular and incomplete
Intravenous
Advantages/Disadvantages
(1) Advantages:
• rapid and predictable absorption
• dosing is more accurate
• avoid destruction by low gastric pH
• useful if unconscious, uncooperative, vomiting and in emergencies
(2) Disadvantages:
• asepsis must be maintained
• less safe than oral
• painful
• self-medication more difficult
• expensive
Subcutaneous
Advantages/Disadvantages
Advantages:
-- ease of administration
-- relatively rapid absorption from aqueous solutions
-- rate of absorption can be altered e.g. vasoconstrictors
• Disadvantages:
- only suitable for small volumes of non-irritating solutions
- pain, tissue necrosis, bacterial infections
Intramuscular
-Similar to subcutaneous route, but for irritating solutions
-Relatively rapid absorption but can be altered--e.g. “depot preparations” in oil will provide slow, even absorption
intra-arterial
mostly used for administration of diagnostic agents
intrathecal
used in CNS infections, spinal anesthesia
Drugs are inhaled as gases (e.g. volatile anesthetics), aerosols of solution or powder
Very rapid onset of action, but of limited use: e.g. anesthesia treatment of asthma, and other respiratory diseases; substance abuse; etc.
Topical application:
(1) Mucous membranes: conjunctiva,nasopharynx,vagina
(2) Skin (drug must be highly lipid soluable)
Transdermal therapeutic systems (TTS):
A 4-layer delivery system applied toskin--slow release of potent lipid-soluble drugs for prolonged systemic effects
Factors affect the rate and extent of drug distribution into tissues:
1) Regional blood flow to the tissue
2) Permeability of membrane barriers to the drug
3)Extent of plasma protein and tissue binding.
4) Regional difference in PH.
5) Presence of transport mechanisms
Capillary endothelium is a _________ barrier to a drug
freely permeable
Cell membrane as drug barrier
lipid soluble drugs pass freely.
Blood-brain barrier as drug barrier
Entry of polar drugs into the CNS is greatly restricted; highly lipid soluble drugs enter readily.
Blood-brain barrier consists of __________
Tight junctions between capillary endothelial cells; capillaries are also covered by glial cells.
Placenta as barrier for drugs
Drugs cross the placenta, primarily by simple diffusion
• Lipid-soluble, non-ionized drugs readily enter the fetal blood from the maternal circulation and expose the fetus to drugs.
Drug reservoirs
1)Plasma proteins
2) Cellular reservoirs: Tissues e.g., skeletal muscle, heart; liver.
3)Fat: Important reservoir for lipid soluble drugs, e.g. thiopental.
4) Bones: tetracycline and heavy metals,e.g.,lead.
Many drugs are bound to plasma protein, especially plasma albumin for_____ drugs and a 1- acid glycoprotein for ______drugs.
acid/ basic
plasma protien binding is __________
Reversible, non-covalent binding
Plasma protein binding alters drug concentration in tissues and at its site of action. It also limits _____________of drug. It does NOT affect ________ or biotransformation.
glomerular filtration /renal tubular secretion
Volume of distribution (Vd)
Total amount of drug in body/ Concentration of drug in plasma.
Vd is
the apparent volume of fluid required to contain all of the drug in the body at the same concentration as in plasma
The total volume of fluid compartment of the body is approximately _____ . These compartments include plasma water ____, interstitial fluid _____, and the intracellular fluid _____.
40L/5L/10–15L/20L
Vd is _____when the drug is highly concentrated in tissues (e.g. high lipid-solubility; tissue binding).
large
Vd is ______when the drug is highly concentrated in plasma (e.g. bound to plasma protein).
small