AMDE Flashcards
How a drug moves from its site of
administration into the bloodstream
Absorption
Movement of the drug between blood and
tissues
Distribution
Conversion of drugs into more hydrophilic
metabolites
Metabolism
Removal of drugs and/or metabolites from
the body
Excretion
Where does the majority of the absorption into blood stream from GI tract occur?
Small intestine
If the molecule is larger, it will absorb more or less?
Less movement
Do ionized or non-ionized molecules move better?
Non-ionized
Does increased lipid solubility increase or decrease movement?
Increase movement
Does increased protein binding increase or decrease movement/
Decreases movement
To pass through lipid membranes, drugs
have to be ________
non-ionized (aka: uncharged)
To be water soluble, drugs need to be
_________
ionized (aka: charged)
Most drugs are either ____ acids or _____ bases
Weak acids or weak bases
What is the protonation and ionization of an acid drug in an acidic ph?
non-ionized; protonated
What is the protonation and ionization of an acid drug in an basic ph?
Ionized, deprotonated
What is the protonation and ionization of an basic drug in an acidic ph?
Ionized, protonated
What is the protonation and ionization of an basic drug in an basic ph?
Non-ionized; deprotonated
_____ are non-ionized (fat soluble)
when protonated, ionized (water soluble) when
deprotonated
Acids
_____ are non-ionized when deprotonated,
ionized when protonated
Bases
The ___ is the pH at which there are
equal amounts of protonated and
nonprotonated
pKa
pH __ pKa Protonated equals non-
protonated
pH=pKa
pH __ pKa Protonated form predominates
pH < pKa
pH ___ pKa Non-protonated form predominates
pH > pKa
Only the ________ form of a drug can
readily cross the lipid membrane
non-ionized
Ion Trapping Because ionized molecules (drugs) can’t cross the membrane, can effectively trap them and enhance excretion Principle is very useful in toxicology cases
Ion Trapping
Typically the ____ form of the drug is lipid soluble meaning it readily absorbs into bloodstream
Non-ionized
Will a more acidic or basic local anesthetic get absorbed in an abcess better?
Acidic
According to Fick’s law, what 2 things are proportional to the rate of absorption?
Concentration of drug
Surface Area
Movement of a drug from its site of administration into the central compartment
Process of dissolution and diffusion
Bioavailability more important
Absorption
Fraction of drug that reaches the systemic
circulation intact
IV = 100%
Affected by route of administration
Bioavailability (F)
Fraction of drug in blood that is irreversibly
removed during one pass through the liver
Hepatic extraction ratio
Extent to which a drug is removed by the liver
during its first pass in the portal blood through
the liver to systemic circulation
First pass clearance
Drugs with low hepatic extraction will have
___ first pass clearance
low first pass clearance
\_\_\_\_ extraction Low first pass clearance Change in hepatic enzymes won’t have significant effect on first pass clearance - Increased drug in bloodstream
Low extraction
\_\_\_\_\_ extraction High first pass clearance Changes in enzyme function will have large effect on first pass effect - Decreased drug in bloodstream
High extraction
_____ route of administration:
Hits digestive system before going to bloodstream
Enteral
_____ route of administration:
-Bypasses digestive tract: Decreases first pass effect
Parenteral route
\_\_\_\_\_ administration ADVANTAGES Most common route Safest Easiest Most economical DISADVANTAGES Limited absorption Emetogenic potential Subject to first pass Absorption may be affected by food or other drugs Irregularities in absorption or propulsion
Enteral administration
\_\_\_\_\_\_ Administration ADVANTAGES Not subject to first pass Most rapid onset Ability to titrate Doesn’t require cooperation DISADVANTAGES Greater patient discomfort Requires additional training to administer Concern for bacterial contamination Injection-associated risks Extravasation Intra-arterial injection Limb loss
Parenteral Administration
\_\_\_\_\_ Administration Absorption governed by: Surface area for absorption Blood flow to site of absorption Dosage form administered Ionization status (lipo- vs. hydrophilic) Concentration at site of absorption
Oral Administration
Drugs destroyed by gastric secretions, low pH, or that cause gastric irritation Risk of bezoar formation Delayed Release
Enteric coating
F = 100%● Immediate onset, Bypasses GI absorption
● Best for emergencies
►Intravenous (IV):
75-100%● Irritating drugs given this route
● Not as rapid response as IV
● Depot preparations (sustained release) ie., suspensions, ethylene glycol,
peanut oil- all slow down absorption.
►Intramuscular (IM):
: 75-100%● Slower absorption than IV or IM
● Little risk of intravascular injection
● Examples: Insulin, Mechanical pumps, heparin (DVT prophylaxis)
►Subcutaneous (SQ)
:● Small amounts of drug
● Tuberculosis skin test, Local anesthetics
► Intradermal (ID)
5-100%● Almost as rapid as IV. (Method of abuse)● Delivered directly to lung (good selectivity)- minimal systemic side-effects.
● Gases, aerosols of solutions & powders -good for respiratory conditions.
► Inhalation:
: 5-100%● Vasopressin for tx of diabetes insipidus, calcitonin (osteoporosis).
● Method of drug abuse.
► Intranasal
● Subarachnoid space of spinal cord – into CSF (Lumbar puncture- Baclofen
in MS, regional anesthetic in delivery, morphine drip)
Intrathecal/Epidural:
Skin, oral mucosa, sublingual, rectal (avoids 50% of 1st pass metab)
● When local effect is desired-but can provide systemic effects.
● Sublingual (100%), rectal (50%) bypasses liver- good bioavailability.
● Transdermal Controlled Release- Scopolamine, nitroglycerin, nicotine,
estrogens (BCP), fentanyl.
Topical:
Perio specific uses: doxycycline(Atridox); minocycline(Arestin)
Subgingival:
The administered drug leaves the blood stream and enters other “compartments” Dependent upon: Cardiac output Capillary permeability Blood flow
Distribution
What are the 3 things that distribution is dependent on?
Cardiac output
Capillary permeability
Blood flow
The the heart, liver, kidney, adipose tissue, and brain; rank the amount of blood flow from most to least?
Kidney Liver Heart Brain Adipose tissue
____ compartment
Well perfused organs and tissues (heart, blood, liver, brain, kidney). Drug equilibrates rapidly.
Central
_____ compartment
Less well perfused organs/tissues (adipose, skeletal muscle, etc.)
Peripheral
______ compartments
CSF, CNS, pericardial fluid, bronchial secretions, middle ear
Special compartments
What protein binds acidic drugs?
Albumin
What protein binds basic drugs?
Alpha-glycoprotein
Distribution of a drug that moves From site of action into other
tissues or sites
Redistribution
Lipid solubility Clinical effects Efflux transporters Inflammatory processes
Blood brain barrier
Volume of fluid in which a drug would need to be dissolved to have the same concentration in plasma. Doesn’t represent “real” volume Relationship between dose and resulting Cp
Volume of Distribution (Vd)
Lipophilic drugs tend to have a ___ Vd
larger
Protein bound drugs have ____ Vd
lower
Removal Either metabolized/biotransformed and eliminated or excreted unchanged Must be water-soluble to be removed Lipid solubility good for absorption and distribution, bad for excretion Process of biotransformation Converts drugs into polar metabolites Lipophilic into hydrophilic Liver does the heavy lifting P-450
Metabolized
What organ does the majority of metabolism?
Liver
What cytochrome system does the majority of metabolism in liver, kidneys, and intestines?
P-450
Phase ___ of metabolism
Catabolic
Exposes functional group on parent compound
Usually results in loss of pharmacologic activity
Activation of prodrugs
Phase 1
IF there is a drug inhibitor that inhibits drug binding to enzyme, is there an increased or decreased drug response?
Increased drug response
IF there is a drug inducer that induces drug binding to enzyme, is there an increased or decreased drug response?
Decreases drug response
Phase \_\_\_ of metabolism Occurs after functional groups are exposed Anabolic: adds water soluble molecules to structure Much less interpatient variability Major reactions Glucuronidation Glutathione conjugation Sulfate conjugation Acetylation
Phase II
Removal of unchanged drug
Kidney, lung, feces – primary routes
Polar compounds > lipid soluble
compounds
Excretion
During excretion, is the lipid or water soluble more prevalent?
Water soluble
3 processes Glomerular filtration Active tubular secretion Passive tubular reabsorption Dependent upon renal function Only unbound drug filtered Non-ionized weak acids and bases passively reabsorbed Alkaline urine “traps” ionized, acidic molecules, increases excretion
Excretion
Unabsorbed orally administered meds; the metabolites are excreted in the ____
Bile
_______ is main factor that determines rate of passive transport
Lipid solubility
Only _____ drugs can diffuse across lipid membrane
uncharged
