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What are the three routes of drug administration
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What is the enteral route of administration and what are some examples
- drug is absorbed from the gastrointestinal (GI) tract
- Includes oral, sublingual, Buccal and rectal
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What is the prescription abbreviation for "take by mouth"
PO
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How is the sublingual administration absorbed
through the oral mucosa
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Buccal administration is placed
between the gums and the inner lining of the cheek
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When is rectal administration advised
When the drug is too irritating for the stomach, the patient is vomiting or can't swallow or local effect on the colon
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What is the abbreviation for rectal admininstration
PR- per rectum
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What is parental administration and what are the five routes
- delivers drugs via a needle
- intravenous, intramuscular, subcutaneous, intradermal, and intrathecal
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What is the fastest route of administration
Intravenous- directly in the vein
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What is an example of Intramuscular administration
Hep B vaccine
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Describe the Subcutaneous administration and what are some examples
- into connective tissue under the skin.
- Drug cannot be irritating. Small volumes only
- Ex. dental anesthetics, Insulin
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Describe the Intradermal administration and what are some examples
- directly into dermis (layer beneath the epidermis).
- Ex. Allergen testing, tuberculin skin test
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Describe the Intrathecal administration
delivered into spinal fluid, used for spinal anesthesia
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Describe Topical Administration and what are the routes
- administered directly to surface of body where action is desired. Includes skin, mucous membranes of the gingiva, eyes, ears, gingival crevice of teeth, mouth and throat
- Subgingival, Inhalation, Opthalmic, Otic, Intranasal, Transdermal, Epicutaneous
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Explain the inhalation method of administration and what are some examples
- inhaled through mouth or nose
- inhaler for asthma, rhinitis, diabetes (inhaled insulin), general anesthesia, and moderate sedation with nitrous oxide/oxygen
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Describe otic admininstration
drops and irrigations for local conditions of the ear
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Describe Intranasal administration
nose sprays and drops for local and systemic effects
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Describe Epicutaneous administration and an example
- directly on the skin
- Dental topical anesthetic
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Pharmacokinetics is the
study of drug movement throughout the body, including how a drug gets to the site of action, and how the body handles medications
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Pharmacokinetics is determined by what four processes
- Absorption
- Distribution
- Metabolism (biotransformation)
- Elimination
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Absorption and Distribution is
how a drug gets to the site of action
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Metabolism (biotransformation) is
what the body does to the drug
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Elimination or Excretion is
how drugs move through and exits the body
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The Ultimate goal of pharmacokinetics is
for the drug to reach the site of action (through the bloodstream) in an adequate concentration to produce desired effect prior to elimination
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Drugs are Better absorbed in the small intestine than the stomach due to
the larger surface area
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Absorption is getting the drug ___________ in order to get the drug to the _______ where it will have its effect
- into the blood
- organ or tissue
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To get into the blood, a drug must pass through many _______
cell membranes or tissue barriers
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Cell membranes are composed of two layers of lipids called the __________
biphospholipid layer
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_______ is one of the most important determinants of the pharmacokinetic characteristics of a drug
Lipid solubility
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Lipophilic drugs pass through the cell membrane by ________
diffusion
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Hydrophilic drugs either pass through the _________ or are ________
- aqueous pores of the membrane
- kept outside
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What are the types of cell membranes to get into the blood and what drugs uses which
- Intestinal mucosa–blood barrier: orally administered drugs
- Oral mucosa–blood barrier: sublingually or buccally administered drugs
- Placental barrier: acts as filter to some substances getting into the blood of the fetus
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What are the Types of cell membranes in the body from the blood to the site of action
- Blood-tissue barrier: the membrane between the blood and the organ/tissue of the site of action
- Blood-brain barrier: cell membrane of the brain is very lipid which allows lipid-soluble drugs (ex. general anesthetics, alcohol, anti-anxiety drugs) to go through, but keeps out water soluble drugs
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What are the four processes of absorption
- 1.Passive diffusion
- 2.Facilitated diffusion
- 3.Active transport
- 4.Pinocytosis
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Explain passive diffusion
- -Most drugs follow this route
- –Moves from the higher concentration outside the cell to lower concentration inside the cell
- –No energy is used in passive diffusion
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Explain active transport
- involves the use of carrier proteins against the concentration gradient.
- Energy is used.
- Not common
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Explain pinocytosis
- involves the engulfment of fluids or particles by a cell.
- Cell membrane traps the substance, forms a vesicle that detaches and moves into the cell.
- Involves energy use
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Only the ________ form of the drug is usually ______ soluble and readily crosses the cell membrane (absorbed).
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Pka is the
pH that produces 50% ionized and 50% nonionized molecules of the drug
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How much of the drug is in the ionized or the nonionized form depends on the _______ and _________
pKa of the drug AND the pH of the solution that the drug is in
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What does it mean for a drug to be ionized
charged/water soluble (not going to be absorbed by the cell membrane)
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So most nonionized drugs (including the weak acids) are transported to the ________ where they are absorbed
small intestine
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What are the four factors that influence the rate of absorption
- 1.Blood flow to the organ– more blood flow equals more absorption
- 2.Surface area – larger surface area of the small intestine equals more absorption
- 3.Salt form of the drug – salt form of the drug enhances absorption and stability. Ex. – local anesthetics are combined with an acid to form a salt, allowing them to be combine with sterile water
- 4.Route of drug administration – enteral vs. parenteral. With enteral, food can be a factor
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Local anesthetics are _______ but all anesthetics are ______ prior to injection
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The _____________ determines whether the anesthetic will be charged or uncharged
pH of the surrounding environment
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From the bloodstream drugs taken orally goes into the _______ where it is _________ which is called ________
- liver
- partially or totally biotransformed
- first-pass effect
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What is the Distribution Phase
the time from when a drug is absorbed from the GI tract into the bloodstream, and is distributed (transferred) throughout the body fluids to tissues and organs
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While in the bloodstream, drugs have the opportunity to either exist in _________ or ________
- the free form
- Be reversibly bound to the many proteins, primarily albumin, which is referred to as plasma protein binding
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Drugs that are plasma protein bound are in ______
an inactive state
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Excretion is elimination through the ________ and out of the body in the _____.
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Drugs are eliminated either as the original parent compound or as a _____
drug metabolite
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_________drugs are easily excreted by the kidneys
Water-soluble (hydrophilic)
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To be readily eliminated from the body, a drug must be in a _________ form and the ______ is the primary site of drug biotransformation
- water-soluble/polar (ionic)
- liver
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After the drug is biotransformed, it is referred to as a
metabolite
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What are PRODRUGS
- defined as oral drugs that are inactive and become active only after metabolism in the liver
- Ex. codeine
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Describe Phase I of Biotransformation
The liver uses enzymes (called cytochrome P450 enzymes) to make lipid soluble drugs more water soluble (so they can be excreted). Some drugs may get excreted after Phase I, some will get reabsorbed from the kidneys back into the blood and go to Phase II
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Describe Phase II of Biotransformation
The drug or metabolite from phase I is conjugated or linked with highly water soluble compounds such as glucuronic acid to make it more water-soluble so that it can be excreted
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_______ is the most common enzyme that metabolizes many drugs in dentistry
CYP3A4
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Substrate
The drug being metabolized
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Factors that may influence an individual’s ability to metabolize drugs include
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Most drugs follow _________ of elimination
first-order kinetics
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Explain First-order kinetics
As the drug is eliminated from the body, the concentration of the drug in the plasma will decrease equally over time
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Zero-order kinetics
Elimination of a drug is at a constant rate that is not dependent upon its concentration
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HALF-LIFE
Time it takes for the concentration of the drug in the blood to fall to half (50%) of its original value
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The larger the t½ value, the longer it takes for
a drug to be eliminated from the body
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Drug delivered intravenously has _______ bioavailability
100%
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Loading dose
A high dose of a drug is given initially to rapidly establish a therapeutic plasma drug concentration
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Maintenance dose
Lower doses used to maintain a desired drug level at a steady state plasma concentration
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Therapeutic range
Concentration of the drug in the plasma between the MEC (minimum effective concentration) and the toxic concentration
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Drug clearance
Capacity of the body to remove a drug
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The site where such drug attachment takes place is termed the
receptor
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Receptors are usually a ________. Drugs attach by ______ to the receptor site
- protein
- Van der Waal’s forces (ionic bonds)
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An agonist is
a drug that rapidly combines with a receptor to initiate a response and rapidly dissociates or releases from the receptor
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An antagonist is
a drug that binds to the receptor but does not dissociate and has no positive response and no efficacy. It blocks the reaction of an agonist.
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A partial agonist is
a drug that slowly binds to the receptor and produces a mild therapeutic response (slight efficacy) when administered alone but may inhibit the action of an agonist when given concurrently, acting like an antagonist
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Graded dose
–Observing and measuring the patient’s response obtained at different doses of the drug
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Threshold dose
minimum dose of a drug needed to produce a therapeutic/measurable response
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Efficacy
Ability to produce a therapeutic effect
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Ceiling effect is reached when
the therapeutic response cannot be increased with a higher dose of the drug
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Therapeutic effect
- Desirable/beneficial pharmaceutical effect of that a drug exerts at the target site of action
- Ex. the therapeutic effect of aspirin is pain relief and fever reduction
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Therapeutic index is the
ratio of a drug’s toxic dose to its therapeutic dose
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The effective dose or _____ is the _______
- (ED50)
- the drug dose that produces 50% of the maximum possible response
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Adverse drug event (ADE)
Injury resulting from medical intervention related to a drug
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What are some examples of Type A adverse drug events
- –Providing the correct drug but the wrong route
- –Drug interactions
- –Predictable and preventable
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What are some factors of Type B adverse drug events
- –Dose independent
- –Individual’s response and genetic differences
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Adverse drug reactions (ADR)
Undesirable drug effects
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Generally, adverse effects are
dose related
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Toxic Effect
- Defined as harmful effects associated with drug overdose
- dose dependent and predictable
- Nontarget organs involved
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Idiosyncrasy
the unexplained, uncharacteristic response to a drug caused by hereditary factors or genetic differences
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Allergic response is
when a foreign substance, an antigen (drug) causes the body to produce antibodies in response to that antigen
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Mutagenic Reaction
Caused by drug-induced damage to DNA
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Teratogenic Reaction
Refers to the drug-induced damage that develops in the fetus
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Tachyphylaxis
very rapid development of tolerance
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