Pharmacology Study Guide

1. Lecture 1: Introduction to Pharmacology

a. Pharmacology
i. Study of medicines
ii. The core of patient care, no matter the nursing specialty
iii. Four Basic Terms of Pharmacology
1. Drug: any chemical that can affect living processes
2. Pharmacology: the study of drugs and their interactions with living systems.
Encompasses the study of the physical and chemical properties of drugs as well as
their biochemical and physiological effects. It includes the knowledge of drug
absorption, distribution, metabolism, and excretion
3. Clinical Pharmacology: the study of drugs in humans. Includes the study of
drugs in patients as well as in healthy volunteers (during new drug development)
4. Therapeutics: also known as pharmacotherapeutics; known as the use of drugs
to diagnose, prevent, or treat disease or to prevent pregnancy. Or simply the
medical use of drugs
iv. Responsibility of the Nurse
1. Know the drug being administered
a. Expected therapeutic reaction
b. Possible side effects and adverse reactions
2. Any known allergies to drugs
3. 6 rights (patient, drug, dose, route, time, documentation)
4. What other drugs are contraindicated
5. Understand condition being treated
6. Drug/drug or drug/food interactions
7. Manage toxicity
v. “It is ethically and legally unacceptable for the nurse to administer a drug that is
harmful to the patient, even though the medication has been prescribed by a licensed
provider and dispensed by a licensed pharmacist”
b. The Big Three: Effectiveness, Safety, and Selectivity
i. Effectiveness is the most important property a drug can have
ii. Safety: a safe drug is defined as one that will not cause harmful effects – even if
administered in high doses and for prolonged periods of time. There is no such thing as
a safe drug
iii. A selective drug is one that elicits only the response for which it is given and would not
produce side effects. There is no such thing as a selective drug: all medications cause
side effects
c. The Therapeutic Objective
i. The objective of drug therapy is to provide maximum benefit with minimum harm
d. Legal Terminology
i. Misfeasance – negligence; giving the wrong drug or the wrong dose resulting in the
clients death
ii. Nonfeasance – omission; omitting a drug dose which results in the clients death
iii. Malfeasance – giving the correct drug, but the wrong route, which results in the clients
death
e. Application of Pharmacology in Patient Care
i. Preadministration Assessment

Pharmacology 1
 1. Three basic goals:
a. Collect baseline data needed to evaluate therapeutic and adverse responses
b. Identify high-risk patients
c. Assess the patients capacity for self-care
ii. Dosage and Administration
1. Must know that:
a. Certain drugs have more than one indication, and dosage may differ
depending on which indication the drug is used for
b. Many drugs can be administered by more than one route, and dosage may
differ depending upon the route selected
c. Certain intravenous agents can cause severe local injury if the line through
which they are being infused becomes extravasated
d. Basic Guidelines:
i. Read med order carefully. If unclear verify with the prescriber
ii. Verify identity of patient by comparing the name on wristband
with name on drug order or MAR
iii. Read med label carefully. Verify identity of drug, amount of drug,
and suitability for administration by intended route
iv. Verify dosage calculations
v. Implement any special handling the drug may require
vi. Don’t administer any drug if you don’t understand the reason for
its use
f. Drug Names
i. Chemical
1. Exact description of the drug’s composition
2. Chemical structure
ii. Generic
1. Official name (nonproprietary name)
2. Given by the manufacturer who first develops the drug before the drug is
approved
3. Only one generic name
iii. Trade/Brand
1. Name in which the manufacturer markets the drug (also known as the proprietary
name)
2. Created with the intention that they be easy for nurses, physicians, pharmacists,
and consumers to recall and pronounce
g. Federal Legislation: public is protected from drugs that are impure, toxic, ineffective, or not
tested before public sale
i. Recent study estimated the cost to bring a new drug to market at $800 million
ii. Takes an average of 6-12 years to get FDA approval for new drugs
h. Food and Drug Administration (FDA) : Stages of Approval
i. Preclinical Testing (in animals): Toxicity, Pharmacokinetics, Possible Useful Effects 
Investigational New Drug (IND) Status 
Clinical Testing (in humans): Phase 1 (Subjects: healthy volunteers. Tests: metabolism,
pharmacokinetics, and biologic effects)  Phase 2 (Subjects: patients. Tests: therapeutic
utility and dosage range)  Phase 3 (Subjects: patients. Tests: safety and effectiveness)
 Conditional approval of New Drug Application (NDA)  Phase 4 (postmarketing
surveillance)

Pharmacology 2
 1. Preclinical Investigation
a. Extensive laboratory research
b. Studies done on human and microbial cells cultured in the lab
c. Studies performed on animals to look at drug’s effectiveness at different
doses and to look for adverse effects
d. May take up to 5 years
e. For every 5,000 agents that are submitted for preclinical testing, only 5
will make it for clinical review
2. Clinical Investigation
a. Longest part of the drug approval process
b. Consists of “clinical phase trials”
i. Researchers try to determine:
1. Proper dosage
2. Effectiveness
3. Possible adverse effects
4. If the drug worsens other medical conditions
5. Drug interactions
a. At the conclusion of the clinical trials, the company
will write a NDA
c. Studies are first done on healthy volunteers
d. Studies are then done on a select group of people with a particular disease
e. Takes 2-10 years to complete this step
3. Review of the New Drug Application
a. FDA is permitted 6 months to initially review the application
i. If approved, the application moves to the final stage
ii. If there are concerns, the pharmaceutical company will be required
to address them
b. The average NDA Review time is 17-24 months
i. The NDA may contain over 100,000 pages
4. Post Marketing Surveillance
a. Purpose is to survey for harmful drug effects in a larger population over a
longer period of time
i. History of Drug Regulation and Standards
i. 1906: The Pure Food and Drug Act gave the government the power to control the
labeling of medicines
ii. 1912: Sherley Amendment prohibited the sale of drugs labeled with false therapeutic
claims
iii. 1938: Food, Drug and Cosmetic Act
1. Prevented marketing of drugs not thoroughly tested
2. Required a “New Drug Application” be submitted to the FDA prior to marketing
3. Required all new drugs undergo testing for toxicity
iv. 1962: Harris-Kefauver Amendment
1. Drugs must be proved “effective” before marketing
2. First law to actually demand that drugs offer some benefit
3. Established rigorous procedures for testing new drugs
v. 1970: Controlled Substance Act
1. Set rules for manufacture and distribution of drugs considered to have potential
for abuse

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 2. Defines categories into which controlled substances are placed
a. Schedule I, II, III, IV, and V
i. Schedule I: no accepted medical use in the US and high potential
for abuse (Heroin and LSD)
ii. Schedules II-V: have acceptable use but also potential for abuse
1. Schedule V drugs have less potential for abuse than
Schedule II drugs
vi. 1992: Accelerated Approval for Drugs for AIDS and Cancer
1. FDA recognized the need to permit accelerated approval of Drugs for AIDS and
cancer
2. Drugs could be approved for marketing prior to completion of phase III trials
3. Rigorous follow-up studies must be in place during phase IV
vii. 1994: Dietary Supplement Health and Education Act
1. Requires clear labeling of dietary supplements
viii. 1997: FDA Modernization Act
1. Allowed the FDA to hire more employees and restructure it’s organization to
more efficiently handle the processing of huge numbers of new drug applications
2. FDA hired nearly 700 new employees
3. Modernization Act among with other issues, granted financial incentives to do
pediatric research on existing drugs
a. However they did not “demand” pediatric research
4. Allowed fast track approval for other serious and life-threatening illness (besides
just AIDS and cancer)
5. Allowed drug companies to give prescribers journal articles and information
regarding “off-label” uses of drugs
a. Prior to the Modernization Act, companies could not discuss “off-label”
use
ix. 2002: Best Pharmaceuticals for Children Act (BPCA)
x. 2003: Pediatric Research Equity Act (PREA)
1. Both laws were designed to promote much-needed research on Pediatric Drug
Research
2. BPCA offers a 6-month patent extension to manufacturers who evaluate a drug
already on the market for its safety, efficacy and dosage in kids
3. PREA gives the FDA the power to “require” drug companies to conduct pediatric
clinical trials on new medications that might be used on kids
j. FDA Pregnancy Categories
i. Category A: no risk to fetus
ii. Category B: assumed little or no risk. Adverse effect may have been evident on animals,
but not on humans
iii. Category C: adverse effect on animals, but not adequate studies on humans
iv. Category D: risk to human fetus has been proven
1. Used in life threatening conditions
2. Risk versus benefit of the drug must be determined
v. Category X: drug should be avoided during pregnancy
k. New Drug Patent
i. The original “drug developer” has exclusive rights to name and market a drug for 17
years after a new drug application is submitted to the FDA
ii. The amount of time spent in approval is subtracted from the 17 years

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l. Brand Name vs. Generic Drugs
i. Generic drugs (store brands) are cheaper because manufactures don’t have to do all the
clinical development and testing
ii. Generic drugs have the same active ingredient. However, generic drugs may have
different fillers and binders that alter the drugs efficacy by altering the absorption rate
and therefore the generic may require more time to take effect
iii. Generic drugs have to be FDA approved:
1. If the serum concentration falls within 80% and 125% of the brand drug, it is
considered equivalent
iv. Brand Name Drugs should be preferred when ordering:
1. Anticonvulsants
2. Anticoagulants
3. Lanoxin for CHF
4. Large doses of aspirin for Rheumatoid Arthritis
m. Classification of Drugs
i. Drugs are categorized by similar characteristics
ii. Drug classification may indicate:
1. The effect of the drug on the body system
2. The symptoms the drug relieves
3. The drugs desired effect
iii. Drugs may be in classifications such as:
1. Cardiovascular agents
2. Respiratory agents
3. Gastrointestinal agents
iv. Each class of drugs contains agents that are prescribed for similar types of health
problems:
1. Cardiovascular agents:
a. Antianginal
b. Antihypertensives
c. Anticoagulants
v. The physical and chemical composition of drugs within a class is not necessarily the
same:
1. The drug may do the same thing, but may have a different mechanism of action
a. To treat hypertension, you may use: diuretics, calcium channel blockers,
or beta blockers
vi. A drug may be in more than one category:
1. Ibuprofen is categorized as: antipyretic, anti-inflammatory agent, and analgesic
n. Over The Counter Medications
i. Americans spend about $20 billion annually on OTC drugs
ii. More than 60-95% of all illnesses are initially treated with OTC products
iii. The average home medicine cabinet contains 24 OTC preparations
iv. FDA is in the process of making many drugs OTC
v. FDA is working to standardize the labels and provide better information for OTC drugs
o. Terminology
i. Addiction: continued use of a specific psychoactive substance despite physical,
psychological, or social harm

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 ii. Physical Dependence: nervous system adapts to the continual presence of the drug.
Body begins to believe that it is normal and necessary for the drug to be present and
“withdrawal” will result if the agent is not present
iii. Withdrawal (abstinence syndrome): physical effects such as nausea, convulsions that
result from a drug being stopped
iv. Psychological Dependence: intense, overwhelming desire or craving for a drug
1. Not a physical addiction, no physical discomfort after the agent is discontinued
2. The intense craving may continue for months or even years after the agent is
discontinued
3. Relapses are common
v. Tolerance: body adapts to a substance
1. Over time higher doses of the agent are required to produce the same initial effect
2. Tolerance is not a sign of addiction or abuse, but rather a natural consequence
vi. “Cross-Tolerance”: possible with drugs that are closely related
1. People who have developed a tolerance to alcohol, will show tolerance to other
CNS depressants

*Know commonly abused substances (Table 39-1, p. 421 and Table 39-2, p. 423)

2. Lecture 2: Pharmacokinetics and Pharmacodynamics

a. Nature of Drug Actions:
i. Two Phases:
1. Pharmacokinetic Phase
a. Absorption
i. Passage of the drug molecule into the bloodstream
ii. Drugs are absorbed through the:
1. Skin
2. Mucous membranes
3. GI tract lining
4. Respiratory tract
iii. Bioavailability:
1. The percentage of the administered drug dose that reaches
the systemic circulation
a. Bioavailability of oral drugs is always less than
100%
2. Oral doses may need to be 3-5x larger than the IV dose of
the same drug due to the bioavailability
iv. Factors that will affect absorption:
1. IV drugs are already there
2. Enteric coated drugs:
a. Resist disintegration in the gastric acid of the
stomach
b. Disintegration does not occur until these drugs
reach the small intestine
i. More alkaline environment
c. Enteric coating is used for:
i. Protecting drugs from acid and pepsin in the
stomach

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 ii. Protecting the stomach from drugs that can
cause gastric discomfort
d. Disadvantages of enteric coating:
i. Absorption time will vary
ii.  onset of these drugs will be reliant on the
gastric emptying time
iii.  may be within minutes, or hours
iv. Enteric coatings may fail to dissolve
v.  medications will pass right through the
GI system
vi. Is the stomach is alkaline the medication
may dissolve while in the stomach
3. Sustained Release preparations
a. Tablets or capsules filled with tiny spheres that
contain the actual drug
b. The spheres have coatings that dissolve at variable
rates
c. Some spheres dissolve more slowly, releasing the
medication throughout the day
4. Rate of dissolution
a. Elixirs and syrups will absorb faster than pills and
tablets
b. Disintegration: breakdown of a tablet into smaller
particles
c. Dissolution: dissolving of the smaller particles in
the GI fluid before absorption
d. Rate limiting: the term used to define the time it
takes for the drug to be available for absorption
e. Tablets are not 100% drug ----- they contain fillers
i. Fillers allow drugs to have various colors,
sizes, and shapes
ii. Fillers have ingredients that allow for better
dissolution and absorption
5. Body surface area
a. There is a greater surface area in the small intestine
than the stomach
b. Most drugs given po will absorb from the small
intestine
6. Blood flow
a. Drugs are absorbed faster from sites where blood
flow is high
b. There is more blood flow to the deltoid muscle than
the gluteal muscle
c. Subcutaneous tissue has fewer blood vessels than
muscle
d. Sublingual, buccal, and rectal medications absorb
fast
7. pH partitioning

Pharmacology 7
 a. drugs will have a greater desire to move across the
membrane is they will be ionized on the other side
b. for example: a weak acid will move faster over to
an area that is alkaline
8. Drug-Drug or Drug-Food interactions
a. Tetracycline will not be absorbed is given with food
b. Some drugs are destroyed by digestive enzymes in
the small intestine
i. Insulin and growth hormones
ii. These drugs are given by injection
c. Some drugs are inactivated by hydrochloric acid
i. Penicillin G
ii. Given IM
v. Time of administration will affect absorption:
1. Most po meds will absorb more rapidly when given
between meals
2. Food, milk, and antacids may alter the pH, thus altering
absorption
3. Don’t usually give milk or antacids 2 hours before and 1
hour after medication administration
a. Unless otherwise directed from drug book
4. Conditions at the absorption site:
a. Poor circulation as a result of shock or
vasoconstriction drugs will decrease the blood flow
b. Thus absorption will be hampered
vi. Digestive motility will affect the speed of absorption:
1. If the function of the small intestine is altered by
drugs/diseases….then absorption will be altered
a. Such as hypermotility of the GI tract
2. Pain, stress, and foods that are solid, hot and fatty will slow
down gastric emptying time
3. Drugs remain in the stomach longer
4. If drugs remain in the longer, than more of the drug may be
absorbed
5. Exercise will decrease blood flow to the stomach
a. Blood will be shunted to the peripheral muscles
6. Decreased blood flow to the stomach will decrease
absorption of po medications
b. Distribution
i. The rate and extent of distribution depends on the:
1. Blood flow to tissues and organs
a. Abscesses and solid tumors
i. Difficult to deliver medication to either
ii. No blood supply to the inner mass of an
abscess
iii. Solid tumors have a huge blood supply to
the outer edges but very little blood supply
to the core

Pharmacology 8
 iv. Poor circulation to the feet of a diabetic
patient will alter the availability of a drug to
that site
v. Poor circulation to an area of a badly burned
area will alter the availability of a drug to
that site
2. Ability of the drug to exit the vascular system
a. Drugs in the vascular system leave the blood in
capillary beds
b. Most drugs leave the vasculature by passing
through the pores in the capillary wall
i. Passing between capillary cells
3. Ability of a drug to enter the cells
ii. Protein Binding:
1. Most drugs bind to the protein (albumin) somewhat in your
bloodstream
2. The percentage of the drug molecules that will bind to the
protein is determined by the strength of the attraction
between the albumin and the drug
3. The “free drug” is the drug that creates the action desired
4. As the free drug is metabolized and excreted, the protein
bound drug is then released into the blood stream
5. Decreased albumin level is expected in:
a. Elderly, those with liver disease, and those with
malnutrition
6. Potential for increased drug activity or toxicity
7. Plasma protein/albumin levels are checked
8. When two highly protein bound drugs are given together
(Lasix and Ibuprofen) they compete for the protein sites
9. This causes more free drug to be released than anticipated
a. Thus you get higher blood concentrations of one of
the drugs -----
i. possible toxicity
iii. Anatomical Barriers to Distribution:
1. The brain and the placenta provide an anatomical barrier
that inhibits many chemicals and medications from entering
2. Blood-Brain Barrier
a. Tight junction between the cells
b. So tight that they prevent drug passage
c. Only drugs that are lipid soluble, or have a transport
mechanism can pass
d. Some meds such as sedatives and anticonvulsants
readily pass the BBB
e. Most antitumor meds will not pass the BBB making
brain cancer difficult to treat
3. Fetal-Placental Barrier
a. The membranes of the placenta separate the
maternal circulation from the fetal circulation

Pharmacology 9
 b. This membrane does NOT constitute an absolute
barrier
c. Lipid soluble and non-ionized agents easily pass
across the membrane
iv. Accumulation of Medications:
1. Some tissues have the ability to accumulate and store drugs
after absorption
a. Bone marrow – teeth – eyes – adipose tissue
2. Valium and lipid soluble vitamins (A, D & K) will store in
the adipose tissue
3. Tetracycline binds to calcium salts and will accumulate in
the bones and teeth
c. Metabolism
i. Biotransformation – enzymatic alteration of drug structure
1. When drugs are biotransformed, the consequences may be:
a. Accelerated renal excretion of drugs
i. Most drugs are inactivated by the liver
enzymes and are then transformed to
inactive metabolites or water soluble
substances for excretion
ii. The kidneys cannot excrete lipid soluble
drugs so if the drugs are lipid-soluble, the
liver will metabolize the lipid-soluble drug
to a water-soluble substance for renal
excretion
b. Drug inactivation
c. Increased therapeutic action
i. Some drugs are transformed into active
metabolites
ii.  They now have an increased
pharmacologic response
iii. Codeine undergoes transformation to
morphine  greater pain relief after
transformation
d. Activation of prodrugs
i. Prodrugs – a compound that is
pharmacologically inactive as administered
and then undergoes conversion to its active
form within the body
ii. Lotensin & Cozaar
e. Increased toxicity
i. Metabolism can change relatively safe drugs
into forms that may be toxic
ii. Acetaminophen when metabolized results in
a toxic metabolite to the liver
f. Decreased toxicity
i. Most drugs are converted into inactive forms
and thus decrease risk of toxicity

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 ii. The primary site of metabolism is the liver
iii. Cytochrome P450 Enzymes:
1. Most drug metabolism in the liver is performed by the P450
enzyme system
2. Cytochrome P450 is not a single molecular entity, but
rather a group of 12 closely related enzymes
3. Three of the P450 enzymes are responsible for drug
metabolism
a. CYP1, CYP2, and CYP3
b. Each type metabolizes certain drugs
iv. Special considerations for metabolism:
1. AGE:
a. Infants have decreased ability to metabolize drugs
i. Liver does not mature until about 1 year
after birth
2. NUTRITIONAL STATUS:
a. Malnourished patients may have deficient hepatic
enzymes essential cofactors
v. First-Pass Effect:
1. Remember: in the liver, most of the drug is metabolized to
an inactive form, thus reducing the amount of active drug
2. Remember: that after oral drugs are absorbed, they go first
to the liver via the portal vein
3. Certain drugs are completely inactivated on this first pass
though the liver therefore they can have no therapeutiv
effect
4. Drugs that have a first-pass effect: Lidocaine and
Nitroglycerine (Not given PO b/c most of the drug
would be inactivated) as well as Coumadin and Morphine
5. Drugs that have a first-pass effect will usually have a lower
bioavailability such as 20 – 40%
6. Higher doses are prescribed knowing that the first pass
affect will reduce the amount of active drug
a. Patient with cirrhosis or hepatitis:
i. Will have altered liver function
ii. Metabolism will be affected
iii. Patient will end up with drug toxicity b/c the
drug cannot be metabolized to an inactive
form
iv. Drug accumulation occurs
v. Nurses should watch lab values for liver
enzymes
d. Excretion
i. Elimination
1. Exits: kidneys, bowel, lungs, saliva, sweat, and breast milk
ii. Steps in Renal Drug Excretion:
1. Glomerular Filtration

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 a. Blood flows through the glomerualr capillaries,
fluids and small molecules are forced through the
pores of the capillary wall
b. Blood cells and large molecules will not pass
c. Protein (and protein bound drugs) will not pass
2. Passive Tubular Reabsorption
a. Lipid soluble drugs that are in the renal tubule after
entering the glomerular then undergo passive
reabsorption from the tubule back into the blood
stream
b. b/c they are lipid soluble, they easily pass through
the membrane
c. the drug concentration is less in the blood stream
than in the tubule, so the drug passes due to the
concentration gradient
d. this is why lipid soluble drugs are not excreted from
the kidneys
3. Active Tubular Secretion
a. There are certain active transport systems in the
kidney tubules that pump drugs from the blood to
the tubular urine
b. P-Glycoprotein will be one pump that will work to
pump certain agents into the urine
iii. Factors that Modify Excretion:
1. Urine pH affects drug excretion
a. Acidic urine eliminates weak base drugs (ionized)
b. Alkaline urine eliminates weak acid drugs (ionized)
c. Remember, that if an acid is exposed to alkaline
environment, it becomes ionized
d. If it becomes ionized, it will not pass as a lipid
soluble
e. Therefore passive tubular reabsorption will not
occur
f. Aspirin is a weak acid drug
i. More readily excreted in alkaline urine
g. If a person takes an overdose of aspirin, sodium
bicarbonate will be given
h. This will make the urine more alkaline and will
readily excrete the aspirin
i. Large quantities of cranberry juice will decrease the
pH  causing acidic urine  inhibiting elimination
of aspirin
j. Diazepam (Valium) is excreted faster with a slightly
more acidic urine pH
k. An overdose of valium can be treated with the
administration of ammonium chloride  this will
acidify the filtrate

Pharmacology 12
 l. If pt has renal disease, drug excretion is slowed or
impaired
m. If blood flow to the kidneys is decreased, then
elimination will be decreased
n. If pt has altered kidney function, the doses of
medication for pt should be reduced
2.
iv. Plasma Half-Life:
1. Time it takes for a medication to decrease concentration in
the plasma by one-half after administration
2. Metabolism and elimination affect the half-life of a drug
3. For the patient with liver or kidney dysfunction:
a. The half-life will be prolonged
b. Less drug is metabolized and eliminated
4. A drug has several half-lives
5. The first half life is the time it takes for the drug
concentration to reduce in half
6. The second half life is the time it takes for the second half
of the drug concentration to be reduced by half again
7. Typically takes about 4 half lives for any drug to be almost
out of the blood stream
8. A drug with a long half life, such as Valproic Acid (15 hrs)
will take days for the drug to be completely out of the
system
9. Drug doses are determined by the half life of the drug
10. A drug with a short half life will have to be given more
frequently in order to maintain a constant blood serum level
2. Pharmacodynamic Phase
a. The study of the biochemical and physiologic effects of drugs and the
molecular mechanisms by which effects are produced
i. what drugs do to the body, and how they do it
b. Therapeutic Effect:
i. Also called the primary effect; is the expected or predictable
physiological response, the reason the drug was intended
c. Adverse Drug Reactions:
i. Side Effects
1. Predictable “secondary effect”
a. Sometimes harmless
b. Sometimes causes injury
c. Sometimes beneficial
2. May outweigh the benefit
ii. Toxicity
1. When a drug accumulates in the blood above a therapeutic
level (overdose of insulin causes blood sugar levels to
decrease)
iii. Allergic Reaction
1. Unpredictable immune response; mild or severe
a. Urticaria – hives

Pharmacology 13
 b. Eczema – rash
c. Pruritus – itching of the skin
d. Rhinitis – swelling and clear drainage from nose
e. Wheezing – constriction of the smooth muscles
surrounding the bronchioles
iv. Idiosyncratic Effect
1. Unpredictable; client overreacts or underreacts to a drug
v. Physical Dependence
vi. Carcinogenic Effect
1. Ability of medications, environment and chemicals to cause
cancer
vii. Teratogenic Effect
1. Drug induced birth defects
d. Onset – Peak – Duration of Action:
i. Goal: constant blood level within a safe therapeutic range
ii. Repeated doses are required to achieve a constant therapeutic
concentration
iii. MEC: minimum effective concentration
iv. MTC: minimum toxic concentration
v. Onset of Action: period of time it takes after the drug is given to
create a response
1. Minimum effective concentration
vi. Peak Action: time it takes for a drug to reach it’s highest blood
concentration
1. The highest concentration, peak, occurs just before the last
of the drug is absorbed
vii. Duration of Action: length of time during which the drug is
present in a concentration great enough to produce a response
viii. Drug Dosing:
1. Based on the Onset, Peak, and Duration
a. If you are not maintaining the MEC, than the dosing
is incorrect  if you are dipping into the MTC than
the dosing is incorrect
2. Remember the Serum Half Life
a. The time it takes for excretion processes to lower
the serum drug concentration by half
b. In order to maintain a therapeutic dose, the next
dose should be given about the time of the first half
life
e. Therapeutic Index:
i. Aka the Therapeutic Range
ii. The ratio of a drug’s “LD” to it’s “ED”
1. ED: average effective dose
a. The dose that is required to produce a defined
therapeutic response in 50% of the population
2. LD: average lethal dose
a. The dose that is lethal to 50% of the animals treated
iii. Estimates the margin of safety of a drug

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 iv. Drugs with a “low” therapeutic index have a “narrow margin” of
safety
1. With these drugs, serum levels need to be monitored
v. Drugs with “high” therapeutic index, have a “wide margin” of
safety
1. Less danger of toxic effects with high therapeutic index
drugs
vi. Calculating the Therapeutic Index
1. ED = average effective dose for a particular medication;
LD = average lethal dose for a particular medication
a. to determine therapeutic index the LD is compared
to the ED
i. therapeutic index = LD/ED
ii. if TI is 2, it means that it would take an error
of 2x the average dose to be lethal to a
patient
f. Cellular Receptors
i. Many drugs work because they bind to a particular receptor
ii. These receptors exist normally in the body to bind with
endogenous hormones, growth factors and neurotransmitters
iii. A drug attaches to its receptor in a specific manner, similar to a
lock and key
1. Meds effecting the autonomic nervous system may trigger
the alpha or beta receptors
g. Peak and Trough Serum Levels
i. Peak: highest plasma concentration
1. Peak time will vary depending on drug and route
a. May be 10 minutes for drugs given IV or 4 hours if
given PO
2. Drug guide will tell you the proposed peak time
3. Blood sample is drawn at the proposed peak time
4. Measures the rate of absorption  indicates the MTC
ii. Trough: lowest plasma concentration
1. Blood is drawn before the next dose is due
2. Measures the rate of elimination  indicates the MEC
iii. Peak and trough levels are drawn on drugs with a narrow
therapeutic index (such as Gentamycin)
1. If the peak is too high the patient may become toxic
2. If the trough is too low the patient is not getting a constant
therapeutic level of the drug
b. Movement of Drugs Across the Membranes
i. Drugs have to move from site of administration to the blood stream to the site of action
to the kidneys for elimination
ii. Three ways to cross a cell membrane:
1. Pass through channels or pores
a. Only very small ions such as potassium and sodium
b. Go around the cells
2. Pass with the aid of a transport system

Pharmacology 15
 a. Different transport mechanisms
b. Most transport systems are selective for the drug
c. P-Glycoprotein
i. A protein that transports a wide variety of drugs out of cells
ii. Present in the liver, kidneys, placenta, intestine and capillaries of
the brain
iii. Transports the drug out of the cell, so that it can be eliminated
iv. Pumps drugs out of the cells in the kidney, into the urine
v. Pumps drugs out of the cells in the brain into the bloodstream
3. Direct penetration of the membrane
a. Most common
b. Lipid soluble drugs can directly penetrate membranes
c. Membranes are primarily composed of lipids
d. The drug will dissolve into the lipid membrane and cross to the other side
e. Molecules that are not lipids, will not be able to penetrate the membrane
i. Water soluble medications and ionized agents cannot dissolve into
the lipid membrane of cells
1. Water soluble drugs need a carrier
a. Lipids and water separate
2. The carrier will either be an enzyme or a protein that will
help the drug molecules pass through the membrane
3. Basically:
a. Lipid soluble across the membrane
b. Non-ionized agents move across the membrane
c. Water soluble agents and ionized agents do not
move across the membrane
iii. Transport of Ions
1. Molecules that have a net electrical charge
2. Except for very small molecules, ions are unable to cross membranes
3. Certain drugs can exist in either a charged or uncharged form
a. The pH of the surrounding area, will determine if the molecule has an
electrical charge
4. Aspirin is a “weak acid”
a. When aspirin (weak acid) is in the stomach (acidic environment) it is not
ionized ------ can pass because it is nonionized
b. Is aspirin is in the small intestine (more alkaline environment) it would not
be able to pass ------ cannot pass because it is ionized
c. Aspirin will “ionize” in an alkaline environment
i. Become an ion
ii. Cannot cross cell membranes
5. An amphetamine agent is a “weak base”
a. Amphetamines will “ionize” in an acidic environment
i. Become an ion
6. Nonionized drugs can pass through membranes
c. Drug Interactions
i. Drug – Drug Interaction
1. An altered effect of a drug as a result of an interaction with another drug
2. Not to be confused with an adverse drug reaction

Pharmacology 16
 a. Adverse drug reaction:
i. Undesirable drug effect, includes hypersensitivity and anaphylaxis
3. Categories of Drug Interactions:
a. Direct Chemical or Physical Interactions
i. Drugs interact due to their chemical or physical properties
ii. Usually both drugs are inactivated
iii. Often called a “Drug Incompatibility”
1. A chemical or physical reaction that occurs among two or
more drugs
2. Most commonly will occur in the IV container or tubing
3. Never administer an IV drug that is discolored/cloudy
b. Pharmacokinetic Interactions
i. Absorption
1. The rate of absorption of one or both drugs can change
2. One drug can block, decrease, or increase the rate of
absorption of the other drug
a. Decreasing/Increasing gastric emptying time
i. The longer the drug stays in the stomach or
in the intestines, the greater the amount of
drug absorption
ii. Drugs that increase gastric emptying such
as laxatives, increase the gastric and
intestinal motility and decrease absorption
iii. Drugs that decrease gastric emptying such
as narcotics, cause an increase in
absorption
b. Changing the gastric pH
i. When the gastric pH is decreased, a weak
acid drug, such as aspirin is absorbed faster
ii. Drugs that increase the pH of gastric juices
decrease the absorption of weak acid drugs
iii. Antacids such as Maalox and Amphojel,
raise the gastric pH and block or slow
absorption
iv.   increase in pH = alkaline
c. Forming drug complexes
i. Some drugs can react chemically to other
drugs
ii.   tetracycline, if given with antacids,
will form a complex and will not be
absorbed
iii.   tetracycline also forms complexes
with dairy products
ii. Distribution
1. When 2 drugs are given together that are highly bound to
protein (albumin) sites in the plasma, they compete for the
albumin sites

Pharmacology 17
 2. When one drug takes all of the albumin spots, it leaves the
other drug “free floating” so more is distributed and can
lead to drug toxicity
3. When two highly-bound albumin drugs need to be given
together, doses may need to be decreased
4. Coumadin and NSAIDS are both highly protein bound
drugs
iii. Metabolism (Biotransformation)
1. Certain drugs can stimulate liver enzymes
a. Enzyme inducers
b. Drugs that stimulate the synthesis of the CYP
enzymes are “inducers”
i. Enzyme inducers will increase the metabolic
rate of other drugs
ii. Increase in metabolism will cause more
rapid drug excretion and a decrease in drug
concentration in the blood
2. Certain drugs can inhibit hepatic enzymes
a. Enzyme inhibitors
b. Drugs that inhibit the CYP enzymes are “inhibitors”
i. Enzyme inhibitors will decrease the
metabolic rate of other drugs
ii. If metabolism is decreased, the plasma
concentrations of the other drugs will be
increased  toxicity is likely
iv. Excretion
1. Changing urine pH affects drug excretion
a. Alkaline urine
i. Promotes the excretion of drugs that are
weak acids, such as aspirin and barbiturates
b. Acidic urine
i. Promotes the excretion of drugs that are
weak bases such as Quinidine
c. Sodium bicarbonate (antacid) causes the urine pH to
be alkaline
2. Drugs that decrease cardiac output, will decrease blood
flow to the kidneys and decrease glomerular filtration
a. Will delay or decrease drug excretion
3. Drugs that increase or decrease renal excretion, have an
effect on the excretion of other drugs
a. Diuretics promote water and sodium excretion from
the renal tubules
b. Diuretics decrease reabsorption of water, sodium,
and potassium

c. Pharmacodynamic Interactions
i. Onset, Peak, Duration of Action
ii. The combined effect of the drugs will have a:

Pharmacology 18
 1. Additive Effect
a. The sum of the effect of the two drugs
i. When two drugs with similar action are
administered, the drug interaction is called
an “additive effect”
ii. The effect can be desirable or undesirable
iii.   Tylenol and Codeine = desirable
effect
iv.   Apresoline (antihypertensive) given
with Nitroglycerine = undesirable
hypotensive effect
2. Synergistic Effect
a. One drug can potentiate another
b. Greater than the combined effect of the two drugs
c. The effect can be desirable or undesirable
i. Demerol and Phenergan given together =
phenergan enhances the effects of Demerol
so less Demerol is needed = desirable effect
ii. Alcohol and Demerol = increases the CNS
depression and leads to decreased
respirations = undesirable effect
3. Antagonistic Effect
a. Drugs that block a response
i. When two drugs are combined that have
opposite effects
ii. May be desirable or undesirable
iii.   Isuprel (beta adrenergic stimulant)
given with Inderal (beta adrenergic blocker)
= cancel each other out
d. Combined Toxicity (p. 60)
ii. Drug – Food Interaction
1. Food can increase, decrease or delay drug absorption
2. Food can bind with drugs, causing less or slower drug absorption
a. TCN binds with food (dairy products)
3. Some drugs have increased drug absorption with food
a. Lopressor and Macrodantin
4. MAO Inhibitors, such as Marplan, should not be taken with Tyramine-rich foods
a. Cheese, wine, organ meats, beer, yogurt, sour cream, bananas…
b. More norepinephrine is released and the result could be hypertensive crisis
c. Avoid these foods for 2 weeks following taking this drug
5. Theophylline cannot be taken with caffeine
a. Will produce exaggerated CNS excitation
6. Grapefruit Effect
a. Grapefruit juice can inhibit the metabolism of certain drugs
b. In one study, coadministration of grapefruit juice produced a 406%
increase in blood levels of Felodipine (Plendil) a calcium channel blocker
c. The more grapefruit juice that the patient drinks, the greater the inhibition
d. Inhibition can persist for up to 3 days after the last glass

Pharmacology 19
 iii. Drug – Laboratory Interaction
1. Abnormal plasma or serum electrolyte concentrations can affect certain drug
therapies
2. Patient with a decreased serum potassium level or an increase in serum calcium
level will be more prone to Dig Toxicity
3. Frequently patients on Digoxin, will also be taking a “potassium-wasting diuretic”
d. Pediatric and Geriatric Implications
i. b/c of the immature organs in infants, the changing metabolic rate in the preschool and
school-aged child, and the declining organ function in the elderly, the effect of drug
therapy should be closely monitored
ii. many drugs are not approved by the FDA for pediatric patients
iii. not much research is done on pediatric patients
1. difficult to get a large enough study sample due to informed consent
2. fewer financial resources put forth by pharmaceutical companies due to the
decrease in numbers of prescriptions for kids compared to adults and elderly
3. some people think that pediatric research is unethical
iv. doctors will prescribe these meds for kids anyways
1. ¼ of all medications carry federally approved indications for kids
2. Whereas ¾ of all meds are used on kids
a. Marketed for adults only
v. Dosing of pediatric medications
1. Pediatric doses are often calculated according to BSA or BW
2. Pediatric dose ranges have been established for many drugs and can be found in
the Drug Reference guides
vi. Pharmacokinetics: Pediatrics
1. Absorption:
a. Reduced gastric acid production/ higher gastric pH
i. Infants under 1 year of age have alkaline gastric juices
ii. The pH of gastric juices drops to the adult normal level at age of 2
iii. The difference in pH may hinder or enhance drug absorption
iv. Some drugs such as PCN absorb faster in higher pH
1. Lower drug doses may be required for kids
v. Acidic pH favors absorption of acidic drugs
1. Therefore in infants, these drugs would absorb slower
because they have alkaline gastric juices
b. Slow or irregular peristalsis
i. Gastric emptying is prolonged in infants, but speeds up as kids get
older
ii. Delayed emptying in kids, although will allow for more
absorption, resulting in decreased PEAK concentrations
iii. Irregular peristalsis, associated with diarrhea or vomiting will
decrease absorption time for meds
1. Thus less absorption

c. Topical drugs
i. May be absorbed faster and in greater concentration in kids
ii. The skin is thinner and more porous
iii. Kids also have a proportionally greater body surface area

Pharmacology 20
 iv. Be careful with topical drugs: kids can get a systemic effect that is
unwanted
2. Distribution:
a. Lower blood pressure affects the blood flow to tissues
i. Liver and brain are proportionally larger and receive more blood
flow
ii. Kidneys and peripheral tissues receive less blood flow
b. Infants are composed of 70% water
i. Premature infants are about 85% water
ii. As kids grow, the percentage decreases to about 50 – 60% water
iii. Water soluble drugs are diluted in the large volume of their body
fluid
iv. A larger drug dose may be needed to achieve the desired plasma
concentration
1. Due to the drug dilution
2. Until the age of 2
c. Infants have less albumin than older kids
i. With less albumin, there will be fewer protein binding sites
ii. Protein bound drugs will have to be given in lower doses
iii. If an infant has a high bilirubin level, the bilirubin molecules will
bind with the protein sites that are available, thus they wont be
available for the medications that rely on protein-binding
3. Metabolism:
a. Infants have an immature liver and kidneys
i. This will lead to a decrease in the metabolism and excretion of
drugs
ii. The liver and kidneys will mature by the age of 1
1. At age 1-2 months, these organs are more mature than with
the neonate
iii. Before the age of 1 year, the liver enzymes are decreased
1. With decreased metabolism, there will be a prolonged half-
life and possible toxicity if not dosed correctly
b. Metabolism in older children is faster than with adults
i. Drug half-life in the older child can be shorter due to the increased
metabolic rate
ii. Higher doses for the older child might be needed to off-set the
increased metabolic rate
4. Excretion:
a. Drug elimination via the kidneys is decreased until 9 months of age
i. This happens due to a lower blood pressure that reduces the blood
flow to the kidneys
ii. This may lead to a (shorter/longer) half- life of the drug
vii. Pharmacodynamics: Pediatrics
1. Peak, onset and duration will be affected by the pharmacokinetics discussed
2. Immaturity of the organs in the infant will affect the drug action and drug dose
frequently
3. Receptor site sensitivity will differ with the neonate, infant and young child
4. Some tissues are more sensitive to certain drugs

Pharmacology 21
 5. Some drugs are more toxic to adults than to children
viii. Geriatric Pharmacology
1. Growing number of older people in society coupled with the number of meds that
they each take, has led to serious problems with drug interactions and drug
misuse/abuse
2. Approximately 70% of clients older than 65 years of age take at least one to two
prescribed drugs daily
3. The other 30% of older adults take 5 or more prescribed drugs daily
4. Besides just taking the prescription drugs, problems arise due to:
a. The older patient also takes a lot of OTC drugs
b. The older client may take too much or too little of their medication due to
memory problems
c. Taking many drugs together can lead to confusion, falls, malnutrition,
renal and liver dysfunction and nonadherence
5. Physiological changes in the elderly that have an effect on drug therapy:
a. p. 97 Table 11-1
b. Gastrointestinal:
i. Alkaline gastric secretions
1. Acidic drugs are poorly absorbed
ii. Decreased peristalsis
1. Delayed gastric emptying time
c. Cardiac and Circulatory:
i. Decreased cardiac output
1. Decreases blood flow to all parts of the body including the
liver and kidneys
d. Hepatic:
i. Decreased enzyme function
1. Decreases the livers ability to metabolize and detoxify
drugs
2. Increases the risk of drug toxicity
e. Renal:
i. Decreased blood flow
ii. Decreased functioning nephrons
iii. Decreased glomerular filtration rate
1. Will prolong the drug half-life
2. Will increase the risk of drug accumulation and drug
toxicity
6. Pharmacokinetics: Geriatrics
a. Absorption:
i. Decrease in gastric acid alters absorption of weak acid drugs such
as aspirin
ii. Enteric coated meds are made to break down in alkaline fluids, so
they more readily break down in the stomach of an elderly person
iii. Decreased blood flow to the GI tract
1. Caused by decreased cardiac output
2. Slows down absorption
iv. Reduction in GI motility rate may delay onset of action
b. Distribution:

Pharmacology 22
 i. Decrease in body water
1. So water soluble drugs are (more/less) concentrated
ii. Increase in fat-to-water ratio, so fat-soluble drugs are stored and
likely to accumulate
iii. Decreased serum-protein (albumin) levels
1. Fewer protein binding sites resulting in more “free” drug
2. Increased drug interactions due to lack of available protein
sites
c. Metabolism:
i. Decrease in hepatic enzyme production
ii. Decrease in hepatic blood flow and total liver function
iii. These physiologic changes lead to an (increase/decrease) in drug
metabolism
iv. Reduction in the metabolic rate will:
1. (increase/decrease) the drug half-life
2. An increase in the drug half-life will (increase/decrease) the
risk of drug toxicity
d. Excretion:
i. Decrease in renal blood flow
ii. Decrease in glomerular filtration rate by 40 – 50%
iii. These changes will (increase/decrease) the drug half-life

Pharmacology 23
3. Lecture 3: Integumentary
a. Topical Glucocorticoids
i. Used for numerous inflammatory or pruritic dermatoses
1. Atopic and Contact dermatitis
2. Psoriasis
3. Eczema
4. Insect bite reactions
ii. Mechanisms of Action
1. Topical corticosteroids diffuse across cell membranes and induce cutaneous
vasoconstriction
2. The vasoconstriction inhibits the migration of macrophages and leukocytes into
the area
3. The degree of vasoconstriction is commensurate with the potency
iii. Topical Corticosteriods
1. Topical corticosteroids are ranked according to potency
a. Group I is the most potent
b. Group VII as the least potent
c. Group VII is often the OTC agents
2. Potency is the most important variable when a topical steroid is chosen
iv. Absorption varies depending on:
1. The vehicle used
a. Ointments are more occlusive, thus more potent than creams and lotions
2. The amount of skin surface area covered
3. Location of the skin
a. Face, scrotum… have thinner skin layers
4. Condition of the skin
5. Temperature of the skin
6. Use of occlusive dressing
v. Occlusive Dressings
1. Use of plastic wrap
2. Increases skin penetration 10-fold
3. May be beneficial in resistant cases
4. May lead to increased adverse effects and possible adverse systemic effects
vi. Dosing and Special Considerations
1. Apply sparingly!
2. Preparations of mild to intermediate strength should be considered when large
areas are treated because of the likelihood of systemic absorption
3. After long term use of with high potency agents, Topical Corticosteroids should
not be abruptly discontinued
a. May lead to rebound effect
4. Treatment should be discontinued when the skin condition has resolved. Tapering
the corticosteroid will prevent recurrence of the skin condition
vii. Topical Corticosteroids: Geriatric Client
1. Geriatric patients are more susceptible to secondary infection when steroids are
used
2. Geriatric patients are more susceptible to the systemic effects because their skin
tends to be thinner
viii. Topical Corticosteroids: Pediatric Client

Pharmacology 24
 1. May be more susceptible to systemic adverse effects
2. The least-potent strength compatible with effective treatment should be used
3. Potent corticosteroids should typically not be used in children
4. May lead to delays in growth and development in children
ix. Monitoring the Patient
1. With Mid to High Potency Products, monitor for:
a. Superinfection
b. Adverse Effects (Cushing Symptoms)
c. Growth and development in children
d. Blood glucose and serum potassium levels
x. Patient Education
1. Use exactly as prescribed
2. Demonstate the “amount” of the medication to apply
a. Pea size, spread thinly over the area
3. Instructions on “occlusion” if it is warranted
4. Report any adverse effects
b. Acne Preparations
i. Acne
1. Inflammatory disorder of the sebaceous glands
2. Sebacious glands remain small throughout childhood
3. During Puberty, hormone levels (specifically androgens) rise and cause an
increase in sebum secretion
4. The face, chest back and upper arms have the largest and most numerous
sebaceous glands
5. Acne is further be exaggerated by “Propionibacterium Acnes.”
a. Propionibacterium Acnes
i. (P. Acnes)
ii. A normal skin resident
iii. A microbe that converts sebum into an irritant fatty acids
iv. P. Acnes promotes inflammation by attracting leukocytes
ii. Classifaction System
1. Treatment is based on severity and type of lesion present
2. Mild
a. Comedones (Blackheads)
b. Noninflammatory lesion of acne
3. Moderate
a. Papules and Pustules
4. Severe
a. Cystic Acne
iii. Benzoyl Peroxide
1. Bactericidal agent against P Acnes
a. Does not promote resistance of P Acnes
2. Used for mild to moderate acne
3. Available OTC and by prescription
a. Most common OTC medication
4. Available as a cream, lotion, gel or wash
5. Has a “keratolytic” effect
a. Helps to dry out and shed the outer layer of the epidermis

Pharmacology 25
 6. Client should be instructed to:
a. Apply once a day in the beginning
b. Increase frequency of application to a maximum of three times daily as
tolerated.
c. Wear sunscreen when outdoors.
iv. Topical Clindamycin or Erythromycin
1. For mild to moderate acne
2. Works by suppressing “P Acnes”
3. Antibacterial and antiimflammatory action
4. Therapeutic response seen in 6-12 weeks
5. Combination products available with Benzoyl Peroxide
a. Monotherapy with either antibiotic will quickly lead to resistance
v. Topical Retinoids
1. Considered 2nd or 3rd line therapy
2. Derivatives of vitamin A (retinol)
3. Retinoids are used against both inflamed and noninflamed acne lesions
4. Can be used alone or in combination with antibiotics
5. Effect may not be seen for 2 to 3 weeks
6. Can be extremely irritating to the skin
7. Patient should use a small amount
a. Pea size
8. Wait for 20 – 30 minutes after washing face to apply
9. Will cause severe sun sensitivity
a. Avoid the sun, or wear sunscreen
10. Avita and Retin-A Micro are newer formulations of the original “Retin-A”
a. The newer formulations may have less intense localized effects.
vi. Systemic Antibiotics
1. Used for moderate to severe acne that does not respond to topical treatment
2. Works by suppressing the growth of P. Acnes and decreasing inflammation
3. Usually used in combination with a topical retinoid
4. Minocycline and Doxycycline are the agents of choice
a. Tetracycline and Erythromycin are alternatives
b. Resistance to Tetracycline and Erythromycin is common
5. Good results with systemic antibiotics, but takes 3 – 6 months to reach maximum
benefit
6. After symptoms have controlled with an oral antibiotic, patients should be
switched to a topical antibiotic for long-term maintenance
vii. Isotretinoin (Accutane)
1. Derivative of vitamin A
2. Very potent and effective
3. Reserved for severe cystic acne
a. Due to severe side effects
4. Treated for 20 weeks
5. If a second course of treatment is necessary, the client should wait 8 weeks before
starting again
6. Accutane:
a. Decreases sebum production
b. Decreases inflammation

Pharmacology 26
 c. Causes Keratinization
d. Lowers the skin population of P. acnes
7. Side Effects:
a. Dry skin & mucous membranes
b. Nasal irritation/ nose bleeds
c. Dry eyes/ Photosensitivity
d. Elevated blood triglyceride levels
i. Etoh intake escalates triglyceride levels
e. Teratogenic effects
i. Not to be taken by sexually active females
ii. Category X
f. Arthralgia
g. Rare: Mood changes/ Depression/ Suicide tendencies
h. Risk of Toxicity
i. Tetracyclines and Vitamin A supplements increase risk of toxicity
ii. Should be discontinued before starting Isotretinoin (Accutane)
i. Risk of Teratogenic Effects
i. Fetal abnormalities include:
1. Hydrocephalus, microcephaly, facial malformation, cleft
palate, cardiovascular defects and abnormal formation of
the outer ear

8. iPLEDGE
a. Name of a very strict risk management program
b. Went into effect in December, 2005
c. The iPLEDGE program has rules that apply to the physician, patient, and
pharmacist
d. All transactions involving Isotretinoin (Accutane) must be processed
through a central automated system
e. Pregnancy must be ruled out prior to prescribing and again before each
monthly refill
i. Two negative pregnancy tests are required before the first dose
f. Each patient must use two effective forms of birth control, even if one is a
tubal or vasectomy
g. Birth control measures must be implemented at least 1 month before
starting isotretinoin (Accutane), and continue for one month following the
last administration
h. Informed consent must be signed
i. Patient must register with iPLEDGE
j. Physician must be registered with iPLEDGE
k. Pharmacist must be registered with iPLEDGE and obtain the drug from a
registered iPLEDGE wholesaler
c. Treatment of Burns
i. Topical Sulfonamides
1. Used to suppress bacterial colonization in patients with 2nd and 3rd degree burns.
ii. Agents:
1. Silver Sulfadiazine (Silvadene)
2. Mafenide (Sulfamylon)

Pharmacology 27
 iii. Administration:
1. Premedicate with analgesic before application
2. Cleanse and debride prior to administration
3. Use sterile technique to apply
4. Burn should be coated at all times with thin layer
iv. Adverse Effects:
1. Nephritis
a. Monitor Renal function
i. Creatinine and BUN
ii. Urine output
2. Leukopenia
a. Monitor CBC
3. Silver Sulfadiazine may cause skin discoloration
4. Lecture 4: Neurological Agents
a. Peripheral Nervous System
i. Consists of Two Divisions:
1. Somatic Motor System
a. Voluntary
b. Acts on Skeletal Muscles
2. Autonomic Nervous System
a. Involuntary
b. Controls or regulates the functions of the heart, respiratory system, smooth
muscles, GI system and glands
b. Autonomic Nervous System
i. Consists of two divisions:
1. Sympathetic Nervous System
a. Fight or Flight
i. Also Called Adrenergic
ii. Main neurotransmitter is Norepinephrine

Pharmacology 28
 iii.

Dilate
Relax Pupils Dilate
Uterine
Bronchioles
muscles

Relax
Bladder Increase
muscles Heart Rate
Sympathetic
Relax Smooth
Muscles of GI Constrict
Tract Blood
Mobilizes Vessels
Stored
Glucose
2. Parasympathetic Nervous System
a. Rest and Digest
i. Also called Cholinergic
ii. Main neurotransmitter is Acetylcholine
iii.

Constricts
Constricts the Bronchioles
Pupil Increases
Salivation

Parasympathetic
Response
Constricts
Bladder Decreases
Heart Rate
Dilates
Increases Blood
Peristalsis Vessels

c. Receptors of PNS
i. Two Basic Categories of Receptors
1. Cholinergic Receptors
a. Respond to Acetylcholine
2. Adrenergic Receptors
a. Respond to Norepinephrine and Epinephrine

Pharmacology 29
d. Subtypes of Cholinergic & Adrenergic Receptors
i. Subtypes of Cholinergic Receptors
1. Nicotinic and Muscarinic
ii. Subtypes of Adrenergic Receptors
1. Alpha 1, Alpha 2, Beta 1 and Beta 2
e. Adrenergic Receptors: Alpha 1 and Alpha 2
i. Alpha 1 is located on the blood vessels and causes vasoconstriction
ii. Alpha 2 is located on the postganglionic nerve endings and cause decrease in
vasoconstriction (dilation)

f. Adrenergic Receptors: Beta 1 and Beta 2

i. Beta 1: Located primarily in the heart
ii. Beta 1 = “1” heart
iii. Beta 1 is also located in the kidney
1. Causes the release of renin into the blood
iv. Beta 2 located primarily in the lungs
v. Beta 2 = “2” lungs
vi. Beta 2 is also in the arterioles and uterus
1. Relaxes uterine smooth muscles
2. Dilates arterioles in the heart, lungs and skeletal muscles

g. Adrenergic Agonists
i. Stimulates the Sympathetic Nervous System
1. Also Called:
a. Adrenergics
b. Adrenergic Agonists
c. Sympathomimetics

Pharmacology 30
h. Adrenergic Drugs
i. Most Sympathomimetics act by directly binding to and activating adrenergic receptors
1. Some Sympathomimetics act by causing a release of norepinephrine
2. Some Sympathomimetics act by inhibiting the reuptake or destruction of
norepinephrine
i. Chemical Classification of Adrenergic Agonists
i. Adrenergics are divided into two chemical classifications:
1. Catecholamines and Noncatecholamines
a. Catecholamines
i. Epinephrine, Norepinephrine, Isoproterenol, Dopamine and
Dobutamine
ii. Cannot be taken orally
iii. Short half life
iv. Do not cross the blood brain barrier
b. Noncatecholamines
i. Ephedrine, Phenylephrine, and Terbutaline
ii. Half life is longer than the catecholamine group
iii. Can be taken orally
iv. Does cross the blood brain barrier
ii. Adrenergics: work on one or more of the receptor sites
iii. Alpha 1 Receptor Agonists
1. Used for:
a. Vasoconstriction in blood vessels of the skin, viscera and mucous
membranes
i. Treatment of nasal congestion
ii. To stop bleeding (nose bleeds)
iii. To elevate blood pressure
1. Not the primary medication used
b. Mydriasis during ophthalmic examinations
i. Not used often for this purpose
ii. If applied topically to the eye, should not lead to vasoconstriction
or elevation in blood pressure
iv. Adverse Effects of Alpha 1 Activation
1. Hypertension
2. Bradycardia
a. Reflex slowing of the heart triggered from a response by the baroreceptors
responding to hypertension
3. Necrosis at IV site with infiltration into tissues
a. Due to vasoconstriction
v. Alpha 2 Receptor Agonists
1. Used for Hypertension
2. Also used via an Epidural for management of cancer pain unresponsive to opioids
3. Example:
a. Clonidine (Catapres)
4. Be careful in Geriatric population
a. May lead to orthostatic hypotension
vi. Beta 1 Receptor Activation
1. Treatment of cardiac arrest

Pharmacology 31
 a. Can initiate contraction in a heart that has stopped
2. Treatment of shock
a. Increases heart rate, force of contraction and cardiac output
vii. Adverse Effects of Beta 1 Activation
1. Altered heart rate or rhythm
a. Tachycardia and dysrhythmias may result
2. Angina Pectoris
a. Increases cardiac oxygen demand
viii. Beta 2 Receptor Activation
1. Treatment of Asthma
a. Promotes bronchodilation
2. Treatment of Preterm Labor
a. Relaxes uterine smooth muscles (give beta 2 agonist)
ix. Adverse Effects of Beta 2 Activation
1. Hyperglycemia
a. Promotes breakdown of glycogen into glucose
b. Is a problem only in patients with diabetes
c. Insulin doses may need to be increased
2. Tremors
a. Enhances contraction of the receptors in skeletal muscles
b. This effect generally fades over time
x. Adrenergic Agonist Agents:
1. Epinephrine:
a. Alpha 1
b. Beta 1
c. Beta 2
d. Catecholamine
2. Administered topically, by injection and by inhalation
a. Cannot be given orally
b. Catacholamines undergo destruction before reaching the systemic
circulation
3. Because it activates so many receptors, expect side effects
a. Hypertension, Angina, Necrosis following IV Extravasation,
Hyperglycemia (Beta 2), Dysrhythmias (Beta 1)
4. The Epi Pen
xi. Isoproterenol Hydrochloride (Isuprel)
1. Activates Beta 1 and Beta 2
2. Used for Bronchospasms with anesthesia
3. Used for Cardiovascular Disorders
a. AV heart block, cardiac arrest and increase cardiac output
4. Undesirable effects of Isuprel:
a. Can lead to tachydysrhythmias and Angina
b. Can cause Hyperglycemia in Diabetic clients
5. Terbutaline (Brethine)
a. Primarily Beta 2, Minimal Beta 1
i. If administered in large doses, will have beta 1 activation
b. Primary reaction is bronchodilation and uterine relaxation
c. Noncatecholamine

Pharmacology 32
 d. Stops preterm labor and respiratory problems
6. Dopamine
a. Catecholamine
b. Binds to Beta 1and Dopamine receptors
c. At high doses, will also bind to alpha 1
d. Used to treat:
i. Shock (Increases cardiac output and dilates renal blood vessels)
ii. Heart Failure (increases myocardial contractility)
iii. Acute Renal Failure (Increases renal blood flow and urine output.
7. Dobutamine
a. Causes selective activation of beta 1 receptors
b. The only indication is for treatment of heart failure
xii. Adrenergic Antagonists
1. Also called:
a. Adrenergic Blockers
b. Sympatholytic Agents
xiii. Alpha Blockers
1. Drugs that Block Alpha 1will be used in the:
a. Treatment of Hypertension
i. Through Vasodilation
b. Treatment of Peripheral Vascular Disease (Raynaud’s Disease)
c. Treatment of Pheochromocytoma
i. Catecholamine secreting tumor usually located in the adrenal
medulla
ii. Treatment of choice is removal of the tumor, but Alpha 1 Blockers
can be given with inoperable tumors or preopertively
d. Treatment of Benign Prostatic Hyperplasia
i. Decreases contraction in smooth muscle in the bladder neck
e. Reversal of Toxicity form Alpha 1 Agonist
i. In the event of an overdose or intravenous extravasation, an Alpha
1 blocker can be administered
ii. If an IV line containing an alpha agonist infiltrates, necrosis can
occur
iii. Alpha 1 blocker (Phentolamine) can be injected into the region and
will prevent injury
xiv. Adverse Effects of Alpha Blockers
1. Orthostatic Hypotension
a. Alpha Blockers reduce the muscle tone in the venous wall
b. Blood tends to pool when the patient stands up
2. Reflex Tachycardia
a. Increases heart rate by triggering the baroreceptor reflex
b. Can be suppressed by use of beta blockers
3. Nasal Congestion
a. Dilates the blood vessels of the nasal mucosa
4. Inhibition of Ejaculation
a. May lead to impotence
b. Reversible when the alpha blocker is stopped
xv. Adrenergic Alpha Blockers

Pharmacology 33
 1. Prazosin (Minipress)
a. Selective for Alpha 1 Receptor
b. Causes dilation of arterioles and veins (orthostatic hypotension)
c. Causes relaxation in the bladder neck and prostatic capsule
d. Used for hypertension, and BPH
e. Watch out for orthostatic hypotension!!
f. Can lead to impotence and nasal congestion
2. Phentolamine
a. Blocks Alpha 1 and Alpha 2
b. Used in the treatment of Pheochromocytoma
c. Used to prevent tissue necrosis following extravasation of drugs that
produce alpha 1 vasoconstriction
i. Norepinephrine
d. Can cause orthostatic hypotension, nasal congestion and inhibition of
ejaculation
3. Terazosin (Hytrin)
a. Selective antagonist for alpha 1 receptors
b. Approved for use with hypertension and BPH
4. There is minimal recognizable therapeutic application to blocking alpha 2
xvi. Adrenergic Beta Antagonists
1. Also called
a. Beta Blockers
b. Beta Adrenergic Blockers
c. Sympatholytic Agents
d. Beta Blockers end in “lol”
e. Drugs that block the beta receptors
i. Beta 1 and/or Beta 2
f. Practically all of the therapeutic effects of the beta adrenergic antagonists
result from blockade of the Beta 1 receptor.
i. Reduces heart rate
ii. Reduces the force of the cardiac contraction
iii. Reduces the velocity of the impulse conduction through the AV
node
g. Beta Blockers will be used to treat:
i. Angina pectoris
1. Decreases cardiac workload
ii. Hypertension
1. Reduces peripheral vascular resistance
iii. Cardiac Dysrhythmias
iv. Myocardial Infarction
1. Can reduce pain, infarct size and mortality
v. Hyperthyroidism
1. Will decrease the heart rate
vi. Migraine Headaches
1. When taken prophylactically
2. Will not treat the headache itself
vii. Pheochromocytoma

Pharmacology 34
 1. Can prevent the cardiac stimulation caused from the
catecholamine secretion
viii. Stage Fright
1. Help prevent the fear associated with a generalized
discharge from the Sympathetic Nervous System
xvii. Adverse Effects of Beta Blockers: Beta 1
1. Bradycardia
2. Reduced Cardiac Output
a. Reduces heart rate and force of contraction
b. Extreme caution in patients with heart failure
3. Precipitation of Heart Failure
a. Due to suppression of heart function
xviii. Adverse Effects of Beta Blockers: Beta 2
1. Bronchoconstriction
a. Be careful with COPD or asthma
b. Lopressor is selective for Beta 1, therefore will not have an effect on
bronchioles
2. Inhibition of Glycogenolysis
a. Insignificant effect for patients who aren’t Diabetic
b. Beta 1 Selective Blocker should be used for Diabetics who require a Beta
Blocker
xix. Beta Blocker Agents
1. Propranolol Hydrochloride (Inderal)
a. Nonselective for Beta 1 and Beta 2
b. Treats angina, cardiac dysrhythmias, hypertension, and MI
i. Contraindicated with respiratory patients
c. See the similarity in names
“Inderal and Isuprel” – Be careful!!
2. Metoprolol (Lopressor, ToprolXL)
a. Blocks Beta 1 Receptors only
i. At higher doses, it will also block beta 2
3. Atenolol (Tenormin)
a. Blocks Beta 1 Receptor only
b. These are the preferred Beta Blocking agents for patients with asthma or
diabetes
c. Primarily used to treat Hypertension
j. Cholinergics
i. Stimulates the Parasympathetic Nervous System
ii. Also Called:
1. Cholinergic Agonists
2. ParaSympathomimetics
3. Muscarinic Agonists
iii. Two Types of Cholinergic Receptors:
1. Muscarinic Receptors
a. Stimulates the parasympathetic responses
2. Nicotinic Receptors
a. Contraction of the Skeletal Muscles
iv. Major uses of Cholinergic Drugs:

Pharmacology 35
 1. Stimulate the Bladder and GI Tone
2. Constrict the Pupils
v. Other Effects of Cholinergic Drugs:
1. Decreases heart rate/ blood pressure
2. Increased salivary and bronchial secretions
vi. Adverse Effects: Parasympathomimetics
1. Profuse salivation
2. Increased muscle tone
3. Urinary Frequency
4. Abdominal cramping and diarrhea
5. Bronchoconstriction
6. Bradycardia
7. Hypotension
vii. Bethanechol (Urecholine)
1. Cholinergic agent that elicits all of the parasympathetic responses
a. Activates muscarinic receptor activation
2. Therapeutic Use
a. Relieves urinary retention
3. Adverse Effects
a. With oral dosing, side effects are rare
b. Could have full range of parasympathomimetic responses
viii. Anticholinergics
1. Inhibits the action of Acetylcholine
2. Also called
a. Parasympatholytics
b. Antimuscarinic Agents
3. Major Responses include:
a. Increase in the pulse rate
b. Decrease in GI motility
c. Relaxation of the bronchi
d. Decrease in salivation
e. Dilation of the pupils
ix. Anticholinergic Agents: Atropine
1. Used as:
a. Preop med to decrease salivary secretions and maintain heart rate
b. Increase heart rate when bradycardia is present
c. Dilate pupils for eye exams/eye surgery
2. Adverse Effects: Anticholinergics
a. Tachycardia
b. Urinary retention
c. Dry mouth/ Dry eyes
d. Blurred vision
i. Increase in intraocular pressure
1. Contraindicated in patients with glaucoma
e. Constipation
x. Other common uses of Anticholinergics
1. Oxybutynin (Ditropan)
a. Urinary Tract Antispasmodic

Pharmacology 36
 b. Treats an overactive bladder
c. Used for Incontinence
2. Tolterodine (Detrol)
a. Used for overactive bladder only
3. Scopolamine
a. Motion sickness and eye examinations
4. Ipratropium (Atrovent)
a. Used for asthma, COPD and rhinitis
b. Administered by inhaler
5. Dicyclomine (Bentyl)
a. Used for irritable bowel syndrome
6. Exposure to nerve agents in a bioterrorism attack
a. All manifestations of nerve gas exposure are due to the over-stimulation of
Acetylcholine
i. Increase salivation
ii. Increase sweating
iii. Muscle twitching
iv. Involuntary urination and defecation
v. Confusion
vi. Convulsions
vii. Respiratory Distress & Respiratory Failure
7. Treated with anticholinergic agent
a. Injector kits are carried which contain Atropine
k. Drugs for Neurodegenerative Disorders
i. Parkinsons Disease
1. A Disease of the Extrapyramidal System
2. The most common neurodegenerative disorder after Alzheimer’s Disease
3. Incidence increases with age
4. No cure
ii. Extrapyramidal System
1. The functional system that is important in maintenance of equilibrium and muscle
tone
iii. Diseases that effect the extrapyramidal system result in symptoms such as:
1. Tremors
2. Rigidity
3. Postural instability
4. Slow movements
l. Parkinson’s Disease
i. Caused by death of neurons that produce the neurotransmitter Dopamine
1. Between 70 – 80% of these neurons must be lost before symptoms of Parkinson’s
are obvious
ii. Results in an imbalance between Dopamine and Acetylcholine in the basal ganglia
1. Decreased amount of dopamine and normal amount of acetylcholine
iii. Parkinsonism Drugs
1. Antiparkinsonims agents are given to restore the balance of dopamine and
acetylcholine
a. Dopaminergics  increase dopamine
i. Increase Dopamine levels in the Corpus Striatum of the Brain

Pharmacology 37
 ii. Used more commonly than Anticholinergics
iii. Levodopa
1. Traditionally has been the drug of Choice for Parkinson’s
Disease
a. Newer recommendations lead to Dopamine
Agonists instead
2. Levodopa will increase Dopamine (chatecholamine 
cannot pass BBB) levels in the brain
a. Will turn into Dopamine after biosynthesis in the
brain
3. Levodopa can pass the blood-brain barrier
a. Dopamine, if administered, will not cross the blood-
brain barrier
4. Levodopa is thought to be more effective than the
Dopamine Agonists, but with long term use, may end up
with disabling dyskinesias and decrease in effectiveness
a. Dyskinesia: A defect in the ability to perform
voluntary movement
5. With long term use of Levodopa, adverse effects tend to
increase, and therapeutic effects tend to diminish
6. Great results during the first 2 years
a. By the 5th year, many patients are back to pre-
treatment symptoms
b. May be more of a sign of disease progression and
not tolerance to the drug
7. Adverse Effects:
a. Dyskinesias
b. Postural hypotension
c. Psychosis
i. Develops in about 20% of clients
ii. Hallucinations, nightmares, paranoid
ideation
d. Darkened color of sweat and/or urine
e. “On-Off” Phenomonon
i. Abrupt loss of effect
ii. Occurs even when drug levels are high
iii. “Off” times may last from minutes to hours
iv. Over the course of the treatment, “Off”
hours will occur more and more frequently
f. Food Interactions
i. High protein foods can reduce therapeutic
responses
ii. Reduces amount of levodopa absorbed
iii. Reduces amount transported into the brain
iv. May be the cause of the “off” phenomenon
v. Patients are advised to spread their protein
consumption evenly throughout the day
g. Drug Holidays

Pharmacology 38
 i. “Drug Holidays” may be recommended
ii. Brief interruption of treatment
iii.  @10 days
iv. Must be hospitalized during the drug holiday
v. May lead to severe psychologic distress,
immobility, aspiration pneumonitis,
decubitus ulcers…
iv. Levodopa/Carbidopa
1. Combination drug
2. Carbidopa enhances the effect of Levodopa (synergistic
effect)
a. Carbidopa has no therapeutic effect by itself
b. Allows the dosage of Levodopa to be reduced by
about 75%
3. Examples: Sinemet and Paracopa
v. Dopamine Agonists (younger pt’s or beginning stages)
1. Stimulate Dopamine receptors directly
2. Recommended as the initial drug of choice for patients with
mild to moderate symptoms
a. May be supplemented with Levodopa
b. Levodopa is still the drug of choice for elderly and
those with advanced disease
3. Examples: Pramipexole (Mirapex) and Ropinirole (Requip)
vi. Advantages/Disadvantages of Dopamine Agonists
1. Advantages
a. Don’t compete with dietary proteins for absorption
and transport across the blood-brain barrier
b. Lower incidence of response failure if used long
term
2. Disadvantages
a. Hallucinations
b. Daytime sleepiness
b. Anticholinergics  decrease acetylcholine
i. Blocks the effects of Acetylcholine in the brain, decreasing
symptoms
1. Remember, the symptoms of Parkinson’s is due to an
imbalance of Dopamine and Acetylcholine
a. Low Dopamine compared to Acetylcholine
ii. Examples:
1. Tihexphenidyl (Artane)
2. Benztropine (Cogentin)
iii. Anticholinergics are not as effective as levodopa in treating
Parkinson’s
1. Used early in the course of the disease
2. Used in patient’s who cannot tolerate Levodopa
iv. What are the side effects of Anticholinergics?
1. Constipation, tachycardia, urinary retention, dry mouth,
blurred vision

Pharmacology 39
 v. Selegiline or Rasagiline
1. Newer agents
2. MAO-B Inhibitors (parkinson’s disease)
a. Inactivates MAO by irreversibly binding to it at
type B (brain) sites
b. MAO-B is an enzyme that inactivates dopamine
c. Leads to increased amounts of dopamine available
in the CNS
d. Nonselective (depression) MAO inhibitors used for
depression inhibit serotonin, norepenephrine and
Dopamine
vi. MAO – B Inhibitors
1. May be used as drug of choice for patients with mild
symptoms
2. May also be given during “off” times with Levodopa
therapy
2. Pharmacotherapy will not cure Parkinson’s, but rather will reduce symptoms
m. Alzheimer’s Disease
i. Degenerative Disorder characterized by progressive memory loss, confusion and inability
to think or communicate effectively
ii. Associated with cerebral atrophy
iii. Treatment of AD
1. Acetylcholine is the neurotransmitter responsible for learning and memory
a. In patients with advanced Alzheimer’s Disease, levels of acetylcholine are
90% below normal
2. Choline Acetyl Transferase
a. Enzyme responsible for Acetylcholine Synthesis
3. Acetylcholinesterase
a. An enzyme that stops the action of acetylcholine
4. Acetylcholinesterase Inhibitors are the most widely used agents for Alzheimer’s
Disease
5. When Acetylcholinesterase is inhibited, Acetylcholine levels become elevated
iv. Acetylcholinesterase Inhibitors
1. These agents are Parasympathomimetics
2. These agents are only used in the early stages of Alzheimers
a. They only work if there are functioning neurons
b. As the disease progresses, these agents are usually discontinued
3. Examples:
a. Donepezil hydrochloride (Aricept)
i. Once a day schedule
ii. Best tolerated
b. Galantamine (Reminyl)
c. Tacrine (Cognex)  4x day dosing
4. What side effects would you expect to see? Diarrhea, abdominal cramping, pupil
constriction, bronchi constriction
5. Should this drug be use by patients with asthma or COPD? NO à constriction of
bronchi

Pharmacology 40
 6. Should this agent be used in a patient that has a history of peptic ulcer disease?
NO à increases gastric motility
v. Memantine
1. Newest Drug approved for Alzheimers Disease
a. Approved in 2003
b. In use in Germany since 1983
2. Indicated for moderate to severe disease
3. Thought to slow the cognitive decline
4. Works by slowing/controlling the influx of calcium into the cells
n. Drugs for Seizures
i. Called Antiepileptics
ii. Seizures:
1. Caused from abnormal electrical discharge from the Cerebral Neurons
iii. Antiepileptics suppress the Abnormal Electrical Impulses
iv. Suppress seizures, but do not treat the cause of the seizures
v. Goal of antiepileptic agents:
1. Suppress neuronal activity to prevent abnormal firing
vi. Four mechanisms by which Antiepileptics act:
1. Potentiating GABA
2. Blocking the receptors for Glutamate
3. Delaying an influx of Sodium
4. Delaying an influx of calcium
vii. Drugs that Potentiate GABA
1. GABA:
a. An inhibitory neurotransmitter that is widely distributed throughout the
brain
2. These agents decrease neuronal excitability
3. Drugs that potentiate GABA work by:
a. Directly binding to GABA receptors and thus increase the effectiveness
i. Benzodiazepines and Barbiturates
4. Promote GABA release
5. Inhibit GABA reuptake
6. Inhibiting the enzyme that degrades GABA
viii. Blocking the Receptors of Glutamate
1. Glutamic acid (Glutamate)
a. Primary excitatory transmitter in the CNS
2. If receptor is blocked, will decrease the neuronal excitation
a. Felbimate
b. Topiramate
ix. Suppression of Sodium and Calcium Influx
1. When sodium ions and Calcium ions are delayed from moving across the
neuronal membrane, the CNS activity will be suppressed
x. Types of Seizures
1. Partial (focal) Seizures
a. Localized symptoms
b. Discrete symptoms that are determined by the brain region involved
2. Generalized Seizures

Pharmacology 41
 a. Seizure activity is caused from abnormal electrical activity that is
conducted widely throughout both hemispheres of the brain
3. Absent Seizures
a. Zone out – stay awake but do not respond for 10-30 seconds, do not
remember what happened
4. Pharmacologic choice will be dependent on type of seizure activity
5. Phenytoin is effective with Partial and Tonic-Clonic, but not with absence
seizures
6. Valproic Acid seems to be effective with all types of seizures
xi. Special Considerations
1. Plasma Drug Levels
a. Monitored on most Antiepileptics (narrow therapeutic range)
b. To establish a safe and effective plasma level
2. Promoting patient Adherence
a. Extremely important on these agents
b. Narrow therapeutic range
3. Discontinuance of the agents
a. These agents must be withdrawn slowly over a period of 6 weeks to
several months
4. Most anticonvulsants are cytochrome P450 Inducers
a. Many drug-drug interactions
5. May reduce the effectiveness of birth control pills
xii. Two Categories of Antiepileptic Agents
1. Traditional Agents
a. Last agent approved in 1978
b. Cost less
c. More extensive experience
d. Troublesome side effects
e. Complex drug interactions
f. Phenytoin (Dilantin)
i. Most widely used antiepileptic agent
ii. Works through inhibition of sodium channels
iii. Used to treat all forms of seizures except absence seizures
g. Narrow therapeutic range
i. Doses of phenytoin needed to produce therapeutic effects are only
slightly smaller than the doses that may cause toxicity
ii. As doses rise slightly, the drug will saturate the liver and
overwhelm the liver’s ability to metabolize
iii. According to your text “small changes in dosage produce large
changes in drug levels”
h. Therapeutic Range
i. 10 – 20 mcg/mL
ii. Doses must be individualized based on careful serum monitoring
i. Gingival hyperplasia
i. Excessive growth of gum tissues
ii. Side effect in about 20% of clients
iii. Nurses must teach patients about good oral hygiene including gum
massage

Pharmacology 42
j. Teratogenic effects to the fetus if used during pregnancy
i. Pregnancy Category D
ii. Can lead to:
1. Cleft palate, heart malformations, motor or mental
deficiency, microcephaly…
2. Also causes bleeding tendencies in the newborn because it
decreases the synthesis of vitamin K
k. Drug interactions
i. Liver Enzyme Inducer
1. Decreases the effect of other drugs such as Warfarin, Oral
contraceptives…
ii. Highly Protein Bound
1. Valproic Acid elevates levels of free phenytoin by
displacing it from protein binding sites
l. Carbamazepine (Tegretol)
i. Effective against tonic-clonic and partial seizures, but not absence
seizures
ii. Works by suppressing sodium influx
iii. May be used for Bipolar Disorder
iv. Liver Enzyme Inducer
1. Increases it’s own metabolism over time
2. Half life will decrease over time
a. Initial treatment: Half life of 40 hours
b. With continue treatment: Half life of 15 hours
v. Adverse Effects
1. Minimal effect on cognitive function
a. Often the drug of choice for younger children
vi. Hematologic Effects
1. Bone marrow suppression
a. Leukopenia, anemia and thrombocytopenia
b. CBC should be monitored
vii. Teratogenic Effects
1. Category D
m. Valproic Acid (Depakene, Depakote)
i. Will treat all major seizure types
ii. Also used in the treatment of Bi-Polar Disorder and migraine
headaches
iii. Works by three mechanisms:
1. Suppresses sodium and calcium influx, also augments
GABA
iv. Causes minimal sedation and cognitive impairment
v. Teratogenic Effects
1. Category D
2. Neural Tube defects
a. Women are encouraged to take a folic acid
supplement
vi. May be hepatotoxic
1. Rare

Pharmacology 43
n. Ethosuximide (Zarontin)
i. Drug of choice for absence seizures
ii. Will not work for other types of seizures
iii. Does not require serum level monitoring
1. Dose is determined by watching the incidence of the
seizure activity
o. Phenobarbital
i. One of the oldest antiepileptic agents
ii. Considered a “barbiturate”
1. Can cause physical dependency
iii. Significant side effects
1. Learning impairment, Lethargy, Depression
iv. Not used as commonly as it once was
p. Oxcarbazepine (Trileptal)
i. Newer Antiepileptic Agents
ii. Most commonly prescribed of the newer agents
iii. A derivative agent of Carbamazepine
1. As effective
2. More expensive
3. Better tolerated
iv. Adverse Effects
1. Dizziness and Drowsiness
2. Hyponatremia
a. Sodium levels are monitored if patient is on any
other medications that effect sodium concentration
(diuretics)
3. Does not cause the severe hematologic problems seen with
carbamazepine
4. Pregnancy category C
a. Women should use effective contraceptives
q. Management of Status Epilepticus
i. Continuous tonic-clonic seizure that lasts at least 20 - 30 minutes
1. Patient develops tachycardia, hypertension, hypoxia,
acidosis and hypoglycemia
2. Can lead to permanent neurologic injury or death
ii. Goal of treatment:
1. Maintain airway
2. Correct hypoglycemia
3. Stop the seizure
iii. IV started
1. Glucose solution infused
2. Antiepileptic agent infused
iv. Lorazepam (Ativan) or Diazepam (Valium) are the agents of
choice
1. These drugs are “Benzodiazepines”
2. Effects of Ativan can last for 72 hours, so it is now the drug
of choice

Pharmacology 44
 v. Benzodiazepines are usually prescribed for short term control of
seizures
vi. If prescribed for long term therapy, the client will develop a
tolerance
vii. Once the seizurs have been stopped, Phenytoing (Dilantin) or
Fosphenytoin (Cerebyx) may be given for long term suppression
2. Newer Agents
a. Approved in 1993 or later
b. Cost more
c. Less experience, therefore, prescribed less frequently
d. Smaller risk of teratogenic effects
e. Fewer drug interactions
3. Both groups appear equally effective
4. Both groups have their advantages and disadvantages
o. Psychotherapeutic Drugs
i. Schizophrenia
1. Chronic psychotic illness
2. Characterized by disordered thinking and difficulty comprehending reality
ii. Symptoms of Schizophrenia:
1. Hallucinations, delusions, agitation and paranoia
2. Lack of motivation, blunt affect, social withdrawal
3. Disordered thinking, memory and learning difficulties, inattentiveness
iii. Cause of Schizophrenia
1. Exact etiology is unknown
2. Thought to be caused from an excess of Dopamine in the brain
a. All antipsychotic drugs work by competing with the Dopamine receptor
sites
b. Thus, they block Dopamine receptors in the brain
i. Thought to be “Dopamine Antagonists”
3. DISEASE CAUSED FROM “LACK OF DOPAMINE” 
iv. Two Major Categories of Antipsychotic Agents
1. First Generation (Conventional) Agents
a. Further classified as low potency, medium potency or high potency
b. Block receptors for Dopamine
c. EPS symptoms likely
d. Two chemical categories of Conventional Agents
i. Phenothiazines
1. Chlorpromazine (Thorazine)
2. Thioridazine (Mellaril)
ii. Butyrophenones (Phenothiazine-Like)
1. Haloperidol (Haldol)
e. Adverse Effects of Conventional Antipsychotic Agents
i. Drowsiness
ii. Anticholinergic Effects
iii. Orthostatic Hypotension
iv. Extrapyramidal Symptoms
f. Extrapyramidal Symptoms (EPS)
i. Acute Dystonias

Pharmacology 45
 1. Severe muscle spasms
2. Tongue, neck, face or back
3. Opisthotonic Posturing
ii. Akathisia
1. Inability to rest or relax
2. Pacing and squirming
iii. Parkinsonism
1. Tremors
2. Mask Like Face
3. Stooped posture
4. Rigidity
5. Shuffling Gait
6. Pill-Rolling
7. Bradykinesia
iv. Tardive Dyskinesia
1. Develops in 20% of patients with long-term therapy
2. Serious Side Effect
3. Protrusion of tongue is accompanied by sucking, smacking
lips, involuntary movements of the body and extremities
4. Med should be stopped immediately if symptoms are
exhibited
5. For many patients, the symptoms are not reversible
6. Results in speaking and nutritional difficulties
2. Second Generation (Atypical) Agents
a. Moderately block receptors for Dopamine
i. Lower risk of EPS symptoms
b. Stronger block of receptors for Serotonin
c. Newer drugs on the market
d. Have become the drug of choice for treatment of Psychoses
e. Greater therapeutic Effects
f. Not likely to cause EPS Symptoms
g. Also called: Second Generation
v. Atypical Antipsychotic Agents
1. Mechanism of Action
a. Block Dopamine Receptors (loosely)
b. Also block Serotonin and Alpha-adrenergic receptors
2. Examples:
a. Risperidone (Risperdal)
b. Olanzapine (Zyprexa)
c. Dibenzodiazepine (Clozapine)
vi. Side Effects of Atypical Antipsychotics
1. Weight Gain
a. May quickly lead to obesity
b. Especially Clozapine (Clozaril) and Olanzapine (Zyprexa)
2. Increase in prolactin levels
a. Leads to menstrual disorders, sexual dysfunction and osteoporosis
3. Teratogenic effects
a. Contraindicated during pregnancy and lactation

Pharmacology 46
 4. Diabetes
a. New onset
p. Depression
i. Three Types of Depression
1. Reactive
a. Sudden onset with precipitating factors
b. Normal grief/sadness
c. Appropriate reaction to a major life stressor
2. Unipolar
a. Major depression
b. Loss of interest in work and home
c. Considered an illness
3. Bipolar
a. Manic and depressive
ii. Depression is most common psychiatric disorder
iii. Affects 30% of population
iv. Only 30% of population with depression are treated with medication
1. Depression is under-diagnosed and under-treated
v. Theory of Depression
1. Caused from insufficient amount of monoamine neurotransmitters
a. Norepinephrine
b. Serotonin
vi. Antidepressants
1. St John’s Wort:
a. Herbal Supplement
b. Decreases the reuptake of the neurotransmitters:
i. Serotonin, Norepinephrine & Dopamine
2. Conflicting study results regarding effectiveness
3. Thought to be as effective as the Tricyclic antidepressants in treating mild to
moderate depression
4. Not shown to be effective in treating severe depression
5. Known to interact adversely with many other drugs
a. Induces cytochrome P450 enzymes
b. Induces P- Glycoprotein
c. Intensifies the serotonin effects
i. May lead to fatal serotonin syndrome
vii. Five Groups of Antidepressants
1. Tricyclic (TCA’s)
a. Available in the late 1950’s
b. Blocks the uptake of norepinephrine and serotonin
c. Less expensive than the SSRI’s
d. Therapeutic response takes 2-6 weeks
e. Gradually withdrawn when discontinuing
f. Used most commonly for major Depression
g. Examples:
i. Amitriptyline (Elavil)
ii. Imipramine (Tofranil)
h. Side Effects:

Pharmacology 47
 i. Sedation
ii. Anticholinergic effects
iii. Orthostatic Hypotension
1. Blocks Alpha 1 receptors
iv. Increase risk of suicide early in treatment
1. Could overdose on the medication
2. Supply should be limited to one week in the beginning of
therapy
2. Selective Serotonin Reuptake Inhibitors
a. Introduced in 1987
b. Most commonly prescribed antidepressant
c. $3 Billion in annual sales
d. SSRI’s Block the reuptake of serotonin
i. Do not block the uptake of dopamine or norepinephrine
e. More expensive than the Tricyclics
f. Do not block cholinergic and alpha 1 adrenergic receptors
i. Fewer side effects
g. Used for major Depression
h. Also used to treat:
i. Obsessive/Compulsive
ii. Panic
iii. Phobias
iv. PTSD
v. Anxiety
i. Examples of SSRI’s:
i. Fluoxatine (Prozac)
ii. Fluxovamine (Luvox)
iii. Sertraline (Zoloft)
iv. Paroxetine (Paxil)
v. Citalopram (Celexa)
vi. Escitalopram (Lexapro)
j. Side Effects
i. Sexual dysfunction
1. Up to 70% of men and women may experience decreased
libido and lack of ability to reach an orgasm
2. May result in noncompliance with medication
ii. Insomnia
iii. Headache
iv. Weight gain
v. Serotonin Syndrome (SES)
1. May occur when taking SSRI’s along with other
medications that increase serotonin levels
a. MAOI’s, Tricyclics, Lithium
2. Occurs if Serotonin levels accumulate in the body
3. Symptoms include:
a. Confusion, anxiety, restlessness, hypertension,
tremors…

Pharmacology 48
 4. Recommended treatment is supportive and discontinue the
SSRI.
a. If untreated, may result in death
vi. Withdrawal Syndrome
1. Abrupt discontinuation of SSRI’s can cause a withdrawal
syndrome.
2. Symptoms include:
a. Headache
b. Dizziness
c. Nausea
d. Tremors
e. Anxiety
3. Symptoms can last for 1 – 3 weeks
4. Drug must be tapered slowly
3. Serotonin/Norepinephrine Reuptake Inhibitors (S/NRI’s)
a. Block reuptake of serotonin and norepinephrine
b. Similar effect to SSRI’s
i. SSRI’s seem to be better tolerated
c. Two drugs in this category:
i. Venlafaxine (Effexor)
ii. Duloxetine (Cymbalta)
iii. Desvenlafaxine (Pristiq)
4. Monoamine Oxidase Inhibitors (MAOI’s)
a. The first drug approved to treat depression in the 1950’s.
b. Inactivates Monoamine Oxidase
c. Monoamine Oxidase is an enzyme found in the liver, the intestine & the
brain
i. The function of Monamine Oxicase is to:
1. inactivates the three neurotransmitters
2. Inactivates tyramine in foods
d. Examples:
i. Tranylcypromine (Parnate)
ii. Isocarboxazid (Marplan)
iii. Phenelzine (Nardil)
e. Used to treat reactive or unipolar depression
f. Very effective
g. Due to severe side effects, not used often
h. Only used when other antidepressants are not effective
i. Drug – Food Interactions
i. Normally, dietary Tyramine is metabolized by MAO in the
intestinal wall and in the liver
ii. Tyramine, if not metabolized, will promote the release of
norepinephrine from the sympathetic system
iii. MAOI’s inactivate the enzymes that detoxifies Tyramine
1. will cause a hypertensive crisis due to a drastic release of
norepinephrine into the blood stream
iv. Tyramine Rich Foods

Pharmacology 49
 1. Cheese, cream, yogurt, bananas, raisins, coffee, chocolate,
Italian green beans, liver, sausage, soy sauce, beer, red
wine
j. Drug – Drug Interactions
i. MAOI’s used concurrently with other antidepressants or
sympathomimetic drugs
1. Can cause a hypertensive crisis
2. Due to the drastic increase in norepinephrine
ii. MAOI’s used concurrently with SSRI’s
1. Serotonin Syndrome
iii. MAOI’s will potentiate the hypoglycemic effect of insulin and oral
hypoglycemic agents
5. Atypical Antidepressants
a. Available in the 1980’s
b. Used for major and reactive Depression
c. They affect one or two of the three neurotransmitters
d. Examples:
i. Trazadone (Desyrel)
ii. Bupropion (Wellbutrin)
iii. Mirtazapine (Remeron)
q. Mood Stabilizers
i. Used to treat Bi Polar Disorder
ii. Effective in controlling the Mania and Depression
iii. Mood Stabilizers:
1. Lithium
2. Valproic Acid
3. Carbamazepine
iv. Many patients also receive an antipsychotic, and some may require an antidepressant
v. Lithium
1. Approved in the US in 1970
2. Drug of choice for controlling acute manic episodes and for long-term
prophylaxis against recurrence
3. Narrow Therapeutic Range
a. 0.6 to 1.5mEq/L
b. Death has resulted from Lithium levels > 2.5mEq/L
4. Serum Lithium levels should be monitored frequently
a. Every 1 to 3 days when beginning therapy
vi. Lithium/Sodium Relationship
1. Lithium is a salt
2. Low serum sodium level will increase risk of lithium toxicity
3. Important that serum sodium levels remain normal
4. Sodium levels will be affected by:
a. Vomiting/ Diarrhea
b. Sweating
c. Use of diuretics….
5. Lithium is excreted by the kidneys
6. Renal excretion of lithium is affected by blood levels of sodium
7. Lithium excretion is reduced when blood levels of sodium are low

Pharmacology 50
 8. When the kidneys sense that sodium levels are inadequate, it retains lithium in an
attempt to compensate
9. If the sodium levels are low, the lithium will be retained and accumulate rapidly
to toxic levels
vii. Valproic Acid and Carbamezapine
1. These antiepileptic drugs can suppress mania and stabilize mood in patients with
Bi-Polar Disorder
2. Valproic Acid is very effective and gaining popularity as drug of choice
r. Sedative Hypnotic Agents
i. CNS Depressants
ii. Used to treat anxiety
1. Anxiolytic agents
2. Antianxiety agents
iii. Used to treat insomnia
1. Called Hypnotics
iv. Terms: Sedative Hypnotic
1. Sedative Effect: Depresses physical and mental responses but does not alter
consciousness
2. Hypnotic Effect: A form of natural sleep, Not hypnosis
3. Sedative-Hypnotic Effects are sometimes derived from the same drug, using
different dosing
4. Three classes of CNS Depressants are used to treat Anxiety and Insomnia
a. Barbiturates
i. Secobarbital
ii. Barbiturates used to be the drug of choice for treatment of anxiety
and insomnia.
1. They have since been replaced by safer agents
iii. Barbiturates…
1. can lead to tolerance and dependence, have a high abuse
potential.
2. are powerful respiratory depressants and can be fatal with
an overdose
iv. Barbiturates are still used in seizure control and anesthesia
v. Barbiturates act by binding to GABA receptor channels
1. Intensifies the effect of GABA
2. GABA is the natural “inhibitory” neurotransmitter
vi. Barbiturates are classified as:
1. Long Acting
2. Short to Intermediate Acting
3. Ultrashort Acting
vii. Long Acting:
1. Phenobarbital
2. Used to treat epilepsy
viii. Short to Intermediate acting:
1. Secobarbital (Seconal)
2. Short term treatment for insomnia
ix. Ultrashort Acting:
1. Thiopental

Pharmacology 51
 2. General Anesthetic
b. Benzodiazepines
i. Diazepam
ii. Drug of first choice in treating anxiety and insomnia
iii. Also used for:
1. general anesthesia, seizure disorders, muscle spasms, panic
disorder and alcohol withdrawal
iv. Potentiates the action of GABA
v. Lipid soluble so they readily cross the blood-brain barrier
vi. Greater margin of safety than the Barbiturates
1. Lower potential for abuse
2. Produce less tolerance and dependence
3. Fewer drug interactions
4. Low risk of respiratory depression
vii. Anxiolytics:
1. Librium
2. Xanax
3. Ativan
4. Valium
5. Tranxene
viii. Insomnia Therapy:
1. Estazolam
2. Restoril
3. Halcion
4. Doral
c. Benzodiazepine Like Drugs
i. Zolpidem
ii. Three Benzodiazepine-Like Drugs are available
iii. Used for insomnia
1. Not indicated for anxiety
iv. Structurally different from the Benzodiazepines
1. But act as agonists as the receptor site on the GABA
receptor
v. Zolpidem (Ambien)
1. Approved for short term use of insomnia
2. Many patients use it on a long term basis
a. No apparent tolerance
b. Little dependence
c. Minimal withdrawal symptoms
3. Should not be combined with other CNS depressants such
as alcohol
vi. Eszopiclone (Lunesta)
1. Approved by the FDA in 2005
2. Approved for long term use
a. Ambien is approved only for short term use
b. Not necessarily safer than Ambien, but the
pharmaceutical company had it tested over a 6
month time period, whereas Ambien was not

Pharmacology 52
 vii. Zaleplon (Sonata)
1. First drug in a new class of hypnotics
2. Approved for short term use
a. Does not seem to produce tolerance
3. Rapid onset and short duration of action
a. Beneficial in helping patients fall asleep
viii. Melatonin Agonist
1. Ramelteon (Rozerem)
2. Relatively new hypnotic
3. Activates the receptors for melatonin
4. Long-term use is permitted
5. Very well tolerated
v. Attention Deficit/Hyperactivity Disorder
1. Unknown cause
2. Positive family history is common
a. No specific genetic marker has been identified
3. Attention and inhibition requires coordination of cortical and subcortical
functioning
4. The ability to inhibit distractions is cortically mediated at the prefrontal cortex.
a. Dopamine and norepinephrine are important in linking subcortical areas to
the frontal lobe
5. Disproven as causative factors:
a. Chocolate/ Sugar
b. High Carbohydrate foods/ beverages
c. Food additives
6. Affects 4 – 12% of school-aged children and 3 – 4% of adults
7. All races and socioeconomic strata
8. 6:1 male: female ration
9. 65% of children with ADHD have at least one other comorbid condition
a. Depression, conduct disorder, oppositional defiant disorder, learning
disorder…
10. Three Subtypes of ADHD
a. ADHD: Predominantly Inattentive Type
i. Inattention is the major problem
ii. Diagnosis may not be made early because they are not disruptive
b. ADHD: Predominantly Hyperactive-Impulsive Type
i. Often diagnoses in preschool or kindergarten
c. ADHD: Combined Type
d. ADHD in Childhood is characterized by:
i. Poor attention span
ii. Cannot stay focused on one task at a time
iii. Behavior control issues
iv. Sleep disturbance
v. Impulsiveness….
e. ADHD in Adulthood is characterized by:
i. Difficulty with attention
ii. May underperform at work
iii. Similar to mood disorders

Pharmacology 53
 1. Depression, Anxiety
11. Agents for ADHD
a. CNS Stimulants are the Drug of Choice
i. Amphetamine and Amphetamine-Like Drugs
b. These agents work because they heighten alertness and increase focus
i. Release norepinephrine, dopamine and serotonin
12. Examples of CNS Stimulants Used in the Treatment of ADHD
a. Methylphenidate (Ritalin and Concerta)
i. Drug of choice
ii. 70% of children on this drug
iii. Typically administered before breakfast and lunch
1. 2.5 – 5mg
2. Dose increased at weekly intervals
iv. Concerta is a sustained release agent administered once daily
v. Daytrana is a transdermal patch.
1. Onset is about 2 hours
2. Peaks in 9 hours. Patch removed each day at about 9 – 10
hours
a. Effects will last about 3 hours after patch removal
vi. High potential for developing dependence when used for extended
periods
1. Recommend periodic “drug-free holidays”
vii. Ritalin has a high abuse potential
1. $10.00 per pill on the street
viii. Anorexia, weight loss and growth/development delays are common
1. Anorexia is common with all CNS stimulants
ix. May lower the convulsive threshold in patients with prior history
of seizures
x. Sudden death has been reported on children with structural cardiac
dysfunction
xi. SIDE EFFECTS OF CNS STIMULANTS

xii. Amphetamines and Amphetamine-Like Drugs should not be taken

in the evening or bed time due to insomnia
xiii. Overdose is treated with Increasing Acidity of Urine
xiv. Acidic Urine decreases the half-life of the amphetamine
b. Dexmethylphenidate (Focalin)
c. Dextroamphetamine (Dexedrine)
d. Amphetamine mixture (Adderall)
i. Amphetamine Salt
ii. Available in short and long duration formulas
iii. Approved for use in children and adults
iv. Similar to Methylphenidate in side effects

e. Atomoxetine (Strattera)

Pharmacology 54
 i. Newer agent now being used for ADHD that is NOT a CNS
Stimulant
1. No potential for abuse
ii. Approved for use in children, adolescents and adults with ADHD
iii. Classified as a “norepinephrine reuptake inhibitor”
iv. Efficacy appears to be equivalent to Methylphenidate
1. Although the drug is too new for true comparison
v. Atomoxetine is administered once daily
vi. Carries a blackbox warning advising of an increased risk for
suicidal ideation
vii. May increase blood pressure and heart rate
1. Use cautiously in kids with cardiovascular disease
13. Cardinal Points of Treatment
a. Treatment options listed in order of preference:
i. Counseling for parent/guardian
ii. First Line Agent
1. Typically Methylphenidate (Ritalin)
2. Long acting Methylphenidate (Concerta) if multiple dose
schedule is not desired
3. Blocks the reuptake of norepinephrine and Dopamine
iii. Amphetamine Salt
1. Adderall, Dexedrine
iv. Atomoxetine (Strattera)
1. Norepinephrine reuptake inhibitor
2. Not a CNS stimulant
v. Tricyclic Antidepressant
1. Norepinephrine reuptake inhibitor
2. Desipramine (Norpramin) or Nortriptyline (Pamelor)
vi. Bupropion (Wellbrutin)
1. For patients with a history of a cardiac disease or other
medical contraindications to stimulants
s. Analgesia/Pain Management
i. Acute Pain
1. Related to an identifiable injury, surgery, trauma or infection
2. Resolves within a predictable and expected time interval
ii. Chronic Pain
1. Seems to be the result of physiologic changes int eh nervous system
2. Often caused by untreated or undertreated persistent acute pain
3. Estimated 50 million Americans suffer from chronic pain
iii. Terminology:
1. Opium
a. A milky extract from the unripe seeds of the poppy plant
b. Opium consists of about 10% morphine and about 1.5% Codeine
c. These natural substances are called opiates
2. Opiates
a. The natural substances (morphine and codeine) found in opium
3. Opioid
4. General term referring to any of the opiate substances, natural or synthetic

Pharmacology 55
 5. Scientist have created synthetic opiates, similar to the natural ones found in opium
iv. Mu, Kappa and Delta Receptors
1. Opioids exert their action by stimulating these particular receptors
a. Primarily the Mu and kappa
2. Activation of the Mu Receptors cause:
a. Analgesia, Euphoria, Physical Dependence, and Respiratory Depression
3. Activation of the Kappa Receptors cause:
a. Analgesia, Miosis, Sedation and Respiratory Depression
4. Some Opioid Agonists activate both receptors, others activate one, and block the
other…
5. Opioid Antagonists such as Naloxone (Narcan) block the Mu and Kappa receptors
a. Compete for the Mu and Kappa receptors
v. Opioid Side Effects
1. Euphoria
2. Pupillary Miosis
3. Respiratory depression
a. Caused by a direct effect on the brainstem
b. Brainstem becomes less responsive to carbon dioxide
4. Depressed cough reflex
5. Nausea and vomiting
6. Orthostatic hypotension
a. Reduced peripheral vascular resistance and inhibited baroreceptor reflex
7. Decrease in gastric motility
a. Increases esophageal reflux
b. Leads to constipation
8. Inhibits urinary voiding reflex
a. Leads to urinary retention
vi. Dependence:
1. All Opioids have the potential to cause physical and psychological dependence
2. Most likely to occur when taking high doses for extended periods
3. Studies have shown that most nurses “undermedicate” for pain due to a fear of
addiction and respiratory depression
4. Studies have also shown that dependence rarely occurs when opioids are given to
treat “acute” pain.
a. Hospitalized patients receiving morphine for acute pain, up to 2 weeks,
will show no sign of dependence
5. To reduce the risk of dependence, combination products are frequently used
a. Narcotic/ nonnarcotic analgesics are combined
i. Dose of the narcotic can be kept small
ii. Synergistic effect for pain relief
6. Common Combination Analgesics are:
a. Vicodin (Hydrocodone and acetaminophen)
b. Percocet (Oxycodone HCl and acetaminophen)
c. Percodan (Oxycodone HCl and aspirin)
d. Darvocet (Propoxyphene and acetaminophen)
vii. Tolerance:
1. State in which a larger dose is required to produce the same response
2. Tolerance develops to analgesia, euphoria and sedation

Pharmacology 56
 3. Tolerance also develops to respiratory depression
a. Therefore those patients requiring higher doses due to drug tolerance, will
not be at an added risk for respiratory depression
4. Tolerance will not develop for constipation and miosis
a. Constricted pupils are characteristic
b. Constipation is a chronic problem
viii. Treatment Principles: Chronic Pain
1. Requires routine administration
2. Encourage the patient to take medication before the pain is severe
a. Will take less pain medication
3. Addiction generally is not a concern for patients with chronic pain or terminal
illness
4. Pain of greatest severity may be relieved by combining therapies
5. Unrealistic to expect total pain relief
6. Depression, anxiety and insomnia are common and augment the pain sensation
ix. Treatment Principles: Acute Pain
1. Determine the cause
2. Encourage nonpharmacologic therapies
3. Educate the patient
a. Reduces fear, which reduces pain perception
4. For mild to moderate pain, start with Acetaminophen or NSAIDs
5. Combination of NSAIDS and Acetaminophen is unlikely to improve pain
management
6. Be aware of maximum Acetaminophen dosage
a. 4000mg daily
7. Side effect of NSAIDs include GI bleeding, elevated blood pressure, fluid
retention and may provoke renal failure in the elderly
8. Opioids
a. If non-opioid treatment is not effective
b. May give opioid alone or in a combination with acetaminophen
c. Fear of addiction does not justify withholding of opiates or inadequate
management of pain
d. Educate client on side effects
e. Consider prophylaxis for constipation
9. Start at the lowest possible dose
a. Especially for clients who have not taken Opiates before
10. Adjust the dosage to achieve pain relief with acceptable levels of adverse effects
11. The ceiling dose is limited only by side effects.
12. Elderly patients are more susceptible to CNS side effects and to constipation
13. Educate your client to avoid alcohol use
14. In the case of head injury and increased intracranial pressure, opioids may
obscure the clinical picture
x. A – A – B – C – D – E – E
1. The Agency for Health Care Policy and Research (AHCPR) clinical practice
guidelines, include the following principles of pain assessment:
a. A = Ask about pain at every assessment
b. A = Assess pain systematically. Be consistent in using the same pain
intensity scale for pain measurement

Pharmacology 57
 c. B = Believe the patient and the family
d. C = Choose pain control options that are appropriate
e. D = Delivery of pharmacologic or nonpharmacologic interventions should
be timely, coordinated and logical
f. E = Empower the patient and family
g. E = Enable them to control their course to the greatest extent possible
xi. Morphine Sulfate
1. Primary opioid analgesic
2. Other opioids are compared with Morphine in terms of efficacy
3. Available in oral, rectal, sublingual, intramuscular, subcutaneous and intravenous
routes
4. Available in immediate-release and extended release formulations
a. Extended release formulations are MS Contin and Avinza
b. Given twice a day will provide 24 hour coverage
xii. Codeine
1. Schedule II and III
2. Analgesic and Antitussive
3. 10% of codeine is metabolized to morphine
4. Relatively less potent than morphine
a. Does not have the abuse potential of morphine
5. More likely than other opioids to cause constipation
xiii. Hydrocodone (Lortab, Vicodin)
1. Schedule III
2. Primary actions affects the CNS and smooth muscle organs
3. Available in combination with acetaminophen, aspirin or ibuprofen
4. Also available in combination with antihistamines, decongestants ad expectorants
for cough suppression
5. Less constipating than Codeine
xiv. Oxycodone
1. Schedule II
2. Available in combination with Acetaminophen and aspirin
a. Percocet (with Acetaminophen)
b. Percodan (with Aspirin)
3. Oxycontin
a. Time release formula
4. High abuse potential
xv. Hydromorphone (Dilaudid)
1. Schedule II
2. Very potent
3. Five times the potency of morphine
a. 2mg of Hydromorphone is equivalent to 10 mg Morphine
4. Produces less sedation, nausea, vomiting and constipation than Morphine
5. Respiratory depression is a major concern
xvi. Meperidine (Demerol)
1. Schedule II
2. Less potency than morphine
3. May be used for preoperative sedation, obstetric anesthesia and postoperative
analgesia

Pharmacology 58
 4. The major metabolite, normeperidine, can cause irritability and seizures
a. Should not be used for chronic pain due to risk of seizures
xvii. Fentanyl
1. Intravenous Fentanyl is a very potent, short-acting opioid
2. 0.1mg is equivalent to 10mg of morphine
a. 100 times as potent.
3. Transdermal Fentanyl is used in the outpatient setting for long-term relief of pain
a. Not appropriate to use for management of postoperative, mild or
intermittent pain due to risk of respiratory depression.
4. Very lipid soluble, has enhanced CNS penetration
5. Also available as a transmucosal “lozenge on a stick” product
xviii. Methadone (Dolophine)
1. Schedule II
2. Used primarily in the detoxification, treatment and maintenance of persons with
opiate addiction
3. May be used orally for treatment of severe and chronic pain in patients who
cannot tolerate other opiates
4. Long acting (36 – 48 hours)
5. Less sedating and euphoric
6. Respiratory depression is a major concern
t. Migraine Headaches
i. Approximately 29.5 million Americans suffer with Migraine Headaches
ii. Usually begins in the teenage years
1. Peaking between the ages of 25 and 34.
iii. Careful assessment should be done to rule out other causes for the headache
1. Tension Headaches
2. Influenza
3. Tumors
iv. Phases of a Migraine
1. Prodrome
a. Starts 24 hours before migraine
b. Irritability, food cravings, speech difficulties…
2. Aura
a. 30 – 60 minutes before the headache
b. Visual disturbances, numbness or tingling…
3. Headache (See table 20-1, page 305)
a. Described as severe, pulsating, unilateral or bilateral
b. Accompanied by nausea and vomiting, photophobia
c. May last for 4 – 72 hours
4. Postdrome
a. Fatigue, aching muscles
b. May last for 24 hours
v. Physiology:
1. Inflammation and Dilation of the Blood Vessels in the Cranium
2. Two compounds that have been shown to be altered during a migraine headache:
a. Calcitonin Gene-Related Peptide (CGRP)
i. Levels rise during a migraine
ii. Promotes vasodilation and inflammatory response

Pharmacology 59
 b. Serotonon (5-HT)
i. Levels fall during a migraine
ii. Cranial vessel vasodilation
vi. Two Categories of Agents Used for Migraine Headaches
1. Agents that will abort a Migraine Headache
a. Aspirin/ Acetaminophen
b. Serotonin (5-HT) Agonists (Triptans)
c. Ergot Alkaloids
2. Agents that will prevent Migraine Headaches from occurring
a. Beta Blockers
b. Calcium Channel Blockers
c. Tricyclic Antidepressants
d. Antiepileptic agents
vii. Serotonin (5 – HT) Agonists (Triptans)
1. Newest Group
2. First-line treatment for abortive therapy
3. Selective for the 5-HT receptors intracranial blood vessels
4. Produce vasoconstriction of certain intracranial vessels
5. Sumatriptan (Imitrex) was the first Triptan marketed in 1993.
6. Available in oral, subcutaneous, and and intranasal form
viii. Other Triptans:
1. Rizatriptan (Maxalt)
2. Zolmitriptan (Zomig)
ix. All Triptans are contraindicated in patients with coronary artery disease or uncontrolled
hypertension
x. Contraindicated in pregnancy
xi. Don’t use a Triptan if an Ergotamine Compound has been used in the past 24 hours
xii. May end up with Serotonin Syndrome if used concurrently with MAO inhibitors or
SSRI’s
xiii. Ergot Derivatives
1. Ergotamine (Ergostat)
2. Dihydroergotamine (DHE)
a. Vasoconstrictor
b. Inhibits the reuptake of norepinephrine
i. Allows more norepinephrine to attach to adrenergic sites, causing
prolonged vasoconstriction of cranial blood vessels
c. Available in oral, sublingual, inhalation and rectal suppository forms
d. Ergotamine compounds are pregnancy category X agents
3. Causes Nausea and Vomiting
a. Pretreatment with an antiemetic is beneficial
4. Should be limited to two doses, twice a week or less
a. Drug-Rebound headaches may occur if misused.
5. Use cautiously in patients with hypertension, coronary artery disease or peripheral
vascular disease due to the vasoconstriction action
xiv. DHE
1. Is an Ergot, as well as a 5HT receptor agonist
2. Not as selective as the Triptans
3. Binds to norepinephrine and Dopamine receptors

Pharmacology 60
 4. Does not cause the same peripheral vasoconstrictor effects as other Ergotamine
products
a. Safer to use.
xv. Treatment Guidelines: Abortive
1. Analgesics such as aspirin, NSAIDS, and acetaminophen are used for mild to
moderate migraines
2. OTC Combination products that include caffeine are approved for migraine
treatment
3. Triptans and Ergot Derivatives should not be used more than 2 days per week
a. Rebound headache
4. Both the Triptans and Ergotamine Drugs have the same cardiovascular cautions.
xvi. Preventive Treatment of Migraine Headaches
1. Beta Blockers
a. Proranolol (Inderal)
b. First line choice for prophylaxis
c. Thought to stabilize vascular tone
d. Also thought to work because it decreases cardiac output, thus decreases
blood flow to the brain
2. Calcium Channel Blockers
a. Regulates vascular smooth muscle contraction
b. Prevents vasospasms of the cerebral arteries.
3. Tricyclic Antidepressants
a. Amitriptyline (Elavil)
b. Blocks the uptake of Norepinephrine and Serotonin in the Brain
c. Allows more Serotonin for 5-HT Receptors
5. Lecture 5:

Pharmacology 61