Pharmacology Study Guide1. Introduction to Pharmacologya.
Pharmacology i. Study of medicines ii. The core of patient care, no
matter the nursing specialtyiii. 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 excretion3. 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 Nurse1. Know the drug being administereda.
Expected therapeutic reactionb. Possible side effects and adverse
reactions 2. Any known allergies to drugs3. 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 drugiii. 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 Objectivei. The objective of drug therapy is to provide
maximum benefit with minimum harm d. Legal Terminologyi.
Misfeasance negligence; giving the wrong drug or the wrong dose
resulting in the clients deathii. 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 1. Three basic goals:a. Collect
baseline data needed to evaluate therapeutic and adverse responses
b. Identify high-risk patientsc. Assess the patients capacity for
self-care ii. Dosage and Administration1. Must know that:a. Certain
drugs have more than one indication, and dosage may differ
depending on which indication the drug is used forb. 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 MARiii. Read med label carefully. Verify identity of
drug, amount of drug, and suitability for administration by
intended routeiv. Verify dosage calculations v. Implement any
special handling the drug may require vi. Dont administer any drug
if you dont understand the reason for its use f. Drug Namesi.
Chemical1. Exact description of the drugs composition 2. Chemical
structure ii. Generic1. Official name (nonproprietary name) 2.
Given by the manufacturer who first develops the drug before the
drug is approved 3. Only one generic nameiii. Trade/Brand1. 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
salei. 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) 1.
Preclinical Investigationa. Extensive laboratory research b.
Studies done on human and microbial cells cultured in the labc.
Studies performed on animals to look at drugs effectiveness at
different doses and to look for adverse effectsd. May take up to 5
yearse. 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 processb.
Consists of clinical phase trialsi. Researchers try to determine:1.
Proper dosage2. Effectiveness3. Possible adverse effects4. If the
drug worsens other medical conditions5. Drug interactionsa. 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
stageii. If there are concerns, the pharmaceutical company will be
required to address them b. The average NDA Review time is 17-24
monthsi. 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 timei. History of Drug
Regulation and Standardsi. 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 tested2. 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 Amendment1. 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 Act1. Set rules for manufacture and
distribution of drugs considered to have potential for abuse 2.
Defines categories into which controlled substances are placeda.
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 cancer2. 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 its 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 humansiv.
Category D: risk to human fetus has been proven 1. Used in life
threatening conditions2. 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 l. Brand Name vs. Generic
Drugsi. Generic drugs (store brands) are cheaper because
manufactures dont 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 Drugsi.
Drugs are categorized by similar characteristicsii. Drug
classification may indicate:1. The effect of the drug on the body
system 2. The symptoms the drug relieves3. The drugs desired effect
iii. Drugs may be in classifications such as:1. Cardiovascular
agents2. Respiratory agents 3. Gastrointestinal agentsiv. Each
class of drugs contains agents that are prescribed for similar
types of health problems:1. Cardiovascular agents:a. Antianginalb.
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 actiona. 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
Medicationsi. 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. Terminologyi. Addiction: continued use
of a specific psychoactive substance despite physical,
psychological, or social harm 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 stoppediv. Psychological
Dependence: intense, overwhelming desire or craving for a drug1.
Not a physical addiction, no physical discomfort after the agent is
discontinued2. 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 substance1. 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 related1. People who have developed a tolerance to alcohol,
will show tolerance to other CNS depressants 2. Pharmacokinetics
and Pharmacodynamics a. Nature of Drug Actions:i. Two Phases:1.
Pharmacokinetic Phasea. Absorption i. Passage of the drug molecule
into the bloodstreamii. Drugs are absorbed through the: 1. Skin 2.
Mucous membranes3. GI tract lining 4. Respiratory tractiii.
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
there2. Enteric coated drugs:a. Resist disintegration in the
gastric acid of the stomachb. 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 ii. Protecting the stomach from drugs that
can cause gastric discomfort d. Disadvantages of enteric coating:i.
Absorption time will varyii. onset of these drugs will be reliant
on the gastric emptying timeiii. may be within minutes, or hours
iv. Enteric coatings may fail to dissolvev. 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
preparationsa. 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 dissolutiona. Elixirs
and syrups will absorb faster than pills and tabletsb.
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 fillersi. Fillers
allow drugs to have various colors, sizes, and shapesii. Fillers
have ingredients that allow for better dissolution and absorption
5. Body surface areaa. 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 flowa. 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 partitioninga. 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. Dont usually give milk or antacids 2 hours before and 1 hour
after medication administration a. Unless otherwise directed from
drug book4. 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 organsa. 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 iv. Poor
circulation to the feet of a diabetic patient will alter the
availability of a drug to that sitev. 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 bloodstream2. 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 checked8. 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 cellsb. So tight that they prevent drug passagec. Only
drugs that are lipid soluble, or have a transport mechanism can
passd. Some meds such as sedatives and anticonvulsants readily pass
the BBBe. Most antitumor meds will not pass the BBB making brain
cancer difficult to treat 3. Fetal-Placental Barriera. The
membranes of the placenta separate the maternal circulation from
the fetal circulation 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 drugsi. 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
inactivationc. 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
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 system2. 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 drugsi. 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 affectediii. 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 Filtrationa. 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 passc. Protein (and protein bound drugs) will
not pass2. 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 membranec.
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 urineb. 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 ionizedd. 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 drugi. More
readily excreted in alkaline urineg. 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 l. If pt has renal disease,
drug excretion is slowed or impairedm. 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 prolongedb. Less drug is metabolized and
eliminated 4. A drug has several half-lives5. The first half life
is the time it takes for the drug concentration to reduce in half6.
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 drug10. 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
Phasea. 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 Effects1. Predictable
secondary effecta. Sometimes harmlessb. Sometimes causes injuryc.
Sometimes beneficial 2. May outweigh the benefit ii. Toxicity1.
When a drug accumulates in the blood above a therapeutic level
(overdose of insulin causes blood sugar levels to decrease) iii.
Allergic Reaction1. Unpredictable immune response; mild or severe
a. Urticaria hivesb. Eczema rashc. Pruritus itching of the skind.
Rhinitis swelling and clear drainage from nose e. Wheezing
constriction of the smooth muscles surrounding the bronchioles iv.
Idiosyncratic Effect1. Unpredictable; client overreacts or
underreacts to a drug v. Physical Dependencevi. Carcinogenic Effect
1. Ability of medications, environment and chemicals to cause
cancervii. Teratogenic Effect1. 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 concentrationiii. MEC: minimum effective
concentrationiv. 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 its 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 Durationa. 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 Lifea. 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 Rangeii. The ratio of a drugs LD to its ED 1.
ED: average effective dosea. 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 iv.
Drugs with a low therapeutic index have a narrow margin of safety1.
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 Index1. 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 EDi. 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
concentration1. Peak time will vary depending on drug and routea.
May be 10 minutes for drugs given IV or 4 hours if given PO2. 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 toxic2. 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 poresa. Only very small
ions such as potassium and sodiumb. Go around the cells2. Pass with
the aid of a transport systema. Different transport mechanismsb.
Most transport systems are selective for the drug c. P-Glycoprotein
i. A protein that transports a wide variety of drugs out of
cellsii. 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 urinev. 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
membraneb. Non-ionized agents move across the membrane c. Water
soluble agents and ionized agents do not move across the
membraneiii. 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 forma. The pH of the surrounding area, will
determine if the molecule has an electrical charge 4. Aspirin is a
weak acida. 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 ionii. Cannot cross cell membranes5. 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 Interactionsi. Drug Drug Interaction1. 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 a. Adverse
drug reaction:i. Undesirable drug effect, includes hypersensitivity
and anaphylaxis 3. Categories of Drug Interactions:a. Direct
Chemical or Physical Interactionsi. 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. Absorption1. 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 timei. 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 absorptioniii.
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 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
enzymesa. 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 excretiona. Alkaline urinei.
Promotes the excretion of drugs that are weak acids, such as
aspirin and barbiturates b. Acidic urinei. 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 Interactionsi. Onset, Peak, Duration of
Action ii. The combined effect of the drugs will have a:1. Additive
Effecta. 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 Effecta. 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 Effecta. 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
absorptiona. TCN binds with food (dairy products) 3. Some drugs
have increased drug absorption with fooda. 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 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. of all medications carry
federally approved indications for kids 2. Whereas 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: Pediatrics1. 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 pH1. 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 drugsi. 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 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% wateri. 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 sitesii. 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 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 problemsc. 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 11-1b. Gastrointestinal:i. Alkaline gastric
secretions1. Acidic drugs are poorly absorbed ii. Decreased
peristalsis 1. Delayed gastric emptying time c. Cardiac and
Circulatory:i. Decreased cardiac output1. Decreases blood flow to
all parts of the body including the liver and kidneys d. Hepatic:i.
Decreased enzyme function1. Decreases the livers ability to
metabolize and detoxify drugs 2. Increases the risk of drug
toxicity e. Renal: i. Decreased blood flowii. Decreased functioning
nephronsiii. Decreased glomerular filtration rate 1. Will prolong
the drug half-life2. 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 tract1.
Caused by decreased cardiac output 2. Slows down absorption iv.
Reduction in GI motility rate may delay onset of action b.
Distribution: i. Decrease in body water1. 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-life2. An
increase in the drug half-life will (increase/decrease) the risk of
drug toxicity d. Excretion: i. Decrease in renal blood flowii.
Decrease in glomerular filtration rate by 40 50% iii. These changes
will (increase/decrease) the drug half-life
3. Integumentary a. Topical Glucocorticoids i. Used for numerous
inflammatory or pruritic dermatoses 1. Atopic and Contact
dermatitis2. Psoriasis3. Eczema4. Insect bite reactionsii.
Mechanisms of Action1. Topical corticosteroids diffuse across cell
membranes and induce cutaneous vasoconstriction 2. The
vasoconstriction inhibits the migration of macrophages and
leukocytes into the area3. The degree of vasoconstriction is
commensurate with the potencyiii. Topical Corticosteriods1. Topical
corticosteroids are ranked according to potencya. Group I is the
most potent b. Group VII as the least potentc. Group VII is often
the OTC agents2. Potency is the most important variable when a
topical steroid is choseniv. Absorption varies depending on:1. The
vehicle useda. Ointments are more occlusive, thus more potent than
creams and lotions2. The amount of skin surface area covered3.
Location of the skina. Face, scrotum have thinner skin layers4.
Condition of the skin5. Temperature of the skin6. Use of occlusive
dressingv. Occlusive Dressings1. Use of plastic wrap2. Increases
skin penetration 10-fold3. May be beneficial in resistant cases4.
May lead to increased adverse effects and possible adverse systemic
effectsvi. Dosing and Special Considerations1. Apply sparingly!2.
Preparations of mild to intermediate strength should be considered
when large areas are treated because of the likelihood of systemic
absorption3. After long term use of with high potency agents,
Topical Corticosteroids should not be abruptly discontinueda. May
lead to rebound effect4. Treatment should be discontinued when the
skin condition has resolved. Tapering the corticosteroid will
prevent recurrence of the skin conditionvii. Topical
Corticosteroids: Geriatric Client1. Geriatric patients are more
susceptible to secondary infection when steroids are used2.
Geriatric patients are more susceptible to the systemic effects
because their skin tends to be thinnerviii. Topical
Corticosteroids: Pediatric Client1. May be more susceptible to
systemic adverse effects2. The least-potent strength compatible
with effective treatment should be used3. Potent corticosteroids
should typically not be used in children4. May lead to delays in
growth and development in childrenix. Monitoring the Patient1. With
Mid to High Potency Products, monitor for:a. Superinfection b.
Adverse Effects (Cushing Symptoms)c. Growth and development in
childrend. Blood glucose and serum potassium levelsx. Patient
Education1. Use exactly as prescribed2. Demonstate the amount of
the medication to applya. Pea size, spread thinly over the area3.
Instructions on occlusion if it is warranted4. Report any adverse
effectsb. Acne Preparationsi. Acne1. Inflammatory disorder of the
sebaceous glands2. Sebacious glands remain small throughout
childhood3. During Puberty, hormone levels (specifically androgens)
rise and cause an increase in sebum secretion4. The face, chest
back and upper arms have the largest and most numerous sebaceous
glands5. Acne is further be exaggerated by Propionibacterium
Acnes.a. Propionibacterium Acnesi. (P. Acnes) ii. A normal skin
residentiii. A microbe that converts sebum into an irritant fatty
acids iv. P. Acnes promotes inflammation by attracting
leukocytesii. Classifaction System1. Treatment is based on severity
and type of lesion present2. Milda. Comedones (Blackheads)b.
Noninflammatory lesion of acne3. Moderatea. Papules and Pustules4.
Severea. Cystic Acneiii. Benzoyl Peroxide1. Bactericidal agent
against P Acnesa. Does not promote resistance of P Acnes2. Used for
mild to moderate acne3. Available OTC and by prescriptiona. Most
common OTC medication4. Available as a cream, lotion, gel or wash5.
Has a keratolytic effecta. Helps to dry out and shed the outer
layer of the epidermis6. Client should be instructed to:a. Apply
once a day in the beginningb. Increase frequency of application to
a maximum of three times daily as tolerated.c. Wear sunscreen when
outdoors.iv. Topical Clindamycin or Erythromycin1. For mild to
moderate acne2. Works by suppressing P Acnes3. Antibacterial and
antiimflammatory action4. Therapeutic response seen in 6-12 weeks5.
Combination products available with Benzoyl Peroxidea. Monotherapy
with either antibiotic will quickly lead to resistancev. Topical
Retinoids1. Considered 2nd or 3rd line therapy2. Derivatives of
vitamin A (retinol)3. Retinoids are used against both inflamed and
noninflamed acne lesions4. Can be used alone or in combination with
antibiotics5. Effect may not be seen for 2 to 3 weeks6. Can be
extremely irritating to the skin7. Patient should use a small
amounta. Pea size8. Wait for 20 30 minutes after washing face to
apply9. Will cause severe sun sensitivitya. Avoid the sun, or wear
sunscreen10. Avita and Retin-A Micro are newer formulations of the
original Retin-Aa. The newer formulations may have less intense
localized effects.vi. Systemic Antibiotics1. Used for moderate to
severe acne that does not respond to topical treatment2. Works by
suppressing the growth of P. Acnes and decreasing inflammation3.
Usually used in combination with a topical retinoid4. Minocycline
and Doxycycline are the agents of choicea. Tetracycline and
Erythromycin are alternativesb. Resistance to Tetracycline and
Erythromycin is common5. Good results with systemic antibiotics,
but takes 3 6 months to reach maximum benefit6. After symptoms have
controlled with an oral antibiotic, patients should be switched to
a topical antibiotic for long-term maintenancevii. Isotretinoin
(Accutane)1. Derivative of vitamin A2. Very potent and effective3.
Reserved for severe cystic acnea. Due to severe side effects4.
Treated for 20 weeks5. If a second course of treatment is
necessary, the client should wait 8 weeks before starting again6.
Accutane:a. Decreases sebum productionb. Decreases inflammationc.
Causes Keratinization d. Lowers the skin population of P. acnes7.
Side Effects:a. Dry skin & mucous membranesb. Nasal irritation/
nose bleedsc. Dry eyes/ Photosensitivityd. Elevated blood
triglyceride levelsi. Etoh intake escalates triglyceride levelse.
Teratogenic effectsi. Not to be taken by sexually active femalesii.
Category Xf. Arthralgia g. Rare: Mood changes/ Depression/ Suicide
tendenciesh. Risk of Toxicityi. Tetracyclines and Vitamin A
supplements increase risk of toxicityii. Should be discontinued
before starting Isotretinoin (Accutane)i. Risk of Teratogenic
Effectsi. Fetal abnormalities include:1. Hydrocephalus,
microcephaly, facial malformation, cleft palate, cardiovascular
defects and abnormal formation of the outer ear
8. iPLEDGEa. Name of a very strict risk management programb.
Went into effect in December, 2005c. The iPLEDGE program has rules
that apply to the physician, patient, and pharmacistd. All
transactions involving Isotretinoin (Accutane) must be processed
through a central automated systeme. Pregnancy must be ruled out
prior to prescribing and again before each monthly refilli. Two
negative pregnancy tests are required before the first dosef. Each
patient must use two effective forms of birth control, even if one
is a tubal or vasectomyg. Birth control measures must be
implemented at least 1 month before starting isotretinoin
(Accutane), and continue for one month following the last
administrationh. Informed consent must be signedi. 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 wholesalerc. Treatment of Burnsi. Topical
Sulfonamides1. Used to suppress bacterial colonization in patients
with 2nd and 3rd degree burns. ii. Agents:1. Silver Sulfadiazine
(Silvadene)2. Mafenide (Sulfamylon)iii. Administration:1.
Premedicate with analgesic before application2. Cleanse and debride
prior to administration3. Use sterile technique to apply4. Burn
should be coated at all times with thin layeriv. Adverse Effects:1.
Nephritisa. Monitor Renal function i. Creatinine and BUNii. Urine
output2. Leukopenia a. Monitor CBC3. Silver Sulfadiazine may cause
skin discoloration
4. Neurological Agentsa. Peripheral Nervous Systemi. Consists of
Two Divisions:1. Somatic Motor Systema. Voluntaryb. Acts on
Skeletal Muscles2. Autonomic Nervous Systema. Involuntaryb.
Controls or regulates the functions of the heart, respiratory
system, smooth muscles, GI system and glandsb. Autonomic Nervous
System i. Consists of two divisions:1. Sympathetic Nervous Systema.
Fight or Flighti. Also Called Adrenergicii. Main neurotransmitter
is Norepinephrine iii. 2. Parasympathetic Nervous Systema. Rest and
Digesti. Also called Cholinergicii. Main neurotransmitter is
Acetylcholineiii. c. Receptors of PNS i. Two Basic Categories of
Receptors1. Cholinergic Receptorsa. Respond to Acetylcholine2.
Adrenergic Receptorsa. Respond to Norepinephrine and Epinephrined.
Subtypes of Cholinergic & Adrenergic Receptorsi. Subtypes of
Cholinergic Receptors1. Nicotinic and Muscarinic ii. Subtypes of
Adrenergic Receptors1. Alpha 1, Alpha 2, Beta 1 and Beta 2e.
Adrenergic Receptors: Alpha 1 and Alpha 2i. Alpha 1 is located on
the blood vessels and causes vasoconstrictionii. 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 heartii. Beta 1 = 1 heartiii. Beta 1 is also
located in the kidney1. Causes the release of renin into the
bloodiv. Beta 2 located primarily in the lungsv. Beta 2 = 2
lungsvi. Beta 2 is also in the arterioles and uterus1. Relaxes
uterine smooth muscles2. Dilates arterioles in the heart, lungs and
skeletal muscles
g. Adrenergic Agonistsi. Stimulates the Sympathetic Nervous
System1. Also Called:a. Adrenergics b. Adrenergic Agonistsc.
Sympathomimetics h. Adrenergic Drugsi. Most Sympathomimetics act by
directly binding to and activating adrenergic receptors1. 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 Agonistsi.
Adrenergics are divided into two chemical classifications: 1.
Catecholamines and Noncatecholamines a. Catecholamines i.
Epinephrine, Norepinephrine, Isoproterenol, Dopamine and Dobutamine
ii. Cannot be taken orallyiii. Short half lifeiv. Do not cross the
blood brain barrier b. Noncatecholamines i. Ephedrine,
Phenylephrine, and Terbutaline ii. Half life is longer than the
catecholamine groupiii. Can be taken orallyiv. Does cross the blood
brain barrierii. Adrenergics: work on one or more of the receptor
sitesiii. Alpha 1 Receptor Agonists1. Used for:a. Vasoconstriction
in blood vessels of the skin, viscera and mucous membranesi.
Treatment of nasal congestionii. To stop bleeding (nose bleeds)iii.
To elevate blood pressure1. Not the primary medication usedb.
Mydriasis during ophthalmic examinationsi. Not used often for this
purposeii. If applied topically to the eye, should not lead to
vasoconstriction or elevation in blood pressureiv. Adverse Effects
of Alpha 1 Activation1. Hypertension2. Bradycardia a. Reflex
slowing of the heart triggered from a response by the baroreceptors
responding to hypertension3. Necrosis at IV site with infiltration
into tissuesa. Due to vasoconstrictionv. Alpha 2 Receptor
Agonists1. Used for Hypertension2. Also used via an Epidural for
management of cancer pain unresponsive to opioids 3. Example:a.
Clonidine (Catapres)4. Be careful in Geriatric populationa. May
lead to orthostatic hypotensionvi. Beta 1 Receptor Activation1.
Treatment of cardiac arresta. Can initiate contraction in a heart
that has stopped2. Treatment of shocka. Increases heart rate, force
of contraction and cardiac output vii. Adverse Effects of Beta 1
Activation1. Altered heart rate or rhythma. Tachycardia and
dysrhythmias may result2. Angina Pectorisa. Increases cardiac
oxygen demandviii. Beta 2 Receptor Activation 1. Treatment of
Asthmaa. Promotes bronchodilation 2. Treatment of Preterm Labora.
Relaxes uterine smooth muscles (give beta 2 agonist) ix. Adverse
Effects of Beta 2 Activation 1. Hyperglycemiaa. Promotes breakdown
of glycogen into glucoseb. Is a problem only in patients with
diabetesc. Insulin doses may need to be increased2. Tremorsa.
Enhances contraction of the receptors in skeletal musclesb. This
effect generally fades over timex. Adrenergic Agonist Agents:1.
Epinephrine:a. Alpha 1b. Beta 1c. Beta 2d. Catecholamine2.
Administered topically, by injection and by inhalationa. Cannot be
given orallyb. Catacholamines undergo destruction before reaching
the systemic circulation3. Because it activates so many receptors,
expect side effectsa. Hypertension, Angina, Necrosis following IV
Extravasation, Hyperglycemia (Beta 2), Dysrhythmias (Beta 1) 4. The
Epi Penxi. Isoproterenol Hydrochloride (Isuprel)1. Activates Beta 1
and Beta 22. Used for Bronchospasms with anesthesia3. Used for
Cardiovascular Disordersa. AV heart block, cardiac arrest and
increase cardiac output4. Undesirable effects of Isuprel:a. Can
lead to tachydysrhythmias and Anginab. Can cause Hyperglycemia in
Diabetic clients5. Terbutaline (Brethine)a. Primarily Beta 2,
Minimal Beta 1i. If administered in large doses, will have beta 1
activationb. Primary reaction is bronchodilation and uterine
relaxationc. Noncatecholamine d. Stops preterm labor and
respiratory problems 6. Dopaminea. Catecholamineb. Binds to Beta
1and Dopamine receptorsc. At high doses, will also bind to alpha
1d. 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 receptorsb. The only indication is for treatment of heart
failurexii. Adrenergic Antagonists 1. Also called:a. Adrenergic
Blockersb. Sympatholytic Agentsxiii. Alpha Blockers1. Drugs that
Block Alpha 1will be used in the:a. Treatment of Hypertensioni.
Through Vasodilation b. Treatment of Peripheral Vascular Disease
(Raynauds Disease)c. Treatment of Pheochromocytoma i. Catecholamine
secreting tumor usually located in the adrenal medullaii. 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 Hyperplasiai. Decreases contraction in smooth
muscle in the bladder necke. Reversal of Toxicity form Alpha 1
Agonisti. In the event of an overdose or intravenous extravasation,
an Alpha 1 blocker can be administeredii. If an IV line containing
an alpha agonist infiltrates, necrosis can occuriii. Alpha 1
blocker (Phentolamine) can be injected into the region and will
prevent injuryxiv. Adverse Effects of Alpha Blockers 1. Orthostatic
Hypotensiona. Alpha Blockers reduce the muscle tone in the venous
wallb. Blood tends to pool when the patient stands up2. Reflex
Tachycardiaa. Increases heart rate by triggering the baroreceptor
reflexb. Can be suppressed by use of beta blockers3. Nasal
Congestiona. Dilates the blood vessels of the nasal mucosa4.
Inhibition of Ejaculationa. May lead to impotenceb. Reversible when
the alpha blocker is stoppedxv. Adrenergic Alpha Blockers 1.
Prazosin (Minipress)a. Selective for Alpha 1 Receptorb. Causes
dilation of arterioles and veins (orthostatic hypotension) c.
Causes relaxation in the bladder neck and prostatic capsuled. Used
for hypertension, and BPHe. Watch out for orthostatic
hypotension!!f. Can lead to impotence and nasal congestion2.
Phentolamine a. Blocks Alpha 1 and Alpha 2b. Used in the treatment
of Pheochromocytoma c. Used to prevent tissue necrosis following
extravasation of drugs that produce alpha 1 vasoconstrictioni.
Norepinephrine d. Can cause orthostatic hypotension, nasal
congestion and inhibition of ejaculation3. Terazosin (Hytrin)a.
Selective antagonist for alpha 1 receptorsb. Approved for use with
hypertension and BPH4. There is minimal recognizable therapeutic
application to blocking alpha 2xvi. Adrenergic Beta Antagonists 1.
Also calleda. Beta Blockersb. Beta Adrenergic Blockersc.
Sympatholytic Agentsd. Beta Blockers end in lol e. Drugs that block
the beta receptorsi. Beta 1 and/or Beta 2f. Practically all of the
therapeutic effects of the beta adrenergic antagonists result from
blockade of the Beta 1 receptor. i. Reduces heart rateii. Reduces
the force of the cardiac contractioniii. Reduces the velocity of
the impulse conduction through the AV nodeg. Beta Blockers will be
used to treat: i. Angina pectoris1. Decreases cardiac workloadii.
Hypertension1. Reduces peripheral vascular resistanceiii. Cardiac
Dysrhythmias iv. Myocardial Infarction1. Can reduce pain, infarct
size and mortalityv. Hyperthyroidism1. Will decrease the heart
ratevi. Migraine Headaches 1. When taken prophylactically 2. Will
not treat the headache itselfvii. Pheochromocytoma 1. Can prevent
the cardiac stimulation caused from the catecholamine
secretionviii. Stage Fright1. Help prevent the fear associated with
a generalized discharge from the Sympathetic Nervous Systemxvii.
Adverse Effects of Beta Blockers: Beta 11. Bradycardia 2. Reduced
Cardiac Outputa. Reduces heart rate and force of contractionb.
Extreme caution in patients with heart failure3. Precipitation of
Heart Failurea. Due to suppression of heart functionxviii. Adverse
Effects of Beta Blockers: Beta 2 1. Bronchoconstriction a. Be
careful with COPD or asthmab. Lopressor is selective for Beta 1,
therefore will not have an effect on bronchioles2. Inhibition of
Glycogenolysis a. Insignificant effect for patients who arent
Diabeticb. Beta 1 Selective Blocker should be used for Diabetics
who require a Beta Blocker xix. Beta Blocker Agents1. Propranolol
Hydrochloride (Inderal)a. Nonselective for Beta 1 and Beta 2b.
Treats angina, cardiac dysrhythmias, hypertension, and MIi.
Contraindicated with respiratory patientsc. See the similarity in
namesInderal and Isuprel Be careful!!2. Metoprolol (Lopressor,
ToprolXL)a. Blocks Beta 1 Receptors onlyi. At higher doses, it will
also block beta 2 3. Atenolol (Tenormin)a. Blocks Beta 1 Receptor
onlyb. These are the preferred Beta Blocking agents for patients
with asthma or diabetesc. Primarily used to treat Hypertensionj.
Cholinergicsi. Stimulates the Parasympathetic Nervous Systemii.
Also Called:1. Cholinergic Agonists2. ParaSympathomimetics 3.
Muscarinic Agonistsiii. Two Types of Cholinergic Receptors:1.
Muscarinic Receptorsa. Stimulates the parasympathetic responses2.
Nicotinic Receptorsa. Contraction of the Skeletal Musclesiv. Major
uses of Cholinergic Drugs: 1. Stimulate the Bladder and GI Tone2.
Constrict the Pupilsv. Other Effects of Cholinergic Drugs:1.
Decreases heart rate/ blood pressure2. Increased salivary and
bronchial secretionsvi. Adverse Effects: Parasympathomimetics 1.
Profuse salivation2. Increased muscle tone3. Urinary Frequency4.
Abdominal cramping and diarrhea5. Bronchoconstriction 6.
Bradycardia 7. Hypotensionvii. Bethanechol (Urecholine) 1.
Cholinergic agent that elicits all of the parasympathetic
responsesa. Activates muscarinic receptor activation2. Therapeutic
Usea. Relieves urinary retention3. Adverse Effectsa. With oral
dosing, side effects are rareb. Could have full range of
parasympathomimetic responsesviii. Anticholinergics 1. Inhibits the
action of Acetylcholine2. Also called a. Parasympatholytics b.
Antimuscarinic Agents3. Major Responses include:a. Increase in the
pulse rateb. Decrease in GI motilityc. Relaxation of the bronchid.
Decrease in salivatione. Dilation of the pupilsix. Anticholinergic
Agents: Atropine1. Used as:a. Preop med to decrease salivary
secretions and maintain heart rateb. Increase heart rate when
bradycardia is presentc. Dilate pupils for eye exams/eye surgery2.
Adverse Effects: Anticholinergicsa. Tachycardiab. Urinary
retentionc. Dry mouth/ Dry eyesd. Blurred visioni. Increase in
intraocular pressure1. Contraindicated in patients with glaucomae.
Constipationx. Other common uses of Anticholinergics 1. Oxybutynin
(Ditropan) a. Urinary Tract Antispasmodicb. Treats an overactive
bladderc. Used for Incontinence2. Tolterodine (Detrol)a. Used for
overactive bladder only3. Scopolaminea. Motion sickness and eye
examinations4. Ipratropium (Atrovent)a. Used for asthma, COPD and
rhinitisb. Administered by inhaler5. Dicyclomine (Bentyl)a. Used
for irritable bowel syndrome6. Exposure to nerve agents in a
bioterrorism attacka. All manifestations of nerve gas exposure are
due to the over-stimulation of Acetylcholinei. Increase
salivationii. Increase sweatingiii. Muscle twitchingiv. Involuntary
urination and defecationv. Confusion vi. Convulsionsvii.
Respiratory Distress & Respiratory Failure7. Treated with
anticholinergic agenta. Injector kits are carried which contain
Atropinek. Drugs for Neurodegenerative Disordersi. Parkinsons
Disease1. A Disease of the Extrapyramidal System2. The most common
neurodegenerative disorder after Alzheimers Disease3. Incidence
increases with age4. No cure ii. Extrapyramidal System1. The
functional system that is important in maintenance of equilibrium
and muscle toneiii. Diseases that effect the extrapyramidal system
result in symptoms such as:1. Tremors2. Rigidity3. Postural
instability4. Slow movementsl. Parkinsons Diseasei. Caused by death
of neurons that produce the neurotransmitter Dopamine1. Between 70
80% of these neurons must be lost before symptoms of Parkinsons are
obviousii. Results in an imbalance between Dopamine and
Acetylcholine in the basal ganglia1. Decreased amount of dopamine
and normal amount of acetylcholine iii. Parkinsonism Drugs1.
Antiparkinsonims agents are given to restore the balance of
dopamine and acetylcholinea. Dopaminergics increase dopaminei.
Increase Dopamine levels in the Corpus Striatum of the Brainii.
Used more commonly than Anticholinergics iii. Levodopa1.
Traditionally has been the drug of Choice for Parkinsons Diseasea.
Newer recommendations lead to Dopamine Agonists instead2. Levodopa
will increase Dopamine (chatecholamine cannot pass BBB) levels in
the braina. Will turn into Dopamine after biosynthesis in the
brain3. Levodopa can pass the blood-brain barriera. Dopamine, if
administered, will not cross the blood-brain barrier4. 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 effectivenessa. Dyskinesia: A defect in the ability to perform
voluntary movement5. With long term use of Levodopa, adverse
effects tend to increase, and therapeutic effects tend to
diminish6. Great results during the first 2 yearsa. By the 5th
year, many patients are back to pre-treatment symptomsb. May be
more of a sign of disease progression and not tolerance to the
drug7. Adverse Effects: a. Dyskinesias b. Postural hypotensionc.
Psychosisi. Develops in about 20% of clientsii. Hallucinations,
nightmares, paranoid ideationd. Darkened color of sweat and/or
urinee. On-Off Phenomonon i. Abrupt loss of effectii. Occurs even
when drug levels are highiii. Off times may last from minutes to
hoursiv. Over the course of the treatment, Off hours will occur
more and more frequentlyf. Food Interactionsi. High protein foods
can reduce therapeutic responsesii. Reduces amount of levodopa
absorbediii. Reduces amount transported into the brainiv. May be
the cause of the off phenomenonv. Patients are advised to spread
their protein consumption evenly throughout the dayg. Drug
Holidaysi. Drug Holidays may be recommendedii. Brief interruption
of treatment iii. @10 daysiv. Must be hospitalized during the drug
holidayv. May lead to severe psychologic distress, immobility,
aspiration pneumonitis, decubitus ulcersiv. Levodopa/Carbidopa1.
Combination drug2. Carbidopa enhances the effect of Levodopa
(synergistic effect)a. Carbidopa has no therapeutic effect by
itselfb. Allows the dosage of Levodopa to be reduced by about 75%3.
Examples: Sinemet and Paracopa v. Dopamine Agonists (younger pts or
beginning stages) 1. Stimulate Dopamine receptors directly2.
Recommended as the initial drug of choice for patients with mild to
moderate symptomsa. May be supplemented with Levodopa b. Levodopa
is still the drug of choice for elderly and those with advanced
disease3. Examples: Pramipexole (Mirapex) and Ropinirole
(Requip)vi. Advantages/Disadvantages of Dopamine Agonists 1.
Advantagesa. Dont compete with dietary proteins for absorption and
transport across the blood-brain barrierb. Lower incidence of
response failure if used long term2. Disadvantagesa.
Hallucinationsb. Daytime sleepinessb. Anticholinergics decrease
acetylcholine i. Blocks the effects of Acetylcholine in the brain,
decreasing symptoms1. Remember, the symptoms of Parkinsons is due
to an imbalance of Dopamine and Acetylcholinea. Low Dopamine
compared to Acetylcholineii. Examples:1. Tihexphenidyl (Artane)2.
Benztropine (Cogentin)iii. Anticholinergics are not as effective as
levodopa in treating Parkinsons1. Used early in the course of the
disease2. Used in patients who cannot tolerate Levodopa iv. What
are the side effects of Anticholinergics?1. Constipation,
tachycardia, urinary retention, dry mouth, blurred visionv.
Selegiline or Rasagiline1. Newer agents2. MAO-B Inhibitors
(parkinsons disease) a. Inactivates MAO by irreversibly binding to
it at type B (brain) sitesb. MAO-B is an enzyme that inactivates
dopaminec. Leads to increased amounts of dopamine available in the
CNSd. Nonselective (depression) MAO inhibitors used for depression
inhibit serotonin, norepenephrine and Dopaminevi. MAO B
Inhibitors1. May be used as drug of choice for patients with mild
symptoms 2. May also be given during off times with Levodopa
therapy2. Pharmacotherapy will not cure Parkinsons, but rather will
reduce symptomsm. Alzheimers Disease i. Degenerative Disorder
characterized by progressive memory loss, confusion and inability
to think or communicate effectivelyii. Associated with cerebral
atrophyiii. Treatment of AD1. Acetylcholine is the neurotransmitter
responsible for learning and memorya. In patients with advanced
Alzheimers Disease, levels of acetylcholine are 90% below normal2.
Choline Acetyl Transferase a. Enzyme responsible for Acetylcholine
Synthesis3. Acetylcholinesterase a. An enzyme that stops the action
of acetylcholine4. Acetylcholinesterase Inhibitors are the most
widely used agents for Alzheimers Disease5. When
Acetylcholinesterase is inhibited, Acetylcholine levels become
elevatediv. 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
neuronsb. As the disease progresses, these agents are usually
discontinued3. Examples:a. Donepezil hydrochloride (Aricept)i. Once
a day scheduleii. Best toleratedb. Galantamine (Reminyl)c. Tacrine
(Cognex) 4x day dosing4. 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 constriction of bronchi 6. Should this agent be used in a
patient that has a history of peptic ulcer disease? NO increases
gastric motility v. Memantine1. Newest Drug approved for Alzheimers
Diseasea. Approved in 2003b. In use in Germany since 19832.
Indicated for moderate to severe disease3. Thought to slow the
cognitive decline4. 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 Neuronsiii. Antiepileptics suppress the
Abnormal Electrical Impulses iv. Suppress seizures, but do not
treat the cause of the seizuresv. Goal of antiepileptic agents:1.
Suppress neuronal activity to prevent abnormal firingvi. Four
mechanisms by which Antiepileptics act:1. Potentiating GABA2.
Blocking the receptors for Glutamate3. Delaying an influx of
Sodium4. Delaying an influx of calciumvii. Drugs that Potentiate
GABA1. GABA:a. An inhibitory neurotransmitter that is widely
distributed throughout the brain2. These agents decrease neuronal
excitability3. Drugs that potentiate GABA work by:a. Directly
binding to GABA receptors and thus increase the effectivenessi.
Benzodiazepines and Barbiturates4. Promote GABA release5. Inhibit
GABA reuptake6. Inhibiting the enzyme that degrades GABAviii.
Blocking the Receptors of Glutamate 1. Glutamic acid (Glutamate)a.
Primary excitatory transmitter in the CNS2. If receptor is blocked,
will decrease the neuronal excitationa. 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 suppressedx. Types of Seizures 1. Partial
(focal) Seizuresa. Localized symptomsb. Discrete symptoms that are
determined by the brain region involved2. Generalized Seizuresa.
Seizure activity is caused from abnormal electrical activity that
is conducted widely throughout both hemispheres of the brain3.
Absent Seizuresa. Zone out stay awake but do not respond for 10-30
seconds, do not remember what happened4. Pharmacologic choice will
be dependent on type of seizure activity5. Phenytoin is effective
with Partial and Tonic-Clonic, but not with absence seizures6.
Valproic Acid seems to be effective with all types of seizuresxi.
Special Considerations 1. Plasma Drug Levelsa. Monitored on most
Antiepileptics (narrow therapeutic range) b. To establish a safe
and effective plasma level2. Promoting patient Adherencea.
Extremely important on these agentsb. Narrow therapeutic range3.
Discontinuance of the agentsa. These agents must be withdrawn
slowly over a period of 6 weeks to several months4. Most
anticonvulsants are cytochrome P450 Inducersa. Many drug-drug
interactions5. May reduce the effectiveness of birth control
pillsxii. Two Categories of Antiepileptic Agents1. Traditional
Agentsa. Last agent approved in 1978b. Cost lessc. More extensive
experienced. Troublesome side effectse. Complex drug interactionsf.
Phenytoin (Dilantin)i. Most widely used antiepileptic agentii.
Works through inhibition of sodium channelsiii. Used to treat all
forms of seizures except absence seizuresg. Narrow therapeutic
rangei. Doses of phenytoin needed to produce therapeutic effects
are only slightly smaller than the doses that may cause toxicityii.
As doses rise slightly, the drug will saturate the liver and
overwhelm the livers ability to metabolizeiii. According to your
text small changes in dosage produce large changes in drug levelsh.
Therapeutic Rangei. 10 20 mcg/mLii. Doses must be individualized
based on careful serum monitoringi. Gingival hyperplasiai.
Excessive growth of gum tissuesii. Side effect in about 20% of
clientsiii. Nurses must teach patients about good oral hygiene
including gum massagej. Teratogenic effects to the fetus if used
during pregnancyi. Pregnancy Category Dii. Can lead to:1. Cleft
palate, heart malformations, motor or mental deficiency,
microcephaly2. Also causes bleeding tendencies in the newborn
because it decreases the synthesis of vitamin Kk. Drug
interactionsi. Liver Enzyme Inducer1. Decreases the effect of other
drugs such as Warfarin, Oral contraceptivesii. Highly Protein
Bound1. Valproic Acid elevates levels of free phenytoin by
displacing it from protein binding sitesl. Carbamazepine (Tegretol)
i. Effective against tonic-clonic and partial seizures, but not
absence seizuresii. Works by suppressing sodium influxiii. May be
used for Bipolar Disorderiv. Liver Enzyme Inducer1. Increases its
own metabolism over time2. Half life will decrease over timea.
Initial treatment: Half life of 40 hoursb. With continue treatment:
Half life of 15 hoursv. Adverse Effects1. Minimal effect on
cognitive functiona. Often the drug of choice for younger
childrenvi. Hematologic Effects1. Bone marrow suppressiona.
Leukopenia, anemia and thrombocytopeniab. CBC should be
monitoredvii. Teratogenic Effects1. Category D m. Valproic Acid
(Depakene, Depakote) i. Will treat all major seizure typesii. Also
used in the treatment of Bi-Polar Disorder and migraine
headachesiii. Works by three mechanisms:1. Suppresses sodium and
calcium influx, also augments GABAiv. Causes minimal sedation and
cognitive impairmentv. Teratogenic Effects1. Category D2. Neural
Tube defectsa. Women are encouraged to take a folic acid
supplementvi. May be hepatotoxic 1. Raren. Ethosuximide
(Zarontin)i. Drug of choice for absence seizuresii. Will not work
for other types of seizuresiii. Does not require serum level
monitoring1. Dose is determined by watching the incidence of the
seizure activityo. Phenobarbital i. One of the oldest antiepileptic
agentsii. Considered a barbiturate1. Can cause physical
dependencyiii. Significant side effects1. Learning impairment,
Lethargy, Depressioniv. Not used as commonly as it once was p.
Oxcarbazepine (Trileptal) i. Newer Antiepileptic Agentsii. Most
commonly prescribed of the newer agentsiii. A derivative agent of
Carbamazepine 1. As effective2. More expensive3. Better
toleratediv. Adverse Effects1. 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 Ca. Women should use effective
contraceptivesq. Management of Status Epilepticusi. Continuous
tonic-clonic seizure that lasts at least 20 - 30 minutes1. Patient
develops tachycardia, hypertension, hypoxia, acidosis and
hypoglycemia2. Can lead to permanent neurologic injury or deathii.
Goal of treatment:1. Maintain airway2. Correct hypoglycemia3. Stop
the seizureiii. IV started1. Glucose solution infused 2.
Antiepileptic agent infusediv. Lorazepam (Ativan) or Diazepam
(Valium) are the agents of choice1. These drugs are
Benzodiazepines2. Effects of Ativan can last for 72 hours, so it is
now the drug of choicev. Benzodiazepines are usually prescribed for
short term control of seizuresvi. 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 suppression2. Newer Agentsa. Approved in
1993 or laterb. Cost morec. Less experience, therefore, prescribed
less frequentlyd. Smaller risk of teratogenic effectse. Fewer drug
interactions3. Both groups appear equally effective4. Both groups
have their advantages and disadvantageso. Psychotherapeutic Drugsi.
Schizophrenia1. Chronic psychotic illness2. Characterized by
disordered thinking and difficulty comprehending realityii.
Symptoms of Schizophrenia:1. Hallucinations, delusions, agitation
and paranoia2. Lack of motivation, blunt affect, social
withdrawal3. Disordered thinking, memory and learning difficulties,
inattentivenessiii. Cause of Schizophrenia1. Exact etiology is
unknown2. Thought to be caused from an excess of Dopamine in the
braina. All antipsychotic drugs work by competing with the Dopamine
receptor sitesb. Thus, they block Dopamine receptors in the braini.
Thought to be Dopamine Antagonists3. DISEASE CAUSED FROM LACK OF
DOPAMINE iv. Two Major Categories of Antipsychotic Agents1. First
Generation (Conventional) Agentsa. Further classified as low
potency, medium potency or high potencyb. Block receptors for
Dopaminec. EPS symptoms likelyd. Two chemical categories of
Conventional Agentsi. Phenothiazines 1. Chlorpromazine
(Thorazine)2. Thioridazine (Mellaril)ii. Butyrophenones
(Phenothiazine-Like)1. Haloperidol (Haldol)e. Adverse Effects of
Conventional Antipsychotic Agentsi. Drowsinessii. Anticholinergic
Effects iii. Orthostatic Hypotensioniv. Extrapyramidal Symptomsf.
Extrapyramidal Symptoms (EPS) i. Acute Dystonias 1. Severe muscle
spasms2. Tongue, neck, face or back3. Opisthotonic Posturingii.
Akathisia 1. Inability to rest or relax2. Pacing and squirmingiii.
Parkinsonism1. Tremors 2. Mask Like Face3. Stooped posture4.
Rigidity5. Shuffling Gait6. Pill-Rolling7. Bradykinesia iv. Tardive
Dyskinesia 1. Develops in 20% of patients with long-term therapy2.
Serious Side Effect3. Protrusion of tongue is accompanied by
sucking, smacking lips, involuntary movements of the body and
extremities4. Med should be stopped immediately if symptoms are
exhibited5. For many patients, the symptoms are not reversible6.
Results in speaking and nutritional difficulties2. Second
Generation (Atypical) Agentsa. Moderately block receptors for
Dopaminei. Lower risk of EPS symptomsb. Stronger block of receptors
for Serotoninc. Newer drugs on the marketd. Have become the drug of
choice for treatment of Psychosese. Greater therapeutic Effectsf.
Not likely to cause EPS Symptomsg. Also called: Second Generationv.
Atypical Antipsychotic Agents1. Mechanism of Actiona. Block
Dopamine Receptors (loosely)b. Also block Serotonin and
Alpha-adrenergic receptors2. Examples:a. Risperidone (Risperdal)b.
Olanzapine (Zyprexa)c. Dibenzodiazepine (Clozapine)vi. Side Effects
of Atypical Antipsychotics1. Weight Gaina. May quickly lead to
obesityb. Especially Clozapine (Clozaril) and Olanzapine
(Zyprexa)2. Increase in prolactin levelsa. Leads to menstrual
disorders, sexual dysfunction and osteoporosis3. Teratogenic
effects a. Contraindicated during pregnancy and lactation4.
Diabetesa. New onsetp. Depressioni. Three Types of Depression1.
Reactivea. Sudden onset with precipitating factorsb. Normal
grief/sadnessc. Appropriate reaction to a major life stressor2.
Unipolar a. Major depressionb. Loss of interest in work and homec.
Considered an illness3. Bipolara. Manic and depressiveii.
Depression is most common psychiatric disorderiii. Affects 30% of
populationiv. Only 30% of population with depression are treated
with medication1. Depression is under-diagnosed and under-treatedv.
Theory of Depression1. Caused from insufficient amount of monoamine
neurotransmittersa. Norepinephrine b. Serotoninvi. Antidepressants
1. St Johns Wort:a. Herbal Supplementb. Decreases the reuptake of
the neurotransmitters:i. Serotonin, Norepinephrine & Dopamine2.
Conflicting study results regarding effectiveness3. Thought to be
as effective as the Tricyclic antidepressants in treating mild to
moderate depression4. Not shown to be effective in treating severe
depression5. Known to interact adversely with many other drugsa.
Induces cytochrome P450 enzymesb. Induces P- Glycoproteinc.
Intensifies the serotonin effectsi. May lead to fatal serotonin
syndromevii. Five Groups of Antidepressants 1. Tricyclic (TCAs)a.
Available in the late 1950sb. Blocks the uptake of norepinephrine
and serotoninc. Less expensive than the SSRIsd. Therapeutic
response takes 2-6 weekse. Gradually withdrawn when discontinuingf.
Used most commonly for major Depressiong. Examples:i. Amitriptyline
(Elavil)ii. Imipramine (Tofranil)h. Side Effects:i. Sedationii.
Anticholinergic effectsiii. Orthostatic Hypotension1. Blocks Alpha
1 receptorsiv. Increase risk of suicide early in treatment1. Could
overdose on the medication2. Supply should be limited to one week
in the beginning of therapy2. Selective Serotonin Reuptake
Inhibitors a. Introduced in 1987b. Most commonly prescribed
antidepressantc. $3 Billion in annual salesd. SSRIs Block the
reuptake of serotonini. Do not block the uptake of dopamine or
norepinephrine e. More expensive than the Tricyclics f. Do not
block cholinergic and alpha 1 adrenergic receptorsi. Fewer side
effectsg. Used for major Depressionh. Also used to treat:i.
Obsessive/Compulsiveii. Paniciii. Phobiasiv. PTSDv. Anxietyi.
Examples of SSRIs:i. Fluoxatine (Prozac)ii. Fluxovamine (Luvox)iii.
Sertraline (Zoloft)iv. Paroxetine (Paxil)v. Citalopram (Celexa)vi.
Escitalopram (Lexapro)j. Side Effectsi. Sexual dysfunction1. Up to
70% of men and women may experience decreased libido and lack of
ability to reach an orgasm2. May result in noncompliance with
medicationii. Insomniaiii. Headacheiv. Weight gain v. Serotonin
Syndrome (SES) 1. May occur when taking SSRIs along with other
medications that increase serotonin levelsa. MAOIs, Tricyclics,
Lithium2. Occurs if Serotonin levels accumulate in the body3.
Symptoms include:a. Confusion, anxiety, restlessness, hypertension,
tremors4. Recommended treatment is supportive and discontinue the
SSRI.a. If untreated, may result in deathvi. Withdrawal Syndrome1.
Abrupt discontinuation of SSRIs can cause a withdrawal syndrome. 2.
Symptoms include: a. Headacheb. Dizzinessc. Nausead. Tremorse.
Anxiety3. Symptoms can last for 1 3 weeks4. Drug must be tapered
slowly3. Serotonin/Norepinephrine Reuptake Inhibitors (S/NRIs)a.
Block reuptake of serotonin and norepinephrine b. Similar effect to
SSRIsi. SSRIs seem to be better toleratedc. Two drugs in this
category:i. Venlafaxine (Effexor)ii. Duloxetine (Cymbalta)iii.
Desvenlafaxine (Pristiq)4. Monoamine Oxidase Inhibitors (MAOIs)a.
The first drug approved to treat depression in the 1950s.b.
Inactivates Monoamine Oxidase c. Monoamine Oxidase is an enzyme
found in the liver, the intestine & the braini. The function of
Monamine Oxicase is to:1. inactivates the three neurotransmitters2.
Inactivates tyramine in foodsd. Examples:i. Tranylcypromine
(Parnate)ii. Isocarboxazid (Marplan)iii. Phenelzine (Nardil)e. Used
to treat reactive or unipolar depressionf. Very effectiveg. Due to
severe side effects, not used oftenh. Only used when other
antidepressants are not effectivei. Drug Food Interactionsi.
Normally, dietary Tyramine is metabolized by MAO in the intestinal
wall and in the liverii. Tyramine, if not metabolized, will promote
the release of norepinephrine from the sympathetic systemiii. MAOIs
inactivate the enzymes that detoxifies Tyramine 1. will cause a
hypertensive crisis due to a drastic release of norepinephrine into
the blood streamiv. Tyramine Rich Foods1. Cheese, cream, yogurt,
bananas, raisins, coffee, chocolate, Italian green beans, liver,
sausage, soy sauce, beer, red winej. Drug Drug Interactions i.
MAOIs used concurrently with other antidepressants or
sympathomimetic drugs1. Can cause a hypertensive crisis2. Due to
the drastic increase in norepinephrine ii. MAOIs used concurrently
with SSRIs1. Serotonin Syndromeiii. MAOIs will potentiate the
hypoglycemic effect of insulin and oral hypoglycemic agents5.
Atypical Antidepressantsa. Available in the 1980sb. Used for major
and reactive Depressionc. They affect one or two of the three
neurotransmittersd. Examples:i. Trazadone (Desyrel)ii. Bupropion
(Wellbutrin)iii. Mirtazapine (Remeron)q. Mood Stabilizers i. Used
to treat Bi Polar Disorderii. Effective in controlling the Mania
and Depressioniii. Mood Stabilizers:1. Lithium2. Valproic Acid3.
Carbamazepine iv. Many patients also receive an antipsychotic, and
some may require an antidepressantv. Lithium1. Approved in the US
in 19702. Drug of choice for controlling acute manic episodes and
for long-term prophylaxis against recurrence3. Narrow Therapeutic
Rangea. 0.6 to 1.5mEq/Lb. Death has resulted from Lithium levels
> 2.5mEq/L4. Serum Lithium levels should be monitored
frequentlya. Every 1 to 3 days when beginning therapyvi.
Lithium/Sodium Relationship1. Lithium is a salt2. Low serum sodium
level will increase risk of lithium toxicity3. Important that serum
sodium levels remain normal 4. Sodium levels will be affected by:a.
Vomiting/ Diarrheab. Sweatingc. Use of diuretics.5. Lithium is
excreted by the kidneys6. Renal excretion of lithium is affected by
blood levels of sodium7. Lithium excretion is reduced when blood
levels of sodium are low8. When the kidneys sense that sodium
levels are inadequate, it retains lithium in an attempt to
compensate9. If the sodium levels are low, the lithium will be
retained and accumulate rapidly to toxic levelsvii. Valproic Acid
and Carbamezapine1. These antiepileptic drugs can suppress mania
and stabilize mood in patients with Bi-Polar Disorder2. Valproic
Acid is very effective and gaining popularity as drug of choicer.
Sedative Hypnotic Agents i. CNS Depressantsii. Used to treat
anxiety1. Anxiolytic agents2. Antianxiety agentsiii. Used to treat
insomnia1. Called Hypnoticsiv. Terms: Sedative Hypnotic 1. Sedative
Effect: Depresses physical and mental responses