PHARMACOLOGY NOTES

Chapter 1 – Nursing Process & Drug Therapy:

The Six Rights of Medication Administration:
1. Right Drug
2. Right Dose
3. Right Time
4. Right Route
5. Right Patient
6. Right Documentation

Chapter 2 – Pharmacologic Principles:

● Drug
o Any chemical that affects the physiologic processes of a living organism
● Pharmacology
o The study or science of drugs

Drug Names
● Chemical Name
o Describes the drugs chemical composition and molecular structure
● Generic Name (Non-Proprietary name)
o Name given by the United States Adopted Name Council (All drugs have a
generic name, even when they are new; Main focus of this course!!)
● Trade Name (Proprietary Name)
o The drug name has a registered trademark; Use of the name is restricted by the
drugs patent owner (which is usually the manufacturer)
Pharmacology Principle
● Pharmaceutics
● Pharmacokinetics
● Pharmacodynamics
● Pharmacotherapeutics
● Pharmacognosy
Pharmaceutics
● Definition: The study of how various drug forms influence pharmacokinetic and
pharmacodynamic activities (Which basically means the dosage form design and how it
impacts the dissolution of a drug)
Pharmacokinetics
● Definition: The study of what the body does to the drug
o Absorption
o Distribution “THINK ADME”
o Metabolism
o Excretion (Or Elimination)

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Pharmacodynamics
● Definition: The study of what the drug does to the body
o The mechanism of drug actions in living tissues

**The MOA is the most IMPORTANT thing for this class!!!!!!!

Pharmacotherapeutics
● Definition: The use of drugs and the clinical indications for drugs to prevent and treat
diseases
Pharmacognosy
● Definition: The study of natural (plant and animal) drug sources
Drug Absorption of Various Oral Medications
● Liquids, elixirs, and syrups FASTEST
● Suspension solutions
● Powders
● Capsules
● Tablets
● Coated Tablets
● Enteric- Coated Tablets** SLOWEST
**Designed to purposefully be slow because they can cause stomach ulcers and are
instead dissolved in the intestines (and not the stomach) to prevent ulcers from forming.
Pharmacokinetics: Absorption
● Definition: The rate at which a drug leaves its site of administration and the extent to
which absorption occurs.
o Bioavailability
▪ (The % of administered dose of unchanged drug that reaches systemic
circulation; Incomplete absorption; First-pass effect.
o Bio-equivalency
▪ (Everything is the same but the names are different; like the brand name
and the generic name)
Factors that Affect Absorption
● Absorption characteristics vary according to the dosage form and route
o Food or fluids administered with the drug
▪ (Slows absorption; Decreases the irritation of a drug)
o Dosage formulation
▪ (Help it disintegrate and dissolve before absorption)
o Status of the absorptive surface
▪ (Absorbed mostly in the intestines because of the increased surface area)
o Rate of blood flow to the small intestines
o Acidity of the stomach

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▪ (Acidic drugs like acidic environments; basic drugs like basic
environments)
o Solution of GI motility
▪ (Keeping it in the stomach too long and taking it longer for the drug to get
to the intestines)
Routes
● A drugs route of administration affects the rate and extent of absorption of that drug
o Enteral (GI Tract)
o Parenteral (**FASTEST** EX: IVs)
o Topical

Enteral Route
● The drug is absorbed into the systemic circulation through the oral or gastric mucosa (In
the stomach lining) of the small intestine
o Oral
o Sublingual FASTEST ABSORPTION
o Buccal
o Rectal

First-Pass: Effect
● The metabolism of a drug and its passage from the liver into the circulation
o A drug given via the oral route may be extensively altered by the liver before
reaching the systemic circulation (high first-pass effect)
o The same drug given by IV bypasses the liver, preventing the first-pass effect
from taking place, and more drug reaches the circulation
▪ (But, when given by IV, it goes directly to the systemic circulation)
▪ (The first-pass effect means that you can get a medication orally but its
sent to the liver 1st and the rest of your body (systemic circulation) 2nd
▪ (Must be taken orally to have the effect)
▪ (Hepatic portal systems sends medication to the liver 1st)
Parenteral Route
● Intravenous (Fastest delivery to blood circulation)
● Intramuscular
● Subcutaneous
● Intradermal
● Intraarterial- artery (given here to go directly to certain organs)
● Intrathecal- spine
● Intraarticular- joint
Topical Route
● Skin (Including transdermal patches)
● Eyes
● Ears
● Nose

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● Lungs (Inhalation) 🡪 Inhalers
● Rectum (Can be external as well; you don’t completely bypass the first-pass effect; about
50/50)
● Vagina
Distribution
● The transport of a drug in the body by the bloodstream to its site of action
o Protein binding
▪ FATS want to go with fats; keeps it in the blood and allows for more drug
interactions
o Water soluble vs. fat (lipid) soluble
▪ Lipid (fat) soluble drugs penetrate membranes much easier because they
prefer to be in fat; Most are fat soluble to get through membranes faster
o Blood-brain barriers
▪ Defensive mechanisms; protect the CNS; SMALL lipid soluble compounds
can get through the barrier
o Areas of rapid distribution: heart, liver, kidneys, brain
▪ Drugs tend to go here FIRST
o Areas of slow distribution: Muscle, skin, fat

Metabolism/ Biotransformation
● Definition: The biochemical transformation of a drug into an inactive metabolite, a mere
soluble compound, or a more potent metabolite
o Liver
o Skeletal Muscle
o Kidneys
o Lungs
o Plasma
o Intestinal Mucosa
▪ The liver makes things more polar because they are easier to eliminate at
that point
▪ The metabolism makes the compound less lipid soluble and more polar so
it CANNOT be reabsorbed and is then ELIMINATED
● Biologic transformation of a drug into:
o An inactive metabolite
o A more soluble compound
▪ (A more potent metabolite)
● Factors that decrease metabolism
o Cardiovascular dysfunction
o Renal insufficiency
o Starvation
o Obstructive jaundice (Clogged bile duct)
o Slow acetylator (Conjugation reaction; There are also fast acetylators and it is
dependent on genetics whether they are fast or slow)
o Erythromycin or ketoconazole drug therapy
● Factors that increase metabolism

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o Fast acetylator (Genetically decided whether you’re fast or slow)
o Barbiturate therapy (Need a long half-life)
o Rifampin therapy (Increases enzymes; Need a long half life)
● Delaying drug metabolism causes
o Accumulation of drugs
o Prolonged action of the drugs 🡪 drug toxicity
● Stimulating drug metabolism causes
o Diminished pharmacologic effects

Excretion
● Definition: The elimination of drugs from the body
o Kidneys (Main Organ)
o Liver
o Bowel
▪ Biliary excretion
▪ Enterohepatic recirculation
Half-Life
● The time it takes for one half of the original amount of drug to be removed from the body
● A measure of the rate at which a drug is removed after about 5 half-lives
● Steady state
o The longer the half-life, the longer it will take you to get to the steady state
o Amount removed= amount absorbed; Use blood plasm serum; not always
accurate (Used to determine the concentration of the drug in your body)
Onset, Peak, and Duration
● Onset
o Definition: The time it takes for the drug to elicit a therapeutic response
● Peak
o Definition: The time it takes for a drug to reach its maximum therapeutic
response
● Duration
o Definition: The time a drug concentration is sufficient to elicit a therapeutic
response
Therapeutic Drug Monitoring
● Peak level: Highest blood level
● Trough level (nadir): lowest blood level
Pharmacodynamics: MoA
● Receptor interactions
● Enzyme interactions **General**
● Nonselective interactions
Pharmacotherapeutics: Typed of Therapies

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● Acute therapy (Short-term)
● Maintenance Therapy (Treats symptoms)
● Supplemental/ Replacement therapy (Insulin/Iron)
● Palliative Therapy (Try to make the patient comfortable)
● Supportive Therapy (EX: Fluids and electrolytes)
● Prophylactic Therapy (Preventative)
● Empiric Therapy (Based on an educated guess for treatment)
Contraindications
● Definition: Any characteristics of the patient, especially a disease state, that makes the
use of a given medication dangerous for the patient.
● It is important to assess for contraindications
o Doesn’t mean that the drug won’t work but it causes harm

Monitoring
● Therapeutic index
o Definition: Ratio of a drug’s toxic level to the level that provides therapeutic
benefits
▪ (Toxic dose/ effective dose)
● Tolerance
o Definition: Decreasing response to repeated drug doses
▪ Pain medications and opiods
● Dependence
o Definition: Physiologic or psychological need for a drug
● Interactions may occur with the other drugs or food
o A drug interaction is the alteration of a drug’s action by:
▪ Other prescribed drugs
▪ OTC Medications
▪ Herbal therapies
● Drug Interactions
o Additive
o Synergistic
o Potentiation
o Antagonistic
o Incompatibility

Drug Sources
● Four main sources for drugs
o Plants
o Animals
o Minerals
o Laboratory Synthesis

Chapter 3 – Life Span Considerations:

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PHARMACOLOGY NOTES
Life Span Considerations
● Pregnancy
● Breastfeeding
● Neonatal
● Elderly
Pregnancy
● The 1st trimester is the period of the greatest danger for drug-induced developmental
defects
● Drugs cross the placenta by diffusion
● During the last trimester the greatest percentage of maternally absorbed drug gets to the
fetus
● FDA Pregnancy Safety Categories
Breastfeeding
● Breastfed infants are at risk for exposure to drugs consumed by the mother
● Consider the risk-to-benefit ratio
Neonatal & Pediatric Considerations: Pharmacokinetics
● Absorption
o Gastric PH less acidic
o Gastric emptying is slowed
o Intramuscular absorption faster & irregular
● Distribution
o The younger the person, the greater the % of total body water (TBW)
o Greatest TBW means fat content is lower
o Decreased level of protein binding
o Immature blood-brain barrier; more drugs enter the brain
● Metabolism
o Liver immature, does not produce enough microsomal enzymes
o Older children may have increased metabolism; requiring higher doses than
infants
● Excretion
o Kidney immaturity affects glomerular filtration rate and tubular secretion
o Decreased perfusion rate at the kidneys may reduce excretion of drugs

Factors Affecting Pediatric Drug Dosages

● The skin is thin and permeable

● Stomach lacks acid to kill the bacteria
● Lungs have weaker mucus barriers
● Body temperature is less well regulated and dehydration occurs easily
● Liver and kidneys are immature, impairing drug metabolism and excretion
Methods of Dosage, Calculations for Pediatric Patients

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● Body surface area method
o Using the west nomogram
● Body weight dosage calculations
o Using mg/kg

The Elderly
● Elderly: Older than 65
● Use of the OTC medications
● Increased incidence of chronic illnesses
● Polypharmacy
Physiologic Changes in Elderly Patients
● Cardiovascular
● Gastrointestinal
● Hepatic
● Renal
The Elderly: Pharmacokinetics
● Absorption
o Gastric pH less acidic
o Gastric emptying slowed
o Movement therapy GI tract slowed
o Blood flow to the GI tract reduced
o Use of laxatives may accelerate GI motility
● Distribution
o Lower total body water (TBW) percentages
o Increased fat content
o Decreased production of proteins by the liver, resulting in decreased protein
binding of drugs (and increased circulation of free drugs)
● Metabolism
o Aging liver produces fewer microsomal enzymes, affecting drug metabolism
o Reduced blood flow to the liver
● Excretion
o Decreased glomerular filtration rate
o Decreased number of intact nephrons

Chapter 4 – Cultural, Legal, and Ethical Considerations:

Controlled Substances: Schedule Categories

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Schedule Abuse Potential Medical Use
C-1 High None
C-II High Accepted
C-III Less than C-II Accepted
C-IV Less than C-III Accepted
C-V Less than C-IV Accepted

Chapter 5 – Medication Errors: Preventing & Responding:

Medication Errors
● Preventable
● Common cause of adverse health care outcomes
● Effects can range from no significant effect to directly causing disability or death
o There are a lot of drugs on the market, which leads to confusion because there are
so many that look and sound similar
Common Classes of Medications Involved in Serious Errors
● Antibiotics
● Anticoagulants
● Antidiabetic Drugs (Particularly insulin)
● Cardiovascular drugs
● CNS- Active Drugs (Opioids and anesthetic)
● Vaccines
● Antineoplastic (anticancer) drugs
Preventing Medication Errors
● Minimize verbal or telephone orders
o Repeat order to prescriber
o Spell the drug name aloud
o Speak slowly & clearly
● List indication next to each other
● Avoid medical shorthand, including abbreviations and acronyms
● Never assume anything about items not specified in a drug order (EX: Route)
● Do NOT hesitate to question a medication order for any reason when in doubt
● Do NOT try to decipher illegibly written orders; contact prescriber for clarification
● NEVER use “trailing zeroes” with medication orders
o Do NOT use 1.0mg; use 1 mg
● ALWAYS use a “leading zero” for decimal dosage
o Do NOT use .25 mg; use 0.25 mg
● ALWAYS listen to and honor any concerns expressed by the patients regarding meds
● Check patient allergies and identification

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Chapter 7 – OTC drugs, Herbal, & Dietary Supplements:
Criteria for OTC Status
● Indication for use:
o Consumer must easily be able to:
▪ Diagnose condition
▪ Monitor effectiveness
o Benefits of correct usage must outweigh the risk
● Safety Profile
o Drug should have
▪ Favorable adverse event profile
▪ Limited interaction with other drugs
▪ Low potential for abuse
▪ High therapeutic index
● Practicality for OTC use
o Drug should be
▪ Easy to use
▪ Easy to monitor
Conventional Medicines Derived From Plants
Medicine Plant
Atropine Atropos Belladonna
Capsaicin Capsicum Frutescence
Cocaine Erythroxylon Coca
Codeine Papaver Somniferum
Ipecac Cephaelis Ipecauariha
Quinine Cinehana Officinalis
Scopolamine Datura Fastuosa
Senna Cassia Acutifolia
Paclitaxel Taxis Brevifolia
Vincristine Catharanthus Roseus

Use of OTCs/Herbal Products

● May postpone effective treatment of more chronic disease states
● May delay treatment of serious and/or life-threatening disorders
● May relieve symptoms of a disorder but not the cause
Herbal Products

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● Dietary Supplement & Health Education Act (DSHEA) of 1994
o Herbal products are considered “dietary supplements” & NOT drugs
o No proof of efficacy or safety required
o No standards for quality control
o May claim effect but cannot promise a specific cure
o Supplement manufacturer does not have to provide the FDA with evidence on
which it relies to substantiate for safety or effectiveness of a product before or
after it makes the products
o Other countries (UK, France, Canada, Germany) require manufacturers to meet
quality and safety standards
Commonly Used Herbal Products
● Aloe:

● Feverfew:

● Ginkgo:

● Goldenseal:

● St. John’s Wort:

● Valerian:

● Kava:

● Echinacea:

● Garlic:

● Ginseng:

● Hawthorn:

● Saw Palmetto:

● Melatonin:

Chapter 10 - Analgesic Drugs:

Analgesics

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● Medications that relieve pain without causing loss of consciousness
o “Painkillers”
o Opiods
o Acetaminophen
o NSAIDS

Classification of Pain by Onset & Duration

● Acute Pain
o Sudden in onset
o Usually subsides once treated
● Chronic Pain
o Persistent or reoccurring
o Lasting 3-6 months or longer
o Often difficult to treat
▪ WILL OFTEN LEAD TO TOLERANCE

Pain Transmission

● Tissue injury causes the release of:

o Bradykinin
o Histamine
o Prostaglandins
o Serotonin
▪ **These substances stimulate nerve ending, starting the pain process**
● Your body has endogenous neurotransmitters
o Enkephalins
o Endorphins
▪ They are produces by the body to fight pain
▪ They bind with opioid receptors
● Rubbing a painful area with massage or liniment stimulates large sensory fibers
o Results:
▪ Recognition of pain is reduced
▪ Use the same pathway as opiates

Opioid Ceiling Effect

● Drug reaches a maximum analgesic effect

● Analgesia does NOT improve, even with higher doses
o Pentazocine
**PARTIAL AGONIST**
o Nalbuphine

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Opioid Analgesics

● Pain relievers that contain opium, derived from the opium poppy or chemically related to
opium
● Narcotics: Very strong pain relievers

Means Opioid

● Codeine Sulfate

● Methadone HCl (Dolophine) (Long half-life; less withdrawal)

● Propoxyphene HCl

● Oxycodone

● Meperidine HCl (Demerol) (Acute use because when metabolized, its toxic)

● Hydromorphone

● Fentanyl (Very potent; even a small dose is lethal)

Opioid Analgesics: MoA

● Three classifications based on their actions:

o Agonist
o Partial agonist
o Antagonist

Agonists

● Bind to an opioid pain receptor in the brain

● Cause an analgesic response (reduction of pain sensation)
o **Basically they alter the perception of pain**

Agonists – Antagonists

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● Bind to a pain receptor
● Cause a weaker neurologic response than a full agonist
● ALSO CALLED PARTIAL-AGONIST or mixed agonist
o Good for a patient who used to be an opioid addict
o Bad for someone who is currently opioid dependent because they cause withdraw

Antagonist

● Reverse the effects of these drugs on pain receptors

● Bind to a pain receptor and exert no response
● Also known as competitive antagonists
o These COMPETE with AGONIST

Opioid Receptors

● Mu Primary
● Kappa Receptors
● Delta
● Sigma
● Epsilon

Opioid Analgesics: Indications

● Main Use: To alleviate moderate to severe pain

● Often given with adjuvant analgesic drugs to assist the primary drugs with pain relief
o NSAIDs (Help with inflammation)
o Acetaminophen
o Antidepressants
o Anticonvulsants
o Corticosteroids
● Opioids are also used for:
o Cough center suppression (Works in the medulla; First-pass effect is bypassed
with codeine)
o Treatment of diarrhea (Most common adverse effect is constipation)
o Balanced anesthesia (Used with general anesthesia)

Opioid Analgesics: Contraindications

● Known drug allergy

● Severe asthma

USE WITH EXTREME CAUTION IF:

● Respiratory insufficiency

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PHARMACOLOGY NOTES
● Elevated intracranial pressure (Increase in pCO2 which increases vasodilation that
causes intracranial pressure)
● Morbid obesity
● Sleep apnea
● Paralytic ileus

Opioid Analgesics: Adverse Effects

● Euphoria 🡪 The feel good effect

● CNS Depression
o Leads to respiratory depression
o MOST SERIOUS EFFECT
● Nausea and vomiting 🡪 Stimulates CTZ in the medulla
● Urinary retention
● Diaphoresis** and flushing (**Excessive sweating)
● Pupil constriction (miosis) 🡪 Impairs night vision
● Constipation 🡪 VERY COMMON
● Itching 🡪 Stimulates the release of histamine

Opiates: Opioid Tolerance

● A common physiologic result of chronic opioid treatment

o Results: Larger dose of opioids is required to maintain the same level of analgesia

Opioids: Physical Dependence

● Physiologic adaptation of the body to the presence of an opioid

● Opioid tolerance and physical dependence are expected with long-term opioid treatment
and should not be confused with psychologic dependence (addiction)

Opioids: Psychologic Dependence

● A pattern of compulsive drug use characterized by a continued craving for opioid and the
need to use the opioid for effects OTHER THAN pain relief **ADDICTION**

Opiates

● Misunderstanding of these terms leads to ineffective pain management and contributes

to the problem of undertreatment
● Physical dependence is seen when the opioid is abruptly discontinued or when an opioid
antagonist is administered
o Opioid withdraw/opioid abstinence syndrome
▪ Leads to withdraw
▪ You want to make the patient comfortable and then deal with their
dependence later on if they survive

Toxicity and Management of Overdose

● Naloxone (Narcan) 🡪 Short half-life and works fast

*ANTAGONIST
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● Naltrexone (Revia) 🡪 Longer half-life than naloxone
o These drugs bind to opiate receptors and prevent a response
o Used for the complete or partial reversal of opioid induced respiratory depression
● Regardless of withdraw symptoms, when a patient experience sever respiratory
depression, an opioid antagonists should be given 🡪 GIVEN TO PEOPLE WHO OD
● Opioid withdraw/ opioid abstinence syndrome
● Manifested as:
o Anxiety, irritability, chills & hot flashes, joint pain, lacrimation, rhinorrhea,
diaphoresis, nausea, vomiting, abdominal cramps, diarrhea, and confusion
o Withdraw is the OPPOSITE of what the drug does for you

Nonopioid Analgesic: Acetaminophen

● Analgesic and antipyretic effects

● Little to no anti-inflammatory effects
● Available OTC and in combination products with opioids
● MoA
o Similar to salicylates
o Blocks pain impulses peripherally by inhibiting prostaglandin synthesis
● Indications
o Mild to moderate pain
o Fever
o Alternative for those who CANNOT take aspirin products
● Toxicity and Managing Overdose
o Even though available OTC, lethal when overdosed
o Overdose, whether intentional or due to chronic unintentional misuse, causes
hepatic necrosis 🡪 Destroys liver; acute
o Long-term ingestion of large doses also causes nephropathy (Chronic Kidneys)
o Recommended ANTIDOTE: Acetylcysteine Regimen 🡪 Only works if its caught
early enough
● Dosage
o Maximum daily dosage for adults is 3000 mg per day
o Inadvertent excessive doses may occur when different combination drug products
are taken together
o Be aware of acetaminophen content of all the medications taken by the patient
(OTC & Prescription)
● Interactions
o Dangerous interactions may occur when taken with alcohol or other drugs that
are hepatotoxic
o Should not be taken in the presence of:
▪ Drug allergy
▪ Liver dysfunction
▪ Possible Liver failure
▪ G-6-PD deficiency

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Chapter 44 – Anti-inflammatory & Anti-gout Drugs:
NSAIDs

● Large and chemically diverse group of drugs with the following properties:
o Analgesic (pain)
o Anti-inflammatory
o Antipyretic (fever)
o Antirheumatic (arthritis)

NSAIDs: MoA

● Activation of the arachidonic acid pathway causes:

o Pain
o Headache
o Fever
o Inflammation
● Analgesia- treatment of headaches, mild to moderate pain & inflammation
o Block the chemical activity of either both COX enzymes (prostaglandin [PG]
pathway)
o Result: limits the undesirable inflammatory effects of PGs
● Antipyretic: reduces fever
o Inhibit prostaglandin E2 within the area of the brain that controls temperature

Chemical Categories of NSAIDs

● Salicylates
● Acetic acid derivatives
● Cyclooxygenase-2 (COX-2) inhibitors
● Enolic acid derivatives
● Propionic acid derivatives

NSAIDs: Salicylates

● Salicylates also have antiplatelet activity

o Inhibit platelet aggregation
▪ This is an irreversible reaction but is not permanent to the body because
we produce more platelets
o Examples: Aspirin, diflunisal (Dolobid)

NSAIDs: Acetic Acid

● Indomethacin (Indocin) 🡪 Very potent; Given to infants whose hearts won’t close on their
own
● Ketorolac (Toradol)

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● Diflofenac Sodium (Voltaren)
● Sulindac (Clinoril)
● Tolmetin (Tolectin)
● Etodolac (Lodine)

NSAIDs: COX-2 Inhibitor

● Celecoxib (Celebrex)
o First and only remaining COX-2 Inhibitor
o Indicated for osteoarthritis, rheumatoid arthritis, acute pain syndromes,
ankylosing spondylitis, and primary dysmenorrhea
▪ Less harsh on the body (specifically the GI tract); ulcers
▪ COX-1 DOES ITS OWN THING

NSAIDs: Enolic Acid Derivatives

● Piroxicam (Feidene)
● Meloxicam (Mobic) Non-selective COX Inhibitors
● Nabumetone (Relafen)

NSAIDs: Propionic Acids

● Fenoprofen (Nalfron)
● Flurbiprofen (Ansaid)
● Ibuprofen (Motrin, Advil)
● Ketoprofen (Orudis KT)
● Naproxen (Naprosyn, Aleve)
● Oxaprozin (Daypro)

NSAIDs: Indications

● Analgesia (mild to moderate)

● Antigout effects
● Anti-inflammatory effects
● Antipyretic effects
● Relief of vascular headaches
● Platelet inhibition (ASA)
● Relief of mild to moderate pain
● Acute gout
● Various bone, joint, and muscle pain
● Osteoarthritis
● Rheumatoid Arthritis
● Juvenile Rheumatoid Arthritis

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PHARMACOLOGY NOTES
● Dysmenorrhea
● Fever

NSAIDs: Salicylates

● Salicylates (Aspirin)
o More potent effect on platelet aggregation
▪ Analgesic
▪ Antipyretic
▪ Anti-inflammatory
▪ Antithrombotic effect: Used in the treatment od MI and other
thromboembolic disorders
● Non-selective COX-Inhibitor
● Should NOT be used with kids who have a viral infection
● Oldest, most used, and hardest on the GI tract

NSAIDs: Adverse Effects

● Gastrointestinal
o Dyspepsia, heartburn, epigastric distress, nausea
▪ GI bleeding*
▪ Mucosal lesions*
● Misoprostol (cylotec) can be used to reduce these dangerous
effects
● Promote mucus formation in the GI tract
● ULCERS****
● Renal
o Reductions in creatine clearance
o Acute tubular necrosis with renal failure
▪ Renal failure especially in the elderly

NSAIDs: Salicylate Toxicity

● Serious interactions can occur when given with:

o Anticoagulants
o Aspirin
o Corticosteroids and other ulcerogenic drugs
o Protein bound drugs
▪ 99% protein bound & will compete with other drug; free drugs

Antigout Drugs

● Gout: Condition that results from inappropriate uric acid metabolism

o Decreased excretion of uric acid
o Excessive production of uric acid
● Uric acid crystals are deposited in tissues and joints, resulting in pain

Antigout Drugs: Indications

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PHARMACOLOGY NOTES
● Allopurinol (Zyloprim)
o Used to reduce production of uric acid
● Colchine 🡪 Used for acute attacks
o Reduces inflammatory response to the deposits of urate crystals in joint tissue
● Probenecid (Benemid), Sulfinparazone (Antorlane)
o Increases excretion of uric acid in the urine
o Decreases uric acid amount; prevent gout attack

Chapter 11 – General & Local Anesthetics:

Anesthetics

● Drugs that depress the central nervous system (CNS)

o Depression of consciousness
o Loss of responsiveness to sensory stimulation (Including pain)
o Muscle relaxation

Anesthesia

● A state of depressed CNS activity

● Two types
o General anesthesia
o Local anesthesia
● Balanced anesthesia
o Usually used for general anesthesia

General Anesthetics

● Drugs that induce a state in which the CNS is altered to produce varying degrees of:
o Analgesia
o Depression of consciousness
o Skeletal muscle relaxation
o Reflex reduction
o VERY DANGEROUS AND BRINGS PEOPLE JUST ABOVE DEATH
● Inhaled anesthetics 🡪 Slow onset but easy to control
o Volatile liquids or gases that are vaporized/mixed in O2 and inhaled
● Parenteral anesthetics 🡪 Work very FAST
o Administered by IV!

Inhaled Anesthetics

● Inhaled gas
o Nitrous oxide 🡪 Very safe and not potent: AKA laughing gas; Used when you don’t
need to be completely knocked out
● Inhaled Volatile Liquids
o Desflurance
o Enflurance (Ethrane)

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PHARMACOLOGY NOTES
o Halothane (Fluothane)
o Isoflurane (Forane)
o Methoxyflurane (Penthrane)
o Sevoflurane

Injectable Anesthetics

● Used:
o To induce or maintain general anesthesia
o To induce amnesia
o As an adjunct to inhalation- type anesthetics
▪ Makes it happen very quickly
● Etomidate (Amidate)
● Ketamine (Ketalar)
● Methohexital (Brevital)*
● Propofol (Diprivan)* 🡪 Quickly metabolized; Can be used for controllability
● Thiamylal (Surital)
● Thiopental (Pentothal)* 🡪 Thio= sulfur; sulfur is very lipid soluble
o *May also be used as adjunctive drugs at lower doses

Adjunct Drugs

● Sedative-hypnotics
o Barbiturates (pentobarbital, secobarbital)
o Benzodiazepines (diazepam, midazolin)

Relax, decrease seizure

risk, cause amnesia

o Hydroxyzine 🡪 Antihistamine
o Promethazine 🡪 Prevent nausea
▪ All are apart of balanced anesthesia; used to lower the dosage of the
general anesthesia because its potent and this makes it safe.
● Neuromuscular blocking drugs (NMBDs)
o Depolarizing drugs (succinylcholine)
o Nondepolarizing drugs (pancuronium, d-tuboocurarine, vecurconium)
● Anticholinergics
o Atropine, glycopyrrolate, scopolamine
▪ Decrease secretions in the respiratory tract

Inhaled Anesthetics: MoA

● Varies according to drug

● Overton-Meyer theory 🡪 Lipid soluble compound; stabilize so they don’t depolarize
● Overall effect

21
PHARMACOLOGY NOTES
o Orderly & systemic reduction of sensory and motor CNS functions
o Progressive depression of cerebral & spinal cord functions

Indications

● General anesthetics used during surgical procedures to produce:

o Unconsciousness
o Skeletal muscle relaxation
o Visceral smooth muscle relaxation
● Rapid onset; quickly metabolized
● Also used in electroconvulsive therapy treatments for depression
o Not commonly used anymore, except in severe cases

Adverse Effects

● Vary according to the dosage and the drug used

● Sites that are primarily affected:
o Heart, peripheral circulation, liver, kidneys, and the respiratory tract
● Myocardial depression is commonly seen
o **Respiratory and cardiovascular**
● Malignant hyperthermia 🡪 GENETIC PREDISPOSITION
o Occurs during or after general anesthesia or use of the NMBD succinylcholine’s
▪ A large dose of calcium is released into the body
o Sudden elevation in body temperature (greater than 104 ◦F)
o Tachypnea, tachycardia, muscle rigidity
o LIFE THREATENING EMERGENCY
o Treated with dantrolene (skeletal muscle relaxant)

Moderate Sedation

● Also called conscious sedation or procedural sedation

● Combination of an IV benzodiazepine and an opiate analgesic
● Anxiety and sensitivity to pain are reduced, and the patient cannot recall the procedure
● Preserves the patients ability to maintain their own airway and to respond to verbal
commands
● Used for diagnostic procedures and minor surgical procedures that do NOT require deep
anesthesia
● Topical anesthetic may be applied
● Rapid recovery time and greater safety profile than general anesthesia

Local Anesthetics

● Also called regional anesthetics

● Used to render a specific portion of the body insensitive to pain
o Interfere with nerve impulse transmission to specific areas of the body
o Does NOT cause loss of consciousness
● Topical

22
PHARMACOLOGY NOTES
o Applied directly to the skin or mucous membranes
o Creams, solutions, ointments, gels, ophthalmic drops, lozenges, and
suppositories
● Parenteral
o Injected parenterally or into the CNS by various spinal injection techniques

Types of Local Anesthetics

● Spinal or intraspinal
o Intrathecal
o Epidural
● Infiltration
● Nerve block
● Topical

Local Anesthetics

● Procaine (Novocain)
● Tetracaine (Pontocaine)
● Lidocaine (Xylocaine)
● Mepivacaine (Carbocaine) AMI LOCAL
● Bupivacaine ANESTHETICS

Drug Effect: Paralysis

● First, autonomic activity is lost

● Then, pain and other sensory functions are lost
● Last, motor activity is lost
● As local drugs wear off, recovery occurs in reverse order (motor, sensory, and then
autonomic activity is restored

Indications

● Local anesthetics are used for:

o Surgical, dental, and diagnostic procedures
o Treatment of certain types of chronic pain
o Spinal anesthesia: To control pain during surgical procedures and child birth
● Local anesthetics are given by:
o Infiltration anesthesia
o Nerve block anesthesia
● Infiltration anesthesia
o Minor surgical and dental procedures
o Injection of the anesthetic solution intradermally, subcutaneously, or
submucosally across the path of nerves supplying the target area
o May be given in a circular patten around the operating area

23
PHARMACOLOGY NOTES
● Infiltration anesthesia and epinephrine
o Some local anesthetics used for infiltration or nerve block are combined with
vasoconstrictors
▪ To prevent systemic absorption of anesthetic
▪ To help confine local anesthetic to injected area
▪ To reduce local blood loss during the procedure
▪ Epinephrine, phenylephrine, and norepinephrine
● They don’t want vasodilation because it PROMOTES absorption;
so they add a vasoconstrictor
● You don’t want a local anesthetic to be absorbed because it causes
TOXICITY
● Nerve block anesthesia
o Used for surgical, dental, and diagnostic procedures
o Also used for therapeutic management of pain
o The anesthetic drug is injected directly into or around the nerve trunks or nerve
ganglia that supply the area in pain to be numbed

Adverse Effects

● Usually limited
● Adverse effects result if:
o Inadvertent intravascular injection occurs
o Excessive dose or rate of injection is given
o Slow metabolic breakdown occurs
o Injection into highly vascular tissue occurs
o “Spinal headache”, treated with an epidural blood patch

Neuromuscular Blocking Drugs

● Also known as NMBDs

● Prevent nerve transmission in certain muscles; resulting in muscle paralysis
● Used with anesthesia during surgery 🡪 USED FOR BALANCED ANESTHESIA!!!!!
● When used during surgery, artificial mechanical ventilation is required
o These drugs paralyze respiratory and skeletal muscles
o Patient cannot breathe on his or her own
o Does NOT cause sedation or pain relief
o Patient may be paralyzed yet conscious
● Depolarizing Drugs

24
PHARMACOLOGY NOTES
● Nondepolarizing drugs
o Short acting
o Intermediate acting
o Long acting

NMBDs: Depolarizing Drug

● Succinylcholine
o Works similarly to neurotransmitter acetylcholine (Ach), causing depolarization
o Metabolism is slower then Ach, so as long as succinylcholine is present,
repolarization CANNOT occur
o Result: Flaccid muscle paralysis
▪ Succinylcholine is metabolized much slower than Ach!!!!!!

NMBDs: Nondepolarizing Drugs

● Short-acting
o Mivacurium (Mivacron)
● Intermediate acting
o Atracurium (Tracrium), vecuronoim (Norcuron)
o Rocuronium (Zemuron)
● Long-acting
o Pancuronium (Pavulon), doxacurium (Nuromax)
o D-tubocurarine
▪ Look for the “cur” in the word to know it’s an NMBD

Nondepolarizing NMBDs

● Prevent Ach from acting at neuromuscular junctions

● Muscle fibers are not stimulated
● Skeletal muscle contraction does not occur

Neuromuscular Blocking Drugs

● First sensation is muscle weakness

● Followed by a total flaccid paralysis
● Small, rapidly moving muscles affected first (fingers & eyes), then the limbs, neck, and
trunk
● Finally, intercostal muscles and diaphragm affected, resulting in cessations of
respirations
● Recovery of muscular activity usually occurs in reverse order
● Transient muscle fasciculations may result in later muscle softness

NMBDs: Indications

● Main Use: Maintaining controlled ventilation during surgical procedures

● Endotracheal intubation (short-acting)
● To reduce muscle contraction in an area that needs surgery

25
PHARMACOLOGY NOTES
o Blocks respiration

NMBDs: Adverse Effect

● Few when used appropriately

● May cause:
o Hypotension (blockade of autonomic ganglia)
o Tachycardia (Blockade of muscarinic receptors)
o Hypotension (Release of histamine)

NMBDs: Safety

● Respiratory muscle paralysis occurs with these drugs

o Emergency ventilation equipment must be immediately available

NMBDs: Overdose

● Overdose causes prolonged paralysis requiring prolonged mechanical ventilation

● Cardiovascular collapse may occur

Chapter 12 – CNS Depressants & Muscle Relaxants:

CNS Depressants

● Sedatives
o Drugs that have an inhibitory effect on the CNS to the degree that they reduce:
▪ Nervousness
▪ Excitability
▪ Inability without causing sleep
● At a higher dose it can cause sleep!!
● Hypnotics
o Causes sleep
o A sedative can become a hypnotic if it is given a large enough dose
● Sedative- hypnotics: Dose dependent
o At low doses, calm the CNS without inducing sleep
o At high doses, calm the CNS to the point of causing sleep
▪ Barbiturates
▪ Benzodiazepines

Sleep

● Normal sleep is cyclic and repetitive

● A sleeping person is unaware of sensory stimuli within the immediate environment

26
PHARMACOLOGY NOTES
● Rapid eye movement (REM) sleep
● Non-rapid eye movement (non-REM) sleep
● Sleep stages
● REM rebound 🡪 With medication; Help you sleep but you only have non-REM sleep;
When off the medication your body goes into REM sleep and causes nightmares

CNS Depressants: Benzodiazepines

● A commonly prescribed drug class

● Favorable drug effect profiles, efficacy, and safety

Benzodiazepines: Classification

● Classified as either:
o Sedative-hypnotic
o Anxiolytic (medication that relieves anxiety)

Benzodiazepines: Sedative-Hypnotic Types

● Long-Acting
o Estazolam (Prosom), Flurazepam (Dalmane), Lorazepam (Ativan)
▪ Anxiety, seizures, panic, sedation, sleep disorder, alcohol dependence
● Short-Acting
o Temazepam (Restoril), Alprazolam (Xanax), Triazolam (Halcion)
▪ Amnesia, insomnia
● Intermediate Acting
o Estazolam

CNS Depressants: Nonbenzodiazepine Hypnotics

● Share many of the same characteristics as benzodiazepines

● Used to treat insomnia
o EX: Zaleplon (Sonata), Zolpidem (Ambien), Eszopiclone (Lunesta)
● Eszopiclone & extended release zolpidem (Ambien CR [Controlled Release]) approved
for long-term therapy
o Not benzodiazepines but they think that they are
● Ramelteon (Rozerem)
o No potential for abuse “el” means melatonin
o No withdraw signs & symptoms
▪ Control circadian rhythm; does not work like a benzodiazepine

Benzodiazepines: MoA

● Depress CNS activity

● Affects hypothalamic, thalamic, and limbic systems of the brain
● Benzodiazepine receptors
● Do NOT suppress REM sleep as much as barbiturates do
● Do NOT increase metabolism of other drugs

27
PHARMACOLOGY NOTES
Benzodiazepines: Drug Effects

● Calming effect on the CNS

● Useful in controlling agitation and anxiety
● Reduce excessive sensory stimulation, inducing sleep
● Induce skeletal muscle relaxation

Benzodiazepines: Indications

● Sedation
● Sleep induction 🡪 Done with a HIGH dose
● Skeletal muscle relaxation
● Anxiety relief
● Treatment of alcohol withdraw 🡪 Can be very serious; causes seizures which this class of
medication treats/prevents
● Agitation
● Depression 🡪 Anxiety driven
● Epilepsy
● Balanced anesthesia 🡪 Lower general anesthesia dose is needed
● Moderate/conscious sedation

Benzodiazepines: Adverse Effects

● Mild and infrequent

o Headache
o Drowsiness
o Dizziness
o Vertigo
o Lethargy
o Fall hazard for frail elderly people
o “Hangover” effect/daytime sleepiness
▪ Has a very high therapeutic index, which is good!!

Benzodiazepines: Toxicity and Overdose

● Somnolence
● Confusion
● Coma
● Diminished reflexes
● Do NOT cause hypotension and respiratory depression unless taken with other CNS
depressants
● Treatment symptomatic and supportive
o Flumazenil as an ANTIDOTE 🡪 Blocks benzodiazepine receptors

Herbal Products: Kava

● Used to relieve ANXIETY, stress, and restlessness and to promote sleep

● May cause temporary yellow skin discoloration (extended, continued intake)

28
PHARMACOLOGY NOTES
● May cause visual disturbances
● Potential interactions with alcohol, barbiturates, and psychoactive drugs
● Contraindicated in liver disease and alcoholism
● Patient should not operate heavy machinery during use

Herbal Products: Valerian

● Used to relieve anxiety, restlessness, and sleep disorders

● May cause CNS depression, hepatotoxicity, nausea, vomiting, anorexia, restlessness, and
insomnia
● Many interactions, including with CNS depressants, MAOIs, phenytoin, warfarin, and
alcohol
● Contraindicated in cardiac & liver diseases
● Patient should not operate heavy machinery during use

Sedative – Hypnotics: Barbiturates

● First introduced in 1903; were the standard drugs for insomnia & sedation
● Habit forming; LOW therapeutic index
● Only a handful commonly used today due in part to the safety and efficacy of
benzodiazepines
o Controlled substance
o Benzo’s are used more because they are SAFER!

Therapeutic Index

● Ratio between the toxic and therapeutic concentrations of a drug

● Barbiturates have a very low therapeutic index
o Which is even lower when mixed with another CNS depressant

Barbiturates: Mechanism of Action

● Site of action
o Brainstem (reticular formation)
● By facilitating GABA, nerve impulses traveling in the cerebral cortex are inhibited
o Do NOT bind to benzo-receptors

Barbiturates: Drug Effects

● Low doses: Sedative effects

● High doses: Hypnotic effects (also lower respiratory rate)
● Notorious enzyme inducers
o Stimulate liver enzymes that cause the metabolism or breakdown of many drugs
o Result: shortened duration of action

Barbiturates: Indications

● Hypnotics 🡪 Sleep
● Sedatives 🡪 Relax

29
PHARMACOLOGY NOTES
● Anticonvulsants 🡪 Epilepsy & Seizures
● Anesthesia for surgical procedures

Barbiturates: Four Categories

● Ultra-short-acting
o Anesthesia for short surgical procedures
● Short-acting
o Sedation/sleep induction and control of convulsive conditions
● Intermediate-acting
o Sedation/sleep induction and control of convulsive conditions
● Long-acting
o Sleep induction, epileptic seizure prophylaxis
● Ultrashort
o Methohexital
o Thiopental

● Short
o Phenobarbital
o Secobarbital
● Intermediate
o Butobarbital
● Long
o Phenobarbital
o Mephobarbital

Barbiturates: Adverse Effects

Body System Adverse Effects

CNS Drowsiness, lethargy, vertigo, and mental

depression
Respiratory depression, apnea,
bronchospasms, and cough
Respiratory
GI Nausea, vomiting, diarrhea, and constipation

Agranulocytes, hypotension, and Stevens-

Johnson Syndrome
Other

● Reduced REM sleep, resulting in:

o Agitation
o Inability to deal with normal stress

30
PHARMACOLOGY NOTES
Barbiturates: Toxicity & Overdose

● Overdose frequently leads to respiratory depression, and subsequent respiratory arrest

● Overdose produces CNS depression (sleep to coma & death)
● Can be therapeutic
o Anesthesia induction
o Uncontrollable seizures: “Phenobarbital coma”
● Treatment of overdose:
o Symptomatic & seizures
o Maintain adequate airway
o Assisted ventilation/oxygen therapy
o Fluids
o Pressor Support
o Activated charcoal

Barbiturates: Drug Interactions

● Additive effects
o ETOH, antihistamines, benzodiazepines, opioids
● Metabolism inhibited by other drugs
o MAOIs will prolong effects of barbiturates
● Increased metabolism of other drugs
o Reduced anticoagulant response, leading to possible clot formation

Muscle Relaxants

● Act to relieve pain associated with skeletal muscle spasms

● Majority are central-acting
o CNS is the site of action
o Similar in structure and action to other CNS depressants
● Direct-acting
o Act directly on the skeletal muscle
o Closely resemble GABA

Muscle Relaxants: Indications

● Relief of painful musculoskeletal conditions

o Muscle spasms
o Management of spasticity of severe chronic disorders ( EX: Multiple sclerosis
cerebral palsy)
● Work best when used along with physical therapy
● Dantrolene (Dantrium)

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PHARMACOLOGY NOTES
o Malignant hyperthermia 🡪 Massive Ca+ release

Muscle Relaxants: Adverse Effects

● Extension of effects on CNS and skeletal muscles

o Euphoria
o Dizziness
o Fatigue
o Lightheadedness
o Drowsiness
o Muscle weakness

Common Muscle Relaxants

● Baclofen (Lioresal) 🡪 Good for hiccups

● Cyclobenzaprine (Flexeril) Central-Acting
● Dantrolene (Dantrium) 🡪 Direct- Acting
● Metaxalone (Skelaxin)
● Tizanidine (Zanaflex) 🡪 Decreases sympathetic response Central-Acting

Chapter 13 – CNS Stimulants & Related Drugs:

Stimulants

● Drugs that stimulate specific areas of the brain or spinal cord

o Increases excited transmitter
● Sympathomimetic drugs

CNS Stimulants: Uses

● Analeptics (CNS Stimulants)

o CNS Stimulant for the purpose of respiratory stimulation
● Appetite suppressants (anorexiant)
● Treatment of:
o Attention deficit hyperactivity disorder (ADHD)
o Narcolepsy
o Migraine Headaches

CNS Stimulants: Indications

● ADHD
o Stimulate areas in the brain responsible for mental alertness and attentiveness
● Anorexiant
o Suppress appetite control center in the brain
● Analeptic
o Neonatal apnea, bronchopulmonary dysplasia, postanesthetic respiratory
depression
o NOT USED VERY OFTEN

32
PHARMACOLOGY NOTES
● Narcolepsy
o Increase mental alertness
● Migraine headaches
o Caffeine, co-administered with other drugs, used to treat headache
o Vascular headaches caused by vasodilation

Adverse Effects

● Tend to “speed up” the body systems

● Common adverse effects include:
o Palpitations, tachycardia, hypertension, angina, dysrhythmias, nervousness,
restlessness, anxiety, insomnia, nausea, vomiting, diarrhea, dry mouth, increased
urinary frequency

CNS Stimulants

● ADHD 🡪 Increase the release and block the uptake of

o Amphetamine (Adderall)
o Methylphenidate (Concerta, Ritalin)
o Atomoxetine (Strattera)
▪ Nonaddictive
▪ May cause suicidal thinking and behavior
● Narcolepsy
o Modafinil (Provigil)
o Decreases GABA; increases norepinephrine & dopamine
● Anorexiants
o Sibutramine (Meridia)
o Phentermine (Lonamin) 🡪 Suppress appetite
o Orlistat (Xenical)
▪ Lipase inhibitor, NOT a CNS stimulant
▪ Also used to treat obesity
▪ May cause fecal incontinence
▪ Does not allow you to absorb fat in the GI tract
● Antimigraine (serotonin agonists) 🡪 Serotonin receptors stimulated which causes vasoconstriction
o Almotriptan (Axert)
o Eletriptan (Relpax)
o Frovatriptan (Frova)
o Naratriptan (Amerge)
o Rizatriptan (Maxalt)
o Sumatriptan (Imitrex)
o Zolmitriptan (Zomig)
● Analeptics
o Used less frequently
o Still used for neonatal apnea
o Examples:

33
PHARMACOLOGY NOTES
▪ Doxapram (Dopram)
▪ Methylxanthines, such as aminophylline, theophylline, and caffeine
● Caffeine
o Found in:
▪ OTC drugs
▪ Combination prescription drugs
▪ Foods and beverages
o Use with caution in patients with a history of:
▪ Peptic ulcers
▪ Recent myocardial infarction (heart attack)
▪ Dysrhythmia
▪ Stimulates acid secretion
o Many Uses
▪ Neonatal apnea
▪ Respiratory depression in adults
▪ Enhances effects of analgesics and migraine medications
▪ Stimulates CNS (NoDoz, vivarin) 🡪 Will keep you awake

Chapter 14 – Antiepileptic Drugs:

Epilepsy

● Seizure
o Brief episode of abnormal electrical activity in nerve cells of the brain
● Convulsion
o Involuntary spasmodic contractions of any or all voluntary muscles throughout
the body, including skeletal and facial muscles
● Epilepsy
o Chronic, recurrent pattern of Seizures
● Primary (idiopathic)
o The cause cannot be determined
o More than 50% of epilepsy cases
● Secondary
o Distinct cause is identified
▪ Trauma, infection, cerebrovascular disorder

Classification of Epilepsy

● Partial-onset seizures 🡪 ONE side of the brain

o Simple (formerly known as petit mal seizures)
o Complex
o Secondary generalized tonic-donic
● Generalized-onset seizures 🡪 BOTH sides of the brain are involved
o Formerly known as grand mal seizures 🡪 You lose consciousness
● Unclassified seizures

34
PHARMACOLOGY NOTES
● Status epilepticus

Antiepileptic Drugs

● Also known as anticonvulsants

● Goals of therapy:
o To control or prevent seizures while maintaining a reasonable quality of life
o To minimize adverse effects and drug-induced toxicity
● AED therapy is usually lifelong
● Combination of drugs may be used
● Single-drug therapy started before multiple-drug therapy is tried
● Serum drug concentrations must be measured
o Therapeutic drug monitoring
● Patients who are seizure free for 1 to 2 years may be able to discontinue antiepileptic
therapy

Mechanism of Action

● AED therapy must:

o Prevent generation and spread of excessive electrical discharge from abnormally
functioning nerve cells
▪ Slow down neurons firing or don’t allow it to spread to other areas
o Protect surrounding normal cells
● AEDs thought to alter movement of sodium, potassium, calcium or magnesium ions
across nerve cells in the brain
o Reduce the nerves ability to be stimulated
o Suppress transmission of impulses from one nerve to the next
o Decrease speed of nerve impulse conduction within a neuron
● Overall effect
o Neurons are stabilized
o Neuron hyperexcitability is decreased
o Spread of excessive nerve impulses is decreased

Antiepileptic Drugs: Indications

● Prevention or control of seizure activity

● Long term maintenance therapy for chronic, recurring seizures
● Acute treatment of convulsions and status epilepticus

Antiepileptic Drugs

● Adverse effects often necessitate a change in medication

● Black box warning as of 2008 Usually Pregnancy
o Suicidal thoughts and behavior levels C & D

35
PHARMACOLOGY NOTES
● Long-term therapy with phenytoin may cause gingival hyperplasia, acne, hirsutism, and
Dilantin facies
● Phenobarbital (Solfoton)
o Old drug; VERY long half-life; Used for EVERY seizure; inexpensive
● Primidone
o Metabolized phenobarbital & ?
● Carbamazepine (Tegretol)
o 2nd most common; used for simple-partial
● Valproic Acid
o Used for general & partial seizure
● Phenytoin (Dilantin)
o #1 most commonly used; BLOCKS NA+ channels; Used for tonic & partial
● Fosphenytoin
o Pro-drug (means it’s inactive); used for NPO (nothing by mouth) patients
because it’s easier on the patients veins than phenytoin; metabolized into
phenytoin; done through an IV

● Succinimides, such as ethosuximide (Zarontin)

o Drug of choice for absent seizures
● Benzodiazepines (Clonazepam and clorazepate)
● Gabapentin (Neurontin)
o Increases GABA synthesis to decrease neural activity; partial seizures &
neuropathic pain
● Lamotrigine (Lamictal)
o Blocks NA+ channels; partial seizures
● Pregabalin (Lyrica)
o Additive drug (not used alone) for partial seizures
● Levetiracetam (Keppra)
● Topiramate (Topamax) Antiepileptics
● Tiagabine (Gabitril)

Chapter 15 - Antiparkinsonian Drugs:

Parkinson’s Disease

● Chronic, progressive, degenerative disorder

● Affects dopamine- producing neurons of the brain
● Caused by an imbalance of 2 neurotransmitters
o Dopamine 🡪 Inhibitory
o Acetylcholine 🡪 Excitatory
● Signs and symptoms occur when about 80% of the dopamine stored in the substantia
nigra of the basal ganglia is depleted
● Signs and symptoms can be partially controlled as long as there are functioning nerve
terminals that can take up dopamine
o Usually it is caught too late

36
PHARMACOLOGY NOTES
● Signs and Symptoms include:
o Akinesia
▪ Reduction in or absence of psychomotor activity resulting in mask-like
facial expression and impaired postural reflexes
o Bradykinesia
▪ Slowness of movement
o Rigidity
▪ Resistance to passive movement
o Tremor
▪ Tremor of the thumb against the forefinger, seen mostly at rest and less
severe during voluntary activity; Usually starts one ONE side then
progresses to the other; Is a presenting sign in 70% of cases
o Postural Instability
▪ Unsteadiness that leads to the danger of falling
● A progressive condition
● Rapid swings in response to levodopa occur (Known as the “on-off phenomenon”)
o PD worsens when too little dopamine is present
o Dyskinesia occurs when too much dopamine is present

Dyskinesia

● Difficulty in performing voluntary movements

● Two common types of dyskinesias:
o Chorea: Irregular, spasmodic, involuntary movements of the limb OR facial
muscles
o Dystonia: Abnormal muscle tone leading to impaired or abnormal movements

Levodopa Therapy

● Levodopa is a precursor of dopamine

● Blood-brain barrier does not allow exogenously supplied dopamine to enter, but does
allow levodopa to enter
o Dopamine cannot make it through the blood-brain barrier but
levodopa can!
● Levodopa is taken up by the dopaminergic terminal, converted into dopamine, then is
released as needed
● As a result, neurotransmitter imbalance is controlled in patients with EARLY PD who
still have FUNCTIONING nerve terminals
● As PD progresses, it becomes more difficult to control it with levodopa
● Ultimately, levodopa no longer controls the PD, and the patient becomes seriously
debilitated
o This generally occurs 5-10 years after the start of levodopa therapy
o Summary: Levodopa therapy is used in patients with PD who still have
functioning nerve terminals. The therapy is used to slow the disease down BUT is

37
PHARMACOLOGY NOTES
NOT a treatment because things will get progressively worse well on the
levodopa.

Drug Therapy for PD

● Aimed at increasing the levels of dopamine as long as there are functioning nerve
terminals remaining
● Antagonize or blocks the effects of Ach
● Slows the progression of the disease
● Indirect-acting dopamine-receptor agonists
o MAO-B inhibitors: Selegiline, Rasagiline
▪ Metabolize dopamine and make it last longer
o COMT inhibitors: Entocapone and Tolcapone
▪ Levodopa and dopamine metabolizer; longer half-life
o Presynaptic dopamine release enhancer: Amantadine
▪ Stimulates the release of dopamine presynaptically; ONLY works when
the neurotransmitters are FUNCTIONING
● Anticholinergic Drugs
o Benztropine
o Trihexyphenidyl
● Antihistamines 🡪 Have anticholinergic effects
o Diphenhydramine
● NONdopamine-receptor agonists 🡪 NOT dopamine but STIMULATE dopamine receptors
o Ergot: Bromocriptine
o Nonergot: Pramipexole, Ropinirole, Apomorphine
● Dopamine Replacent Drugs
o Carbidopa, Carbidopa-levodopa

Selective MAOI Therapy: Selegiline

● MOA breaks down the catecholamines in the CNS, primarily in the brain
● Selegiline is a selective MAOB inhibitor
o Causes an increase in levels of dopaminergic stimulation in the CNS
● Selegiline is a newer, potent, and irreversible MAOI that selectively inhibits MAOB
● Does not elicit the “cheese effect” of the nonselective MAOIs used to treat depression (if
10mg or less is used)
● Used in combination with levodopa or carbidopa-levodopa
● Used as an adjunct when a patients response to levodopa is fluctuating
● Allows the dose of levodopa to be DECREASED
o Delays the development of unresponsiveness to levodopa therapy
● Improves function ability
● Decreases severity of signs and symptoms
● Only 50% to 60% of patients show a positive response to therapy
● Prophylactic selegiline may delay the development of serious debilitating PD for 9 to 18
years

38
PHARMACOLOGY NOTES
● Rasagiline approved in 2008 with similar action as selegiline
o Does not work for everyone but this could delay the progression of the disease
● Adverse effects are usually mild
o Nausea, lightheadedness, dizziness, abdominal pain, insomnia, confusion, and
dry mouth
o Doses that are higher than 10 mg per day may cause more serious adverse effects
such as hypertensive crisis

Presynaptic Dopamine Release Enhancer

● Amantadine (Symmetrel)
o Indirect-acting
o Causes the release of dopamine from the storage sites at the end of nerve cells
that are still INTACT
o Blocks reuptake of dopamine into the nerve endings, allowing more to
accumulate both centrally and peripherally
o Does not stimulate dopamine receptors directly
▪ Works for about 6-12 months
o Used early in the course of the disease
o Usually effective for only 6-12 months
o Also used as an antiviral for influenza virus infection

COMT Inhibitors

● Indirect-acting
● Tolcapone (Tasmar) 🡪 Longer half-life and can get through the blood-brain barrier
● Entacapone (Comtan)
● Inhibit COMT, the enzyme responsible for the breakdown of the levodopa, the dopamine
precursor
● Prolong the duration of action of levodopa; reduce wearing off phenomenon
● Tolcapone (Tasmar)
o Has caused severe liver failure
o Requires monitoring of liver enzymes
o Not used unless other drugs do not woek

Direct-Acting Dopamine Receptor Agonists

● Non-dopamine dopamine receptor agonists

o Ergot derivatives (bromocriptine)
o Non-ergot drugs (Pramipexole, Ropinirole, Apomorphine)
● Dopamine Replacement Drugs
o Levodopa, carbidopa, carbidopa-levodopa (Sinemet)
▪ Stimulate dopamine receptors but are NOT dopamine
● Non-dopamine dopamine receptor agonists
o Ropinirole (Requip)
▪ Newer, non-ergot

39
PHARMACOLOGY NOTES
▪ Used for PD and restless leg syndrome
o Apomorphine (Apokyn)
▪ Newer, non-ergot dopamine agonist
▪ Subcutaneous injection
o Rotigotine
▪ Transdermal patch
● Direct-acting
o Bromocriptine (Parlodel)
● Directly stimulate dopamine receptors
● Activate dopamine receptors and stimulate production of more dopamine

Dopamine Replacement Drugs

● Replacement drugs (presynaptic)

o Work presynaptically to increase brain levels of dopamine
o Levodopa is able to cross the blood-brain barrier, and then it is converted to
dopamine
o However, large doses of levodopa needed to get dopamine to the brain also cause
adverse effects
▪ Need a large dose to get through the blood-brain barrier but dopamine
peripherally causes adverse effects which is BAD
● Replacement drugs
o Carbidopa is given with levodopa
o Carbidopa does NOT cross the blood-brain barrier and prevents levodopa
breakdown
o As a result, more levodopa crosses the blood-brain barrier, where it can be
converted into dopamine
▪ Only inhibits peripherally but not in the CNS; decreases the toxicity of
levodopa!

Anticholinergic Therapy

● Anticholinergics block the effects of Ach

● Used to treat muscle tremors and muscle rigidity associated with PD
o These two symptoms are caused by excessive cholinergic activity
● Does not relieve bradykinesia (extremely slow movements)
● Ach dominates because of the imbalance of dopamine
● As a result, overstimulation of the cholinergic excitatory pathway occurs
o Muscle tremors and muscle rigidity
o Cogwheel rigidity
o Pill-rolling movement of fingers & head-bobbling while at rest
● Benztropine mesylate (Cogentinin)

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PHARMACOLOGY NOTES
o Also used to treat extrapyramidal symptoms caused by use of antipsychotic drugs
▪ Block dopamine receptors
● Trihexyphenidyl (generic only)
● Antihistamines also have anticholinergic properties
o Diphenhydramine (Benadryl)

Anticholinergic Therapy: Indications

● Used in the treatment of PD to cause smooth muscles to relax, resulted in reduced

muscle rigidity and akinesia
● Also used to treat drug-induced extrapyramidal reactions to certain antipsychotic drugs

Anticholinergic Therapy: Adverse Effects

● Drowsiness, confusion, disorientation

● Constipation, nausea, vomiting
● Urinary retention, pain or urination
● Blurred vision, mydriasis (dilated pupils), photophobia (bright light reactions), & dry
skin
● Decreased salvation which leads to a dry mouth

Salvation Lacrimation Urination Gi Distress

Chapter 16: Psychotherapeutic Drugs:
Psychotherapeutic Drugs

● Used in the treatment of emotional and mental disorders

o Ability to cope with emotions can range from occasional depression or anxiety to
constant emotional distress
o When emotions significantly affect an individual’s ability to carry out normal
daily functions, treatment with a psychotherapeutic drug is a possible option
● Three main emotional and mental disorders:
o Anxiety
o Affective Disorders
o Psychoses
● Types of psychotherapeutic drugs
o Antianxiety drugs
o Antimanic drugs
o Antidepressant drugs
o Antipsychotic drugs

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PHARMACOLOGY NOTES
Biochemical Imbalance

● Other biochemicals are necessary for normal mental function

o GABA
o Acetylcholine (Ach)
o Sodium, potassium, magnesium

Anxiety

● Unpleasant state of mind, characterized by a sense of dread and fear

● May be based on actual anticipated experiences or past experiences
● May be exaggerated responses to imaginary negative situations

Anxiety Disorders

● Six major anxiety disorders (persistent anxiety)

o Obsessive-compulsive disorder (OCD)
o Posttraumatic stress disorder (PTSD)
o Generalized Anxiety Disorder (GAD)
o Panic disorder
o Social phobia
o Simple phobia

Affective Disorders (Mood Disorders)

● Changes in mood that range from mania (abnormally pronounced emotions) to

depression (abnormally reduced emotions)
● Some patients may exhibit both mania and depression: bipolar disorder (BPD)

Psychosis

● Severe emotional disorder that impairs the mental function of the affected individual to
point that the individual cannot participate in activities of daily living
● Hallmark: loss of contact with reality
● Examples:
o Schizophrenia
o Depressive and drug-induced psychoses

Psychotherapeutics: Pathophysiology

● Biochemical imbalance theory

o Mental disorders are associated with abnormal levels of endogenous chemicals,
such as neurotransmitters, in the brain
o Brain levels of certain neurotransmitters play an important role in maintaining
mental health
o Catecholamines
▪ Dopamine
▪ Norepinephrine

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PHARMACOLOGY NOTES
o Indolamines
▪ Serotonin
▪ Histamine

Antianxiety Drugs

● Reduce anxiety by reducing overactivity in CNS

o Benzodiazepines
▪ Depress activity in the brainstem and limbic system
o Miscellaneous drug: Buspirone (BuSpar)
▪ Non-sedating and non-habit forming
▪ May have drug interactions with SSRIs (serotonin syndrome)
▪ Do not administer with MAOIs

Antianxiety Drugs: Indications

● Anxiety
● Insomnia
● Sedation
● Muscle Spasms
● Seizure Disorder
● Adjuncts in anesthesia
● Adjuvant therapy for depression
● Alcohol (ethanol) withdrawal

Common Benzodiazepines

● Diazepam (Valium)
● Lorazepam (Ativan)
● Alprazolam (Xanax)
● Clonazepam (Klonopin)
● Chlordiazepoxide (Librium)
● Midazolam (Versed)
o Reduces anxiety and patient’s memory of painful procedures that do not require
anesthesia (moderate sedation)
o Injection only
▪ Limited to use as sedative and anesthetic during invasive medical or
surgical procedures

Benzodiazepines

● Potentially habit-forming and addictive

● Should be used at lowest effective dosages and frequencies needed for symptom control

Benzodiazepines: Adverse Effects

● Benzodiazepine adverse effects are an overexpression of their therapeutic effects

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PHARMACOLOGY NOTES
o Decreased CNS activity, sedation
o Hypotension
o Drowsiness, loss of coordination, dizziness, headaches
o Nausea, vomiting, dry mouth, constipation

Benzodiazepines: Overdose

● Dangerous when taken with other sedatives or alcohol

● Treatment is generally symptomatic and supportive
● Flumazenil may be used to reserve benzodiazepine effects

Affective Disorder Drugs

● Mood stabilizers
o Used to treat bipolar disorder
▪ Involved cycles of mania, hypomania, and depression
● Antidepressants
o Used to treat depression

Mood Stabilizers: Antimanic Drugs

● Lithium is the drug of choice for the treatment of mania:

o It is thought to potentiate serotonergic neurotransmission
o May be used with other medications to stabilize mood
o Narrow therapeutic range: Maintenance serum levels should range between 0.6
and 1.2 mEq/L
o Monitor sodium levels
o Low TI (Therapeutic Index)

Depression

● Etiology
o Biogenic amine hypothesis
▪ Depression and mania are caused by an alteration in neuronal and
synaptic catecholamine concentration at adrenergic receptor sites in the
brain
● Depression: Deficiency of catecholamine, especially
norepinephrine
● Mania: excessive amines
o Permissive hypothesis
▪ Affective disorders are caused by decreased concentration of serotonin
● Depression results from decreases in both serotonin and
catecholamine levels

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PHARMACOLOGY NOTES
● Mania results from an increased catecholamine level but a
decreased serotonin level

Antidepressants

● Tricyclic antidepressants
● Monoamine oxidase inhibitors (MAOIs)
o Selective serotonin reuptake inhibitors (SSRIs)
o Second and third generation antidepressants

Tricyclic Antidepressants: First-Generation Antidepressants

● Have largely been replaced by SSRIs as first-line antidepressant drugs

● Considered second-line
o For patients who fail with SSRIs or newer-generation antidepressants
o As adjunct therapy with newer generation antidepressants

Common Tricyclics

● Amitriptyline (Elavil,Endep)
● Doxepin (Sinequan)
● Imipramine (Tofranil)
● Desipramine (Norpramin)
● Nortriptyline (Aventyl, Pamelor)

Mechanism of Action

● Block reuptake of neurotransmitters, causing accumulation at the nerve endings

● It is thought that increasing concentrations of neurotransmitters will correct the
abnormally low levels that lead to depression

Drug Effects

● Blockade of norepinephrine reuptake

o Antidepressant*, tremors, tachycardia
● Blockade of serotonin reuptake
o Antidepressant*, nausea, headache, anxiety, and sexual dysfunction
▪ *= Desired therapeutic Effect

Indications

● Depression
● Childhood enuresis (imipramine)
● Obsessive-compulsive disorders (clomipramine)
● Adjunctive analgesics for chronic pain conditions, such as trigeminal neuralgia

Adverse Effects

● Sedation
● Impotence

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PHARMACOLOGY NOTES
● Orthostatic hypotension
● Dysrhythmias
● Seizures
● Older patients
o Dizziness, postural hypotension, constipation, delayed micturition, edema,
muscle tremors

Overdose

● Lethal – 70% to 80% die before reaching the hospital

● CNS and cardiovascular systems are mainly affected
● Death results from seizures or dysrhythmias
● NO SPECIFIC ANTIDOTE
o Decrease drug absorption with activated charcoal
o Speed elimination by alkylating urine
o Manage seizures and dysrhythmias
o Basic life support

MAOIs

● Highly effective
● Considered second-line treatment for depression, not responsive to cyclics
● DISADVANTAGE: potential to cause hypertensive crisis when taken with tyramine
● Examples:
o Phenelzine (Nardil)
o Tranylcypromine (Parnate)

MAOIs: Mechanism of Action

● Inhibit MAO enzyme in the CNS

● Amines (dopamine, serotonin, norepinephrine) are not broken down, resulting in higher
levels in the brain
● Result: Alleviation of symptoms of depression

MAOIs: Indications

● Depression, especially types characterized by increased sleep and appetite

● Depression that does not respond to other antidepressants

Hypertensive Crisis and Tyramine:

● Ingestion of foods or drinks with tyramine leads to hypertensive crisis, which may lead to
cerebral hemorrhage, stroke, coma, or death
● Avoid foods that contain tyramine !
o Aged, mature cheese (cheddar, blue cheese, and swiss)
o Smoked/pickled or aged meats, fish, poultry
o Yeast extracts

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PHARMACOLOGY NOTES
o Red wines
o Italian bread beans

MAOIs

● Concurrent use of MAOIs and SSRIs may lead to serotonin syndrome

● If the decision is made to switch to an SSRI, there must be a 2-5 week “wash-out” period
between MAOI therapy and SSRI therapy

Newer-Generation Antidepressants

● Fewer adverse effects than tricyclics and MAOIs

● Very few drug-drug or drug-food interactions
● Still takes about 4-6 weeks to reach maximum clinical effectiveness
● Now considered first-line drugs for depression
● Trazadone (Desyrel)
● Bupropion (Wellbutrin)
● SSRIs
o Fluoxetine (Prozac)
o Paroxetine (Paxil)
o Sertraline (Zoloft)
o Fluvoxamine (Luvox)
o Citalopram (Celexa)
o Escitalopram (Lexapro)
o Venlafaxine (Effexor)
o Nefazodone (Serzone)
o Mirtazapine (Remeron)
o Duloxetine (Cymbalta)
o Desvenlafaxine (Pristiq)

SSRIs: MoA

● Selectively inhibit serotonin reuptake

● Little or no effect on norepinephrine or dopamine reuptake
● Result in increased serotonin concentrations at nerve endings
● Advantage over tricyclics and MAOIs: Little or no effect on the
cardiovascular system

Newer-Generation Antidepressants:

● Depression
● Bipolar Disorder
● Obesity
● Eating Disorders

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PHARMACOLOGY NOTES
● Obsessive-Compulsive Disorder
● Panic attacks or disorders
● Social anxiety disorders
● PTSD
● Treatment of various substance abuse problems (bupropion is used for smoking
cessation treatment)

Newer Generation Antidepressants: Adverse Effects

Body System Adverse Effects

CNS Headache. Dizziness, tremor, nervousness,
insomnia*, fatigue
GI Nausea, diarrhea, constipation, dry mouth
Other Sexual dysfunction, weight gain*, weight
loss*, sweating
*Most common and bothersome adverse effects

Serotonin Syndrome

● Signs/symptoms
o Delirium, tachycardia, hyperreflexia, shivering, agitation, sweating, muscle
spasms, coarse tremors
● Signs/symptoms of severe cases
o Hyperthermia, seizures, renal failure, rhabdomyolysis, dysrhythmias,
disseminated intravascular coagulation (DIC)

Newer-Generation Antidepressants: Drug Interactions

● Highly bound to protein plasmas

● Compete with other protein-binding drugs, resulting in more free, unbound drug to
cause a more pronounced drug effect
● Inhibition of cytochrome P-450 system
● MAOIs

Antipsychotics

● Drugs used to treat serious mental illness

o Behavioral problems or psychotic disorders
● Have been known as tranquilizers or neuroleptics
● Thioxanthenes: thiothixene (Navane)
● Butyrophenones: haloperidol (Haldol)
● Dihydroindolones: molindone (Moban)
● Dibenzoxazepine: Loxapine (Loxitane)

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PHARMACOLOGY NOTES
● Phenothiazines
● Atypical antipsychotics: new class

Mechanism of Action

● Block dopamine receptors in the brain (limbic system, basal ganglia)- areas associated
with emotion, cognitive function, motor function
● Result: Tranquilizing effect in psychotic patients

Atypical Antipsychotics: Second-Generation Antipsychotics

● Clozapine (Clozaril)
● Risperidone (Risperdal)
● Olanzapine (Zyprexa)
● Quetiapine (Seroquel)
● Ziprasidone (Geodon)
● Aripiprazole (Abilify)
● Paliperidone (Invega)

Atypical Antipsychotics: Mechanism of Action

● Block specific dopamine receptors: DA-2 (D2) receptors

● Also block specific serotonin receptors: 5HT-2 (5HT2) receptors
o This is responsible for their improved efficacy and safety profiles

Antipsychotics: Indications

● Treatment of serious mental illnesses

o Bipolar affective disorder
o Depressive and drug-induced psychoses
o Schizophrenia
o Autism
● Movement disorders (such as Tourette’s Syndrome)
● Some medical conditions
o Nausea, intractable hiccups

Adverse Effects

Body System Adverse Effects

CNS Sedation, delirium

Cardiovascular Orthostatic hypotension, syncope, dizziness,
ECG changes
Dermatologic Photosensitivity, skin rash,
hyperpigmentation, pruritus
GI Dry mouth, constipation

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PHARMACOLOGY NOTES

GU Urinary hesitancy or retention, impaired

erection
Hematologic Leukopenia and agranulocytes
Metabolic/Endocrine Galactorrhea, irregular menses, increased
appetite, polydipsia
● Neuroleptic malignant syndrome (NMS)
o Potentially life threatening
o High fever, unstable BP, myoglobinemia
● Extrapyramidal Symptoms (EPS)
o Involuntary muscle symptoms similar to those of Parkinson’s disease
o Akathisia (Distressing muscle restlessness)
o Acute dystonia (Painful muscle spasms)
o Treated with benztropine (C0gentin) and trihexyphenidyl (Artane)
● Tardive Dyskinesia (TD)
o Involuntary contractions of oral and facial muscles
o Choreoathetosis (wavelike movements of extremities)
o Occurs with continuous long-term antipsychotic therapy

Herbal Products: St. John’s Wort

● Used for depression, anxiety, sleep disorders, nervousness

● May cause GI upset, fatigue, dizziness, confusion, dry mouth, photosensitivity
● Severe interactions if taken with MAOIs and SSRIs
● Food-drug interaction with tyramine-containing foods

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