Transcript ATH 521 Pharmacology

Pharmacology
INTRODUCTION & PHARMACOKINETIC PRINCIPLES
SEAN BURFEIND, ATC, LAT, OTC
Objectives
 Define drug; differentiate between names
 Explain difference between generic name & drug
 Explain drug classification
 FDA role in development and recall
 Apply drug concepts
 Explain how drug chemical structure determines
biological effects
 Primary mechanisms which drugs cross membranes,
& metabolize
 Discuss drug excretion by kidneys
Drug
 Chemical used to treat or prevent disease
 Shown to be effective
 All have a chemical name
 Generic name is nonproprietary name
 Proprietary name = brand name = trade name
 How do we get a generic drug?
 Differences between generic & trade name products
Differences
Trade-Name Drug
Generic-Name Drug
 Can have multiple trade
 Only one generic name
 Refers to one chemical
names
 Names shorter & easier
to pronounce
 Refers to entire product
 May include more than
one active ingredient
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entity
Less expensive
Not all drugs marked as
generic drugs
Can be marketed by
multiple companies
Must obtain FDA approval
Must be bioequivalent to
trade name drug
Classification of Drugs
 Nonprescription (OTC)
 Lower amount of drug/dose unit compared with prescription
 Contain multiple active ingredients
 Prescription
 Greater potential for adverse effects than OTC
 Used for limited time period
 Medical supervision mandated
 Controlled (Schedule)
 Abuse potential
 More restrictive requirements regarding distribution, storage,
and record keeping
Classification of Controlled Substances
 Schedule I
 High abuse potential; not accepted for medical use in US; may
be used for research
 Schedule II
 High abuse potential; Accepted medical use in US
 Schedule III
 Lower abuse than II; Accepted medical use in US
 Schedule IV
 Lower abuse than III; accepted medical use
 Schedule V
 Lowest potential abuse; contain smaller quantities; some
nonprescription in some states
FDA – New Drug Development
 Responsible for review and approval of all new drugs
before available to public
 Demonstrate safety and effectiveness in clinical trials
before use
 Testing Procedures for new drug
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Preclinical testing (3-6 years)
Phase I (1-2 years)
Phase II (2-3 years)
Phase III ( 3-4 years)
Phase IV (1.5-2.5 years)
FDA – Drug Recalls
www.fda.gov
 Class I
 Reasonable possibility that serious threat to health of
consumer; need for additional labeling or color code on birth
control error
 Class II
 Use of or exposure to produce may cause temporary health
problem that is reversible; contamination in certain lots of
medication
 Class III
 Use of or exposure to is not likely to cause health hazard; when
certain batches of medicine have traces of iron; mislabel of
drug packaging
Drug Information Sources
 Physician’s Desk Referene (PDR)
 Chemical properties of drug; pharmacology and clinical data;
precautions; adverse effects; indications/dosages; routes for
administration
 The Pharmacological Basis of Therapeutics
 Goodman & Gilman
 Drug Facts and Comparisons
 US Pharmacopeia/National Formulary (USP/NF)
 Standards for purity, strength, quality, and analysis of drug
 USP on label if meets standards
 Handbook of Nonprescription Drugs
www.fda.gov/Drugs/default.htm
www.usada.org
www.ncaa.org/health-safety
Pharmacokinetics
 Study of impact of the body on a drug
 Primary focus on rate and extent to which the drug is
absorbed into blood stream, distributed through
body, metabolized and excreted
 Processes affect magnitude & duration of biological
responses
Action
 Site of Action
 To have effect drug must reach site of action(molecular site
where drug produces biological effect)
 Usually receptor on or in cell or enzyme in cell
 Onset of Action
 Time it takes for drug to cause response
 Minimum effective concentration
 Duration of Action
 Time between onset and termination
Clearance rate:
measure of efficiency
of metabolism and
excretion
 Half Life
 Time for drug amount in blood to be reduced by ½ (%)
Bioavailability & Bioequivalence
 To be bioavailable, drug must reach blood
 2 components: amount of drug absorbed & rate of absorption
 Diminished if:
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First pass effect:
 Bioequivalence – refers to comparison of amount
and rate of drug entering circulation
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Generic product
Chemical Structure
 Determines chemical binding forces
 Determines biological effects, rate of absorption,
excretion and metabolism
 Small changes have large biological effects
 Determines size and chemical shape of each
molecule
 Solubility – determines how quickly drug dissolved
in GI tract
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Water vs. lipid
Absorption
 Oral
 Depends on rate of solubility; lipid solubility; stability with
other GI contents
 Must be in a solution
 Once dissolved in intestinal tract must be passed to blood
 Small intestines mostly; passive diffusion mostly
 Liquid best
 With food usually slows absorption; will reduce peak blood
concentration
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Good with NSAIDS
May delay intentionally for longer duration of effect
Administration & Absorption
 Sublingual or Buccal
 Under tongue or against cheek; rich blood supply facilitates
absorption; potent drugs; protect from first pass
 Rectal
 Unconscious, vomiting, or too young; suppository; absorbed
by hemorrhoidal veins; less absorption
 Parenteral
 IV, IM, subcutaneous; most rapid effect; need skill to
administer
 No absorption with IV – best for emergency
 IM more rapid than subcu; drug must cross membrane in both
Administration & Absorption (cont)
 Topical
 Surface application for systemic or local effect
 Rate of absorption depends on surface area and lipid solubility
 If skin moist or blood flow increased permeability increased
 Systemic effect = transdermal delivery
 Inhalation
 Need good technique
 Fast onset
Pharmacology
DRUGS FOR TREATING INFLAMMATION
Objectives
 Describe and explain inflammatory process
 Explain how common chemical mediators affect
inflammatory process
 Explain difference between COX1 & COX2
 Explain how NSAIDS work
 Explain how corticosteroids work
Inflammatory Process
 Normal and necessary process
 If excessive may need to intervene
 Chemical mediators released
 Mast cells and basophils
 Histamine
 Serotonin
 Thromboxanes*
 Leukotrienes*
 Prostaglandins*
 Bradykinin
Arachidonic Acid Metabolites
 COX pathway
 TX, PG, and PGI2
 COX 1
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All tissues; relatively stable rate; maintain normal function of
eicosanoid
COX 2
Brain; female reproductive; blood vessel walls; kidneys
 Induced in response to inflammation
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NSAIDS
 Most frequently prescribed & OTC
 Aspirin is prototype
 Major mechanism to decrease PG production by
inhibiting COX
 Little to no effect on LT pathway
 Selective COX2 NSAIDS
Bextra; Vioxx
Therapeutic Use of NSAIDS
 Tx both acute & chronic
 1-2 weeks typical
 No guidelines to determine which is best for
pathology
 Principal use: pain & inflammation
 Does the use of NSAIDS reduce healing time?
 Analgesic & antipyretic
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Fever = COX 2 response in brain
Therapeutic Uses of NSAIDS
 If inhibit COX 1 = antiplatelet activity
 Anticoauglant effect
 COX 1 ----TXA2; stimulate platelet aggregation
 COX 2 ----PGI2; inhibits platelet aggregation
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Platelet aggregation – blood coagulation factors--thromboembolism --- MI
Low Dose Aspirin treatment
Increased risk of stroke/heart attack with selective COX 2
inhibitors
Dose/Pharmokinetics of NSAIDS
 Absorbed rapidly; oral preparations
 Enteric-coated – delayed absorption
 Liver metabolism to clear
 Pain 400mg 4x; inflammation 600mg 4x
Adverse Effects of NSAIDS
 16k die & > 100k hospitalized from use
 Common sx
 GI irritation, heartburn, nausea, upper GI bleeding, ulcers
 Risk greater in >60 years
 COX 2 selective lower incidence GI, but maybe not
with Upper GI
 New labeling on all NSAIDs (not aspirin)
 Hypersensitivity
 Renal toxicity
NSAIDS Drug Interactions
 Can enhance effect of anticoagulants
 Diminish effects of antihypertensive drugs
 Systemic corticosteroid or alcohol may cause peptic
ulcers
 Need to monitor and educate patient
Corticosteroids
 Adrenal cortex produces 2 types
 Glucocorticoids (cortisol)
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Glucose metabolism
Mineralocorticoids (alderstone)
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Mineral balance, urinary reactions Na&K
 Therapeutic use – potency of anti-inflammatory
 Examples: hydrocortisone, dexamethasone,
prednisone
Therapeutic Use of Corticosteroids
 Suppress immune and acts as anti-inflammatory
 Broader anti-inflammatory effect than NSAID
 Inhibit activity of phospholipase
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PG & LT
 Reduce swelling & pain
 Inhibit phagocytes & lymphocytes
 Treat: RA, Gout, lupus, bronchial asthma, IBD,
tendonitis, bursitis, ocular; allergy
Dose/Pharmokinetics of Corticosteroids
 Variable depending on disorder
 Initiate at low dose for as short as possible
 Trial and error – need to monitor
 Inhalation, topical, injection (local), oral (systemic)
Adverse Effects of Corticosteroids
 Alters normal regulation of corticosteroid
production
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Adrenal cortex uses feedback loop based on amount in blood
(HPA axis)
Hypothalamus
CRH
Anterior Pituitary
ACTH
Adrenal Gland
Cortisol
Inhibition
 Need to be careful about taking off too quickly
Drug
Interactions
Pharmacology
DRUGS FOR TREATING PAIN
Objectives
 Explain how NSAIDS also have analgesic effect
 Explain pharmokinetics for acetaminophen & opioid
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drug
Signs & symptoms for adverse reaction
Identify common drug interactions
Therapeutic advantages for different drugs
Mechanics of actions
Concept of agonist vs. antagonist
Difference between drug addiction & physical
dependence
Foundations
 Terminology
 Analgesic
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Opiates
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Acetominophen
Morphine, Codeine
Opioids
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Oxycodone, Demerol
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Narcotic analgesic
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Narcotic
Nonsteroidal Anti-Inflammatory Drugs
NSAID
COX Inhibitor
Inhibits PG
Decreases Pain
Acetaminophen
 Analgesic and antipyretic efficacy
 Inhibits COX in brain not periphery
Careful with liver
disease & Alcohol
consumption
 No blood clotting issues, GI
 Peaks in blood ~ 1 hr post; t1/2 = 2hr
 325-1000mg; 4-6hr; adult – 24hrs<4000mg
 Ceiling effect for analgesia (650-1300mg)
 Allergic skin reaction; overdose common
 90% metabolized in liver, small amt toxic
 >7.5g adult and 150mg/kg kids
Opioid Analgesics
 Combine with opioid receptors in CNS and PNS
 3 sites: mu(μ,MOR), kappa(κ,KOR), delta(δ,DOR)
 Brain produces natural analgesics (endogenous
opioids)
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β-endorphins, enkephalins, dynorphins
 Most clinically effective result from μ interaction
 Addiction potential; schedule II mostly
 Dependence potential
Opioid Analgesics
 Withdrawal symptoms include
 Duration & intensity depends on duration of action
 Morphine
 Relieve moderate to severe pain; anxiety & stress
 Causes constipation & Sedative properties
 Use to treat diarrhea
Opioid Analgesics
 Other effects (adverse): respiratory depression, miosis,
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urinary retention, orthostatic hypotension, nausea,
vomiting
Available by oral, rectal, or parenteral
Peaks 1.5 hrs post
Adult parenteral dose morphine = 10mg; oral = 2060mg
Watch with CNS depressants
Demerol
Codeine
Methadone
Oxycodone
Ultram
Caffeine
 Enhances analgesic properties
 Creates shorter onset & longer duration
 Stimulant
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drowsiness & fatigue
alertness; 50-200mg
 Physical dependence; withdrawal symptoms
Local Anesthetics
 Topical preparations to alleviate pain
 Inhibit nerve impulse transmission
 Diminished hot, cold and touch
 Quick acting
 Can use parenterally
 Topically to treat pain or itching
Ethyl
Chloride
Cocaine
Lidocaine
Summary
 Defined drug; differentiate between names
 Explained difference between generic name & drug
 Primary mechanisms which drugs cross membranes, &
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metabolize
Discussed drug excretion by kidneys
Described and explained inflammatory process
Explained difference between COX1 & COX2
Explained how NSAIDS work
Explained how NSAIDS also have analgesic effect
Explained pharmokinetics for acetaminophen & opioid
drug
References
 Houglum JE, Harrelson GL. Principles of Pharmacology for Athletic
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Trainers. SLACK Incorporated; 2010.
Golan DE, Tashjian AH, Armstrong EJ. Principles of Pharmacology, The
Pathophysiologic Basis of Drug Therapy. Lippincott Williams & Wilkins;
2011.
Ciccone CD. Pharmacology in Rehabilitation. Philadelphia, PA. F.A. Davis
Company; 2007.
Gladson B. Pharmacology for Physical Therapists. St. Louis, MO: Saunders
Elsevier; 2006.
Harris Interactive, Inc. Attitudes and Beliefs About the Use of Over-theCounter Medications: A Dose of Reality.
Katzung BG, ed. 2009. Basic & Clinical Pharmacology. New York, NY. The
McGraw-Hill Companies, Inc; 2009.
Koester MC, Dunn WR, Kuhn JE, Spindler KP. The efficacy of subacromial
corticosteroid injection in the treatment of rotator cuff disease: A
systematic review. J Am Acad Orthop Surg. 2007;15(1):3-11.
Questions?
Pharmacology
DRUGS FOR TREATING INFECTIONS
Objectives
 Explain differences between infections caused by
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bacteria, fungi or virus
Explain mechanism of action of or antimicrobial,
antifungal, and antiviral meds
Describe process that causes microorganism to
become resistant to drug
Superinfections resulting from antibiotics
Role of antibiotics in UR & LR infections
Differentiate between categories of antibiotics
Discuss superficial vs. systemic fungal
Role of ATC in care of patients on antibiotics
Terminology
 Antimicrobial….
 Antibiotic….
 Antibacterial…
 Fungal…
 Viral…
Antibiotic Categories
 Chemical structure, mechanism of action
 Bactericidal – kill bacteria
 Bacteriostatic – slow growth
 Spectrum (based on gram stain +/-)
 Narrow
 Broad
Antimicrobial Resistance
 Microorganism response to drug
 Sensitive vs. Resistant vs. Susceptible
 Resistance promoted by overuse of antibiotics;
diminish competition of resistant strains
 Change in genetic makeup causes resistance
 Enzyme inactivates drug
 Altered structure of binding site
 Altered entry mechanism
Superinfections
 Develop during treatment of initial
infection
 When antibiotic kills normal flora in GI
 Mostly caused by broad spectrum
antimicrobials & long duration treatment
Selection of Dose Regimen
 Need to consider microorganism, site of
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infection, and patient
Effectiveness in fighting organism most
important
Based on symptoms before lab results
Infection site might limit
Dose and duration depend on
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Site of infection
Immune defense of patient
Respiratory Infections
 Very common illness associated with
inappropriate therapy
 URI
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Pharyngitis – viral; treated with antibiotic
Otitis media & sinusitis
 LRI
 Acute bronchitis – usually viral
 Pneumonia – bacteria (adults); viral (kids)
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Broad spectrum antibiotic
Antibacterial Drugs
 Penicillins
 β-lactam ring – key to binding penicillin to bacteria;
also susceptible to β-lactamases
 Penicillin G first one; from mold
 Can be combined with β-lactamase inhibiters
 High therapeutic index (TI)
 Risk of allergic reaction (10% patients)
 Bactericidal drugs
 Various types so need to pick the one that will target
specific bacteria
 Excreted rapidly by kidney
Antibacterial Drugs
 Cephalosporins
 2 dozen available
 Similar to penicillin….
 Less frequent allergy; cross-reactivity with penicillin in
10%
 First – fourth generation grouping
 Carbapenems
 β-lactam; inhibit cell wall synthesis; bactericidal;
resistant to β-lactamases; useful for skin, UI. LRI,
abdominal, pelvis
 Tetracyclines
Antibacterial Drugs
 Tetracyclines
 >50 years
 Not first choice: bacterial resistance; more cost effective
choices
 Highly effective: Rocky Mountain spotted fever, cholera,
Lyme disease, pneumonia, H. pylori, acne
 Doxycycline – anthrax
 Inhibits protein synthesis; bind to ribosomal RNA
 Bacteriostatic; broad-spectrum effective for gram +/ Not well absorbed – food diminshs; alters intestinal
flora; take 1hr before or 2hr after eating
 Not < 8 yrs, pregnant, nursing
Antibacterial Drugs (cont)
 Macrolides
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Erythromycin, biaxin, zithromax
Bacteriostatic – some bactericidal
Inhibit protein synthesis
Similar to penicillin, but can be used if allergy
GI, genital, respiratory, skin, soft tissue
Adverse: GI irritation, nausea, vomiting
Acid resistant coatings; first pass issues
 Sulfonamides – “sulfa drugs”
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Broad-spectrum bacteriostatic
Inhibit enzyme needed for synthesis of THFA
Pneumonia, URI, topical infections, burns
Crystallize in urine; renal damage
Antibacterial Drugs (cont)
 Aminoglycosides
 Bactericidal; for gram –
 Inhibit protein synthesis; disrupt membrane integrity
 Used parenterally for systemic effect, topically for eye,
orally prior to surgery
 Good in combo with cell wall synthesis inhibitors
 Can cause ototoxicity & nephrotoxicity
 Fluoroquinolones
 Bactericidal, broad spectrum; penetrate many tissues;
effective orally; mild adverse reaction (tendonitis &
cartilage leisons)
Antibacterial Drugs (cont)
 Topical –
 Bacitracin
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Inhibits cell wall synthesis; gram + bacteria
Gram – bacteria; highest incidence of allergic skin reaction
Polymyxin B
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Neosporin
Neomycin
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Polysporin
Gram – bacteria; OTC; prescription for eye; alters cell
membrane structure
Tetracycline
Broad spectrum; bacteriostatic
 Wound infections; acne
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Triple
Antibiotic
Antifungal Drugs
 For systemic infection
 Most occur from inhalation of fungus
 Disrupt normal function of cell membrane
 Cause leaking of cellular contents
 Fungistatic or fungicidal
 Potential for hepatotoxicity – monitor liver
 For superficial infection
 Affect mucous membranes, skin, scalp, nails
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Dermatophytes
 Tinea, ringwrom
May need oral too
Role of ATC
 Education!!!!!!
 Infections
 Compliance
 Monitor!!!!!!!!
 Allergies
 Adverse reactions
 effectiveness
Pharmacology
DRUGS FOR RELAXING SKELETAL MUSCLE
Objectives
 Explain uses & adverse reactions of skeletal muscle
relaxants
 Recognize S&S of anticholinergic adverse effect
 Explain mechanism of action, therapeutic effects,
and dose regimen for drugs used to relax skeletal
muscle
 Summarize role of ATC with patients taking skeletal
muscle relaxants
Muscle Relaxants
 Alleviate muscle spasms
 Involuntary localized muscle contractions caused by…
 Associated with pain
 Block NM function during surgery
 Treat spasticity
 Some combined with analgesic (8.1)
CNS Depression
 Causes drowsiness, dizziness, sedation, respiratory
depression
 Overdose can result in coma/death
 Caused by several classes of drugs (8.2)
 Caution wit operating motor vehicle
 Watch use of alcohol & benzodiazepines
Anticholinergic Adverse Effects
 Anticholinergic effect
 Group of adverse effects from anticholinergic drugs
 Anticholinergic drugs
 Block cholinergic receptors
 Parasympathetic nervous system innervates smooth muscle
and organ tissue
 Receptor called muscarinic receptor
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So drugs also called antimuscarinic drugs
 Effects include….
 Examples…
Mechanism of Action
 Exert action through CNS
 CNS sedative properties – may contribute to action
 Some combine with GABA receptor
 Inhibitory effect
 Nerve impulse transmission in CNS….muscle relaxation
Effects & Dose
 Relieve muscle spasm & pain; increase ROM
 None superior
 Selection depends on adverse effect/physician
preference
 May diminish liver & kidney function
 Hypersensitivity reactions
 Potential for dependence
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Valium & Soma
ATC Role
 Education
 Adherence
 Common adverse effects
 Safety concerns