I N T R O D U C T I O N & P H A R M A C O K I N E T I C P R I N C I P L E S

S E A N B U R F E I N D, AT C, L AT, O T C

Pharmacology

Objectives

Define drug; differentiate between namesExplain difference between generic name &

drugExplain drug classificationFDA role in development and recallApply drug conceptsExplain how drug chemical structure

determines biological effectsPrimary mechanisms which drugs cross

membranes, & metabolizeDiscuss drug excretion by kidneys

Drug

Chemical used to treat or prevent disease Shown to be effective

All have a chemical nameGeneric name is nonproprietary name

Proprietary name = brand name = trade name

How do we get a generic drug?

Differences between generic & trade name products

Trade-Name Drug Generic-Name Drug

Can have multiple trade names

Names shorter & easier to pronounce

Refers to entire product

May include more than one active ingredient

Only one generic nameRefers to one chemical

entityLess expensiveNot all drugs marked as

generic drugsCan be marketed by

multiple companiesMust obtain FDA approvalMust be bioequivalent to

trade name drug

Differences

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 researchSchedule II

High abuse potential; Accepted medical use in USSchedule III

Lower abuse than II; Accepted medical use in USSchedule IV

Lower abuse than III; accepted medical useSchedule 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 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

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

www.fda.gov

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 ComparisonsUS Pharmacopeia/National Formulary

(USP/NF) Standards for purity, strength, quality, and analysis of

drug USP on label if meets standards

Handbook of Nonprescription Drugswww.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 cellOnset of Action

Time it takes for drug to cause response Minimum effective concentration

Duration of Action Time between onset and termination

Half Life Time for drug amount in blood to be reduced by ½ (%)

Clearance rate: measure of efficiency of

metabolism and excretion

Bioavailability & Bioequivalence

To be bioavailable, drug must reach blood 2 components: amount of drug absorbed & rate of

absorption Diminished if:

First pass effect:

Bioequivalence – refers to comparison of amount and rate of drug entering circulation Generic product

Chemical Structure

Determines chemical binding forcesDetermines biological effects, rate of

absorption, excretion and metabolismSmall changes have large biological effectsDetermines size and chemical shape of each

moleculeSolubility – determines how quickly drug

dissolved in GI tract 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 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 absorptionParenteral

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 processExplain how common chemical mediators

affect inflammatory processExplain difference between COX1 & COX2Explain how NSAIDS workExplain how corticosteroids work

Inflammatory Process

Normal and necessary processIf excessive may need to interveneChemical mediators released

Mast cells and basophils Histamine Serotonin Thromboxanes* Leukotrienes* Prostaglandins* Bradykinin

Arachidonic Acid Metabolites

COX pathway TX, PG, and PGI2

COX 1 All tissues; relatively stable rate; maintain normal

function of eicosanoid COX 2

Brain; female reproductive; blood vessel walls; kidneys Induced in response to inflammation

NSAIDS

Most frequently prescribed & OTCAspirin is prototypeMajor mechanism to decrease PG production

by inhibiting COXLittle to no effect on LT pathwaySelective COX2 NSAIDS

Bextra; Vioxx

Therapeutic Use of NSAIDS

Tx both acute & chronic1-2 weeks typicalNo guidelines to determine which is best for

pathologyPrincipal use: pain & inflammationDoes the use of NSAIDS reduce healing

time?Analgesic & antipyretic

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

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 useCommon sx

GI irritation, heartburn, nausea, upper GI bleeding, ulcers

Risk greater in >60 yearsCOX 2 selective lower incidence GI, but

maybe not with Upper GINew 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)

Glucose metabolism Mineralocorticoids (alderstone)

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 NSAIDInhibit activity of phospholipase

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 Adrenal cortex uses feedback loop based on amount

in blood (HPA axis)

Need to be careful about taking off too quickly

Hypothalamus

CRHAnterior Pituitary

ACTH Adrenal Gland Cortisol

Inhibition

Drug Interaction

s

Pharmacology

DRUGS FOR TREATING PAIN

Objectives

Explain how NSAIDS also have analgesic effectExplain pharmokinetics for acetaminophen &

opioid drugSigns & symptoms for adverse reactionIdentify common drug interactionsTherapeutic advantages for different drugsMechanics of actionsConcept of agonist vs. antagonistDifference between drug addiction & physical

dependence

Foundations

Terminology Analgesic

Acetominophen Opiates

Morphine, Codeine Opioids

Oxycodone, Demerol Narcotic analgesic

Narcotic

Nonsteroidal Anti-Inflammatory Drugs

NSAID

COX Inhibitor

Inhibits PG

Decreases Pain

Acetaminophen

Analgesic and antipyretic efficacyInhibits COX in brain not peripheryNo blood clotting issues, GIPeaks in blood ~ 1 hr post; t1/2 = 2hr325-1000mg; 4-6hr; adult – 24hrs<4000mgCeiling effect for analgesia (650-1300mg)Allergic skin reaction; overdose common

90% metabolized in liver, small amt toxic >7.5g adult and 150mg/kg kids

Careful with liver disease & Alcohol

consumption

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) β-endorphins, enkephalins, dynorphins

Most clinically effective result from μ interaction

Addiction potential; schedule II mostlyDependence 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, urinary retention, orthostatic hypotension, nausea, vomiting

Available by oral, rectal, or parenteralPeaks 1.5 hrs postAdult parenteral dose morphine = 10mg; oral =

20-60mgWatch with CNS depressants

Codeine

Demerol

Oxycodone

Methadone

Ultram

Caffeine

Enhances analgesic properties

Creates shorter onset & longer duration

Stimulant

drowsiness & fatigue alertness; 50-200mg

Physical dependence; withdrawal symptoms

Local Anesthetics

Topical preparations to alleviate painInhibit nerve impulse transmission Diminished hot, cold and touchQuick actingCan use parenterallyTopically to treat pain or itching

Ethyl Chloride

Cocaine Lidocaine

Summary

Defined drug; differentiate between namesExplained difference between generic name & drugPrimary mechanisms which drugs cross membranes,

& metabolizeDiscussed drug excretion by kidneysDescribed and explained inflammatory processExplained difference between COX1 & COX2Explained how NSAIDS workExplained how NSAIDS also have analgesic effectExplained pharmokinetics for acetaminophen &

opioid drug

References

Houglum JE, Harrelson GL. Principles of Pharmacology for Athletic 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-the-Counter 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 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 antibioticsRole of antibiotics in UR & LR infectionsDifferentiate between categories of antibioticsDiscuss superficial vs. systemic fungalRole 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 infection, and patient

Effectiveness in fighting organism most important

Based on symptoms before lab results

Infection site might limit Dose and duration depend on

Site of infection Immune defense of patient

Respiratory Infections

Very common illness associated with inappropriate therapy

URI Pharyngitis – viral; treated with antibiotic Otitis media & sinusitis

LRI Acute bronchitis – usually viral Pneumonia – bacteria (adults); viral (kids)

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 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” 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

Inhibits cell wall synthesis; gram + bacteria Neomycin

Gram – bacteria; highest incidence of allergic skin reaction

Polymyxin B Gram – bacteria; OTC; prescription for eye; alters

cell membrane structure Tetracycline

Broad spectrum; bacteriostatic Wound infections; acne

Neosporin

Triple Antibiotic

Polysporin

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

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 surgeryTreat spasticity

Some combined with analgesic (8.1)

CNS Depression

Causes drowsiness, dizziness, sedation, respiratory depression

Overdose can result in coma/deathCaused by several classes of drugs (8.2)

Caution wit operating motor vehicleWatch 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

So drugs also called antimuscarinic drugs

Effects include….Examples…

Mechanism of Action

Exert action through CNSCNS sedative properties – may contribute to

actionSome combine with GABA receptor

Inhibitory effect Nerve impulse transmission in CNS….muscle

relaxation

Effects & Dose

Relieve muscle spasm & pain; increase ROMNone superiorSelection depends on adverse

effect/physician preferenceMay diminish liver & kidney functionHypersensitivity reactionsPotential for dependence

Valium & Soma

ATC Role

EducationAdherenceCommon adverse effectsSafety concerns