APPLIED CLINICAL

THERAPEUTICS
DOS 8300
Sanjay Chand MD
Clinical Professor 1

Division of Integrated Biomedical Sciences

COURSE LAYOUT
• Two semesters (Fall/Winter)
• Coordinated with Pharmacology I / II / III / IV
• Lectures followed by Case based scenarios
• Small group discussions-Team leaders
• Prescription Writing : Antibiotics/ Analgesics/ Hepatic Disease/
Renal Disease
• Clinical Groups A/B/C/D: Mandatory in-person attendance based
off course schedule
2

• Mutual student exchanges may be allowed by course Directors

 FACT OR FICTION?
Rationale: Take all antibiotics as prescribed up to 7-10 days
Vs
Stop antibiotics when the patient is clinically well

• Microbial mutations rarely occur during antibiotic treatment.

• Stepped resistance occurs with prolonged antibiotic use.
• Antibiotic resistance is enhanced by low dose , prolonged
therapy.
4
 ANTIBIOTIC USE AND MISUSE
• Drugs used Freely compared to Drugs of Fear
• Dentists: 7-11% of all common antibiotics
• Inappropriate usage:
• To avoid claims of negligence
• Without Incision and Drainage
• Improper situation, dosage, duration of therapy
• Instead of mechanical therapy in Periodontics
• Replacement for debridement
• Pain relief in Endodontics 5
 CARDINAL RULES IN TREATING ODONTOGENIC
INFECTIONS
• Diagnose the disease and create differential
• Treatment Plan
• Incision and Drainage
• Removal of causative agent
• Choose an effective antibiotic
• Narrowest spectrum

• Good efficacy
• Low toxicity
6

• Minimal side effects

 ODONTOGENIC INFECTIONS

• Most common types of bacteria isolated from odontogenic

infections
• Two categories
• Gram positive
• Micromonas (Peptostreptococcus micros)
• Peptostreptococcus anaerobius
• Gram negative
• Porphyromonas: endodontalis & gingivalis
• Fusobacterium: nucleatum; necrophorum
10
Altered Microbial Flora-Odontogenic Infection
 MICROBIAL SUCCESSION - ODONTONGENIC
INFECTIONS
• Different organisms involved in different stages of infection
• Early Phase (Days 1-2):
• Streptococci, producing enzymes which promote the spread
of infections. Diffuse inflammatory reactions, preparing an
environment suitable for Anerobic invasion
• Cellulitis
• Late Phase (Days 3 or later):
• Anaerobic bacteria
• Suppuration (pus)
• Abscess formation 11
Cellulitis vs. Abscess

12
13
SPECTRUM OF ACTIVITY
• Narrow spectrum (limited): Agents that are active against a single
species or a limited group of pathogens.
• Extended spectrum: drugs which in general retain the spectrum of
the parent drug but differ in having greater activity against gram
negative bacteria

• Broad spectrum (extensive): agents that are active against a wide

range of pathogens. Gram +ve and –ve/ Aerobic and Anerobic
14

• Do NOT combine narrow and broad spectrum antibiotics

 BACTERICIDAL BACTERIOSTATIC
• Penicillin V (Vee K) • Erythromycin (Eryc)
• Amoxicillin (Amoxil) • Clarithromycin (Biaxin)
• Cephalexin (Keflex) • Azithromycin (Zithromax)
• Clindamycin (Ceocin)
• Cefadroxil (Duricef)
• Tetracycline (Achromycin)
• Metronidazole (Flagyl)
• Doxycycline (Vibramycin)
• Ciprofloxacin (Cipro)
• Aminoglycosides
18
(Gentamicin)
 PATIENT POPULATION
• Healthy
• Immuno compromised Bactericidal or bacteriostatic?
• Cardiac /Total Joint prosthesis
• Pregnant
• Pediatric/Geriatric
• Renal / Liver disease

19
DRUG
INTERACTIONS

23
PENICILLINS - DRUG INTERACTIONS

• Probenecid -  renal tubular secretion of penicillin

• Methotrexate – Penicillins  renal secretion of Methotrexate
• NSAIDs (high dose ASA)- Bleeding
• Thrombolytic agents/ Anticoagulants - Bleeding
• Oral Contraceptives- Estrogen/Progesterone
breakdown with antibiotics (Amoxicillin)

24
Macrolides: DRUG INTERACTIONS
• Fentanyl derivatives : Increase plasma levels of Opioids
• Antihistamines: Diphenhydramine, Terfenadine, Astemizole
• Increase cardiotoxicity (prolonged QTs interval and torsades de pointes)
• Hepatotoxic drugs: Alcohol, Ketaconazole, Phenothiazines
• Warfarin: Increase Prothrombin time, Increased risk of bleeding
• Benzodiazepines: Triazolam, Midazolam: Decrease clearance, Enhance
depth & duration of sedation
• Xanthines (Theophylline): Increase serum levels, Cardiotoxicity
Neurotoxicity
 Macrolides: Adverse Drug Effects
• Incidence Less Frequent • Incidence Rare
• Abnormal taste (3%) • Allergy - cross sensitivity with
other macrolides
• Headache (2%)
• Pseudomembranous colitis;
• GI disturbances (2 to 3%) Clostridium difficile
• abdominal pain & • Hepatotoxicity
cramps
• Thrombocytopenia
• nausea & vomiting
• Prolonged QT interval
• Diarrhea • Stevens-Johnson syndrome
• Stomatitis/ Mucositis
28
 METRONIDAZOLE DRUG INTERACTIONS
• Alcohol - Disulfiram-like reaction nausea, giddiness, flushing, abdominal
cramps; accumulation of acetaldehyde.
• Disulfiram - confusion, psychotic reactions, convulsions; 2 week washout
period recommended.
• Anticoagulants - metabolism inhibited; increase plasma levels; monitor
prothrombin time.
• Lithium – may increase serum lithium levels (need to monitor lithium
levels)
• Phenytoin - Increase Phenytoin toxicity.
30
Fluoroquinolones (Ciprofloxacin) – PRECAUTIONS
• Cross-sensitivity with:
• all other Fluoroquinolones
• FDA Pregnancy Category C
• Caution in children <18 years.
• Potential damage to immature cartilage tissue
(weight bearing joints)
• Tendon rupture in elderly patients
31
 ANTIBIOTICS - PREGNANCY
Antibiotic FDA Pregnancy Category
Penicillin VK, Amoxicillin B

Cephalosporins B
Clindamycin B
Erythromycin B
Clarithromycin C
Azithromycin B
Tetracycline, Doxycycline, Minocycline D
Metronidazole B
Ciprofloxacin C

34
CLOSTRIDIODES DIFFICILE INFECTION (CDI)
(PSEUDOMEMBRANOUS COLITIS)
• Risk factors:
• Antibiotics (leading cause)
• Clindamycin, Fluoroquinolones
• Penicillins; Cephalosporins, Macrolides
• Other Drugs
• Proton pump inhibitor: Omeprazole
• Anticancer agents; immunosuppressive agents
• Comorbid diseases; Elderly
• Inflammatory bowel diseases
• Cancer, transplants; genitourinary diseases; uremic patients
 PSEUDOMEMBRANOUS COLITIS
• Treatment
• Clinical features:
• Stop all antibiotics
• High volume, foul smelling
diarrhea • Refer immediately
• May be watery diarrhea • Hydration
• Abdominal Cramps & • TX:
tenderness • Vancomycin;
• Fever, hypotension • Metronidazole
• leukocytosis • Fidaxomicin (Dificid);
Teicoplanin
• Fecal transplant (stool
infusion therapy; fecal
bacteriotherapy)
SIDE EFFECTS OF COMMONLY USED ANTIBIOTICS

1. Penicillin hypersensitivity
2. Cephalosporin hypersensitivity
3. Clindamycin diarrhea, pseudomembrane colitis
4. Aminoglycoside damage to kidney, 8th neurotoxicity
5. Metronidazole* GI disturbance, seizures
6. Vancomycin CN 8 neurotoxicity, thrombophlebitis
7. Chloramphenicol bone marrow suppression
8. Erythromycin mild GI disturbance
9. Tetracyclin* tooth discoloration, photosensitivity
25.4
Antibiotic Prescribing in Dentistry
• Oral bacterial infections: pain, swelling, redness, purulent exudate,
fever, systemic spread, immunosuppression
• Focus on eliminating the pathology
• Use radiographic identification
• Clean periodontal infection
• Provide endodontic treatment
• Incise and drain abscess
• Prevent transition of cellulitis into abscess
• Differential: Fungal, Viral, Ulcers, Chemical and Trauma
Why Do We Prescribe Antibiotics?
• Dental pain and intraoral swelling
• Pulpal and periapical conditions resulting from caries
• Bacteria associated with caries can cause symptomatic irreversible
pulpitis (SIP)inflammation of the pulpal tissue
• Occasional sharp pain, usually stimulated by temperature change
• Worsens to spontaneous, constant, dull or severe pain
• Most cited oral health−related reason for a patient contacting an
emergency department (ED) or physician
 Optimal Antibiotic Prescribing
• Benefit to Risk Ratio
• Toxicity, Allergy, Adverse effects, Drug interactions
• CDI: Clostridioides difficile infection
• Patient comorbidity
• Cytochrome p450 hepatic enzyme inhibition
• Patients on multiple medications
• Substance Use Disorder
• Recreational Drugs
Some Do Not’s
Do not prescribe antibiotics based on:
• Patient demand
• Peer pressure
• Convenience
• Prophylaxis
• Social pressure
• Claimed allergy: 10% report Penicillin allergy, <1% truly allergic
• Little evidence: Shortened course results in antibiotic resistance
• Antibiotics do NOT treat pain!
Antibiotic Prophylaxis in Dentistry
Antibiotic Prophylaxis
•January 2015 ADA clinical practice guideline: For patients with prosthetic
joint implants, prophylactic antibiotics are not recommended prior to
dental procedures
•ADA Chairside Guide: Patients with a history of complications associated
with joint replacement surgery requiring dental procedures with gingival
manipulation or mucosal incision, prophylactic antibiotics should be
considered after consultation with the orthopedic surgeon
•It is appropriate that the orthopedic surgeon recommend the appropriate
antibiotic regimen and write the prescription.
Prevention of Infective Endocarditis
• The current infective endocarditis/valvular heart disease guidelines
• Prosthetic cardiac valves
• Transcatheter-implanted prostheses and homografts
• Prosthetic material in cardiac valve repair (annuloplasty rings and chords)
• History of infective endocarditis
• Cardiac transplant with valve regurgitation (structurally abnormal valve)
• Unrepaired cyanotic congenital heart disease
• Repaired congenital heart defect with residual shunts or valvular
regurgitation at the site of or adjacent to a prosthetic patch or device
Additional Considerations for Prophylaxis
• If patient forgets to premedicate before appointment, the antibiotic may
be given before the procedure
• If not administered before the procedure the dosage may be
administered up to 2 hours after the procedure
• If patient received antibiotic premedication prior to a dental procedure
one day and is scheduled the following day, the antibiotic prophylaxis
regimen should be repeated prior to the second appointment
• A loading dose is given in order to cover the period of potential
bacteremia produced by a single procedure
• Patients who require prophylaxis but are already taking antibiotics for
another condition: Select an antibiotic from a different class
 CASE SCENARIO
• Name: Gregory Thomas, 24, healthy male
• HPI: Presents with pain and swelling in
relation to his left lower wisdom tooth x 4
days.
• Vitals: 110/78, 70, 14, Afebrile
• Allergies: Penicillin
• Clinical examination: Indicates pain on
palpation over the soft tissue #17 region.
• X-ray: Impacted #17, 32 .
• Rx: Surgical extraction #17 under LA
Post-op Antibiotics?
What will be the most appropriate postoperative
antibiotic you would prescribe for this patient?

A. No antibiotics are required.

B. Tetracycline
C. Amoxicillin
D. Clindamycin
PRESCRIPTION
WRITING

AMAN GUPTA, MD
DETROIT MERCY DENTAL
 POOR PRESCRIPTION WRITING

• Statistics –
• Hospitals – Medication errors occur in approximately 1 in every 5 doses
given
• One error per patient per day
• Approximately 1.3 million injuries and 7,000 deaths occur each year in
United States from medication-related errors
 MEDICATION ERROR
• Any preventable event that results in inappropriate medication use or harm
to the patient
• Causes –
• Nomenclature • Monitoring
• Professional practise /procedure • Dispensing
• Health care product
• Administration
• Education
• Labelling
• Documentation
 NOMENCLATURE

• Systematic naming of drugs

• Chemical name (acetyl-P-amino-phenol)
• Generic name (………………….)
• Brand name (Tylenol, Panadol, Paramol etc)
 FACTORS THAT INFLUENCE
MEDICATION ERRORS
• Lack of therapeutic training
• Inadequate drug knowledge and experience
• Inadequate perception of risk
• Overworked or fatigued health care professionals
• Poor communication between health care professional and patient
• Complexity of clinical case, including multiple health conditions,
polypharmacy and high-risk medications
 LEGAL CONTROLS

1: Over the counter (OTC) 2: Behind the counter (BTC)

Safe enough for self treatment of simple Restricted OTCs,
conditions Reasonable access to patients for self
treatment,
Request from and consult the pharmacist.
3: Legend or prescription 4: Controlled
Useful after expert diagnosis of Potential for abuse or psychological or physical dependence,
licensed practitioner, Have filling and refilling restrictions (under DEA classification),
Federal law prohibits dispensing Practitioner must be registered with DEA,
without a prescription, Renew registration periodically,
Should bear a label "Rx only." Certificate of registration must be retained and displayed.
 CLASSIFICATION OF CONTROLLED SUBSTANCES

Schedule V –
• Low potential for abuse than (IV), No special restrictions on refills
• Written oral, fax, OTC
• Examples – Cough medications (Codeine + Dextromethorphan, Codeine + Promethazine), Cannabidiol (CBD)
Schedule IV –
• Low potential for abuse than (III) relative, May refill only up to five times within six months from the date of issue
• Written, oral or fax
• Example – Benzodiazepine (Alprazolam, Clonazepam)
Schedule III –
• Lower potential for abuse than ( I or II), May refill only up to five times within six months
• Written, oral or fax
• Example – Buprenorphine/naloxone, Codeine + APAP, Dronabinol
Schedule II –
• High potential for abuse, No refills – each time a new prescription from your doctor
• Written prescription signed by practitioner (cannot be sent electronically to pharmacy)
• Limit on amount (30-day supply)
• Examples – Opioids (Hydrocodone + APAP, Oxycodone + APAP, Hydromorphone, Fentanyl), Amphetamines, Methylphenidate
Schedule I –
• No currently accepted medical use, High potential for abuse
• Not available for use even with a prescription
• Example – Heroin, Cannabis
 Schedule I –

• No currently accepted medical use, High potential for abuse

• Not available for use even with a prescription
• Example – Heroin, Cannabis, LSD, 3,4-methylenedioxymethamphetamine
(ecstasy)
 Schedule II –
• High potential for abuse,
• No refills – each time a new prescription from your doctor
• Written prescription signed by practitioner (cannot be sent electronically to
pharmacy)
• Limit on amount (30-day supply)
• Examples – Opioids (Hydrocodone + APAP, Oxycodone + APAP,
Hydromorphone, Fentanyl, Methadone, Meperidine), Amphetamines,
Methylphenidate
• Combination products with less than 15 milligrams of Hydrocodone per dosage unit
(Vicodin)
 Schedule III –

• Lower potential for abuse than ( I or II), May refill only up to five times
within six months
• Written, oral or fax
• Example – Buprenorphine/Naloxone, Codeine + APAP, Dronabinol,
Ketamine, Anabolic steroids, Testosterone
• Products containing less than 90 milligrams of codeine per dosage unit
(Tylenol with codeine)
 Schedule IV
• Low potential for abuse than (III) relative, May refill only up to five times within
six months from the date of issue
• Written, oral or fax
• Example – Benzodiazepine (Alprazolam, Clonazepam, Lorazepam, Diazepam)
• Carisoprodol, Zolpidem, Tramadol
❖The Government of Canada's announcement to reclassify tramadol as a Schedule
1 narcotic under the Controlled Drugs and Substances Act (CDSA).Apr 1, 2021
 Schedule V

• Low potential for abuse than (IV), No special restrictions on refills

• Written oral, fax, OTC
• Examples – Cough medications (Codeine + Dextromethorphan, Codeine +
Promethazine), Cannabidiol (CBD)
• Cough preparations with less than 200 milligrams of Codeine per 100
milliliters (Robitussin AC)
• Diphenoxylate / Atropine (Lomotil), Pregabalin
• Gabapentine
 Written or verbal
An instruction from ORDER
Legal document
a prescriber to a Subject to State,
dispenser – Federal and local
regulations

Doctor
Dentist WHAT IS A
Prescriber – Paramedical worker-
• Medical assistant PRESCRIPTION?
• Midwife
• Nurse Practitioner

Pharmacist
Pharmacy
Dispenser – technician
Assistant
Nurse
 NPI

• National Provider Identifier

• An identification number given by the Center for Medicine and Medicaid
Services (CMS)
• Health practitioners must have it to receive reimbursement from insurance
companies and to prescribe medicines
 DEA NUMBER

• Drug Enforcement Administration (DEA)

• DEA registration number (identifier that allows writing prescriptions for
controlled substances)
• Separate DEA registration for each state
• Administrative Controlled Substances Code Number (ACSCN) is a number
assigned to drugs listed on schedules created by Controlled Substances Act
(CSA)
 PRINCIPLES OF PRESCRIBING
• Accurate Diagnoses
• Appropriate Selection of Drug(s), Formulation(s) & Dosage(s)
• Avoid or Minimize Polypharmacy
• Adverse Effects & Drug Interactions
• Avoid Prescribing for the wrong reasons
• Assess Physiological and Biochemical status
• Advise and Instruct patient on taking Medications
• Affordability: Drug Plans?
• Avoid litigation! Violations are subject to penalties
• Heading –

Patient’s information (Name, address, age/DOB, weight)

Date of Order

• Body –

Rx symbol

Medication prescribed –
• Drug name, strength & formulation
• Amount to be taken,
• Route by which it is to be taken
• Frequency (For “as needed” medications, there is a symptom included for when it is to be
taken)
PRESCRIPTION
• Duration

Quantity to be dispensed (Instructions to the pharmacist) – For example: Dispense 50 capsules

FORMAT
How many refills the patient can come back for?

• Closing –

– Signature (Sig): Directions to the patient

– Label (informs the pharmacist how to label the medication)

– Signature of prescriber

– Substitution permissible

– DEA number, NPI number

• Heading –
Patient’s information (Name, address, age/DOB, weight)
Date of Order
• Body –
Rx symbol
Medication prescribed –
• Drug name, strength & formulation
• Amount to be taken,
• Route by which it is to be taken
• Frequency (For “as needed” medications, there is a symptom included for when
it is to be taken)
• Duration
➢Quantity to be dispensed (Instructions to the pharmacist) – For example:
Dispense 50 capsules
➢How many refills the patient can come back for?
• Closing –
– Signature (Sig): Directions to the patient
– Label (informs the pharmacist how to label the medication)
– Signature of prescriber
– Substitution permissible
– DEA number, NPI number
 DRUG NAME

• The medication you want to prescribe –

• Generic name or
• Brand name
• If you do want to prescribe the brand name only, you specifically need to
indicate, “no generics” on the prescription pad (a small box has to be checked to
indicate –
• “brand name only” or “no generics”
 WHY GENERICS?

• Non-proprietary names
– Assigned by U.S. Adopted Names Council
• Many states have mandated dispensing of generic equivalent drugs,
unless specifically prohibited by prescriber
• Maximum allowable cost (MAC) programs
– Require prescriber to certify necessity of prescribing specific brands
US Brand Name
1. Addaprin
2. Advil
3. A-G Profen
4. Bufen
5. Genpril
6. Haltran
7. Ibu
Ibuprofen available OTC and by prescription
8. Ibu-2
9. Ibu-200
10. Ibu-4
• The prescription-only version of Ibuprofen
11. Ibu-6 comes in 400 mg, 600 mg, and 800 mg
12. Ibu-8 tablets.
13. Ibuprohm
14. Ibu-Tab • The OTC version comes in 200 mg tablets
15. I-Prin
16. Midol
or capsules.
17. Motrin
18. Nuprin
19. Proprinal
 STRENGTH

• You need to tell the pharmacist the desired strength as many medications come
in multiple strengths –
• Write which one you want
• Often, the exact strength you want is not available, so the pharmacist will
substitute an appropriate alternative for you
• For example, if you write Ibuprofen 400 mg, and the pharmacy only carries
200 mg tablets, the pharmacist will dispense 200 mg tabs and adjust the
amount the patient should take by a multiple of 2
 AMOUNT

• You would have written, “Ibuprofen 400 mg, one tab….”

• The “one tab” is the amount of the specific medication and strength to take
• Due to the 400 mg tabs not being available, the instructions would be rewritten
by the pharmacist as “Ibuprofen 200 mg, two tabs….” You can see that “one
tab” is now “two”
• Pharmacists make these changes all the time, often without any input from the
physician
 ROUTE
• Note: To help reduce the number of medication errors, prescription writing should be 100% in
English, with no Latin abbreviations.
• There are several routes by which a medication can be taken –
• By mouth (PO),
• Per rectum (PR),
• Sublingually (SL),
• Intramuscularly (IM),
• Intravenously (IV), and
• Subcutaneously (SQ).
• For example, intranasal is often abbreviated “IN,” which, if you write sloppily, can be mistaken for “IM”
or “IV.”
 FREQUENCY
• How often you want the patient to take the medication –
• Once a day,
• Once at night,
• Twice a day, or even once every other week.
• Many frequencies start with the letter “q” – Latin word quaque, which means ONCE
• In the past, if you wanted a medication to be taken once daily, you would write QD, for
“once daily” (“d” is from “die,” the Latin word for DAY)
• To help reduce medication errors, QD and QOD (every other day) are on the
JCAHO “do not use” list
• You need to write out “daily” or “every other day.”
 PRN

• “as needed” medications

• The “Why” Portion
• In latin pro re nata, meaning “as circumstances may require.”
• For example, you may write for Ibuprofen every 4 hours “as needed.”
• Why would it be needed? You need to add this to the prescription
• You should write “PRN headache” or “PRN pain,” so the patient knows
when to take it.
 HOW MUCH?

• How many pills pharmacist should dispense, or how many bottles, or how
many inhalers?
• After “Disp #” write the number –
• Spell it, though not a requirement
• “Disp #30 (thirty)”
• Prevents tampering by adding an extra 0 after 30, turning 30 into 300
 REFILLS
• The last instruction on the prescription
• Informs the pharmacist –
• How many times the patient can use the same exact prescription, i.e. how
many refills they can get
• Example – A physician may prescribe 1 pack of an oral contraceptive with 11
refills, which would last the patient a full year
• Why refills – convenient for patient and physician
• Doxycycline, Fluoride, Pilocarpine, Hydrocortisone, Triamcinolone, Chlorhexidine,
Xylocaine, Cyclobenzaprine
• https://www.revisor.mn.gov/rules/5221.6105/
 * LABEL: INSTRUCTIONS, WARNINGS

• To ensure safety
• Instructions for use,
• Warnings about side effects and
• Possible drug interactions.
 CONTROLLED SUBSTANCES
PRESCRIPTIONS
• Must be dated and signed on the date when issued.
• Must include –
• Patient’s full name and address, and the practitioner’s full name, address, and DEA registration
number
• Drug name, strength, dosage form, quantity prescribed, directions for use, number of refills (if
any) authorized
• Must be written in ink or indelible pencil or typewritten and must be manually signed by the
practitioner on the date when issued
• Designated individual – (Secretary or nurse) may prepare prescriptions for the practitioner’s signature
• Practitioner is responsible for ensuring – All legal requirements, both federal and state are met
• Pharmacists – State rules
 PRESCRIPTION TAMPERING
• Survey in West Virginia
• Fake pain symptoms: 43%
• Patient claims lost/stolen prescription: 28%
• Forged written prescription: 14%
• Altered pill number: 14%
• Fake prescription call-ins: 9%
• Stolen prescription pads: 9%
• Altered numbers on prescriptions: 9%
 SAFEGUARDS FOR PRESCRIBERS

1 – SECURITY 2 – RECORD KEEPING 3 – DISPOSAL AND 4 – MEASURES

CONTROLS REQUIREMENTS (2 VALID PRESCRIPTION
YEARS) REQUIREMENTS
 SAFEGUARD MEASURES

• Prescription pads in a safe place

• Minimize the number of prescription pads in use
• Write out the actual amount prescribed
• Do not use prescription blanks for notes
• Never sign prescription blanks in advance
• Assist the pharmacist to verify information
• Contact DEA field office if suspicious prescription activities
• Use tamper-resistant prescription pads
 ORAL PRESCRIPTION

When prescribing schedule II drugs for emergencies –

Pharmacy must
Pharmacist must receive the written Pharmacists must
Quantity prescribed Pharmacists must
document the oral prescription within 7 Pharmacist must document electronic
and dispensed must notify the DEA if a
prescription days, and it must attach the paper prescriptions with
be limited to an prescriber fails to
information and state on the face prescription to the the original
adequate amount to “Authorization for deliver the written or
verify the identity of emergency oral authorization and
treat the patient Emergency electronic
the prescribing authorization date of the oral
during the emergency Dispensing” with the prescription on time
practitioner order
date of the oral order
 PRESCRIBING ERRORS

• Legible - spelling errors!

• – e-prescriptions
• Unambiguous
• Right dose, right dosing frequency, right route
• Correct units (mg, grams, mcg)
• Decimal points: Floating decimals
• – 0.001 Not .001
• Error-Prone Abbreviations
• Similar sounding names
ERROR-PRONE ABBREVIATIONS
 ERRORS IN SIMILAR SOUNDING NAMES

• Bupropion – Buspirone
• Hydroxyzine – Hydralazine
• Prednisone – Prednisolone
• Diphenhydramine – Dimenhydrinate
• Cotrimoxazole – Clotrimazole
• Risperidone – Ropinirole
 COMMON ROUTE ABBREVIATIONS
• PO (by mouth)
• PR (per rectum)
• IM (intramuscular)
• IV (intravenous)
• ID (intradermal)
• IN (intranasal)
• TP (topical)
• SL (sublingual)
• BUCC (buccal)
• IP (intraperitoneal)
 COMMON ABBREVIATIONS

• daily (no abbreviation)

• every other day (no abbreviation)
• BID/b.i.d. (twice a day)
• TID/t.id. (three times a day)
• QID/q.i.d. (four times a day)
• QHS (every bedtime)
• Q4h (every 4 hours)
• Q4-6h (every 4 to 6 hours)
• QWK (every week)
 BLACK BOX WARNING
• U.S. FDA – Warning formatted
with a 'box' around the text on
the labeling of a prescription
drug or in literature describing it
• Indicates that the drug carries a
significant risk of serious or even
life-threatening adverse effects –
1. NSAIDs, Celebrex (Celecoxib)
for cardiovascular and
gastrointestinal risks
2. FDA: Warfarin for risk of
bleeding to death
• Sertraline – Suicidal thoughts and behaviour
• Potassium supplements and NSAIDs – Increased risk of ulcers
• Antihypertensives and Opioids – Increased risk of hypotension
• Cyclosporine and NSAIDs – Nephrotoxicity
• Amphetamines – Sudden death
• Alprazolam – Highly addictive
• Vicodin ? – Highly addictive
• Carbamazepine – BM depression
• Fluoroquinolones – Tendon rupture
• Macrolides and Statins
• FDA warns about serious breathing problems with seizure and nerve pain
medicines gabapentin (Neurontin, Gralise, Horizant) and pregabalin
(Lyrica, Lyrica CR)
• When used with CNS depressants or in patients with lung problems
 READ THE LABELS
• Dabigatran
• Amphetamine and dextroamphetamine
• Alprazolam
• Ciprofloxacin
• Levothyroxine
• Acetaminophen plus Hydrocodone
• Sertraline
• Bupropion
• Tramadol
• Carbamazepine
 E-Prescribing Errors
• Order entry errors
• Incorrect physician or a patient selected by the pharmacist
• Dispensing errors (errors associated with modified prescriptions)
• Prescriptions for the same patient may not arrive at a single time or may be mixed with
those of other prescriptions
• Patients may have e-prescriptions and paper prescriptions (ie, for controlled
substances)
• Dispensing of discontinued medications or duplicate dispensing
• Delays in processing, increased cost
• Reduced efficiency
• Incomplete prescriptions
 CRITERIA PASS STANDARD NOT MET
Demographics Patient name, address, age, weight, and date Patient name, address, age, weight, or
of order present date of order missing
Superscription (recipe) Rx symbol present Rx symbol missing

Inscription (medication Generic name of the drug (spelled correctly), Generic name of the drug (spelled
information) dose, route, frequency, and duration stated incorrectly), dose, route, frequency, or
duration not stated
Subscription (drug name, Direction to the pharmacist on compounding Direction to the pharmacist on
quantity in numbers and and or dispensing of the drug provided compounding or dispensing of the drug
words) is missing
Signature/transcription Instruction to the patient on how, how much, Instruction to the patient on how, how
when, and how long the drug is to be taken much, when, or how long the drug is to
provided be taken not provided
Special instructions, refills, Special instructions, refills information and Special instructions, refills information
warnings warnings stated clearly or warnings missing

Prescriber information Signature, name, DEA number and phone Signature, name, DEA number or
number of the prescriber written clearly phone number of the prescriber missing
NAME: Smith Brown DATE: 10/12/2020
ADDRESS: 350 Baytown, Michigan AGE: 46
Rx: IBUPROFEN 600 mg PLUS ACETAMINOPHEN(APAP) 500 mg around-the-clock PO every 4-6 hours (MAX
four times a day) for 24 hours
THEN
ACETAMINOPHEN 500 mg as needed for pain PO every 6 hours for next 3 days

DISPENSE: IBUPROFEN 600 mg Tablets # 4 (Four)

ACETAMINOPHEN 500 mg Tablets # 18(Eighteen)

SIG: 2 (two) hours after one tablet of Ibuprofen (600mg) take APAP (1 Tablet). 2 (two) hours later take Ibuprofen 600 mg (1
Tablet). 2 (two) hours after this take APAP (1 Tablet) again. Repeat the regimen for the first 24 hrs.
For the next three days take Acetaminophen (500 mg) as needed (PAIN) every 6(six)hrs.
Do not consume alcohol while you are taking APAP.
REFILLS:
SIGNATURE: AG
NAME: AMAN GUPTA
NPI # 123456 DEA# 313234400
NAME: Kelly Tissot DATE: 9/27/2019
ADDRESS: 13 Sunnyvale Av, Troy, Michigan AGE: 45

Rx: ACETAMINOPHEN (APAP) 500 mg around-the-clock every 8 hours (MAX three times a day) for 48 hours
THEN
ACETAMINOPHEN (APAP) 500 mg as needed for pain every 8 hours for next 3 days

DISPENSE: ACETAMINOPHEN 500 mg Tablets # 15 (Fifteen)

REFILLS:
SIG: Take 1 (one) tablet orally every eight hours for 5 (five) days. Do not consume alcohol while you are taking this
medication.
REFILLS:
SIGNATURE: AG
NAME: AMAN GUPTA
NPI # 123456 DEA# 313234400
NAME: Kelly Tissot DATE: 27/9/2019
ADDRESS: 13 Sunnyvale Av, Troy, Michigan AGE: 45

Rx: ACETAMINOPHEN (APAP) 500 mg PLUS HYDROCODONE 5mg around-the-clock every 6 hours (MAX four times
a day) for 48 hours
THEN
ACETAMINOPHEN (APAP) 500 mg as needed for pain every 6 hours for next 3 days

DISPENSE: ACETAMINOPHEN 500 mg Tablets # 12 (Twenty)

HYDROCODONE 5 mg Tablets # 8 (Eight)
REFILLS: No refills please
SIG: Take Acetaminophen (1 Tablet) every 6 hours and take Hydrocodone (1 Tablet) every 6 hours for first 2 (two) days. For
the next 3 (three) days take Acetaminophen (500 mg) as needed (PAIN) every 6 (six) hrs.

Do not consume alcohol while you are taking these medications.

SIGNATURE: AG
NAME: AMAN GUPTA
NPI # 123456 DEA# 313234400
NAME: Stewart Haggerty DATE: 9/27/2019
ADDRESS: 7 Livernois Avenue, Detroit, Michigan AGE: 54

Rx: CEPHALEXIN 250 mg around-the-clock PO every 6 hours (MAX four times a day) for 5 days

DISPENSE: CEPHALEXIN 250 mg Capsules # 20 (Twenty)

SIG: Take 1 (one) Capsule every 6 (six) hours with or without food for 5 (five) days.
Finish the course.
REFILLS:
SIGNATURE: AG
NAME: AMAN GUPTA
NPI # 123456 DEA# 313234400
NAME: Beatrice Gomez DATE: 9/20/2019
ADDRESS: 102 Field Avenue, Detroit, Michigan AGE: 38

Rx: AMOXICILLIN 500 mg around-the-clock PO every 8 hours (MAX three times a day) for 7 days
PLUS
METRONIDAZOLE 250 mg around-the-clock PO every 6 hours (MAX four times a day) for 7 days

DISPENSE: AMOXICILLIN 500 mg Capsules # 21 (Twenty one)

METRONIDAZOLE 250 mg Capsules # 28 (Twenty eight)

SIG: Take 1 (one) capsule Amoxicillin every 8 (eight) hrs and 1 (one) capsule Metronidazole every 6 (six) hrs with or without food for
7 (seven) days. Finish the course.
Do not drink alcohol while you are taking METRONIDAZOLE and for 3 (three) days after you stop taking it.
REFILLS:
SIGNATURE: AG
NAME: AMAN GUPTA
NPI # 123456 DEA# 313234400
• https://www.sciencedaily.com/releases/2019/05/190514090953.htm
ANALGESICS- DENTAL
THERAPEUTICS

Sanjay Chand MD
• The magnitude of pain in the United States is
astounding. More than 116 million Americans have
pain that persists for weeks to years. The total financial
costs of this epidemic $560 to 635 billion per year.
• Dentists should manage acute pain and prevent
conversion into chronic pain
• Neuropathic pain should be managed with atypical
analgesic agents
• Such as_____________?
 Centrally ActingAnalgesics
Peripherally ActingAnalgesics
• Acetaminophen
• ASA • Opioids
• NSAIDs (COX-1 inhibitors) PAIN • Tramadol
• COX-2 inhibitors
Thalamus

• Acetaminophen
INJURY • Opioids
• Tramadol

Nerve AnalgesicAdjuvants
• Fluoxetine
• Carbamazepine
• Gabapentin
• Pregabalin
LocalAnesthetics • Amitriptyline
(Long acting) • Caffeine
 Pain Management for Moderately invasive Dental Procedure

Pre-emptive? Surgery / Post-operative Analgesics

Extraction Time

Local Analgesics
Anesthesia
Acetaminophen ± weak opioid
Long-acting NSAIDs (Ibuprofen; Naproxen, Ketorolac)
Local Tramadol ± Acetaminophen
Anesthetics Acetaminophen ± weak opioids
NSAIDs ± weak opioids
Weak/ Moderate opioids: Codeine, hydrocodone, oxycodone
Strong Opioids: Fentanyl 5
0
Which of the following analgesics are relatively
safe in a patient on Warfarin anticoagulant
therapy?

A. Ibuprofen
B. Naproxen
C. Acetaminophen
D. Aspirin
Acetaminophen and Warfarin Interaction
• Acetaminophen may potentiate the hypoprothrombinemic effect of
warfarin
• Vitamin K antagonists have similar effects
• Mechanism of interaction has not been established
• A toxic metabolite of APAP is thought to be involved by interfering with
vitamin K-dependent clotting factors
• The interaction has generally been associated with prolonged ingestion
of dosages greater than 1.3 g/day continuously for greater than 1 week
• Not with brief, intermittent exposures of average doses
• Reported increases in prothrombin time or INR from most studies were
often small but statistically significant
– Acetaminophen (500mg mg q6-8h) [Generic]
– NSAIDs
–Ibuprofen (600 mg q6-8h) [Motrin]; Naproxen (500 mg q12h) [Aleve]
– Celecoxib (200 mg q12h) [Celebrex]
– Tramadol (50 mg) [Ultram]

– Acetaminophen + weak opioid

–Acetaminophen + Codeine [Tylenol #3]
–Acetaminophen + hydrocodone (Vicodin; Lortab; Norco)
–Acetaminophen + oxycodone (Percocet)*

– Acetaminophen + Tramadol [Ultracet]

– Ibuprofen + weak opioid

–Ibuprofen + hydrocodone [Vicoprofen]*
–Ibuprofen + oxycodone [Combunox]*

– ASA + oxycodone [Percodan]*

– Acetaminophen + Ibuprofen
 OPIOIDS
• Opioids have been categorized by their pharmacological activity at
different receptors.

• Agonists, antagonists, and mixed agonist-antagonists.

• Agonist: Binding and triggering the μ and Κ receptors. eg: Morphine (considered the
prototypical opioid), meperidine, codeine, and propoxyphene.
• Antagonists bind to all three receptors but do not stimulate them. eg: reversal agents
naloxone and naltrexone.
• Mixed agonist-antagonist, have properties of both previously mentioned groups.
Certain receptors are triggered (agonist), whereas other receptors are antagonized.
Pentazocine, for example, activates the Κ receptor but antagonizes the μ receptors.
CODEINE
• Codeine is closely related in structure to morphine, possessing a methyl group that
protects it from rapid degradation in the liver.
• It is 1/3 rd as potent as Morphine.
• Doses of 120 mg will produce respiratory depression similar to that resulting
from 10 mg of Morphine
• Codeine’s oral efficacy is because it converts into Morphine.
• The usual adult dosage is 30 to 60 mg orally every 4 to 6 hours as needed, with a
maximum dose of 360 mg in 24 hours.
• This has led to formulations that combine codeine with other analgesics such as
acetaminophen and Ibuprofen.
• In doing so, analgesic synergism will reduce the total dose requirements for codeine.
HYDROCODONE
• It is derived from the opioid alkaloid
• It has antitussive and analgesic properties.
• Approximately six times more potent than codeine on a weight-per-
weight basis.
• It is an oral semisynthetic μ opiate receptor agonist.
• Equipotent doses of codeine and hydrocodone have similar efficacy and
severity of adverse side effects.
• The combination of acetaminophen and hydrocodone are used
together to treat moderate to severe pain.
OXYCODONE
• Oral semi-synthetic opiate agonist derived from the opioid alkaloid.
• 10 to 12 times more potent than codeine on a weight-per- weight basis
• Extensive first-pass metabolism, oxycodone is orally administered
• Acetaminophen- oxycodone formulations (Percocet) work
synergistically
• Dosage of oxycodone is 5 to 10 mg
• Oral administration of acetaminophen-oxycodone has an onset of analgesia
in 30 minutes and a peak analgesic effect in 90 minutes.
• The duration of analgesia is 3 to 4 hours
• Metabolism of both drugs is mediated through cytochrome P450.
57
 ACETAMINOPHEN
• As an analgesic and antipyretic, acetaminophen is equal in potency and efficacy
to aspirin and presumably may be somewhat inferior to ibuprofen and other
NSAIDs as well.
• Dose: 3200 mg/ day (New FDA recommendation: 2600 m/day)
• 300/ 325 mg of Acetaminophen + (5/ 7.5/10 mg Hydrocodone) = Vicodin

• Liver damage: It is attributed to a toxic metabolite that cannot be adequately

conjugated when dosages exceed 200-250 mg/kg in a 24-hour period.

• Chronic Alcoholic Liver Disease- Max Dosage: 2000 mg/ day

Hepatotoxicity with Acetaminophen
NSAIDS
• Non-steroidal anti-inflammatory drugs reduce pain, decrease inflammation, decrease
fever, and prevent blood clots.
• Side effects depend on the specific drug, its dose and duration of use, but largely
include an increased risk of gastrointestinal ulcers and bleeds, heart attack, and kidney
disease
• NSAIDs inhibit Cyclooxygenase enzymes ( COX-1 and COX-2 isoenzymes)
• These enzymes synthesize biological mediators (prostaglandins and thromboxane)
• Two types of NSAIDs: Non-selective and COX-2 selective (Celecoxib)
• COX-2 selective inhibitors have fewer gastrointestinal side effects, but promote
thrombosis
• Substantially increase the risk of cardiovascular disease
• By inhibiting physiological COX activity, NSAIDs may cause deleterious effects on kidney
function with decreased Renal blood flow
IBUPROFEN

61
62
 NSAIDS- ADVERSE EFFECTS
• GI disturbance: blocking both COX enzymes, the gastroprotective functions
produced from PGE1/2 produced by the COX-1 enzyme are not present
• Susceptible to GI ulcers, dyspepsia, and gastric bleeding.

• Increased bleeding risk: Inhibition of COX-1 in platelets by conventional

NSAIDs results in modulation of platelet function leading to prolonged
bleeding.

• Serious Renal problems requiring hospitalization occur in 0.5%-1.0% of

long-term NSAID users.
The following opioid has the LOWEST abuse
potential ________

A.Morphine
B.Tramadol
C.Fentanyl
D.Hydrocodone
TRAMADOL
• Synthetic, centrally acting analgesic that is thought to relieve pain through
synergistic monoaminergic and μ-opioid mechanisms of action
• It is widely used for the treatment of acute and chronic pain but has low abuse
potential (Cicero et al., 1999)
• Unlike pure opioids clinically relevant effects on respiratory or cardiovascular
parameters are rare at recommended doses for postoperative pain (Scott and Perry,
2000).
• In patients with dental pain, tramadol 100mg provided at least equivalent analgesia
compared with an opioid combination (e.g. codeine/aspirin 60 mg/650 mg or
propoxyphene/acetaminophen [APAP] 100 mg/650 mg).
• Tramadol peak concentrations are not reached until 1.6 h after a single dose in healthy
adults
• Ultram/ Ultracet (Combination with Acetaminophen) 65
ANALGESICS and OPIOIDS Part 2-
Applied Clinical Therapeutics
Sanjay Chand MD

46
Quiz!
Opioid overdose deaths in US between 2022-2023?

1. 800
2. 8000
3. 18000
4. 100000
2021-2022
Which of the following caused most
overdose-related deaths in the US?
1. Heroin
2. Cocaine
3. Amphetamine
4. Fentanyl
Lethal dose of Fentanyl?
MME (Morphine Mg Equivalent)
• Equates different types of opioids into one standard value
• Based on Morphine and its potency
• Determines the potency of persons’ opioid doses
Morphine milligram equivalent per day (MME/day):
• Strength per unit x (number of units/ days of supply) x
MME conversion factor
• Number of units and days of supply come from the
prescription.
• MME conversion factor : From the National Drug Code
• Data files of select controlled substances:
cdc.gov/drugoverdose/resources/data.html
Which Health Care Provider in the US is the highest
prescriber of Opioids to 12-21 yr olds?

1. Pediatrician
2. Ob-Gyn
3. Internist
4. Dentist
Opioid Prescriptions by Age and Specialty

JAMA 2011, Characteristics of Opioid

Prescriptions
 Role of Dentist in the Opioid Crisis
• Dentists: 1 and 1.5 billion doses of opioids annually
• Approximately 12% of all opioid prescriptions
• > 40% of dental patients are prescribed opioids post-extraction
• Rate among adolescents: 61%
• 96% of prescribers instruct ‘prn’ use
• Patients report 54% of prescription left-over
• 52 million opioid doses taken non-medically traced to dental
practices
• Dentist are leading prescribers to young people (10-19 years)
• Adolescent non-medical users of prescription opioids-27%
obtained from dentist (2nd highest)
 Alternatives to Opioids
‘PLAN’
• Pre-emptive use of NSAIDS
• Long-Acting Local
Anesthetics (Liposomal
Bupivacaine)
• Acetaminophen + NSAIDS
• NSAIDS First
 Patients at Highest Risk
• Substance abuse histories or current use
• Already on Opioids
• History of DUI or substance-related arrest
• Cigarette Smokers
• Victims of Sexual Abuse
• Depression
• Anxiety
Behavioral Characteristics of Drug Seeking Patients
• Requesting specific opioids
• From out of town/area
• Refuse treatment/request meds
• Request early refills
• Lost or stolen prescriptions
• Make up pain
• Often irritable, hyperactive, malnourished, unkempt, non-
compliant or appear impaired or sedated
 Clinical Pearls for NSAIDS
• Be aware of other medications and disease states
• GERD
• PUD
• Coagulopathies/ Bleeding disorders
• Hypertension: ACE inhibitors/ CCBs and ARBs
• Verify a medication record prior to adding any
new medications
• Patients should take NSAIDs after meals
• Be aware of patients on Warfarin therapy
Substance/Opioid Use Disorder (SUD/ OUD)
3 symptom manifestations for > 1 month:
1. Strong sense of compulsion to take substance/opioids
2. Impaired capacity to control substance-taking behavior
3. Physiologic withdrawal state with reduced intake
4. Tolerance: Increased amounts required
5. Preoccupation with obtaining the opioid
6. Persistent opioid use despite clear evidence of harmful
consequences.