PHAR 266: LO3 LS1-2- Determine the DH Implications of Drugs used in Dentistry

pain

-unpleasant sensory & emotional experience associated with tissue damage

-acute or chronic

what does pain affect?

-CNS

-cardiovascular system

-pulmonary system

-endocrine system

-GI system

what may happen if acute pain is not correctly managed?

-may become chronic pain

pain pathways

-initiation

-conduction

pain pathway: initiation

-release of chemical mediators (bradykinin, cytokines, serotonin, and prostaglandins)

-stimulate nociceptors (pain receptors)

pain pathway: conduction

-nerve fibres conduct pain to spinal cord

-spinal cord synapses with subnucleus caudalis then thalamus then cerebral cortex

convergence

-nociceptors from teeth, TMJ, muscles of mastication, oral cavity, and face all converge to the subnucleus caudalis

what is the reason for large areas of pain referral and occasional difficulty localizing the source?

-convergence

pain management: options to block pain at 4 sites

1. peripherally at site of tissue damage (where chemical mediators are released) using NSAIDS (ASA, ibuprofen, naproxen)

2. afferent nerves in soft tissue (carry pain signals from site to spinal cord) using LA

3. spinal cord (synapses w/ dorsal root and thalamus) using opioids, NSAIDS, and acetaminophen

4. cerebral cortex using opioids, NSAIDS and. acetaminophen

descending anti-nociceptive tract (DANT)

-in doral root of spinal cord

-inhibites the transmission of pain signal

-triggered by opioid/narcotic analgesics

what are analgesics?

-pain relievers

what are the 2 main types of analgesics?

-non-opioids (non-narcotics analgesics)

-opioids (narcotic analgesics)

non-opioid analgesics

-relieve mild to mod pain

-include acetylsalicylic acid, acetaminophen, ibuprofen, naproxen

opioid analgesics

-relieve mild to sev pain

opioid analgesics: weakest types

-hydrocodone (Vicodin) and codeine

opioid analgesics: moderate types

-oxycodone (Percodan, Percocet) and pentazocine (Talwin), tramadol

opioid analgesics: most potent

-morphine, methadone, meperidine (Demerol) and hydromorphone (Dilaudid)

NSAIDS

-non-steroid anti-inflammatory drugs

what do NSAIDS do?

-inhibit COX (cyclo-oxygenase enzyme)

what are the 3 sites that NSAIDS block pain?

-inhibit prostaglandins PGI2, PGE3 and thromoxane TXA2

-inhibit spinal dorsal root

-inhibit cerebral cortex

what are the 2 types of NSAIDS?

-non-selective COX I, II inhibitors (ASA, ibuprofen, naproxen, diclofenac, ketorolac)

-selective COX II inhibitors (celcoxib)

selective COX II inhibitors

-celcoxib (Celebrex)

-less GI upset

-no anti-platelet effect

non-selective COX I, II inhibitors

-ibuprofen (Motrin, Advil)

-naproxen (Rx and OTC, Aleve)

-acetylsalicylic acid (Aspirin, Entrophen)

-diclofenac (Voltaren)

-ketorolac (Toradol)

what are adverse reactions of non-selective COX I, II inhibitors?

-GI (upset, bleeding, nausea, vomiting)

-hypersensitivity (common)

-drug interactions (antagonist to some CV drugs and potentiate other CV drugs)

-anti-coagulation (if taken for another reason)

-cardiovasc. effects (may increase risk of MI and stroke)

-renal effects (fluid retention, hypertension, renal failure)

pharmacological effects of non-selective COX I, II inhibitors

-analgesic

-anti-pyretic

-anti-inflammatory

-anti-coagulant (if taken for this reason)

what are precautions/contraindications to COX inhibitors

-asthma

-GI probs (ileitis, colitis, ulcers)

-allergies

-many drugs (including cardiac drugs)

-already on anti-coagulant therapy

-pregnancy

-children w/ viral infections (Reye's syndrome)

acetaminophen: how does it work

-works centrally to block production of prostaglandins in cerebral cortex)

-does not work peripherally to inhibit nociceptor stimulation

-not as effective for dental pain as NSAIDS but fewer contrainications

acetaminophen: doses

-325 mg regular strength, 500 mg extra strength

-650-1000 mg q 4-6 hours

acetaminophen: pharmacological effects

-analgesics

-anti-pyretic

acetaminophen: adverse reactions

-dose dependent hepatotoxin (leading cause of liver failure in North America)

-contraindicated if liver disease

which drugs will raise pain threshold?

-anti-anxiety meds (benzodiazepine)

best practices for pain management

-more effective to prevent pain, rather than trying to catch up

-use analgesics by the clock, rather than by prn (as needed)

-do not exceed daily maximums

-consider long- acting LA to improve pain management

pain management steps

1. NSAID or acetaminophen

2. if analgesia inadequate, both NSAID and acetaminophen

3. if analgesia still inadequate, add first line opioid (codeine or Tramadol)

4. if analgesia STILL inadequate, change opioid to oxy

5. also consider LA w/ long-acting anesthetic to break the pain cycle

opiods: how do they work

-act centrally

-inhibit release of neurotransmitters at synapses in spinal cord

-activate the descending anti-nociceptive tract

opioids: least potent

-hydrocodone (Vicodin) and codeine

opioids: moderate potency

-oxycodone (Percodan, Percocet) and pentazocine (Talwin), tramadol

opioids: most potent

-fentanyl (Sublimaze), morphine, methadone, meperidine (Demerol) and hydromorphone (Dilaudid)

opioids: pharmacological effects

-analgesia

-sedation

-antitussive (cough suppressant)

-decreases GI motility (treat diarrhea)

opioids: adverse reactions

-addiction

-abuse

-hypersensitivity

-toxicity (too much CNS depression- causes respiratory depression)

-drug interactions (combo w/ other CNS depressants such as alcohol- too much CNS depressant)

-teratogenic if chronic use

-tolerance (need for larger doses w/ repeated doses)

-large doses can be fatal

combination drugs

-combine opioid & non-opioid

-potentiation drug interaction

acetaminophen & codeine: tylenol 1

-12 mg codeine

acetaminophen & codeine: tylenol 2

-15 mg codeine

acetaminophen & codeine: tylenol 3

-30 mg codeine

acetaminophen & codeine: tylenol 4

-60 mg codeine

methadone

-opioid used for severe pain & for treating opioid addiction

-long-acting opioid used to replace shorter acting opioid such as heroin, oxy or fentanyl

-prevents withdrawal symptoms & reduces drug cravings

-used as harm reduction for ppl who are addicted to opioids

fentanyl

-very potent opioid (more potent than heroin or morphine)

-medical fentanyl: prescription for management of severe pain

-illegal fentanyl in Canada (imported from foreign countries, illegal labs, theft/diversion of medical grade)

opioid prescriptions

-controlled substance

-carefully monitored by College of Physicians and Surgeons of Sk

-prescription requires more info

-written for only small amounts

-must be careful that numbers cannot be changed

-cannot be called into pharmacy

what are indications for opioids in dentistry

-not used much for general dentistry

-NSAIDS are usually more effective bc anti-inflammatory

-prescribed more by OMFS and endodontists

Narcan®naloxone

-opioid antagonist (binds to opioid receptors in CNS & displaces opioid)

-used to treat opioid poisoning

-injectable or nasal spray

gout

-joint disease

-accumulation of uric acid crystals in joints (increased production or decreased excretion of uric acid)

-usually involves great toe

-treated w/ drugs

which drugs can treat gout?

-NSAIDS (for acute attacks, indomethacin- Indocin)

-allopurinol (to prevent attacks, also sometimes used during chemo, may be hepatotoxic)

which drugs treat migraines?

-triptans (sumatriptin, rizatriptin): block serotonin receptors and cause vasoconstriction of cranial vessels

-ergotamine (Ergostat): alpha-blocker drug that causes vasoconstriction of cranial vessels

-propranolol (Inderal): beta-blocker with unknown mechanism

-nifedipine (Procardia) and verapamil (Isoptin): calcium channel blockers with unknown mechanism

cannabis

-psychoactive drug used for recreational & medical purposes (palliative care, pain and/or muscle spasms with MS, spinal cord injury, cancer, AIDS, arthritis, epilepsy, anti-emetic)

-THC: cannabinoid that causes a high intoxication

-CBD: cannabinoid that does not produce a high or intoxication

DH implications of cannabis

-increased anxiety

-increased heart rate & BP

-increase bleeding

-drug interactions

-impaired healing

-impaired judement and consent issues

-xerostomia and food cravings (increased risk of dental diseases)

what is the cannabis protocol?

-do not proceed if impaired (reschedule)

-confirm if able to give valid informed consent

-measure BP and pulse

-stress red. protocol

-limit epi in LA

-use local hemorrhage protocol

-impaired healing (possible poor outcomes to perio therapy) -CNC interval

-xerostomia management

-possible increased caries risk

mechanism of action: anti-infectives

-kill or interfere w/ growth of mo's

-antibiotic absorbed into blood stream and carried to site of infection

-proper blood level must be maintained for antibiotic to kill/inhibit mo's

-proper blood levels are maintained by following dosing schedule (q6h/q8h, not just when remembered)

-if blood levels fall too low (missed dose), mo's are exposed to dose that will not kill them and can become resistant

antibiotics: spectrum

-range of activity of the antibiotic

-list of microorganism types that antibiotic kills or inhibits

-influences decision on which antibiotic to describe

antibiotic: narrow spectrum

-kills only a few types

antibiotics: broad spectrum

-kills many different types

microorganism resistance

-microorganisms can mutate and become resistant to being killed by antibiotic

-develops with repeated, improper exposure

-very common due to improper use of anti-infectives (Rx when not needed, incorrect dose, incorrect dose interval, stopping too soon)

-MRSA is a serious problem in hospitals

MRSA

-methicillin resistant Staphylococcus aureus

-10% of people admitted to hospital will develop a hospital-acquired infection

-60% of hospital acquired infections are MRSA

-can cause serious wound infections

antibiotic: culture

-procedure for identifying mo's causing infection

-sample of mo's is obtained, grown in an incubator, and tested to determine specific type

-done with urine analysis, throat swabs, nasopharyngeal swab

antibiotic: sensitivity testing

-lab procedure for determining which antibiotic(s) will kill/inhibit the mo's causing the infection

culture & sensitivity testing in sensitivity

-not done much bc we know which antibiotics will treat oral infections and is therefore not needed

-use empiric therapy (most likely pathogen given s&s and site of infection)

guidelines for prescribing antibiotics

-benefits must be greater than risks

-must be infection or high risk of infection

-antibiotic must be effective

-client must not be allergic

antimicrobial stewardship (AMS) in dentistry

-antibiotics are essential in dentistry for preventing distant infections (infective endocarditis), preventing surgical site infections and treating serious odontogenic infections

-dentistry contributes to antimicrobial resistance (AMR)

-AMS- prescribe only when indicated

antibiotic: adverse reactions

-GI complains (nausea, vomiting, cramps, diarrhea)

-hypersensitivity

-superinfection (secondary infection: development of another infection (clostridium difficile))

-drug interactions: antibiotics inhibit absorption of BCP (controversial) and interact oral anti-coagulants (Warfarin)

-pregnancy: metronidazole is contraindicated

antibiotics: indications

-therapeutic uses: infection present, used to treat an infection

-prophylaxis uses: increased risk of infection, used to prevent an infection

antibiotics: contraindications

-no infection

-low risk of infection

-hypersensitivity

penicillins

-bactericidal (inhibit cell wall synthesis and lead to lysis)

-narrow spectrum (penicillin G, penicillin VK, gram + cocci and most gram - oral anaerobes)

-penicillinase-resistant (methicillin, oxacillin, cloxacillin, dicloxacillin, nafcillin, gram + cocci)

penicillin: penicillinase-resistant

-methicillin

-oxacillin

-cloxacillin

-dicloxacillin

-nafcillin

-gram + cocci

penicillin: broad spectrum

-amoxicillin, amoxicillin w/ clavulante, ampicillin

-gram + cocci and most gram - oral anaerobes

penicillin: anti-pseudomonal penicillins

-carbenicillin, ticarcillin w/ clavulanic acid, piperacillin, mexocillin

-gram -

penicillin in dentistry: oral infections

-penicillin VK 600mg q6h for 7-10 days or

-amoxicillin 500mg q8h for 7-10 days

penicillin in dentistry: antibiotic prophylaxis

-amoxicillin 2g 1 hour prior to appt

antibiotic: clavulanic acid

-Augmentim (amoxicillin & clavulanic acid)

-beta lactamase inhibitor

-sometimes added w/ amoxicillin or ticarcillin to improve effectiveness by decreasing resistance & increasing the spectrum

antibiotic: cephalosporins

-bactericidal (inhibit cell wall synthesis & lead to lysis)

-1st gen: cefalexin, cefazolin

-2nd gen: mod. spectrum. Cefaclor, cefuroxime

-3rd gen: cefixime, ceftriaxone

-used as second line antibiotic for oral inections

cephalosporins: spectrum

-most gram + cocci and some gram - oral anaerobes

cephalosporins: 1st gen. spectrum

-narrowest spectrum

cephalosporins: 3rd gen. spectrum

-widest spectrum

cephalosporins: contraindications

-if allergic to penicillin b/c high risk of allergic reaction

antibiotic: macrolides

-erythromycin, clarithromycin, azithromycin

-bacteriostatic

-interfere w/ protein synthesis by inhibiting peptide transferase enzyme at the 50S ribosomal subunit

macrolides antibiotic: erythromycin

-gram + and some gram - aerobes

-similar spectrum to penicillin

-often used if allergic to penicillin

-not used in dentistry bc not effective against anaerobic Bacteriodes

common side effect of erythromycin

-GI upset

macrolides antibiotic: azythromycin

-gram + and some gram - aerobes and anaerobes

-sometimes used if allergic to penicillin

advantage of azithromycin

-better compliance (1 dose per day and only 5 days total)

azithromycin dose

-500mg day one, then 250 on days 2,3,4,5

antibiotics: lincosamides

-clindamycin

-bacteriostatic- interfere w/ protein synthesis by inhibiting peptide transferase enzyme at the 50S ribosomal subunit

-gram + cocci and most gram - oral anerobes

when are lincosamides (clindamycin) commonly prescribed

-if allergic to penicillin

lincosamides (clindamycin): oral infection dosing

-300mg q6h for 7-10 days

lincosamides (clindamycin): side effects

-GI effects (nausea, vomiting, cramps, diarrhea)

-may cause antibiotic-related colitis (sev. inflammation of colon w/ sev. diarrhea- also occurs w/ ampicillin, tetracycline, and cephalosporins)

tetracyclines

-tetracycline, doxycycline, minocycline

-broad spectrum against gram + and gram - organisms

what can tetracyclines cause

-staining of enamel that is developing at time of administration

which tetracycline is sometimes used for treatment of perio disease?

-doxycycline (Atridox, Periostat)

when are tetracyclines contraindicated?

-during last half of pregnancy and in children under age 9

metronidazole

-bacteriocidal

-spectrum against obligate anaerobes

-contraindicated during pregnancy

-added to penicillin VK and amox. for second line for stage 2 infections

oral infections: localized dental infections

-usually periodontal or endodontic

-normally managed w/ drainage

-anti-infectives may not be indicated

oral infections: systemic dental infections (systemic symptoms of fever, malaise)

-usually managed w/ drainage and anti-infectives

first line antibiotics

-penicillin VK 600mg q6h OR amox 500mg q8h for 7-10 days

-if allergic to penicillin, azithromycin 500mg day 1 then 250mg OD for 5 days or doxycycline 100mg q12h for 10 days, or clindamycin 300mg q6h for 7-10 days

second line antibiotic

-add metronidazole 250mg q8h for 7-10 days (add to penicillin VK or amoxicillin)

-or change to amoxicillin-clavulanate 875mg q12h for 7-10 days

-or change to cephalexin 500 mg q8h and metronidazole 250 mg for 7-10 days

-no second line if allergic to penicillin