Pharmacology

• Analgesia: relieving pain by inhibiting specific pain pathways
• arthritis
• dysmenorrheal
• inflammatory conditions

• Acute pain: type that is most associated with dental pain. It is a recent onset of pain.
• Chronic pain: Pain that has lasted 3-6 months (found info online) and is thought that it may never leave

• adenosine
• adenosine triphosphate
• serotonin
• histamine
• bradykinin
• cytokines
• prostaglandins
• neuroactive substances

• substance P
• calcitonin-gene-related peptide (CGRP)
• glutamate: thought to be primary pain neurotransmitter

primarily nerves in the TRIGEMINAL system

Tissue injury - glutamate neurotransmitter activates nociceptive recepters which generates impulses that are transmitted to the CNS - The detection of pain stimuli in the orofacial region is conveyed by cranial nerves (trigeminal) - then macrophages and other cells of immune system invade damaged area; inflammatory process triggers formation of prostaglandins; may also provoke vasoconstriction - within the brain endogenous peptides are released causing analgesia

• enkephalins
• endorphins
• dynorphins

• Attention: conscious (or mind) control; pt has a choice; attend to noxious sensation or attend to signals that can exclude pain perception from conscious awareness - - hypotic procedures, music during procedures, holding a leg up to distract and suppress gag reflex
• Cognition: thought processes of experience; memory of past experience, discrimination between oral procedures, judgmental function

• anguish
• postural displays
• groaning
• wincing
• grimacing
• Pts in pain tend to behave in ways appropriate to their cultural heritage: Americans want quick relief

• Primary dental care: removing the dental cause of the pain
• local anesthesia
• analgesics

• Nonopioid analgesics: cyclooxygenase inhibitors, reduce fever (antipyresis), inhibit prostaglandin synthesis, act within the CNS to variable degrees
• opioid analgesics: derived from opium, act as agonists at opioid receptors, act in CNS
• adjuvant drugs: enhances efficacy of an analgesic or have an analgesic activity of its own,

• Nonopioid: reduce fever, inhibit prostaglandin synthesis, all inhibit COX
• Opioid: do not reduce fever, act as agonists at opioid receptors

• acetylsalicylic acid (ASA, Anacin, others): 4,000 mg
• APAP: (tylenol, others): 4,000 mg
• Ibuprofen (Advil, Motrin, others): 2,400 mg
• Naproxen (Naprosyn): 1,250 mg
• Naproxen sodium (Aleve, Anaprox, others): 1,375 mg

• Caffeine: in doses of 65-100 mg enhances effect of acetylsalicylic acid, APAP, and I-bu
• antihistamine hydroxyzine: in doses of 25-50 mg enhances analgesic effect of opioids
• corticosteroids

arachidonic acid: one of the key elements of cell damage, comes from cell mambrane phopholipids; it is metabolized by 2 pathways, one ix COX and the other uses lipoxygenase (LP) COX breaks AA down to prostaglandins, aka prostanoids, which lower the pain threshold to painful stimuli (make one more likely to feel pain), promote inflammation and fever, and affect vascular tone and edema

• they lower the pain threshold to painful stimuli
• promote inflammation and fever
• affect vascular tone and permeability (edema)

• COX-1: major isoform expressed; protect gastric mucosa by enhancing gastric blood flow, increase mucous and bicarbonate secretion, and inhibit acid output; others promote platelet aggregation and clot formation; COX-1 inhibitors include ASA and other NSAIDs such as I-but
• COX-2: expressed primarily in the brain, kidneys, female reproductive system, and bones; induces prostacyclin, which prevents platelet aggregation, and promotes vasodilation; COX-2 inhibitors include celebrex
• COX-3: isoforms are expressed primarily in the CNS; COX-3 inhibitor includes APAP

• Mu: endorphans and endomorphins
• Delta: enkephalins
• Kappa: dynorphins
• Opioid-receptor-like: orphanin FQ or nociceptin

• It interacts with opioid receptors in the CNS to produce analgesia that are also the natural binding sites for a number of endogenous peptides. endogenous peptide chemicals are responsoble for the 'high' and lack of pain long-distance runners feel when they complete. they produce analgesia by virtue of their interaction with opioid receptors in the brain, brain stem, spinal cord, trigeminal nucleus and peripheral terminals of primary afferent neurons
• COX-1 increase pain threshold by reducig prostaglandin synthesis

• rate of absorption of an acidic COX-1 is decreased in an alkaline GI environment
• presence of food

because of significant first-pass metabolism in the liver

• "By the clock": administration of analgesics is much more effective than waiting for pain to return before giving the next dose; it may actually reduce the total dosage required for the management of a painful episode
• Once pain is recieved it is harder to relieve

• Over-the-counter formulations of:
• ASA: 650 mg
• APAP: 650 mg
• ibuprofen: 200 mg
• naproxen sodium: 275 mg

It interacts with many drugs because it has a high affinity for protein-binding in the plasma, and may prevent a second drug from binding, therefor causeing high plasma levels of the second drug resulting in increased effets

• Yes they can
• Therapeutic APAP doses (4,000mg/day) are safe for treating dental pain in the pt with alcohol-related liver disease

• ceiling dose: 1,000 mg
• max for adults: 4.000 mg
• max for children: 1,200 mg

COX-1 inhibitors

The only COX-2 inhibitor currently on the market is CELECOXIB (CELEBREX)

• 400-800 mg of IBUPROFEN
• 650 mg of APAP with 200 mg of Ibuprofen
• Naproxen

Naproxen

• indication: acute odontogenic pain, in situations where COX-1 inhibitors or opioid analgesics are contraindicated (peptic ulcer disease or substance abuse recover)
• classification: nonopioid agent that binds to opioid receptors to produce an analgesic effect; it also blocks the reuptake of norepinepnrine and serotonin
• Dose: 50 mg

• Opioids: morphine
• hydromorphone
• methadone
• levorphanol
• oxycodone
• theses drugs can relieve practically all forms of pain: somatic pain, and visceral pain
• oxycodone in combination with a COX-1 inhibitor or a COX-3 inhibitor: is the drug of choice for severe odontogenic pain

• Intolerance
• GI effects: epigastric discomfort, nausea, vomiting, exacerbate symptoms of peptic ulcer disease, gastric bleeding leading to iron-deficiency anemia, abdominal pain, diearrhea, dyspepsia
• Antithrombotic effect: they impair platelet aggregation, prolongation of bleeding
• Risks in pregnancy: no evidence that therapeutic doses of ASA cause any fetal abnormalities, other than reduced birth weight, drug should be avoided, increased incidence in postpartum bleeding
• local and systemic salicylate toxicity: tinnitus, headache, mental confusion, sweating, thirst, hyperventilation, hyperthermia, dehydration, and renal dysfunction (overdose)
• Hepatic toxicity
• Renal toxicity

• mechanism: primarily through inhibition of thromboxane A₂ synthesis, a component of the COX cascade
• This effect is dose independant, and lasts for the life span of the affected platelets (~8 days) and increases the bleeding time for 4-7 days after the last dose of ASA
• platelet function returns back to normal when most of these drugs have been eliminated from the body

• allergy
• thromboembolic disease
• severe hepatic disease
• vitamin-K deficiency
• hereditary coagulopathies
• in those treated with anticoagulants (warfarin, heparin)
• pregnancy
• If they have factors predisposing liver toxicity
• IN CHILDREN WHEN VIRAL INFECTION IS SUSPECTED

100 mg

• There is no evidence that therapeutic doses of ASA cause any fetal abnormalities other than reduced birth weight, but the drug should be avoided during pregnancy. It can cause excessive intrapartum and postpartum maternal bleeding, with potential for life threatening hemorrhage, has been noted when ingestion has occurred within 5 days of delivery
• it may lead to fetal cardiac faiure
• APAP is a suitable substitute for ASA and other COX-1 inhibitors for mild to moderate pain

• In an overdose, ASA causes salicylate toxicity called salicylism which represents an acute medical emergency
• effects are: tinnitus
• headache
• mental confusion
• sweating
• thirst
• hyperventilation
• hyperthermia
• dehydration
• renal dysfunction

• COX-1 decrease the synthesis of renal prostaglandins, decrease renal blood flow, cause fluid retention, and may precipitat renal failure in susceptible pts.
• risk factors include: old age, chronic renal insufficiency, congestive heart failure, hepatic cirrhosis, and concurrent diuretic use
• hephrotic syndrome, acute interstitial nephritis, and an increased incidence of end-stage renal disease have been reported int pts treated chronically with other COX-1,2 or 3 inhibitors

• Gastrophy: nausea, vomiting, and constipation; most common adverse effects
• Intolerance: allergy - rare
• Cardiovascular effects: after supine may lead to orthostatic hypotension
• Respiratory effects: respiratory depression most common cause of death in an opioid overdose
• central nervous system: mood behavior, drowsiness and euphoria, or anxiety and dysphoria

• head injuries
• elderly
• debilitated
• pulmonary disease: particularly severe asthma
• pregnant and nursing women: APAP is appropriate for pain
• reduce dosage for elderly
• when a history of drug abuse is suspected or reported

respiratory depression

• modulate mood and behavior
• drowsiness and euphoria in some
• anxiety and dysphoria in others
• produce miosis as a result of an excitatory action on the autonomic segment of the nucleus of the oculomotor nerve
• pinpoint pupils: pathognomonic of opioid use/abuse, such as with heroin overdose

• the use is discouraged because of their general CNS-depressant effects on the fetus and infant
• short-term use of therapeutic doses of codeine in combination with APAP is appropriate for the management of mod-severe-odontogenic pain

reduce doses by as much as 1/2 to 1/4 to avoid both toxic and paradoxical effects (dizziness, hallucination)

• It is influenced by dose, frequency, and the specific opioid administered.
• Tolerance develops to most of the adverse effects of opioids, including respiratory and CNS depression
• no tolerance develops to their GI and papillary actions
• pts taking opioids for acute pain rarely develop psychological dependence
• clinically significant dependance develops only after several weeks of chronic tx w/relatively large doses

prescribed for a short amount of time, less than 6 days, with NO REFILLS allowed

• dilated pupils
• rapid pulse
• gooseflesh
• muscle jerks
• flulike syndrome
• vomiting
• diarrhea
• tremors
• yawning
• sleep

• constricted pupils (miosis)
• depressed-to-absent respiration with cyanosis (due to depressed respiratory chemoreceptor sensitivity to carbon dioxide)
• hypotension (sometimes leading to shock)
• hypothermia
• sedation
• stupor
• coma
• convulsions

nalaxone