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Define the terma analgesia and list influences associated with pain.
- Analgesia: relieving pain by inhibiting specific pain pathways
- inflammatory conditions
Differentiate between the influences of acute pain, and chronic pain.
- 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
List algogenic substances.
- adenosine triphosphate
- neuroactive substances
List the primary neurogenic substances involved in transmitting pain responses.
- substance P
- calcitonin-gene-related peptide (CGRP)
- glutamate: thought to be primary pain neurotransmitter
Which cranial nerve transmits orofacial painful stimuli to the CNS?
primarily nerves in the TRIGEMINAL system
Describe what occurs from the stimulus of pain to the perception of pain.
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
List endogenous peptides that relieve pain.
Identify features of attention and cognition in the pain response.
- 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
List signs of acute odontogenic pain.
- postural displays
- Pts in pain tend to behave in ways appropriate to their cultural heritage: Americans want quick relief
Describe the 3 methods to relieve most odontogenic pain.
- Primary dental care: removing the dental cause of the pain
- local anesthesia
Describe the features of the 3 types of COX-1 analgesics for odontogenic pain.
- 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,
List differences between nonopioid analgeiscs and opioid analgesics
- Nonopioid: reduce fever, inhibit prostaglandin synthesis, all inhibit COX
- Opioid: do not reduce fever, act as agonists at opioid receptors
Note the therapeutic doses of each product in Table 8-1 and the maximum dose.
- 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
List adjuvant products used for analgesic effects.
- 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
Describe the role of AA in cellular damage leading to COX formation
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
How do prostaglandins cause pain?
- they lower the pain threshold to painful stimuli
- promote inflammation and fever
- affect vascular tone and permeability (edema)
Describe the features of COX-1, COX-2, and COX-3 chemicals in pain; give examples of drugs in each category.
- 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
List opioid receptors.
- Mu: endorphans and endomorphins
- Delta: enkephalins
- Kappa: dynorphins
- Opioid-receptor-like: orphanin FQ or nociceptin
Describe the mechanism of action of opioid agonists to reduce pain, compared to that of COX-1.
- 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
List factors that can delay absorption of COX-1.
- rate of absorption of an acidic COX-1 is decreased in an alkaline GI environment
- presence of food
Why are some opioids given by injections?
because of significant first-pass metabolism in the liver
Describe the purpose of 'by the clock' administration of analgesics.
- "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
Identify analgesics for mild odontogenic pain and their appropriate doses.
- Over-the-counter formulations of:
- ASA: 650 mg
- APAP: 650 mg
- ibuprofen: 200 mg
- naproxen sodium: 275 mg
What is the main potential problem with ASA when other drugs are taken?
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
Can APAP be recommended to individuals who drink alcohol? If so, what are the dosing instructions?
- Yes they can
- Therapeutic APAP doses (4,000mg/day) are safe for treating dental pain in the pt with alcohol-related liver disease
What is the ceiling dose of APAP? What is the maximum dose (child, adult)?
- ceiling dose: 1,000 mg
- max for adults: 4.000 mg
- max for children: 1,200 mg
What is the drug of choice for moderate-severe dental pain for an individual with a history of substance abuse?
List available COX-2 inhibitors.
The only COX-2 inhibitor currently on the market is CELECOXIB (CELEBREX)
Identify the agents most effective for relieving dental pain.What dosage is most efficacious?
- 400-800 mg of IBUPROFEN
- 650 mg of APAP with 200 mg of Ibuprofen
Which COX-1 is most efficacious when a long duration of analgesia is desired?
Describe the indication, classification, benefits, and dose of tramadol for dental pain.
- 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
Discuss agents for the tertiary treatment of odontogenic pain.
- Opioids: morphine
- 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
Identify potential adverse drug events associated with COX-1.
- 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
Describe the mechanism for antithrombotic effects of COX-1, and dose levels resulting in an increased bleeding time. When will normal bleeding time resume?
- 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
Identify conditions that contraindicate use of ASA.
- thromboembolic disease
- severe hepatic disease
- vitamin-K deficiency
- hereditary coagulopathies
- in those treated with anticoagulants (warfarin, heparin)
- If they have factors predisposing liver toxicity
- IN CHILDREN WHEN VIRAL INFECTION IS SUSPECTED
Identify safe levels for coagulation tests.
Describe the risks of taking COX-1 during pregnancy. Which analgesic is indicated during pregnancy?
- 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
List potential toxic effects of salicylates.
- In an overdose, ASA causes salicylate toxicity called salicylism which represents an acute medical emergency
- effects are: tinnitus
- mental confusion
- renal dysfunction
Describe the potential for renal toxicity when COX-1 are taken?
- 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
List common adverse effects of opioid analgesics.
- 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
Identify conditions that contraindicate use of opioids for odontogenic analgesia.
- head injuries
- 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
Identify the most likely cause of death from opioid toxicity.
Describe the effect of opioids on the CNS.
- 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
Are opioids appropriate for the pregnant or lactating woman?
- 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
Describe rules for opioid use in the elderly pt.
reduce doses by as much as 1/2 to 1/4 to avoid both toxic and paradoxical effects (dizziness, hallucination)
Describe the effects of tolerance and dependence during opioid use.
- 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
Describe prescribing recommendations for opioids when used for dental pain.
prescribed for a short amount of time, less than 6 days, with NO REFILLS allowed
What are symptoms of withdrawal from opioid intoxication?
- dilated pupils
- rapid pulse
- muscle jerks
- flulike syndrome
Describe signs of opioid overdose
- constricted pupils (miosis)
- depressed-to-absent respiration with cyanosis (due to depressed respiratory chemoreceptor sensitivity to carbon dioxide)
- hypotension (sometimes leading to shock)
Identify the opioid antagonist used for opioid toxicity.