3 OCCUR NATURALLY IN THE BODY produced in one organ and are transported via the lymph systemAll occur (made) naturally in the body.
4 Terms & Definitions Autacoids - Examples: Prostaglandins – lipids that are synthesized locally by inflammatory stimuli –↑↑ PAIN receptorsThromboxanes (a vasoconstrictor and a potent hypertensive agent, and facilitates platelet aggregation [clotting]).Leukotrienes (Inflammatory molecules; precursor of prostaglandins)“-kinins” - messengers
7 PAIN Perception Reaction The Physical component of pain: The Message that is carried from theInjured tissue to the brain;It is the ability to realize you are hurtThe Psychological component:The patient’s emotional response;Differs from person to person;Several factors will affect reaction
11 NON-OPIODS Non opioid analgesics are also called: nonnarcotic, peripheral, mild, andAntipyretic (agents that reduce fever)Opioid analgesics are also called:narcotic,central, orstrong analgesics.
12 Classification of Analgesic Agents Nonopioids (nonnarcotics)Act primarily at the: peripheral nerve endingsInhibit prostaglandin synthesis (regulating the contraction and relaxation of smooth muscle tissue)Not effective for severe pain3 subgroups:Salicylates (aspirin-like group)NSAIDsAcetaminophen2. Opioids (narcotics)Act primarily within the: central nervous systemDepress the central nervous systemEffective for severe painExamples: Morphine, Codeine, Agents in cough suppressantsWe will discuss this area more in the next chapterDifference is in their site of actionDifference in their mode of actionLOOD AT FIGURE 5-2, PAGE 50 IN TEXTBOOK FOR REVIEW
14 acetyl salicylic acid (ASA) – THE CHEMICAL NAME FOR ASPIRIN SALICYLATESASPIRIN is the most useful and common salicylate to reduce pain (analgesic action)acetyl salicylic acid (ASA) – THE CHEMICAL NAME FOR ASPIRIN
15 WHAT DOES NSAIDS STAND FOR AND WHAT DOES IT MEEAN?
17 SalicylatesAspirin belongs to a class of medications called nonsteroidal antiinflammatory drugs (NSAIDs).Aspirin and other NSAIDs, for example, ibuprofen (eg. Motrin, Advil) and naproxen (eg. Aleve), are widely used to treat fever (antipyretic action), pain (analgesic action), and inflammatory (anti-inflammatory action) conditions such as arthritisAspirin is also known for its anti-platelet actionBOX 5-2; PAGE 51
18 ASA Aspirin have: anti-inflammatory, antipyretic, analgesic, and Salicylates:MECHANISM OF ACTIONAspirin have:anti-inflammatory,antipyretic,analgesic, andantiplatelet actions.These actions are related to the ability to inhibit prostaglandin synthesisWhereas, Acetaminophen drugs have only antipyretic & analgesic actions.REMEMBER: Prostaglandins INCREASE pain perception at the site of infection. Therefore, in order to DECREASE pain, we need to block/inhibit prostaglandin synthesis.
19 ASASalicylates:MECHANISM OF ACTIONAspirin inhibits cyclo-oxy-genase (COX) to block production of prostaglandinsProstaglandins can sensitize pain receptors to substances such as BRADYKININ (SEE NOTE)A reduction in prostaglandins results in a reduction in pain‘kinin’ acts as messengers; Bradykinins is a very powerful vasodilator and increases capillary permeability; in addition, it constricts smooth muscle and stimulates pain receptors
21 REMEMBER NOT TO APPLY TOPICALLY TO ORAL MUCOSA!!!! 30 MINUTESREMEMBER NOT TO APPLY TOPICALLY TO ORAL MUCOSA!!!!
22 ASPIRIN’S EFFECTS BY DOSE HIGHASPIRIN’S EFFECTS BY DOSELOWChapter 5; page 53
23 ASA Reye’s Syndrome ADVERSE REACTIONS Salicylates:ASAADVERSE REACTIONSReye’s SyndromeAssociated with use of aspirin in children & adolescents who took it when they had the chickenpox or influenzaFatal disease that causes numerous detrimental effects to many organs, especially the brain and liver.ACETAMINOPHEN and NSAIDs are now used for fever (antipyretic action) or pain (analgesic action) in pediatric and adolescents to reduce the chances of Reye’s SyndromeFYI: Reye's syndrome is a potentially fatal disease that has numerous detrimental effects to many organs, especially the brain and liver, as well as causing a lower than usual level of blood sugar (hypoglycemia)The classic features are a rash, vomiting, and liver damage. The exact cause is unknown and, while it has been associated with aspirin consumption by children with viral illness, it also occurs in the absence of aspirin use.
25 WARFARINA drug interaction between aspirin and Warfarin can result in significant bleeding
26 NSAIDsA rapidly growing group with important application in dentistryMechanism of action and many of their pharmacologic effects and adverse reactions resemble aspirinMany authors agree that the NSAIDs are the most useful drug group for the treatment of dental pain.Most are available without a prescription.
29 NSAIDs Most NSAIDs peak in about 1-2 hours PHARMACOKINETICSMost NSAIDs peak in about 1-2 hoursWell absorbed orally and food reduces the rate but not the extent of absorptionMetabolized in liver, excreted in kidneys
30 PHARMACOLOGIC EFFECTS NSAIDsPHARMACOLOGIC EFFECTShave a significant anti-inflammatory effectSimilar as aspirin:analgesicantipyreticanti-inflammatoryThey inhibit prostaglandin synthesis
32 NO!NSAIDs are not addicting, tolerance does NOT develop, and no withdrawal syndrome can be induced.
33 NSAIDs 7. Pregnancy and Nursing Contraindicated in pregnancy; ADVERSE REACTIONS7. Pregnancy and NursingContraindicated in pregnancy;Like aspirin, NSAIDs given late in pregnancy can prolong gestationIBUPROFEN is drug of choice for nursing
34 DENTAL PAIN IS BEST MANAGED BY HOW MUCH MG OF IBUPROFEN?
35 400MGIn usual prescription doses, NSAIDs can be shown to be statistically significantly better than codeine alone, aspirin, acetaminophen, or placebo.
36 CONTRAINDICATIONS & CAUTIONS Contraindicated in pregnancy NSAIDsCONTRAINDICATIONS & CAUTIONSNSAIDs should be used with caution in patients with:asthmacardiovascular diseaseRenal diseases with fluid retentioncoagulation problemspeptic ulcer diseaseulcerative colitisContraindicated in pregnancyUlcerative colitis is a type of inflammatory bowel disease (IBD) that affects the lining of the large intestine (colon) and rectum.peptic ulcer disease, is the most common ulcer of an area of the gastrointestinal tract that is usually acidic and thus extremely painful.
41 AcetaminophenUsed as an analgesic and antipyretic in children and adults when aspirin is contraindicatedHas no anti-inflammatory action
42 Acetaminophen PHARMACOKINETICS Rapidly and completely absorbed from the GI tractPeak plasma level in 1 – 3 hoursHalf life of 1 to 4 hoursMetabolized by the liverExcreted by the kidneys in 24 hoursWhen large doses are ingested, an intermediate metabolite is produced that is thought to be hepatotoxic and possibly nephrotoxic..Hepatotoxic: Damaging or destructive to the liverNephrotoxic: Destructive to kidney cells
43 AN ACUTE OVERDOSE OF ACETAMINOPHEN CAN CAUSE WHAT?
45 Acetaminophen Acetaminophen is used as an: Analgesic agent (↓ pain) USESAcetaminophen is used as an:Analgesic agent (↓ pain)Antipyretic agent (↓ fever)FYI: chemical name is 4-hydroxyacetanalide. Its chemical formula is C 8 H 9 NO 2
46 AcetaminophenUSESUsed when hypersensitivity to aspirin or for patients experiencing aspirin-gastric induced irritation.Used as an antipyretic instead of aspirin for young children; due to aspirin’s association with Reye’s syndrome.Can be used in all stages of pregnancy (always ask doctor)
49 Drugs Used to Treat Gout Allopurinol (Zyloprim)used in PREVENTION of a gout attack.Inhibits the synthesis of uric acidAlso used in patients receiving either chemotherapy or irradiationIf a pruritic rash should occur, the drug should be promptly discontinuedProbenecid (Benemid)Is an uricosuric drug that increases uric acid excretion in the urine
52 MODERATE TO SEVERE PAIN At first referred to drugs that are derivatives of opium poppyOpioid or narcotic analgesics are used to manage dental pain in patients in whom NSAIDs are contraindicated
53 CLASSIFICATION -THREE GROUPS- Mechanism of action at the receptor site:GROUPSUBGROUPEXAMPLEOPIOID AGONISTSmorphine, codeineMIXED OPIOIDSAGONIST-ANTAGONISTSPARTIAL AGONISTpentazocinebuprenorphineANTAGONISTSNaloxone
54 BOX 6-1 OPIOD ANALGESIC AGENTS BY STRUCTURE GROUP CLASSIFICATION:CHEMICAL STRUCTUREBOX 6-1 OPIOD ANALGESIC AGENTS BY STRUCTURE GROUPMORPHINE AND CODEINE(Largest Group)hydromorphone (Dilaudid) agonisthydrocodone (in Vicodin) agonistdihydrocodeine (in Synalgos-DC)oxycodone (in Percodan, Percocet, Tylox) agonistMETHADONEmethadone (Dolophine) agonistpropoxyphene (Darvon) agonistMORPHINANbutorphanol (Stadol) agonist-antagonistpentazocine (in Talwin-NX) agonist-antagonistMEPERIDINEmeperidine (Demerol) agonistfentanyl (Sublimaze) agonistdiphenoxylate (in Lomotil)OTHERbuprenorphine (Buprenex, Subutex) partial agonistDo not give any of these drugs if the patient has an allergy to morphine or codeineMep-pear-a-d-ene BOX 6-1 page 66 NOTE: the drug names bolded will appear on the test – they are discussed throughout the slides and key points to know for each drug are highlighted in red.
56 Codeine (in Tylenol#3) and Hydrocodone (in Vicodin) are some of the weakest
57 SCHEDULE FOR CONTROLLED SUBSTANCE DRUG NAME (SOME EXAMPLES)COMMENTSSCHEDULE FOR CONTROLLED SUBSTANCESTRONGESTMORPHINEStandard agent; prototypeIIMERPERIDENE(Demerol)Abused by professionalsINTERMEDIATEOXYCODONE(in Percocet)Popular with addicts ‘shopping’ for opioidsWEAKESTHYDROCODONE(in Vicodin)IIICODEINE(in Tylenol#3)#2=15mg; #3-30mg; #4=60mgSEE BOX 6-2; PAGE 66 FOR A FULL LIST
61 RELIEVE PAIN AND RELAXATION Natural opioids (also called endogenous opioids), include:EnkephalinsEndorphinsDynorphinsThese are the chemicals that make sure we can function during accidents, like after breaking our leg…
62 The Discovery of 3 Groups of Endogenous Substances MECHANISM OF ACTIONThe Discovery of 3 Groups of Endogenous Substancesstimulates delta() receptorEnkephalinsEndorphinsDynorphinsAll 3 have opioid-like action and are found in the body.They are naturally occurring peptides that possess analgesic action and addiction potentialProbably function as neurotransmitters, although their exact function has not been elucidated.reduces pain & positively affects mood.stimulates the kappa ()-receptorEnkephalin - Endogenous opioid ligand; stimulates -receptor.Endorphin - Group of chemicals produced in the brain; reduces pain and positively affects mood.Dynorphin - Endogenous opioid ligand; stimulates the -receptor.
64 Duration – necessitates dosing every 4-6 hours WITHIN 1 HOURThe dosing intervals of most opioids are between 4-6 hours; the usual dose depends on the drug.Duration – necessitates dosing every 4-6 hours
66 REDUCES THE BIOAVAILABILITY Undergoes first pass metabolism in the liver and intestine, reducing its bioavailability.
67 PHARMACOKINETICSDistribution:Oral bioavailability of opioids is primarily limited by first pass metabolism.Undergoes first pass metabolism in the liver and intestine, reducing its bioavailability.Degree of first pass differs among individuals.May cause respiratory depression in fetus when mother is given opioids near term.
68 Metabolized opioids and the unchanged drug are excreted in the urine. PHARMACOKINETICSA.D.M.EExcretion:Most opioids are excreted through the kidneys, but this action does not selectively affect their availability after oral administration.Metabolized opioids and the unchanged drug are excreted in the urine.
69 severity of side effects is proportional to the efficacy (strength)? True or false?
70 TRUEA pharmacologic effect may also be an adverse reaction, depending on the clinical use of the agent.
72 Morphine is the opioid agonist by which all others are measured. THE STRONGESTMorphine is the opioid agonist by which all others are measured.Strongest can relieve severe pain while weaker agents mixed with non-opioids are equivalent to NSAIDs.
73 PHARMACOLOGIC EFFECTS AnalgesiaWhat do aspirin, acetaminophen, ibuprofen, and codeine have in common?Aspirin (ASA) and ibuprofen (NSAID) are analgesic, antipyretic, and antiinflammatory, and they inhibit platelet aggregation.Acetaminophen is analgesic and antipyretic.Codeine is analgesic.
76 Gastrointestinal Effects PHARMACOLOGIC EFFECTSOpioid analgesics ↑ smooth muscle tone and ↓ propulsive contractions and motility (some opioids have constipation as a side effect).Useful for treating diarrhea.Example: diphenoxylate (in Lomotil)Opioids are not used for depression, infections, or hypertension
77 ADVERSE REACTIONS TRUE or FALSE Combining an opioid with a nonopioid analgesic produces an additive analgesic effect with fewer adverse reactions.TRUEThese agents work at two different levels on pain and produce an additive analgesic effect. In combination products, lower doses of each analgesic may be used, and a potential exists for a reduction in adverse reactions.
78 DO OPIODS INCREASE OR DEPRESS THE RESPIRATORY CENTRE?
79 DEPRESS THE RESPIRATORY CENTER IN A DOSE RELATED MANNER The rate and depth of breathing are reduced.The depression is related to a decrease in the sensitivity of the brainstem to carbon dioxide.
80 Respiratory Depression (RP) ADVERSE REACTIONSRP is usually the cause of death with an overdoseNot a problem with usual doses in normal patients
81 ADVERSE REACTIONSNausea and EmesisAnalgesic doses of opioids often produce nausea and vomiting.Result of their direct stimulation of the chemoreceptor trigger zone (CTZ) located in the medulla.Repeated administration of regular doses can prevent vomiting at the vomiting center (VC).M-E-sis
82 WHAT IS A VERY COMMON SIDE EFFECT OF OPIOD USE?
83 Their duration outlasts their analgesic effect CONSTIPATIONTheir duration outlasts their analgesic effect
87 such as naloxone (in Narcan) AN ANTAGONISTan antagonistsuch as naloxone (in Narcan)
88 Biliary Tract Constriction ADVERSE REACTIONSBiliary Tract ConstrictionOpioids may constrict the biliary duct, causing biliary colic (bile duct obstruction leading to gall stones).Importance in patients passing gallstones who are being treated with opioids.BIB-LEE-AIR-E
89 A MOTHER ON OPIODS – WHAT CAN HAPPEN TO THE BABY?
90 THE INFANT MAY HAVE DEPRESSED RESPIRATION AND WITHDRAWL SYMPTOMS Not teratogenic, but may prolong labor or depress fetal respiration if given near term..Not usually a problem with mother’s milk with therapeutic doses.
91 Use of opioids is NOT contraindicated in hypertensive patients.Page 69 Table 6-4 FOR TESTING PURPOSE: KNOW THE CONDITIONS THAT ARE CONTRAINDICATED/CAUTION FOR THE USE OF OPIOIDS
92 Addiction ADVERSE REACTIONS The degree of addiction potential is proportional to analgesic strength.An addict will develop tolerance to the effects of opioids, EXCEPT for miosis and constipation.Addiction - Dependence on a substance (e.g., alcohol, other drugs) or an activity to the point that stopping is very difficult and causes severe physical and mental reactions.Tolerance: ability of the body to alter its response (to adapt) to drug effects so that the effects are minimized over time.
93 AN ADVANTAGE OF NSAIDs OVER OPIOIDS: ADVERSE REACTIONSAddictionSince the duration of use in dentistry is usually short – addiction for dentistry does not pose a problemNSAIDs should be used to control dental pain in the addict.AN ADVANTAGE OF NSAIDs OVER OPIOIDS:NSAIDs are not addictive, tolerance does not develop, and no withdrawal syndrome can be induced.
94 IF A CLIENT CLAIMS ALLERGIES TO NSAIDS, WHAT COULD THIS MEAN?
95 TERMED ‘SHOPPERS’ THE CLIENT IS LOOKING FOR A SPECIFIC OPIOD. OPIOD ADDICTTERMED ‘SHOPPERS’ THE CLIENT IS LOOKING FOR A SPECIFIC OPIOD.KEEP IN MIND – THIS ISNT ALWAYS THE CASE…LOOK FOR OTHER SIGNS NOT JUST ONE
96 Identification of an Addict ADVERSE REACTIONSAddiction:Identification of an AddictThe “shoppers” - What to look for:Asks for the opioid analgesic by name and says that this is the only drug that works for them.Claims allergies to NSAIDs .Cancels dental appointment but still requests the opioid analgesic even though they will be “out of town on business”.Experiences pain for days after scaling and root planingMoves from office to office because “others don’t understand”.Claims a “low pain threshold”.Needs refills several days after a procedure without complications.Calls with a request for an opioid analgesic just as the office is closing or after hours.
98 USED TO TREAT OPIOD ADDICTION AND WITHDRAWL Maintaining patients on high doses of methadone (methadone maintenance).
99 Addiction: 4 Treatment Options ADVERSE REACTIONSAddiction: Treatment OptionsAddiction, overdose, and withdrawal can be treated with opioid antagonistsSubstituting addict with oral opioid (methadone).Going cold turkey and using medication such as phenothiazines, clonidine or benzodiazepines (to alleviate symptoms of withdrawal).Maintaining patients on high doses of methadone (methadone maintenance).Administering an orally effective, long-acting antagonist Naltrexone (Trexan).NAL-TREX-IN
100 Addiction: Treatment Options Example: The Heroin Addict ADVERSE REACTIONSAddiction: Treatment OptionsExample: The Heroin AddictThe following drugs can be used to treat heroin addictionMETHADONE, is used by substituting methadone for heroin and then tapering off or maintaining the addict on oral methadone.FYI: Naltrexone is basically used for people suffering from alcoholism and opioid dependence. This drug is an receptor antagonist, the drug simply blocks the normal reaction of the part of the brain that produces the feeling of pleasure when opioids are taken.Methadone: (also known as Symoron, Dolophine, Amidone, Methadose, Physeptone, Heptadon and many other names) is a synthetic opioid. It is used as a pain (mostly for severe) reliever and as part of drug addiction detoxification and maintenance programs.NALTREXONE, a long-acting opioid antagonist, is used to block the action of usual doses of opioid administered illegally
102 NOMost common types of true allergic reactions to opioids is dermatologic in nature.Due to the histamine-releasing properties of opioid analgesics.Includes skin rashes and urticaria.GI side effects are often reported.
103 Because they are all members of the same morphine and codeine group. This includes:oxycodonehydromorphone,hydrocodone, anddihydrocodoneBecause they are all members of the same morphine and codeine group.A patient with a true allergy to codeine should NOT be given an analgesic in that groupSEE BOX 6-1 PAGE 66
107 The prototype opioid agonist which other opioids are measured SPECIFIC OPIODSAgonists: MorphineThe prototype opioid agonist which other opioids are measuredParenterally: used to control postoperative painOrally: used primarily in the treatment of cancer
108 SPECIFIC OPIODSAgonists: OxycodoneUsed alone or combined with aspirin (in Percodan) or acetaminophen (in Percocet, Tylox) with fewer adverse reactions.For moderate to severe pain.It is located in the middle of the chart for strength value.
109 Agonists: Hydrocodone SPECIFIC OPIODSAgonists: HydrocodoneWeak opioid analgesic with fewer adverse reactions.Less potential for abuse.Combination of Hydrocodone (5mg) with acetaminophen (500mg) is recommended for the majority of dental patients with painIn Vicodin, it has been reported as being safe to use when breastfeeding
111 CODEINEMost commonly used opioid in dentistry and is often combined with acetaminophen (Tylenol #3) for oral administration
112 SPECIFIC OPIODSAgonists: MeperidineFavorite drug of abuse for medical personnel; 100mg meperidine=10mg morphine.For acute management of moderate to severe pain.Poor choice for oral use because it has a high first pass effect; short duration of action.Less constipating, and without miosis or cough suppression.EXAMPLE: meperidine HCl (Demerol)
114 MANAGEMENT OF SEVERE PAIN, MORE POTENT THEN MORPHINE
115 Agonists: Hydromorphone SPECIFIC OPIODSAgonists: HydromorphoneAn orally effective opioid, reserved for management of severe pain.More potent than morphineSimilar adverse reactions to morphine.Favourite of the addicts because of its high strength; requires careful monitoring.EXAMPLE: Dilaudid
116 Agonists: Methadone Used primarily to treat any opioid addicts SPECIFIC OPIODSAgonists: MethadoneSlower onset and longer duration of action.Similar to morphine.Methadone is used either to withdraw the patient gradually or for methadone maintenance. Because it has a longer duration of action, withdrawal from methadone is easier than from heroin. Because it is an opioid analgesic, however, the risk for dependence still exists.EXAMPLE: DolophineUsed primarily to treat any opioid addicts(eg. Heroin addicts)
117 Antagonists naloxone (Narcan) SPECIFIC OPIODSnaloxone (Narcan)Naloxone will block the therapeutic and toxic actions of opioidsMethadone is an opioid used in treatment of addiction, but will exacerbate symptoms of an opioid overdose.An pure opioid antagonist that is active parenterally.Drug of choice for treating agonist or mixed opioid overdoses.Naloxone, used if overdose occurs, is effective parenterally but not orally because it is inactivated
119 An orally administered non-opioid with weak analgesic activity (ULTRAM)An orally administered non-opioid with weak analgesic activity
120 SPECIFIC OPIODS Tramadol (Ultram) Few studies have confirmed its efficacy:Binds with mu (μ) opioid receptors; inhibits reuptake of serotonin and norepinephrine, and modifies ascending pain pathways.Its analgesic efficacy is equivalent to that of codeine.Side effects can include: miosis and CNS effects, such as dizziness, headache and stimulation and GI tract effects include nausea, diarrhea, constipation and vomiting.Is moving up the top 200 most prescribed drugs.
121 DENTAL USE OF OPIODS Most dental pain can be managed with NSAIDs. If NSAIDs are contraindicated - the DDS has a wide variety of opioids to choose from.Eg. Beginning with codeine or hydrocodone combinations, and progressing to oxycodone combinations.Only in rare cases and for short periods of time (approx. 1-2 days) should stronger opioids be prescribed for outpatient dental pain.
123 ACUTE IS PREFERRED* BUT CAN BE USED FOR CHRONIC PAIN
124 REVIEW: USE OF OPIODS Opioids are considered first-line therapy for: Pain associated with procedures (bone marrow biopsy)Pain due to trauma or cancer (burns)Visceral pain (appendicitis)Majority used to relieve acute or chronic pain.Few, such as fentanyl (Sublimaze, Duragesic), alfentanil (Alfenta), and sufentanil (Sufenta), are primarily indicated for preoperative sedation to reduce patient apprehension.Also used to suppress cough and treat diarrheaA BRIEF SUMMARY - FOUND THROUGHOUT THE SLIDES
125 Some of the Opioids found in the TOP 200 #1. Hydrocodone#32. Tramadol#105. Oxycodone#133. OxyContin#156. Fentanyl transdermal#175. Methadone HCl noninjectable