Presentation on theme: "CHAPTER 5 Pharmacology. WHAT ARE AUTACOIDS? PRODUCED IN ONE ORGAN AND ARE TRANSPORTED VIA THE LYMPH SYSTEM ALL OCCUR (MADE) NATURALLY IN THE BODY. OCCUR."— Presentation transcript:
CHAPTER 5 Pharmacology
WHAT ARE AUTACOIDS?
PRODUCED IN ONE ORGAN AND ARE TRANSPORTED VIA THE LYMPH SYSTEM ALL OCCUR (MADE) NATURALLY IN THE BODY. OCCUR NATURALLY IN THE BODY
Terms & Definitions Autacoids - Examples: Prostaglandins – lipids that are synthesized locally by inflammatory stimuli –↑↑ PAIN receptors Thromboxanes (a vasoconstrictor and a potent hypertensive agent, and facilitates platelet aggregation [clotting]). Leukotrienes (Inflammatory molecules; precursor of prostaglandins ) “-kinins” - messengers
IS PAIN DIFFERENT FOR EVERYONE?
PerceptionReaction PAIN The Psychological component: The patient’s emotional response; Differs from person to person; Several factors will affect reaction The Physical component of pain: The Message that is carried from the Injured tissue to the brain; It is the ability to realize you are hurt
WHAT ARE PLACEBOS?
FOR SOME PEOPLE, PAIN CAN ALSO BE EFFECTIVELY TREATED WITH INACTIVE PILLS (PLACEBOS) ‘’FAKE’ DRUGS
WHAT ARE ANTIPYRETICS ALSO CALLED?
NON OPIOID ANALGESICS ARE ALSO CALLED: NONNARCOTIC, PERIPHERAL, MILD, AND ANTIPYRETIC (AGENTS THAT REDUCE FEVER) OPIOID ANALGESICS ARE ALSO CALLED: NARCOTIC, CENTRAL, OR STRONG ANALGESICS. NON-OPIODS
1.Nonopioids (nonnarcotics) peripheral nerve endings Act primarily at the: peripheral nerve endings Inhibit prostaglandin synthesis Inhibit prostaglandin synthesis (regulating the contraction and relaxation of smooth muscle tissue) Not effective for severe pain 3 subgroups: SalicylatesSalicylates (aspirin-like group) NSAIDsNSAIDs AcetaminophenAcetaminophen 2. Opioids (narcotics) Act primarily within the: central nervous system Depress the central nervous system Effective for severe pain Examples: Morphine, Codeine, Agents in cough suppressants We will discuss this area more in the next chapter Difference is in their site of action Classification of Analgesic Agents Difference in their mode of action
WHAT CATEGORY IS ASPIRIN UNDER?
ASPIRIN IS THE MOST USEFUL AND COMMON SALICYLATE TO REDUCE PAIN (ANALGESIC ACTION) ACETYL SALICYLIC ACID (ASA) – THE CHEMICAL NAME FOR ASPIRIN SALICYLATES
WHAT DOES NSAIDS STAND FOR AND WHAT DOES IT MEEAN?
NONSTEROIDAL ANTI- INFLAMMATORY DRUGS
Salicylates Aspirin NSAIDsAspirin 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 arthritis –Aspirin is also known for its anti-platelet action
ASA Aspirin have: –anti-inflammatory, –antipyretic, –analgesic, –analgesic, and –antiplatelet –antiplatelet actions. inhibit prostaglandin synthesisThese actions are related to the ability to inhibit prostaglandin synthesisSalicylates: Acetaminophen Whereas, Acetaminophen drugs have only antipyretic & analgesic actions.
ASA Aspirin inhibits cyclo-oxy-genase (COX) to block production of prostaglandins Prostaglandins can sensitize pain receptors to substances such as BRADYKININProstaglandins can sensitize pain receptors to substances such as BRADYKININ (SEE NOTE) –A reduction in prostaglandins results in a reduction in pain Salicylates:
HOW LONG BEFORE ASPIRINS PEAK EFFECT?
REMEMBER NOT TO APPLY TOPICALLY TO ORAL MUCOSA!!!! 30 MINUTES
ASPIRIN’S EFFECTS BY DOSE LOW HIGH
ASA 3.Reye’s Syndrome Associated with use of aspirin in children & adolescents who took it when they had the chickenpox or influenza Fatal 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 SyndromeACETAMINOPHEN and NSAIDs are now used for fever (antipyretic action) or pain (analgesic action) in pediatric and adolescents to reduce the chances of Reye’s SyndromeSalicylates:
WHAT DRUG SHOULD YOU NOT TAKE WITH ASPIRIN?
A DRUG INTERACTION BETWEEN ASPIRIN AND WARFARIN CAN RESULT IN SIGNIFICANT BLEEDING WARFARIN
NSAIDs A rapidly growing group with important application in dentistry –Mechanism of action and many of their pharmacologic effects and adverse reactions resemble aspirin Many authors agree that the NSAIDs are the most useful drug group for the treatment of dental pain.Many authors agree that the NSAIDs are the most useful drug group for the treatment of dental pain. –Most are available without a prescription.
WHEN IS THE PEAK PERIOD FOR MOST NSAIDS?
NSAIDs Most NSAIDs peak in about 1-2 hoursMost NSAIDs peak in about 1-2 hours –Well absorbed orally and food reduces the rate but not the extent of absorption Metabolized in liver, excreted in kidneys
NSAIDs have a significant anti-inflammatory effecthave a significant anti-inflammatory effect Similar as aspirin: –analgesic –antipyretic –anti-inflammatory They inhibit prostaglandin synthesis
ARE NSAIDS ADDICTING?
NSAIDS ARE NOT ADDICTING, TOLERANCE DOES NOT DEVELOP, AND NO WITHDRAWAL SYNDROME CAN BE INDUCED. NO!
NSAIDs 7. Pregnancy and Nursing ContraindicatedContraindicated in pregnancy; Like aspirin, NSAIDs given late in pregnancy can prolong gestation IBUPROFENIBUPROFEN is drug of choice for nursing
DENTAL PAIN IS BEST MANAGED BY HOW MUCH MG OF IBUPROFEN?
IN USUAL PRESCRIPTION DOSES, NSAIDS CAN BE SHOWN TO BE STATISTICALLY SIGNIFICANTLY BETTER THAN CODEINE ALONE, ASPIRIN, ACETAMINOPHEN, OR PLACEBO. 400MG
NSAIDs NSAIDs should be used with caution in patients with: 1.asthma 2.cardiovascular disease 3.Renal diseases with fluid retention 4.coagulation problems 5.peptic ulcer disease 6.ulcerative colitis Contraindicated in pregnancy
WHAT IS THE MOST COMMONLY USED NSAID?
WHAT HAS NO ANTI- INFLAMMATORY EFFECT?
Acetaminophen analgesicantipyreticUsed as an analgesic and antipyretic in children and adults when aspirin is contraindicated Has no anti-inflammatory actionHas no anti-inflammatory action
Acetaminophen Rapidly and completely absorbed from the GI tractRapidly and completely absorbed from the GI tract Peak plasma level in 1 – 3 hours Half life of 1 to 4 hoursHalf life of 1 to 4 hours Metabolized by the liver Excreted by the kidneys in 24 hours When large doses are ingested, an intermediate metabolite is produced that is thought to be hepatotoxic and possibly nephrotoxic.When large doses are ingested, an intermediate metabolite is produced that is thought to be hepatotoxic and possibly nephrotoxic..
AN ACUTE OVERDOSE OF ACETAMINOPHEN CAN CAUSE WHAT?
Acetaminophen Acetaminophen is used as an: –Analgesic agent (↓ pain) –Antipyretic agent (↓ fever)
Acetaminophen hypersensitivity to aspirin aspirin-gastric induced irritation.Used when hypersensitivity to aspirin or for patients experiencing aspirin-gastric induced irritation. antipyretic instead of aspirin for young childrenUsed 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)
WHAT DRUGS ARE USED TO TREAT GOUT?
Allopurinol AND Probenecid
Drugs Used to Treat Gout Allopurinol (Zyloprim) used in PREVENTION of a gout attack.used in PREVENTION of a gout attack. –Inhibits the synthesis of uric acid –Also used in patients receiving either chemotherapy or irradiation –If a pruritic rash should occur, the drug should be promptly discontinued Probenecid (Benemid) used in PREVENTION of a gout attack.used in PREVENTION of a gout attack. –Is an uricosuric drug that increases uric acid excretion in the urine
WHAT ARE OPIODS USED TO TREAT?
AT FIRST REFERRED TO DRUGS THAT ARE DERIVATIVES OF OPIUM POPPY OPIOID OR NARCOTIC ANALGESICS ARE USED TO MANAGE DENTAL PAIN IN PATIENTS IN WHOM NSAIDS ARE CONTRAINDICATED MODERATE TO SEVERE PAIN
1. Mechanism of action at the receptor site 1. Mechanism of action at the receptor site: 53 CLASSIFICATION -THREE GROUPS- GROUPSUBGROUPEXAMPLE OPIOID AGONISTS morphine, codeine MIXED OPIOIDS AGONIST- ANTAGONISTS PARTIAL AGONIST pentazocine buprenorphine ANTAGONISTSNaloxone
54 CLASSIFICATION: CHEMICAL STRUCTURE BOX 6-1 OPIOD ANALGESIC AGENTS BY STRUCTURE GROUP MORPHINE AND CODEINE (Largest Group) hydromorphone (Dilaudid) agonist hydrocodone (in Vicodin) agonist dihydrocodeine (in Synalgos-DC) oxycodone (in Percodan, Percocet, Tylox) agonist METHADONE methadone (Dolophine) agonist propoxyphene (Darvon) agonist MORPHINAN butorphanol (Stadol) agonist-antagonist pentazocine (in Talwin-NX) agonist-antagonist MEPERIDINE meperidine (Demerol) agonist fentanyl (Sublimaze) agonist diphenoxylate (in Lomotil) OTHER buprenorphine (Buprenex, Subutex) partial agonist Do not give any of these drugs if the patient has an allergy to morphine or codeine
WHAT ARE WEAKER FORMS OF OPIODS?
Codeine (in Tylenol#3) and Hydrocodone (in Vicodin) are some of the weakest
57 DRUG NAME (SOME EXAMPLES) COMMENTSSCHEDULE FOR CONTROLLED SUBSTANCE STRONGEST MORPHINEStandard agent; prototype II MERPERIDENE (Demerol) Abused by professionals II INTERMEDIATE OXYCODONE (in Percocet) Popular with addicts ‘shopping’ for opioids II WEAKEST HYDROCODONE (in Vicodin) III CODEINE (in Tylenol#3) #2=15mg; #3-30mg; #4=60mg III
WHERE DO NONOPIODS ACT?
OPIOIDS BIND TO RECEPTORS IN BOTH THE CENTRAL NERVOUS SYSTEM (CNS) AND THE SPINAL CORD, PRODUCING AN ALTERED PERCEPTION OF REACTION TO PAIN PERIPHERAL NERVE ENDINGS
WHAT ARE NATURAL OPIODS?
NATURAL OPIOIDS (ALSO CALLED ENDOGENOUS OPIOIDS), INCLUDE: ENKEPHALINS ENDORPHINS DYNORPHINS THESE ARE THE CHEMICALS THAT MAKE SURE WE CAN FUNCTION DURING ACCIDENTS, LIKE AFTER BREAKING OUR LEG… RELIEVE PAIN AND RELAXATION
1. Enkephalins 2. Endorphins 3. Dynorphins All 3 have opioid-like action and are found in the body. They are naturally occurring peptides that possess analgesic action and addiction potential 62 The Discovery of 3 Groups of Endogenous Substances Probably function as neurotransmitters, although their exact function has not been elucidated. reduces pain & positively affects mood. stimulates delta( ) receptor stimulates the kappa ( )- receptor MECHANISM OF ACTION
WHEN DO OPIODS START WORKING?
THE DOSING INTERVALS OF MOST OPIOIDS ARE BETWEEN 4-6 HOURS; THE USUAL DOSE DEPENDS ON THE DRUG. DURATION – NECESSITATES DOSING EVERY 4-6 HOURS WITHIN 1 HOUR
WHAT IS THE FIRST PASS EFFECT?
UNDERGOES FIRST PASS METABOLISM IN THE LIVER AND INTESTINE, REDUCING ITS BIOAVAILABILITY. REDUCES THE BIOAVAILABILITY
D Distribution: 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. 67PHARMACOKINETICS
E E xcretion: 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. 68 A.D.M. E PHARMACOKINETICS
TRUE OR FALSE? severity of side effects is proportional to the efficacy (strength)?
A PHARMACOLOGIC EFFECT MAY ALSO BE AN ADVERSE REACTION, DEPENDING ON THE CLINICAL USE OF THE AGENT. TRUE
IS MORPHINE THE STRONGEST OR WEAKEST OPIOD?
MORPHINE 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. THE STRONGEST
analgesic Aspirin (ASA) and ibuprofen (NSAID) are analgesic, antipyretic, and antiinflammatory, and they inhibit platelet aggregation. analgesic Acetaminophen is analgesic and antipyretic. analgesic. Codeine is analgesic. 73 Analgesia PHARMACOLOGIC EFFECTS What do aspirin, acetaminophen, ibuprofen, and codeine have in common?
WHAT IS AN ANTITUSSIVE?
DEXTROMETHORPHAN SUPRESSES A COUGH
Opioid 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) 76 Gastrointestinal Effects Opioids are not used for depression, infections, or hypertension PHARMACOLOGIC EFFECTS
77 ADVERSE REACTIONS TRUE or FALSE TRUE These 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.
DO OPIODS INCREASE OR DEPRESS THE RESPIRATORY CENTRE?
THE RATE AND DEPTH OF BREATHING ARE REDUCED. THE DEPRESSION IS RELATED TO A DECREASE IN THE SENSITIVITY OF THE BRAINSTEM TO CARBON DIOXIDE. DEPRESS THE RESPIRATORY CENTER IN A DOSE RELATED MANNER
80 Respiratory Depression (RP) Not a problem with usual doses in normal patients RP is usually the cause of death with an overdose ADVERSE REACTIONS
81 Nausea and Emesis nausea and vomiting. Analgesic 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). ADVERSE REACTIONS
WHAT IS A VERY COMMON SIDE EFFECT OF OPIOD USE?
THEIR DURATION OUTLASTS THEIR ANALGESIC EFFECT CONSTIPATION
AN ANTAGONIST SUCH AS NALOXONE (IN NARCAN) AN ANTAGONIST
88 Biliary Tract Constriction biliary colic Opioids may constrict the biliary duct, causing biliary colic (bile duct obstruction leading to gall stones). ADVERSE REACTIONS Importance in patients passing gallstones who are being treated with opioids.
A MOTHER ON OPIODS – WHAT CAN HAPPEN TO THE BABY?
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. THE INFANT MAY HAVE DEPRESSED RESPIRATION AND WITHDRAWL SYMPTOMS
NOT Use of opioids is NOT contraindicated in hypertensive patients. NOT Use of opioids is NOT contraindicated in hypertensive patients.
92 ADVERSE REACTIONS Addiction The degree of addiction potential is proportional to analgesic strength. EXCEPT for miosis and constipation. An addict will develop tolerance to the effects of opioids, EXCEPT for miosis and constipation.
93 Addiction Since the duration of use in dentistry is usually short – addiction for dentistry does not pose a problem NSAIDs 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. ADVERSE REACTIONS
IF A CLIENT CLAIMS ALLERGIES TO NSAIDS, WHAT COULD THIS MEAN?
TERMED ‘SHOPPERS’ THE CLIENT IS LOOKING FOR A SPECIFIC OPIOD. KEEP IN MIND – THIS ISNT ALWAYS THE CASE…LOOK FOR OTHER SIGNS NOT JUST ONE OPIOD ADDICT
96 Addiction: Identification of an Addict The “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 planing Moves 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. ADVERSE REACTIONS
WHAT IS METHADONE?
MAINTAINING PATIENTS ON HIGH DOSES OF METHADONE (METHADONE MAINTENANCE). USED TO TREAT OPIOD ADDICTION AND WITHDRAWL
99 Addiction: 4 Treatment Options Addiction, overdose, and withdrawal can be treated with opioid antagonists methadone 1. Substituting addict with oral opioid (methadone). 2. Going cold turkey and using medication such as phenothiazines, clonidine or benzodiazepines (to alleviate symptoms of withdrawal). 3. Maintaining patients on high doses of methadone (methadone maintenance). Naltrexone 4. Administering an orally effective, long-acting antagonist Naltrexone (Trexan). ADVERSE REACTIONS
100 Addiction: Treatment Options Example: The Heroin Addict Example: The Heroin Addict The following drugs can be used to treat heroin addiction ADVERSE REACTIONS METHADONE METHADONE, is used by substituting methadone for heroin and then tapering off or maintaining the addict on oral methadone. NALTREXONE NALTREXONE, a long-acting opioid antagonist, is used to block the action of usual doses of opioid administered illegally
IS TRUE OPIOD ALLERGY COMMON?
MOST 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. NO
103 This includes: oxycodone hydromorphone, hydrocodone, and dihydrocodone Because they are all members of the same morphine and codeine group.
WHAT IS THE PROTOTYPE OPIOD AGONIST WHICH OTHER OPIODS ARE MEASURED?
The prototype opioid agonist which other opioids are measured 107 SPECIFIC OPIODS Parenterally: used to control postoperative pain Orally: used primarily in the treatment of cancer
Used 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. 108 SPECIFIC OPIODS
Weak 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 pain 109 SPECIFIC OPIODS In Vicodin, it has been reported as being safe to use when breastfeeding
WHAT IS THE MOST COMMON OPIOD IN DENTISTRY?
MOST COMMONLY USED OPIOID IN DENTISTRY AND IS OFTEN COMBINED WITH ACETAMINOPHEN (TYLENOL #3) FOR ORAL ADMINISTRATION CODEINE
Favorite 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) 112 SPECIFIC OPIODS
WHAT IS HYDROMORPHINE USED FOR?
MANAGEMENT OF SEVERE PAIN, MORE POTENT THEN MORPHINE
An orally effective opioid, reserved for management of severe pain. More potent than morphine Similar adverse reactions to morphine. Favourite of the addicts because of its high strength; requires careful monitoring. EXAMPLE: Dilaudid 115 SPECIFIC OPIODS
116 SPECIFIC OPIODS 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. Used primarily to treat any opioid addicts (eg. Heroin addicts) Similar to morphine. Slower onset and longer duration of action. EXAMPLE: Dolophine
117 SPECIFIC OPIODS block the therapeutic and toxic actions of opioids Naloxone will block the therapeutic and toxic actions of opioids Methadone 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.
WHAT IS TRAMADOL?
AN ORALLY ADMINISTERED NON-OPIOID WITH WEAK ANALGESIC ACTIVITY (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. 120 SPECIFIC OPIODS Tramadol (Ultram)
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. 121 DENTAL USE OF OPIODS
ARE OPIODS USED FOR CHRONIC OR ACUTE PAIN?
ACUTE IS PREFERRED* BUT CAN BE USED FOR CHRONIC PAIN
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 diarrhea 124 REVIEW: USE OF OPIODS
#1. Hydrocodone #32. Tramadol #105. Oxycodone #133. OxyContin #156. Fentanyl transdermal #175. Methadone HCl noninjectable 125 Some of the Opioids found in the TOP 200