pharmacology nonnarcotic and narcotic analgesics

pain

• Pain is the means by which the body is made urgently aware of the presence of tissue damage

• Two components of pain

  • perception

  • reaction

perception

The physical component of pain. The message of pain carried via nerves to the cortex. Perception is uniform for everyone

reaction

the psychological component, emotional response to pain, wide range of response

nonopioids (nonnarcotic) categories

• salicylates

• nonsteroidal anti0inflammatory drugs (NSAIDs)

• nonsalicylate/ nonnarcotic (acetaminophen- Tylenol)

salicylates

• salicin extracted from willow bark has been used to reduce fever for years

• many have since been synthesized

acetylsalicylic acid (asprin)

• oral salicylate nonnarcotic analgesic

•Broken down into acetic acid (HA) and salicylic acid

•A strong odor of vinegar indicates the bottle of as_ pirin is old and should be thrown away because:

•Salicylic acid is a strong keratolytic agent (used to remove warts) and may cause additional adverse GI effects if old aspirin is taken

•Analgesic, antipyretic, anti-inflammatory, and anti platelet effects related to ability to inhibit prostaglandin synthesis

•Prostaglandins lower pain threshold, cause inflammation and fever, and can cause edema by affecting vascular tone

aspirin pharmacokinetics

• Rapidly and almost completely absorbed from stomach and small intestines. Peak effect on empty stomach 30minutes. Buffered tablet reaches peak effect in 20 minutes

• Widely distributed in most body tissues and fluids

• Poorly bound to plasma proteins

• Exhibits zero-order kinetics which means a constant amount of the drug is metabolized rather than a constant percentage per hour. Thus metabolism is based on dosage. Higher dosage=longer half life

aspiring pharmacological effects

• analgesic effect

• antipyretic effects

• antiplatelet effects

antipyretic effect aspirin

• Inhibition of prostaglandin synthesis in hypothalamus creates effect

• Has no effect on normal body temperature, in large doses can cause Hyperthermia

analgesic effect of aspirin

• Relieves mild to moderate pain such as that in arthritis, headache, toothache

antiplatelet effect aspirin

• Irreversibly binds to platelets

• Clinically effective for secondary MI prevention in adults, primary prevention of coronary artery disease, and treatment of an ischemic event

• Effects are dose dependent

aspirin adverse effects

• GI effects

  • Most common side effect is related to GI

  • Dyspepsia, N/V, or gastric bleeding

  • Result of direct gastric irritation and inhibition of prostaglandins

• Bleeding

  • At usual therapeutic doses irreversibly interferes with clotting

  • Platelets affected until new platelets are formed (4-7 days).

  • Normal clotting will be seen after 20% platelet replacement (about 1.5 days)

additional adverse effects of aspiring

• Reye syndrome

  • In children and adolescents with chickenpox or influenza aspirin has been associated with Reye syndrome

  • Associated with hepatotoxicity and encephalopathy. Commonly fatal

• Hepatic and renal effects

  • Rare that it will cause hepatotoxicity

  • Renal papillary necrosis and interstitial nephritis may be seen with administration of aspirin and acetaminophen together

• Pregnancy and nursing

  • Human studies have shown only a slight correlation between long-term aspirin use and congenital birth defects

  • Increase of stillbirth, neonatal death, decreased birth weight with aspirin abuse

  • Usual therapeutic doses do not present a problem for healthy nursing infant

aspirin hypersensitivity

allergy is uncommon

• Usually, patients who report an allergy to aspirin report stomach problems

• Has cross sensitivity with NSAIDs

• Some people with asthma cannot take aspirin of NSAIDs because of the aspirin hypersensitivity triad called Samter’s triad

  • Aspirin hypersensitivity

  • Asthma

  • Nasal polyps

  • Occurs in 30-40% of people who have asthma and nasal polyps

aspirin toxicity

• Overdose can have harmful effects and even cause death

• Symptoms

  • Salicylism occurs with blood lever of salicylates reaches a certain point

  • Tinnitus, headache, N/V, dizziness, and dimness of vision

  • Hyperthermia and electrolyte imbalance

  • At higher blood levels stimulates respiration leading to hyperventilation producing respiratory alkalosis. Compensatory alkalosis results in renal loss of bicarbonate, sodium, and potassium. Respiratory acidosis and metabolic acidosis ensues. Death occurs from acidosis and electrolyte imbalance

• Children primary victims of poisoning. Lethal dose is 500mg/kg of weight. Prevention  is proper storage and childproof caps.

• Treatment includes removing excess drug from stomach, other symptoms treated symptomatically

aspirin drug interactions

•Warfarin: can result in bleeding

•Probenecid: Aspirin interferes with the uricosuric effect of probenecid. Can precipitate an acute attack of gout

•Methotrexate: Aspirin can displace from protein binding site and interfere with MTX clearance. Can lead to MTX toxicity such as bone marrow suppression

•Sulfonylurea: Higher doses of aspirin (more than 2g) may produce hypoglycemic effect

•Antihypertensives: Aspirin reduces antihypertensive effects. Requires several doses over a few days

aspirin uses

• General uses include

  • Mild to moderate pain control

  • Antipyretic (except in children)

  • Anti-inflammatory for rheumatic fever and arthritis

• Low-dose aspirin

  • Used to prevent unwanted clotting for patients who have had stroke, heart attack, angina, or peripheral vascular disease

  • Patients experience MI can chew on one low-dose aspirin (81mg) at onset of symptoms (used for pts at an increased risk for myocardial infarction)

  • Used for patients who have not had a heart attack or stroke, but who are at an increased risk for these events

aspirin combinations

• With Buffer

  • Absorbed more rapidly. Claims to have less GI effects, but no proof

• With another analgesic

  • Can be combined with opioid analgesics or acetaminophen

  • Allows for less opioid to be used, therefore less side effects from opioid

• With sedatives

  • Can make aspirin more effective if anxiety is a component of pain

  • However, a separate antianxiety agent is more easily controlled and preferred

• With caffeine

  • Caffeine potentiates analgesic effect. Addition of 130mg caffeine is equivalent to increasing aspirin dose by one-third

nonacetylated salicylates common agents

•Sodium salicylate- anti-inflammatory purposes

•Magnesium salicylate- arthritis, musculoskeletal pain

•Salicylamide- used for mild pain relief

•Salsalate- chronic inflammatory conditions such as osteoarthritis

nonacetylated salicylates

•No cross sensitivity with aspirin

•Magnesium contraindicated in patients with renal disease

•Sodium contraindicated in patients with cardiovascular disease

•Have no effect on platelet aggregation

• sodium salicylate, magnesium salicylate, salicylamide, salsalate

diflunisal

• nonacetylated salicylate

• Peak action occurs 2-3 hours after ingestion

• Half life 8-12 hours in a normal patient

• As effective as other NSAIDs in treating pain

• Can be administered before a dental appointment to delay onset of postsurgical pain

• Classified as an NSAID

nonsteroidal anti-inflammatory drugs

• Many prescribers agree most useful drug group for treatment of dental pain

• Many OTC options that are usually lower dose than prescription

NSAIDs

• Mechanism of action: reduce the production of prostaglandin precursors and thromboxane from arachidonic acids.

• Pharmacokinetics:

  • Peak in 1-2 hours

  • Food my effect absorption rate, but not extent of absorption

  • Antacids have no effect on absorption except for diflunisal (reduces)

  • Analgesic and anti-inflammatory effects are responsible for actions in treating gout, independent of their effect on uric acid

NSAIDs adverse reactions

•GI effects: GI irritation, pain, bleeding problems. Can interfere with normal protective mechanisms in stomach and increase acid secretion. Can cause ulceration or perforation

•CNS effects: Dose dependent side effects- sedation, dizziness, confusion, mental depression, headache, vertigo, and convulsions. Not addictive, no tolerance developed

•Blood clotting: Reversibly inhibit platelet aggregation. Effects remain only as long as drug is present in blood. 1 day for ibuprofen, 4 days for naproxen, 2 weeks for oxaprozin

•CV effects: Increased risk of serious CV events (MI, Stroke) highest with diclofenac, lowest with naproxen

additional NSAID adverse reactions

• Renal effects: All NSAIDs inhibit renal prostaglandins, decrease renal blood flow, cause fluid retention, and may cause hypertension and renal failure especially in elderly. Increase risk of cystitis and UTI. Little effect on patient with normal kidney function

• Oral effects: ulcerative stomatitis, gingival ulcerations, dry mouth

• Other effects: muscle weakness, ringing in the ears, hepatitis, hematologic problems, blurred vision. Celecoxib may cause cholestatic jaundice do not use in person with sulfonamide allergies

• Hypersensitivity: can have a wide range of reactions including Stevens-Johnson syndrome, exfoliative dermatitis, epidermal necrosis

• Pregnancy/Nursing: Like aspirin, in late pregnancy can lead to prolonged gestation, delay parturition, produce dystocia (premature closure of ductus arteriosus.  Contraindicated in pregnancy

NSAIDs drug interactions

• Lithium- increased effect

• methotrexate - increased effect of MTX leads to bone marrow toxicity

• diuretics, angiotensin-converting enzyme inhibitors (ACEis), B-blockers - reduced antihypertensive effect

• Digoxin - increased digoxin effect

NSAIDs contraindications and cautions

• Patients with asthma, CV or renal diseases with fluid retention, coagulopathies, peptic ulcer, and ulcerative colitis should be given NSAIDs cautiously

• All have been associated with development of acute kidney injury

• Due to cross-sensitivity with aspirin NSAIDs should be used with caution in asthmatic patient.

• ALL contain block box warnings for cardiovascular disease (may increase risk of serious CV thrombotic events, MI, and stroke), and may also increase risk for serious GI events including bleeding, ulceration, and perforation

NSAIDs therapeutic uses

• Medical: Osteoarthritis, gouty arthritis, fever, dysmenorrhea, and pain. Off label bursitis and tendonitis

• Dental: Studies show analgesic efficacy of NSAIDs equivalent to that of opioid analgesic.

acetaminophen (tylenol)

• Exact mechanism and site of action unknown. Thought to elevate pain threshold

• Pharmacokinetics: rapidly and completely absorbed from GI tract. Peak plasma level in 1-3 hours. Half-life 1-4 hours. Metabolized in liver. Equal in effectiveness, and potency as aspirin

• Adverse Reactions: Mainly hepatic necrosis and nephrotoxicity

• Hepatic effects: Alters plasma enzyme levels, elevated bilirubin, prolongation of prothrombin time. May progress to encephalopathy, coma, and death. Avoid in patients with history of hepatic disease. Patients who drink 3 or more alcoholic beverages a day should not take acetaminophen as alcohol stimulates the enzyme that metabolizes acetaminophen to its toxic metabolite

acetaminophen adverse reactions

• Treatment of overdose toxicity begins with gastric lavage followed by administration of activated charcoal. Minimum toxic dose of acetaminophen for a single ingestion is 7.5-10 g in adults.

• Nephrotoxicity: Associated with long-term usage. Not generally a concern in dental usage as short-term use is the normal in dentistry

• Skin reactions: Risk of three rare but potentially fatal skin reactions

  • Stevens-Johnson syndrome

  • Toxic epidermal necrolysis

  • Acute generalized exanthematous pustulosis.

  • Should stop taking acetaminophen if skin reaction (rash or blister) occurs

acetaminophen drug interactions

•At therapeutic dose free of drug interactions

•Long-term ingestion of large doses of alcohol can increase toxicity

•Hepatotoxicity may be potentiated by administration of barbiturates, carbamazepine, phenytoin, and rifampin

drugs used to treat gout

• is an inherited disease mostly in men with onset in one joint (usually big toe or knee). Excess uric acid and urate crystals accumulate in joint

• Colchicine: Used solely for treatment of acute attack of gout

• Febuxostat: reduces the amount of uric acid in body. Treats chronic gout and hyperuricemia

• Allopurinol: inhibits synthesis of uric acid. Used in patients undergoing chemo or irradiation, both lead to death of many cells releasing large amounts of uric acid precursors

• Probenecid: Blocks tubular reabsorption of filtered urate, prevents formation of urate crystals

drugs used to treat arthritis

• is an autoimmune disorder

• NSAIDs are often prescribed to treat RA, but they only reduce pain, do not slow disease progression

• Disease-Modifying Antirheumatic Drugs: Slow and stop progression of RA. Suppress overactive immune and inflammatory systems

  • Immunosuppresives: interfere with the formation of immune cells, patient at higher risk for developing infections

  • Tumor Necrosis Factor (TNF)-alpha inhibitors: Genetically engineered drugs that block the inflammatory process associated with release of high concentration of TNF-α. Called monoclonal antibodies (Humira an example.  All of them increase the risk for opportunistic infections including TB and fungal infections

• Biologic response modifiers- inhibit or modify immune system response. Increased risk of infection

nonopioid analgesic dental hygiene considerations

• If nonopioid analgesics are necessary, the dental hygienist should conduct a thorough medication/health history in order to determine whether the patient has any contraindications to these drugs or risks of potential drug interactions.

• Information regarding salicylates, NSAIDs, and acetaminophen should include warnings to not exceed the manufacturer’s recommended daily dose over a 24-hour period.

• The dental hygienist should encourage patients to check the OTC labels for any overlapping ingredients. Often, these products contain ibuprofen, aspirin, acetaminophen, or any combination of the three with antihistamines and decongestants.

• The dental hygienist should also be aware of the fact that many opioid analgesics are combined with nonopioid analgesics. Remind the patient to not supplement with an OTC analgesic if a combination nonopioid/opioid analgesic is prescribed.

• Warnings about significant side effects associated with OTC nonopioid analgesics (such as bleeding) should be given to the patient along with instructions to call the dental practice if an adverse reaction occurs.

• NSAIDs should be avoided in persons with asthma.

• If patients complain of GI adverse effects, they may require a semi-supine chair position during dental treatment.

• Patients taking DMARDs and biologic response modifiers should be carefully assessed for signs of infection since these drugs weaken the immune system.

opioid analgesics

•Opioid analgesics are used to manage dental pain in patients in whom NSAIDs are contraindicated

•Opium was used as early as 4000bc for its euphoric effects

•In early 1800s, morphine and codeine were isolated from opium.

•Medicines containing opium were used for numerous uses up until 1920

•When these orally administered agents became illegal, narcotic abuse by injection began, and continues today

opioid narcotic classification

• One way to classify clinically useful opioids is by their mechanism of action at the receptor sites.

  • Agonists

  • Mixed opioids: Agonists-antagonists, Partial agonists

  • Antagonists

opioid narcotics mechanism of action

• Bind to receptors in both the central nervous system and the spinal cord, producing an altered perception of reaction to pain.

• Three group of endogenous substances with opioid-like action helped explain presence of these receptors

  • Enkephalins

  • Endorphins

  • Dynorphins

• The exact action of these substances is not understood, but may account for analgesic action of a placebo, and enhancement of well-being that occurs with running

μ-receptors

stimulation of these receptors produces analgesia

k-receptors

responsible for dysphoria (discontent, unhappiness)

δ-receptors

associated with autonomic stimulation, dysphoria, hallucinations, nightmares, and anxiety

opioid narcotic pharmacokinetics

•Absorption: absorbed will when taken orally. Absorption from lungs, nasal and oral mucosa. Absorption occurs through the mucous membranes of the nose and the intact skin

•Distribution: opioids undergo variable first-pass metabolism in the liver or intestinal cell wall reducing bioavailability. Opioids are bound to plasma proteins to varying degrees.  Distributed throughout the body

•Metabolism: Major route is conjugation with glucuronic acid in liver. Oral administration provides 4-6 hours of analgesia

•Excretion: Once metabolized excreted by glomerular filtration as their metabolites, excreted in urine

opioid narcotic pharmacologic effects

• Analgesia: Varying degrees of analgesia depending on strengths of agents

• Morphine is the opioid agonist by which other opioids are measured

• Strongest opioids can reduce the  most severe pain; weaker agents mixed with non-opioids are equivalent to NSAIDs in pain relief

• Sedation and Euphoria: in usual therapeutic doses the opioid analgesics produce sedation by κ-receptors, which may potentiate their analgesic effect and relieve anxiety. Additive with other CNS depressants such as alcohol. Larger doses, of if pain suddenly removed euphoria can result.

• Cough suppression: Antitussive action by depressing cough center in the medulla. Much lower dose than required for analgesia. Least potent agents (codeine) used

• GI effects: Increase smooth muscle tone of the intestinal tract, and decrease motility. Useful to treat diarrhea. Lomotil (no analgesic effects) used for diarrhea

opioid narcotic adverse reactions

• Unlike many other drugs, adverse reactions are not related to direct damage on hepatic, renal, or hematologic tissues.  Rather an extension of pharmacologic effects.

• Adverse effects are proportional to the analgesic strength of the opioid.

contraindications and cautions for use of opioids

• alcoholism or addiction

• head injury

• chronic pain

• respiratory disease

• pregnancy

• nursing - no problem but watch infant

• nausea

• constipation

opioid respiratory depression

•Depresses respiratory center in a dose-related manner

•Usually the cause of death with an overdose.

•Opioids decrease sensitivity of the brain stem to carbon dioxide

•Usual dose of morphine in elderly can reduce pulmonary ventilation, which leads to vasodilation, which increases intracranial pressure

•Opioids may mask CNS diagnostic symptoms

•Hypothyroid patients more sensitive to respiratory depression

•Children younger than 12, or under 18 if they have had tonsils and adenoids removed should not receive codeine or tramadol.

opioid narcotic adverse effects

•Nausea and emesis: Analgesic doses. Stimulates chemoreceptor trigger zone in medulla. Reduced if patient is not ambulatory. Continued, regular doses can prevent vomiting

•Constipation: Opioids cause tonic contraction of GI tract. Duration outlasts analgesic effect. No tolerance to this effect

•Miosis: contraction of pupils. Pinpoint pupils are an important sign of opioid overdose. No tolerance to this effect

•Urinary retention: Opioids increase the smooth muscle tone of urinary tract. Also stimulate release of antidiuretic hormone

•CNS Effects: May at times produce CNS stimulation: anxiety, restlessness or nervousness

•CV Effects: May depress vasomotor center, stimulate vagus nerve. High doses can cause postural hypotension, bradycardia, and syncope

•Billiary Tract Constriction: May constrict biliary duct resulting in biliary colic (pain associated with gallstones)

•Histamine Release: Histamine release can cause itching and urticaria

•Pregnancy/Nursing: No teratogenicity shown. May prolong labor or depress fetal respiration. Infant born to an addict may go through withdrawals. Not an issue for nursing

opioid addiction

• A disease of the brain that involves both physical and psychological dependence.

• Two major signs of addiction

  • Cravings: and intense and overwhelming desire for the drug

  • Loss of control of the ability to stop using, or control the amount used

• Long term usage leads to tolerance, habituation, and dependence

• Short term use as used for dental procedures (1-3 days) does not usually lead to tolerance or addiction

• NSAIDs should be used in known addicts

• Addiction potential is directly related to analgesic strength. Rate of development likewise dependent on strength and frequency of use

opioid overdose

•Major symptom is respiratory depression. Pinpoint pupils and coma. Treated with an opioid antagonist, Naloxone

opioid withdrawl

•Symptoms yawning, lacrimation, perspiration, rhinorrhea, gooseflesh, irritability, nausea, vomiting, tachycardia, tremors, and chills. “cold turkey” comes from the goosebumps which resemble a plucked turkey

identification of opioid addicts

•“Shoppers” patients who go from one doctor to the next seeking their drug of choice

• Requests a certain drug and says it is better; he or she may stumble over the name

• Claims many allergies and says lots of pain medications do not work

• Cancels dental appointments because he or she claims to be going out of town on business

• Experiences pain for days after scaling and root planing

•Moves from dental office to dental office because “others do not understand”

•Claims a “low pain threshold”

•Calls with a request for an opioid analgesic just as the office is closing, or after hours with the promise of coming in for an examination the next day

•Needs refills several days after a dental procedure without complications

opioid allergic reactions

• True allergy is uncommon

• Most common reaction is dermatologic: rashes and urticaria

• GI effects are not allergic reactions

• Topical exposure can cause contact dermatitis

• Must differentiate allergic reactions from histamine-releasing properties

• for severe pain, alternatives may include codeine or morphine, with mild cases may include NSAIDs

opioid drug interactions

• Respiratory depression of opioids is additive to other CNS depressants

• All opioids interact with MAO inhibitors, used to treat depression, Should be used with caution

mixed opioids

• Agonist-Antagonist opioids

  • Pentazocine is only one

  • CNS effects similar to opioid agonists

  • Pentazocine is combined with Naloxone to prevent abuse as parenterally administered naloxone prevents the opioid action of pentazocine.  Naloxone does not affect pentazocine if taken orally.

• Partial Agonists

  • Buprenorphine: only partial agonist

  • Suppresses withdrawal and craving symptoms for recovering opioid addict

  • Abuse potential is moderate

opioid antagonists

• Naloxone: reverses opioid overdose. It is a pure opioid antagonist. Given alone has few pharmacologic effects. Must be given parenterally, not effective orally. Can cause withdrawal if too much is given

• Nalmfene: Parenteral opioid antagonist to reverse opioid overdose

• Naltrexone: Used to prevent opioid and alcohol use in addicts

• Long acting, orally effective opioid antagonist

• Maintenance of opioid-free state in detoxified, former opioid-dependent patient

• Should not be administered until patient has been opioid free for 1 week

• Should not give these patients any opioids for dental pain management

full agonist/reuptake inhibitors

•Tapentadol: oral opioid receptor agonist and norepinephrine reuptake inhibitor. Has potential for abuse and misuse. Should not be taken within 14 days of taking an MAOI

•Tramadol: has opioid agonist action and inhibits serotonin and norepinephrine reuptake

•Analgesic efficacy unimpressive

•Lack of addiction potential is questionable

dental hygiene considerations for opioids

• If analgesics are necessary, the dental hygienist should conduct a thorough medication/health history of the patient to determine whether there are any contraindications or drug interactions.

• The dental hygienist should be aware that many opioid analgesics are combined with nonopioid analgesics. Remind patients to not supplement with over-the-counter (OTC) analgesics if a combination nonopioid/opioid analgesic is prescribed.

• The most common side effect of the opioid analgesics is sedation. Other sedating drugs should be avoided or used with caution if they are essential.

• Patients should avoid anything that requires thought or concentration while taking an opioid analgesic.

• If patients complain of gastrointestinal adverse effects, they may require a semisupine chair position during dental treatment.

• The dental hygienist should be aware of the signs of opioid addiction and how to identify an addict.