Chp 6 Drugs for Pain control

sensory and reactionary

• The actual painful stimulus
• comes from the PNS.

• The emotional response to pain
• originates from the CNS

short time course. Usually simple to evaluate and treat

undetermined time course, more complex evaluation, treatment not as successful

• Nociceptive pain
• Neuropathic pain

pain arising from a stimulus such as injury to tissue, bone, joint muscle or connective tissue outside of the CNS. A scaler/currette

also called neuralgia. Originates in a damaged or compromised nerve

somatic or visceral

sharp, well-localized sensations

• a generalized dull, throbbing or aching, poorly localized pain.
• referred pain, which detects the painful stimulus in areas removed from the site where the pain originated

• nociceptors
• noxious stimuli

trigeminal neuralgia, postherapeutic neuralgia, burning mouth, burning tongue syndrome

• tricyclic antidepressants, analgesics, and anticonvulsants
• gabapentin (Neurontin) (antiepileptic drug that enhances neuronal stability, which results in pain relief)
• 5% lidocaine patch
• Tricyclic antidepressants

chronic neuropathic pain

• Nonnarcotic (nonopioid) analgesics–Nonsteroidal anti-inflammatory drugs (NSAIDs)
• Narcotic (opioid) analgesics–Ex. codeine, hydrocodone

• salicylates (Aspirin)
• acetaminophen (Tylenol)
• Nonsteroidal anti-inflammatory drugs (NSAIDs)including selective COX2 inhibitors

• phospholipase A
• arachidonic acid
• phospholipids on cell membrane

• lipoxygenase
• Cyclooxygenase (COX) I and II enzymes

• Leukotrienes
• bronchoconstriction (in asthma) and other localized allergic reactions

Prostaglandins, Prostacyclin and Thromboxane A2

• Fatty acids found in all tissues
• cell during inflammation
• Promote pain, inflammation, and fever
• Protect lining of stomach from damaging acid
• Cause uterine contractions during labor
• Maintain renal (kidney) blood flow

• Prostaglandin E2 PGE2
• inflammatory periodontitis

• platelets
• Prevents bleeding; potent vasoconstrictor which induces platelet aggregation for clotting

• blood vessel cell walls
• Prolongs bleeding; vasodilator (opposite function of thromboxane A2), prevents platelet aggregation

• "Housekeeping enzyme”
• most cells in the body
• GI tract, kidney, platelets
• Protect the lining of the stomach from stomach (gastric) acids, maintain normal platelet function, and regulate renal blood flow

during inflammation

acetylsalicylic acid

• COX-1 and COX-2
• COX-1
• GI problems –Bleeding, ulcer

• Analgesia
• Anti-inflammatory
• Antipyretic
• Antiplatelet effects

Due to inhibition of prostaglandins and bradykinin (bradykinin, an inflammatory mediator, sensitizes nociceptor peripheral terminals) reducing pain threshold

Increasing dose beyond a point does not increase analgesia

–blocking formation of PGE2

inhibiting thromboxane A2

• 81
• prophylactic treatment for heart attacks and stroke
• thromboxane A2

325

• prevent a first cardiovascular event for most patients who are at moderate risk
• prevent cardiovascular or cerebrovascular events in patients with a history of heart conditions

primarily a children’s disease. Children are at increased risk to develop Reye’s Syndrome if they take aspirin to treat viral illnesses including chicken pox or flu

developing bronchoconstriction and anaphylaxis

• Gastrointestinal upset–Reduces some with enteric-coated tablets
• Bleeding
• Salicylism (toxicity)
• Nausea/vomiting
• Renal dysfunction
• Excessive doses stimulate the depth and rate of respiration (hyperventilation)

• Oral antidiabetic: increases Hypoglycemic response of oral antidiabetic drugs
• Angiotensin-converting enzyme (ACE) inhibitors: decreases effectiveness of the hypertensive drug
• Other aspirin-containing OTC drugs: increases Aspirin effects
• Thiazide or loop diuretics: decreases Actions of diuretic
• Anticoagulants (e.g., warfarin): increases Bleeding
• Alcohol: increases GI irritation and bleeding
• Herbs (dong quai, chamomile, ginseng, ginger, and red clover): Increased bleeding

• 1 g (1000 mg)
• 10 g

• Dolobid
• –Derivative of salicylic acid but is not converted to salicylic acid
• –It is a more potent anti-inflammatory than aspirin, and it is an inhibitor of cyclooxygenase.
• It does not have antipyretic activity because it penetrates poorly into the CNS
• –Anti-inflammatory for arthritis and for dental pain
• –Less intense gastrointestinal and antiplatelet effects than aspirin
• Good for dental pain
• Use loading dose of 500-1000mg followed by 250-500mg q8-12h

• ibuprofen
• Advil, Motrin

• Block the COX enzymes and reduce prostaglandins throughout the body
• Ongoing inflammation, pain, and fever are reduced
• –Reduces protection of gastric mucosa Ulcers
• NSAIDs differ in how strongly they inhibit COX-1 and thus their tendency to cause ulcers and bleeding is less than aspirin

• Analgesia –Dental pain – very effective.
• Anti-inflammatory
• Antipyretic

• Inhibition of COX-1 also inhibits the production of thromboxane A2, which prevents platelet aggregation
• NSAIDs do not covalently bind to the cyclooxygenase enzymes and do not irreversibly inhibit platelet function as does aspirin

• –Due to COX-1 inhibition, which decreases GI mucosal defense mechanisms and increases gastric acid secretion, which leads to ulceration
• Take with food or milk
• Kidney function –Depressed due to inhibition of prostaglandin synthesis, which plays a protective role in kidney function
• All NSAIDs can lead to the onset of new hypertension or worsening of preexisting disease

asthma and nasal polyps

• Counteracts the antihypertensive effects of angiotensin converting enzyme inhibitors (ACE inhibitors) and beta-blockers 
•  increases Lithium levels by decreasing renal excretion of lithium (can cause lithium toxicity)
• increases bleeding with anticoagulants
• increases Hypoglycemic effects with oral antidiabetic drugs

• Celecoxib (Celebrex)
• increased risk of cardiovascular events as well as serious and potentially life-threatening gastrointestinal bleeding

• Only inhibits cyclooxygenase-2Inhibits prostaglandin synthesis
• Analgesic
• Antipyretic
• Anti-inflammatory
• Antiplatelet–Not used for prevention of strokes/heart attacks because it reversibly binds to the platelets

• Tylenol
• its lack of effect on platelet function and less or no gastric irritation

30 to 60

• Hepatotoxicity (liver necrosis)
• acetylcysteine

3 to 4 g

• Alcohol–Increase liver damage (hepatotoxicity)
• Carbamazepine (Tegretol), phenytoin (Dilantin), and rifampin (Rifadin)–Increase liver damage (hepatotoxicity)

B

• central components
• opiate receptors
• CNS

• Enkephalins and endorphins are released from neurons in the brain and activate opioid receptors, thereby blocking the transmission of pain impulses
• These substances are the body’s natural opiates that inhibit painful stimuli

• Mu (μ)
• Delta (δ)
• Kappa (κ)

mu and kappa

analgesic, respiratory, depressant, and euphoric effects

respiratory depression, miosis (pupil constriction), and sedation

• CNS
• –Respiratory depression
• –Cough suppression
• –Nausea/vomiting
• GI
• –Constipation
• Tolerance can develop

• Antihistamines, sedative/hypnotics, alcohol, and psychotropics
• –Increased CNS effects (e.g., sedation)

GI tract, nasal mucosa, and lungs (smoke)

• Full agonists: Strong or moderate in producing an analgesic (relief of pain) effect
• Mixed opioid agonist/antagonists: Analgesic effect with some antagonist activity
• Pure antagonists: No analgesic effects; used in opioid overdose

Morphine

• Analgesia
• Drowsiness and sleep
• Cough suppression
• Vomiting (due to stimulation of chemoreceptor trigger zone in the brain)Hypotension
• Miosis (papillary constriction)
• Respiratory depression (high doses) –Major toxic effect and cause of death because no tolerance is developed to respiratory depression
• Euphoria (ecstasy; develop tolerance rapidly to euphoric actions)
• Increased release of ADH (antidiuretic hormone), which causes urinary retention

• Constipation (due to stimulation of cholinergic activity in the GI tract)
• Body warmth/flushing/itching (due to histamine release)

• Long-acting synthetic morphine derivative used orally in the treatment of opioid (usually heroin) addiction
• “Wean” patients off narcotics because it does not produce euphoria (ecstasy).

is a less effective analgesic than morphine with half the duration of action (75 mg meperidine IM [intramuscular injection] = 10 mg morphine IM)

Respiratory depression, antitussive, constipation, and dependence

III

Vicodin

Lortab

Vicoprofen

Percocet / Tylox

Percodan

Combunox

pure oxycodone HCl extended release for long term pain control

• opium poppy
• morphine

codeine

• Less respiratory depressant and constipation and has less dependence potential
• other nonnarcotic drugs such as acetaminophen (Tylenol) for the relief of acute nociceptive mild to moderate dental pain
• Antitussive–Cough syrups (Schedule V)

• Monitor patient for dry mouth; fluoride rinses if indicated.
• Monitor vital signs because of potential effects on the heart and respiratory system.
• Causes drowsiness/sedation

• –Opioid without any analgesic activity
• –High antitussive effects
• Cough medicines: Some trade names are Benylin, Delsym, and Vicks

• Imodium
• –Opioid without analgesic effects
• –Increases smooth muscle tone in the gastrointestinal tract and is used as an antidiarrheal

• –Antidiarrheal
• –Combined with atropine in a product called Lomotil
• It can cause severe respiratory depression, coma, and death after overdose in children

• Ultram
• –Unique analgesic having both opiate and central acting adrenergic qualities 
• Not a controlled substance
• FDA approved for moderate to moderately severe pain
• Can cause serious neurotoxicity and is not the first-line drug of choice