Anti-Inflammatory and Analgesics

Question 1

Narcotic Analgesics

Answer 1

Used in treating moderate to severe pain
Most effective drugs for pain management
Drugs
Opiate agonists, mixed agonist-antagonists, and antagonists
Activity at three sites of brain: mu, kappa, and delta

Question 2

Opioid Receptors

Answer 2

Four opioid receptors: delta (δ), mu (μ), sigma (σ), kappa (κ)
Stimulation of sigma results in hallucinations
Stimulation of mu (μ) and kappa (κ) and possibly delta (δ) results in analgesia

Question 3

Adjuvants

Answer 3

Often added to opioids to assist in relieving pain and reduce some of the adverse effects of the narcotics
Antidepressants, antiepileptic’s (can be used for chronic neuropathic pain), antiemetic’s (to combat nausea/vomiting), sedatives, corticosteroids

Question 4

What are Opioid Analgesics?

Answer 4

Agonist – binds to an opioid receptor in the brain and causes an analgesic response
Partial Agonist – binds to a pain receptor but causes a weaker neurologic response than a full agonist
Mixed Agonist-Antagonist – agonist effects at some opioid receptors and weak antagonist effects at other receptors. Can be used for chronic pain management, less of a risk of respiratory stress/addiction

Question 5

Chemical Classification of Opioids

Answer 5

Meperidine-like drugs:
Meperidine, fentanyl, remifentanil, sufentanil, alfentanil

Methadone-like drugs:
Methadone, Propoxyphene

Morphine-like drugs:
Morphine, Heroin, Hydromorphone, Oxymorphone, Codeine, Hydrocodone, Oxycodone

Other: Tramadol

Question 6

Indications for use of Opioids

Answer 6

Morphine-like opioids are often used to control postoperative pain and other types of pain.
These are usually first-line analgesics due to the fact that some are readily available in injectable form.
Opioids also suppress the medullary cough center, which results in cough suppression
Always assess O2 Stat, Respiratory rate from heavy opioid effects. Check gag/cough reflex, as a result of CNS depression.
Opioids are used especially as a chest surgery medication to prevent coughing/opening of wound

Question 7

Morphine

Answer 7

Treatment of moderate to severe acute or chronic pain
Dyspnea with acute left ventricular failure and pulmonary edema (vasodilating effect, lowers afterload to help heart)
Pain of MI: MONA (morphine, oxygen, nitroglycerin, aspirin)

Agonist at mu, kappa, and possibly delta opiate receptors
Reduction in release of neurotransmitters in presynaptic space
Decrease in the release of substance P
Alters release of pain responsive neurons

Question 8

Morphine (Primary and Adverse Effects)

Answer 8

Vasodilator: Could be adverse (hypotensive patient)
Elevates intracranial pressure
Stimulates mainly the mu (U) receptor 
Depresses respiratory function
Constipation (Adverse)
Causes urinary retention (adverse)
Lowers blood pressure 
Bradycardia 
Constricts the pupils (miosis). NORMAL RESPONSE. Check symmetry
Vomiting

Question 9

Morphine Contraindications/Precautions

Answer 9

Contraindications
Hypersensitivity, pre-existing respiratory depression, acute or severe bronchial asthma, and upper airway obstruction
Premature neonates and labor and delivery where premature neonate is anticipated
Heart failure from lung disease, cardiac arrhythmias, increased intracranial pressure, head injury, brain tumor, acute alcoholism, or delirium tremens

Precautions
Patients receiving other CNS depressants, those who are old or debilitated or have renal or hepatic impairment

Question 10

Morphine Adverse Effects

Answer 10

Excessive CNS depression: respiratory depression,
hypoventilation, apnea, respiratory arrest, circulatory
depression, cardiac arrest, shock, and coma
Most frequent effects: respiratory depression, apnea,
bradycardia, light-headedness, dizziness, sedation, nausea and vomiting, sweating

Drug Interactions:
CNS depressants, anti-depressants, H2 blockers
Barbiturate anesthetics

Question 11

Morphine Therapeutics Effects

Answer 11

Assessing pain using pain assessment tools
Location, intensity, quality, and character
Providing analgesia
Administering before level of pain gets severe; around the clock or continual administration
Titrating dose based on patient’s response

Minimizing Adverse Effects
Performing frequent and astute assessment
Using patient-controlled analgesia (PCA)

Question 12

Toxicity and Management of

Opioid Analgesic Overdose

Answer 12

Opioid antagonist (ex. Narcan, ReVia, Revex)
will reverse not only respiratory suppression but will also reverse the pain control

The nurse must be cautious of adverse effects of reversal medications. Ex. HTN, arrhythmias, pulmonary edema, withdrawal, nervousness, headache, N/V

Question 13

Naloxone (Narcan)

Answer 13

Naloxone (Narcan)
Narcotic antagonist used to reverse the effects of opiates (respiratory depression) or overdose
Competes for opiate receptor sites
Adults, children, and neonates
Administration IM, SC (sub-q), or IV; most rapid onset via IV administration (2 minutes)
Careful monitoring of the patient necessary – shorter duration of action than opioids
Repeated doses may be necessary
N/V, sweating, tachycardia, ↑BP, tremors. Cardiac dysrhythmia can occur from rapid reversal

The half life of the reversal agent is much shorter than the narcotic/opioid analgesic

Question 14

hydromorphone (Dilaudid)

Answer 14

Semi-synthetic opium analogue
Actions: almost identical to morphine
Indications: same as MSO4
1-1.5mg of hydromorphone = 10mg MSO4
More potent than morphine, use small doses
Less respiratory depression (it does cause it) & physical dependence
Can cause transient hyperglycemia

Question 15

meperidine (Demerol)

Answer 15

Synthetic opioid
Action: same as MSO4…binds to receptors in CNS
Indications: treat pain pre- & post-op, support anesthesia, during labor

Pharmacokinetics:
less potent than MSO4
Longer half-life
Accumulation of active metabolite- normeperidine:
15-30 hr ½ life. CNS toxin, can cause tremors, seizures, & changes in LOC. Worse if renal impairment.
Interaction w/ antiepileptic hydantoins- ↓effect of meperidine

Question 16

fentanyl (Sublimaze, Duragesic)

Answer 16

Actions: very potent analgesic 100:1 over MSO4 (0.1mg = 10 mg MSO4)
Indications: severe pain, chronic pain (patches w/ 72 hr duration), adjunct to general anesthetics, epidural PCA (off-label). Contraindicated in opioid naïve pts.
Pharmacokinetics:
transdermal- 24 hr to achieve effect.
Fewer respiratory and emetic effects than morphine
Drugs that inhibit cytochrome P-450 3A4 will ↑↑plasma concentrations of Fentanyl

Question 17

methadone (Methadose, Dolophine)

Answer 17

Actions: like MSO4
Indications: pain, prevention of withdrawal symptoms from heroin, maintenance tx for narcotic abuse.
Pharmacokinetics: longer ½ life (15-30 hrs vs. 1.5-2hrs)
High abuse potential

Question 18

Codeine

Answer 18

Treatment of mild to moderate pain and cough suppression
Available in oral tablets and injectable form; combined with acetaminophen
Antitussive properties

Similar action to morphine but milder
Action at specific opioid receptors in CNS
Direct action on medullary cough center; drying effect on mucous membranes

Question 19

Codeine Precautions

Answer 19

Patients who need cough to maintain airway and those with asthma and emphysema
Patients with preexisting cardiac disease
Pregnant and lactating women
Hypersensitivity and history of narcotic addiction
Patients needing to be alert or drive and those with suspected head injury or have had a craniotomy

Question 20

Codiene Adverse Effects

Answer 20

Similar to morphine but less severe
Drowsiness, sedation, dry mouth, nausea, vomiting, constipation
Allergic reactions
Respiratory depression and cardiovascular effects with higher doses

Drug Interactions
Other CNS depressants
Histamine -2 antagonists (cimetidine - Tagamet)

Question 21

Drugs Closely Related to Codeine

Answer 21

Hydrocodone
as antitussive when combined w/ homatropine (Hycodan); expectorant in a syrup or formula for coughs
For moderate to severe pain when combined w/ acetaminophen (Lorcet, Lortab, Vicodin); or w/ibuprofen (Vicoprofen)

Propoxyphene (Darvan)
Treatment of mild to moderate pain
Drug-related death with excessive doses
Avoid other CNS depressants 
Not to be prescribed to suicidal patients or those with addictive tendencies

Question 22

Fever

Answer 22

increased mobility of leukocytes 
enhanced leukocytes phagocytosis 
endotoxin effects decreased 
increased proliferation of T Cells 
enhanced activity of interferon

Question 23

Methotrexate

Answer 23

Treatment of various malignancies
Management of adult and juvenile rheumatoid arthritis and psoriasis through its immunosuppressive effects

Induction of folate depletion
Folate is needed for purine base synthesis
Inhibits DNA and RNA synthesis
Toxic effect on rapidly dividing malignant cells
Inhibition of T lymphocyte replication and function

Question 24

Methotrexate Contraindications

Answer 24

Contraindications 
Immunosuppression
Pre-existing blood dyscrasias: changes in RBC/WBC, thrombocytopenia, leukopenia
Impaired bone marrow function
Pregnancy and lactation

Precautions
Pre-existing hepatic or renal dysfunction, malnutrition, or ulcerative colitis

Question 25

Methotrexate Contraindications

Answer 25

Adverse Effects Stomatitis & oral ulcers, mild alopecia and hair thinning, GI upset r/t folic acid antagonism Headache, fatigue, & feeling “wiped out” (“MTX fog”) Suppression of bone marrow function Pneumonitis, elevated liver enzymes & cirrhosis (rare) Lymphoma (rare)

Question 26

Methotrexate Therapuetic Effects

Answer 26

Maximizing Therapeutic Effects Weekly administration as ordered Adequate water intake Continuation with therapy Minimizing Adverse Effects Administration of Vitamin B (folic acid) 1 mg every day to decrease the potential for adverse effects Allopurinol prescription for mouth ulcers Protection from ultraviolet light exposure

Question 27

Gout

Answer 27

Gout: condition that results from inappropriate uric acid metabolism Underexcretion of uric acid Overproduction of uric acid Uric acid crystals are deposited in tissues and joints, resulting in pain

Question 28

NSAID's Anti Gout Drugs

Answer 28

Allopurinol (Zyloprim) Used to reduce production of uric acid Colchicine Reduces inflammatory response to the deposits of urate crystals in joint tissue (NSAID of Gout drugs) Probenecid (Benemid), Sulfinpyrazone (Anturane) Increase excretion of uric acid in the urine

Question 29

Colchicine

Answer 29

Treatment of acute gouty arthritis Possibly effective for other types of arthritis Pharmacokinetics Oral or IV administration Never IM or SC administration due to severe local irritation Pharmacodynamics Inhibition of leukocyte activity Decrease in migration to affected area, interrupting cyclic inflammatory process Prevention of release of an inflammatory glycoprotein from phagocytes

Question 30

Colchicine Contraindications

Answer 30

Contraindications Severe cardiac disease, hepatic disease, renal disease Higher risk for adverse effects Precautions Pre-existing GI disease or depressed bone marrow function Pregnancy category C drug (oral); category D (parenteral form)

Question 31

Adverse Effects of Colchicine

Answer 31

GI tract effects: nausea, vomiting, diarrhea, abdominal pain, paralytic ileus Can be indicative of toxicity Long-term effects: bone marrow depression S&S of SEVERE adverse effects: Fever, chills, or sore throat; wheezing or difficulty breathing; swelling of face or mouth; integumentary effects.

Question 32

Patient Teaching of Colchicine

Answer 32

Diets high in uric acid: Red meats, seafood (esp. shellfish), alcohol & beer Intake of alcohol esp. beer Fluid intake Taking at first sign of a gout attack Taking missed dose immediately, but If it is almost time for the next dose, only that dose should be taken Reporting GI adverse effects Avoiding alcohol, purines Keeping colchicine away from light and out of the reach of children

Question 33

NSAID's: Mechanism of Action

Answer 33

Analgesia and anti-inflammatory: treatment of headaches, mild to moderate pain, and inflammation Block the chemical activity of either or both COX enzymes (prostaglandin pathway) and lipoxygenase (leukotriene pathway) Result: limits the undesirable inflammatory effect of prostaglandins Antipyretic: reduce fever Inhibit prostaglandin E2 within the area of the brain that controls temperature

Question 34

COX Inhibition: NSAID's

Answer 34

Analgesic, antipyretic, and anti-inflammatory activity are achieved principally through COX-2 inhibition COX-1 inhibition is responsible for its unwanted effects on the GI mucosa. Before giving an NSAID, check Renal insufficiency, Hepatic insufficiency, GI health (bleeding)

Question 35

NSAIDs: Interactions

Answer 35

Serious interactions can occur when given with: Anticoagulants Corticosteroids and other ulcerogenic drugs

Question 36

Aspirin

Answer 36

Pharmacotherapeutics Treatment of headache, neuralgia, dysmenorrhea, arthralgia, postpartum pain, myalgia, dental pain Preferred agent for juvenile arthritis, rheumatoid arthritis, fever, pleurisy, arthritis, tendonitis, and bursitis Used for treating pericarditis, preventing or reducing the risk of MI and recurrent transient ischemic attacks because of its anti-platelete reaction

Question 37

Aspirin Cont.d

Answer 37

Analgesic, anti-inflammatory, antipyretic, and antithrombotic drug Antipyretic effects of aspirin due to inhibited prostaglandin synthesis in the hypothalamus Anti-inflammatory action due to peripheral inhibition of prostaglandin synthesis Antithrombotic effect from inhibition of thromboxane A2

Question 38

Aspirin Contraindications

Answer 38

Contraindications Patients with salicylate hypersensitivity, peptic ulcer disease, bleeding disorders, anticoagulation therapy Patients with gout, renal or liver impairment; children with varicella or flu-like illness (development of Rhys Syndrome); pregnant or lactating women Avoidance by smokers and patients with history of alcohol abuse due to ulcerogenic effects Precautions Patients with asthma, nasal polyps, hyperuricemia Patients older than 60 years and those taking corticosteroids

Question 39

Aspirin Adverse Effects

Answer 39

Salicylism: Mild aspirin toxicity from high doses or long-term use Salicylate poisoning: Life-threatening event Common adverse effects are related to prostaglandin inhibition

Question 40

Salicylate Toxicity S&S

Answer 40

Tinnitus and hearing loss (most common) Increased HR, RR, headache, confusion, drowsiness, GI distress, hyperthermia, can lead to coma and death Mostly Metabolic acidosis and respiratory alkalosis may be present Renal failure / impaired renal function

Question 41

Salicylate Treatment

Answer 41

Dosage reduction or discontinuation of salicylates Symptomatic and supportive therapy Gastric emptying, gastric lavage, activated charcoal Fluid replacement and electrolyte therapy Support respirations if needed Seizure prevention or treatment

Question 42

Health Considerations: Aspirin

Answer 42

Evaluating gross hearing and baseline CBC, platelet count, renal and hepatic function Life Span and Gender Pregnancy Ages less than 16 years or over 60 years

Question 43

Special Populations for Aspirin: Pediatrics

Answer 43

Salicylates are NOT to be given to children under age 18 with varicella or flu-like illness because of the risk of Reye syndrome Because these drugs generally cause GI distress, they are often better tolerated if taken with food, milk, or an antacid to avoid irritation Educate patients about the various adverse effects of NSAIDs, and to notify their physician if these effects become severe or if bleeding or GI pain occurs

Question 44

Ibuprofen

Answer 44

Pharmacotherapeutics Rheumatoid arthritis, osteoarthritis, mild to moderate pain, primary dysmenorrhea, fever, migraine headache Pharmacokinetics Approximately 80% absorbed from GI tract; absorption slowed with food Analgesic and antipyretic effects within 2 to 4 hours Therapeutic inflammatory response in a few days to 2 weeks

Question 45

Ibuprofen Contraindications

Answer 45

Pharmacodynamics Effects secondary to inhibited synthesis or release of prostaglandins Peripheral action as analgesic Antipyretic through action on the hypothalamus Contraindications Hx of or active GI disease, regular consumption of alcohol, or smoke tobacco Third trimester of pregnancy Prolong/inhibits labor Premature closure of the ductus arteriosus Precautions Pre-existing hepatic, renal, or hematopoietic dysfunction Patients over age 60 Hx of MI or stroke

Question 46

Ibuprofen Adverse Effects

Answer 46

Nausea, vomiting, diarrhea, constipation, flatulence, and abdominal pain; peptic ulcer disease or gastritis Blurred vision, decreased visual acuity, and corneal deposits Tinnitus (sign of toxicity) Acute renal failure; sodium and water retention Abnormal or excessive bleeding; hepatoxicity

Question 47

Ibuprofen Minimizing Adverse Effects

Answer 47

``` Obtaining periodic CBC, platelet count, and liver and renal function tests Administering misoprostol (Cytotec) to patients at high risk for developing gastropathies ```

Question 48

Propionic Acids

Answer 48

fenoprofen, flurbiprofen, ketoprofen, naproxen (Naprosyn, Anaprox), oxaprozin Similar in action to ibuprofen; differences only in onset, peak, and duration of action Naproxen may be better tolerated than other NSAIDS