NPLEX Ortho Tests with Indications (Dr. Rachel Klein)

1. Orthopedic tests: vertebral column

A. Adam’s sign. + when rib hump is noted indicating a structural scoliosis

B. Adson’s test. + when radial pulse is diminished indicating TOS

C. Braggard's test. + when leg pain is present indicating a nerve root lesion.

D. Bechterew’s test. + when leg pain is present indicating a nerve root lesion.

E. Burns’ bench test. + when there is an exaggerated pain response indicating malingering.

F. cervical spine compression test. + when there is arm pain indicating a nerve root lesion or

neck pain indicating a joint or ligamentous injury

G. cervical spine distraction test. + when arm pain is decreased indicating a nerve root

lesion or neck pain indicating ligamentous or joint injury.

H. East’s test (Roos’ test). + when patient cant maintain position due to increased

tingling/numbness of arms indicating TOS.

I. Hoover’s test. + when contraction is felt in “paralyzed” leg, indicating malingering.

J. Kemp’s test. + when there is back pain with leg pain indicating nerve root lesion or local

back pain indicating sprain/strain or facet issues.

K. Kernig's test. + when there leg indicating nerve root lesion or increased resistance due to

tight hamstring.

L. Lasegue’s test (straight-leg raise). + when there is leg pain indicating a nerve root lesion

or local back pain indicating si/lumbar sprain strain.

M. Lindner’s test. + when there is pain locally and radiates indicating nerve root lesion.

N. Milgram’s test. + when there is pain indicating a space occupying lesion usually a disc.

O. Minor’s sign. + when patient walks hands up in order to get up from a seated to standing

position indicating a lumbar/si pathology.

P. shoulder depression test. + when there is arm pain indicating radiculopathy, nerve root

lesion, or local neck pain indicating cervical sprain/strain.

Q. Soto Hall test. + when there is radiating pain indicating nerve root lesion or local neck

pain indicating cervical sprain/strain.

R. valsalva test. + when radicular pain is intensified indicating space occupying usually a

disc.

S. vertebral artery test. + when there is dizziness or nystagmus. Supposedly indiciates “impending VBA dissection” J

T. Wright's (hyperabduction) test. + when there is a reproduction of tingling, numbess, or

weakness indicating TOS.

2. Orthopedic tests: shoulder

A. Apley's scratch test. + when there is pain indicating shoulder pathology including ac joint

issues, rotator cuff issues etc. + when inability to perform maneuver indicating gh

contracture or rotator cuff m tightness.

B. drop-arm test (Codman’s). + when pain is noted due to rotator cuff injuries, + when

patient is unable to maintain abducted arm position against gravity most likely indicating

rotator cuff tear.

C. glenohumeral apprehension test. + when maneuver is performed and patient makes a

funny face indicating prior glenohumeral dislocation.

D. impingement test (Hawkins-Kennedy,

Neer’s ). + for pain indicating supraspinatus strain. Neers + pain when hand is supinated

indicates biceps tendintis, hand pronated indicates supraspinatus.

E. Lippman’s test. + for pain indicates bicipital tendinitis or + apprehension indicates prior

subluxating bicipital tendon.

F. Speed’s test. + pain indicates bicipital strain or possible SLAP lesion.

G. Yergason’s test. + pain indicates bicipital tendinitis, + when there is a pop indicating

subluxating long head of biceps.

3. Orthopedic tests: wrist, hand, and elbow

A. Cozen’s test. + pain indicates tennis elbow or lateral epicondylitis.

B. Finkelstein’s test . + pain indicates deQuervain's synovitis.

C. Mill’s test. + pain indicates tennis elbow or lateral epicondylitis.

D. Phalen's test. + pain of anterior wrist and increasing numbness over median nerve

distribution, carpal tunnel.

E. retinacular test + when patient cannot actively flex digits, but they can be passively flexed. Indicates tightened retinaculum.

F. Tinel's sign. + when tapping at the cubital fossa of the elbow causes tingling, numbness of

medial portion of arm and hand indicating ulnar neuropathy. (Tinel’s indicates nerve irritation and can be done over any nerve in question, classically the ulnar n.)

G. valgus/varus stress test. Valgus + when there is pain or laxity of ulnar collateral ligament

indicating ulnar collateral ligament sprain. Varus + when there is pain or laxity of radial

collateral ligament indicating radial collateral ligament sprain.

4. Orthopedic tests: hip and pelvis

A. Ely’s test. + for pain in SI joint dysfunction or when ROM is limited due to rectus femoris

tightness or hip pathology.

B. Gaenslen’s test. + for pain when there is a SI sprain/dysfunction.

C. Hibb's test. + for pain for SI Joint, hip, or pain down the leg indicating piriformis

entrapment of sciatic n.

D. Nachlas test. + pain indicating SI joint issue or pain in the anterior thigh indicating femoral

nerve entrapment.

E. Ober’s test. + pain for hip or greater trochanter indicating trochanteric bursitis.

F. Ortolani click. + when there is an audible click indicating femoral head dislocation seen in

congenital dislocations of hip in infants.

G. Patrick’s test (Patrick-Fabere). + for pain in hip or SI indicates dysfunction where pn is felt. Classically hip problem.

H. pelvic rock test. + when there is pain indicating SI lesion.

I. telescoping test. + when there is excess movement of hip indicating dislocation of the hip.

J. Thomas’ test. + when straight leg is elevated indicating a tight ilipsoas.

K. Trendelenburg test. + when there is a lateral pelvic shift to the side opposite of the weak

gluteus medius.

L. Yeoman’s test. + when there is pain in the sacroiliac region  indicating SI jt problem or pain in the anterior thigh indicating a femoral nerve tension.

5. Orthopedic tests: knee

A. anterior/posterior drawer sign. Anterior drawer sign is + when there is pain indicating an

ACL sprain. Posterior drawer sign is + when there is pain indicating a PCL sprain. Greater

than a 6 mm movement during joint play indicates tear of ligament.

B. Apley's compression test. + when compression causes pain and is alleviated by

distraction indicating a mensical lesion.

C. Apley's distraction test. + when distraction alleviates the pain following compression

indicating a meniscal lesion. Also + when there is pain indicating joint or ligamentous lesion.

D. apprehension test (for patellar dislocation). + when patient is apprehensive upon doc

moving patella indicating patellar instability. Usually dislocates laterally.

E. bounce home test. + when there is pain in the joint line indicating meniscal lesion.

F. Lachman’s test. Gold standard of ACL lesion. + when pain is noted indicating ACL

sprain. Pain with increased anterior translation indicates ACL tear.

G. McMurray’s test. When toes are pointed laterally, pain or clicking indicates lateral

meniscus while toes pointed medially indicates medial meniscus. (Medial meniscus classic use of test.)

H. patella femoral grinding test (including Clark’s test). + when there is pain behind the

patella indicating chondromalacia patella.

I. reduction click. An extension of McMurray's Test performed at 100 deg to full extension of

the knee. + findings similar to those found in McMurrays. Meniscus injury

J. valgus and varus stress test. valgus test is + when there is pain or laxity indicating MCL

lesion. Varus test is + when there is pain or laxity indicating LCL lesion.

K. knee joint effusion tests (ballotable patella test [major effusion]; bulge test [minor effusion] + when patella “floats” back to place after compression, indicating swelling posterior to the patella

6. Orthopedic tests: ankle and foot

A. anterior/posterior drawer test. + when there is increased motion of the ankle indicating

damage to the ligaments of the ankle specifically the anterior and posterior talofibular

ligament.

B. dorsiflexion test. + when there is pain indicating nerve irritation in the tarsal tunnel/tarsal tunnel syndrome.

C. forefoot adduction test. Testing for the integrity of the talofibular ligaments.

D. forefoot squeeze test (Morton’s test). + when there is pain indicating Morton's Neuroma or

fracture of metatarsal head.

E. Homan's sign. + pain in the calf indicating thrombophlebitis/DVT.

F. talor tilt test. Eversion tests the integrity of the deltoid ligaments while inversion tests the

integrity talofibular ligaments.

G. test for rigid or supple flat feet. – I have no idea what this means. Uuuhhh. Palpation?

H. Thompson's (squeeze) test. + When there is no visible plantar flexion indicating Achilles

tendon tear.

I. tibial torsion test. + when there is pain in the knee indicating a meniscal lesion. OR + when an angle is noted, indicating tibial torsion.

Porphyria

BASICS

Porphyria describes a variety of disorders of heme biosynthesis.

Description

• Heme: Primarily synthesized in erythropoietic cells for hemoglobin synthesis and liver parenchymal cells for cytochrome and hemoprotein synthesis (1):
  • Liver rate-limiting step: 5-aminolevulinic acid synthase (ALAS)
  • Erythroid cell rate limiting step: Iron availability
• Porphyria: Inherited and acquired metabolic disorders due to defect in heme biosynthesis leading to accumulation and excessive excretion of porphyrins (2):
  • 8 enzymes involved in synthesis of heme: Defect at any step leads to porphyria
  • Complete enzyme deficiencies incompatible with life
• Classification:
  • Acute vs. chronic porphyrias (2,3)
  • Acute: AIP, HCP, VP, ALAD-P
  • Chronic: PCT, HEP, EPP, CEP
• System(s) affected: Gastrointestinal; Skin/Exocrine; Hematologic/Lymphatic/Immunologic; Nervous
• Acute porphyrias:
  • Acute intermittent porphyria (AIP) (2):
    • Inheritance: Autosomal dominant
    • Classification: Acute
    • Deficiency of porphobilinogen deaminase
    • Symptoms: Purely neurologic (question whether ALA or PBG is neurotoxic)
  • Hereditary coproporphyria (HCP) (2):
    • Inheritance: Autosomal dominant
    • Classification: Acute
    • Deficiency of coproporphyrinogen oxidase
    • Symptoms: Neurovisceral, dermatologic (5%)
  • Variegate porphyria (VP) (2):
    • Inheritance: Autosomal dominant
    • Classification: Acute
    • Deficiency of protoporphyrinogen oxidase
    • Symptoms: Neurologic and dermatologic (60%) (1):
      • Dermatologic symptoms do not respond to phlebotomy or chloroquine.
      • Acute attacks peak in 20s; more common in women
    • Specific labs: Plasma fluorescence emission spectroscopy peak at 624–628 nm distinguishes VP from AIP and HCP (both have peaks at 620 nm).
  • δ-Aminolevulinate dehydratase deficiency porphyria (ALAD-P) (2):
    • Rarest form of porphyria
    • Inheritance: Autosomal recessive
    • Classification: Acute
    • Deficiency of δ-aminolevulinic acid dehydratase (ALAD) causing unopposed ALAS expression in liver:
      • Acute attack due to overexpression of ALA synthetase (ALAS) in liver due to lack of negative feedback from deficient ALAD
      • Partial deficiency does not produce clinical symptoms.
    • Specific labs: Urinary coproporphyrin III and erythrocyte zinc-protoporphyrin
• Chronic porphyrias:
  • Porphyria cutanea tarda (PCT) (1,2):
    • Most common and readily treated porphyria, indistinguishable from VP
    • Inheritance: Autosomal dominant in 20% (type II, expressed in all tissues), may be acquired mutation (type I; expressed only in the liver)
    • Classification: Chronic
    • Deficiency of uroporphyrinogen decarboxylase
    • Symptoms: Dermatologic: Blood vessels of papillary dermis site of injury:
      • Skin fragility: Negligible trauma causes superficial erosion that eventually forms crust; secondary infection common
      • Hypertrichosis
      • Increased pigmentation
    • Specific labs: Plasma fluorescent spectrum to differentiate VP and PCT
    • Specific treatment:
      • Phlebotomy for 3–6 months (this is the treatment of choice in patients with hemochromatosis)
      • Chloroquine (low dose) over 6–12 months only if no hemochromatosis
• Erythropoietic protoporphyria (EPP) (1,2):
  • Inheritance: Autosomal dominant vs. co-inheritance
  • Deficiency of mitochondrial ferrochelatase
  • Classification: Chronic
  • Symptoms: Dermatologic, GI:
    • Dermatologic: Transient skin redness, swelling, pruritus, burning after sunlight exposure
    • GI: Liver dysfunction, gallstones, cholestatic liver failure due to accumulation of protoporphyrin
  • Specific labs: High protoporphyrin in RBCs, bone marrow, and plasma
  • Specific treatment:
    • Skin burning: Apply cold water
    • Afamelanotide: α-melanocyte-stimulating hormone analogue to induce photoprotective epidermal melanin formation
    • Oral β-carotene if nonsmoker
    • Cholestyramine or activated charcoal for liver dysfunction
    • Transplantation for liver failure
• Congenital erythropoietic porphyria (CEP) (1,2):
  • Rare and panethnic
  • Inheritance: Autosomal recessive
  • Classification: Chronic
  • Deficiency of uroporphyrinogen III cosynthase
  • Symptoms:
    • Dermatologic: Photosensitivity
    • Ocular: Chronic ulcerative keratitis, corneal scarring
  • Specific treatment:
    • Photoprotection: Change day-night rhythm
    • Splenectomy (reduces hemolysis and platelet consumption)
    • Bone marrow transplantation
• Hepatoerythropoietic porphyria (HEP) (1,2,3):
  • Inheritance: Autosomal recessive
  • Classification: Chronic
  • Deficiency of uroporphyrinogen decarboxylase
  • Symptoms: Presents in infancy or childhood with red urine, blistering, skin lesions, hypertrichosis, and scarring
  • Specific treatment: Phlebotomy and chloroquine not effective; primary treatment is photoprotection (avoid sunlight)

Epidemiology

• Gender prevalence: Female > Male (3)
• AIP (4):
  • Incidence: 1 per 100,000
  • Onset: 20–40 years old, rarely before puberty
• VP (4):
  • Incidence: 1 per 300 in South Africa, rare elsewhere
  • Onset: 20–30 years, rare before puberty
• HCP (4):
  • Incidence: <50 total cases
  • Onset: Rare before puberty
• ALAD-P (4):
  • Incidence: <10 total cases
  • Onset: Bimodal in early and late years
• PCT (4):
  • Incidence: Most common porphyria worldwide
  • Onset: 30–40 years, rare before puberty
• EPP (4):
  • Incidence: 2nd most common of cutaneous porphyrias
  • Onset: 1–4 years, rare later in life
• CEP (4):
  • Incidence: ~150 total cases
  • Onset: Infancy to 1st decade of life
• HEP (4):
  • Incidence: ~25 total cases
  • Onset: Early infancy

Prevalence

• More common in whites than in Asians or individuals of African descent
• PCT: 1/10,000; most common of the porphyrias in the US and Europe
• AIP, HCP, VP: 1/10,000–1/100,000. The prevalence in Europe is ∼1/75,000. In northern Sweden, because of a founder effect, the estimated prevalence is 1/1,000 (1).

Risk Factors

• Acute porphyria triggers (AIP, HCP, VP, ALAD-P) (3):
  • Viral infections
  • Hypocaloric diet
  • Alcohol
  • Drugs (e.g., barbiturates, sulfa)
  • Stress
  • Steroid hormones
  • Pregnancy
• Hexachlorobenzene exposure

Genetics

See within descriptions of each porphyria above.

DIAGNOSIS

Physical Exam

Symptoms of acute attacks (1):

• Duration: 1–2 weeks
• Mortality up to 10%
• Prodromic phase with behavioral changes (anxiety, restlessness, insomnia)
• GI: Abdominal pain, nausea, vomiting, constipation
• Psychiatric: Anxiety, depression, disorientation, hallucination, paranoia, confusion seen in 20–30%
• Cardiac: Tachycardia, hyperhidrosis, hypertension
• Imaging: Abdominal x-ray normal or with mild bowel ileus
• Labs: Dehydration, hyponatremia due to inappropriate antidiuretic hormone secretion in 40%, electrolyte imbalance
• Neurologic: Seizures due to hyponatremia or hypomagnesemia, neuropathy (mostly motor), normal CSF
• Urine: Excretion red or dark-colored urine

Tests

• Urinary porphobilinogen, porphyrins, 5-aminolevulinic acid
• Genetic studies when applicable

Lab

• Gold standard: DNA analysis to identify causative mutation (3):
  • ALAD-P: ALAD, chromosome 9q34
  • AIP: HMBS, chromosome 11q24
  • VP: PPOX, chromosome 3q19
  • HCP: CPOX, chromosome 1q22–23
  • CEP: UROS, chromosome 10q25.2
  • PCT: UROD, chromosome 1p34
  • EPP: FECH, chromosome 18q21.3
  • HEP: UROD, chromosome 1p34
• Urine: Assess for excess alanine (ALA) and porphobilinogen (1,3):
  • Acute attack confirmed by excretion >10× upper limit
• Serum: ALA levels to differentiate from other causes of abdominal pain (1,3)
• Plasma fluorescence emission spectroscopy (3)

Differential Diagnosis

• The differential diagnosis includes a spectrum of neurologic, psychiatric, and dermatologic disorders.
• Pseudoporphyria is a rare syndrome—indistinguishable from porphyria cutanea tarda—caused by some NSAIDs (e.g., nabumetone and naproxen) and flutamide.

TREATMENT

Medication (Drugs)

First Line

Acute porphyrias:

• Preventive: Avoid sun exposure, precipitating drugs, alcohol, smoking, cannabis, dieting, fasting (1):
  • List of safe and unsafe drugs at www.drugs-porphyria.org (3)
• First-line treatment (1):
  • IV heme:
    • Monitor urinary porphobilinogen excretion to document response.
    • Administer with 1:1 dilution in 4–20% human serum albumin to increase solubility, stability, and lower risk of vein injury.
    • Can be used during pregnancy
    • Monitor for iron overload using iron studies.
  • Monitor fluids and electrolytes:
    • Avoid hyponatremia.
    • Maintain caloric intake with PO carbohydrate-rich food supplements or IV normal saline with 5% dextrose.

• Supportive treatment (1):
  • Abdominal pain: Opiates, aspirin
  • Vomiting: Antiemetics
  • Constipation: Laxatives
  • Hypertension and tachycardia: β-Blockers
  • Neuropathy: Opiates, physiotherapy
  • Adrenergic symptoms: IV magnesium sulfate

• Chronic porphyrias: Specific treatments listed in the “Description” section.

Additional Treatment

General Measures

• Neuropsychiatric–abdominal: Avoid precipitating drugs, alcohol, known toxins.
• Dermatologic: Shade, protective clothing, avoid skin trauma; for porphyria cutanea tarda, weekly or monthly phlebotomy may help to prevent attacks.
• Congenital erythropoietic porphyria: Consider bone marrow transplant.

Ongoing Care

Diet

Neuropsychiatric: Anecdotal evidence carbohydrates help to reduce symptoms or frequency of attacks

Patient Education

• The American Porphyria Foundation, P.O. Box 22712, Houston, TX 77227; 713-266-9617 or 1-866-APF-3635 (toll-free); fax: 713-840-9552; www.porphyriafoundation.com/
• The Drug Database for Acute Porphyria: www.drugs-porphyria.org/
• European Porphyria Network: www.porphyria-europe.com/

Prognosis

• In all porphyrias:
  • Asymptomatic or minimally symptomatic: Unaffected longevity
  • Neurologic complications (e.g., peripheral neuropathy, neurosis, or hemiplegia) may be permanent.
• In AIP:
  • Acute attacks have 25% mortality.
  • Increased risk of hepatocellular carcinoma
• <10% of patients develop recurrent acute attacks (1).

Porphyria Cutanea Tarda: 

Porphyria cutanea tarda (PCT) is a condition resulting from a defect in the heme biosynthesis pathway—reduced activity of the hepatic uroporphyrinogen decarboxylase (UROD) enzyme, which is the 5th enzyme in the heme biosynthetic pathway. This causes buildup of uroporphyrinogens in blood and urine. The buildup of porphyrins in the blood causes skin manifestations.

Image (induced by Tomoxifen)

Tramadol (ULtram)

Today's med: Tramadol  (TRA ma dole) 
(brand names: ConZip, Rybix ODT, Ryzolt, Ultram, Ultram ER)

Drug Class: Analgesic, Opiod

Other Drugs in this class: Oxycodone,Acetaminophen,Hydrocodone/Acetaminophen, 
Gabapentin,Codeine, Ibuprofen, Morphine,Buprenorphine,Oxycodone/Acetaminophen, Ketoprofen,Methadone, Tapentadol, Aspirin,Hydroxyzine, Hydromorphone, Meperidine,Fentanyl, Loperamide,
Phenazopyridine,Butorphanol, Oxymorphone,Hydrocodone/ibuprofen, Remifentanil,Menthol, Sufentanil, Magnesium salicylate, Alfentanil, Loperamide Hydrochloride, Ziconotide, Levorphanol,Oxycodone Hydrochloride,
Propoxyphene,Gabapentin enacarbil,Hydrocodone/Chlorpheniramine,
Codeine/Guaifenesin,Hydrocodone/Homatropine,Tramadol/Acetaminophen,Oxycodone/Ibuprofen,Morphine/naltrexone, Fentanyl Citrate,Hydromorphone Hydrochloride, Meperidine Hydrochloride, Propoxyphene Napsylate,Propoxyphene/Acetaminophen,Oxymorphone Hydrochloride, Tapentadol hydrochloride, Methadone hydrochloride,Levorphanol tartrate, Propoxyphene Hydrochloride, Sufentanil citrate, …

Indications: 

Use: Labeled Indications

Relief of moderate to moderately-severe pain

Extended release formulations are indicated for patients requiring around-the-clock management of moderate to moderately-severe pain for an extended period of time

Contraindications: Hypersensitivity to tramadol, opioids, or any component of the formulation

Additional contraindications for Ultram®, Rybix™ ODT, and Ultram® ER: Any situation where opioids are contraindicated, including acute intoxication with alcohol, hypnotics, centrally-acting analgesics, opioids, or psychotropic drugs

Additional contraindications for ConZip™, Ryzolt™: Severe/acute bronchial asthma, hypercapnia, or significant respiratory depression in the absence of appropriately monitored setting and/or resuscitative equipment

Canadian product labeling:

Tramadol is contraindicated during or within 14 days following MAO inhibitor therapy

Extended release formulations: Additional contraindications:

Ralivia™, Tridural™: Severe (Cl_cr <30 mL/minute) renal dysfunction, severe (Child-Pugh class C) hepatic dysfunction

Durela™ and Zytram® XL: Severe (Cl_cr <30 mL/minute) renal dysfunction, severe (Child-Pugh class C) hepatic dysfunction; known or suspected mechanical GI obstruction or any disease/condition that affects bowel transit; mild, intermittent or short-duration pain that can be managed with other pain medication; management of peri-operative pain; obstructive airway, acute respiratory depression, cor pulmonale, delirium tremens, seizure disorder, severe CNS depression, increased cerebrospinal or intracranial pressure, head injury, breast-feeding, pregnancy; use during labor and delivery

Actions: Tramadol and its active metabolite (M1) binds to μ-opiate receptors in the CNS causing inhibition of ascending pain pathways, altering the perception of and response to pain; also inhibits the reuptake of norepinephrine and serotonin, which also modifies the ascending pain pathway

Warnings: 

Concerns related to adverse effects:

• Anaphylactoid reactions: Rare but serious anaphylactoid reactions (including fatalities) often following initial dosing have been reported. Pruritus, hives, bronchospasm, angioedema, toxic epidermal necrolysis (TEN), and Stevens-Johnson syndrome also have been reported with use. Previous anaphylactoid reactions to opioids may increase risks for similar reactions to tramadol.

• CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving).

• Seizures: Even when taken within the recommended dosage seizures may occur; risk is increased in patients receiving serotonin reuptake inhibitors (SSRIs or anorectics), other opioids, tricyclic antidepressants or other cyclic compounds (including cyclobenzaprine, promethazine), neuroleptics, MAO inhibitors, drugs which may lower seizure threshold, or drugs which impair metabolism of tramadol (ie, CYP2D6 and 3A4 inhibitors). Patients with a history of seizures, or with a risk of seizures (head trauma, metabolic disorders, CNS infection, malignancy, or during alcohol/drug withdrawal) are also at increased risk.

Disease-related concerns:

• Abdominal conditions: May obscure diagnosis or clinical course of patients with acute abdominal conditions.

• Drug abuse: Use with caution in patients with a history of drug abuse or acute alcoholism; potential for drug dependency exists.

• Ethanol use: Use with caution in heavy alcohol users.

• Head trauma: Use with extreme caution in patients with head injury, intracranial lesions, or elevated intracranial pressure; exaggerated elevation of ICP may occur.

• Hepatic impairment: Use with caution and reduce dosage in patients with mild-to-moderate hepatic impairment; extended release formulations should not be used in severe hepatic impairment (Child-Pugh class C); Ryzolt™ (extended release tablet) should not be used in any degree of hepatic impairment.

• Renal impairment: Use with caution and reduce dosage in patients with mild-to-moderate renal impairment; extended release formulations should not be used in severe renal impairment Cl_cr <30 mL/minute.

• Respiratory disease: Patients with respiratory disorders (eg, significant chronic obstructive pulmonary disease (COPD), cor pulmonale, hypoxia, hypercapnia) may be at greater risk of respiratory depression.

• Suicide risk: Avoid use in patients who are suicidal; use with caution in patients taking tranquilizers and/or antidepressants, or those with an emotional disturbance including depression.

Concurrent drug therapy issues:

• CNS depressants: Use with caution and reduce dosage when administering to patients receiving other CNS depressants; may cause CNS depression and/or respiratory depression.

• Serotonin syndrome: Avoid, if possible, use with serotonergic agents such as TCAs, MAO inhibitors (use with extreme caution; contraindicated in Canadian product labeling), triptans, venlafaxine, trazodone, lithium, sibutramine, meperidine, dextromethorphan, St John’s wort, SNRIs, and SSRIs; use caution with drugs which impair metabolism of tramadol (ie, CYP2D6 and 3A4 inhibitors); concomitant use may increase the risk of serotonin syndrome.

Special populations:

• Debilitated patients: Use with caution in debilitated patients; there is a greater potential for critical respiratory depression, even at therapeutic dosages.

• Elderly: Extended-release formulation should be used with extreme caution in the elderly (particularly >75 years of age); may be more sensitive to adverse effects. Reduce initial dose.

Dosage form specific issues:

• Extended release tablets: Caution patients to swallow tablets whole. Rapid release absorption of tramadol from tablets that are broken, crushed, or chewed may lead to a potentially-lethal overdose.

• Phenylalanine: Some products may contain phenylalanine.

Other warnings/precautions:

• Abuse/misuse/diversion: Healthcare provider should be alert to problems of abuse, misuse, and diversion.

• Withdrawal: Tolerance or drug dependence may result from extended use (withdrawal symptoms have been reported); abrupt discontinuation should be avoided. Tapering of dose at the time of discontinuation limits the risk of withdrawal symptoms.

Monitoring Parameters

Pain relief, respiratory rate, blood pressure, and pulse; signs of tolerance, abuse, or suicidal ideation

Pregnancy Risk Factor  C

Standard Dosing: Oral: Moderate-to-severe pain:

Children ≥17 years and Adults:

Immediate release: 50-100 mg every 4-6 hours (not to exceed 400 mg/day).For patients not requiring rapid onset of effect, tolerability may be improved by starting dose at 25 mg/day and titrating dose by 25 mg every 3 days, until reaching 25 mg 4 times/day. The total daily dose may then be increased by 50 mg every 3 days as tolerated, to reach dose of 50 mg 4 times/day. After titration, 50-100 mg may be given every 4-6 hours as needed up to a maximum 400 mg/day.

Orally-disintegrating tablet (Rybix™ ODT): 50-100 mg every 4-6 hours (not to exceed 400 mg/day); for patients not requiring rapid onset of effect, tolerability may be improved by starting dose at 50 mg/day and titrating dose by 50 mg every 3 days, until reaching 50 mg 4 times/day. After titration, 50-100 mg may be given every 4-6 hours as needed up to a maximum 400 mg/day.

Adults: Extended release:

U.S. labeling: ConZip™, Ryzolt™, Ultram® ER:

Patients not currently on immediate-release tramadol: 100 mg once daily; titrate every 5 days (ConZip™, Ultram® ER) or every 2-3 days (Ryzolt™); maximum dose: 300 mg daily

Patients currently on immediate-release tramadol: Calculate 24-hour immediate release total dose and initiate total extended release daily dose (round dose to the next lowest 100 mg increment); titrate as tolerated to desired effect (maximum: 300 mg daily)

Canadian labeling: Note: Patients currently on immediate-release tramadol: When switching to extended release, initiate at the same or lowest nearest total daily tramadol dose. Not to exceed recommended maximum daily dosing.

Durela™, Ralivia™, Tridural™: Patients not currently on immediate-release tramadol or opioids: Initial: 100 mg once daily; titrate every 5 days (Durela™, Ralivia™) or every 2 days (Tridural™) as needed based on clinical response and severity of pain (maximum: 300 mg daily)

Zytram® XL: Patients not currently on immediate-release tramadol or opioids: 150 mg once daily; if pain relief is not achieved may titrate by increasing dosage incrementally, with sufficient time to evaluate effect of increased dosage; generally not more often than every 7 days (maximum: 400 mg daily)

Elderly >65 years: Use caution and initiate at the lower end of the dosing range

Elderly >75 years:

Immediate release: Do not exceed 300 mg/day; see dosing adjustments for renal and hepatic impairment.

Extended release: Use with great caution. See adult, renal, and hepatic dosing.

Lab Test Interferences

May interfere with urine detection of PCP (false-positive).

Drug interactions: Link: http://www.drugs.com/drug-interactions/tramadol.html 

A total of 660 drugs (3852 brand and generic names) are known to interact with tramadol.

• 349 major drug interactions (1774 brand and generic names)
• 307 moderate drug interactions (2063 brand and generic names)
• 4 minor drug interactions (15 brand and generic names)

Show all medications in the database that may interact with tramadol.

• SSRIs, MAO inhibitors and Tricyclic antidepressants may increase risk of seizure!!!
• Vit K antagonist
• Zolpidem may enhance CNS depressant effect and may increase diuretic effect of thiazide diuretics.
• DO NOT use with alcohol
• CYP3A4 Inducers (Strong): May increase the metabolism of CYP3A4 Substrates. Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Consider therapy modification
• Monitor paitent for respiratory symptoms.  

               THIS IS A SCHEDULE IV DRUG!