You are in: eMedicine Specialties > Neurology > Neurological Infections HIV-1 Associated Distal Painful Sensorimotor PolyneuropathyArticle Last Updated: Feb 23, 2007AUTHOR AND EDITOR INFORMATIONSection 1 of 10
  Author: Niranjan N Singh, MD, DNB, Fellow in Neurophysiology, Department of Neurology, St Louis University School of Medicine Niranjan N Singh is a member of the following medical societies: American Academy of Neurology Coauthor(s): Florian P Thomas, MD, MA, PhD, Drmed, Director, Spinal Cord Injury Unit, St Louis Veterans Affairs Medical Center; Director, National MS Society Multiple Sclerosis Center; Associate Program Director, Professor, Department of Neurology and Psychiatry, Associate Professor, Institute for Molecular Virology, and Department of Molecular Microbiology and Immunology, St Louis University Editors: William J Nowack, MD, Associate Professor, Department of Neurology, Epilepsy Center, University of Kansas Medical Center; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; Glenn Lopate, MD, Associate Professor, Department of Neurology, Division of Neuromuscular Diseases, Washington University School of Medicine; Chief of Neurology, St Louis ConnectCare, Consulting Staff, Barnes Jewish Hospital; Selim R Benbadis, MD, Professor, Director of Comprehensive Epilepsy Program, Departments of Neurology and Neurosurgery, University of South Florida School of Medicine, Tampa General Hospital; Nicholas Y Lorenzo, MD, Chief Editor, eMedicine Neurology; Consulting Staff, Neurology Specialists and Consultants Author and Editor Disclosure Synonyms and related keywords: acquired immunodeficiency syndrome, AIDS, HIV-1 associated peripheral neuropathy, HIV infection, neurotoxic drugs, vitamin deficiencies, nutritional deficiencies, drug toxicity, didanosine, stavudine, zalcitabine, lamivudine INTRODUCTIONSection 2 of 10
  BackgroundA distal painful sensorimotor polyneuropathy is the most common type of HIV-1 associated peripheral neuropathy. It usually develops during late HIV infection. PathophysiologyMore than one pathophysiologic mechanism likely exists:
FrequencyUnited StatesDistal painful sensorimotor polyneuropathy is clinically apparent in 10-30% of patients with AIDS. Subclinical forms occur in many more patients who are HIV positive. It is found at autopsy in almost 100% of patients with AIDS. The prevalence of distal painful sensorimotor polyneuropathy continues to rise because of increased life expectancy in the HAART era. SexDistal painful sensorimotor polyneuropathy is more prevalent in males than in females. AgeDistal painful sensorimotor polyneuropathy is more common in persons older than 50 years. It rarely occurs in children. CLINICALSection 3 of 10
History
Physical
DIFFERENTIALSSection 4 of 10
Acute Inflammatory Demyelinating Polyradiculoneuropathy Chronic Inflammatory Demyelinating Polyradiculoneuropathy Diabetic Neuropathy HIV-1 Associated Multiple Mononeuropathies Nutritional Neuropathy Toxic Neuropathy Uremic Neuropathy Vitamin B-12 Associated Neurological Diseases
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| Drug Name | Amitriptyline (Elavil) |
|---|---|
| Description | Increases synaptic concentration of serotonin and norepinephrine by reuptake inhibition at presynaptic neuronal membrane; dose may be increased slowly, until pain relief or intolerable side effects occur; doses >125 mg qhs rarely are helpful; if no response, a different TCA may be tried, but drugs from a different category such as anticonvulsants are usually preferable. |
| Adult Dose | Starting dose: 10-25 mg PO qhs; increase prn, as tolerated, in 3-7-d intervals and 25-mg steps up to 125 mg PO qhs; >75 mg obtain ECG before each further dose increase to rule out AV block |
| Pediatric Dose | Children: 0.1 mg/kg PO qhs; increase, as tolerated, over 2-3 wk to 0.5-2 mg/kg PO qhs Adolescents: Starting dose of 25 mg PO qhs; increase gradually to 100 mg qhs |
| Contraindications | Documented hypersensitivity; in patients with AV block or who have taken MAOIs or fluoxetine in the past 14 d |
| Interactions | Metabolized by the P 450 2D6 system; drugs that inhibit this enzyme system (eg, cimetidine, quinidine) may increase tricyclic levels; phenobarbital may increase metabolism of amitriptyline and decrease efficacy; blocks uptake of guanethidine and prevents its hypotensive actions; may interact with thyroid medications, alcohol, CNS depressants, barbiturates, and disulfiram |
| Pregnancy | D - Unsafe in pregnancy |
| Precautions | Caution in patients with seizures, renal or hepatic impairment, cardiac disease, conduction disturbances, cognitive impairment, urinary retention, hyperthyroidism, or who receive thyroid hormones; particular caution in older patients; less sedative drugs may be tolerated better |
| Drug Name | Nortriptyline (Aventyl HCl, Pamelor) |
|---|---|
| Description | Demonstrated effectiveness in neuropathic pain; increases synaptic concentration of serotonin and norepinephrine by reuptake inhibition at presynaptic neuronal membrane; additional pharmacodynamic effects such as desensitization of adenyl cyclase and downregulation of beta-adrenergic and serotonin receptors appear to be involved. |
| Adult Dose | Starting dose: 10-25 mg PO qhs; increase prn, as tolerated, in 3-7 d intervals and in 25-mg steps to about 125 mg qhs; >75 mg obtain ECG before each further dose increase to rule out AV block |
| Pediatric Dose | 25-35 kg: 10-20 mg PO qhs 35-54 kg: 25-35 mg PO qhs |
| Contraindications | Documented hypersensitivity; in patients with AV block or who have taken MAOIs or fluoxetine in the past 14 d |
| Interactions | Cimetidine may increase levels when used concurrently; may increase PT in patients on warfarin |
| Pregnancy | D - Unsafe in pregnancy |
| Precautions | Caution in patients with seizures, renal or hepatic impairment, cardiac disease, conduction disturbances, cognitive impairment, urinary retention, hyperthyroidism, or who receive thyroid hormones; particular caution in older patients; less sedative drugs may be tolerated better |
| Drug Name | Desipramine (Norpramin) |
|---|---|
| Description | Useful for neuropathic pain; may increase synaptic concentration of norepinephrine by reuptake inhibition at presynaptic neuronal membrane; may desensitize adenyl cyclase and downregulate beta-adrenergic and serotonin receptors. |
| Adult Dose | Starting dose: 10-25 mg PO qhs; increase prn, as tolerated, in 3-7 d intervals and in 25-mg steps to about 125 mg PO qhs; >75 mg obtain ECG before each further dose increase to rule out AV block |
| Pediatric Dose | <12 years: Not established >12 years: Initially 25 mg PO qhs; gradually increase to 100 mg PO qhs |
| Contraindications | Documented hypersensitivity; in patients that have taken MAOIs or fluoxetine in the past 14 d |
| Interactions | Decreases antihypertensive effects of clonidine but increases effects of sympathomimetics and benzodiazepines; phenytoin, carbamazepine, and barbiturates decrease effects |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| Precautions | Caution in patients with seizures, renal or hepatic impairment, cardiac disease, conduction disturbances, cognitive impairment, urinary retention, hyperthyroidism, or who receive thyroid hormones; particular caution in older patients |
Gabapentin alleviates painful dysesthesias and spasms. It is well tolerated with a wide dose range. Drug levels are not available, indicated, or meaningful. Lamotrigine has been shown to be effective in distal painful sensorimotor polyneuropathy but not ATN.
| Drug Name | Gabapentin (Neurontin) |
|---|---|
| Description | Shares pharmacologic properties with other anticonvulsants; exact mechanism of action is unknown; structurally related to GABA but does not interact with GABA receptors. |
| Adult Dose | Start at low dose as described to minimize side effects: Day 1-3: 300 mg PO qd Day 4-6: 300 mg PO bid Day 7-9: 300 mg PO tid Day 10-12: 600 mg PO qam, 300 mg PO qpm, 300 mg PO qhs Day 13-15: 600 mg PO qam, 300 mg PO qpm, 600 mg PO qhs Day >16: 600 mg PO tid Following this regimen, increase prn, as tolerated, not to exceed 1200 mg PO tid; younger, otherwise fairly healthy individuals often tolerate faster dose increase; dose needs to be adjusted for renal impairment |
| Pediatric Dose | <12 years: Not established >12 years: Administer as in adults |
| Contraindications | Documented hypersensitivity |
| Interactions | Antacids may reduce bioavailability of gabapentin by about 20%; administer at least 2 h after antacid administration; cimetidine may reduce gabapentin clearance but this may not be of clinical significance; may increase norethindrone levels by 13% |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| Precautions | Caution in patients with severe renal disease; may cause sedation, although less commonly than with tricyclic antidepressants; occasionally efficacy decreases after several weeks; may necessitate further dose increase |
| Drug Name | Carbamazepine (Tegretol, Carbatrol, Epitol) |
|---|---|
| Description | Has antineuralgic effects; may depress activity of the nucleus ventralis of the thalamus or decrease synaptic transmission or summation of temporal stimulation by limiting influx of sodium ions across cell membrane or by other unknown mechanisms. |
| Adult Dose | Initial dose: 200 mg PO bid; increase gradually prn over 2-wk interval to 200 mg PO tid; target blood serum concentrations are 4-12 mg/L Sustained release dosing: Therapeutic dose bid |
| Pediatric Dose | <6 years: Initially 10-20 mg/kg/d PO; titrate dose prn 6-12 years: Initially 100 mg PO bid; titrate dose prn >12 years: Initially 200 mg PO bid; titrate dose prn |
| Contraindications | Documented hypersensitivity; bone marrow suppression; MAOIs |
| Interactions | May interact with many drugs including cyclosporine, oral contraceptives, TCAs, warfarin, phenytoin, doxycycline, neuroleptics, fentanyl, calcium channel blockers, macrolide antibiotics, isoniazid, cimetidine, lamotrigine, and propoxyphene |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| Precautions | Discontinue MAOIs for a minimum of 14 d before carbamazepine is begun; caution in patients with history of cardiac damage or hepatic disease; blood cell abnormalities have been reported following treatment with this medication; check CBC once or twice a year; may worsen seizures in persons with primary generalized epilepsy and atypical absence seizures; 0.5-1% risk of spina bifida in children born to mothers who take carbamazepine during pregnancy |
| Drug Name | Lamotrigine (Lamictal) |
|---|---|
| Description | Triazine derivative useful in treatment of neuralgia. Inhibits release of glutamate and inhibits voltage-sensitive sodium channels, which stabilizes neuronal membrane. Follow manufacturer's recommendation for dose adjustments. |
| Adult Dose | Monotherapy: 50-100 mg/d PO divided bid initial dose; 100-400 mg/d PO qd or divided bid maintenance; not to exceed 500 mg/d Adjunct therapy with valproic acid: 25 mg PO qod initial dose; 50-200 mg/d PO qd or divided bid maintenance; not to exceed 200 mg/d |
| Pediatric Dose | 2-12 years: Monotherapy Weeks 1-2: 0.6 mg/kg/d PO divided bid, rounded down to nearest 5 mg Weeks 3-4: 1.2 mg/kg/d PO divided bid, rounded down to nearest 5 mg Maintenance: 5-15 mg/kg/d PO; not to exceed 400 mg/d divided bid; to achieve usual maintenance dose, increase subsequent doses q1-2wk as follows: calculate 1.2 mg/kg/d and round down to nearest 5 mg; add this amount to previously administered daily dose Concomitant therapy with valproic acid >12 years: Concomitant therapy with valproic acid Weeks 1-2: 25 mg PO qod |
| Contraindications | Documented hypersensitivity |
| Interactions | Acetaminophen increases renal clearance of medication, decreasing effects; similarly, phenobarbital and phenytoin increase lamotrigine metabolism, causing a decrease in lamotrigine levels; administration of valproic acid with lamotrigine increases half-life; succinimide anticonvulsants (eg, methsuximide, phensuximide) decrease lamotrigine levels |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| Precautions | Use appropriate dosing if used concurrently with valproic acid; caution in impaired renal or hepatic function; need to warn patients of potential rash (Stevens-Johnson syndrome) |
These agents are used to induce localized analgesia.
| Drug Name | Lidocaine (Lidoderm 5% patch) |
|---|---|
| Description | Several recent studies have advocated topical administration of lidocaine as treatment of PHN. In placebo-controlled study, lidocaine gel (5%) showed significant relief in 23 patients. By contrast, The Lidoderm-HIV Neuropathy Group showed that lidocaine 5% gel was ineffective in the treatment of pain associated with HIV distal painful sensorimotor polyneuropathy. |
| Adult Dose | Apply to affected area prn Leave on for 12 h, then remove patch for 12 h between applications |
| Pediatric Dose | Not established |
| Contraindications | Documented hypersensitivity to amide-type local anesthetics; avoid in Adams-Stokes syndrome and Wolf-Parkinson-White syndrome; avoid in severe sinoatrial, atrioventricular (AV), or intraventricular block, if artificial pacemaker not in place |
| Interactions | Coadministration with cimetidine or beta-blockers, increases toxicity of lidocaine; coadministration with procainamide and tocainide may result in additive cardiodepressant action; may increase effects of succinylcholine |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| Precautions | Use a solution without preservatives; caution in heart failure, hepatic disease, hypoxia, hypovolemia or shock, respiratory-depression and bradycardia; may increase risk of CNS and cardiac side effects in elderly persons; high plasma concentrations can cause seizures, heart block, and AV conduction abnormalities |
| Drug Name | Capsaicin (Dolorac, Zostrix) |
|---|---|
| Description | Natural chemical derived from plants of Solanaceae family. Penetrates deep for temporary relief of minor aches and pains of muscles and joints associated in inflammatory reactions. May render skin and joints insensitive to pain by depleting substance P in peripheral sensory neurons. Has demonstrated effectiveness in several studies of diabetic neuropathic pain and in other types of neuropathic pain. |
| Adult Dose | Apply to affected area tid/qid for 3-4 consecutive wk and evaluate efficacy; not to exceed 4 applications/d; wash hands with soap and water after applying |
| Pediatric Dose | Not established |
| Contraindications | Documented hypersensitivity; broken or irritated skin |
| Interactions | None reported |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| Precautions | For external use only; avoid contact with eyes; do not use tight bandage; discontinue use if condition worsens or symptoms persist for 14-28 d |
HIV-1 Associated Distal Painful Sensorimotor Polyneuropathy excerpt
Article Last Updated: Feb 23, 2007
