The science behind the pills that manage pain

We all feel pain differently, depending on the severity of the injury or ache, as well as our health and our pain threshold. When you are in pain, nerve endings transmit the pain signal to the brain via the spinal cord. The brain then interprets the level of pain. There are two key types of painkillers that are commonly used. The first include ibuprofen and paracetamol, which block the body’s ‘prostaglandins’ (chemicals that produce swelling and pain) at the source of the pain, reducing swelling in the area and reducing the intensity of pain. These ‘aspirin medicines’ are used frequently for mild to moderate pain, but they can only work up to a certain intensity of pain. There are different types of painkillers within this group, such as anti-inflammatory medicines, like ibuprofen, which are commonly used to treat arthritis, sprains and strains. Aspirin is used to help lower the risk of blood clots when used in a low dosage, as they thin the blood. Paracetamol is what’s known as an analgesic, which is used for reducing pain and lowering a temperature. The second type of painkillers include morphine and codeine (narcotic medicines), which block the pain messages in the spinal cord and the brain. This is for much more severe pain. As both types of painkillers use slightly different methods to treat pain, they can be combined, such as in co-codamol, which blends codeine and paracetamol.

Pain Medications: Dosage and Indications MEDICATION STANDARD DOSAGE COMMENTS

Abbreviations: CrCl = creatinine clearance; GI = gastrointestinal; HIV-SN = HIV sensory neuropathy; LBP = low back pain; OA = osteoarthritis; PN = peripheral neuropathy; TCAs = tricyclic antidepressants

Acetaminophen 1 g Q6H PRN or 650 mg Q4H PRN Maximum dosage: 4 g per 24 hours or 2 g per 24 hours in patients with comorbid liver disease

First-line analgesia in noninflammatory

mild OA, LBP, mild PN because of

safety profile

Possible adverse effects: hepatotoxicity

(especially if taken with alcohol),

nephrotoxicity (with chronic overdose):

monitor liver and renal function when

using maximal dosages

Use caution and consider reducing total

dosage for patients with comorbid liver

disease or excessive alcohol intake

NSAIDs Ibuprofen

600-800 mg TID PRN for pain

Take with food

Schedule around the clock for

inflammatory condition (eg,

inflammatory OA) or persistent

symptoms

Can titrate up as tolerated and

based on risks to 800 mg TID

Maximum dosage: 3,200 mg/day in

divided doses or 1,800 mg/day for

patients at increased risk of adverse

effects Alternative NSAIDs Naproxen: 250-500 mg BID Sulindac: 150-200 mg BID Celecoxib: 200 mg QD Meloxicam: 7.5 mg QD For chronic pain, use for 2 weeks at initial dosage and reevaluate efficacy; titrate up as needed and if safe; if not effective after a 4-week trial, consider changing NSAID, or adding or changing to another intervention

For persistent noninflammatory and

inflammatory OA, LBP, mild PN

Possible adverse effects: GI bleeding,

abdominal pain, rash and

hypersensitivity, renal and hepatic

impairment, platelet aggregation

abnormalities

Avoid use in patients with peptic ulcer

disease or cirrhosis

Avoid ibuprofen in patients with history

of aspirin-induced asthma

Increased bleeding risk with concurrent

warfarin; if used, monitor closely

Increased risk of renal impairment in

patients on diuretics and those with

baseline renal dysfunction, congestive

heart failure, or cirrhosis

To minimize risks, use the lowest

effective dosage and try to use for short

periods of time

COX-2 inhibitors, such as celecoxib,

have higher risk of cardiovascular events

MEDICATION STANDARD DOSAGE COMMENTS

but fewer GI side effects than

nonselective COX inhibitors

Indomethacin is associated with

increased joint destruction; avoid using

for OA or LBP

Antidepressants: TCAs and others

Amitriptyline Start at 10-25 mg QHS; titrate upward every 3 days by 25 mg to achieve symptom relief, if tolerated; maximum daily dosage is 150 mg (use lower dosages for older patients) Nortriptyline Start at 10-25 mg QHS; titrate upward every 3 days by 25 mg to achieve symptom relief, if tolerated; maximum daily dosage is 150 mg (use lower dosages for older patients)

Consider for patients with comorbid

depression

Consider for neuropathic pain; also as

an adjunct in any type of LBP

unresponsive to acetaminophen and

NSAIDs

Small studies of PN have shown limited

or negative results with antidepressants

Drug interactions: RTV and other PIs

may increase the level of TCAs; start at

low dosage, increase slowly

Monitor serum TCA levels to avoid

cardiotoxicity at higher dosage levels

Possible TCA adverse effects:

anticholinergic (dry mouth, dizziness,

constipation, urinary retention, blurred

vision, orthostatic hypotension),

extrapyramidal symptoms,

incoordination; risk of cardiac conduction

abnormalities and overdose at higher

dosages

For neuropathic pain, other potential

agents include venlafaxine and

duloxetine; these are inadequately

studied in people with HIV infection or

show limited efficacy

Anticonvulsants Gabapentin: start at 300 mg QHS;

may increase every few days, as

tolerated, to achieve symptom relief;

first increase to BID, then TID, then

Consider for PN

Gabapentin: considered first-line for HIV-

SN (SeePeripheral Neuropathy)

Common adverse effects include

nausea, constipation, fatigue,

MEDICATION STANDARD DOSAGE COMMENTS

increase by 300 mg per dose to

maximum of 1,200 mg TID

Pregabalin: start at 25-50 mg TID;

may increase by 25-50 mg per dose

every few days as tolerated to

achieve symptom relief; maximum

dosage: 200 mg TID

Lamotrigine: start at 25 mg every

other day; titrate slowly to 200 mg

BID over the course of 6-8 weeks

somnolence, dizziness, truncal ataxia,

weight gain

To discontinue, taper over course of ≥7

days

Pregabalin: sometimes better tolerated

than gabapentin

Uncertain efficacy in HIV-related PN

Possible adverse effects include

somnolence, constipation, dizziness,

ataxia, and weight gain

To discontinue, taper over course of ≥7

days

Lamotrigine: has shown the greatest

efficacy in clinical trials for HIV-SN

Possible adverse effects: rash (including

Stevens-Johnson syndrome),

cytopenias, dizziness

To discontinue, taper slowly

Drug interactions: LPV/r may decrease

lamotrigine levels; may need to increase

lamotrigine dosage for therapeutic effect

Muscle relaxants (nonbenzo- diazepines)

Cyclobenzaprine (Flexeril) 5-10 mg TID; start with 5 mg doses for elderly patients and those with hepatic impairment; maximum dosage is 30 mg per 24 hours Baclofen 5-10 mg TID or QID; start with 5 mg doses for elderly patients and those with renal impairment; maximum dosage is 80 mg QD in divided doses

May be useful as adjunctive therapy for

acute back pain but not recommended

for chronic or subacute back pain

Common adverse effects include

drowsiness, dry mouth, and dizziness

Severe adverse effects include

arrhythmias, altered mental status, and

seizures

Opiate analgesics Options include: Tramadol (not a typical opiate; exact mechanism of action is unknown; acts in part as a central opioid agonist) Start with 50 mg QAM PRN pain, titrate upward by 50 mg/day every 3 days to 50 mg Q6H Maximum dosage: 400 mg/day, or 300 mg/day if >70 years of age; to

Use opioids for patients who have

severe pain refractory to other

interventions (pharmacologic or

nonpharmacologic) or who cannot

receive those interventions

MEDICATION STANDARD DOSAGE COMMENTS

discontinue, taper dosage in the same way In renal insufficiency with CrCl <30, reduce dose frequency to Q12H, and maximum dosage to 200 mg/day Weak opioids

Codeine

15-30 mg every 4-6 hours; titrate up

by 15 mg every 2-3 days to achieve

pain relief, if tolerated

Maximum dose: 60 mg; take with

food

Hydrocodone + acetaminophen

5 mg/500 mg fixed-dose tablet, 1-2

tablets Q6H PRN pain

Maximum dosage: 12 tablets per 24

hours; 6 tablets for elderly patients

and those with liver disease

Oxycodone + acetaminophen

5 mg/325 mg fixed-dose tablet (other

dosages available), 1-2 tablets Q6H

PRN pain

Maximum dosage: 12 tablets per 24

hours; 6 tablets for elderly patients

and those with liver disease Strong opioids

Morphine (immediate release)

10-30 mg every 3-4 hours PRN pain

Morphine (sustained release)

15-30 mg Q12H as scheduled

Start with weak opioids, assess safety,

efficacy, and usage; titrate up and move

to stronger opioids as needed

Use the lowest effective dosage

Use opioids cautiously in elderly patients

If needed for acute flares, try to limit use

to a designated short period of time

If needed for chronic pain, try to use a

sustained-release opioid (eg, sustained-

release morphine) around the clock, plus

shorteracting opioids (eg, hydrocodone)

for breakthrough pain as needed

Opioid therapy for chronic pain should

use a fixed-dose schedule, not PRN

dosing

Methadone may have utility for

neuropathic pain owing to its action on

NMDA receptors; start at low dosage

and titrate slowly because of its long

half-life; consult with pharmacist

Risk of dependence, overdose

(accidental or deliberate); monitor

closely

Adverse effects include oversedation,

hypotension and respiratory depression,

central nervous system stimulation or

somnolence, dizziness, constipation,

nausea, pruritus

Codeine and morphine can cause

urticarial reactions (hives)

For patients with renal and hepatic

impairment, use low dosages and

monitor carefully

When prescribing opioids, remember to

also give treatment for constipation

(docusate and senna)

MEDICATION STANDARD DOSAGE COMMENTS

doses; if pain control is inadequate,

consider dosing Q8H; may titrate up

by 15-30 mg PRN pain

Oxycodone (immediate release)

5-30 mg Q4H PRN pain

Oxycodone (sustained release)

10 mg Q12H as scheduled doses;

titrate up by 10-20 mg PRN; monitor

carefully

Methadone

Consult with pharmacist

Hydromorphone 2-4 mg Q4H PRN

Fentanyl transdermal

12-100 mcg patch Q72H; a small

proportion of patients will need

dosing Q48H to maintain a stable

blood level

Appropriate only for patients already

on stable dosage of other opiates;

start at equianalgesic (or lower)

dosage; consult with pharmacist;

use for chronic severe pain

Note that tramadol 37.5 mg +

acetaminophen 325 mg has shown pain

relief equivalent to codeine 30 mg +

acetaminophen 325 mg but with fewer

adverse effects (major adverse effect:

headache)

Chronic opioid therapy should

incorporate an opioid use agreement

that includes functional goals for

outcome, not reduction of pain intensity

alone