Analgesics

pain

* 5th VS
* a SUBJECTIVE experience
* always listen to pt and trust their interpretation

tolerance

when a larger dose is required to produce the same response that could formerly be elicited by a smaller dose

dependence

withdrawal syndrome will occur if drug is stopped/reduced

addiction

compulsive substance use despite harmful consequences, both tolerance and dependence occur

nociceptive pain

* direct stimulation of pain receptors
* somatic: skin, bone, joint, muscle, connective tissue
* dull, aching, throbbing pain
* well-localized pain
* visceral: internal organs (large intestine, pancreas)
* deep, aching, squeezing pain
* referred/well-localized pain

neuropathic pain

caused by peripheral nerve *injury* rather than stimulation of pain receptor

* causes: diabetic peripheral neuropathy, HIV, antiretroviral therapy
* burning, tingling, “pins and needles”
* does not respond well to traditional analgesics
* meds:
* TCAs
* anticonvulsants
* SSNRI
* gaba analog

non-pharmacologic relief

* simple
* heat/cold
* exercise
* massage/relaxation
* minimally invasive
* TENS (electrical nerve stimulation)
* acupuncture
* ultrasound
* invasive
* surgery
* radiation
* nerve block
* psychotherapy (better for chronic pain)
* counseling
* support groups
* meditation
* hypnosis
* pt education

simple analgesics

* for acute to moderate pain
* ceiling effect
* DO NOT produce tolerance/physiological dependence
* majority OTC
* aspirin
* acetaminophen
* NSAIDs

aspirin (salicylated)

* inhibits COX 1 & 2 centrally and peripherally
* decreases prostaglandins & inhibits platelet aggregation
* dose depends on indication
* low → antiplatelet (75-81 mg)
* medium → antipyretic/analgesic (650-4000 mg)
* high → anti-inflammatory (4000-8000 mg)
* primarily used for mild/moderate pain; **antiplatelet agent**

aspirin ADRs

* GI issues (dyspepsia, ulcers)
* anticoagulant, bleeding
* impaired kidney function
* ==**salicylism → tinnitus, HA, dizziness**==
* ==**reye’s syndrome → avoid in children**==

simple analgesic effects

* analgesic - decrease pain
* anti-inflammatory - decrease inflammation
* antipyretic - decrease fever
* anti-platelet - decrease clotting

NSAIDs

* non-salicylated
* inhibits COX 1 & 2, decreases prostaglandin synthesis
* use: analgesic, antipyretic, anti-inflammatory
* mild to moderate pain
* first line analgesic

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NSAID ADRs

* renal dysfunction
* GI inhibition of gastric mucosa
* BLACK BOX:
* MI
* stroke
* GI bleeding/ulcers

2nd gen NSAIDs

* cox-2 inhibitors
* selectively inhibits cox 2
* preserves protective effects of prostaglandins on GI mucosa
* increase risk of adverse cardiac effects (pulled off market)

NSAID interactions

* anticoagulants
* increased bleeding risk
* steroids/glucocorticoids
* increased gastric bleeding/ulceration risk
* alcohol
* increased bleeding risk
* ibuprofen + low dose aspirin
* decreases antiplatelet effect

acetaminophen

* inhibits COX in brain but not a peripheral sites
* use: analgesic, antipyretic, NO anti-inflammatory/antiplatelet effects
* max daily dose
* acute: 4 g
* chronic: 3 g
* caution in hepatic impairment/heavy alcohol users
* limit ≤2 mg/day

acetaminophen ADRs

* minimal!
* BLACK BOX:
* overdose on APAP if also using narcotic combo product
* voted to reduce max daily dose to

topical NSAIDs

* when used for superficial + localized pain → can achieve high local concentration w/ low systemic exposure
* ==for acute **sprain and strains**==
* reduced pain by at least 1/2 in 20-50% people when used for 7 days
* ==for hand and knee **osteoarthritis**==
* reduced pain by at least 1/2 in 10-20% people when used for 6-12 weeks
* ADRs: skin irritation

topical rebufacients

* MOA: causes skin irritation → vasodilation; results in reddening of skin + soothing feeling of warmth
* no studies showing benefit for acute/chronic pain
* ADRs: skin irritation → pain, swelling, blistering
* not common

topical capsaicin

* MOA: binds to receptors in skin responsible for sending signals that cause pain perception
* produced mild tingling/burning sensation
* do not use on broken/irritated skin
* no good evidence to support use
* high-concentration form approved in US for peripheral postherpetic neuralgia (Rx)
* must continue 3-4 days if relief achieved

topical capsaicin ADRs

* 40% experience itching/rash
* cough, runny nose if particles inhaled
* use gloves/thoroughly wash hands

topical lidocaine

* MOA: numbs superficial nerves/blocks pain signals; blocks impulse propagation → dampens pain signal tranmission
* does NOT decrease inflammation
* ==**for post-herpetic neuralgia**==
* ADRs: skin rash, itching, hives

opioids

* MOA: binds to opiate receptors in brain to alter perception of pain
* for moderate to severe pain
* multiple receptor types (mu, kappa, delta, nociceptin)
* no ceiling effect, easily titrated
* ADRs:
* **CONSTIPATION (most common)**
* **RESPIRATORY DEPRESSION**
* drowsiness/sedation
* itching/pruritus
* N/V

morphine

* prototype opioid analgesic
* natural substance from opioid plant
* first line agent for moderate/severe pain
* PO, IV, IM, SQ, PR (rectal), IT (intrathecal)
* immediate/sustained release forms

hydromorphone

morphine-like opioid

* brand - Dilaudid
* moderate/severe pain
* more potent than morphine
* IV, IM, SQ

oxycodone

morphine-like opioid

* brand - Oxycontin
* moderate/severe pain
* immediate/sustained release
* only PO
* 2/3 potency of morphine
* available as combination w/ ASA, APAP, ibuprofen

meperidine

morphine-like opioid

* brand - Demerol
* 1/10 potency of morphine
* shorter duration of action than morphine
* IV, IM, SQ, PO
* ==**active metabolite (normeperidine) can cause tremor, muscle twitching, seizures**==
* ==caution in elderly, pts w/ renal impairment==

fentanyl

morphine-like opioid

* 80x potency of morphine
* shorter acting than morphine
* often used in anesthesiology as adjunct to general anesthesia for surgery
* no PO forms

methadone

* similar potency of morphine
* PO, IV, IM, SQ
* ==delayed onset, longer duration of action==
* used for chronic pain, ***narcotic treatment programs (ex. heroin addiction)***

partial opioid agonists

* stimulates receptor, but not to full degree

advantages

* less addictive potential
* less respiratory depression

disadvantages

* ceiling effect
* ADRs: may precipitate withdrawal in opioid tolerant pts

pure antagonists

* MOA: affinity for all opioid receptors; completely reverses effects of opioid overdose
* ==**rapidly reverses respiratory depression**==
* treats opioid induced pruritus
* intranasal most common form
* IV, IM, SQ available
* short duration of action
* ADRs: severe withdrawal reaction

central analgesics

* MOA: bind to Mu opioid receptors
* less respiratory depression than natural opioids
* very addicting
* ADRs: severe withdrawal reactions

muscle relaxants

* for muscle spasms (involuntary muscle contractions, can cause intense pain)
* causes:
* inadequate blood supply
* dehydration
* pregnancy
* muscle injury/overuse
* neurogenerative disease

central analgesic interactions

* CNS depressants
* increased respiratory depression/sedation
* anticholinergic drugs
* increased constipation/urinary retention
* hypotensive agents
* increased hypotension

adjuvant medications

1. **laxatives**


1. senna + docusate
2. bisacodyl
2. **antihistamines**


1. diphenhydramine
2. hydroxyzine
3. **antiemetics**


1. prochlorperazine
2. promethazine

neuropathic pain

* pain from nerve injury
* causes
* diabetic peripheral neuropathy
* HIV and antiretroviral therapy
* description of pain
* burning, tingling, “pins and needles”
* does not respond well to traditional analgesics
* may require non-analgesic therapy

neuropathic pain treatment

* tricyclic antidepressants
* anticonvulsants
* SSNRIs
* pregabalin

analgesic treatment failure

* inappropriate dx or unknown etiology
* misunderstanding of pharmacology/pharmacokinetics
* adverse effects
* fear of addiction
* unrealistic goals for therapy
* patient barriers

muscle spasms

* involuntary contractions of a muscle/group of muscles
* muscles become tightened/fixed
* intense pain
* causes:
* inadequate blood supply
* dehydration
* pregnancy
* muscle injury/overuse
* neurodegenerative disease
* MS
* MG
* stroke/spinal cord injury

dantrolene

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* interferes w/ the release of calcium ions in skeletal muscle (contraction)
* uses:
* @@**muscle spasms**@@
* @@**malignant hyperthermia**@@

dantrolene ADRs

* ADRs
* liver toxicity/failure
* CNS → confusion, speech/visual disturbances, seizures, severe sedation
* pleural effusion

baclofen

* may involve GABA inhibition
* appears to affect monosynaptic reflexes
* uses:
* @@**muscle spasms**@@
* @@**alcoholism**@@

baclofen ADRs

* ADRs:
* CNS → dizziness, sedation, weakness, fatigue
* anticholinergic
* SEVERE WITHDRAWAL SYMPTOMS

baclofen withdrawal symptoms

* withdrawal syndrome
* worse w/ long term use
* symptoms
* visual/auditory hallucinations
* delusions
* agitation
* seizures
* prevent by slow dose reduction before stopping

cyclobenzaprine

* works in CNS to decrease muscle spasm activity
* no direct effect on muscle function

cyclobenzaprine ADRs

* effects similar to TCAs
* seizures
* arrhythmias
* anticholinergic effects
* CNS depression
* sedation

tizanidine

* central alpha 2 agonist
* uses:
* @@**back spasms (not pain)**@@
* @@**multiple sclerosis**@@
* @@**anticonvulsant**@@

tizanidine ADRs

* ADRs
* liver failure
* hypotension
* increased spasms
* CNS depression
* constipation
* diarrhea
* stomach pain