PHARMACOLOGY N388 Analgesic-Antipyretics-Anti-Inflammatory

Drugs

Janet Raman, EdD, NP-C, RN, CEN, CNE

PAIN

• What is pain?– Sensation of discomfort, hurt, or distress– JCAHO: the “FIFTH VITAL SIGN”– Pain is reported by the patient (subjective)– Most common cause for seeking health care– Relieve pain asap– Anticipate pain and prevent or reduce whenever

possible

NERVOUS SYSTEM REVIEW

Anatomy:• The nervous system is a network of nerve cells

called neurons and supporting cells called ganglia • CNS is composed of the brain and spinal cord, the

PNS is made up of all other neurons and ganglia including the cranial nerves which extend to the face, tongue, and nose

• The brain is a concentrated network of neurons

NERVOUS SYSTEM REVIEW

Anatomy- Neurons

NERVOUS SYSTEM REVIEW

Functions:• Sensory perception (the 5 senses)• Motor function (voluntary and involuntary

movement)• Higher brain functions eg. the limbic system,

language interpretation, etc., which involve the integration of large amounts of information from various stimuli

• The Limbic system plays a role in regulating emotions

NEUROTRANSMITTERS

• Neurotransmitters are molecules that are used to communicate information between neurons to activate or suppress biological functions

• Specific neurotransmitters are associated with specific biological responses

• Acetylcholine causes salivation, lacrimation, urination, and defecation

• Serotonin modulated mood and plays an important role in psychiatric illness

NEUROTRANSMITTERS ASSOCIATED WITH PAIN

• Prostaglandins– Sensitize neurons to painful stimuli

• Endorphins (endogenous morphine)– Block painful stimuli and stimulate pleasure

centers in the brain• GABA (gamma amino butyric acid)

– Reduces neuronal hyperexcitability related to epilepsy and neuropathic pain

TYPES OF PAIN- NOCICEPTIVE PAIN

Nociceptive Pain can be either• Somatic, that is pain that arises from skin, bone,

joint, muscle, or connective tissue-OR-

• Visceral pain which arises from internal organs such as the large intestine or pancreas. Visceral pain often results in a phenomena known as “referred pain” where pain is felt in areas other than source, eg. during MI pain radiates down left arm

TYPES OF PAIN- NOCICEPTIVE PAIN

We are all familiar with the experience of nociceptive pain. A stubbed toe, broken bone, headache, or burn on the skin are all sources of nociceptive pain.

NOCICEPTIVE PAIN- HOW IT WORKS

Stimulation:• Nociceptors, which are sensory neurons, exist

throughout the body. They are activated or sensitized by mechanical, thermal, and chemical impulses. Examples of chemical stimuli are prostaglandins and Substance P.

Transmission:• Receptor activation leads to action potentials that are

transmitted along afferent nerve fibers to the spinal cord brain

NOCICEPTIVE PAIN- HOW IT WORKS

Pain perception:• Pain is experienced once the signals have

reached the brain.• The intensity of the pain experienced is

influenced by psychological factors• Relaxation and distraction can lessen pain• Anxiety and depression can worsen pain

NOCICEPTIVE PAIN- HOW IT WORKS

Modulation:• The body releases endorphins (endogenous

morphine) to reduce painInflammation:• Damaged tissue becomes inflamed which

promotes healing but is painful itself. Although inflammation serves a biological purpose, in medicine we usually reduce the pain associated with inflammation using NSAIDS

TYPES OF PAIN- NEUROPATHIC PAIN

Neuropathic pain is pain that arises from the nerves themselves. Often does not involve noxious stimuli. Patients present with pain that is described as burning, stinging, or shooting. Diseases associated with neuropathic pain include diabetic neuropathy and postherpetic neuralgia.

TYPES OF PAIN- NEUROPATHIC PAIN

Occasionally neuropathic pain is the result of complex neurophysiological processes. This is termed “learned pain” and is evident in phantom limb patients.

http://www.youtube.com/watch?v=gc3CmS8_vUI&feature=related

REFERRED PAIN

ACUTE VS CHRONIC PAIN

Acute pain• Usually nociceptive but can be neuropathic• Common causes include: illness, surgery,

trauma, laborChronic pain• Can be nociceptive, neuropathic, or both.• Causes include: fibromyalgia (neuropathic),

cancer pain

PAIN RELIEF- NONPHARMACOLOGICAL

• Rest• Hot/cold compresses• Massage• Psychological support• Music• Humor• Aromatherapy

PAIN RELIEF- TOPICAL AGENTS

• Used for minor aches and pains• Work by distracting peripheral nerves from

painful stimuli• Examples: Capsaicin (Zostrix®), Menthol (Mineral

Ice® and Bengay®), Lidocaine patch (Lidoderm®)• Not to be confused with agents applied topically

for systemic absorption such as fentanyl or diclofenac patches or diclofenac gel

PAIN RELIEF- NSAIDS

NSAIDS or Non-steroidal anti-inflammatory drugs are an important class of drugs used to treat mild to moderate pain. Members of this class include ibuprofen, naproxen, meloxicam, aspirin, and many others. Agents vary in duration of action: ibuprofen works for 4-6 hours, naproxen for 12 hours, meloxicam and celebrex for 24 hours.

*Avoid ASA in children (Reye’s Syndrome)

PAIN RELIEF- NSAIDS

MOA: Inhibit the formation of prostaglandins (which cause pain) and thromboxanes (which cause inflammation)

SE: Stomach ache, stomach ulcer, rarely can cause blood dyscrasias (instruct patients to take with food)

CI: patients with stomach ulcers, allergy to NSAIDS. Used with caution in the elderly due to ↓ kidney function (NSAIDS are renally excreted)

Notable agents: Celebrex and meloxicam cause less stomach irritation. Toradol is the only IV NSAID. Diclofenac is available as a topically applied gel.

PAIN RELIEF- ACETAMINOPHEN

Also used for mild to moderate pain, however NOT useful for treating inflammation.

MOA: inhibits synthesis of prostaglandins but not thromboxanes

SE: hepatotoxicityCI: patients with liver disease, safer to use in the

elderly than NSAIDS*Note both NSAIDS and acetaminophen are also

have antipyretic properties

Maximum Doses• Acetaminophen: 4g/d (3kg/lifetime)• Motrin: 3200mg/d

Antidote for Acetaminophen• Mucomyst: acetylcysteine

PAIN RELIEF- OPIOIDS

Used for moderate to severe nociceptive or neuropathic pain. Members of this class include codeine, hydrocodone (in Vicodin®), oxycodone, morphine, methadone, fentanyl, and meperidine. All have a short duration of action of about 4 hours except for methadone.

* When first taking methadone the duration of action is about 4 hours, after repeated doses the duration of action approaches 24 hours.

PAIN RELIEF- OPIOIDS

Listed in descending order of strength:1. morphine, hydromorphone (Dilaudid®),

oxycodone, fentanyl, methadone2. Hydrocodone, codeine3. Tramadol

PAIN RELIEF- OPIOIDS

MOA: binds to opiate receptors in the CNS, altering the perception and response to pain

SE: constipation, drowsiness, euphoria, hives, dependence/addiction, respiratory depression in overdose

CI: since hydrocodone, oxycodone, morphine and others are structurally similar, an allergy to one of these agents will exclude all opioids as treatment options except for methadone, fentanyl, and meperidine which are structurally dissimilar to the rest of them. Drug addiction is not a CI for receiving opiates.

PAIN RELIEF- OPIOIDS

Opioid dosing for chronic pain• Patients with chronic pain experience what is

called “breakthrough pain”, or a spike in intensity of pain from their baseline

• Chronic pain patients usually receive a long acting extended release product such as Oxycontin ® or Fentanyl patches to be administered routinely as well as an instant release agent for breakthrough pain administered as needed

METABOLISM• Oral=first pass• Metabolized in liver• Excreted via kidneys• CNS Depression/Respiratory Depression (Fatal

Overdose/Resuscitative Equipment)• GI System: decreased motility• Binds to opioid receptors in Brain, Spinal Cord,

Peripheral Tissues• Opioid Effects: Analgesia, CNS

Depression,Sedation, Pupillary Constriction, Euphoria, Physical Dependence)

Routes for Opioid Analgesics• Oral (tablets-fast and slow release, elixir)• Buccal • Lollipop • SL• SC• IM• Intrathecal• Epidural• Transdermal

CONTRAINDICATIONS• Liver Dx• Kidney Dx• Premature Infants• Increased Intracranial Pressure• Prostatic Hypertrophy(relative contraindications)

MORE ON OPIOIDS• CODEINE: Analgesic/Antitussive• FENTANYL (Sublimaze): More Potent IV, IM, Transdermal Transdermal: Ionsys: short-term tx, (PCA) Electric Current Duragesic: slow onset (12-24h) lasts 72 hours then, lasts another 24 hours **Look for Fentanyl patches*** When assessing patient AMS Respiratory Depression/Arrest Applying another patch

MORE ON OPIOIDS• Hydrocodone (Vicodin:Hydrocodone/Tylenol)• Hydrocodone (Zohydro ER), no Tylenol, great abuse potential• Hydrodmorphone (Dilaudid)• Meperidine (Demerol): Dirty Drug• Methadone (Dolophine): synthetic, long-acting used in severe pain (think Cancer) detox and maintenance (Heroin Addicts) very difficult to resuscitate individual in OD• Oxycodone (Percocet:Oxycodone/Tylenol) OxyContin: slow-release product: popular drug of

abuse, easy to overdose when crushed, snorted or injected• Propoxyphene (Darvon, Darvocet OFF THE MARKET)• Tramadol (Ultram) oral, synthetic, became a controlled

substance in NY 2013-opioid-like, less respiratory depression

OPIOID ANTAGONISTS

• Naloxone (Narcan ®) and Naltrexone• Knocks opioids off the receptor• Used in cases of overdose

OPIOID ANTAGONIST• Naloxone (Narcan): Antidote Titrate dose to reverse effects of opioid drug Give cautiously to opioid abusers Suspect opioid overdose?Check Blood GlucoseCheck for brain injuryCheck for ETOHEvzio: Naloxone autoinjection system for

emergency home use

ABUSE DETERRANT OPIOIDS

• Oxycodone hydrochloride and Naloxone hydrochoride ER (Targiniq ER):

For patients who need daily, round-the-clock, long term opioid treatment

When taken orally will not deter abuse, but when crushed, snorted or injected, the naloxone will block euphoria

Can still cause respiratory depression when overdosed

ABUSE DETERRANT OPIOIDS

• Morphine Sulfate and Naltrexone HCL (Embeda ER)

For management of severe pain Deters oral and Intranasal abuse when crushed Not sure yet if it will deter IV abuse• Hydrocodone Bitartrate (Hysingla ER): Hard to crush Turns into a thick gel when someone tries to

dissolve it to make an injectable liquid

PATIENT TEACHING• Support use of nonpharmacologic interventions• Support use of non-narcotic pain relievers• Watch upper limits of “harsh” drugs, especially in

combination-individuals don’t always know what they are taking..or mixing with OTC meds

• Avoid ETOH• Avoid using with meds that also cause drowsiness such

as antihistamines• Maintain safety:consider not smoking, driving, operating

heavy machinery• Maximize pain relief experience• Stay well-hydrated, avoid constipation

DRUG, ROUTE, DOSE SELECTION

Prescriber should start low and slow so there is room to go

No person should suffer pain needlesslyIndividuals should have whatever they

need Titrate upDependency rarely results from

medications taken for physical painRN is patient advocate for pain relief

NURSING ACTIONS• Medications can be given in combination (long acting, with meds for break through

pain)• Round-the-clock vs PRN (intervals not

written in stone)• Non-ceiling drug• Watch for tolerance

SPECIAL POPULATIONS• Drug Abusers• Elderly• Peds

BONE PAIN

Causes:• Osteoarthritis, Paget’s disease, bone cancer

Treatment:• Bisphosphonates

» The same class of drugs that’s used to treat osteoporosis• Steroids

PAIN RELIEF- NEUROPATHIC AGENTS

Lyrica® (pregabalin) and Gabapentin• Used for diabetic peripheral neuropathy, fibromyalgia,

postherpetic neuralgia (also used for epilepsy)• MOA: ↓ neuronal excitability• *Actual MOA is complicated and not fully understood

to date. For this class just understand that they calm nerves down.

• SE: Dizziness, headache, drowsiness• SE are largely dose dependent and patients receive a wide range

of doses (pregabalin 50-600mg/day, gabapentin 300-1800mg/day)

PAIN RELIEF- NEUROPATHIC AGENTS

Cymbalta® (duloxetine) and other antidepressants• Can be used for neuropathic pain which is

increasingly believed to have a depression component

• MOA: blocks the reuptake of serotonin (Cymbalta also blocks the reuptake of norepinephrine)

• SE: ↓libido, erectile dysfunction, can cause either drowsiness or insomnia

ADMINISTRATION

• Nurses are patient advocates for pain relief• Monitor for pain and monitor for adverse effects such

as oversedation with opioids.• Many opiates come as oral tablets, other forms

include IV morphine which is often administered by the patient using a PCA or “patient controlled analgesia” device. Fentanyl is also available as a patch and in lozenges.

• *Fentanyl and meperidine are also available for IV use

PAIN LADDER

MONITORING- PATIENT REPORTING PAIN SCALE

MONITORING- PATIENT REPORTING PAIN SCALE

PCA

Patient-Controlled Analgesia

NCLEX-RN STYLE QUESTION

After administering acetylcysteine (Mucomyst) to a client who overdosed on acetaminophen (Tylenol), a nurse should recognize which outcome as an indicator of the therapeutic effects of acetylcysteine?

• Absence of jaundice • Clear breath sounds• Increased bowel sounds• Palpable pedal pulses

QUESTIONS???