PHARM quiz 10 - IBS and analgesic

what is IBS

IBS is chronic large bowel disease characterized by cramping abdominal pain, bloating, and gas. Cause is unknown and is diagnosed of exclusion. Types are IBS-C and IBS-D.

IBS treatment of symptoms

diet (reducing certain carbohydrates)

stress relief

probiotics

medications for IBS-C

• linaclotide (Linzess)

  • binds to intestinal epithelium to accelerate GI transit and increased intestinal fluid

• plecanaide (motegrity)

  • an analog of human uroguanylin

  • binds to intestinal epithelium to accelerated GI transit and increased intestinal fluid

• lubiprostone (amitiza)

  • increase intestinal fluid secretion

medications for IBS-D

• alosetron (lotronex)

  • serotonin receptor antagonist that decreases peristaltic activity

  • can cause ischemic colitis (black box warning)

• dicyclomine (bentyl)

  • anticholinergic agents that has antispasmodic activity that slows peristaltic activity

  • many anticholinergic ADRs

how do emotions influence a patients pain

Pain is influenced by individuals psychological, situational, and emotional state. It is subjective and both a sensation and an emotion

describe the difference between tolerance, physical dependence and addiction

Tolerance- a state in which a larger dose is required to produce the same response that could formerly be elicited by a smaller dose

Dependence- a state in which a withdrawal syndrome will occur if the drug is stopped or if the dose is rapidly reduced (physical and/or mental)

Addiction – a disease manifested by compulsive substance use despite harmful consequences. Characterized by both tolerance and dependence

types of pain

Nociceptive pain- direct stimulation of pain receptor

• Somatic nociceptive pain- arising from skin, bone, joint, muscle, or connective tissue. Well localized pain. Dull, aching, throbbing pain

• Visceral nociceptive pain- arising from internal organs (large intestine or pancreas). Referred or well localized pain. Deep, aching, squeezing

Neuropathic pain- caused by peripheral nerve injury rather than stimulation of pain receptor

PQRST

P – palliative factors/ provocative factors (what makes it better/worse)  

Q – quality (describe pain)

R – radiation (where is the pain and does it move)

S – severity  (scale of 1-10)

T – temporal (time)

how we measure pain

Most common is numeric pain intensity scale

Wong-baker faces pain scale is used for peds and non English speaking

list examples of somatic therapies for pain management: simple, minimally invasive, and invasive

a.      Simple: heat/cold, exercise, massage/ relaxation

b.      Minimally invasive: TENS, acupuncture, ultrasound

c.      Invasive: surgery, radiation, nerve block

psychological therapy in pain management

Psychotherapy, meditation, hypnosis, pt education

Psychological therapies do not change the pain or the injury they only change the perspective and how the person perceives pain

apsirin brand names

ecotrin

ascriptin

bufferin

therapeutic category of aspirin

salicylate NSAID (but not known as a NSAID)

acetylsalicylic acid (ASA)

use, dose, MOA or aspirin

Effective for mild to moderate pain – but used for ANTI PLATELET agent most

Daily dose dependent upon indication

• Low dose (75-81mg for antiplatelet activity)

• Medium dose (650-4000 mg antipyretic and analgesic

• High dose (4000-8000 mg) anti-inflammatory

MOA: inhibits cyclooxygenase and therefore prostaglandins

• Also inhibits platelet cyclooxygenase – which prevents formation of thromboxane A2 and inhibits platelet action permanently. Aspirin dose inhibits all platelets for life of that platelet (why its good)

complications from Aspirin

Gastrointestinal (dyspepsia and irritation or ulceration)

Anticoagulant effects (increase bleeding risk)

Impaired kidney function (from kidney not being perfused)

Salicylism (tinnitus, HA, dizziness)

Reyes syndrome (avoid in children especially concurrent with viral illness)

NSAID category, MOA, and use

Nonsteroidal anti-inflammatory drugs

• Non salicylate NSAID

MOA: inhibits prostaglandin synthesis via the inhibition of both COX 1 and COX 2

Use: analgesic, antipyretic, anti-inflammatory  

• Mild to moderate pain – first line analgesic in many setting

• Large inter-patient variability in therapeutic response to individual NSAIDs

NSAID drug interactions

Anticoagulants (heparin, warfarin), increase risk of bleeding

Glucocorticoids/steroids – increase risk of gastric bleeding/ulceration

Alcohol – increase risk of bleeding

Ibuprofen + low dose aspirin – decreases aspirins antiplatelet effect

NSAID first gen meds

ibuprofen (Advil)

Naproxen (Aleve)

indomethacin (Indocin)

diclofenac (Voltaren)

ketorolac (Toradol

Ketorolac- very potent NSAID, only used for <5 days to treat severe pain  

etodolac (Lodine)

ketoprofen (Orudis)

cautions in NSAIDs

Renal (NSAID induced renal dysfunction)

• Mechanism: inhibition of renal prostaglandin synthesis and vasoconstriction

GI – inhibition of protective effects of prostaglandins on the gastric mucosa

• Minimize risk: H2 receptor antagonist and proton pump inhibitor (maybe misoprostil?)

selective COX 2 inhibitor meds

celecoxib (Celebrex) - full agonist

meloxicam (Mobic) partially selective

MOA, advantages, and disadvantages of COX 2 inhibitors/ 2nd gen NSAID

MOA: selectively inhibit COX 2

Preserves protective effects of prostaglandins on GI mucosa (decrease GI bleeding and ulcer)

Increase risk of adverse cardiac events

acetaminophen MOA, use

MOA: inhibits COX in the brain but not at the peripheral sites – not an anti-inflammatory

Use: analgesic and antipyretic (NO anti-inflammatory or antiplatelet effects)

acetaminophen brand name

tylenol

acetaminophen dosing

max daily doses

acute use (less than a week) : 4 grams/day

chronic use: 3 grams/day

hepatic impairment or heavy alcohol users: 2 or less mg/day

caution of acetaminophen

hepatic impairment or heavy alcohol

topical NSAID products

diclofenac - OTC

ketoprofen or ibuprofen - compounding only

rationale, use, and ADR of topical NSAIDs

Rationale: when used for superficial and localized pain can achieve high local concentrations with low systemic exposure

Use: overall not great with pain relief – acute strain and sprains or hand and knee osteoarthritis

ADRs: skin irritation

rubefacient products

methyl salicylate

rationale, use, ADRs of rubefacients

Rational: cause skin irritation causing blood vessels to dilate which results in feeling warmth. May produce counterirritant effect

Use: no studies showing benefit for acute or chronic pain

ADRs: skin irritation including pain, swelling, or blistering

Capsaicin products

 zostrix, capzasin, salonpas, capsicum patch

rationale, use, and ADRs of topical capsaicin

a.      Rationale: produces mild tingling/burning sensation. Binds to the receptors in the skin responsible for sending signals that cause the perception of pain

b.      Use: no good evidence to support use, high dose used for peripheral postherpetic neuralgia, if relief achieved must use 3-4 times per day

c.      ADRs: itching and rash. Cough, runny nose if particles inhaled. Use gloves or wash hands after use

lidocaine products

aspercreme with lidocaine, solarcaine

topical lidocaine rationale, use, ADRs

a.      Rationale: a topical anesthetic agent that numbs superficial nerves and blocks pain signals. Blocks impulse propagation and thuse dampens pain signal transmission- does not decrease inflammation

b.      Uses: post herpetic neuralgia

c.      ADRs: skin rash, itching, hives

what is the ceiling effect and what class does it apply to

Certain dose is the max and upping the dose will not cause anymore beneficial effects

simple analgesics and partial opioid agonist have a ceiling

black box warning for NSAIDs

a.      Black box warning: increased risk of cardiovascular thrombotic events (myocardial infarction and stroke) and gastrointestinal risk (bleeding, ulceration, and perforation of stomach or intestines) both of which can be fatal

all NSAIDs - be able to identify

Oral

• First gen

  • Ibuprofen, naproxen, indomethacin, diclofenac, ketorolac, etodolac, ketoprofen

• Second gen

  • Celecoxib and meloxicam

Topical

• Diclofenac, ketoprofen, ibuprofen

MOA of opioid analgesics

binds to opiate receptors altering the perception and response to pain

difference between full agonist, partial agonist, and antagonist

Full agonist – intrinsic activity is 1 (max)

Partial agonist – bind receptor but intrinsic activity never reaches 1 (receptor open)

Antagonist – blocks receptor

morphine like analgesics

a.      Morphine

b.      Hydromorphone

c.      Oxymorphone

d.      Levorphanol

e.      Oxycodone

f.        Codeine

g.       Hydrocodone

toxicity associated with meperidine

Active metabolite can cause tremor, muscle twitching, and seizures

Caution in renal impairment and the elderly

rationale for use of methadone in narcotic treatment programs

It has a long duration of action which prevents pts from experiencing the highs and lows and stay at a consistent level controlling addictions

it eliminated withdrawal symptoms by working on the same receptors that narcotics act on

difference in potency and efficacy of analgesics

Potency refers to the strength of a medication – amount of drug it takes to reach effect

Efficacy refers to the drugs capacity to reach a certain effect

advantages and disadvantages of partial opioid agonists

Advantages: less addictive potential and less respiratory depression

Disadvantages: ceiling effect often seen, ADRs- may precipitate withdrawal in opioid tolerant patients

partial agonist meds

pentazocine, butorphanol, nalbuphine, buprenorphine

opioid antagonist meds

Naloxone (narcan)

Naloxone (narcan) actions and uses

Pure antagonist with an affinity for all opioid receptors

If pt is  experiencing overdose due to opioids it will block their action and stop the effects of the overdose temporarily

Can precipitate a severe withdrawal reaction in opioid users

• Shaking, vomiting, rapid breathing, body aches sweating, lay on left side to avoid aspiration

Short duration of action – call 911 when administering

No harm if pt not experiencing an opioid overdose

route of administration of naloxone

IV, SubQ, IM, Nasal (OTC)

side effects associated with opioids

constipation

respiratory depression

drowsiness and sedation

itching and pruritus

nausea and vomiting

constipation treatment and development with opioids

Most common chronic ADR

Tolerance does NOT develop

Differs by agent

Treatment – laxatives (stool softeners or osmotic)

• If laxatives stop working on chronic constipation use naldemedine and naloxegol (these work on peripheral mu receptor antagonists, monitor for opioid withdrawal, abdominal pain, diarrhea, flatulence, and headache)

respiratory depression in relation to opioids

Most serious ADR – occurs if resps drop below 8 breaths per minute

drowsiness and sedation in response to opioid use

Very common during first few days but resolves after about 5-7 days

Different levels of sedation with each opioid – monitor

itching and pruritus treatment and development with opioid use

most common with parenteral administration

can be co administered with antihistamines

nausea and vomiting in relation to opioid use

Stimulates the chemoreceptor trigger zone

Usually at the start of therapy or with increase in dose

Tolerance develops in 7-10 days

Can be treated with antiemetic agents

treatment strategies for opioids

Short acting opioids and long acting opioids

• Long acting used for chronic pain while short acting is used for breakthrough pain

Non-opioid / opioid combination

• Two different mechanisms of action and may require a lower dose of opioid

• Examples: codeine/acetaminophen, hydrocodone/acetaminophen, hydrocodone/ibuprofen, hydrocodone/aspirin

drug interactions associated with opioids

CNS depressants

• Increased respiratory depression and sedation

• Antihistamines, sedatives, anti anxiety

Anticholinergic drugs

• Increased constipation and urinary retention

• Antipsychotics and antidepressants

Hypotensive agents

• Increased hypotension

drug classes that treat neuropathic pain

Tricyclic antidepressants – amitriptyline

Anticonvulsants  - gabapentin

Serotonin and norepinephrine reuptake inhibitors (SNRIs) – duloxetine (FDA approved)

Pregabalin – controlled substance and has anaphylaxis and angioedema warning

muscle relaxants

dantrolene

baclofen

cyclobenzaprine

tizanidine

dantrolene uses and ADR

use: muscle spasms and malignant hyperthermia

ADRs: liver toxicity/failure, CNS (confusion, speech and visual disturbances, seizures, severe sedation), pleural effusion

baclofen uses and ADRs:

Uses: muscle spasms and alcoholism

ADRs: CNS (sedation, dizziness, weakness, fatigue), anticholinergic

Withdrawal syndrome:

1.      Worse with long term use and prevented by titrating dose down prior to stopping (cannot just quit)

2.      Symptoms: visual and auditory hallucinations, delusions, agitation, seizures

cyclobenzaprine uses and ADRs

seizures, arrythmias, anticholinergic effects, CNS depression, sedation

tizanidine uses and ADRs

Uses: back spasms, multiple sclerosis, anticonvulsant

ADRs: liver failure, hypotension, increased spasms, CNS< depression, constipation, diarrhea, stomach pain

reasons for analgesic treatment failure

inappropriate diagnosis or unknown etiology

misunderstanding of pharmacology or pharmacokinetics

adverse effects

fear of addiction

unrealistic goals for therapy

patient barriers

morphine

prototype opioid analgesic

natural substance isolated from the opium plant

first line agent to treat moderate to severe pain

PO, IV, IM, SubQ, PR, IT - versatility

immediate and sustained release formulation

hydromorphone

brand name: dilaudid

used for management of moderate to severe pain

more potent that morphine

IV, IM, SubQ- poor oral absorption

oxycodone

brand names: oxycontin

treatment of moderate to severe pain

immediate and sustained release products

only available PO

2/3 potency to morphine

available as combo products with ASA, APAP, and ibuprofen

fentanyl

brand name: actiq, duragesic, lonsys, fentora

80x potency of morphine but shorter acting than morphine (shortest duration of action of opioids)

used often in anesthesiology as adjunct to geral anesthesia during surgery