SG 5: GIT & Pain management Flashcards
GERD therapeutic goals
- alleviate symptoms
- promote esophageal healing
- prevent recurrence
- avoid long-term complications.
One long-term consequence is Barrett’s esophagus, or Barrett’s metaplasia, which is identified in 10% to 15% of GERD patients on endoscopic evaluation. This premalignant condition may predispose the patient to esophageal adenocarcinoma. GERD is a chronic disease that carries the potential for serious complications.
What pharmacological therapies are available for GERD?
- Medications that suppress gastric acid production are the mainstay of GERD therapy:
- Antacids: do not prevent GERD. Therefore their role is limited to on-demand use for relief of mild GERD symptoms that occur less than once a week.
- H2-RECEPTOR BLOCKERS (H2RAs): Cimetidine, Ranitidine, Famotidine, Nizatidine
- PPI: Omeprazole, etc…
- Metoclropramide
- Sucralfate
Metoclopramide MOA
Metoclopramide may provide relief of symptoms of GERD but is ineffective in healing erosive esophagitis. It is less effective than PPIs and H2Ras and is now rarely used in this setting. The mechanism of action of metoclopramide is as follows:
- It facilitates acetylcholine release from enteric neurons;this action maybe mediated indirectly by several different mechanisms, including antagonism at 5- HT3 receptors and activation of 5-HT4 receptors.
- central and peripheral D2 antagonist. The central antidopaminegic action is responsible for its antinauseant and antiemetic properties; the peripheral antidopaminergic action contributes to its prokinetic activity.
DIAGNOSTIC TESTING FOR H PYLORI
ENDOSCOPIC TESTING
- Histology: Gold standard
- Rapid urease test: detects pH changes due to presence of bacterial urease cleaving urea to CO2 and ammonia.
- Culture: used mainly for antibiotic sensitivity testing to detect resistant organisms.
NONENDOSCOPIC TESTING
- Serum antibody testing: useful in ruling out the diagnosis; not reliable (because of persisting antibodies) in documenting eradication.
- Urea breath test: patient ingests a urea solution labeled with a carbon isotope C-13 or C-14. Isotopes detected by a MS or scintillation counter, respectively.
- Fecal antigen test:
What are the regimens available for eradication of H pylori?
- Typically antibiotics plus PPIs.
- PPIs suppress H. pylori, and the increased gastric pH accompanying their use can enhance tissue concentration and efficacy of antimicrobials, creating a hostile environment for H. pylori.
- 1st-line regimen: PPI plus clarithromycin, and either amoxicillin or metronidazole. The recommended duration of treatment in the US is 14 days. International guidelines recommend 7-10 days. These treatments cure infection in > 95% of cases. 10 to 14 d
- Quadruple therapy: PPI, tetracycline and bismuth subsalicylate and metronidazole. 10 to 14 d
What are the potential renal adverse effects of NSAIDs?
Decrease In Renal Blood Flow
NSAIDs have little effect on renal function or blood pressure in normal human subjects. However, in patients with congestive heart failure, chronic kidney disease, and other situations in which there is reduced renal perfusion (due to vasoconstriction stimulated by angiotensin II, vasopressin, or norepinephrine), synthesis of vasodilating PGs (PGE2 and PGI2) becomes crucial in maintaining GFR. NSAID-induced decreases in PGs may lead to sodium and water retention, edema, increased blood pressure, hyperkalemia, and acute renal failure.
Analgesic Nephropathy
Analgesic nephropathy is a condition in which chronic interstitial nephritis is caused by prolonged and excessive consumption of analgesics, particularly combinations of different agents. The use of the NSAID phenacetin, which is no longer available, was particularly associated with analgesic nephropathy.
What is the treatment for A.D.’s gastric ulcer?
- NSAIDs should be stopped if at all possible and therapy with a PPI or an H2 antagonist started. Due to their effectiveness as once a day therapy and rapid healing rates, PPIs are usually the drugs of choice.
- The patient’s H. pylori status should also be assessed (if not done previously); if positive, appropriate therapy should be instituted.
- For patients who must remain on NSAID therapy, PPIs are the drugs of choice.
- For mild to moderate pain, acetaminophen can be used instead of the NSAID. If antiinflammatory action is needed for her arthritic knee, a COX2 selective NSAID should be considered.
Risk for NSAID GI toxicity
High risk
- History of a previously complicated ulcer, especially recent
- Multiple (>2) risk factors
Moderate risk (1 – 2 risk factors)
- Age >65 years
- High-dose NSAID therapy
- A previous history of uncomplicated ulcer
- Concurrent use of aspirin (including low dose) corticosteroids or anticoagulants
Low risk
- No risk factors
NSAID GI toxicity management
High Risk Patients
Among high risk patients it is best to avoid NSAID treatment entirely; however, if anti-inflammatory treatment must be used, a COX-2 inhibitor plus misoprostol or PPI should be employed.
Moderate Risk Patients
Patients at moderate risk can be treated with a COX-2 inhibitor alone or a traditional nonselective NSAID plus misoprostol or a PPI.
Low Risk Patients
Patients without risk factors can be treated with a nonselective NSAID. No protective measures are required.
AD has a history of prior ulcer and ulcer-related upper GI bleed. She is at high-risk for future NSAID-related ulcers and complications, and thus requires an effective risk-reduction strategy. Additionally, AD has other factors that contribute to her high-risk status, including her age and concurrent use of nonselective NSAIDs. She should be switched to celecoxib and given a PPI.
Misoprostol including Adverse
- synthetic prostaglandin E1 analog.
- Misoprostol has both acid inhibitory and mucosal protective properties. It stimulates production of mucus and bicarbonate and enhances mucosal blood flow.
Adverse
- potential to cause diarrhea (in up to 30% of patients) and abdominal cramping, nausea and flatulence.
- Misoprostol is an abortifacient because of its uterotropic effects.
What is the concern regarding the use of COX-2 inhibitors and the risk for cardiovascular toxicity?
- Adverse cardiovascular events associated with NSAIDs are thought to be caused by NSAIDs upsetting the balance between vasoconstricting, platelet-aggregating TXA2 (produced by COX-1) and vasodilating, platelet-inhibiting PGI2 (produced by COX-2). Preferential inhibition of COX-2 may lead to vasoconstriction, platelet aggregation, and thrombosis.
- The risk for cardiovascular events in patients taking COX-2 inhibitors increases with increased COX-2 selectivity,
- Naproxen has the lowest cardiovascular risk and is usually the preferred NSAID in patients with increased cardiovascula
In what way is tramadol different from other opioid analgesics?
- Tramadol is a weak μ-opioid receptor agonist. Additionally, part of its analgesic effect is due to inhibition of uptake of NE and 5-HT. Tramadol activates monoaminergic spinal inhibition of pain by inhibiting NE and 5-HT uptake.
- indicated for the treatment of moderate to severe pain. It has also been effective for treatment of neuropathic pain.
- used in the treatment of pain due to osteoarthritis, neuropathy and chronic lower back pain.
What is the analgesic ceiling effect? Which classes of analgesics exhibit this effect and which ones do not?
- The analgesic ceiling effect of a drug refers to the dose beyond which there is no additional analgesic effect.
- NSAIDs have an analgesic ceiling.
- Pure opioid agonists such as morphine, hydromorphone, or fentanyl, have no analgesic ceiling effect
- When using a combination of an opioid with acetaminophen or an NSAID, the analgesic ceiling of acetaminophen or the NSAID should be the dose-limiting factor.
- Mixed agonist-antagonist opioids, such as pentazocine, butorphanol, nalbuphine, and buprenorphine, do have a ceiling effect and are poor choices for patients with severe pain. Additionally, if combined with a pure opioid agonist, these medications may precipitate acute pain and opioid withdrawal symptoms.
Give examples of initial regimens for different pain levels based on the WHO guidelines.
Mild pain: 1-3
- Nonopioid analgesic. Taken on a regular schedule, not as needed.
- Acetaminophen Ibuprofen
Mod pain: 4-6
- Add opioid for moderate pain. Taken on a regular schedule, not as needed.
- Acetaminophen + codeine Acetaminophen + oxycodone Tramadol
Severe: 7-10
- Switch to high potency opioid. Taken on a regular schedule, not as needed.
- Morphine, Hydromorphone
What opioids are used for mild-moderate pain? What opioids are used for moderate-severe pain?
Mild-Moderate Pain
- Codeine
- Hydrocodone
- Oxycodone
- Meperidine
- Propoxyphene
Moderate-Severe Pain
- Morphine
- Hydromorphone
- Oxymorphone
- Levorphanol
- Fentanyl
- Sufentanil
- Methadone
