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  2. Visceral pain treatment • It is unlikely that a single analgesic or targeted agent will significantly reduce most visceral pains since multiple neurotransmitters, channels, and receptors are responsible for this type of pain. • Analgesics combinations are anticipated to be better than single analgesics.

  3. Visceral pain treatment • Analgesics which are ineffective as single agents or ineffective at a particular dose may have supra-additive analgesia for visceral pain when combined with a second analgesic. • Hence, single-drug trials may not predict the merit of an analgesic supra-additive analgesic combinations cannot be predicted based on single-drug activity.

  4. Visceral pain treatment • Analgesic dose response relationships for visceral pain may be distinctly different from somatic pain. • Opioids for somatic pain may in fact not work well for visceral pain and visa-versa. (kappa agonist - Alvimopan).

  5. Visceral pain treatment • There is little doubt that central sensitization plays a role in maintaining visceral pain. • As a result, uncontrolled acute visceral pain will likely lead to central neuroplasticity and chronic pain despite the resolution of underlying cause for pain. • Certain analgesics will need to penetrate the CNS to fully and effectively relieve pain.

  6. Visceral pain treatment Paracetamol • weak COX-2 inhibitor and a selective COX-3 inhibitor. • It also increases brainstem serotonin neurotransmission, redirects beta-endorphin, and inhibits 5-HT3 receptors which are pronociceptive.

  7. Visceral pain treatment • Paracetamol is commonly used for pain, but little is known about visceral pain responses since most studies have not focused on visceral pain. • In an acetic acid peritonitis model, combinations of ketoprofen-paracetamol were synergistic at a dose ratio of 3:1 (paracetamol to ketoprofen).

  8. Visceral pain treatment • Several other studies involving animal models of visceral pain have confirmed benefits of NSAIDs plus paracetamol combinations. • In a qualitative systematic review of paracetamol-NSAIDs combinations were superior to paracetamol alone in 85% and NSAIDs alone in 64% of studies.

  9. Visceral pain treatment • Ibuprofen was the most commonly used in the 21 studies reviewed. • Drug combinations reduced pain by 35% and analgesic supplemented by 38%. • This combination was superior in gynecology surgical studies (83%) indirectly confirming benefits for visceral pain.

  10. Visceral pain treatment • NSAIDs are effective in reducing cancer pain in the dose-dependent fashion. • Multiple studies have found that NSAIDs are effective for biliary colic and are as effective as opioids with fewer side effects. • One of the mechanisms by which NSAIDs work in renal or biliary colic may involve acetylcholine blockade.

  11. Visceral pain treatment • NSAIDs were superior to anticholinergics in relieving biliary colic to treat and prevented progression to cholecystitis, and also in relieving renal colic. • NSAIDs were superior to opioids in reducing renal colic. • both NSAIDs and opioids provide effective analgesia in acute renal colic, but opioids are associated with a higher incidence of adverse events (vomiting).

  12. Visceral pain treatment • 9% patients with IBS treated with NSAIDs deteriorate clinically and improve once the NSAID is discontinued. • Loss of prostaglandin by the NSAID leads to microvascular dysfunction and sustained inflammation.

  13. Visceral pain treatment • Opioids reduce pain; however, poor coping skills, depression, and catastrophization correlate better with dose than the degree pathology. • Opioids add a symptom burden associated with dysmotility. • Proactive use of laxatives and bowel softeners are needed.

  14. Visceral pain treatment • Morphine can produce visceral hyperalgesia which is suppressed by gabapentinoids (the advantages of this combination). • Features of hyperalgesia are increased pain intensity extent of pain area, or radiation with reduced responsiveness to opioid analgesia. • Paradoxically, opioid dose reduction may improve pain control.

  15. Visceral pain treatment • Sustained release oxycodone significantly reduces chronic cancer-related visceral pain (pancreatic cancer). • Intranasal fentanyl was effective in managing acute visceral pain in the emergency department.

  16. Visceral pain treatment • the triple combination of fentanyl-trazodone-paracetamol analgesic effects in writhing test (acetic acid). • ketorolac alone was ineffective, and morphine modestly effective, but the combination of ketorolac-morphine synergistic antinociception (rat colorectal distention model). • tramadol-morphine, tramadol-fentanyl synergistic antinociception in the writhing test but not in hot plate test.


  18. Gastrointestinal pain • Antacid drugs • Antispasmodic medication

  19. Antacid drugs • antacids either directly neutralize acidity, increasing the pH, or reversibly reduce or block the secretion of acid by gastric cells to reduce acidity in the stomach. • when gastric HCl reaches the nerves in the GI mucosa, they signal pain to the CNS. • this happens when these nerves are exposed. 

  20. Antacid drugs • are generally the first line of defense a physician will recommend when a patient presents with epigastric pain and acid reflux symptoms.   • some antacids also coat the surface of the oesophagus (gullet) with a protective barrier against stomach acid or produce a gel on the stomach’s surface which helps stop acid leaking into the oesophagus.

  21. Antacid drugs • are used to treat dyspepsia, as symptomatic relief of gastritis or peptic ulcer. • are taken by mouth to relieve heartburn, the major symptom of GERD.  • are available over the counter from pharmacies • antacids in common use salts of magnesium, aluminium and calcium. • some mixtures contain sodium and should be used with caution in patients who should avoid excess sodium intake.

  22. Antacid drugs • alginates are sometimes combined with antacids for use in GERD. • alginates float on top of the gastric contents and act as a barrier between the acidic contents of the stomach and the lower esophageal sphincter, preventing erosion of the lower esophagus and therefore not creating the pain experienced in GERD.

  23. Antacid drugs Common side effects include: • diarrhoea • constipation • flatulence • stomach cramps • feeling sick or vomiting

  24. Antacid drugs Carbonate and bicarbonate • alkalosis (which in turn may result in altered excretion of other drugs, and kidney stones). • distension, headaches, decreased muscle flexibility (chemical reaction between the carbonate and hydrochloric acid carbon dioxide gas).

  25. Antiacid drugs • Aluminium hydroxide • formation of insoluble aluminium-phosphate-complexes risk for hypophosphatemia, osteomalacia.  • aluminium accumulation renal insufficiency. • constipation • neurotoxicity • C.I. : pregnancy.

  26. Antiacid drugs • Magnesium hydroxide - diarrhea - hypermagnesiemia, cardiovascular, neurological complications (in patients with renal failure). • Sodium hydroxide: - increased intake of sodium HTA, heart failure, renal diseases.

  27. Antispasmodic drugs • are used to counteract the smooth muscle contraction, especially in tubular organs of the GIT. • the effect is to prevent spasms of the stomach, intestine, biliary or urinary bladder.  Two main types: - antimuscarinics (dicycloverine, hyoscine, atropine). - smooth muscle relaxants (alverine, mebeverine, peppermint oil).

  28. Antispasmodic drugs • antimuscarinics inhibit the action of Ach. • they stop the transmission of parasympathetic nerve impulses therefore lessen the spasms of smooth muscle, such as in the GIT and in the bladder. • reducing the muscle contractions in this way often helps to relieve some of the symptoms (IBS). • smooth muscle relaxants work directly on the smooth muscle in the wall of the gut. Here they help to relax the muscle and relieve the pain associated with a contraction of the gut.

  29. Antispasmodic drugs The most common side-effects are: • flatulence and bloating • heartburn • constipation • dry mouth

  30. Antispasmodic drugs C.I.: - paralytic ileus (paralysis of the gut muscles), • myasthenia gravis (a condition causing muscle weakness), • pyloric stenosis (narrowing of the outlet from the stomach) • prostatic hypertrophia. • pregnancy or breast-feeding mothers.

  31. Antispasmodic drugs • atropine, propantheline, • butylscopolamine, metoclopramid. • selective anticholinergic drugs (rec. M1) (pirenzepine, telenzepine)

  32. Antispasmodic drugs • Direct acting on smooth muscle (anticholinergics and Ca channels blockers): - otilonium bromide - pinaverium; - propiverine, rociverine • temiverina, • mebeverine- GIT specificity • alverine, • drotaverine. Indications: IBS, GD ulcer, biliarycolics.

  33. Cardiac pain • nitrates • nitrites

  34. Antianginal drugs • the dull, tight chest pain of angina occurs when the heart's muscular wall is not getting enough oxygen. • by relaxing the blood vessels, antiangina drugs reduce the heart's work load and increase the amount of oxygen rich blood that reaches the heart. 

  35. Nitrates, Nitrites - have been prescribed to patients with stable angina for more than 100 years, and are still widely used in the treatment of such patients. - are safe and effective in symptomatic management of patients with acute and chronic ischemic syndromes due to coronary artery disease. - in patients with stable angina, improve exercise tolerance, time to onset of angina, and ST-segment depression during the effort.

  36. Nitrates, Nitrites • cause vasodilation of the venous capacitance vessels by stimulating the endothelium-derived relaxing factor. • are used to relieve both exertional and vasospastic angina by allowing venous pooling, reducing the pressure in the ventricles reduce wall tension and oxygen requirements in the heart. • short-acting nitrates (angina attacks), • longer-acting nitrates (prophylactic, chronic).

  37. Nitrates, Nitrites • are used in three main ways: • taken regularly over a long period, they reduce the number of angina attacks. • taken just before some activity that usually brings on an attack, such as climbing stairs, they prevent attacks. • taken when an attack begins, they relieve the pain and pressure.

  38. Nitrates, Nitrites • nitroglycerine (glyceryl trinitrate) • pentaerythritol tetranitrate (PETN) • isosorbide dinitrate (ISDN) • isosorbide mononitrate (ISMN)

  39. Nitrites, Nitrates - many different forms: • tablets and capsules that are swallowed; • tablets that are held under the tongue, inside the lip, or in the cheek until they dissolve; • stick-on patches; • ointment; • in-the-mouth sprays.

  40. Nitrates, Nitrites Adverse effects • headache just after taking a dose of the medicine (usually become less noticeable as the body adjusts to the drug). • dizziness, • tachyphilaxia • lightheadedness, • fast pulse, • flushed face and neck, • nausea or vomiting, • restlessness. 

  41. Nitrates, Nitrites C.I.: • kidney disease • liver disease • severe anemia • overactive thyroid • glaucoma • recent head injury.

  42. Nicorandil • is an anti-angina drug that has the dual properties of a nitrate and K+ATP channel agonist. • in humans, the nitrate action of nicorandil dilates the large coronary arteries at low plasma concentrations. • at high plasma concentrations nicorandil reduces coronary vascular resistance, which is associated with increased K+ATP channel opening.

  43. Nicorandil Indications: • prophylactic treatment of angina • long curative treatment of angina • tachiphylaxia to nitrates.

  44. Nicorandil Adverse effects: • flushing • palpitations • weakness • headache • mouth ulcers.

  45. Molsidomin • is an orally active, long acting vasodilating agent • is metabolized in the liver to the active metabolite linsidomine (an unstable compound that releases NO upon decay as the actual vasodilating compound). • decreases levels of intracellular Ca in smooth muscle cells relaxation of smooth muscle vasculature, • inhibits platelets aggregation • indirect antiproliferative effect.

  46. Molsidomin Indications: • prophylactic treatment of angina • long curative treatment of angina • myocardial infarctus • corronary insufficiency • in patients with severe headache after nitrates.

  47. Molsidomin • headache,  • anorexia,  • facial flushing, • nausea, vomiting,  • orthostatic hypotension


  49. GINECOLOGIC PAIN • hormonal medication (oral contraceptive drugs) • progestatives

  50. Oral contraceptive drugs • second therapy line drugs in primary dysmenorrhea • reduces the volume of menstrual fluid, block the ovulation ( Pgl concentration decrease uterine smooth muscle contraction) • the effect starts after 2-3 weeks (in this period: intermittent adm. NSAIDs). • Disadvantage: - continuous administration