Pharmacology Case Study

1. Suggest why Tramadol was given during the immediate post-operative period and explain its mode of action.

Tramadol is a potent analgesic classified under opioids and is given as part of anaesthesia during surgery and post-surgery for pain remedy. The drug mode of action is different compared to other narcotic analgesics like morphine. The mode of action is by acting directly to the brain to decrease the brains perception to pain. Pain is transmitted to the brain by nerves. When nerves are stimulated, the signalling speed increases greatly and this is perceived by the brain as pain. Tramadol works through several ways to remedy pain.

Based on clinical studies (Frink et al, 1030), Tramadol acts as a mu-opioid receptor agonists, norepinephrine reuptake inhibitor, serotonin releasing agent, nicotinic acetylcholine receptor antagonists, and muscarinic acetylcholine receptor antagonist. According to Hara et al (1404), the effect of Tramadol on mu-opioid receptors is mild therefore, O-desmethyltramadol, the active metabolic inhibits the uptake of norepinephrine.

Tramadol has several side effects and reactions. According to Hara (1400-5), the side effects of the drug include dizziness, vomiting, nausea, sedation, and dry mouth. In normal cases, these effects are well-tolerated, but if severe, dose adjustment is recommended. Some of the side effects that may warrant medical concern if they are observed include allergic reactions, cardiac abnormalities, CNS (Central Nervous System) defects, respiratory defects, and gastric symptoms. According to Stamer et al (928), these the majority of side effects will fade after the first month of using the drug in long term use cases.

1. Explain the mode of action of Diclofenac and likely side effects.

Diclofenac is a non-steroid anti-inflammatory drug (NSAIFD) used to treat pain and inflammation for arthritis, dental pain, gout, post-surgery pain, and migraine among others. Diclofenac works to relieve pain by blocking the effect of cyclo-oxygenase (COX) enzymes a group of chemicals (Scholer). The inhibition of these chemicals inhibits the synthesis of prostaglandin. The inhibition of COX decreases prostaglandins production which means inflammation and pain are eased. In addition, the drug prevents bacterial DNA synthesis through its bacteriostatic activity. The proliferation of bacteria in some pain instances, e.g. dental pain is associated with bacterial growth therefore; reduced bacterial growth eases pain.

According to Dutta (336-340), there are two forms of diclofenac – diclofenac potassium and diclofenac sodium. Diclofenac potassium is absorbed more quickly than its sodium counterpart. For immediate pain relieve purposes, diclofenac potassium is recommended. A single dose of the drug remains active for 6 to 8 hours because of it’s up to 11 hours persistence in synovial fluids.

Diclofenac just like other drugs has a number of side effects (Scholer) even though not everybody experiences them. These include feeling sick, diarrhea, dizziness, indigestion, heartburn, stomach pain and wind. These effects will usually improve as the body gets used to the drug. Nevertheless, in severe cases, counter remedies are available for example, the in the case of heartburns and stomach pains, the drug should be taken after a mean if that is not the case already. In severe cases of the side effects, it is recommended that taking the drug be discontinued. Severe side effect cases include passing blood or black stool or vomiting blood, breathing difficulties, and allergic reaction e.g. swelling of the mouth area or itchy skin.

1. Discuss the relevant issues regarding the use of ‘indigestion medicine’ in cases such as these, with reference to relevant literature.

Dyspepsia is a side effect of some drugs. According to Westbrook & Talley, (1171-8), the most common drugs that have dyspepsia effects are anti-inflammatory medicines. Others that might cause dyspepsia or make it worse   include steroids, antibiotics, antagonists, and biophosphates. Therefore, it is likely that in this case, it is the side effect of Tramadol.

The indigestion medication taken is not known from the case scenario. Nevertheless, it was taken without any medical investigation and befits the over-the-counter treatments. According to Drossman, it is acceptable to institute treatment for dyspepsia for patients under 55 years of age and with non alarming symptoms. The most common over-the-counter indigestion medicines are Zantac, Rennie, and Gaviscon from Reckitt Benckiser, GlaxoSmithKline, and Roche pharmaceutical companies (Westbrook & Talley, 1171-8). Alarming signs include unintentional weight loss of more than 3 kgs, unexplained iron deficiency anaemia, persistent and continuous vomiting, previous gastric surgery, epigastria mass, gastro-intestinal bleeding seen as blood or black stool and vomiting blood, and previous gastric ulcer.

For patients over 55 years old, it is recommended that a prompt endoscopy should be undertaken at the first dyspepsia (Drossman). In cases where the patient was under antisecretory drugs before dyspepsia manifested itself, the treatment should be discontinued for at least 4 weeks as it has been shown to mask significant endoscopy diagnoses.

For the case of Marianne, she is 35 years old and none of the alarming signs are indicated in the case study therefore, it was medically acceptable to institute the indigestion medicine, but not medically recommended. According to Hallas & Bytzer (27-32), without a medical investigation, the cause of the indigestion can only be speculated. It could be because of Helicobacter pylori hence not treatable with ordinary over-the-counter medication.

1. Discuss the issues that may arise from taking St John’s wort in combination with the other drugs taken in this case, with reference to relevant literature.

St. John’s wort (Hypericum perforatum) is an herb whose flowers and leaves are used to make medicine. The medicine can be used orally or topically. The oral form has been use in Europe as a prescription drug for depression. However and according to Clauson et al (42), recent research to evidence that St. John’s wort is effective for depression in not conclusive. It is worth noting that in America, the drug is not approved as an over-the-counter drug or as a prescription drug by the Food and Drug Administration.

St. John’s wort works through the chemicals hypericin and hyperforin that act on body chemical messengers to regulate mood (Larzelere et al, 213-236). The drug exhibits side effects and has shown to react with other prescription drugs. Combination of Str. John’s wort with certain antidepressants poses life threatening effects. The drug increases serotonin, which is targeted by antidepressants like Tramadol, leading to the condition known as serotonin syndrome. Symptoms for this condition include tremor and diarrhoea, dangerous confusion, drop in body temperature, muscle stiffness, and death.

St. John’s wort has also been shown to affect birth control pills to weaken their effect. Some birth control pills contain estrogens. The body then breaks down the estrogens to get rid of it and St. John’s wort acts by increasing the breakdown process. Therefore; talking St. John’s wort along with birth control pills increases the estrogens breakdown process decreasing the effectiveness of the contraceptive drug. Other drugs whose effectiveness is decreased by St John’s wort include cyclosporine which is used to prevent the body immune system from rejecting transplanted organs, digoxin, a medication for heart diseases, HIV drugs e.g. indinavir, irinotecan a cancer medication, and warfarin a blood thinner.

Works cited

Clauson K.A., Santamarina M.L., Rutledge J.C.. Clinically relevant safety issues associated with St. John’s wort product labels.  BMC Complementary and Alternative Medicine. 2008;8:42.

Drossman D.A., Corrazziari E., Talley N.J. Rome II: The functional gastrointestinal disorders. 2nd Ed. McLean: Degnon, 2000

Dutta N.K., Mazumdar K., Dastidar S.G., Park J.H. Activity of diclofenac used alone and in combination with streptomycin against Mycobacterium tuberculosis in mice. Int. J. Antimicrob. Agents 30 2007 (4): 336–340

Frink M.C., Hennies H.H., Englberger W., Haurand M., Wilffert B. Influence of tramadol on neurotransmitter systems of the rat brain. Arzneimittel-Forschung 46 November 1996 (11): 1029–36

Hallas J., Bytzer P. Screening for drug related dyspepsia: An analysis of prescription symmetry. Eur J Gastroenterol Hepatol 1998;10 (1):27–32.

Hara K., Minami K., Sata T. The effects of tramadol and its metabolite on glycine, gamma-aminobutyric acid A, and N-methyl-D-aspartate receptors expressed in Xenopus oocytes. Anesthesia and Analgesia 100 May 2005 (5): 1400–5

Larzelere M.M., Campbell J.S., Robertson M. Complementary and alternative medicine usage for behavioral health indications.  Primary Care. 2010;37(2):213–236.

Linde  K., Berner M.M., Kriston L. St. John’s wort for major depression. Cochrane Database of Systematic Reviews. 2009; (4):CD000448

Scholer. Pharmacology of Diclofenac Sodium. Am J of Medicine Volume 80 April 28, 1986

Stamer U., Stuber F., Muders T., Musshoff F. Respiratory Depression with Tramadol in a Patient with Renal Impairment and CYP2D6 Gene Duplication. Anesthesia & Analgesia 2008; 107: 926–929.

Westbrook J.I., Talley N.J. Diagnostic investigation rates and use of prescription and non-prescription medications amongst dyspeptics: A population-based study of 2300 Australians. Aliment Pharmacol Ther 2003;17:1171–8