Considerations before administration
Before administration of the drug, renal function must be assessed because; the drug is eliminated through the renal system. This ensures that the drug does not reach toxic levels. The route of administration is also considered; in this case, the patient is suffering from angina. The drug, therefore, requires to be given through a route that will quickly alleviate angina. The sublingual route is effective because the drug is absorbed efficiently, and is known to reach a therapeutic level in a short while. The duration of action is 15-30 minutes; therefore, the drug should be administered many times (Akporiaye et al., 2009, pp. 513). If a longer duration of action is necessary, oral formulations can be given. Another option is slow-release formulations, for instance, buccal or transdermal preparations. However, the dosage must be closely monitored to prevent excessive effects of the drug.
Important considerations in the history
The patient has stage one hypertension. His heart rate is within the normal range. His respiratory rate is, however, and he needs reassurance that he will be well. The characteristics of the pain point towards angina. The pain is central, gripping, and it does not subside no matter what he does. It can, therefore, be classified as unstable angina. The patient is also on atorvastatin, a drug taken in dyslipidaemic conditions. Dyslipidaemia predisposes one to coronary heart disease (Rang et al. 2007, pp. 325-327).
Pharmacodynamics
- The drug causes decreased demand for oxygen by the myocardium.
- It decreases the heart rate, contractility of the heart, blood pressure, ventricular volume, and ejection fraction.
- In the heart, vasodilatation of coronary vessels ensures sufficient perfusion.
- It is effective in the treatment of unstable and prinzmetal angina.
- The side effects of this drug are throbbing orthostatic hypotension, syncope, dizziness, reflex tachycardia, headache and flushing.
- In severe cases, it causes methemoglobinaemia and cyanosis.
Mechanism of action
- Once the drug is administered, it is broken down to produce nitric oxide as the final product.
- Nitric oxide is a potent vasodilator.
- The nitric oxide also acts to increase the activity of guanyl cyclase.
- This enzyme increases the production of cyclic guanine monophosphate, which causes relaxation of muscles, therefore, decreases contractility.
Pharmacokinetics
- The drug has a first-pass effect, therefore, should not be administered through the mouth. The sublingual route bypasses the first-pass effect of the liver (Neal, 2002, pp. 38-39).
- The drug has 100% bioavailability when administered sublingually, while that for the oral administration is 10-20%
- It reaches therapeutic levels in fifteen minutes.
- Its duration of action is fifteen to thirty minutes.
- It is excreted as glucuronide derivatives of dinitrate metabolites through the kidney.
Recommendations for use
- Take the drug while sitting, because it may cause orthostatic hypotension and he should not stand quickly.
- He should also ensure that he strictly follows the therapeutic dosages to prevent toxicity or tolerance.
Interpretation of the ECG
- The electrocardiogram shows a sinus rhythm, with a heart rate of 75 beats per minute (300÷ number of half centimeter boxes between two Q waves (Ganong, 2005, pp. 624)). The QRS complex is normal because it is 0.08 (0.04×2) seconds. The P wave is also normal as it 0.08(0.04×2) seconds (Guyton, 2006, pp. 123-129).
- The heart has, for this reason, shown normal activity, an improvement from the first ECG when the rate was high.
Patient transportation
- The patient should not be allowed to stand on his own since he may collapse; he requires to be transported by use of a wheelchair to the ambulance.
Aspirin
Pharmacodynamics
- Aspirin inhibits the production of thromboxanes, which are, potent vasoconstrictors, while prostacyclin continues to be produced, and it is a vasodilator. Secondly, this reduces platelet aggregation, thereby, reducing the risk of thromboembolic disease.
- The effectiveness of the drug is dependent on the time of administration. In angina, it is effective in the acute state. After acute states of angina, the drug has limited effectiveness.
Side effects
- It causes peptic ulcer disease because, it inhibits cycloxygenase, which is, the enzyme involved in the production of prostaglandins which are protective to the intestinal mucosa. This may result in dyspepsia and perforation.
- It also causes allergic reactions for instance urticaria, rhinitis, angioedema, skin eruptions, bronchospasms, and dyspnoea.
- It may cause hepatotoxicity in patients with juvenile idiopathic arthritis and other connective tissue diseases.
- In children, it has been shown to cause Reye syndrome, which is, hepatic encephalopathy.
- In high doses, it may cause salicylism especially after excessive use of topical salicylates. Salicylism is characterized by deafness, headache, dizziness, tinnitus, nausea, vomiting, and confusion.
- Acute poisoning with aspirin, the patient may present with hyperventilation leading to respiratory alkalosis and compensatory metabolic acidosis. It also causes ketosis, hypoglycemia, fever and restlessness.
- In severe central nervous system depression, the patient may end up in a coma; consequently, leading to cardiovascular collapse and respiratory failure.
Mechanism of action
It irreversibly binds cycloxygenase-1 at low doses, thereby inhibiting the production of thromboxanes which cause platelet aggregation leading to thromboembolism. Thromboxanes are also vasoconstrictors, and so when their production is inhibited, ischaemia is alleviated.
The considerations before use
- The patient has been shown to have dyslipidaemia; thus, the patient should be reviewed to determine that the coronary vessels have not undergone atherosclerosis, because if so, the patient would, subsequently, get Still’s disease. This is a disease that occurs because coronary vessels that have undergone atherosclerosis cannot dilate and this would then lead to blood being shunted from constricted vessels to those that can dilate. This worsens angina. Aspirin is, therefore, used with caution in patients known to have atherosclerosis.
- Review whether the patient has a peptic ulcer, because it causes erosion of the gastric mucosa and these patients require the drug to be administered through another route or in enteric-coated capsules.
- Hepatic and renal function must also be reviewed because; the drug is eliminated through the liver, and salicylates can be excreted unchanged through the kidney.
Recommendations for use
- The patient should constantly come for review to ensure that he does not get gastritis. He should report any epigastric pain, hematemesis, hematochisia or melena.
- The patient will also be advised to take the drug as it has prophylactic properties against future myocardial infarction or thromboembolic states.
Clopidogrel
Pharmacodynamics
Clopidogrel inhibits platelet aggregation. It is more effective than aspirin, but it is more expensive (Craig, C and Stitzel, R., 2005, pp. 263).
Side effects
- It causes blood dyscrasias for instance anemia, neutropenia and thrombotic thrombocytopenic purpura.
- Gastrointestinal disturbances like nausea, dyspepsia and diarrhea.
- Other side effects are skin rashes and bleeding.
Mechanism of action
- Clopidogrel inhibits platelet aggregation by irreversibly binding adenosine diphosphate receptor p2y12 (Griffin and O’Grady, 2006, pp. 83). It, hence, inhibits platelet aggregation.
During coronary angiography, the clopidogrel is used to reduce thrombosis; therefore, it is standard to use thienopyridines before the procedure.
Clopidogrel cannot be administered in liver failure, because it is a pro-drug that undergoes activation in the liver.
References
Akporiaye et al., 2009. Basic and Clinical Pharmacology. China; McGraw- Hill Companies.
Craig, C and Stitzel, R., 2005. Modern Pharmacology with Clinical Applications. London: Elsevier.
Ganong, W., 2005. Review of Medical Physiology. China: McGraw-Hill Companies.
Golan, DE., 2008. Principles of Pharmacology: The Pathophysiologic Basis of Drug Therapy. Philadelphia: Lippincott Williams & Wilkins.
Griffin, J and O’Grady, J., 2006. Textbook of Pharmaceutical Medicine. Victoria: Blackwell Publishing Company.
Guyton, AC., 2006. Textbook of Medical Physiology. Philadelphia: Elsevier Saunders.
Neal, MJ, 2002. Medical Pharmacology at a Glance. Victoria: Blackwell Publishing Company.
Rang, HP, Dale, MM, Ritter, JM, AND Flower, RJ., 2007. Rang and Dale’s Pharmacology. London: Elsevier.
Rosenfeld, G and Loose, D., 2006. Pharmacology. Philadelphia: Lippincott Williams & Wilkins.
Waller, DG, Andrew, G and Hillier K., 2009. Medical Pharmacology and Therapeutics. London: Elsevier Saunders.