Advanced Pharmacology Paper
Pharmacology Of Agents Used
Glipizide is an oral hypoglycemic agent that falls under the second generation of sulfonylureas. It binds to and blocks ATP-dependent potassium ion channels receptors which cause promotion of insulin secretion by pancreatic beta cells, decreased hepatic gluconeogenesis, and increased peripheral insulin sensitivity (Correa et al., 2022).
It can be used alone or in combination with other anti-diabetic agents such as biguanides like metformin and insulin. Hypoglycemia, allergy, weight gain, gastrointestinal upset, and bone marrow suppression are some of the commonly encountered side effects. Exacerbation of hypoglycemia by beta-blockers such as atenolol can occur. Concomitant administration with thiazide can impair its function and result in hyperglycemia, thus poor glucose control.
Metformin is an oral biguanide that increases peripheral insulin sensitivity in addition to decreasing gluconeogenesis. It is eliminated unchanged in the urine and causes adverse effects such as nausea and vomiting, lactic acidosis, and vitamin B12 deficiency, although tolerance is generally good (Corcaran et al., 2022). Use with other anti-diabetic agents significantly increases the risk of hypoglycemia.
Hydrochlorothiazide is a thiazide diuretic that lowers the blood pressure by inhibiting sodium chloride co-transporter of the distal convoluted tubule, thus increasing renal sodium and water loss (Herman et al., 2020). Its use is associated with effects such as hyponatremia, hypokalemia, impaired glucose tolerance, and hypersensitivity.
Atenolol is an anti-hypertensive selective beta 1 adrenergic antagonist that inhibits sympathetic activity in vascular and cardiac muscles. Adverse events include constipation, difficulty breathing, confusion, and heart block, especially when used concomitantly with verapamil. Hydralazine is a directly acting arterial vasodilator used in treating hypertension, though not as a first-line drug of choice (Herman et al., 2022). Adverse effects include hydralazine-induced lupus erythematosus, hypotension, tachycardia, and awareness of the heartbeat.
Verapamil is an anti-hypertensive non-dihydropyridine calcium channel blocker that causes vasodilatation. Its undesired effects include hyperplasia of the gingival tissue, hypotension, myalgia, and hypersensitivity reactions. Simvastatin is a statin that works to manage hyperlipidemia by inhibiting the HMG-CoA reductase enzyme, thus reducing cholesterol synthesis. The administration is associated with angioedema, myalgias, and myopathy. Its toxicity is increased by concurrent administration with verapamil.
Beta-blockers are not recommended as a first-line treatment for hypertension. This is because they are associated with an increased risk of cardiovascular events (Sharma, 2018), thus the need to terminate its use in this patient with a history of strokes. This is further supported by the increased risk of heart block from co-administration with verapamil. Hydralazine can also be withdrawn since verapamil can be used to achieve similar therapeutic effects.
Using both glipizide and metformin will increase the risk of hypoglycemia, thus the need for monotherapy or reducing their doses. This is keeping in mind that hydrochlorothiazide antagonizes the therapeutic effects of glipizide, which makes metformin a better choice. The dose of simvastatin should be reduced to prevent toxicity potentiated by concurrent administration of verapamil.
An angiotensin-converting enzyme inhibitor such as captopril can be substituted for atenolol. Alternatively, an ARB such as losartan can also be used. Both of these aforementioned drugs cause vasodilation by blocking the vasoconstriction by angiotensin. This is because guidelines recommend the use of angiotensin receptor blockers, calcium channel blockers, angiotensin-converting enzyme inhibitors, and thiazide diuretics as drugs of choice in the treatment of hypertension (Arnett et al., 2018). Due to the recurrent episodes of strokes, the patient can also be put on prophylactic anticoagulation such as aspirin or warfarin.
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Corcoran, C., & Jacobs, T. F. (2022). Metformin. In StatPearls. StatPearls Publishing.
Correa, R., Quintanilla Rodriguez, B. S., & Nappe, T. M. (2022). Glipizide. In StatPearls. StatPearls Publishing.
Herman, L. L., & Bashir, K. (2022). Hydrochlorothiazide. In StatPearls. StatPearls Publishing.
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