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Oral Anti-diabetic Drugs

Info: 3498 words (14 pages) Essay
Published: 29th Nov 2017 in Nursing

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  • Chua Mei Yi

Module

Topic

Drug 1

Drug 2

3

Oral analgesics used to treat acute nociceptive pain

Oxycodone

Tramadol

4

Oral antiepileptic drugs

Phenytoin sodium

Topiramate

5

Oral hypoglycaemic drugs (used for T2DM)

Metformin

Gliclazide

6

Oral anti-hypertensive agents (excluding diuretics)

Atenolol

Nifedipine

7

Oral medications used to manage asthma

Salbutamol

Beclomethasone Dipropionate

8

Oral medications used to treat GORD

Cimetidine

Omeprazole

10

Medications used to treat osteoporosis

Risedronate sodium

Strontium ranelate

No

Generic name

Mode Of Action

Pharmacology

ADR

 

Oxycodone

Its an opioid agonist that acts mildly at its receptors within the central nervous system, typically affecting mu-type opioid receptors. Binding of the opiate inhibits the release of nociceptive neurotransmitters and vasopressin, resulting in reduced neuronal excitability.

Oxycodone is rapidly absorbed and binded by plasma protein which are then distributed to the skeletal muscles, organs as well as brain. After metabolisation in the liver, oxycodone produces noroxycodone, oxymorphone and noroxymorphone, which are the major circulating metabolites causing drug interactions and analgesic effects. It is excreted as urine.

Common:

  • Nausea
  • Drowsiness
  • Vomiting,
  • Constipation
  • Drowsiness,
  • Weakness,
  • Lightheadedness

Rare:

  • Tightness of the chest
  • Swelling of the face or throat
  • Difficulty breathing
  • Seizures
  • Hallucinations
 

Tramadol

Besides belonging to a synthetic analgesics class, it also has opioid-like effects which derives from binding of mono O-desmethyl tramadol to mu-opioid receptors by inhibiting the reuptake of noradrenaline and serotonin. The analgesic effect is dose dependent and varies between individuals.

Tramadol is rapidly absorbed and distributed in the body.

Besides plasma protein binding, it crosses both the placenta and the blood brain barrier, therefore tramadol must be used with caution, not suitable for use in pregnant and lactating mothers. It is metabolized in the liver and excreted by the kidney as urine.

Common:

  • Nausea
  • Vomiting
  • Constipation

Rare:

  • Orthostatic dysregulation
  • Tachycardia
  • Flushing
 

Phenytoin sodium

It stabilizes the threshold against hyperexcitability cells by reducing the gradient of sodium ions through membranes in the motor cortex, which helps to shortens the tonic phase of grand mal seizures.

With a narrow therapeutic index and protein binding characteristics, blood serum needs to be regularly checked for toxicity. Alcoholic intake may affect phenytoin serum level. Slow metabolism rate of phenytoin in some individuals maybe due to genetics issues. It is metabolize in the liver and excreted as urine.

Common:

  • Nausea
  • Vomiting
  • Constipation
  • Nystagmus
  • Ataxia
  • Gingival hyperplasia

Rare:

  • Stevens-Johnson syndrome
  • Toxic epidermal necrolysis
  • Acute hepatic failure
  • Chorea
  • Dystonia
 

Topiramate

Topiramate is classified as a sulfamate substituted Monosaccharide. It blocks voltage-dependent sodium channels, enhance the activity of the neurotransmitter gamma-aminobutyrate acid, antagonizes the AMPA/kainate subtype of theglutamate receptor, and inhibits the carbonic anhydrase enzyme.

Topiramate was rapidly absorbed and distributed in the body. It is metabolize in the liver and excreted via kidney as urine.

Adequate hydration is important to reduce risk of nephrolithiasis. Caution use in lactating woman.

Common:

  • Loss of appetite
  • Tingling sensations in arms and legs
  • Dizziness
  • Taste change
  • Nervousness
  • Weight loss

Rare:

  • Neutropenia
  • Anorexia
  • Metabolic acidosis
  • Depression
  • Psychotic disorder
 

Metformin

Being a biguanide, metformin inhibits gluconeogenesis and glycogenolysis in the liver without stimulating insulin secretion, and therefore does not produce hypoglycaemia. In addition, it improves insulin sensitivity, boost peripheral glucose uptake, and limit glucose absorption from the gastrointestinal tract.

Metformin’s absorption rate is fair, distributed via blood flow. The intravascular administration of iodinated contrast in radiologic studies can lead to renal failure and lactic acidosis, therefore, metformin must be discontinued either 48 hours before the test or from the time of the test.

Common:

  • GI upset
  • Taste disturbance

Rare:

  • Lactic acidosis
  • Urticaria
  • Decrease of vitamin B12 absorption with a decrease of serum levels
  • Erythema
  • Pruritus
 

Gliclazide

It is a sulfonylurea hypoglycaemic agent which stimulates insulin secretion from functional pancreatic beta-cells and increases sensitivity of the beta-cells. Besides the strong selectivity and reversible binding to pancreatic beta-cells, it has low vascular and cardiac complication. Studies have shown decreases hepatic glucose production, leading to improvement of HbA1c results.

Gliclazide is absorbed and distributed via extracellular fluid.

It crosses the placental barrier and blood brain barrier, therefore usage during pregnancy and lactation is contraindicated.

Having high degree of protein binding component,

dose adjustment and strict monitoring of toxicity should be observed.

Common:

  • Hypoglycaemia
  • Epigastric discomfort
  • Heartburn
  • Transient itching

Rare:

  • Anemia
  • Leucopenia
  • Thrombocytopenia
  • Agranulocytosis
 

Hydralazine

Being a vasodilator, hydralazine reduces peripheral resistance directly by relaxing the smooth muscle cell layer in arterial vessels through alteration of calcium ions, resulting in decreased arterial blood pressure (diastolic more than systolic).

Rapidly absorbed and distributed in the body, hydralazine is also bounded to plasma protein. It crosses the placental barrier and also passes into human milk, therefore pregnant and lactating woman have to take with caution. Metabolism depends on patient’s acetylator and hydroxylator status. It is excreted as urine and glucuronic acid.

Common:

  • Tachycardia
  • Palpitation
  • Flushing
  • Hypotension
  • Headache
  • Joint swelling

Rare:

  • Paradoxical pressor responses
  • Peripheral Neuritis
  • SLE-like syndrome
  • Retroperitoneal fibrosis
 

Nifedipine

As a calcium channel blockers, it reduces the heart’s workload by relaxing the smooth muscles and widening the lumen of the blood vessels through selectively inhibiting calcium ions into cardiac and smooth muscle, resulting in reduction of free calcium ions available, thus reducing blood pressure as vasodilation takes place.

Being Rapidly absorbed and 95% bound to plasma protein, means that it has high tendency of drug interaction. Grapefruit should be avoided because of possible interaction. It is metabolized in the liver and within gut wall

Excreted as urine and feces.

.

 

Common:

  • Asthenia
  • Edema
  • Headache
  • Palpitation

Rare:

  • Hypoaesthesia
  • Somnolence
  • Chest pain
  • Eye pain
 

Salbutamol

Being a beta 2 adrenoceptor agonist, it binds to its receptors in the bronchioles of the respiratory system, activating adenylate cyclase which catalyzes the conversion of adenosine triphosphate (ATP) to cyclic adenosine monophosphate. The activation inhibits release of mediators of immediate hypersensitivity from mast cells, as well as relaxing bronchial smooth muscle.

Salbutamol is delivered to the lungs at the recommended inhaled doses for fast acting effect.

Salbutamol is not metabolized in the lung but excreted in the urine and feces.

Salbutamol crosses placenta, therefore it should not be used in pregnant woman unless contraindicated.

Common:

  • Palpitation
  • Sinus tachycardia

Rare:

  • Taste perversion
  • Epistaxis
  • Depression
 

Beclomethasone Dipropionate

Being a synthetic glucocorticoid, it has multiple anti-inflammatory effects which includes both inhibiting inflammatory cells and releasing of inflammatory mediators. It acts at the site of bronchial tree, controlling symptoms and improving lung function in asthmatic patient.

Beclomethasone dipropionate is hydrolyzed in the lungs to beclomethasone monopropionate and is further metabolized during its passage through the liver. It is excreted as urine and feces. Beclomethasone dipropionate should be avoided for use in pregnancy and breast feeding mothers unless the expected benefit to the patient outweighs the risk.

Common:

  • Dryness in mouth, nose, throat
  • Mild cough
  • Wheezing due to chemical irritation

Rare:

  • Increased asthma symptoms
  • Chest pain
  • Asthenia
  • Back pain
  • Fatigue
  • Edema
  • Neuropathy
 

Cimetidine

It is the first available agent that blocked the action of histamine at the receptor site of parietal cells by competitive inhibition of gastric acid secretion during day and night time. Besides not having a classical anticholinergic effect, it only interacts with H2 receptors.

.

It is rapidly absorbed in the stomach, and excreted by kidney via urine.

Being 22% bound to human plasma protein, it has higher drug interaction possibility. Cimetidine crosses the placental barrier and can

cross the blood brain barrier of neonatal animals,

therefore, usage in pregnancy should be carefully considered by doctor.

Common:

  • Headache
  • Diarrhoea
  • Constipation

Rare:

  • Fever
  • Hepatitis
 

Omeprazole

The inhibitory effect is dose-related, inhibiting both basal acid secretion and stimulated acid secretion, irrespective of the stimulus to acid production, temporarily reducing gastric acid secretion.

However, treatment with omeprazole may lead to slight increased risk of gastrointestinal infections.

Gastric’s acidity influenced omeprazole’s absorption, therefore is administered orally as enteric coated tablet.

Being a plasma protein binding, it is rapidly absorbed in the body, metabolized in the liver and excreted as urine.

Not suitable for breastfeeding and pregnant mothers as it causes fetal damage and is excreted via breast milk.

Common:

  • Diarrhoea
  • Constipation
  • Abdominal pain
  • Nausea/vomiting
  • Headache

Rare:

  • Dyspepsia
  • Haemorrhagic necrotic gastritis
  • Hepatitis
  • Stevens-Johnson Syndrome
  • Gynaecomastia
  • Myalgia
 

Risedronate sodium

Risedronate, classified as an antiresorptive medication, is a potent pyridinyl bisphosphonate that binds to bone hydroxyapatite and inhibits osteoclast mediated bone resorption. It prevents bone loss and lowers the risk of breaking bones.

Risedronate is rapidly absorbed throughout the upper gastrointestinal tract and Excreted through urine and feces.

There is no evidence of systemic metabolism of risedronate.

Risedronate is about 24% binded with human plasma protein and the bioavailabilty of Risedronate is decreased when administered with food.

Common:

  • Abdominal pain
  • Musculoskeletal pain

Rare:

  • Abnormal liver function tests
  • Iritis
  • Angioedema
  • Uveitis
 

Strontium ranelate

Besides increasing bone formation by osteoblasting precursor replication and collagen synthesis, it reduces bone resorption and improved bone biomechanical properties.

The absorption, distribution and binding to plasma proteins are low. As a divalent cation, strontium is not metabolized, but rapidly eliminated via the kidneys and the gastrointestinal tract. Intake of strontium ranelate with calcium or food reduces drug’s absorption rate. Not suitable for long term administration at high doses, woman who are pregnant and lactating, as well as pediatrics.

Common:

  • Nausea
  • Diarrhoea
  • Dermatitis
  • Myocardial infarction
  • Headache
  • Memory loss

Rare:

  • Stevens-Johnson syndrome
  • Toxic epidermal
  • Necrolysis

Several factors that need consideration when comparing two oral anti-diabetic drugs include degree of glycemic lowering needed to attain target goal range, effect of the medication on weight and lipid profiles, contraindications, side effects, cost, and potential level of adherence to the regimen. The two drugs for comparison are namely metformin and gliclazide.

Besides having the same level of glycemic lowering percentage, both metformin and gliclazide are also considered one of the least expensive oral anti-hyperglycemic agents (Reinhold & Earl, 2014; Mozaffari, 2013; Holt, Cockram, Flyvbjerg & Goldstein, 2011). One of the potential problems with anti-diabetic medication, is that the conventional dosage form is given in 2 to 3 doses daily, and it causes a conflict in compliance rate for the elderly who has poor memories. In this circumstance, both metformin and gliclazide offers the option of single daily dose with either extended-release metformin or gliclazide modified release tablets. Of course the side effects, improvements and degree of glycemic lowering are the same as conventional tablets (Unger, 2013; Barnett, 2012).

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Metformin is well known for being the first line drug against diabetes type II treatment over the past decades for some reasons. First, Metformin as a biguanide, acts on pancreas independently, inhibiting the liver’s production of glucose, thus controlling blood glucose by improving insulin sensitivity and reducing insulin requirement. If it’s taken when blood glucose is normal or low, it does not stimulate insulin release in the pancreas, thus poses little threat of hypoglycemic (Lehne, 2013). Second, Metformin treatment results in a moderate reduction in circulating triglyceride levels, causing an improvement in lipid profiles that leads to the occurrence of weight loss (Goldstein & Muller-Wieland, 2013). Third, having a high frequency of GI side effects due to the inhibition of carbohydrates being digested can be minimized by slow-dose titration and by taking the medication with food.

No matter how safe a medication is, contraindications and adverse side effects still need to be observed. As for metformin, renal or hepatic dysfunction patients are contraindicated, and lactic acidosis due to metformin’s accumulation, is considered one of the rare but fatal adverse side effect. The only down side of metformin is, it should be withhold prior to radiological procedures involving contrast dye, as it predisposes patients to acute renal impairment (Reinhold & Earl, 2014).

Gliclazide, on the other hand, is classified as sulfonylureas. It works by increasing insulin release from pancreatic beta cells, driving blood glucose levels down, causing hypoglycemia if taken when blood glucose is normal or low, thus should only be prescribed to patients likely to have regular food intake. Driving or operating machinery during the initial treatment phase needs to be careful as hypoglycemia might occur (Lehne, 2013). Besides having minimal effect on lipid profile, Gliclazide causes undesirable weight gain due to increased insulin secretion and reduced glucose excretion (Meeking, 2011). Contraindications, particularly renal or liver disease patients, as well as rare but fatal adverse side effects of gliclazide, impairment of liver function, must still be observed (MIMS Australia, 2014).

In conclusion, while there is significant debate regarding specific treatment for patients with type II diabetes, most experts agreed upon metformin’s usage as first line drug, judging from its effectiveness, generally well-tolerated cost effective and long term usage.

References

Barnett, A. (2012). Oxford diabetes library: Type 2 diabetes (2nd ed.). UK: Oxford University Press.

Goldstein, B. J., & Muller-Wieland, D. (2013). Type 2 diabetes: Principles and practice (2nd ed.). USA: Informa Healthcare.

Holt, R. I. G., Cockram, C., Flyvbjerg, A., & Goldstein, B.J. (2011). Textbook of diabetes (4th ed.). UK: Wiley-Blackwell.

Lehne, R. A. (2013). Pharmacology for nursing care. (8th ed.). USA: Elsevier Saunders.

Meeking, D. R. (2011). Understanding diabetes and endocrinology: A problem-orientated approach. UK: Manson Publishing Ltd.

MIMS Australia. (2014). Mimsonline. Retrieved on 28.3.2014, from

https://www-mimsonline-com-au.libraryproxy.griffith.edu.au/Search/Search.aspx.

Mozaffari, M. S. (2013). New strategies to advance pre/diabetes care: Integrative approach by PPPM. USA: Springer.

Reinhold, J. A., & Earl, G. (2014). Clinical therapeutics primer: Link to the evidence for the ambulatory care pharmacist. USA: Jones & Bartlett Learning.

Unger, J. (2013). Diabetes management in primary care (2nd ed.). China: Williams & Wilkins.

MIMS Australia. (2014).

 

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