NUR 2047 Pharmacology Lecture 5 PDF

NUR 2047 Pharmacology Lecture 5 Drugs affecting the Digestive and the Endocrine System Digestive System  Learning Objectives After this lecture, students should be able to:- ❖Understand gastric ulcer and GERD ❖Describe the mechanism of action of drugs for gastric ulcer and GERD...

NUR 2047 Pharmacology Lecture 5 Drugs affecting the Digestive and the Endocrine System Digestive System  Learning Objectives After this lecture, students should be able to:- ❖Understand gastric ulcer and GERD ❖Describe the mechanism of action of drugs for gastric ulcer and GERD ❖Describe the mechanism of action of different group of laxatives The digestive system List some ways you can celebrate Asian Pacific Heritage Month. Here are a few examples: Discover Asian Pacific American artists Read Asian Pacific American authors Listen to Asian Pacific American Heritage musicians Learn important moments of Asian Pacific American Heritage history Natural defenses against stomach acid List the resources you used for your research: Source #1 Source #2 Source #3 Mechanism of peptic ulcer formation List some ways you can celebrate Asian Pacific Heritage Month. Here are a few examples: Discover Asian Pacific American artists Read Asian Pacific American authors Listen to Asian Pacific American Heritage musicians Learn important moments of Asian Pacific American Heritage history  Functions of stomach acid Importance of HCL secretion ❖Create an acidic environment Inactivate pathogenic microbes Protect us from infection ❖Helps pepsin digest protein Gastric acid formation https://www.youtube.com/watch?v=oAEwnbi9Cio https://www.youtube.com/watch?v=Fz871WjMzdU  Gastric ulcers ❖Gnawing or burning or pain at upper abdomen ❖If the erosion progresses deeper into the mucosa, bleeding or perforation will occur Helicobacter pylori (H pylori) ❖Bacteria that is usually found in the stomach ❖Can penetrate the mucoid lining of the stomach to cause infection ❖Has been associated with the cancers of the stomach, esophagus, colon, rectum  Gastroesophageal reflux disease (GERD) ❖Common condition in which the acidic contents of the stomach move upwards into the esophagus ❖Causes an intense burning known as heartburn and may lead to ulcers in the esophagus  Drug therapy ❖Proton-pump inhibitors (PPIS) ❖H2 receptor blockers ❖Antacids ❖Antibiotics  Proton-pump inhibitors (PPIS) ❖Proton pump –secrete gastric acid ❖PPIs act by blocking the enzyme responsible for secreting hydrochloric acid in the stomach. This group is the most potent acid inhibitors ❖Reduce acid secretion into the stomach by binding irreversibly to the enzyme H+, K+, ATPase on the parietal cells https://www.youtube.com/watch?v=MTOkPl5deHw ❖Most effective medications available for reducing acid secretion and thus are preferred drugs for the treatment of peptic ulcer disease and GERD ❖Treatment of ulcers, GERD, H pylori infection ❖Omeprazole (Losec), Esomeprazole (Nexium), Pantoprazole, Lansoprazole, Rabeprazole Proton-pump inhibitors (PPIS) https://www.youtube.com/watch?v=oAEwnbi9Cio  H2 receptor blockers ❖H2 receptor -- Responsible for acid production in the stomach ❖Blocking the H2 receptor will reduce the acid production ❖Treatment of ulcers, GERD ❖Famotidine (Pepcidine), Cimetidine (Tagamet), ❖Ranitidine (Zantac) Antacids ❖Rapidly neutralize stomach acid ❖Compounds of aluminum, magnesium or calcium ❖Combinations of aluminum hydroxide and magnesium hydroxide are the most common type ❖Reduce the symptoms of Peptic ulcer disease and GERD ❖Triact (AL hydroxide + Mg hydroxide)  Nursing considerations ❖PPIs Side effects – headache, dizziness, diarrhea, abdominal pain, cough Take 15-30 mins before food Do not chew ❖ H2 receptor blockers Side effects – dizziness, headache, diarrhea, Take with food ❖Antacids Side effects – constipation, diarrhea Triact – need to chew Take with/after food Administer apart from other drugs (1 hour before or 2 hours after)  Antibiotics to treat Helicobacter pylori ❖Antibiotics are administered to eliminate Helicobacter Pylori ❖Amoxicillin (Amoxil) ❖Clarithromycin ❖Metronidazole (Flagyl) ❖Tetracycline  H pylori eradication First line therapy (triple therapy) ❖14 day course ❖PPI, Clarithromycin, Amoxicillin Second line therapy (quadruple therapy) ❖14 day course ❖PPI, Bismuth, Tetracycline, Metronidazole Sequential therapy ❖5 day course (dual therapy) – PPI, Amoxicillin ❖5 day course (triple therapy) – PPI, Clarithromycin, Amoxicillin  Constipation ❖Infrequent bowel movements ❖Difficult passage of stool ❖Less than 3 bowels movements/week ❖Persist for several weeks or longer ❖Constipation commonly occurs when stool moves too slowly through the digestive tract or cannot be effectively eliminated from the rectum, which causes the stool to become hard and dry  Bulk-forming Laxatives ❖Absorb water, add to size of the fecal mass ❖Distend bowel to stimulate peristalsis (initiate bowel activity) ❖Prevent and treat constipation ❖Not used when a rapid and complete bowel evacuation is needed E.g Psyllium husk ❖ Insoluble fiber, indigestible and not absorbed by the GI tract ❖ With water, it swells and increases the size of the fecal mass ❖ Metamucil Nursing considerations ❖ Take with one full glass of water ❖ Takes around 1 to 3 days to work ❖ May cause fecal impaction  Osmotic Laxatives ❖Increases osmotic pressure in the colon and attracts water into the colon ❖Water is retained in the fecal mass ❖Hydrates, softens the stool and eases defecation ❖May cause dehydration and electrolyte depletion ❖E.g Lactulose, Klean prep Nursing considerations ❖ Increase fluid intake to prevent dehydration ❖ Use with caution in patients with conditions e.g electrolytes imbalance, cardiac and renal disease ❖ Takes around 1 to 3 days to work ❖ May cause diarrhoea  Stool softeners/Surfactants ❖Lowers surface tension of the stool so that water can penetrate into the stool ❖Makes stool more soft and loose so that it is easier to pass out E.g. Docusate Nursing considerations ❖Takes around 1 to 3 days to work ❖May cause diarrhoea  Stimulants ❖Promote peristalsis by irritating the bowel mucosa and causes increased smooth muscle contraction ❖Also leads to increased water and electrolyte into the colon ❖Rapid-acting ❖More likely to cause diarrhea and cramping ❖Should only be used occasionally, may cause dependence and depletion of fluid and electrolytes ❖E.g Bisacodyl (Dulcolax) Senna (usually taken at bedtime)  Stimulants Nursing considerations ❖Oral route takes around 6 to 12 hours to work ❖Rectal route takes around 20 mins to work ❖May cause diarrhea, abdominal cramps Endocrine System  Learning Objectives After this lecture, students should be able to:- ❖Understand feedback mechanism of endocrine system ❖Describe the mechanism of action of drugs for diabetes mellitus The Endocrine system  Hormones ❖Chemical messengers released in response to a change in the body’s internal environment ❖In the endocrine system, it is common for one hormone to control the secretion of another hormone ❖Most endocrine glands work by feedback mechanism ❖Feedback mechanism is a loop system in which the system responds by Activation of one component leads to the activation of another (+ve feedback) Activation of one component results in the inhibition of another (-ve feedback) Hormones associated with the Hypothalamus and Pituitary Gland  Hypothalamus and Pituitary ❖The hypothalamus secretes chemicals called releasing factors/hormones ❖They travel (via blood vessels) a short distance to the anterior pituitary gland ❖The releasing factors tell the pituitary which hormone to release ❖After the pituitary releases it, the hormone travels to its target organ to cause its effect ❖Hormones are used as replacement therapy, anti-neoplastics, or as antihormones  Hormone replacement therapy Goals vary widely ❖Hormones administered to patients who are unable to secrete sufficient quantities of their own endogenous hormones ❖Used in cancer chemotherapy to shrink size of hormone- sensitive tumors Tamoxifen (a selective estrogen receptor modulator, which attaches to hormone receptors in breast cancer cells. It prevents the cancer cells from accessing the hormone they need to multiply and grow)  Thyroid Glands ❖The thyroid gland controls the basal metabolic rate and affects virtually every cell in the body ❖Thyroid hormones is a combination of two different hormones, tyroxine (T4) and triiodothyronine (T3), both of which require iodine for their synthesis ❖Thyrotropin-releasing hormone (TRH) from the hypothalamus stimulates the pituitary to secrete thyroid stimulating hormone (TSH) ❖Thyroid-stimulating hormone (TSH) then stimulates the thyroid gland to release thyroid hormone (T3, T4) ❖As blood levels of thyroid hormone increase, negative feedback suppresses the secretion of TRH and TSH Feedback mechanism of the Thyroid Gland  Hypothyroidism ❖Caused by insufficient secretion of either TSH or thyroid Hormone ❖Hypothyroidism – weakness, muscle cramps, dry skin, slow metabolism, fatigue, slurred speech, bradycardia, weight gain, low body temperature, intolerance to cold environment ❖If left untreated, can lead to coma or death ❖Causes: autoimmune disease (Hashimoto’s disease), surgical removal of the thyroid gland or aggressive treatment with anti-thyroid drugs ❖Treatment with natural or synthetic thyroid hormone ❖Levothyroxine  Levothyroxine Nursing considerations ❖Usually starts with a low dose and titrated with blood levels monitoring ❖Over supplementation can cause hyperthyroidism ❖Avoid taking with calcium and iron rich foods/supplements as it interferes with the absorption ❖Avoid taking with grapefruit juice ❖Avoid taking with high fiber foods ❖Take on an empty stomach (at least 30 mins before food) in the morning  Hyperthyroidism ❖Caused by an overactive thyroid where the thyroid gland Produces too much of the thyroid hormones ❖Symptoms: goiter, nervousness, tremors, irritability, insomnia, tachycardia, palpitations, weight loss, hyperthermia, heat intolerance ❖Causes: autoimmune disease (Graves disease), thyroid nodules, some medication Treatment ❖Surgical removal of thyroid gland (thyroidectomy) ❖Anti-thyroid medication (Carbimazole, Propylthiouracil(PTU)) ❖Radioactive iodine treatment to kill or inactivate some of the hyperactive thyroid cells  Carbimazole Nursing considerations ❖Usually takes 2 to 3 months for the full benefits of the medication ❖Drug dose is monitored with blood results ❖Not suitable for pregnant women (carbimazole) ❖Over treatment can cause hypothyroidism Diabetes Mellitus (DM) ❖Type 1 – body cannot produce insulin ❖Type 2 – body cannot produce enough insulin or there is insulin resistance Caused by a deficiency of insulin (either the pancreas does not produce enough insulin or the body cannot effectively use the insulin) ❖Insulin receptors in the target tissues have become unresponsive to the hormone Insulin resistance Usually controlled by non-insulin anti-diabetic drugs Proper diet and exercise can sometimes increase the sensitivity of insulin receptors to the point that drug therapy is unnecessary in Type 2 diabetes  Diabetes Mellitus (DM) ❖Signs and symptoms High fasting blood sugar on two separate occasions Polyuria (excessive urination) Polyphagia (increased hunger) Polydipsia (increased thirst) Glycosuria (presence of glucose in urine) Weight loss Fatigue Microscopic view of Islet of Langerhans Insulin, Glucagon and Blood Glucose levels  Oral and parenteral hypoglycemic drugs Classified by their chemical structures and mechanism of action ❖Sulfonylureas ❖Biguanides ❖Alpha-glucosidase inhibitors ❖Dipeptidyl peptidase-4 inhibitors (DPP-4) ❖Insulin  Sulfonylureas ❖Used in type 2 diabetes ❖Act by increasing the secretion of insulin from the beta cells in the pancreas ❖First generation Tolazamide, Tolbutamide ❖Second generation Glibenclamide (Daonil), Gliclazide (Diamicron) ❖Third generation Glimepiride (Amaryl) Sulfonylureas  Sulfonylureas Mechanism of action ❖Sulfonylureas bind to and close ATP-sensitive K+ channels on the cell membrane of pancreatic beta cells, which depolarizes the cell by preventing potassium from exiting ❖The rise in K+ causes depolarization and opens Ca2+ channels ❖The rise in intracellular Ca2+ leads to increased secretion of insulin https://www.youtube.com/watch?v=iacmy7v9mdw  Sulfonylureas ❖Side effects Can cause hypoglycemia (as a result of excess insulin production and release) GI distress (nausea, vomiting, epigastric discomfort) Weight gain ❖ Nursing considerations Give 15 mins before meals, followed by a proper meal Monitor blood glucose levels Carry simple carbohydrates or sugars all the time Control of diabetes is also by lifestyle management (diet, exercise, stress) Contraindicated in severe hepatic or renal impairment  Biguanides ❖Used in type 2 diabetes ❖First line therapy especially for obese patients ❖Decreases intestinal absorption and hepatic production of glucose and reduces insulin resistance ❖Does not promote insulin release from pancreas ❖In addition to lowering blood glucose levels, it also lowers triglyceride and total and low-density lipoprotein cholesterol levels ❖Metformin (Glucophage)  Biguanides Mechanism of action ❖Do not affect the output of insulin ❖Reduce glucose absorption from GI tract ❖Increase insulin sensitivity, leading to reduced blood glucose levels, increased uptake and utilization of glucose by the cells and decreased gluconeogenesis Biguanides ❖Side effects GI related (nausea, vomiting, dyspepsia, abdominal discomfort, bloating, diarrhea, metallic taste) Rare but serious/fatal (lactic acidosis) – increased risk in patients with chronic kidney disease ❖Nursing considerations Give with meals Monitor blood glucose levels for effect Control of diabetes is also by lifestyle management (diet, exercise, stress) Contraindicated in severe hepatic or renal impairment Stop 24 hours before investigations with contrast/dye and restart only 48 hours later  Alpha-Glucosidase Inhibitors ❖Used in type 2 diabetes ❖Act by slowing the digestion of carbohydrates ❖Establish better glycemic control with regard to postprandial hyperglycemia ❖Acarbose (Glucobay)  Alpha-Glucosidase Inhibitors Mechanism of action ❖ The digestion of dietary starch and disaccharides is dependent on the action of alpha-glucosidase (enzyme located in the border of the intestinal tract) ❖Hence alpha-glucosidase inhibitors slow the digestion of starch and disaccharides, leading to a decreased rate of glucose absorption ❖Resulting in lowered levels of postprandial blood glucose  Alpha-Glucosidase Inhibitors ❖Side effects GI related (flatulence, diarrhoea) ❖Nursing considerations Give at the start of meals Monitor blood glucose levels for effect Control of diabetes is also by lifestyle management (diet, exercise, stress) Contraindicated in severe hepatic or renal impairment  Dipeptidyl peptidase-4 inhibitor (DPP-4) ❖Used in type 2 diabetes ❖The incretins are peptide hormones, released by beta cells of the pancreas, into the circulation in response to incoming nutrients, within minutes of eating ❖Two hormones (incretins) Gastric inhibitory polypeptide (GIP) Glucagon like peptide-1 (GLP-1) Sitaglipitin (Januvia) Linaglipitin (Trajenta) Vildagliptin (Galvus)  Dipeptidyl peptidase-4 inhibitor (DPP-4) Mechanism of action ❖ Work by inhibiting the degradation of the incretin hormones(GIP and GLP-1) that stimulate the release of insulin and inhibit the release of glucagon in response to a meal ❖Increase insulin from beta cells and reduce glucose levels ❖Decrease glucagon production from alpha cells → reduced glucose conversion ❖As a result → reduce blood glucose levels  Dipeptidyl peptidase-4 inhibitor (DPP-4) ❖Side effects GI upset – nausea, stomach pain, diarrhoea Headache Increased risk of pancreatitis Nursing considerations Give with meals Monitor blood glucose levels Control of diabetes is also by lifestyle management (diet, exercise, stress)  Insulin ❖Insulin is a naturally occurring hormone made by the pancreas that helps the body use sugar for energy → lower blood sugar levels Type 1 DM Life-long insulin injections for Type 1 DM patients Type 2 DM May be given in Type 2 DM patients (short term and long term)  Insulin Mechanism of action ❖ Insulin acts on specific receptors located on the cell membrane of every cell ❖This stimulates the glucose transport across the cell membrane ❖The end result is reduced blood glucose levels  Insulin ❖Rapid-acting insulin ❖Short-acting insulin ❖Intermediate-acting insulin ❖Long-acting insulin ❖Combination insulin (short and intermediate acting insulin)  Insulin Insulin type Onset Peak time Duration Examples Rapid acting 15 mins 1 hour 2-4 hours Novorapid Given right before a meal Short acting 30 mins 2-3 hours 3-6 hours Actrapid, Humulin R Given 15-30 mins before a meal Intermediate acting 2-4 hours 4-12 hours 12-18 hours Humulin NPH, Protaphane Given 15-30 mins before a meal Long acting 2 hours No peak Up to 24 hours Lantus, Levemir  Insulin ❖Side effects Hypoglycemia Injection site (redness, pain ,lipodystrophy) ❖Nursing considerations Give before meals Monitor blood glucose levels Carry simple carbohydrates or sugars all the time Rotate sites of injection Control of diabetes is also by lifestyle management (diet, exercise, stress)  References ❖ Holland, L.N., Adams, M., and Brice, J., (2017). Core concepts in Pharmacology. 5th edition. Pearson. ❖ Karch, A. M. (2020). Lippincott Pocket Drug Guide for Nurses (p.115). Wolters Kluwer Health. Kindle Edition. ❖ Skidmore-Roth, L. (2009). Mosby’s nursing drug reference (22nd edn.). St. Louis: Mosby. Q&A