Diabetes Types & Classification Summary PDF

Types and Classification of Diabetes 1. Type 1 Diabetes Mellitus (T1DM): Results from β-cell destruction, typically causing absolute insulin deficiency. 2. Type 2 Diabetes Mellitus (T2DM): Ranges from predominant insulin resistance with relative insulin deficiency to insulin...

Types and Classification of Diabetes 1. Type 1 Diabetes Mellitus (T1DM): Results from β-cell destruction, typically causing absolute insulin deficiency. 2. Type 2 Diabetes Mellitus (T2DM): Ranges from predominant insulin resistance with relative insulin deficiency to insulin secretion defects with insulin resistance. 3. Other Specific Types: Includes genetic defects in β-cells or insulin action, exocrine pancreas diseases, endocrinopathies, drug or chemical-induced diabetes, and infections. 4. Gestational Diabetes (GDM): Diagnosed during pregnancy. Complications of Diabetes Mellitus - Insulin inhibits glycogenolysis and gluconeogenesis in liver  Macrovascular and Microvascular Damage: Affects the = ↳ isused a ideas eyes, kidneys, and nervous system. ---...j, 4 -  Associated Conditions: Major cause of blindness, renal - failure, heart attack, and stroke. ---- Treatment Goals for Type 2 Diabetes  Primary Goals: o Maintain blood glucose within normal limits. o Prevent long-term complications of the disease   Long-acting insulins: Provide stable, basal coverage throughout the day.  Factors Affecting Insulin Activity:  sequences. & Onset and duration vary due to differences in amino acid  External factors include dose, injection site, temperature, and - - physical activity. - -  Forms of Insulin:  Rapid-acting and short-acting insulins are clear solutions with added zinc for stability.  Intermediate-acting insulins are turbid suspensions with protamine for extended effects.  An inhalable powder form of rapid-acting insulin is available for alveolar absorption..  Manufacturing of Insulin:  Current Treatment Regimens:  Human insulin is produced using bacterial recombinant DNA technology. =>  Long-acting insulins provide consistent background  Modifications to the amino acid sequence create various coverage. - insulin types.  Rapid-acting insulins are used at mealtimes for effective - glucose control. ~  Types of Insulin Preparations:  Rapid-acting insulins: Fast onset, used to manage mealtime blood sugar spikes. Key Comparisons:  Intermediate-acting insulins: Such as NPH, modified for prolonged action.  Onset of Action: Ultrashort-acting insulins (Insulin Lispro, Aspart, Glulisine) have the fastest onset* (10-15 minutes), --  while long-acting insulins (Insulin Glargine, Detemir) take o The most common method for insulin delivery. 1-2 hours. - - o Allows for the gradual absorption of insulin into the (2-3 hours), - bloodstream. -  Peak Effect: Regular insulin has a distinct peak E while long-acting insulins are designed to have >no peak L 2. Intravenous (I.V.) Injection: effect for steady coverage. - - o Used in hyperglycemic emergencies for rapid action.  - Duration of Action: Short-acting insulins last for a shorter o Regular insulin is typically administered this way. duration (5-8 hours), whereas long-acting insulins can last 3. Intravenous Infusion: more than 24 hours. o Continuous delivery method to avoid multiple  Administration Routes: Regular insulin can be given injections. o Useful in hospital settings for precise control of intravenously in emergencies, while intermediate and long- acting insulins are typically administered subcutaneously. blood glucose levels.  Special Features: Ultrashort-acting insulins allow for 4. Insulin Pumps (Open-loop Pumps): o Provide continuous subcutaneous insulin flexible dosing and reduced risk of hypoglycemia, while administration. long-acting insulins provide a steady insulin level throughout o Eliminate the need for multiple daily injections. the day. o Devices are user-programmable to deliver  Various premixed combinations of human insulins: personalized basal and bolus doses based on self- 70% NPH insulin + 30% regular insulin monitored blood glucose levels. 50% NPL insulin + 50% lispro insulin 5. Portable Pen Injectors: 75 % NPL insulin + 25% lispro insulin o Contain insulin cartridges and replaceable needles for convenience. o Allow for easy and discreet self-administration of Insulin Administration insulin. 6. Aerosol Preparation: Why Insulin is Not Administered Orally: o Inhaled insulin is a powdered form designed for absorption through the alveolar walls.  Insulin is a polypeptide hormone that is degraded in the o Challenges include creating particles small enough to gastrointestinal tract, rendering it ineffective when taken navigate the bronchial tree without being trapped. orally. Administration Methods: Insulin is inactivated by insulin- degrading enzyme (also called insulin 1. Subcutaneous Injection:  3. Allergic Reactions and Local Injection Site Reactions protease, which is found mainly in the o Type: Immediate-type hypersensitivity (rare), may include urticaria. liver and kidney) o Mechanism: Caused by histamine release from tissue mast cells sensitized by anti-insulin IgE antibodies. o Treatment: Antihistamines or corticosteroids are Adverse Reactions to Insulin commonly used. 1. Hypoglycemia (Most Common) 4. Weight Gain o Impact: Can be a common side effect of insulin o Cause: Often due to an overdose of insulin. o Symptoms: Tachycardia, confusion, vertigo, therapy. diaphoresis. 5. Insulin Immune Resistance o Cause: Development of high-titer circulating IgG o Treatment:  Conscious Patient: Administer orange juice, anti-insulin antibodies. glucose, sugar-containing beverages, or food.  Unconscious Patient (Severe Note: Hypoglycemia):  Intravenous Infusion: 20-50 mL of  Renal Insufficiency Consideration: Diabetics with renal 50% glucose solution over 2-3 insufficiency may require insulin dose adjustments. minutes.  In Absence of IV Access: Administer 1 mg of glucagon (subcutaneous or intramuscular) to restore consciousness within about 15 minutes, followed by food consumption. 2. Lipodystrophy o Description:  Atrophy of subcutaneous fat due to concentrated insulin preparations.  Hypertrophy of subcutaneous fatty tissue from repeated injections at the same site.   Designed for the treatment of patients with Type 2 Diabetes Administ Type of Classifica Onset of Peak Duration Special Pregnanc ration Insulin tion Action Effect of Action Features y Use Route Subcutan Rapidly lowers who cannot manage their condition through diet alone. May be used in combination with insulin or other eous, Regular Insulin Short- acting 30 minutes 2 to 3 hours 5 to 8 hours intraven ous in blood sugar; Safe if needed  hypoglycemic agents to control hyperglycemia, particularly to 1 hour safe for emergen pregnanc cies y Flexible dosing; Only if in patients with long-standing diabetes. Insulin Ultrashor 15 30 to 90 3 to 5 Subcutan lower clearly Lispro t-acting minutes minutes hours eous risk of needed Important Considerations: hypoglyc emia Flexible dosing; Only if Insulin Ultrashor 10 to 20 1 to 3 3 to 5 Subcutan lower clearly Aspart t-acting minutes hours hours eous risk of hypoglyc emia needed  Not for Type 1 Diabetes: Oral hypoglycemic agents should Flexible dosing; not be prescribed to patients with Type 1 diabetes. Why?. Only if Insulin Ultrashor 15 30 to 90 3 to 5 Subcutan lower clearly Glulisine t-acting minutes minutes hours eous risk of needed Non-Insulin Antidiabetic Drugs: hypoglyc emia Slower onset Intermed and Key Points Lente 1 to 2 6 to 12 12 to 18 Subcutan Not iate- peak, Insulin hours hours hours eous specified acting sustaine d action; not for IV  Insulin Secretagogues stimulate the pancreas to release Contains Useful NPH Intermed protamin except in Insulin 1 to 2 4 to 10 10 to 16 Subcutan iate- e for diabetic (Isophan e) acting hours hours hours eous prolonge d action ketoacid osis more insulin. Provides steady  Insulin Sensitizers improve the body’s response to insulin.  Alpha-Glucosidase Inhibitors slow carbohydrate basal coverage Safe for Insulin Long- 1 to 2 Subcutan No peak 24 hours ; pregnanc Glargine acting hours eous precipita tion at y absorption in the intestines. injection site  Amylin Analog helps regulate blood sugar by slowing gastric emptying and promoting satiety. Dose- depende nt Insulin Detemir Long- acting 1 to 2 hours No peak More than 24 Subcutan eous hypoglyc emic Safe for pregnanc  Gastrointestinal Hormones include incretin mimetics and hours effect; administ y DPP-4 inhibitors that enhance insulin secretion. er twice daily  SGLT2 Inhibitors promote glucose excretion through the urine. Summary Non-Insulin Antidiabetic Drugs  Insulin Secretagogues are primarily used to stimulate the Purpose: pancreas to produce insulin, but they carry a risk of hypoglycemia.   Insulin Sensitizers improve the body's response to insulin,  Glucagon Reduction: Lower serum glucagon levels. with metformin being the most common first-line agent.  Insulin Receptor Binding: Enhance the binding of insulin Thiazolidinediones can lead to weight gain and fluid to its receptors. retention.  Alpha-Glucosidase Inhibitors focus on slowing Pharmacokinetics: carbohydrate absorption, making them effective for controlling post-meal blood sugar levels but may cause  Administration: Orally. gastrointestinal issues.  Protein Binding: Bind to serum proteins.(lipid soluble )  Amylin Analog is used to complement insulin therapy  Duration of Action: o Tolbutamide: 6-12 hours.  Use Cases: Incretin analogs are used when more aggressive o Second-Generation Agents: Approximately 24 glycemic control is needed, while DPP-4 inhibitors offer a hours. more convenient option for patients requiring less intensive  Metabolism: Primarily in the liver. management.  Excretion: Drugs and metabolites excreted by the kidneys. Adverse Effects: Insulin Secretagogues 2  Weight Gain: Common. 1. Sulfonylureas  Hyperinsulinemia: Increased insulin levels.  Hypoglycemia: Risk of low blood sugar. Examples:  Fetal Impact: Can deplete fetal pancreatic insulin; caution in pregnant women with type 2 diabetes.  First-Generation: Tolbutamide  Second-Generation: Glyburide, Glipizide, Glimepiride Mechanism of Action: 2. Meglitinide Analogs #  Insulin Release: Stimulate insulin secretion from pancreatic β-cells by blocking ATP-sensitive K+ channels, causing Examples: Repaglinide, Nateglinide - depolarization and opening of voltage-gated calcium Mechanism of Action: channels, leading to increased intracellular calcium and insulin secretion. iiiiiiiii I : a Love - - one : "  55.  Postprandial Regulation: Act as postprandial glucose Insulin Sensitizers 2 regulators, effectively stimulating early insulin release after meals. 1. Biguanides (Metformin)  Pancreatic Dependency: Action depends on functional pancreatic β-cells. Overview:  Binding Site: Bind to a distinct site on the sulfonylurea receptor of ATP-sensitive potassium channels, triggering  Only Available Biguanide insulin secretion.  Requires insulin for action  Increases glucose uptake and decreases insulin resistance Pharmacokinetics: without increasing insulin secretion.  Lower risk of hypoglycemia compared to sulfonylureas.  Administration: Orally, taken 1-30 minutes before meals.  Absorption: Well absorbed. Mechanism of Action:  Metabolism: Metabolized by CYP3A4 to inactive products in the liver.  Reduces hepatic glucose output by inhibiting  Excretion: Excreted through bile. gluconeogenesis. =  Slows intestinal absorption of sugars. Adverse Effects:  Reduces LDL and VLDL cholesterol, increases HDL cholesterol.  Hypoglycemia: Lower incidence compared to sulfonylureas.  Effects may take 4-6 weeks to become apparent.  Caution: Use with caution in patients with hepatic impairment. Pharmacokinetics:  Weight Gain: Less significant than with sulfonylureas.  Absorption: Well absorbed orally, highest concentrations in Drug Interactions: saliva and intestinal wall.  Protein Binding: Not bound to serum proteins. 1. Enzyme Inhibitors: (e.g., ketoconazole, itraconazole)  Metabolism: Not metabolized; excreted unchanged in urine. enhance repaglinide's effect. 2. Enzyme Inducers: (e.g., barbiturates, carbamazepine, Adverse Effects: rifampin) decrease its glucose-lowering effect. Gluto 3. Risk of Severe Hypoglycemia: Possible with certain 1. Gastrointestinal disturbances (diarrhea, nausea). interactions.  2. Interference with vitamin B12 absorption (long-term use).  Act on peroxisome proliferator-activated receptor gamma 3. Rarely, can cause fatal lactic acidosis. (PPAR-γ), a nuclear hormone receptor.  Pioglitazone also targets PPAR-α. Contraindications: i  Increase insulin sensitivity and improve hyperglycemia, hyperinsulinemia, hypertriacylglycerolemia, and HbA1c  Renal disease. levels.  Hepatic disease.  Cardiac or respiratory insufficiency. Pharmacokinetics:  History of alcohol abuse.  Severe infections.  Absorption: Well absorbed after oral administration.  Pregnancy.  Protein Binding: Extensively bound to serum albumin.  Metabolism: Metabolized by cytochrome P450 enzymes. Drug Interactions:  Excretion: Metabolites excreted in urine; parent compound eliminated via bile.  Enhanced effects with cimetidine, furosemide, nifedipine. - - - Adverse Effects: Other Uses:  Fluid retention, mild anemia, peripheral edema (especially  Effective in treating polycystic ovary syndrome (PCOS), when combined with insulin). => lowering insulin resistance, promoting ovulation, and  Increased risk of heart failure. potentially pregnancy.  Weight gain due to fluid retention.  Hepatotoxicity associated with Troglitazone (monitor liver function); no hepatotoxicity reported for Rosiglitazone or 2. Thiazolidinediones (Glitazones) Pioglitazone.  May reduce the efficacy of estrogen-containing Overview: contraceptives.  Examples: Pioglitazone, Rosiglitazone (Troglitazone Contraindications: withdrawn due to hepatotoxicity).  Insulin sensitizers that do not promote insulin release from  Pregnancy. pancreatic β-cells (no hyperinsulinemia).  Liver disease.  Heart failure. Mechanism of Action: Other Uses: Contraindications  Improve insulin sensitivity and may induce ovulation in  Inflammatory bowel disease, colonic ulceration, intestinal women with PCOS. obstruction. Because these patients already have the side effects so if we give them this leads to worsening symptoms Alpha-Glucosidase Inhibitors Hypoglycemia Management Key Drugs  Can occur when combined with sulfonylureas or insulin; treat with glucose, not sucrose.  Acarbose  Miglitol Amylin Analog: Pramlintide Mechanism of Action Overview  Inhibition: Reversible competitive inhibitors of intestinal α- glucosidases, reducing the digestion and absorption of  Pramlintide is a synthetic analog of amylin, a hormone carbohydrates. produced by pancreatic β-cells that plays a role in glycemic control. Pharmacokinetics Mechanism of Action  Acarbose: Poorly absorbed; metabolized by intestinal bacteria; some metabolites excreted in urine.  Actions:  Miglitol: Well absorbed but excreted unchanged by the o Suppresses glucagon release. kidneys o Slows gastric emptying.  Miglitol more potent than acarbose (6 times) o Reduces appetite via central nervous system (CNS)  We need drug that is poorly absorbed because we need effects. localize effect on GIT and less systemic efect Pharmacokinetics Adverse Effects  Administration: Subcutaneous injection.  Flatulence, diarrhea, abdominal cramping.  Absorption: Rapidly absorbed.   Duration: Short duration of action.  Exenatide: Shorter half-life; twice-daily dosing.  Combination: Often used with insulin to help control  Caution in patients with severe renal impairment. postprandial glucose levels. Adverse Effects Adverse Effects  Common: Nausea, vomiting, diarrhea, and constipation.  Serious: Potential for pancreatitis and concerns over thyroid  Risk of hypoglycemia. C-cell tumors (Liraglutide). Gastrointestinal Hormone Modulators Dipeptidyl Peptidase-4 (DPP-4) Inhibitors 1. Incretin Analog: Exenatide  Examples: Sitagliptin, Vildagliptin, Saxagliptin  Incretins: Hormones (GIP and GLP-1) produced in response Mechanism of Action to nutrient intake; in T2DM, GLP-1 levels are significantly reduced.  DPP-4 inhibitors block the DPP-IV enzyme, which is  Exenatide: A polypeptide homologous to GLP-1, acts as a responsible for inactivating incretin hormones such as GLP- GLP-1 receptor agonist. 1. ‫يرتبط مبستقبل الهرمون‬  Prolonging incretin activity enhances insulin secretion in Mechanism of Action response to meals and reduces inappropriate glucagon release, helping regulate blood glucose.  Enhances glucose-dependent insulin secretion.  Slows gastric emptying. Pharmacokinetics  Decreases food intake and postprandial glucagon secretion.  Promotes β-cell proliferation.  Administered orally.  Reduces weight gain and lowers postprandial hyperglycemia  High oral bioavailability. and HbA1c levels.  Sitagliptin undergoes minimal hepatic metabolism via CYP 450 3A4; 79% excreted unchanged in the urine. Pharmacokinetics  Saxagliptin is metabolized primarily by CYP 3A4.  Administered via subcutaneous injection. Uses  Liraglutide: Long half-life; once-daily dosing.   Can be used as monotherapy or in combination with other  Effective at reducing hemoglobin A1c levels by enhancing diabetes medications like sulfonylureas, metformin, glucose elimination through urine. glitazones, or insulin. Adverse Effects Adverse Effects  Urinary tract infections (UTIs) and genital fungal  Common: Upper respiratory tract infections, sore throat. infections (especially in females).  Rare: Pancreatitis (especially with saxagliptin).  Low incidence of hypoglycemia (less likely to cause low  No significant risk of hypoglycemia or weight gain blood sugar on their own, but may occur in combination with compared to other diabetes treatments. insulin or insulin secretagogues). Drug Interactions Thyroid Gland and Hormones  Strong CYP3A4/5 inhibitors (e.g., ketoconazole, The thyroid gland plays a critical role in growth, development, and clarithromycin) can increase concentrations of maintaining metabolism for normal tissue function, which includes saxagliptin. regulating growth, body temperature, and energy levels. Sodium Glucose Cotransporter 2 (SGLT2) Inhibitors Key Thyroid Hormones  Examples: Dapagliflozin, Canagliflozin 1. Triiodothyronine (T3) - Active form, contains 59% iodine. 2. Tetraiodothyronine (T4 or thyroxine) - Less active, Mechanism of Action contains 65% iodine.  SGLT2 inhibitors work by blocking the SGLT2 protein in The gland also releases calcitonin, a hormone that helps lower the kidneys, which reduces glucose reabsorption and serum calcium levels. increases glucose excretion in urine. This leads to lowered blood glucose levels. Thyroid Hormone Synthesis and Secretion Pharmacokinetics  Structure: The thyroid gland consists of follicles—single layers of epithelial cells around a colloid core, which  Rapidly absorbed from the gastrointestinal tract. contains thyroglobulin, the storage form of thyroid hormones.   Biosynthesis and Release: Mechanism of Action of Thyroid Hormones (T3 and T4) o Control: Thyroid-stimulating hormone (TSH) from the anterior pituitary stimulates hormone secretion, 1. Entry into Cells: T4 and T3 dissociate from thyroxine- while TSH itself is regulated by hypothalamic binding proteins in the plasma before entering cells by thyrotropin-releasing hormone (TRH). diffusion or active transport. o Transport: Most T3 and T4 circulate in the blood 2. Conversion of T4 to T3: Inside cells, T4 is enzymatically bound to thyroxine-binding globulin. converted to T3, the active form. 3. Nuclear Receptor Binding: T3 enters the nucleus and binds Regulation and Inhibition of TRH and TSH to specific receptors, which initiates RNA production and protein synthesis, essential for normal physiological effects.  Feedback Inhibition: High levels of circulating thyroid hormones suppress TRH. -> TSH / Pharmacokinetics of Thyroid Hormones  Additional Inhibitors: At higher doses, dopamine, somatostatin, and glucocorticoids can also reduce TSH -  Absorption: Both T3 and T4 are well-absorbed orally. However, T4 secretion. absorption can be reduced by food, calcium, and aluminum- containing antacids.  Conversion: T4 is converted to T3 in tissues via two types of deiodinase enzymes.  Metabolism: Thyroid hormones are metabolized by P450 enzymes. Enzyme inducers like phenytoin, rifampin, and phenobarbital can accelerate hormone metabolism, potentially requiring dosage adjustments. Hypothyroidism Treatment Summary 1. Levothyroxine (T4)  Preferred treatment for hypothyroidism due to stable, consistent action.  Body converts T4 to active T3, allowing smooth, sustained hormone levels. 2. Liothyronine (T3) o Radioactive Iodine (131I): Selectively taken up by thyroid cells to destroy the gland via beta radiation.  Rapid-acting form of thyroid hormone. This treatment is often used for younger patients  Less commonly used due to shorter action and potential for without prior methimazole pretreatment, whereas more side effects. older patients are usually pretreated. o Note: Most patients develop hypothyroidism and will require levothyroxine for replacement therapy. 3. T3/T4 Combination Therapy 2. Inhibition of Hormone Synthesis (Thioamides): o Propylthiouracil (PTU): Inhibits iodine  Used in cases where T4 alone doesn’t fully control incorporation and blocks T4 to T3 conversion. symptoms. o Methimazole: Inhibits the synthesis of thyroid  Mimics natural hormone levels but is less commonly hormones by blocking iodination and coupling of prescribed. tyrosines. Hyperthyroidism (Thyrotoxicosis) Summary These drugs do not affect the thyroid hormones already stored in the gland, so clinical effects may take time as  Cause: Excess secretion of thyroid hormone leading to thyroid hormone stores deplete. symptoms such as tachycardia, cardiac arrhythmias, body wasting, nervousness, tremors, and excess heat production.  Diseases: Commonly associated with conditions like Graves' Thyroid Storm Treatment Summary disease, toxic adenoma, and goiter.  Thyroid Storm: A life-threatening condition caused by  Diagnosis: Low TSH levels are typically observed in uncontrolled hyperthyroidism, presenting with severe hyperthyroidism. symptoms like tachycardia, fever, and agitation. Treatment of Hyperthyroidism Treatments: The main goal of treatment is to reduce thyroid hormone synthesis 1. Beta-blockers (e.g., Propranolol): and/or release: o Blunts the sympathetic effects of hyperthyroidism (e.g., tachycardia, tremors). 1. Thyroid Gland Removal: o Administered intravenously for fast action. o Surgical Removal: Part or all of the thyroid gland 2. Calcium-channel blockers (e.g., Diltiazem): can be surgically removed.  o Alternative to beta-blockers for patients with severe Drug Pharmac okinetic Duration Dosing Frequenc heart failure or asthma. Character istics of Action y o Helps control heart rate and symptoms. - Rapidly absorbed 3. Propylthiouracil (PTU): - Short plasma o Inhibits the conversion of T4 to T3, reducing the half-life (1.5 levels of active thyroid hormone. hours) - - Inhibits o More effective in thyroid storm than methimazole. iodine Bioavaila organific bility: 50- ation by 4. Iodides: Propylthi ouracil 80% - 60% for 7 hours Every 6-8 hours o Administered orally. Accumul after a ates in 100 mg o Inhibit iodination of tyrosines and the release of the dose thyroid thyroid hormones. gland - Excreted o Short-term use (a few days): Used in thyroid storm by the kidney or before surgery to reduce thyroid vascularity. within 24 hours o Not for long-term use, as the thyroid gland becomes - Short plasma unresponsive after a few weeks. half-life (6 hours) - Longer o Side Effects: Sore mouth/throat, swelling, rashes, - A 30 mg dose duration of action Less frequent, Methima ulcerations, metallic taste. zole exerts antithyro compare d to typically once 5. Glucocorticoids: id effect for Propylthi ouracil daily o Protect against shock, and reduce inflammation. longer than 24 hours  Gonadal Hormones: Roles, Mechanisms, and Character Administ Side Drug Notes istics ration Effects - Preferre Applications d choice for - thyroid replacem Nervous ness Gonadal hormones play essential roles in reproductive health, therapy, and various physiological processes. Below is a breakdown ent and suppressi on therapy of key hormones, their mechanisms, therapeutic applications, and - Stable, uniform - Heart palpitati Effective for long- effects. Levothyr content, Once ons/tach term oxine low cost daily ycardia thyroid (T4) - Lacks allergeni replacem ent 1. Estrogens c - Heat proteins, intoleran easily measure ce  Estradiol: The most potent natural estrogen, primarily d in labs - Long - produced by the ovaries, essential for female reproductive half-life (7 days); Unexplai ned health. steady state in 6- weight loss  Ethinyl Estradiol: A synthetic estrogen with high stability and potency, often used in oral contraceptives. / 8 weeks - 3-4 times more  SERMs (Selective Estrogen Receptor Modulators): o Tamoxifen: Acts as an estrogen antagonist in breast potent than levothyr oxine Best for tissue, commonly used to treat breast cancer. o Raloxifene: Provides estrogenic effects on bone - Shorter short- half-life term TSH (24 hours), - Higher suppressi on, not while acting as an antagonist in breast tissue, useful Liothyron ine (T3) requires multiple Multiple daily cardiotox routine icity risk therapy in osteoporosis and breast cancer prevention. daily doses due to due to doses potency cost and Mechanism of Action: - Higher monitori cost and ng difficult challeng to es  Estrogens bind to nuclear receptors in cells, initiating RNA monitor - Increase d risk of synthesis that promotes protein production. They support cardiotox icity various functions, including cardiovascular health by increasing nitric oxide and prostacyclin release. Therapeutic Uses:  Contraception: Core ingredient in many contraceptives.   Postmenopausal Therapy: Eases menopause symptoms,  Contraception: Often used alone or in combination with reduces osteoporosis risk; combined with progestin if the estrogens. uterus is intact to lower cancer risk.  Dysfunctional Uterine Bleeding & Dysmenorrhea: Helps  Primary Hypogonadism: Helps young women with low regulate abnormal uterine bleeding. hormone production develop secondary sexual  Endometriosis & Endometrial Cancer: Inhibits the growth characteristics. of endometrial tissue.  Postpartum Lactation Suppression: Reduces milk Adverse Effects: production when necessary.  Common: Nausea, postmenopausal bleeding. Adverse Effects:  Serious: Thromboembolism, rare cases of endometrial cancer with estrogen-alone therapy.  Common: Edema, depression, and increased LDL/HDL ratio.  Other: Acne, hirsutism, and weight gain. Anti-Progestins: 2. Progestins:  Mifepristone: A progesterone receptor antagonist, used for  Natural Progesterone: Secreted by the corpus luteum and early pregnancy termination and to manage uterine placenta, maintains the endometrium for pregnancy and suppresses further ovulation. conditions.  Synthetic Progestins (e.g., Medroxyprogesterone, Norethindrone): More stable and often used in 3. Androgens contraceptives; some have androgenic activity.  Testosterone: The primary male androgen, essential for Mechanism of Action: muscle protein synthesis, sperm production, and male reproductive maturation.  Increase glycogen storage in the liver, reduce sodium  Synthetic Androgens (e.g., Nandrolone, Stanozolol): reabsorption, raise body temperature, and influence nitrogen Anabolic steroids used to treat specific conditions, though excretion. often abused in athletics. Therapeutic Uses: Mechanism of Action:   Testosterone binds to nuclear receptors, promoting effects in Contraceptive Overview muscle and liver. In some tissues, it converts to dihydrotestosterone (DHT), enhancing its potency. Contraceptives are medications that decrease fertility through several mechanisms: Therapeutic Uses: 1. Preventing Ovulation – The most common method.  Hormone Replacement: In males with low testosterone. 2. Impeding Gametogenesis or Gamete Maturation.  Anabolic Effects: Treats osteoporosis, severe burns, and 3. Interfering with Gestation. catabolic states.  Growth Promotion: Used for skeletal growth in boys with Types of Contraceptives growth delays.  Endometriosis: Danazol, a derivative, inhibits hormone 1. Combination Oral Contraceptives synthesis pathways.  Monophasic Pills: Contain a constant dose of estrogen and Adverse Effects: progestin for 21 days, followed by a 7-day placebo period.  Triphasic Pills: Mimic the natural female cycle by  Women: Causes masculinization (e.g., facial hair). providing consistent estrogen with increasing progestin over  Men: Can lead to prostate growth, gynecomastia, reduced three weeks. fertility.  Hormones Used: Estrogens like ethinyl estradiol or  Athletes: Abuse of anabolic steroids risks growth issues, mestranol, and progestins such as norethindrone and liver damage, and psychological effects. levonorgestrel.  Cycle Note: Withdrawal bleeding occurs during the Antiandrogens: hormone-free interval.  Inhibit Synthesis: Ketoconazole blocks steroid synthesis. 2. Transdermal Patch  Receptor Blockers: Flutamide and Bicalutamide treat prostate cancer by blocking androgen receptors.  Contains ethinyl estradiol and progestin (norelgestromin).  Usage: Applied weekly for three weeks, with a patch-free fourth week for withdrawal bleeding.  Consideration: Less effective in women over 90 kg. 3. Vaginal Ring   Contains ethinyl estradiol and etonogestrel.  Types: High-dose progestin (levonorgestrel) or high-dose  Usage: Inserted for three weeks, with a ring-free week for estrogen plus progestin, taken within 72 hours of intercourse. withdrawal bleeding.  Dosage: Often requires a second dose 12 hours after the first.  Notes: Shares efficacy and side effects with oral contraceptives; may occasionally slip out. How Hormonal Contraceptives Work 4. Progestin-only Pills  Estrogen: Suppresses LH and FSH release, inhibiting ovulation.  Ingredients: Typically norethindrone or norgestrel.  Progestin: Enhances suppression of LH, thickens cervical  Usage: Taken daily without breaks, providing low and mucus, and blocks sperm transport. continuous progestin levels.  Cycle Mechanism: Continuous estrogen + progestin for 3  Ideal For: Breastfeeding mothers, smokers, and women who weeks prevents ovulation, with a placebo week to allow cannot tolerate estrogen. withdrawal bleeding.  Drawbacks: Less potent than combination pills, with increased risk of irregular cycles. Adverse Effects of Hormonal Contraceptives 5. Progestin Implants 1. General Side Effects: Breast fullness, mood changes, fluid retention, headache, nausea, and vomiting.  Etonogestrel Implant: Placed under the skin in the upper 2. Cardiovascular Risks: Rare but serious, includes arm, effective for up to 3 years. thromboembolism, thrombophlebitis, hypertension, and  Side Effects: May cause irregular bleeding and headaches. increased risk of myocardial infarction, especially in smokers over 35. 6. Progestin Intrauterine Device (IUD) 3. Cancer Risk: Reduced risk of endometrial and ovarian cancer; benign liver tumors are rare.  Highly effective and lasts up to 5 years. 4. Metabolic Effects: May cause glucose tolerance issues, akin  Suitability: Recommended for women with no history of to pregnancy changes; weight gain is common, particularly pelvic inflammatory disease or ectopic pregnancy. with nortestosterone derivatives. 5. Serum Lipid Impact: Estrogen raises HDL and lowers 7. Postcoital (Emergency) Contraception LDL, while progestins can counteract this benefit. Estrogen- dominant options are favorable for those with high  Purpose: Reduces pregnancy risk after unprotected cholesterol. intercourse. Contraindications Corticosteroid Types and Regulation Oral contraceptives are not recommended for individuals with:  Glucocorticoids (e.g., cortisol): Regulate metabolism and immune response.  Cerebrovascular or thromboembolic disease.  Mineralocorticoids (e.g., aldosterone): Control water and  Estrogen-dependent cancers. electrolyte balance, increasing blood pressure.  Liver disease or pregnancy.  Regulation: Controlled by the hypothalamic-pituitary-  Women over 35 who are heavy smokers should avoid adrenal (HPA) axis via ACTH and CRH. combination oral contraceptives  Athletic Risks: Abuse of anabolic steroids can cause growth issues, liver damage, and psychological changes. Mechanism of Action Adrenal Gland Hormones: Functions, Mechanisms, and  Corticosteroids are mostly bound to plasma proteins; only unbound hormones enter cells and bind to intracellular Therapeutic Uses receptors, forming a receptor-hormone complex that activates gene transcription and protein synthesis, The adrenal glands are divided into two parts, each producing influencing various cellular processes. essential hormones with significant physiological effects. 1. Adrenal Gland Structure and Hormone Production Physiological Effects  Medulla: Secretes epinephrine (adrenaline), which is vital 1. Mineralocorticoids (Aldosterone): Regulate water and for the fight-or-flight response. electrolyte balance by increasing sodium and water  Cortex: Produces corticosteroids and androgens in three reabsorption, thus elevating blood pressure. main zones: 2. Glucocorticoids: o Zona Glomerulosa: Produces mineralocorticoids o Metabolism: Increase gluconeogenesis and lipolysis, like aldosterone. decrease glucose use, and stimulate protein o Zona Fasciculata: Produces glucocorticoids like breakdown for energy. cortisol. o Anti-Inflammatory: Inhibit inflammatory mediators (e.g., histamine, prostaglandins).  o Stress Response: Raise blood glucose, enhance 4. Cushing’s Syndrome Diagnosis: Dexamethasone vascular responsiveness. suppression test helps diagnose. o Other Effects: Impact mood, CNS activity, and alter 5. Fetal Lung Maturation: Betamethasone aids lung blood cell levels. development and reduces the risk of respiratory distress in preterm infants. For Non-Adrenal Disorders Common Corticosteroids and Their Characteristics  Treatment includes inflammatory, infectious, and  Hydrocortisone (Cortisol): Short-acting, used for acute autoimmune conditions, such as systemic inflammation, needs; available in oral, intravenous, and intra-articular organ transplants, allergic reactions, hematologic and forms. pulmonary disorders, and skin and eye diseases.  Prednisolone: Intermediate-acting, commonly used for anti- inflammatory therapy with minimal sodium retention.  Triamcinolone: A fluorinated corticosteroid with no sodium-retaining activity. Adverse Effects of Corticosteroids  Dexamethasone & Betamethasone: Long-acting, potent anti-inflammatory corticosteroids used for therapeutic 1. Endocrine: Iatrogenic Cushing’s syndrome, HPA axis suppression of the adrenal cortex. suppression. 2. Musculoskeletal: Osteoporosis, muscle weakness. 3. Immune System: Immunosuppression, increased infection risk. Therapeutic Uses of Adrenal Corticosteroids 4. Gastrointestinal: Peptic ulcers, hemorrhage. 5. CNS: Mood changes, psychosis, euphoria. 6. Ophthalmic: Risk of cataracts and glaucoma. For Adrenal Disorders 7. Cardiovascular: Hypertension, edema, hypokalemia. 1. Adrenal Crisis: Requires immediate hydrocortisone and 8. Growth Inhibition: Reduced growth in children. electrolyte management. 2. Addison’s Disease: Chronic replacement therapy with Withdrawal Precaution: Corticosteroid withdrawal should be hydrocortisone. gradual to avoid adrenal insufficiency, especially after prolonged 3. Congenital Adrenal Hyperplasia: Managed with therapy. glucocorticoids to inhibit excess androgen secretion. Special Considerations in Pregnancy  Some corticosteroids can be teratogenic; they should be used cautiously and at low doses during pregnancy. Drug Interactions  Increased hypokalemia with digoxin or thiazides.  Increased peptic ulcer risk with NSAIDs.  Reduced efficacy of vaccines and insulin. Inhibitors of Corticosteroid Synthesis and Antagonists 1. Aminoglutethimide: Blocks all steroid synthesis, used in breast cancer and adrenal malignancies. 2. Ketoconazole: Inhibits adrenal and gonadal steroids, useful in Cushing’s syndrome. 3. Mifepristone: Glucocorticoid antagonist used for specific conditions. 4. Spironolactone: Aldosterone antagonist, treats hyperaldosteronism and hypertension, and inhibits testosterone synthesis. Summary of Gastric Acid Regulation and Treatment Approaches for Peptic Ulcer Disease (PUD) Regulation of Gastric Acid Secretion  Controlled by three main agonists: histamine, acetylcholine, and gastrin.  Final pathway: proton pump (H+/K+ ATPase). Pathogenesis of Peptic Ulcer Disease  Causes include NSAID use, H. pylori infection, increased hydrochloric acid secretion, and inadequate mucosal defenses. Treatment Approaches 1. H. pylori eradication with antibiotics. 2. Reduce gastric acid secretion: use of H2 receptor antagonists or proton pump inhibitors (PPIs). 3. Protect gastric mucosa: agents like misoprostol and sucralfate. 4. Neutralize gastric acid with nonabsorbable antacids. 5. Surgery (for acute complications). Medications Antimicrobial Agents for H. pylori Eradication  Triple therapy: PPI + (metronidazole/amoxicillin) + clarithromycin.  Quadruple therapy: bismuth subsalicylate + metronidazole + tetracycline + PPI.  Bismuth salts aid by inhibiting pepsin and increasing mucus secretion. H2-Receptor Antagonists  Examples: Cimetidine, Ranitidine, Famotidine.  Mechanism: Block histamine on stomach cells, reducing acid secretion.  Indications: Peptic ulcers, GERD, erosive esophagitis, Zollinger-Ellison syndrome, pre-anesthesia.  Side Effects: Cimetidine can cause gynecomastia, galactorrhea, and drug interactions (inhibits CYP450). Proton Pump Inhibitors (PPIs)  Examples: Omeprazole, Lansoprazole, Pantoprazole.  Mechanism: Prodrugs activated in acidic conditions to inhibit H+/K+ ATPase.  Indications: Peptic ulcers, H. pylori eradication, NSAID-induced ulcers, GERD, Zollinger-Ellison syndrome.  Side Effects: GI disturbances (diarrhea, nausea), CNS effects, skin reactions, kidney issues (interstitial nephritis). Prostaglandin Analogs  Misoprostol: inhibits HCl secretion, stimulates mucus, used for NSAID-induced ulcers.  Side Effects: Uterine contractions, diarrhea, nausea. Antimuscarinic Agents  Dicyclomine: used for refractory cases, reduces gut motility and secretions.  Side Effects: Cardiac arrhythmias, dry mouth, constipation, urinary retention. Antacids  Types: Aluminum hydroxide, Magnesium hydroxide, Calcium carbonate, Sodium bicarbonate.  Mechanism: Neutralize gastric acid, providing symptomatic relief.  Side Effects: Constipation (aluminum), diarrhea (magnesium), sodium content considerations in hypertension. Mucosal Protective Agents  Bismuth Subsalicylate: Antimicrobial, increases mucus, and inhibits pepsin; promotes ulcer healing.