Pharmacology Exam Review: Hormonal Regulation & Diabetes

Glucagon

Secretion is promoted by decreased blood glucose levels; stimulates glycogenolysis, gluconeogenesis, and lipolysis.

Glycogenolysis

Breaks down glucagon stores.

Gluconeogenesis

Synthesizes glucose from non-sugar sites.

Lipolysis

Starts breaking down fat.

Insulin

Facilitates the rate of glucose uptake into the cells.

Amylin

Delays gastric emptying and promotes satiety; suppresses glucagon secretion.

Somatostatin

Involved in regulating alpha- and beta-cell function.

Gastrin

Hormone secreted by F (PP) cells that regulates carbohydrate, fat, and protein metabolism.

Type 1 Diabetes Mellitus

Peak onset at age 11-13 years; caused by autoimmune beta-cell destruction leading to absolute insulin deficiency.

Type 2 Diabetes Mellitus

Peak onset at age 11-13 years; caused by progressive loss of beta-cell insulin secretion frequently with insulin resistance.

Hypoglycemia

Too much insulin not enough intake; rapid onset.

Diabetic Ketoacidosis (DKA)

Serious complication related to a deficiency of insulin and an increase in insulin counterregulatory hormones; slow onset.

Hyperosmolar Hyperglycemic Nonketotic Syndrome (HHNKS)

Uncommon but significant complication of type 2 diabetes mellitus with high mortality; slowest onset.

Cardiovascular Disease

Includes hypertension, coronary artery disease, cardiomyopathy, and heart failure.

Stroke

A chronic complication of diabetes mellitus.

Peripheral Vascular Disease

Includes claudication, nonhealing ulcers, and gangrene.

Diabetic Retinopathy

Progresses from no visual changes to loss of visual acuity and blindness.

Diabetic Nephropathy

Characterized by microalbuminuria and hypertension progressing to end-stage kidney failure.

Diabetic Neuropathies

Sensorimotor polyneuropathy progressing to distal paresthesias in feet and hands, muscle wasting, and falls.

Pressure ulcers

Skin lesions caused by prolonged pressure, often leading to delayed wound healing.

Abscess formation

A collection of pus that has built up within the tissue of the body.

Necrosis

The death of body tissue, which can lead to gangrene, particularly in toes and feet.

Gangrene

The decay of body tissue due to insufficient blood supply, often affecting toes and feet.

Infection

The invasion of body tissues by pathogens, which can lead to conditions like osteomyelitis.

Osteomyelitis

An infection in the bone, often resulting from an infection spreading from nearby tissue.

Metabolic Syndrome

A cluster of conditions that increase the risk of heart disease, stroke, and diabetes; requires 3 out of 5 criteria to be present.

Increased waist circumference

A measurement indicating abdominal obesity; >40 inches in men and >35 inches in women in the United States.

Plasma triglycerides

A type of fat found in the blood; ≥150 mg/dl indicates a risk factor for metabolic syndrome.

Plasma high-density lipoprotein (HDL) cholesterol

A type of cholesterol; <40 mg/dl in men or <50 mg/dl in women indicates a risk factor for metabolic syndrome.

Blood pressure

The pressure of circulating blood on the walls of blood vessels; systolic ≥130 or diastolic ≥85 mm Hg indicates a risk factor for metabolic syndrome.

Fasting plasma glucose

The level of glucose in the blood after fasting; ≥100 mg/dl indicates a risk factor for metabolic syndrome.

Hilum

A medial indentation in the kidney where blood vessels, nerves, lymphatic vessels, and ureter enter and exit.

Cortex

The outer layer of the kidney.

Medulla

The inner part of the kidney, consisting of regions called pyramids.

Renal Columns

Extensions of the cortex that extend between the pyramids to the renal pelvis.

Minor and Major Calyces

Chambers that receive urine from the collecting ducts and form the entry into the renal pelvis.

Lobe

A structural unit of the kidney, typically 14 to 18 lobes in each kidney.

Nephron

The functional unit of the kidney, with approximately 1.2 million nephrons per kidney.

Renal blood flow

The volume of blood the kidneys receive, typically 1000 to 1200 ml per minute.

Glomerular filtration rate

The filtration of plasma per unit of time, directly related to the perfusion pressure of the glomerular capillaries.

Autoregulation

The kidney's ability to maintain a constant blood flow despite changes in blood pressure.

Renin-angiotensin-aldosterone system (RAAS)

A hormone system that regulates blood pressure and fluid balance, can increase systemic arterial pressure.

Erythropoietin

A hormone that stimulates the production of red blood cells in the bone marrow, released in response to decreased oxygen delivery in the kidneys.

Urodilatin

A renal natriuretic peptide produced by cells in the distal tubule and collecting duct that increases RBF, causing diuresis.

Nephrons

Intertwined with peritubular capillaries and form a countercurrent exchange system that maintains fluid balance.

Tubular reabsorption

The movement of fluids and solutes from the tubular lumen into the peritubular capillary plasma.

Tubular secretion

The transfer of substances from the plasma of the peritubular capillary to the tubular lumen, using both active and passive transport mechanisms.

Excretion

The elimination of a substance in the urine.

Juxtaglomerular cells

Renin-releasing cells located around the afferent arteriole where systemic blood enters the glomerulus.

Renin

Released when blood pressure or blood flow to the kidneys decreases, triggering a cascade that increases blood pressure and sodium retention.

Vasoconstriction

A process that leads to increased blood pressure.

Antidiuretic hormone (ADH)

Controls the specific gravity, or concentration, of the final urine, secreted from the posterior pituitary or neurohypophysis.

Aldosterone

Stimulates epithelial cells of the distal tubule and collecting duct to reabsorb sodium, promoting water reabsorption, and increases the excretion of potassium and hydrogen ion.

Natriuretic peptides

A group of peptide hormones that promote sodium and water excretion.

Vitamin D

Necessary for the absorption of calcium and phosphate by the small intestine.

Glomerular Filtration Rate (GFR)

Provides the best estimate of functioning renal tissue and is important for assessing or monitoring kidney damage and drug dosing.

Blood Urea Nitrogen (BUN)

Concentration of urea, nitrogen in blood; normal range is 10-20 mg/dl.

Creatinine

A natural substance produced by muscle and released into the blood at a relatively constant rate, valuable for monitoring chronic kidney disease; normal range is 0.7 to 1.2 mg/dl.

Cystatin C

A stable protein in serum filtered at the glomerulus and metabolized in the tubules; better for early detection of kidney damage/decreasing GFR; normal range is 0.8-2.1 mg/L.

Urinalysis

An inexpensive, noninvasive test that includes evaluation of color, turbidity, protein, pH, specific gravity, sediment, and supernatant.

Chronic Kidney Disease (CKD)

The progressive loss of renal function indicated by a decline in GFR to below 60 ml/min/1.73 m2 for 3 months or more, irrespective of cause.

Pathophysiology of CKD

Symptomatic changes result from increased plasma levels of creatinine, urea, and potassium.

Stage 1 of Kidney Disease

Normal kidney function with a normal or high GFR (>90 ml/min).

Stage 2 of Kidney Disease

Mild kidney damage with a mild reduction in GFR (60-89 ml/min) and subtle hypertension.

Stage 3 of Kidney Disease

Moderate kidney damage with a GFR of 30-59 ml/min.

Stage 4 of Kidney Disease

Severe kidney damage with a GFR of 15-29 ml/min, presenting moderate signs and symptoms.

Stage 5 of Kidney Disease

End-stage kidney disease with established kidney failure and a GFR of <15 ml/min.

Risk Factors for CKD

Diabetes, older age, cardiovascular disease, ethnic minority (black, native American), exposure to nephrotoxic drugs, family history of CKD and hypertension.

Proteinuria

A condition resulting from glomerular hyperfiltration, increased glomerular capillary permeability, and loss of negative charge, contributing to tubulointerstitial injury.

Angiotensin II activity

Activation of the renin-angiotensin-aldosterone system (RAAS) causing efferent arteriolar vasoconstriction, promoting glomerular hypertension and hyperfiltration.

Hyperglycemia

A condition characterized by high blood sugar levels.

Thiazide Diuretics

Act on the distal convoluted renal tubule to promote sodium, chloride, and water excretion, used to treat hypertension and peripheral edema.

Loop Diuretics

Act on the thick ascending loop of Henle to inhibit chloride transport of sodium into circulation, promoting diuresis and inhibiting sodium reabsorption.

Potassium-sparing Diuretics

Act primarily in the collecting duct renal tubules to promote sodium and water excretion while retaining potassium.

Side Effects of Thiazide Diuretics

May cause hypercalcemia.

Side Effects of Loop Diuretics

Can affect blood glucose and increase uric acid levels, and can increase renal blood flow up to 40%.

Uses of Potassium-sparing Diuretics

Used as mild diuretics or in combination with another diuretic such as hydrochlorothiazide or an antihypertensive drug.

Insulins

Promote use of glucose by body cells.

Use of Insulins

Reduce blood glucose, control diabetes mellitus.

Interactions of Insulins

Increase glucose with thiazides, glucocorticoids, estrogen, thyroid drugs; Decrease glucose with aspirin, oral anticoagulants.

Gastrointestinal secretions and Insulin

Gastrointestinal secretions destroy insulin structure - therefore, no oral insulin.

Side Effects of Insulins

Hypoglycemia, nervousness, trembling, lack of coordination, sweating, tachycardia, headache, confusion.

Somogyi Effect

Occurs in predawn hours; rapid decrease in blood glucose during night stimulates hormonal release to increase blood glucose.

Lipodystrophy

Tissue atrophy from frequent injections.

Dawn phenomenon

Hyperglycemia upon awakening; headache, night sweats, nightmares; increase insulin dose at HS.

Diabetic ketoacidosis

Hyperglycemia - fruity breath, increased thirst, hunger, & urine output (3 P's); leads to fat catabolism - increase in ketones.

Regular insulin

Short acting (IV) (clear); Onset: 30 min; Peak: 1.5-3.5 h; Duration: 4-12 h.

Lispro

Rapid acting (IV) (clear); Onset: 15-30 min; Peak: 30-90 min; Duration: 3-5 h.

NPH

Intermediate acting (SubQ, CANNOT be IV) (Cloudy); Onset: 1.5 h; Peak: 4-12 h; Duration: 14-24 h.

Glargine

Long acting (Cloudy); Onset: 1-1.5 h; Peak: None; Duration: 24 h.

Glipizide

Directly stimulates beta cells in the pancreas to secrete insulin; indirectly alters sensitivity of peripheral insulin receptors.

Side effects of Glipizide

Drowsiness, dizziness, headache, confusion; Adverse Reactions: Hypoglycemia, hyponatremia, angioedema; Life-threatening- Agranulocytosis.

Metformin

Decreases glucose production in the liver by reducing gluconeogenesis; improves tissue sensitivity to insulin.

Side effects of Metformin

Dizziness, headache, weakness, chills, metallic taste, nausea, diarrhea; Life-threatening - lactic acidosis and acute renal failure.

Furosemide

Acts on ascending loop of Henle; excretes sodium, water, K+, Ca+, Mg+.

Common side effects of Furosemide

Electrolyte imbalances: NOTABLY POTASSIUM; orthostatic hypotension, dizziness, headache, weakness, muscle cramps.

Hydrochlorothiazide

Acts on distal convoluted renal tubule; promotes sodium, chloride, water excretion.

Uses of Hydrochlorothiazide

Hypertension, peripheral edema.

Side effects of Hydrochlorothiazide

Orthostatic hypotension, fluid/electrolyte imbalance, gout; Life-threatening: Hypokalemia, renal failure, Stevens-Johnson syndrome.

Spironolactone

Blocks action of aldosterone; promotes sodium/water excretion & K+ retention.