PHARM QUIZ 6

Sodium Glucose Co-Transporter-2 (SGLT2) Inhibitors

- SGLT2 is expressed in the proximal renal tubules which is responsible for the majority of the reabsorption of filtered glucose from the tubular lumen. By inhibiting SGLT2, these agents reduce reabsorption of filtered glucose and lowers the renal threshold of glucose which increase urinary glucose excretion. - Canagliflozin (Invokana) > 100mg prior to first meal of the day, can increase to 300mg daily CrCL 45-60 ml/min: 100mg max dose CrCL < 45 ml/min: Do not use - Dapagliflozin (Farxiga) > 5mg daily in the am; can increase to 10mg daily CrCL < 60 ml/min: do not use -Empagliflozin (Jardinace) CrCl< 45 do not use CI > Severe renal impairement (CrCL < 30ml/min) ESRD, or on dialysis WARNING - Increase in LDL - Dapagliflozin can increase risk of bladder cancer SE Decrease weight by 4-7 pounds Increase in K with canagliflozin Etc. Drug interactions > Monitor digoxin levels if taking digoxin concurrently due to Increase in AUC of digoxin.

Free T4 (FT4)

0.8-2.7 ng/dL

clinically significant hypoglycemia -level what?

2

Free T3

230 to 420 pg/dl

PRE-PRANDIAL GLUCOSE ADA LEVEL

80-130 MG/DL

AACE/ACE LEVEL FOR PRE-PRANDIAL GLUCOSE

<110 MG/DL

POST-PRANDIAL GLUCOSE AACE/ACE LEVEL

<140 MG/DL

POST-PRANDIAL GLUCOSE ADA LEVEL

<180 MG/DL

Clinically significant hypoglycemia - glycemic criteria at level 2?

<54 mg/dl

AAC/ACE LEVEL FOR HGB A1C?

<6.5%

HEMOGLOBIN A1C, ADA LEVEL?

<7.0%

HYPOGLYCEMIA ALERT VALUE - LEVEL 1, GLYCEMIC CRITERIA?

<70 mg/dl

AMYLIN/PRAMLINTIDE

ADJUNCT THERAPY FOR TYPE 1/TYPE 2 DM

GLIMIPERIDE - WHAT BRAND NAME?

AMARYL

PRAMLINTIDE

AMYLIN RECEPTOR AGONIST

alpha-glucosidase

Acarbose Miglitol ADJUCT THERAPY ONLY FOR TYPE II DM AVOID USE IN RENAL DYSFUNCTION, eGFR<30 ML/MIN BASELINE LFTs THEN PERIODICALLY THEREAFTER (ACARBOSE) MAY INFLUENCE ABSORPTION OF OTHER DRUGS C/I IN MALABSORPTION D/O, IBD OR INTESTINAL OBSTRUCTION GLUCOSE (DEXTROSE) IS RECOMMENDED FOR TREATING HYPOGLYCEMIA AS SUCROSE METABOLISM IS INHIBITED

WHAT ARE THE AGENTS FOR DIABETES MELLITUS?

BIGUANIDES MEGLITINIDE SULFONYLUREAS THIAZOLIDINEDIONES ALPHA-GLUCOSIDASE INHIBITORS GLUCAGON-LIKE PEPTIDE-1 AGONISTS DIPEPTIDYL PEPTIDASE-4 INHIBITORS AMYLIN RECEPTOR AGONIST SODIUM GLUCOSE CONTRANSPORTER 2 (SGLT2) INHIBITORS

WHAT ARE THE AGENTS FOR SODIUM GLUCOSE CONTRANSPORTER 2 INHIBITORS?

CANAGLIFLOZIN/INVOKANA, DAPGLIFLOZIN/FARXIGA, AMPAGLIFLOZIN/JARDIANCE, ERTUGLIFLOZIN/STEGLATRO

WHAT IS THE LONG-TERM OUTCOME AND SAFETY ISSUES OF SGLT2?

CARDIOVASCULAR, CANCER RISK

DIABENESE - GENERIC NAME?

CHLORPROPAMIDE

Afrezza contraindications

CHRONIC LUNG DZ BBW/REMS: ACUTE BRONCHOSPASM

GLP-1 agonists

DOES NOT REPLACE INSULIN

BIGUANIDES

DRUG OF CHOICE

LEVEMIR

Detemir (Long Acting)

SULFONYLUREAS - WHAT R THE AGENTS?

GLIPIZIDE, DIABENESE, GLIMEPIRIDE

WHAT IS THE FIRST LEVEL FOR ADA CLASSIFICATION OF HYPOGYCEMIA?

HYPOGLYCEMIA ALERT VALUE - LEVEL 1

SEVERE HYPOGLYCEMIA-LEVEL 3 DESCRIPTION?

HYPOGLYCEMIA ASSOCIATED WITH SEVERE COGNITIVE IMPAIRMENT REQUIRING EXTERNAL ASSISTANCE FOR RECOVERY

what is this premixed insulin's brand name - Insulin lispro protamine suspension/insulin lispro?

Humalog Mix 50/50

NPH/Regular 70%/30% Brand Name?

Humulin 70/30 Novolin 70/30

levothyroxine indication

Hypothyroidism, thyroid-stimulating hormone suppression (pituitary)

WHAT IS METFORMIN'S MOA?

IMPROVES INSULIN SENSITIVITY BY INCREASING GLUCOSE UTILIZATION BY MUSCLE

SGLT2 - BBW?

INCREASED RISK OF LOWER LIMB AMPUTATION (CANAGLIFLOZIN)

DM TYPE 1

INSULIN DEFICIENT

TYPE 2 DM?

INSULIN RESISTANCE COMBINED WITH B-CELL DYSFUNCTION

Thiazolidinediones (TZDs)

Increase insulin sensitivity in peripheral tissue by binding to PPAR-gamma -glitazones Can cause MI, hepatotoxicity, weight gain, and heart failure C/I IN NYHA CLASS III OR IV PTS BBW: CAUSES OR EXACERBATES HEART FAILURE

GLP1 agonists

Incretin therapy Ex = *exenatide, liraglutide*, dulaglutide, albiglutide Synthesized from exendin-4 from Gila Monster saliva which has homology with GLP1 and is resistant to DPP4 *MOA* - activates GLP1r leading to a 10x increase in receptor activation *Side effects* - nausea (improves with time), diarrhea, constipation *Pros* - weight loss *Cons* - must be injected, concern about thyroid c-cell hyperplasia and pancreatitis *Contraindications* - personal or FHx of medullary cancer, don't use with CKD and GFR<30 BBW/REMS: THYROID CANCER/PANCREATITIS

Glucocorticoids MOA

Inhibit NF-κB. Suppress both B- and T-cell function by transcription of many cytokines. more than 30 glucocorticoids are secreted cortisol (hydrocortisone) secreted in highest amount influence the function of most cells in the body

Glulisine (Apidra)

Insulin - Rapid Acting

Novolog (insulin aspart)

Insulin-Rapid Acting Take immediately before meals, counsel on injection technique and hypoglycemia

NPH (Humulin N)

Intermediate-acting insulin. Onset: 2-4 hours. Peak: 4-12 hours. Duration: 12-18 hours.

SGLT2 - RISK?

KETOACIDOSIS

GLARGINE

LANTUS

GLUCOPHAGE - WHAT TO AVOID

LIVER DZ

GLARGINE

Lantus (long acting)

Thyroid Agents

Levothyroxine (Synthroid)

Glargine (Lantus)

Long-acting insulin Onset 1 hour Peak (none) Duration 10-24 hours

NONSULFONYLUREAS?

MEGLITINIDE/GLINIDES

Dipeptidyl Peptidase-4 Inhibitors

MOA > Prevent the enzyme DPP-4 from breaking down incretin hormones, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) - SitaGLIPtin (januvia) - Saxagliptin (Onglyza) Linagliptin (Tradjenta) - Alogliptin (Nesina) - No renal dose adjustment for Trajenta SE > Nasopharyngitits > Upper respiratory tract infections > Peripheral edema > Rash and hypoglycemia > Rarely acute pancreatitis Notes > Natural weight > Saxagliptin is major 3A4 and P-glycoprotein substrate. use the lower 2.5 mg dose with strong CYP3A4 inhibitors. > Linagliptin is a major 3A4 and P-glycoprotein substrate. Linagliptin levels are decreased by strong inducers

Glucocorticoids MOA

Metabolic, catabolic, anti-inflammatory, and immunosuppressive effects mediated by interactions with glucocorticoid response elements and inhibition of transcription factors such as NF-κB.

Mineralocorticoids

Mineralocorticoids are hormones produced by the adrenal cortex that help the body retain sodium and water in the kidneys. They accomplish this by promoting the reabsorption of sodium and chlorine, which together from common salt. When salt is absorbed, so it water.

Gonadocorticoids (Sex Hormones)

Most are androgens (male sex hormones) that are converted to testosterone in tissue cells or estrogens in females May contribute to The onset of puberty The appearance of secondary sex characteristics Sex drive

FDA WARNING - FOURNIER'S GANGRENE?

NECROTIZING FASCITIS OF THE GENITALS

SGLT2 - SAFETY/EFFECTIVENESS?

NOT ESTABLISHED IN PATIENTS YOUNGER THAN 18 YEARS OLD

SULFONYLUREAS - GLIPIZIDE, GLYBURIDE, DIABINESE - WHAT MAY DIMINISH?

OVER TIME RESPONSE TO THERAPY MAY DIMINISH

Affreza

Oral inhaled RAPID ACTING insulin CI in pts with respiratory disease

AMYLIN RECEPTOR AGONIST

PRAMLINTIDE

SYMLIN

PRAMLINTIDE

METFORMIN - WT?

PROMOTES WT LOSS

Amylin receptor agonist

Pramlintide

DPP-4 inhibitors MOA

Prolong action of GLP-1 incretins: -Increase insulin secretion in response to oral glucose -Decreased glucagon secretion -Reduces apoptosis of islet cells -Reduces hunger (due to CNS effect and delayed gastric emptying)

ONSET OF REPAGLINIDE/MEGLITINIDE?

RAPID

MEGLITINIDE - WHAT R THE AGENTS?

REPAGLINIDE (PRANDIN)/NATEGLINIDE (STARLIX)

Lispro (Humalog)

Rapid-acting insulin. Onset: less than 15 minutes. Peak: 0.5-1 hour. Duration: <5 hours.

Total Thyroxine T4

Refelcts the total of both protein bound T4 and free thyroxine 4.8-10.4 mcg/dl

Meglitinides

Repaglinide (Prandin) Nateglinide (Starlix)

PRAMLINTIDE - BBW?

SEVERE HYPOGLYCEMIA WITHIN 3 HOURS OF INJECTION; CAUTION HIGH RISK ACTIVITIES, LIKE DRIVING

NECROTIZING FASITIS OF THE GENITALS IN WHICH CLASS?

SGLT2

MOA OF MEGLITINIDE?

STIMULATES B CELL TO MAKE INSULIN

DIABENES - WHAT CLASS?

SULFONYLUREAS

Regular insulin (Humulin R, Novolin R)

Short-acting insulin ☐ Administer 30 to 60 min before meals to control postprandial hyperglycemia.

Alpha-glucosidase inhibitors MOA

Slows intestinal carbohydrate digestion/absorption

Meglitinides MOA

Stimulate a rapid/ short-lived release of insulin from the pancreas

what is the description of hypoglycemia alert value?

Sufficiently low for tx with fast acting CHO and dose adjustment of glucose-lowering therapy

Level 2 clinically significant hypoglycemia description?

Sufficiently low to indicate serious, clinically important hypoglycemia

Levothyroxine

Synthroid, Levothroid

pituitary gland

The endocrine system's most influential gland. Under the influence of the hypothalamus, the pituitary regulates growth and controls other endocrine glands.

diabetes mellitus

a group of metabolic disorders characterized by hyperglycemia resulting from defects in insulin secretion, insulin action, or both

adrenal glands

a pair of endocrine glands that sit just above the kidneys and secrete hormones (epinephrine and norepinephrine) that help arouse the body in times of stress.

Thyrotropic hormone (TSH)

anterior pituitary hormone that stimulates the function of the thyroid gland 0.4-4 uIU/ml, results in hypothyroidism high, results in hperthyroidism is low

Pituitary

at the base of the brain; stimulates growth and controls functions of other glands

Type 1 DM

autoimmune dysfunction involving the destruction of beta cells, which produce insulin in the islets of Langerhans of the pancreas. Immune system cells and antibodies are present in circulation and also can be triggered by certain genetic tissue types of viral infections. Usually occurs at a young age w/ no successful interventions to prevent.

hypothalamus and pituitary gland

coordinate to serve as a neuroendocrine control center

COX-1 and COX-2

cyclooxyrgenase 1 & 2 are enzymes that convert arachidonic acid to prostaglandin, resulting in pain and inflammation. COX-1 is known to be present in most tissues and maintains the normal lining of the stomach / GI tract. The enzyme is also involved in kidney and platelet function. COX-2 is primarily present at sites of inflammation.

type 2 diabetes mellitus

diabetes caused by either a lack of insulin or the body's inability to use insulin efficiently; usually develops in middle-aged or older adults, and patients usually do not require insulin replacement therapy to control the disorder

WHAT IS CONTRAINDICATED WITH GLUCOPHAGE?

eGFR<30 ML/MIN

Hyperaldosteronism

excessive output of aldosterone, usually as a result of adrenal tumors, from the adrenal gland, leading to increased sodium and water retention and loss of potassium characterized by HTN and hypokalemia

Glucagon-like peptide-1 agonists

exenatide

Synthroid MOA

function as natural or synthetic hormones

GLP-1

glucagon-like peptide 1

levothyroxine mechanism of action

increases energy metabolism, producing loss of weight, improved tolerance to environmental temperature, increased activity, and increased pulse rate agent of choice due to stability, content uniformity, low cost, lack of allergenic foreign protein, easy lab, measurement of serum levels and once daily dosing maximum effect seen after 6-8 weeks of therapy not appropriate for tx of obesity toxicity: symptoms of thyroid excess

GLP-1 MOA

increases production of insulin in response to elevelated BG levels. Also works on incretin system (similar to DPP-4, but injectable). Slows gastric emptying. Decreases A1C 1-1.5%. Weight loss! Low risk hypoglycemia. Avoid with older adults with gastroparesis. Risk of acute pancreatitis.

Tresiba

insulin degludec Insulin - Long Acting Available only as U200 in a pen.

Detemir (Levemir)

long acting insulin

Detemir

long acting insulin, 0.8-2 ONSET, RELATIVELY FLAT PEAK, 5.7-23.2 DURATION OF ACTION

Meglitinides (Glinides)

nonsulfonylureas, glinides monotherapy or comb for type ii dm rapid onset, given with meals short duration of action, requires tid dosing liver dz. use with caution may require dose adjustment for renal dysfunction several drug-drug interactions SE = wt gain; hypoglycemia

Total Triiodothyronine (T3)

normal value is 60+181 ng/dl

hydrocortisone (cortisol)

potent glucocorticoid with antiinflammatory properties prepares body for long term stress

thyroid gland

produces hormones that regulate metabolism, body heat, and bone growth

Mineralocorticoids (aldosterone)

regulate sodium reabsorption in kidney tubule

hypothalamus function

water balance/bp/temp regulation/hunger/thirst/sex homeostasis