Pharmacology Chapter 41 - Pancreatic Hormones and Antidiabetic Drugs

what OGTT 2 hr blood glucose indicates impaired glucose tolerance

140-199 mg/dL

what are the subtypes of type 1 diabetes

1a - immune mediated, most common 1b - idiopathic

what is the duration of action for the most commonly used dosages

4 hrs

what is the cutoff for HbA1C for diabetes

6.5% or greater

dapagliflozin is not recommended for pts with GFR less than

60 mL/min

How is saxagliptin metabolized?

CYP3A4/5

what are the SGLT2 inhibitors

Canagliflozin Dapagliflozin Empagliflozin

what is nateglinide

D-phenylalanine derivative, stimulates insulin release by inhibiting the K ATP channel metabolized by CYP2C9 and CYP3A4 can be used in renal impaired and elderly

how is GLP1 degraded

DPP4 and endopeptidase 24.11

what are the common autoantibodies in type 1 diabetes

GAD 65 ICA 512 ZnT8

canagliflozin and empagliflozin are CI in pts with _ and cause a modest increase in

GFR less than 45 mL/min increase in LDL

what are the toxicities of metformin

GI upset, inferferes with calcium-dependent absorption of B12 in the terminal ileum, and lactic acidosis most likely in conditions of tissue hypoxia AKI can occur in pts receiving radiocontrast agents

what is the modification of exenatide

GLP1 receptor agonist glycine substitution to reduce degradation of DPP4

pts with diabetes concerned with weight gain may benefit from

GLP1 receptor agonist, DPP4 inhibitor, or an SGLT2 inhibitor

pramlintide is not very useful in pts taking

GLP1 receptor agonists

what do the first 6 amino acids of glucagon bind to

Gs receptor

what is the ADA criteria for acceptable control of diabetes

HbA1C less than 7% pre meal glucose 90-130 mg/dL, less than 180 mg/dL after 1 hr, 150 mg/dL after 2 hrs

what are the adverse effects of thiazolidinediones

Hepatotoxicity, CHF, and weight gain

what is pramlintide

IAPP analog with substitutions of proline at positions 25, 28 and 29. soluble and doesn't aggregate

what are the first proteins to be phosphorylated by the insulin receptor

IRS

what happens in immune insulin resistance

IgG neutralizes the action of insulin to a non working extent, may be associated with other systemic AI processes

how do thiazolidinodiones decrease insulin resistance

PPAR gamma ligands, found on fat, muscle, and liver increased GLUT1 and GLUT4 expression, decreased FFA levels, decreased hepatic glucose output, increase adiponectin and decreased release of resistin from adipocytes, and increased differentiation of adipocytes

what are the meglitinide analogs

Repaglinide - fast OOA, controls postprandial glucose, used in elderly and in renal impaired, may be used in T2Ds with sulfur allergy have two binding sites in common with sulfonylureas and one unique binding site

how is glucose reabsorbed in the PCT

SLGTs

where is the favored site for subQ insulin infusions

abdomen

what is gestational diabetes

abnormality in glucose levels noted for the first time during pregnancy most pronounced in the last semester

how is glulisine different from R insulin

asparagine at B13 is replaced by lysine lysine in B29 is replaced by glutamic acid

which insulins are approved for insulin pump use

aspart, lispro, and glulisine

what is metformin

biguanide activates AMPK and reduce hepatic glucose production, may inhibit hepatic metabolism of lactic acid and increase risk of acidosis excreted by the kidneys safely used with GFR 60-45 mL/min; cautiously 45-30 mL/min; CI less than 30 mL/min

what is the first line therapy for type 2 diabetes

biguanides indicated for use in combo with insulin secretagogues or thiazolidinediones in type 2's in which monotherapy is inadequate

linagliptin is primarily excreted in the

bile

what is colesevelam hydrochloride

bile acid sequestrant and cholesterol lowering rug, used as antihyperglycemic interrupts enterohepatic circulation and decrease in FXR activation bile acids are natural ligands of FXR SE include GI complaints and can exacerbate hyperTGemia

how do alpha glucosidase inhibitors work

competitively inhibit the enzymes and reduce post meal glucose excursions by delaying the digestion and absorption of starch and disaccharides

how do you treat severe hypoglycemia

dextrose if conscious and can swallow if unconscious, 1mg glucagon injected subQ or IM

drugs that inhibit insulin release include

diazoxide, phenytoin, vinblastine, and colchicinewhat are the main organs that remove insulin from circulation

when should alogliptin be discontinued

during liver failure

why does GLP1 have a lower risk for hypoglycemia than the sulfonylureas

effect is glucose dependent, so insulin release is more pronounced when glucose is elevated but less when glucose is normal

which GLP1 receptor agonists are available for use

exenatide liraglutide albiglutide dulaglutide

what happens to short acting insulins

exist as dimers, assemble into hexamers in the presence of two zinc ions stabilized by phenolic compounds

how does powder insulin compare to subQ insulin

faster in onset, shorter in duration

what are the side effects of alpha-glucosidase inhibitors

flatulence, diarrhea, and abdominal pain hypoglycemia with sulfonylureas, which is treated with dextrose

how is DKA treated

fluids generally begins with normal saline regular insulin used for IV therapy watch sodium and potassium levels

what are the main adverse effects of SGLT2 inhibitors

genital infections and UTIs

which insulin analogs are long acting

glargine, detemir, and degludec

what is one of the precursors of glucagon

glicentin

acarbose and miglitol are inhibitors of

glucoamylase, alpha amylase, and sucrase

what is the serious side effect of vildagliptin

hepatitis

what is HHS

hyperosmolar hyperglycemic state in pts with T2D with inadequate oral hydration not acidotic unless DKA is present tx includes aggressive rehydration and restoration of glucose/electrolyte homeostasis

what are the adverse effects of pramlintide

hypoglycemia and GI symptoms

what is the major clinical use of glucagon

hypoglycemic emergencies, reverse beta blocker overdoses, aid in x-ray visualization in the bowel

what is insulin allerlgy

immediate hypersensitivity, local or systemic urticaria from IgE

SE of saxagliptin

increased rate of UTIs and URIs increase the risk of HF

nonobese patients with type 2 diabetes frequently have

increased visceral adiposity

how does rosiglitazone affect lipids

increases total cholesterol, HDL cholesterol, and LDL cholesterol doesn't affect TG

DKA occurs more frequently in pts on

insulin pumps

what are the pancreatic hormones and their functions

insulin, storage and anabolic hormone amylin, modulates gastric emptying, glucagon and insulin secretion, and appetite glucagon, mobilizes glycogen somatostatin, inhibits secretory cells PP, facilitates digestion ghrelin, increases pituitary growth hormone release

NPH is an example of which type of insulin?

intermediate acting

which insulin analogs are rapid acting

lispro, aspart, and glulisine

How are sulfonylureas metabolized?

liver excreted by the kidney, for second gens they are also partly excreted in the bile

liver and kid what are the main organs that remove insulin from circulation

liver and kidney

where is glucagon degraded

liver and kidney, as well as in plasma and at its tissue receptor sites

how does pioglitazone affect lipids

lowers TG increases HDL cholesterol without affecting TC and LDL cholesterol

Which *alpha-glucosidase inhibitors* are highly absorbed?

miglitol

pioglitazone + insulin is associated with

more weight gain and peripheral and macular edema

how is sitagliptin metabolized and what kind of pts should have low doses

mostly CYP3A4 those with impaired renal function

adverse effects of linagliptin

nasopharyngitis and hypersensitivity, as well as increased risk of pancreatitis

what are the SE of sitaliptin

nasopharyngitis, URI, headaches acute pancreatitis hypersensitivity reactions

what is the major side effect of exenatide

nausea

Qualitative detection of ketone bodies can be accomplished with the use of what tests?

nitroprusside tests

what is the common amt of insulin units pts inject

no more than 30 units

what is indicated when DKA is recurrent

noncompliance

what kind of pts are CI in exenatide use

not approved for use in pts with GFR less than 30 mL/min since it undergoes glomerular filtration

the combo of a thiazolidinedione and metformine has the advantage of

not causing hypoglycemia

increased insulin requirements typically occur with

obesity, adolescence, and during the latter trimesters of pregnancy

all GLP1 receptor agonists may increase the risk of

pancreatitis

GLP1 receptor agonists should not be used in persons with

past medical/family history of medullary thyroid cancer or MEN2

insulin glargine is described as

peakless

what is hypoglyemic unawareness

person is exposed to frequent hypoglycemic episodes, so the warning signals are less common or absent

in what kind of pts should glucagon not be used

pheochromocytoma

pts with severe insulin resistance may be candidates for pioglitazone

pioglitazone

what is diagnostic of DM

plasma glucose >126 mg/dL on more than 1 occasion or after at least 8 hrs of fasting

how is lispro different from R insulin

proline at position B28 is switched with the lysine at B29

at what times should someone administer a long acting and short acting insulin

rapid acting is 15 mins before a meal long acting is 45 mins before a meal

what are the features of rosiglitazone

rapidly absorbed and highly protein bound thiazolidinedione class metabolized by CYP2C8 mainly and to a lesser extent CYP2C9

what is the ratio of clearance for a regular person's insulin vs insulin-treated diabetics

regular - 60 liver/40 kidney diabetic - 60 kidney/40 liver

human insulin is dispensed as

regular R and neutral protamine hagedorn NPH formulas

how are insulins mixed

regular or rapid acting is drawn first, then the NPH withdraw, then injected immediately

what does glucagon do to the intesine

relaxes the intestine

what is one thing to note about insulin glargine

should not be mixed with other insulins to maintain solubility

what does glucagon do to the heart

similar effect to beta adrenoreceptor agonists without requiring a functioning beta receptor

how is aspart different from R insulin

single sub of proline for aspartic acid at B28

which DPP4 inhibitor has the best bioavailability

sitagliptin

which DPP4 inhibitors are available

sitagliptin saxagliptin alogliptin

powder insulin is CI in

smokers and patients with chronic lung disease, such as asthma or COPD

liraglutide is a _ with major side effects of

soluble fatty acid-acylated GLP1 analog nausea and vomiting

what is the features of pioglitazone

some PPAR-a as well as PPAR-y activity absorption decreased with resins metabolized by CYP2C8 and CYP3A4 affected by estrogen-containing oral contraceptives

stimulatory drugs for insulin secretion include

sulfonylureas, meglitinide and nateglinide, isoproterenol, and ACh

how is detemir different from R insulin

terminal threonine is dropped from the B30 position and myristic acid (C14 FA chain) is attached to the B29 lysine, which prolong the availability

what is the advantage of premixed insulins

they can be given within 15 mins of starting a meal and they are superior in controlling the postprandial glucose rise after a carb rich meal

dose adjustment for saxagliptin is recommended for

those with renal impairment and use of strong CYP3A4/5 inhibitors such as antiviral, antifungal, and certain antibacterial drugs

what is the modifications on insulin degludec

threonine at B30 removed and the lysine at B29 is conjugated to hexadecanoic acid via gamma-L-glutamyl spacer in the presence of phenol and zinc and self associates into large multihexameric chains

why is rotation of insulin injection sites recommended

to avoid problems with absorption due to lipohypertrophy from overuse of injection sites

what are the first gen sulfonylureas

tolbutamide - rapidly metabolized, safe in elderly and in renal impaired; hypoglycemia in pts with antibacterial sulfa drugs, phenylbutazone for arthralgias, and oral azoles chloropropamide - hypoglycemia in elderly, hyperemic flush, hyponatremia tolazamide - more slowly absored

what is the modification of dulaglutide

two GLP1 analog molecules covalently linked to an Fc fragment of human IgG4

what is the modification on insulin glargine

two arginine molecules to the B chain carboxyl terminal and substitution of a glycine for asparagine at the A21 position

what does each beta cell granule contain

two atoms of zinc and six molecules of insulin

what does the insulin receptor look like

two heterodimers that are covalently linked alpha subunit is EC beta subunit is a transmembrane protein which contains a tyrosine kinase

what are the second gen sulfonylureas

used carefully in pts with cardio disease, elderly glyburide - should not go higher than 20 mg/D; flushing, enhances free water clearance, CI in presence of hepatic/renal insufficiency glipizide - shortest half life, recommended starting dose is 5 mg/d; CI in pt with hepatic impairment; preferable to glyburide in elderly and renal impaired glimepiride - achieves target with lowest dose, completely metabolized by liver