Endo

insulin PD

__ PD

• Promotes protein synthesis by increasing AA transport into cells

• Stimulates glucose entry into cells

• Glucose storage as glycogen in muscle and liver cells

• Inhibits glucose production in liver and muscle cells (glycogenolysis)

• Enhances fat storage (lipogenesis) and prevents mobilization of fat for energy (lipolysis and ketogenesis)

• Inhibits glucose formation from noncarbohydrate sources, such as AAs (gluconeogenesis)

insulin considerations

__ considerations

• ADRs = hypoglycemia, diabetic ketoacidosis

• Watch ETOH use - increases hypoglycemia

• BB can mask hypoglycemic symptoms

rapid acting

Type of insulin

• Humalog (lispro)

• Novalog (aspart)

• Apidra (glulisine)

5-30 (min)

Rapid acting insulin onset time

0.5-3 (hrs)

Rapid acting insulin peak time

3-4 (hrs)

Rapid acting insulin duration

short acting

type of insulin

• Regular (Humulin R, Humulin RU-500, Novalin R)

30-60 (min)

short acting insulin onset

2-4 (hrs)

short acting insulin peak

3-7 (hrs)

short acting insulin duration

intermediate acting

type of insulin

• Isophane (NPH, Humulin N)

1-2 (hrs)

intermediate acting insulin onset

4-10 (hrs)

intermediate acting insulin peak

10-16 (hrs)

intermediate acting insulin duration

long acting

type of insulin

• Glargine (Lantus, Lantus U-300)

1-2 (hrs)

long acting insulin onset

none

long acting insulin peak

20-24 (hrs)

long acting insulin duration

30-60 (min combo)

Fixed combination insulin (70/30 or 50/50 NPH/regular) onset time

5-15 (min combo)

Fixed combination insulin (75/25 NPH/lispro or 70/30 NPH/aspart) onset time

dual

Fixed combination insulin peak time

16 (hrs)

Fixed combination insulin duration time

inhaled insulin

Ex: Afrezza

Onset = 12min

Duration = 3-4hrs

Taken prior to meals

u-500

Ex: Humulin-R U-500

Onset = 30-45min

Duration = 8-24hrs

Used if requiring > 200 units/day

t1DM starting dose

__ starting dose:

~ 0.4-0.5 units/kg/d in divided doses

May use higher doses in obesity, sedentary lifestyle, or presenting w/ ketoacidosis

conservative initial doses 0.2-0.4 units/kg/d

T1DM dosage calculation

__ dosage calculation

• Basal insulin generally 50% of daily dose is intermediate or long acting

• Prandial insulin is the remaining half and is short or rapid acting

10 (units) or 0.1-0.2 (units/kg/d)

Initial starting dose for T2DM

•Initial mealtime: 4–5 units or 10% of the basal insulin dose administered before the largest meal of the day

•Rapid acting insulin is usually given in addition to a regimen that includes basal insulin and metformin with or without other noninsulin agents.

•Stepwise addition of mealtime insulin starting with a single meal and progressing to two or more meals as needed every 3 months is associated with a lower risk of hypoglycemia and increased patient satisfaction compared with immediate introduction of a full basal/mealtime regimen (ADA, 2020).

•Consider reducing the total daily dose by 4 units or 10% of the basal insulin dose if HbA1c is less than 8% when initiating prandial insulin.

0.4-1 (units/kg/day)

usual twice daily dosing maintenance range for T1DM

10

Insulin is added for severe or symptomatic hyperglycemia who have inadequate control on oral agents

What A1c would indicate inadequate control?

<7

Goal A1c for diabetic patients

6.5

A1c of __ is diagnostic of diabetes

hypoglycemia risk

What are we always thinking about for diabetic patients

tube feeds

We use regular insulin for….

meal time coverage

We use rapid-acting insulin for…

steroid induced (hyperglycemia)

We use intermediate acting insulin (NPH) for…

Biguanides

Ex: metformin

Use: 1st line for T2DM w/ lifestyle changes

USBW: development of fatal lactic acidosis (getting contrast dye, underlying renal/hepatic impairment)

biguanides PD

__ PD

• Antihyperglycemic (not a hypoglycemic drug).

• Reduces fasting post-prandial hyperglycemia by decreasing glucose production/absorption

• improves insulin sensititivty (increasing peripheral uptake)

• does not stimulate insulin release

• inhibits platelet aggregation

biguanides considerations

__ considerations:

• Renal/hepatic dx or major dysfunction - do not give

• CHF, hypoxia, sepsis - hold in acute settings

• Watch pt w/ vitamin b12 anemia/deficiency (~10% of pts using have this - intrinsic factor interference??)

• Pregnancy category B (not recommended)

• No recommendation for kids <10yo

Not cardioprotective

>60 and <40

Metformin is ok to give someone w/ creatinine clearance or GFR >__ and it must be stopped for creatinine clearance or GFR < __

biguanides monitoring

__ monitoring

• Wt loss

• Low risk of hypoglycemia

• Renal fx

• Ketones

• HbA1c before starting and then q6mo

• B12 q1yr

GI upset

MC ADR for metoformin, often resolves in 2wks

24-48 (hrs)

For how long should metformin be held before diagnostic/ambulatory procedures?

Can be resumed 48hrs after

sulfonylureas

Ex: glipizide, glyburide, glimepiride

PD: stimulate insulin release from pancreas, potentiate ADH

Goes through CYP - interactions

sulfonylureas considerations

__ considerations

• Cross-sensitivity w/ sulfonamides or thiazide diuretics

• Avoid in HF

• Pregnancy category C

• Older adults are more sensitive

• Off-label use in kids 10-18yo

sulfonylureas monitoring

__ monitoring

TZDs (thiazolidinediones)

Ex: piglitazone and rosiglitazone

PD: improve target cell response to insulin and increase utilization of insulin by liver and muscle cells - sensitizers

PK: CYP, highly protein-bound

USBW - increase in plasma volume

Do not cause hypoglycemia, not cardioprotective

TZD a1c

__ a1c

reduced by 0.5-1%

sulfonylureas and biguanides a1c

__ and __ a1c

Reduces by 1-2%

TZDs considerations

__ considerations

• Caution in liver dx - monitor ALT (>2.5x upper limit = do not use)

• Can cause fluid retention - avoid in HF

• Increased risk of bone loss/fracture and bladder cancer w/ pioglitazone (correlation) - avoid w/ smokers

• Not approved for <18yo

TZD adrs

__ adrs

• edema

• URIs

• HA

• Fatigue

gliptins (Dipeptidyl Peptidase-4 Inhibitors)

Ex: sitagliptin (Januvia) and saxagliptin

PD: promotes satiety, inhibits DPP-4, breaks down GLP-1 and gastric inhibitory polypeptide (released in response to meals) → increasing secretion of insulin and suppressing glucagon release, improves pre- and postprandial glucose, mild wt loss

Do not cause hypoglycemia, not cardioprotective

gliptins considerations

__ considerations

• Renal dysfunction

• Pregnancy - caution

• Increased risk of angioedema - do not combine w/ ACEi

• Stop if they develop pancreatitis

gliptin monitoring

__ monitoring

• Monitor for potential thyroid medullary CA - esp in those w/ previous nodules

• Renal function baseline and annual

• HBA1c q3mo

gliptin a1c

__ a1c

reduces by 0.5-0.8%

GLP1

Ex: semaglutide (Ozempic), liraglutide (Victoza), dulaglutide (Trulicity)

PD: promote insulin release from pancreas, mimic natural incretins → slowing glucose absorption from gut

Low hypoglycemia risk and cardioprotective (reduce oxidative stress and inflammation in cardiac myocytes and in BVs)

GLP1 considerations

__ considerations

• Severe GI dx - colitits, Crohn’s

• Pregnancy - caution

GLP1 adrs

__ ADRs

• GI upset

• Acute pancreatitis

• Wt loss

• Risk for medullary thyroid cancer - not strong evidence but some

• Can worsen gastroparesis

GLP1 a1c

__ a1c

Reduces by 0.5-0.8%

SGLT2 (sodium-glucose cotransporter-2 inhibitors)

Ex: “flozin” canagliflozin (Invokana), dapaglidlozin (Farxiga), and empagliflozin (Jardiance)

PD: reduce BG by blocking glucose reabsorption in the kidney “glucoretic”

Cardiac benefit for those w/ EF <45%, nephroprotective w/ diabetic kidney dx w/ albuminuria

SGLT2 a1c

__ a1c

Reduces by 0.7-1.5%

0.4-1%??

SGLT2 adrs

__ adrs

• UTIs

• Genital infection - Fournier’s gangrene, yeast infections

• HoTN

• Increased urination

• Renal dysfunction, hyperkalemia

SGLT2 monitoring

__ monitoring

• renal function baseline, 1mo

• potassium

• infections

70-130

Goal pre-prandial plasma glucose

<180

2 hr postprandial plasma glucose goal for diabetes

70 (w/ symptoms)

BG for hypoglycemia

15 (15 in 15)

15 grams of carbohydrate, repeat BG in __ minutes

hypoglycemia managment

__ management

• 4oz of juice/soda

• Glucose tabs (5g in 1 tab - 3-4 tabs)

• 4-6 pieces of hard candy

• 1 cup ckim milk

• 1 tbsp honey - put under tongue

• Complex carb and protein within next hour (PB and cracker, sandwich)

Be careful to not overshoot

glucagon

An insulin antidote

PD: stimulates gluconeogenesis and glycogenolysis, BG concentrations rise within 10min, max at ~ 30min, NEED to have hepatic stores of glycogen to be effective

PTU (Propylthiouracil)

1st trimester, trying to get pregnant, or in neonates we use __ for hyperthyroidism

antithyroid adrs

__ adrs

• agranulocytosis

• hepatotoxicity

• HA

• drowsiness

• alopecia

• rashes

• pancreatitis (in 1st 90d) - methimazole

antithyroid

Ex: Propylthiouracil (PTU), methimazole (Tapazole)

PD: block synthesis of T4 and T3, neither treats underlying pathology

antithyroid considerations

__ considerations

• pregnancy category D - PTU preferred in pregnancy

• reactions w/ lithium and warfarin

• appears in breastmilk

antithyroid monitoring

__ monitoring

• thyroid studies, CBC, and liver/renal fx prior

• free T4 and T3 2-6wks after start, repeat in 4-6wks, then q 2-3mo once euthyroid lvls

thyroid hormones

Ex: levothyroxine (T4) - drug of choice, liothyronine (T3), liotrix (4:1 mix of T4 and T3)

PD: same as endogenous hormones, negative feedback loop that reduces further secretion of TSH and thyroid hormones

If pregnant - may require higher doses from baseline

Contraindications after acute MI or thyrotoxicosis

levothyroxine adrs

__ adrs

• sx of hyperthyroid

  • angina

  • HTN

  • flushing

  • palpitations

  • anxiety

  • HA

  • insomnia

• Interactions w/ bile acid sequestrants, iron salts, antacids - decrease absorption; estrogen may decrease response

levothyroxine monitoring

__ monitoring

• TSH lvl in 6wks (target 0.3-3 μIU/mL)

• Once stable, annual

• Monitor for osteoporosis in high risk population

levothyroxine edu

__ edu

• take in the morning, before breakfast (absorption increased on empty stomach)

• teach how to measure HR / s&s of hyperthyroidism