ENDO -- pharm

What are the 3 main fcts of thyroid hormones?

• Stimulation of energy use

• Stimulation of the heart

• Promotion of growth and development

What are the two active hormones released by the thyroid gland

T4 (thyroxine) → conversion → T3 (triiodothyronine)

(T/F): T3 is the thyroid lab MC ordered to assess thyroid function.

False! T4 = MC used

± T3 (only when there’s an issue), TSH

What are the sx of hypothyroidism (list 8):

• Fatigue

• C

• Weight gain

• Increased sensitivity to cold

• Dry skin

• Depressed mood

• HTN

• AMS

1st-line DOC for hypothyroidism:

Levothyroxine (T4)

two key differences of liothyronine (T3):

• Shorter half life

• More expensive

What are important PK of levothyroxine

• take on empty stomach → 30 to 60 mins before breakfast

• many D/I → decr. absorption (GI med — acid decr.)

What are common D/I with levothyroxine (list 8):

• H2RA

• PPIs

• Sucralfate

• Aluminum-containing antacids

• Ca supplements

• Iron supplements

• Mg salts

• Orlistat

Warfarin PO has different colors corresponding w/ doses — what thyroid med also does that?

Levothryoxine (PO) — pts. may be on multiple diff. doses

IV PK of levothyroxine, what lab value is ck later?

• 50% of PO

• Long half life of 7 days → ck TSH 6-8 wks after initiating tx or modifying dose

What do medical organizations rec. in regard to switching levothyroxine brands?

try to keep patients on the same product d/t varying sx/labs→ If must switch → recheck TSH in 6 wks

T/F: porcine thyroid ( Armour Thyroid / NP Thyroid / Nature Thyroid) is an appropriate alternative agent for hypothyroidism.

FALSE. It is a desiscated thyroid (combo of T3/T4 in a ratio of ≈10% range) that is NOT rec.

• variable potency

What are the s/s of HYPERthyroidism:

Sweating

Wl

Emotional lability

Appetite increased

Tremor/ tachycardia (arrhythmias)

Intolerance of heat/ Irreg. menorrhea / Irritability

Nervousness

Goiter and GI problems (diarrhea)

±:

• Hair loss

• AMS

• HTN

What is the MOA of methimazole (thioamide):

Prev. oxidation of iodide → blocks synthesis of thyroid hormones

Which drug is considered 1st-line for hyperthyroidism except during the 1st trimester of pregnancy, thyroid storm, or intolerance?

• methimazole

A pt. on methimazole develops a sore throat and fever. These are early signs of a rare but serious ADE. What are you concerned about?

What are the preg. ade of methimazole (list 3)?

• Agranulocytosis

• Preg. effects: neonatal HYPOthyroidism, goiter, congenital HYPOthyroidism

What other thioamide has similar MOA + blocks conversion of T3/T4 & is used as the 1st-line for the exceptions of methimazole?

hint: Pregnancy Thyroid storm Uno

propylthiouracil (PTU)

• 1st trimester

• thyroid storm

• intolerant of methimazole

What are the ADE of propylthiouracil PTU that makes it 2nd-line for HYPERthyroidsm except for when methimazole ≠ be used?

• Agranulocytosis (rare)

• BBW: Hepatotoxicity

What does the Ominous Octet refer to in T2DM?

• Insulin resistance in muscle

• Impaired insulin secretion

• Incr. hepatic glucose production

• NT dysfct

• Incr. glucagon secretion

• Incr. renal glucose reabsorption

• Decr. incretin effect

• Incr. lipolysis

What are sx of HYPERglycemia

• Polyuria

• Polydipsia

• Polyphagia

• Blurry vision

What are sx of HYPOglycemia

hint: cold & clammy, need some candy

• Fatigue

• Shakiness

• Anxiety

• Sweating

What are complications of DM:

• eyes, nerves, kidneys, heart, brain

• Retinopathy

• Neuropathy

• Nephropathy

• Coronary atherosclerosis

• Cerebrovascular sclerosis

What is the fasting PG criteria for dx of DM?

• FPG >126 mg/dL

  fasting: no caloric intake for 8 hrs on two separate occasions

What is the 2 hr PG OGTT criteria for diabetes dx?

>200 mg/dL on two separate occasions

What is the A1C criteria for diabetes dx?

A1C >6.5% on two separate occasions!

A pt. presents with random PG of 220 mg/dL w/ classic sx of HYPERglycemia. What does this confirm?

>200 mg/dl = DM

What does A1C tell us about the structure of RBCs?

% of RBCs that have sugar coated hemoglobin

Why can A1C only be remeasured every 3 months

Because RBCs regenerate roughly q3mos

What is the A1C and PG goal for most DM adults?

• A1C < 7%

• PRE-prandial: 80-130 mg/dL

• Post prandial: <180 mg/dL

What is the A1C goal for patients with limited life expectancy or comorbidities?

<8%

What are 1st line NON-insulin options for T2DM (list 6):

• Metformin

• Sulfonylureas

• Thiazolidinediones (TZDs)

• GLP-1 receptor agonists

• DPP-4i

• SGLT2i

T2DM: What meds are preferred in ASCVD or high risk ASCVD (2+ RF)

• GLP-1 receptor agonists (dula–, lira–, sema– glutides

• SGLT2i (cana–, empa– giflozin)

T2DM: What meds are preferred in CKD

• GLP-1 receptor agonists (dula–, lira–, sema– glutides

• SGLT2i (cana–, empa–, dapa– giflozin)

T2DM: What meds are preferred in HF

SGLT2i (cana–, empa–, dapa–, ertu– giflozin)

T2DM + WL desire: What meds are preferred?

• GLP-1RA

• SGLT2i

• DPP-4i

• metformin

T/F: if hypoglycemia is a concern, sulfinylureas are the preferred agents.

FALSE. Anything except sulfonylureas

What drug classes are preferred if cost is a concern

• Metformin

• Sulfonylureas (SU)

• Thiazolidinediones (TDZs)

What is the MOA of metformin

• Decr. hepatic gluconeogenesis

• Decr. intestinal absorption of glucose

• Improves insulin sensitivity

What are the ADE of metformin

• D + N

• Bloating (titrate dose gradually!)

• Lactic acidosis (rare!) d/t decr. GFR!

• Vit. B12 deficiency

switch to XR formula for decr. GI ades

Severe renal impairment is a C/I for metformin, what is the eGFR limitation?

eGFR <30 —> lactic acidosis!

What patient education is important for metformin

Take with food

what class of drugs are the following: glimepiride, glipizide, glyburide

sulfonylureas (SU)

What is the MOA of sulfonylureas (SU)

blocks ATP-sensitive K-channels → depolarization (Ca influx) → stimulate insulin release from FUNCTIONING beta cells

T/F: SU should be rx for a chronic DM pt

FALSE! chronic DM pts have low pancreatic fct (beta cells)

What are the ADE of sulfonylureas (SU)

• Weight gain

• incr. risk of CV mortality (older SU)

What are precautions for sulfonylureas

Incr. hypoglycemia risk IF renal impairment

What patient education is important for sulfonylureas

Take with meals → risk of hypoglycemia!!!

What is the MOA of thiazolidinediones (TZDs): pioglitazone

Activates PPAR-gamma type (peroxisome proliferator-activated receptor-gamma)

• Incr. glucose uptake in muscle and adipose

• Inhibits hepatic gluconeogenesis

The ADE of TZDs (PPPPPioglitazone) typically outweigh the benefits, what are the ADE?

• Fluid retention (edema)

• Weight gain

• Bone Fx

• Bladder Cx (peepee)

What is a C/i of TZDs (causes edema as an ADE!)

BBW - HF

What patient education is important for TZDs

signs of fluid retention

What is the drug class of the following: dulaglutide, exenatide, liraglutide, semaglutide, tirzepatide?

GLP-1RA ($$$)

What is the MOA of GLP-1RA

• Analog of GLP 1 released in response to FOOD:

  • Stimulate insulin release

  • Inhibit glucagon secretion

  • Lowers hepatic glucose output

  • Delay gastric emptying

What are the ADE of GLP-1RA

• N / V

• C / gastroparesis

• Inj. site rxn

• Pancreatitis*

• Thyroid cell carcinoma**

• UTI?***

*unknown if predisposed to pancreatic cx

**studies in animals, not human

***according to LAB MED/GOOGLE

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What are C/I for GLP-1RA

• Genetic pancreatitis / spontaneous pancreatitis

• Medullary thyroid cancer

What patient education is important for GLP-1RA

• SQ inj. technique

  • start @ small dose → titrate slowly

what class are the following drugs: alogliptin, linagliptin, saxagliptin, sitagliptin?

DPP-4i ($$$)

What is the MOA of DPP-4i

Inhibits dipeptidyl transferase-4 enzyme → prolonged incretin (GLP-1) levels

T/F: it is rec. to Rx a pt. BOTH GLP-1RAs and DPP-4i to optimize the benefits of incretins (GLP1s).

FALSE. no extra benefit, just more $$$

What are ADE of DPP-4i

• Joint pain (rare)

• Pancreatitis*

• Saxagliptin: New / worsening HF

*seen in rodent studies only

What is the MOA of SGLT2 inhibitors

Sodium-glucose-cotransporter-2 inhibition in the proximal renal tubule reduces reabsorption of filtered glucose

1st-line for pts. w/ HF* + CKD + ASCVD

SGLT-2i is a great option for HF! What comorbidity should SGLT-2i be cautiously used?

HF w/ diabetes → risk for HypoTN

What drug has the following ADE profile?

• Euglycemic diabetic ketoacidosis

• Genitourinary infxn

• Bone fx

• HypoTN

• BBW - Lower limb amputations

SGLT2i

*consider lowering doses of diuretics / SU / insulin*

What patient education is important for SGLT2i

s/s of UTI / hypoTN

What drug class are the following drugs: acarbose / miglitol?

Alpha-Glucosidasei

What drug…

• is no longer rec. by the ADA

• can be used as monotherapy

• MOA: Delays digestion of complex carbohydrates → reduced absorption of glucose → smaller rise in postprandial PG

alpha-glucosidasei

the ADE of alpha-glucosidasei diminish overtime / if dose reduction. What are they?

• Flatulence

• Abd.distention

• Loose stools

• D

what class are the following drugs: nateglinide / repaglinide?

meglitinides

What drug…

• is no longer rec. by the ADA

• can be used as monotherapy

• taken BEFORE EACH meal to incr. absorption

• MOA: Stimulate pancreatic beta cells to produce insulin

meglitinides

What are ADE of meglitinides

• Hypoglycemia

• Initial weight gain

What is the MOA of pramlintide (amylin mimetics)?

Synthetic analog of human amylin:

• Prolongs gastric emptying → appetite suppression

• Reduces post-prandial glucagon secretion

amylin mimetics are NOT 1st-line b/c they have a severe BBW ADE when used with what other med?

SQ inj → Severe hypoglycemia (BBW = if used w/ insulin in T1DM w/n 3hrs)

insulin is a molecule consisting of 2 AA chains, what is the main stimulus for its release from pancreatic Beta cells?

rise in blood glucose

What is the PK of the following insulin drugs: Lispro / Aspart / Glulisine

bolus, rapid-acting

• onset w/n 10 → admin. before meals

• lasts 3-6hrs

What bolus, SA insulin has an

• onset of 30 mins → admin before meals

• duration of 3-6 hrs

Regular insulin (novolin)

What is an example of intermediate acting insulin? What is its PK?

NPH insulin

• onset w/n 30-60 minutes

• lasts 6-10hrs

• admin. BID

What classification RE:duration are the following insulin drugs?

• Insulin glargine

• Insulin detemir

• Insulin degludec

long acting basal insulin

What’s unique about the PK of insulin detemir

required BID + dose-dependent PK*

*studies show that action doesn’t peak until 24hrs worth of doses*

What is the onset and duration of long acting insulin

• Onset 3-4 hrs

• Duration 18-24 hrs

• QD or BID @ same-time everyday

Which LA insulin requires BID dosing?

insulin detemir (levemir)

List 3 examples of pre mixed insulin (intermediate + bolus)

• Novolin 70/30 (70% NPH + 30% regular)

• Novolog 70/30 (70% aspart protamine + 30% aspart)

• Humalog 75/25 (75% lispro protamine + 25% lispro)

T/F pre-mixed insulin = 2 doses in AM/PM.

True!

What is the risk of pre-mixed insulin

Incr. risk of low blood sugar

What are some reasons why pre-mixed insulin is Rx?

GAP in duration / MOA of insulin d/t

• no consistent lunch times / skips meals

• 12 hr work shifts

• only affordable option

• unwilling to take 2+ inj.

U-100 vs U-200/300 vs. U-500:

• what is the MC units?

• what is more comfortable to inj.

• which is rec for pt. who need 200+ units/day?

MC = 100 units/mL

U-200 / U-300 = higher concentration; more comfortable to inj.

U-500 regular insulin = it has delayed onset + longer duration but 2-3x/day

T/F: Keep insulin in room temp. since inj. won’t hurt as much compared to when cold

TRUE! only once container is OPEN!!!

*refrigerator not required!*

How long is opened insulin good for?

28 days at fridge or room temperature —> D/C if past

T/F: insulin pens are the better $$$ choice b/c vials/syringe have to constantly be restocked.

FALSE. still

What are mgmt options for T1DM + general pt. education?

• Multiple daily inj. of rapid-acting prandial + basal insulin

• Continuous SQ infusion pump

teach how to match mealtime insulin doses to carb/protein/fat intake ratio + physical act.

Who may be considered for an insulin pump

• all capable T1DM

• T2DM who require multiple injs.

What are advantages of an insulin pump

• Decreases number of injections per day

• Provides bolus insulin throughout the day

What are tips for insulin pump use

• Ask if patient feels comfortable

• In the hospital, ensure pump is disconnected prior to inj. of insulin

• Consult endocrinology for settings

• Consult pharmacy

What is a CGM?

Continous Glucose Monitor:

Wearable technology measuring glucose levels 24hrs

convenient » finger pricks / POC glucometers

How is a CGM worn

• under skin (belly / arm)

• changed q7-14 days

• data on app

How can a CGM notify the pt. when glucose levels are not ideal?

alarms! but app must be near the sensor

T/F: the avg. T1DM should ideally get 4 injections of insulin per day!

TRUE-ISH. bolus for each meal the pt. eats + 1 for basal insulin

on avg. 3 bolus + 1 basal

high-risk pts profile :

• 25-59 y/o

• BMI >35

• FPG >110 mg/dL

• A1C >6.0

• prior gestational DM

What should be the 1st-line T2DM med Rx d/t its low cost and weight loss capabilities?

metformin!!

What is 1st-line tx for gestational DM b/c drugs like metformin / glyburide cross the placenta & may not be able to provide adequate glycemic crtl?

Lifestyle behavior change → ± Insulin

When to consider insulin for T2DM?

“unctrlled” T2DM:

• WL (catabolism)

• hyperglycemic sx

• A1C >10%

• BG >300 mg/dL

in unctrlled T2DM: what drug should be considered before using insulin:

GLP-1RA (if not already on it)