Endocrine

Question 1

Cushing’s Syndrome versus Addison’s Disease
-What are ways to reduce Cushing’s syndrome?

Answer 1

Cushing’s Syndrome: adrenal gland produces too much cortisol or if exogenous steroids are taken in doses higher than normal
-Long Term Effects: psychiatric changes (anxiety, depression, delirium, HA, intracranial HTN, hypothyroidism), glaucoma/cataracts, acne, fat deposits in face (“moon face”) or abdomen/upper back (“buffalo bump”). GI bleeding/esophagitis/ulcers, pink-purple stretch marks, DM, growth retardation/muscel wasting, impaired wound healing, poor bone health

-Women: hirsuitism, irregular/absent menstrual periods

Addison’s Disease: “Cushing Syndrome’s Opposite”: adrenal gland NOT making enough cortisol and if exogenous steroid stopped, adrenal crisis (“Addisonian Crisis”) can occur

Reduce Cushing’s Syndrome:
-QOD steroid dosing
-High doses initial to then taper (ex. Medrol pack)
-For joint inflammation, use intra-articular injections
-Fo GI conditions, use steroids w/ low absorption (e.x DR budesonide)
-For treatment of asthma, use inhaled steroids
-FOr condtions that require long-term steroids (ex. transplant, severe autoimmune condition), use lowest effective dose for shortest period to time

Question 2

Systemic Steroids:
-Different indications

-Which steroids have more glucorticoid activity versus mineralcorticoid activity?

-Why must glucocorticoids be tapered?

Answer 2

TX:
-Inflammatory conditions: rheumatoid arthritis, psoriasis, acute asthma exacerbation
-Immune suppression post-transplant
-Adrenal insufficency (cortisol can be replaced by any steroids, aldosterone replaced by fludrocortisone)
-Fludrocortisone: Addison’s disease, sometimes orthostatic hypotension

Activity:
-More glucocorticoid (anti-inflammatory): hydrocortisone, cortisone, prednisolone
-More fludrocortisone (water and electrolyte balance): fludrocortisone

Taper: systemic steroids can cause the adrenal gland to stop producing cortisol through feedback inhibition (suppression of the hypothalamic pituitary-adrenal or HPA axis)

Question 3

Steroids IV/PO Dose Equivalence:
-List least potent to most potent

-Classify which ones are short, intermediate, and long-acting

Answer 3

Least potent, short-acting:
-Cortisone: 25mg
-Hydrocortisone: 20mg

Intermediate-acting:
-Prednisone: 5mg
-Prednisolone: 5mg
-Methylprednisolone: 4mg
-Triamcinolone: 4mg

Long-acting, most potent:
-Dexamethasone: 0.75mg
-Betamethasone: 0.6mg

“Cute Helpful Pharmacists and Physicians Marry Together and Deliver Babies”

Question 4

Glucocoritcoids: List brand names for the generics and ROAs:
-Dexamethasone
-Hydrocortisone
-Methylprendisolone
-Prednisone

Answer 4

Dexamethasone: DexPak 6, 10, or 13 day (PO), Dextenza (opthalamic), Dexamethasone Intensol (PO solution)

Hydrocortisone: Solu-Cortef (IV or IM), Cortef (PO), Alkindi Sprinkle (PO granule), Anusol-HC (rectal), Cortizone-10 (topical)

Methylprendisolone: Medrol (PO), Solu-Medrol (IV), Depo-Medrol (IM, intr-articular, soft tissue, or intralesional injection)

Prednisone: Deltasone (PO), Prednisone Intensol (PO solution), Rayos (PO)

Question 5

Glucocoritcoids: List brand names for the generics and ROAs:
-Prednisolone
-Trimacinolone
-Betamethasone

Answer 5

Prednisolone: Millipred (PO), Orapred ODT, Pediapred (PO)

Trimacinolone: Kenalog (topical or injection), Nasocort AQ (nasal spray), Pro-C-Dure kits (injection)

Betamethasone: Celestone Soluspan (injection)

Question 6

Glucocorticoids:
-Adminsitration considerations
-Which ones are prodrugs?
-Which one is commonly used in children?

Answer 6

Administration:
-Take PO doses WITH FOOD to decreases GI upse
-If taken once daily, take between 7-8am to mimic the natural diurnal cortisol release (can cause insomnia if taken later in day)

Prodrugs:
-Cortisone: prodrug of cortisol
-Prednisone: prodrug of prednisolone

Commonly used in children: prednisolone

Question 7

Glucocorticoids:
-AVEs short term <1 month usage

-AVEs long term

Answer 7

AVEs short term: (KNOW ALL) fluid retention, stomach upset, emotional instability (euphoria, mood swings, irritabiliy), insomina, increased appetite, weight gain. acute increased BG/BP (with higher doses)

AVEs long term:
-Psychiatric (anxiety/depression, delirium, psychoses), HA, intracranial pressure, hypothyroidism

-Glaucoma/cataracts

-Fat deposits in face (“moon pie”) or abdomen/upper back (“buffalo hump”), acne

-GI bleeding/esophagitis/ulcers

-Pink-purple stretch marks (straie) on abdomen, thighs, breast, and arms; thin skin that bruises easily

-DM, growth retardation, mucsle wasting (thin arms/legs)

-Infection, impaired wound healing

-Poor bone health

-Women: hirsuitism (hair growth on face), irregular/absent menstrual periods

Question 8

Glucocorticoids:
-Warnings
-CIs
-Monitoring

Answer 8

Warnings:
-Adrenal suppression: HPA axis suppression may lead to adrenal crisis and death; if taking longer than 14 days, MUST TAPER SLOWLY (many ways, but can reduce dose by 10-20% each day)

-Immunosuppression (>/=2mg/kg/day or >/=20mg/day of prednisone or prednisone equivalent for >2 weeks), psychiatric disturbances, Kaposi sarcoma

-Can worsen HF, DM< HTN, and osteoporosis

CI: live vaccines (can develop infection if immunosuppresed), serious systemic infections

Monitoring:
-Appetite, weight, growth (children/adolescents), BMD
-BP, BG, electrolytes
-Infections
-IOP if >6 weeks

Question 9

Autoimmune diseases:
-Define, give examples
-Common symptoms
-Labs for general inflammation
-Risks of immunosuppresion therapy

Answer 9

Autoimmune: body’s immune system attacks and destroys healthy body tissue
-Examples: rheumatoid arthritis, systemic lupus erythematosus, multiple scloerosis, celiac disease, Sjogren’s syndrome, Raynaud’s, myasthenia gravis, psoriasis, T1DM, Hoshimotos’ thyroiditis, Grave’s disease

Common symtpoms: fatigue, weakness, pain

General inflammatory labs: erythrocyte sedimentation rate (ESR), C-reactive protein (CRP - produced by liver in acute inflammation), rheumatoid factor (RF - autoantibody), anti-nuclear antibody (ANA - test not suggest autoimmune reaction)

Risks of immunosuppression therapy:
-Reactivation of tuberculosis or hepatitis B/C: testing/TX should be done prior

-Viruses: live vaccines should be given prior to TX

-Lymphomas and certain skin cancers: normally suppressed by competent immune system

-Infections: be wary of vaccinations and timing

Question 10

Rheumatoid Arthritis (RA):
-Define
-S/Sx

Answer 10

RA: chronic, PROGRESSIVE autoimmune disorder that primarily affects joints (can offect kidneys, eyes, heart, lungs

S/Sx:
-BILATERAL symmetrical inflammation (since autoimmune attacking itself regardless where - OA: unilateral) with pain causing warm. tender, swollen, and painful joints
-Systemic disease that can cause fever. weakness, loss of appetite
-Stiffness and pain WORSE AFTER REST (“MORNING STIFFNESS”) –> different from OA where it is NOT prolonged
-With progression: joint erosion and rheumatoid nodules
-Labs: anti-citrulinated peptide antibody (ACPA) and rheumatoid factor (RF) –> RF has LOWER SPECIFICITY (can be positive in other autoimmune conditions)

Question 11

Rheumatoid arthritis: TX

Answer 11

Classifed based on severity of low, moderate, or high disease activity

-ALL severities if SYMPTOMATIC: disease-modifying antirheumatic drug (DMARD) –> slow disease to prevent further joint damage (intial preferred: methotrexate)

-Moderate/high activity: if MTX fail w/ or w/o systemic steroid: combination of DMARDs, tumor necrosis factor (TNF) inhibitor biological or non-TNF biologic w/ or w/o MTX

-NEVER: use two biologic DMARDs in combo (serious fatal infections and not more additional benefit)

-Steroids: for bridging while DMARD is taking effect at low dose

-NSAIDs: weaker anti-inflammatory than steroids and must use high doses (safer, but consider toxicities: GI bleeds, CVD risk)

Question 12

Methotrexate (MTX):
-Brands/ROAs
-MOA
-Indications
-Dosing for RA
-DDIs

Answer 12

Brands:
-Trexall: oral tablet
-Otrexup, Rasuvo: single-dose (needle included) SQ auto-injectors
-Xatmep: oral solution for pediatric pts

MOA: irreversibly binds and inhibits dihydrofolate reducatse, inhibiting foalte, thymidylate synthetase, and purine
-Immune modulator and anti-inflammatory activity
-RA: non-biologic DMARD

TX: RA, cancer (IV/IT injections)

Dosing for RA: 7.5-20mg QWEEKLY (PO, SQ, or IM)
-To avoid error, safest as single dose (rather than divided)
-NEVER DAILY DOSE IN RA (too many incidences of AVEs: mouth sores, intestinal bleeding, LIVER DAMAGE)

DDIs:
-AVOID ALCOHOL (liver toxicity - can be very significant)
-Renal elimination decreased by ASA/NSAIDs, beta-lactams, and probenecid
-Sulfonamides and topical tacrolimus increased AVEs of MTX
-MTX can decrease effectiveness of loop diuretics, and loop diuretics can increase MTX concentration
-MTX and cyclosporine levels will both increasd when used together

Question 13

Methotrexate (MTX):
-AVEs (What can be given to reduce AVEs?)
-CIs
-BBW
-Monitoring

Answer 13

AVEs: vary by route and dosage; N/V/D, increased LFTS, stomatitis, alopecia, photosensitivity, arthralgia, myalgia
-Reduce AVEs w/ folate to decrease hematologic, GI, and hepatic side effects (5mg PO weekly on the day following MTX administration - some take 1mg daily on non-MTX days)
-If pt takes folate same day of MTX, MTX will destroy it
-Injections can be used to bypass common N/V

CI: pregnancy, breastfeeding, alcohol use disorder, chronic liver disease, blood dyscarasias, immunodeficiency syndrome

BBW: HEPATOTOXICITY, MYLEOSUPPRESSION, MUCOSITIS/STOMATITIS, PREGNANCY (teratogenic)
-Others: acute renal failure, pneumonitis, GI toxicity, dermatologic rxns, malignant lymphomas, fatal opportunistic infections
-Renal and lung toxicity MORE likely with higher ONCOLOGIC DOSES

Monitoring: CBC, Chest X-ray, hepatitis B/C serologies (if high risk), SCr, PFTs (if lung symptoms), TB test
-LFTS: baseline, Q2-4 weeks for first 3 months or following dose increases, Q8-12 weeks for 3-6 months, then leass frequently

Question 14

Sulfasalazine:
-Brand
-MOA/Role in RA
-ROA
-AVEs
-Warnings
-CI
-Monitoring

Answer 14

Brand: Azulfidine, Azulfidine EN-tabs

MOA: immune modulator, non-biologic DMARD in RA w/ or w/ MTX

ROA: PO

AVEs: HA, rash, anorexia, dyspepsia, N/V/D, oligospermia (reversible), folate deficiency (give 1mg/day folate supplement), arthralgia, crystalluria (take CF and 8oz of water to prevent), YELLOW-ORANGE COLORATION OF SKIN/URINE

Warnings: blood dyscrasias, severe skin rxns (SJS/TENs), hepatic failure and pulmonary fibrosis (use caution w/ G6PD deficiency)

CI: SULFA OR SALICYCLATE ALLERGY (will cross-react with Bactrim and ASA), GI or GU obstruction. porphyyria

Monitoring: CBC and LFTs (baseline then every other week for first 3 months then monthly for 3 months then once Q3 months), renal fxn

Sulfasalazine:
-Sulfa: sulfa allergy CI
-Sa: salicyclate allergy CI
-La: liver and loss of hair (alopecia)
-I: Impairs color of skin and urine (orange)

Question 15

Hydroxychloroquine
-Brand
-MOA
-Role in RA
-ROA
-AVEs
-Warnings
-Monitoring

Answer 15

Brand: Plaquenil

MOA/Role in ROA: immune modulator (non-biologic DMARD) added w/ or w/o MTX
-Lower risk of liver toxicity than MTX and can be alternative
-Monotherapy: if low disease and symptoms <24 months
-If inadequate or no response after 6 months, consider alternative

ROA: PO

AVEs: VISION CHANGES (dose-related), N/V/D, abdominal pain, rash, pruritus, HA, pigmentation changes of skin/hair (rare), bone marrow suppression (anemia, leukemia, thrombocytopenia) and hemolysis in G6PD deficiency, hepatotoxicity
-Take with food or milk due to N/V/D

Warnings: IRREVERSIBLE RETINOPATHY, cardiomyopathy and QT PROLONGATION, myopathy and neuropathy, hypoglycemia, psychiatric events (including suicidal behaviors), renal toxicity (possibly from phospholipidosis)

Monitoring: CBC, LFTs, and ECG at baseline and periodically; EYE EXAM and muscle strength at baseline and Q3 months during prolonged therapy

Question 16

Leflunomide:
-Brand
-MOA/Role in RA
-AVEs
-Warnings
-CIs
-BBWs
-Monitoring

Answer 16

Brand: Arava

MOA: inhibits pyrmidine synthesis, resulting in anti-proliferative and anti-inflammatory effects
-Prodrug of teriflunomide
-Role in RA: non-biologic DMARD w/ or w/ MTX

ROA: PO

AVEs: increased LFTs, nausea, diarrhea, respiratory infections, rash, HA

Warnings: severe infections, serious skin rxns (SJS/TENs), peripheral neuropathy, interstitial lung disease, HTN
-Accelerated drug elimination procedure to reduce levels of active metabolite, teriflunomide (either use: cholestyrammine 8mg TID x11D OR activated charcoal suspension 50mg BID x11D)

CI: PREGNANCY, severe hepatic impairment, current teriflunomide therapy

BBW:
-do NOT use in pregnancy (teratogenic): must test prior to starting, use two forms of birth control during TX, and if pregnancy desired wait 2 years after D/C or use accelerated drug elimination procedure
-Hepatotoxicity: avoid in pre-existing liver disease or ALT >2x ULN

Question 17

Janus Kinase (JAK) Inhibitors in RA:
-Drugs/brands
-MOA
-ROA
-AVEs
-Warnings
-BBW
-Monitoring

Answer 17

Drugs: tofacitinib (Xelijanz, Xelijanz XR), baricitinib (Olumiant), upadacitinib (Rinvoq)

MOA: inhibit janus kinase enzymes which stimulate immune cell function
-Role in RA: non-biologic DMARD w/ or w/o MTX

ROA: PO

AVEs: URTIs, UTIs, diarrhea, HA, HTN, increased lipids
-Increased risk with Asians

Warnings: GI perforation, increased LFTs, hematologic toxicities
-Avoid live vaccines
-Avoid concurrent use w/ BIOLOGIC DMARDs or POTENT IMMUNOSUPPRESANTS (though this drug class is a non-biologic, they are VERY POTENT)

BBW
-Serious infections (including TB, opportunistic, viral, fungal): screen for active and latent TB
-Malignancy: increased risk for lymphomas and others
-Thrombosis (including DVT/PE)
-Mortality and major CV events (especially in >/=50 yo w/ 1 or more CV risk factor)

Monitoring: CBC (lymphopenia, neutropenia, anemia), new onset abdominal pain, s/sx of infection
-Lipids: baseline then Q4-8 weeks later then Q3 months
-LFTS: baseline and periodically

Question 18

Anti-TNF Biologic DMARDs: list the brand, ROA, dosing frequency for RA (dosing differs for other indications), administeration considerations

-Etanercept

-Adalimumab

-Infliximab

-Certolizumab pegrol

-Golimumab

Answer 18

Etanercept (Enbrel): SQ weekly

Adalimumab (Humira): SQ every other week
-If NOT taking MTX, can do SQ Qweek

Infliximab (Remicade): IV at weeks 0, 2, and 6 then Q8 weeks
-Requires a filter and is stable in NS ONLY
-Infusion rxns (hypotension, fever, chills, pruritus): can premedicate w/ APAP, antihistmine, and/or steroids)
-Delayed hypersensitivity rxn: 3-12 days after administration (fever, rash, myalgia, HA, sore throat)

Certolizumab pegol (Cimzia): SQ every other week

Golimumab (Simponi): SQ monthly
-Requires a filter when IV done (Simponi Aria)

Question 19

Anti-TNF DMARDs for RA:
-Drugs/Brands
-MOA
-Role in RA
-AVEs
-Warnings
-CIs
-BBW
-Monitoring

Answer 19

Drugs: etanercept (Enbrel), adalimumab (Humira), infliximab (Remicade), certolizumab pegol (Cimzia), golimumab (Simponi)

MOA: tumor necrosis factor (TNF) alpha inhibitors

Role in RA: biologic DMARD that can be added first line if initial presentation is severe w/ or w/o MTX, but MTX is usually first DOC

AVEs: infections, injection site rxns, positive anti-nuclear antibodies, HA, nausea, increased CPK (Humira)

Warnings:
-DO NOT USE OTHER BIOLOGIC DMARDS OR LIVE VACCINES
-DEMYLINATING DISEASE, HBV REACTIVATION, HF, HEPATOTOXICITY, LUPUS-LIKE SYNDROME, seizures, myleosupression, severe infections
-Each drug has a PREGNANCY REGISTRY (teratogenic)

CI: active systemic infections, doses >5mg/kg in moderate-severe HF (infliximab), sepsis (etanercept)

BBW:
-SERIOUS INFECTIONS (including TB, viral, fungal, opportunistic): screen for latent TB
-Lymphomas and other malignancies

Monitoring: TB, HBV, s/sx of infection, CBC, LFTs, s/sx of HF, malignancies, vitals (during infliximab infusion)

Question 20

Rituximab in RA:
-Brand
-MOA
-Role in RA
-ROA
-AVEs
-Warnings
-BBW
-Monitoring

Answer 20

Brand: Rituxan

MOA: depletes CD20 B cells believed to have a role in RA development and progression

Role in RA: biologic DMARD used WITH MTX

ROA: IV

AVEs: infusion-related rxns (PREMEDICATE required w/ steroid + APAP + antihistamine), URTIs, UTIs, N/V/D, peripheral edema, weight gain, HTN, HA, angioedema, fever, insomnia, pain

Warnings: infections; DO NOT GIVE W/ OTHER BIOLOGIC DMARDS OR LIVE VACCINES

BBW:
-Fatal/serious INFUSION RXNS (usually w/ first), serious skin rxns (SJS/TEN)
-Progressive multifocal leukoencephalopathy (PML) due to JC virus infection
-HBV reactivation (screen high risk for HBV and HCV prior)

Monitoring: ECG, vitals, infusion rxns, CBC, SCr, electrolytes, HBV prior to TX

Question 21

Anakinra:
-Brand
-MOA
-ROA
-Administration
-TX
-AVEs
-Warnings
-Monitoring

Answer 21

Brand: Kineret

MOA/TX: IL-1 receptor antagonist which mediates immunologic rxns in RA (NOT first line +/- MTX)

ROA: SQ

Adminsitration: do NOT shake or freeze; refrigerate and protecti from light

AVEs: URTIs, HA, N/D, abdominal pain, injection site rxns, antibody development, arthralgias

Warnings: MALIGNANCIES AND SERIOUS INFECTIONS (D/C if serious infection develops, screen for TB prior, and do NOT give w/ other biolgoics or live vaccines)

Monitoring: CBC, SCr, s/sx of infection

Question 22

Abatacept:
-Brand
-MOA/Role in RA
-ROA
-Administration
-AVEs
-Warnings
-Monitoring

Answer 22

Brand: Orencia

MOA: inihbits T cell activation by binding to CD80 and CD86 on antigen presenting cells (blocking interaction w/ CD28)
-Role in RA: biologic DMARD w/ or w/o MTX

ROA: IV or SQ

Administration: stable in NS only, requires filter and light protection during administration, do NOT shake

AVEs: HA, nausea, injection site rxns, infections, nasopharyngitis, antibody development

Warnings: MALIGNANCIES AND SERIOUS INFECTIONS (D/C if serious infection develops, screen for TB prior, and do NOT give w/ other biolgoics or live vaccines), COPD (may worsen symptoms)

Monitoring: s/sx of infection, hypersensitivity

Question 23

IL-6 receptor antagonists for RA:
-Drugs/Brands
-MOA/Role in RA
-ROA
-Adminsitration
-AVEs
-Warnings
-BBW
-Monitoring

Answer 23

Drugs: tocilizumab (Actemra), sarliumab (Kevzara)

MOA: inhibit IL-6 which mediates immunologic rxns in RA (biologic DMARD +/- MTX in RA)

ROA: SQ

Administration:
-dO NOT give SQ injections for IV which contains polysorbate 80
-do NOT start if ALT or AST >1.5x ULN, ANC <2000 cells/mm3, or PLTS <100,000 cells/mm3

AVES: URTIs, HA, HTN, injection site rxns, increased LDL and total cholesterol

Warnings: increased LFTs, neutropenia and thrombocytopenia, GI perforation, demyelinating diseases, hypersenstivity rxns, lipid abnormalities
-do NOT GIVE WITH OTHER BIOLOGIC DMARDS OR LIVE VACCINES

BBW: SERIOUS INFECTIONS (D/C if develops, screen for TB prior)

Question 24

Rasuvo and Otrexup: single-use auto-injector counseling

Answer 24

1. Administer SQ into abdomen (2 inches away from navel) or upper thigh only
   -Otrexup: remove the cap and safety clip first
   -Rasuvo: remove cap prior
   -do NOT inject in arms or other areas of body
2. Inject at 90 degree angle. Press firmly when you hear a click. Hold three seconds for Otrexup and five seconds for Rasuvo.
   -Rasuvo: pinch prior to injection
3. Otrexup: look at viewing window before and after dose given (when full dose given, viewiing window is half blocked with red flag; prior: yellow and full)

Needles are included with single dose SQ auto-injectors.

Question 25

Anti-TNF biologic DMARDs: Adalimumab, Etanercept, and Golimumab: Counseling

Answer 25

1. Store medication in fridge. Protect from light or heat. Do NOT freeze. Do NOT shake. 2. Take medication out of fridge, and let warm to room temperature for 15-30 minutes. Do not re-frigerate. Enbrel and Humira can be stored at room temperature for 14 days. 3. Check the the viewing window to make sure no precipitation, and check the expiration date. 4. Needles are included w/ single dose SQ auto-injector products. Adminster SQ injection as prescribed weekly for Enbrel, Q1-2 weeks for Humira, and Qmonth for golimumab. -Humira, Cimzia: abdomen or thigh -Enbrel, Simponi: abdomen, thigh, or upper arm -Autoinjectors (Enbrel, Humira, Simponi): inject at 90 degree angle and listen for first click (indicates injection starting) and second click (injection done) -Cimzia: inject pre-filled syringe at 45 degree angle 5. Rotate injection sites (stay at least one inch away from last injection site, do NOT inject into damaged skin)

Question 26

Systemic Lupus Erythematosus (SLE): -Define/complications -Risk factors/causes -Laboratory findings

Answer 26

SLE: systemic autoimmune disease that typically causes a distinct, flat "butterfly rash" on the face across the nose bridge and cheeks that is NOT usually painful/itchy that can flare and have remissions -Other symptoms: fatigue, depression, anorexia, weight loss, muscle pain, photosensitivity, joint pain/stiffness -Can cause ORGAN DAMAGE: kidney (lupus nephritis), hematologic, neurologic Risk factors: female (15-45 yo), African Americans and Asian descent, sunlight exposure, viral infections Labs: -Non-specific inflammatory: antinuclear antibodies (ANA) -More specific to SLE: anti-single stranded DNA (anti-ssDNA), anti-double stranded DNA (anti-dsDNA) -Antiphospholipid antibodies

Question 27

Drug-induced lupus erythematosus (DILE)

Answer 27

"My Pretty Pony Miss Muffin The Queen Is A terrific Horse" M: Methimzaole P: Propylthiouracil P: Propylthiouracil M: Methyldopa M: Minocycline T: Terbinafine Q: Quinidine I: Isonazid A: Anti-TNF agents PROCAINAMIDE, HYDRALAZINE (alone and in BiDil)

Question 28

Systemic Lupus Erythematosus (SLE): TX

Answer 28

-D/C any offending agents -Non-pharm: smoking cessation, sunscreen/sun protection -Pharmacological: can take up to 6 months to see maximal benefits (hydroxychloroquine, cyclophosphamide, azathioprine, mycophenolate mofetil, cyclosporine for chronic therapy) -Belimumab: TX of lupus and lupus nephritis -Voclosporin (related to cyclosporine): TX for lupus nephritis -Steroids while other agents starting to work (NSAIDs if mild)

Question 29

Belimumab: -Brand -MOA -ROA -TX -AVEs -Warnings

Answer 29

Brand: Benlysta MOA: IgG1-lambda monoclonal antibody that prevents the survival of B lymphocytes by inhbiting the binding of soluble human B lymphocyte stimulator protein (BLyS) to receptors on B lymphocytes to reduce autoimmune response ROA: SQ or IV TX: systemic lupus erythematosus (SILE) or lupus nephritis AVEs: N/D, fever, depression (including suicidal ideation), insomnia Warnings: INFECTIONS, PML, acute hypersensitivity rxns (consider premedication), malignancy, psychiatric events -DO NOT GIVE WITH OTHER BIOLOGIC DMARDS OR LIVE VACCINES -Cross the placent (caution in pregnancy) -African Americans may have lower response rate

Question 30

Voclosporin: -Brand -MOA -ROA -TX -AVEs -Warnings -BBW

Answer 30

Brand: Lupkynis MOA: calcineurin inhibitor that suppresses immune system by inhibiting T-lymphocyte activation ROA: PO TX: lupus nephritis AVEs: HTN, DIARRHEA, HA, RENAL IMPAIRMENT, anemia, cough, UTI, abdominal pain, dyspepsia, fatigue Warnings: NEPHROTOXICITY, HYPERTENSION, neurotoxicity, QT prolongation, red cell aplasia -DO NOT GIVE WITH LIVE VACCINES -Avoid in pregnancy BBW: INFECTIONS, MALIGNANCIES

Question 31

Multiple Sclerosis (MS): -Define -Who is at risk -S/Sx -TX

Answer 31

MS: chronic, PROGRESSIVE autoimmune disease that immune system attacks myelin sheat, the fatty substance that insulates nerve fibers of the brain and spinal cord axons that has time frames of flares and remissions or progressive decline Risk: women (20-40 yo) S/Sx: -Early: fatigue, tingling/numbness, blurred vision -As worsens: cognitive decline, muscle spasms, pain, bladde spasticitiy, depression, heat sensitivity, sexual dysfunction, difficulty walking/gait instability, visual disturbances -Labs: spinal/brain lesions on MRI, spinal fluid analysis, evoked potentials (test to measure electrical conduction of brain) TX: CANNOT regain lost neuronal function (prevention) -Non-pharm: functional rehabilitation, anti-inflammatory diet, PT/OT -Steroids for relapses (usually 3-7 days of IV methylprednisolone w/ or w/o PO steroid taper afterward) -Disease-modifying therapies (DMTs): glatiramer acetate (preferred in pregnancy), inteferon beta formulations (Betaseron, Avonex, Plegridy, Rebif, Extavia), oral options often for initial TX w/ relapsing remitting MS (fingolimod, teriflunomide, dimethyl fumarate), last line (monoclonal antibodies or chemotherapy drugs such as mitoxantrone)

Question 32

Glatiramer acetate: -Brand -MOA -ROA/Dosing frequency -Administration considerations -TX -AVEs -Warnings

Answer 32

Brand: Copaxone MOA/TX: immune modulator thought to induce and activate T-lymphocyte suppressor cells in relapsing forms of MS (PREFERED in pregnancy) ROA/Dosing: SQ QD or SQ 3x weekly (at least 48 hours apart) Administration: -Check solution for discoloration and discard if present -Can keep at room temp for one month or in fridge (prefererred; if cold, leave at room temp for 20 minutes before injecting) AVEs: INJECTION SITE RXNS, FLUSHING, DIAPHORESIS, DYSPNEA, infection, pain, weakness, anxiety, rash, nausea, nasopharyngitis, vasodilaton, antibody development Warnings: CHEST PAIN, immediate post-injection rxn, lipoatrophy

Question 33

Interferon beta products for MS: -Drugs/brands -MOA -ROA/dosing frequencies -Administration considerations

Answer 33

Drugs: interferon beta-1a (Avonex, Rebif), interferon beta-1b ((Betaseron, Extavia), peinterferon beta-1a (Plegridy) MOA: alters the expression and response to surface antigen, enhancing immune cell function ROA/Dosing: -Beta-1a: Avonex is IM weekly, Rebif SQ 3x per week -Beta-1b: SQ QOD -Peg 1a: SQ Q14 days Administration: -Refrigerate all except Betaseron and Extavia (can store room temp) -do NOT expel the small air bubble in pre-filled syringes due to loss of dose -do NOT shake Avonex, Betasesron, or Extavia

Question 34

Interferon beta products for MS: -AVEs -Warnings -Monitoring

Answer 34

AVEs: FLU-LIKE SYNDROME (lasting minutes to hours after administration, but decreased w/ continued TX, can use APAP/NSAIDs prior or start with lower doses and titrate weekly), visual disturbances, fatigue, depression, pain, UTIs, HA -Some formulations contain albumin (risk of Creutzfeldt-Jakon disease transmission: rare) Warnings: PSYCHIATRIC DISORDERS (depression/suicide), INJECTION SITE NECROSIS, myleosuppression, INCREASED LFTS, THYROID DYSFUNCTION (hypo or hyper), infections, anaphylaxis, worsening CVD, seizure risk Monitoring: LFTS, CBC (at 1, 3, and 6 months then periodically), thyroid Q6 months (w/ dysfunction or as clinically necessary)

Question 35

Sphingosoine 1-phosphate (S1P) receptor modulators: -Drugs/Brands -MOA -ROA -TX -Warnings -CIs

Answer 35

Drugs: fingolimod (Gilenya, Tascenso), oxanimod (Zeposia), ponesimod (Ponvory), siponimod (Mayzent) MOA: blocks lymphocytes from exiting lymph nodes, reducing lymphocytes in the periphery which may limit migration into CNS ROA: PO TX: MS Warnings: -BRADYCARDIA/arrhythmias: when starting, monitor for at least 6 hours after first dose (ECG required at baselin and end of initial observation period or if TX interrupted), caution w/ other drugs that slow HR -Increased infection risk: monitor CVC, screen for VZV antibodies and vaccinate if negative before starting -Others: malignancy, MACULAR EDEMA (monitor w/ eye exams), HEPATOTOXICITY (monitor LFTS), increased BP, decreased lung function, fetal risk (use contraception during and some time after stopping) -MS CAN BE MUCH WORSE WHEN TX STOPPED CIs: -In the last 6 months: MI, unstable angina, stroke/TIA, HF Class III/IV or decompensated -Some arrhythmias -Ozanimod: severe untreated sleep apnea, do NOT use w/ MAOI) -Siponimod: CYP2C9*3/*3 genotype: TESTING REQUIRED BEFORE USE

Question 36

Fumurates or Nuclear Factor (erythroid-derived 2)-like-2 (Nrf2) Activators: -Drugs/brands -MOA -ROA -TX -Considerations

Answer 36

Drugs: dimethyl fumarate (Tecfidera), diroximel fumarate (Vumerity), monomethyl fumarate (Bafiertam) MOA: anti-inflammatory and cytoprotective -Monomethyl fumurate: active metabolite of diroximel fumarate and dimethyl fumarate ROA: PO TX: MS Considerations: -Hepatoxocitiy (monitor LFTs), neutropenia (reversible, but monitor CVC), PML -Can cause flushing (prevent w/ ASA 30 minutes prior to dose and administer CF), GI side effects (less w/ Vumerity) -DO NOT CRUSH, CHEW, OR SPRINKLE CAPSULE CONTENTS ON FOOD

Question 37

Teriflunomide: -Brand -MOA -ROA -TX -Considerations

Answer 37

Brand: Aubagio MOA: pyrmidine synthesis inhibitor; anti-inflammatory; may reduce number of activated lymphocytes in CNS -Active metabolite of leflunomide ROA: PO TX: MS Considerations: -Severe hepatotoxicity and teratogenicity (CI IN PREGNANCY and w/ severe hepatic impairment) -Can use accelerated elimination to remove drug (cholestyramine 8 grams TID x11D or activated charcoal suspension 50g PO BID X11D)

Question 38

CD20-directed monoclonal antibodies for MS: -Drugs/Brands -ROA -Administration considerations -Warnings -CI

Answer 38

Drugs: ofatumumab (Kesimpta, Arzerra for chronic lymphocytic leukemia), ublituximab-xiiy (Briumvi), ocrelizumab (Ocrevus) ROA: -Briumvi, Ocrevus: IV -Kesimpta: SQ Administration: -Briumvi, Ocrevus: premedicate w/ steroid, antihistamine, and/or APAP -Ocrevus: requires 0.22 micron filter in-line filter Warnings: -Increased risk of serious and potentially fatal infections (including PML), avoid live vaccines during TX, fetal risk, infusion rxns, reduction in immunoglobulin levels -Ocrevus: immune-mediated colitis CIs: active HepB (screen before starting)

Question 39

Alemtuzumab: -Brand -MOA -ROA -Administration considerations -TX -CI -BBW

Answer 39

Brand: Lemtrada, Compath for CLL MOA: CD52-directed cytolytic monoclonal antibody ROA: IV Administration: premediacate w/ steroid, antihistamine, and/or APAP; complete all vaccines 6 weeks before TX TX: MS when inadequate response to 2 or more drugs CI: HIV (causes prolongaed decrease in CD4 count) BBW: REMS PROGRAM (serious autoimmune conditions, infusion rxns, malignancies, stroke)

Question 40

Natalizumab: -Brand -MOA -ROA -TX -BBW

Answer 40

Brand: Tysabri MOA: MAB that binds to alpha-4-subunit of integrin molecules ROA: IV TX: MS, Crohn's disease BBW: PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY (PML) --> available only through REMS program

Question 41

Cladribine: -Brand -MOA -ROA -TX -CI -BBW

Answer 41

Brand: Mavenclad MOA: anti-neoplastic ROA: PO TX: MS CI: active malignancy, HIV, or chronic infections BBW: malignancies, teratogenicity (contraception must be used during TX and for 6 months after last dose)

Question 42

Dalfampridine: -Brand -MOA -ROA -TX -CI

Answer 42

Brand: Ampyra MOA: potassium channel blocker that may increase nerve signal conduction ROA: PO TX: MS --> NOT a disease modifying agent, but only increases walking speed (takes up to 6 weeks to show efficacy and most pts do NOT respond) CI: hx of seizures

Question 43

Raynaud's Phenomenon: -Define -Prevention/TX -Drugs that can worsen/cause

Answer 43

Raynaud's Phenomenon: triggered from exposure to cold/stress causing vasospasms in extremeties (typically fingers/toes) in which the skin can turn white then blue followed by painful swelling -Warming of extremeties can be very painful -Can result in amputation Prevention/TX: vasodilation -Nifedipine is commonly used for prevention, but other DHP-CCBs can be used -Additonal for vasodilation: iloprost, topical nitroglycerin, and PDE-5 inhibitors Drugs that worsen/cause: beta-blockers, bleomycin, cisplatin, sympathomimetics from vasoconstriction (amphetamines, pseudophedrine, illict drugs such as cocaine and methamphetamine)

Question 44

Celiac Disease: -Define -S/Sx -What is dermatitis herpetiformis? -How to determine if drug is gluten-free

Answer 44

Celiac disease: immune response to eating gluten (found in wheat, barley, and rye) where antibodies attack and damage lining of small intestine -Complications: vitamin and nutritional deficiencies, small bowel ulcers, amenorrhea, infertility, cancer S/Sx: diarrhea, abdominal pain, bloating, weight loss -Constipation can occur, more common in children Dermatitis herpetiformis: extremely itchy, blistery skin rash w/ chronic erruptions that can occur in celiac disease w/ or w/o intestinal symptoms Determine gluten-free drug: active drugs are gluten-free, but excipients may NOT -Look at package inserts which may contain excipient info -"Starch" could be from corn, potato, tapioca, or wheat --> call manufacturer to determine if its from wheat -Manufacturers can report they do NOT use gluten in their manufacturing process, but they cannot state whether excipients purchased from outside vendors are gluten-free

Question 45

Myasthenia Gravis (MG): -Define -S/Sx -Treatment

Answer 45

MS: autoimmune condition that attacks connections between nerves and muscles, often leading to weakness in muscels that control the eyes, face, neck, and limbs -Most commonly targets acetylcholine (ACh) S/Sx: eye/vision changes (dipolopia, drooping eyelid), difficulty chewing/swallowing, jaw/neck weakness TX: pyridostigmine (Mestinon), cholinesterase inhibitor -Pts that remain symptomatic: immunotherapy (steroids, azathioprine, cyclosporine, methotrexate) -Thymectomy (removal of thymus gland), plasmapheresis, or IV immunoglobulin (IVIG) -Eculizumab (Soliris): injectable complement inhibitor for MG in adults who are ACh-receptor antibody (+) which can decrease the risk of meningococcal infections and has REMS progam to stay up to date on meningococcal vaccine

Question 46

-Drugs that can worsen Myasthenia Gravis

Answer 46

-Select ABXs: aminoglycosides, quinolones, macrolides -Magnesium salts -Select antiarrhythmics -Beta-blockers and CCBs -Select antipsychotics -Muscle relaxants -Botulinum toxin

Question 47

Sjogren's Syndrome: -Define -TX

Answer 47

Sjogren's Syndrome: autoimmune disease characterized by dry eyes and mouth which can be primary or secondary due to other autoimmune diseases (ex. RA, SLE) -Complications: dental caries, corneal ulceration, chronic oral infections TX: NO cure --> symptom reduction TX of Dry Eyes: -Primary TX: OTC artificial teardrops (Systane, Refresh, Clear Eyes, Liquifilm) --> may need to try a few before finding one that provides the most comfort (preservative benzalkonium chloride may be irritating) -Ointment is also preferrable if eyes dry out with artifical teardrops -If OTC eyedrops don't help and other measures do NOT help (such as ductal occlusion) cyclosporine eye drops (Restasis) --> EXPENSIVE -Lifitegrast (Xiidra): first in drug class approved for TX as well TX of Dry Mouth: -Salivary stimulation (sugar-free chewing gum w/ xylitol or lozenges (Aquoral, Mouth Kote, Biotene, Oral Balance) -Daily rinses w/ anti-microbial mouthwash -If OTC does NOT help, oral muscarinic agents (pilocarpine - Salagen, cevimeline - Evoxac): CI in uncontrolled asthma and narrow-angle glaucoma

Question 48

Cyclosporine eye drops: -Brand -AVEs -Counseling

Answer 48

Bramd: Restasis AVE: ocular (BURNING, stinging, redness, pain, blurred vision, foreign body sensation, discharge, itching eye) Counseling: -1 drop in each eye Q12H -Reduce usage of other OTC eye drops and monitor symptoms -Prior to use, invert vial several times to make the emulsion uniform -AVOID INFECTION -May take 3-6 months to notice increase in tear production

Question 49

Psoriasis: -Define -TX

Answer 49

Psoriasis: chronic, autoimmune disease that appears on the skin -Plaque psoriasis: raised, red patches covered w/ silvery-white buildup of dead skin cells TX: -UVB phototherapy: controlled doses from artifical source that can improve mild/moderate psoriasis symptoms -Photochemotherapy: ultraviolet A light w/ psoralen (mild light sensitizer) -Laser light therapy -Topical medications: steroids, vitamin D analog (calcipotriene), anthralin, retinoids, salicylic acid (primarily in shampoo), coal tar, tapinarof --> if these fail, topical calcineurin inhibitors (Protopic, Elidel) also preferred when applying to face -Systemic medications for mor severe symptoms: immunosuppressants (methotrexate, cyclosporine, hydroxyurea), immunomodulators (etanercept, infliximab, adalimumab, certolizumab), PDE-4 inhibitor (apremilast), interleukin receptor antagonists

Question 50

Topical Psoriasis TX: General considerations for -Steroids -Coal Tar products -Anthralin

Answer 50

Steroids: use high-potency for short term as monotherapy or in combo with other products Coal tar products (DHS Tar, Ionil-T, Psoriasin, Pentrax Gold): -Products can be MESSY and stain clothing/bedding -Reasonable cost, many types of products (ex. bar soaps, oils, shampoo, foam, cream) -Used for dandruff and dermatitis -Tarsum: coal tar + salicylic acid -Can cause skin irritation and photosensitivity Anthralin (Zithranol): keratolytic containing salicyclic acid with irritant potential, increase contact time as tolerated up to 30 minutes

Question 51

Topical Psoriasis TX: General considerations for -Calcipotriene -Tapinarof

Answer 51

Calcipotriene (Dovonex, Sorilux): vitamin D analog that should be avoided in hypercalcemia or vitamin D toxicity -DO NOT apply to face, axillae, or groin -Can be combined with betamethasone (ointment: Taclonex, foam: Enstilar) Tapinarof (VTAMA): hydrocarbon receptor antagonist to suppress cytokines -Side effects of folliculitis, nasopharyngitis, contact dermatitis, and pruritis -Wash hands after use

Question 52

Acitretin: -MOA -ROA -TX -BBW

Answer 52

MOA: retinoid ROA: PO TX: psoriasis ONLY IN SEVERE cases where pt unresponsive to numerous other therapies due to CIs and side effects BBW: hepatotoxicity, pregnancy (female must sign informed consent before dispensing)

Question 53

Apremilast: -Brand -MOA -ROA -TX -AVEs -Warnings

Answer 53

Brand: Otezia MOA: phosphodiesterase-4 inhibitor ROA: PO TX: psoriasis AVEs: DIARRHEA, N/V, HA Warnings: WEIGHT LOSS, depression/suicidal ideation

Question 54

Interleukin receptor antagonists for psoriasis: -Drugs/brands -MOA -ROA -AVEs -BBW

Answer 54

Drugs: brodalumab (Siliq), bimekizumab (Bimzelx), guselkumab (Tremfya), ixekizumab (Taltz), risankizumab (Skyrizi), secukinumab (Cosentyx), tildrakizumab (Ilumya), ustekinumab (Stelara) MOA: MAB that binds and interferes w/ proinflammatory cytokines ROA: SQ AVEs: DIARRHEA, URTIs, SERIOUS INFECTIONS (including TB: screen for latent) -Avoid live vaccines -May exacerbate Crohn's disease -Latex hypersensitivity BBW (brodalumab): suicidial ideation and behavior (REMS program required)

Question 55

Deucravacitinib: -Brand -MOA -ROA -TX -AVEs -Warnings

Answer 55

Brand: Sotyktu MOA: selective tyrosine kinase 2 inhibitor ROA: PO TX: moderate/severe plaque psoriasis AVEs: URTIs, elevated CPK, mouth ulcers, acne Warnings: -Increases risk for infections (screen for latent TB) -Avoid live vaccines -Malignancy (including lymphomas) -Rhabdomyolysis -Laboratory abnormalities (elevated TGs and liver enyzmes) -NOT RECOMMENDED in combo w/ other potent immunosuppressors

Question 56

Thyroid Gland: -Role of thyroid gland -Types of thyroid hormone and its signaling pathway

Answer 56

Roles: 1. Create thyroid hormone - only organ that can absorb iodine for production 2. Metabolism - involved in numerous chemical processes: cardiac and nervous system function, body temperature, muscle strength, skin dryness, menstrual cycles, weight, and cholesterol levels Thyroid hormones: -*Triiodothyronine (T3): more potent, shorter T1/2 -Thyroxine (T4): free T4 (FT4) is unbound, active form measured* -Thyroid stimulating hormone (TSH): "thyrotropine", secreted by pituitary gland to stimulate T3 and T4 production Thyroid Signaling: negative feedback loop - less TSH made when thyroid hormone made

Question 57

Hypothyroidism: -Labs and S/Sx -Causes -What is myxedema coma and initial TX -TX -Monitoring

Answer 57

Labs: *low T4, elevated TSH* S/Sx: cold intolerance/sensitivity, dry skin, fatigue, muscle cramps, voice changes, constipation, weight gain, goiter (possibly from low iodine intake), myalgias, weakness, depression, bradycardia, coarse hair or loss of hair, menorrhagia (heavier periods than normal), memory and mental impairment Causes: *most common cause is Hashimoto's disease (autoimmune condition)* Myexedema coma: uncommon, but potentially fatal complication characterized by poor circulation, hypothermia, and hypometabolism --> *IV levothyroxine given* TX: *levothyroxine (DOC) using a consistent manufacturer* -Alternatives: liothyronine (T3), desiccated thyroid (T3 and T4) -Iodine supplementation NOT required in US since most table salt contains iodine Monitoring: -*Primary test is TSH Q4-8 weeks* until normal then 4-6 months later then annually -Important to monitor as pt ages since thyroid requirement can lower (too high thyroid doses can cause atrial fibrillation and fractures in elderly) -In central hypothyroidism (pituitary does NOT produce TSH as well): measure FT4

Question 58

*Drugs that cause hypothyroidism*

Answer 58

interferons, tyrosine kinase inhibitors (ex. sunitinib), amiodarone, lithium, carbamazepine

Question 59

*Levothyroxine:* -Dosing -Administration considerations -Tablet colors and their strengths -IV to PO ratio -Tell your prescriber if __________ since likely a dose increase will be needed

Answer 59

Levothyroxine dosing: -Full replacement dose: 1.6 mcg/kg/day (IBW) -If known CAD, start with 12.5-25mcg QD Levothyroxine administration: -Should be taken with water at same time each day for most consistent absorption -Take at least 60 minutes away before breakfast or at bedtime at least three hours after last meal -Check therapeutic equivalence in Orange book -Oral solution: can be undiluted or diluted in water only (store in original container) Levothyroxine tablet colors: "Orangutans Will Vomit On You Right Before They Become Larger Proud Giants" -25mcg (orange), 50mcg (white - no dye), 75mcg (violet), 100mcg (yellow), 112mcg (rose), 125mcg (brown), 137mcg (turquoise), 150mcg (blue), 175mcg (lilac), 200mcg (pink), 300mcg (green) IV:PO rato of 0:75:1 Pregnancy --> likely need increased thyroid hormone

Question 60

Thyroid Supplementation Medications: -Drugs/Brands -ROA -AVEs -Warnings -CIs -BBWs -Considerations in T3 and dessicated thyroid

Answer 60

Drugs: *levothyroxine (Synthroid, Levoxyl, Unithroid), liothyronine (Cytomel*, Triostat), *dessicated thyroid (Armour Thyroid)*, liotrix (T3 and T4 in 1:4 ratio - Thyrolar) ROA: PO AVEs: hyperthyroid symptoms can occur when dose too high: increased HR, palpitations, sweating, weight loss, arrhythmias, irritability Warnings: *decreased dose in CVD* (chronic hypothyroidism predisposes to coronary artery disease), decreased BMD (osteoporosis risk) CIs: uncorrected adrenal insufficiency BBWs: ineffective and potentially toxic in obesity or weight reduction (especially in euthyroid pts); high doses can be life-threatening particularliy when used with some anorectic drugs (ex. sympathomimetic amines) Liothyronine: *shorter T1/2 causes fluctuations in T3 levels( Dessicated thyroid: natural porcine-derived thyroid containing both T3 and T4 - less predictable stability and potency

Question 61

Drug interactions with thyroid supplementation medications

Answer 61

Drugs that decrease levothyroxine absorption: -*Antacids and polyvalen cations (iron, Ca, Al, Mg): multivitamins, cholestyramine, orlistat, sevelamer, sucralfate* --> seperate by 4 hours -Sodium polystyrene sulfonate and patiromer --> seperate doses by 3 hours -Lanthanum --> seperate doses by 2 hours Others: -Estrogen, SSRIs, and hepatic inducers decrease thyroid levels -Beta-blockers, amiodarone, propylthiouracil, and systemic steroids can reduce efficacy of levothyroxine by preventing conversion of T4 to T3 -Thyroid hormone is highly protein bound (>99%) --> can cause protein-binding site displacement (ex. phenytoin) Thyroid replecement treatment can increase warfarin levels and decrease theophylline levels

Question 62

Hyperthyroidism: -Labs -S/Sx -Causes -General TX

Answer 62

Labs: *high FT4, low TSH* S/Sx: heat intolerance or increased sweating, weight loss, agitation/nervousness/irritability/anxiety, palpitations and tachycardia, fatigue and muscle weakness, frequent bowel movements or diarrhea, insomnia, tremor, thinning hair, goiter, exophthalmos (pertrusion of eyes), diplopia, light or absent menstrual periods Causes: most common is *Grave's disease* (autoimmune condition - antibodies mimic TSH to stimulate to thyroid to produce more T4) TX: medications, surgery, or radioactive iodine (historically preferred in Grave's disease) -*Symptom control: propranolol to reduce palpitations, tremors, and tachycardia -Temporary measure (about 1-3 months) until surgery complete: propylthiouracil (PTU), methimazole --> once symptoms controlled, reduce dose to prevent hypothroidism*

Question 63

*Drugs that cause hyperthyroidism*

Answer 63

interferons, amiodarone, idoine (excess from diet or exposure to radiographic contrast media)

Question 64

Thionamides: -Drugs/Brands -MOA -ROA -Administration considerations -AVEs -Warnings -BBWs -Monitoring

Answer 64

Drugs: *propylthiouracil (PTU), methimazole* (Tapazole) MOA: *inhibits synthesis of thyroid hormones via inhibition of oxidation of iodine in thyroid gland -PTU: also inhibits peripheral conversion of T4 to T3* ROA: PO Administration: -Take with food to reduce GI upset -*Methimzaole is DOC due to lower risk of liver damage (except: PUS in thyroid storm and when methimazole not tolerated) -Pregnancy: PTU preferred in 1st trimester; methimzaole in 2nd and 3rd trimesters* AVEs: *GI upset*, HA, rash (exfoilative dermatitis, pruritus), fever, constipation, loss of taste/taste preversion, lymphadenopathy, bleeding Warnings: *hepatotoxicity*, bone marrow suppression (rare, includes agranulocytosis), *drug-induced lupus erythematosus (DILE)*, vasculitis BBWs: *severe liver injury and acute liver failure, in preganncy PTU preferred in 1st trimester due to incresed risk of fetal abnormalities from methimazole* Monitoring: FT4 and T3 Q4-6 weeks until euthyroid, TSH, CBC, LFTs, PT, s/sx of liver toxicity (yellow skin/eyes, dark urine, nausea, weakness) and infection

Question 65

Iodides: -Drugs/Brands -MOA -ROA -TX -Administration considerations -AVEs -CIs -Monitoring

Answer 65

Drugs: potassium iodide and iodine solution (Lugol's solution), saturated solution of potassium iodide (SSKI, ThyroSafe) MOA: *temporarily inhibit secretion of thyroid hormones - T3 and T4 levels will be reduced for several weeks, but effects won't last* ROA: PO TX: *hyperthyroidism*, expectorant (SSKI) -*Potassium iodide (KI) blocks accumulation of radioactive iodine, preventing thyroid cancer - to take after radiation exposure per advice of public health or emergency management personnel only* Administration: dilute in a glassful of water, juice, or milk - take w/ food or milk to decrease GI upset AVEs: rash, metallic taste, sore throat/gums, GI upset, uticaria, hypo/hyperthyroidism with prolonged use CIs: hypersensitivity to iodine or iodide, dermatitis hyperpetiformis, hypocomplentemic vasculitis, nodular thyroid condition with heart disease Monitoring: thyroid function tests, s/sx of hyperthyroidism

Question 66

Thyroid Storm: -Define -S/Sx -TX

Answer 66

Thyroid storm: *life-threatening medical emergency characterized by decompensated hyperthyroidism* that can be precipitated by infection, trauma, surgery, radioactive iodine treatment, or non-adherence to anti-thyroid medications S/Sx: fever >103F, tachycardia, tachypnea, dehydration, profuse sweating, agitation, delirium, psychosis, coma TX: *PTU + inorganic iodide therapy (SSKI, Lugol's Solution) + propranolol + systemic steroid (ex. dexamethasone) + aggressive cooling* w/ APAP and cooling blankets + supportive treatments (ex. antiarrhythmics, insulin, fluids, electrolytes)

Question 67

Pregnancy recommendations in hypothyroidism and hyperthyroidism

Answer 67

Hypothyroidism: *levothyroxine --> likely need 30-50% increase in dose* -Aggressive control recommended to avoid loss of pregnancy, low birth weight, preamutre birth, and lower IQ Hyperthyroidism: ideally, pregnancy should be prevented until euthyroid -*First trimester: PTU -Second or third trimester: methimazole*

Question 68

*Diabetes: Background Pathophysiology* 1. Insulin is produced by _______ cells in the _________. 2. Insulin removes glucose from the blood into _________________. 3. _________ is the counter to insulin that moves glucose back into the blood from __________. If glycogen is depleted, this will signal fat cells to make __________. 4. What is the imbalances seen in diabetes?

Answer 68

1. Beta cells; pancreas 2. Muscle cells, Liver cells (stored as glycogen), and Fat cells 3. Glucagon; LIver cells (stored as glycogen); Ketones 4. Decreased insulin secretion from pancreas, decreased insulin sensitivity, or both

Question 69

*Type 1 Diabetes (T1DM), Type 2 Diabetes (T2DM), Prediabetes, and Diabetes in Pregnancy:* -Define -Basics of treatment

Answer 69

T1DM: autoimmune destruction of beta cells in pancreas and once all cells destroyed, insulin cannot be produced -Without insulin, body metabolizes fat into ketons which can lead to diabetic ketoacidosis (DKA)\ -Mostly diagnosed in children, but can develop at any age -C-peptide (substance released when insulin produced) will be low or absent and positive for islet autoantibodies (autoimmune marker) -TX: insulin T2DM: insulin resistance and insulin deficiency -Hyperglycemia can develop gradually -Strong associations with obesity, physical inactivity, and family hx Prediabetes: increased risk of diabetes -TX: lifestyle recomemendations, metformin when BMI >/=35, age 25-59 yo, and women w/ hx of gestatoin diabetes Diabetes in Pregnancy: -Types: diabetes prior to becoming pregnant, gestation diabetes (occurs usually 2nd or 3rd trimester) -More stringent BG goals since hyperglycemia can cause infants that are larger than normal (macrosomia) and increased risk for obesity and diabetes -Tested via oral glucose tolerance test (OGTT) -TX: lifestyle management, insulin preferred, sometimes metformin or glyburide

Question 70

Diabetes: -Risk Factors -Symptoms -Who should be screened

Answer 70

Risk Factors: -*Age, high-risk race or ethnicity* (African-Americans, Asian-Americans, Latino/Hispanic-Aermicans, Native Americans, or Pacific Islanders) -*Physical inactivity, overweight (BMI >/=25, >/=23 in Asian-Americans) -Hx of gestational DM, A1c >/=5.7% (prediabetes), first-degree relative with DM* -HDL <35 and/or TG >250, HTN, CVD hx, smoking hx -Conditions that cause insulin resistance (ex. acanthosis nigricans, polycystic ovary syndrome *Symptoms:* -Classic symptoms: polyuria, polyphagia, poldipsia -Others: fatigue, blurry vision, weight loss -T1DM: often initial presentation is DKA from total insulin deficiency Screening: -*No risk factors: all 35 yo AND and older -Asymptomatic who are overweight or obese with one additional risk factor* -Consider for pts who are taking medications that increase BG -Anyone with symptoms

Question 71

*Diabetes:* -Diagnosis -TX goals -Testing frequency -How to interpret A1c with eAG

Answer 71

Diagnosis: three different tests, typically two tests needed 1. Hemoglobin A1c: average BG in past three months (>/=6.5%: DM, 5.7-6.4%: prediabetes) 2. Plasma glucose: BG at any moment; fasting BG (FBG): BG after fasting for >8 hours (random BG >/=200: DM, FBG >/=126: DM, FB 100-125: prediabetes) 3. Oral glucose tolerance test (OGTT): how well glucose after ingestion measured at least 2 hours after drinking (OGTT >/=200: DM, 140-199: prediabetes) TX goals: -Not pregnant: A1c <7%, preprandial BG 80-130, 2-hr PPG <180 -Pregnant: A1c <7%, preprandial BG <95, 1-hr PPG <140, 2-hr PPG <120 Testing frequency: -NOT meeting goals: Q3 months -At goal: Q6 months Interpreting labs: -eAG = estimated average glucose -A1c of 6% is equivalent to eAG of 126mg/dL, each additional 1% increases eAG by 28 -Ex. A1c of 7% = 126 + 28 = 154 eAG

Question 72

*Diabetes: Lifestyle modifications and Natural Products*

Answer 72

1. Weight loss - goal of >/=5% of bodr weight if overweight or obese 2. Physical activity - at least 150 minutes of moderate-intensity aerobic activity per week spread over at least 3 days; reduce sedentary habits by standing Q30 minutes 3. Smoking cessation 4. Individualized medical nutritional therapy - consume natural forms of carbohydrates and sugars, limit alcohol consumption, use carbohydrate-containg in T1DM (15g of carbohydrates = 1 slice of bread, 1/3 cup of cooked rice/pasta, and one small piece of fruit 5. Natural products - *limited evidence: cinnamon, alpha lipoic acid, chromium*, magnesium, ginseng 6. Foot care management - examine feet daily, moisturize top/bottom of feet (but NOT between toes), socks and shoes, elevate feet when sitting and trim toenails with nail file (avoid sharp edges from clipper)

Question 73

Diabetes: Comprehensive Care Recommendations for: -Antiplatelet therapy -Diabetic retinopathy

Answer 73

Antiplatelet therapy: -*ASA 75-162mg/day (usually 81mg QD) for ASCVD secondary prevention (if allergy: clopidogrel) -NOT recommended for primary prevention in most -risk of bleeding about equal to benefit* -CAD/PAD: ASA + low-dose rivaroxaban can be added -*Used in pregnancy to decrease risk of preclampsia* Diabetic retinopathy: *eye exam with dilation at diagnosis --> if retinopathy, repeat annually; if NOT repeat every 1-2 years*

Question 74

Diabetes: Comprehensive Care Recommendations for: -Vaccinations -Neuropathy -Bone health

Answer 74

Vaccinations: *recommended in additional to all age-appropriate vaccines --> HBV series, influenza, penumococcal, COVID-19, RSV per guidelines* Neuropathy: *10-g monofilament test with 1 other test (ex. pinprick, temperature, vibration) to assess sensation annually -TX: gabapentin, pregabalin, SNRIs (duloxetine), TCAs, or sodium channel blockers* Bone Health: *monitor BMD* via DEXA Q2-3 years for adults age >65 (or earlier w/ risk factors) -Consider TX for T score

Question 75

*Diabetes Comprehensive Care Recommendations for*: -Blood pressure -Cholesterol -Kidney disease

Answer 75

Blood pressure: goal of <130/80mmHg -TX: ACEI or ARB in aluminuria or CAD; otherwise: thiazide, DHP CCB, ACEI, or ARB Cholesterol: -High intensity statin for: comorbid ASCVD (LDL goal <55mg/dL), age 40-75 yo w/ 1 or more ASCVD risk factors (LDL goal <70mg/dL) -Moderate intensity statin for: age 45-70 w/ no ASCVD, age 20-39 yo w/ ASCVD risk factors -Add ezetimibe or PSCK9i if LDL remains above goal -Add icosapent ethyl (Vascepa) if LDL in control, but TG 135-499 in ASCVD or risk factors -Monitoring: annually (after initiation: 4-12 weeks) Kidney disease: eGFR <60mL/min and/or albuminuria (UA >/=30mg/24 hr or UACR >/=30mg/g) -Monitor annually -TX: ACEI or ARB, SGLT2 (if eGFR >20), or finerenone (once on max tolerated ARB or ACEI)

Question 76

*T2DM Treatment:* -Algorithim for cardiorenal protection -Drugs with cardiorenal benefit -Drugs best for BG lowering -Drugs best for weight loss

Answer 76

Goal of cardiorenal protection: -ASCVD or high risk: GLP-1a or SGLT2i with benefit --> GLP-1a or SGLT2i if NOT started, TZD --> additional glycemic control or cardiorenal risk reduction f needed -HF: SGLT2i with benefit --> addional glycemic control or cardiorenal risk reduction if needed -CKD: SGLT2i with benefit (CrCl >20mL/min) or GLP1a with CVD benefit --> GLP-1a if NOT started --> additional glycemic control or cardiorenal risk reduction f needed Drugs w/ cardiorenal benefits: -GLP-1a: dulagultide, liraglutide, SC semaglutide -SGLT2i: canagliflozin, dapagliflozin, empagliflozin, etrugliflozin BG lowering drugs: -Very high or high: GLP-1a, tirzepatide, insulin, metformin, SGLT2i, SU, TZD -Intermediate: DPP-4i Weight loss drugs: -Very high or high: tirzepatide, semaglutide, dulaglutide, liraglutide -Intermediate: GLP-1a NOT listed above, SGLT2i -Netural: DPP-4i, metformin

Question 77

*T2DM Treatment:* -When can two drugs be added at baseline? -When can insulin be initiated? -What drug should be considered to add before insulin? -What are drug combinations to avoid?

Answer 77

Two drugs at baseline: when A1c 8.5-10% Insulin initiation: -Severe hyperglycemia (A1c > 10% or BG >/=300mg/dL) -Evidence of catabolism: weight loss or symptoms of hyperglycemia Before insulin: GLP-1a Drug combinations to avoid: -DPP-4i + GLP-1a --> similar MOA -SU + insulin --> hypoglycemia

Question 78

Glucagon-like Peptide 1 (GLP-1) and Glucose-dependent Insulinotropic Polypeptide (GIP) Agonists: -Drugs/Brands -MOA -ROA -Dosing frequency -Renal cutoffs -Administration considerations

Answer 78

Drugs: *liraglutide (Victoza, Saxenda - for weight loss), dulaglutide (Trulicity), semaglutide (Ozempic,* Rybelsus, *Wegovy* -for weight loss), exanatide (Byetta, Bydureon BCise), tirzepatide (Mounjaro, *Zepbound - weight loss*) *MOA:* -GLP-1a: analogs of incretin hrmone GLP-1 which increases glucose-dependent insulin secertion, decreases glucagon secertion, slows gastric emptying, improves satiety, and can result in weight loss -Tirzepatide ("Twincretin"): dual GLP and GIP agonist (GIP similar to GLP effects) ROA: *SC, PO (Rybelsus)* *Dosing Frequency:* -QD: liraglutide, Rybelsus -BID: exanatide (Byetta) -Weekly: dulaglutide, semaglutide, exenatide ER, tirzepatide *Renal Cutoffs:* -Exanatide: NOT recommended in CrCl <30 -Exantatide ER: NOT recommended in eGFR <45 Administration: -*Byetta: give dose within 60 minutes before meals* -Reybelsus: take dose >/=30 minutes before first drink/food/medications of day with 4oz plain water -*Pen needles NOT provided w/ Byetta or Victoza (provided w/ all others that are weekly injections) -Glucose lowering may NOT be seen with initial doses (titrated to reduce GI effects)*

Question 79

Glucagon-like Peptide 1 (GLP-1) and Glucose-dependent Insulinotropic Polypeptide (GIP) Agonists: -Effects on glucose -AVEs -Warnings -BBW -DDIs

Answer 79

Effects: A1c lowering of 0.5-1.5%, decrease postprandial BG, low hypoglycemia risk (unless used w/ insulin) AVEs: *weight loss, N*/V/D (*reduced w/ dose titration*), hypoglycemia, injection site rxns -Tirzepatide: increased HR Warnings: -*Pancreatitis* (can be fatal, risk factors: gallstones, alcoholism, increased TGs), AKI, gallbladder disease -*NOT recommended in severe GI disease including gastroparesis (drug-induced ileus reported) -Bydureon BCise: serious injection site rxns (abscess, cellulitis, necrosis) w/ or w/o SC nodules* -Ozempic, Trulicity, Mounjaro: increased complications w/ daibetic retinopathy BBW *(ALL except Byetta): risk of thyroid C-cell carcinomas* --> do NOT use if personal or family hx of medullary thyroid carcinoma (MTC) or w/ Multiple Endocrine Neoplasia syndrome type 2 (MEN 2) DDIs: -Slow gastric emptying and can reduce absorption of PO drugs --> caution w/ NTIs or drugs that require threshold concentrations for efficacy (ex. ABXs, OCs) -Mounjaro, Zepbound: OCs advised to switch to non-PO or barrier method for 4 weeks after initiation and for 4 weeks after each dose escalation -Exanatide: can increase INR on warfarin (monitor INR) -*Do NOT use w/ DPP-4is (overlapping mechanisms)*

Question 80

Sodium-Glucose Cotransporter 2 Inhibitors (SGLT2is): -Drugs/Brands -MOA -ROA -Administration considerations -Effects on glucose

Answer 80

Drugs: *canagliflozin (Invokana), dapagliflozin (Farxiga), empagliflozin (Jardiance)*, bexagliflozin (Brenzavvy), ertugliflozin (Steglatro) MOA: *inhibits SGLT2 protein expressed in proximal renal tubules that filter glucose, resulting in reduced glucose reabsorption and increased urinary excretion* ROA: PO Administration: -Use NOT recomended in dialysis -Recommended if eGFR >/=20mL/min Effects: decrease A1c by 0.7-1%, low hypoglycemia risk (unless used w/ insulin)

Question 81

Sodium-Glucose Cotransporter 2 Inhibitors (SGLT2is): --AVEs -Warnings -DDIs

Answer 81

AVEs: *increased urination, increased thirst*, hypoglycemia, increased Mg/PO4 -Canagliflozin: hyperkalemia risk when used w/ other drugs that increase K Warnings: -*Ketoacidosis* (can occur w/ BG <250 - "euglycemic"): risk increased w/ acute illness, dehydration, and renal impairement; D/C before surgery -*Genital mycotic infections, UTIs (including urosepsis and pyelonephritis), necrotizing fascitis (perineum) -Hypotension, AKI, renal impairment due to intravascular volume depletion* -Canagliflozin, bexagliflozin: increased *risk of leg and foot amputations* (higher risk w/ hx of amputation, PAD, peripheral neuropathy, and/or diabetic foot ulcers); *risk of fractures* DDIs: -*Increased risk of intravascular volume depletion with diuretics, RAAS inhibitors, or NSAIDs* -UGT inducers (rifampin, phenytoin, phenobarbital) can decrease levels of canagliflozin --> consider higher dose

Question 82

Metformin: -Brand -MOA -ROA -Dosing -Administration considerations

Answer 82

Brand: *Fortamet, Glumetza*, Glucophage (D/C now), Riomet MOA: *biguanide - decreases hepatic glucose production, increases insulin sensitivity, and decreases intestinal absorption of glucose* ROA: PO, liquid (Riomet) *Dosing:* -Initial, IR: 500mg QD or BID -Titrate weekly, usual maintenance dose: 1000mg BID -Max dose: 2000-2550mg/day (2000mg is usually max benefit) Administration: -*Give wth meal to reduce GI upset -ER: swallow whole, can leave ghost tablet -Dose titration recommended to reuce GI effects* (glucose-lowering effecy may NOT be seen w/ initial doses)

Question 83

Metformin: -Effects on glucose -AVEs -Warnings -CIs -BBW -DDIs

Answer 83

Effects on glucose: *decreases A1c by 1-2%, weight neutral, no hypoglycemia* AVEs: GI (*nausea, diarrhea*, flatulence, cramping) which usually resovles over time *Warnings:* -NOT recommended to start if eGFR 30-45 (reassess if eGFR <45 during TX if dose reduction needed) -Vitamin B12 deficiency w/ long-term usage (symptoms: peripheral neuropathy, cognitive impairment --> monitor Q1-2 years) CI: *eGFR <30, acute or chronic metabolic acidosis (including DKA)* BBW: *lactic acidosis (risk increased w/ renal impairment, contrast dye, excessive alcohol or drys - topiramate, and hypoxia)* DDIs: *iodonated contrast media* can cause renal dysfunction, increasing risk of lactic acidosis (*D/C metformin before imaging* and repeat 48 hours after procedure if eGFR stable)

Question 84

Meglitinides: -Under the major drug class ______________ -Drugs/Brands -MOA -Effects on glucose -Administration considerations -AVEs -Warnings -DDIs

Answer 84

Drug class: Insulin Secreatgogues Drugs: repaglinide, nateglinide MOA: *stimulate insulin secretion from pancreatitic beta-cells to decrease postprandial BG -Faster onset and shorter duration compared to SUs* Effects: decrease A1c by 0.5-1.5% *Administration:* -Repaglinide: take within 30 minutes before meals -Nateglinide: take 1-30 minutes before meals -Skip dose if meal skipped AVEs: *weight gain*, HA, URTIs Warnings: *hypoglycemia*, caution w/ severe liver/renal impairment DDis: -*Hypoglycemia in combo w/ SUs or insulin* -Alcohol can increase risk of delayed hypoglycemia -Gemfibrozil and clopidogrel can increase repaglinide levels (CI w/ gemfibrozil)

Question 85

Sulfonylureas (SUs): -Under the major drug class ______________ -Drugs/Brands -MOA -Effects on glucose -Administration considerations -AVEs -Warnings -CIs -DDIs

Answer 85

Drug class: Insulin Secreatgogues Drugs: *glipizide (Glucotrol XL), glimepiride (Amaryl), glyburide (Diabeta), micronized glyburide (Glynase)* MOA: *stimulate insulin secretion from pancreatitic beta-cells to decrease postprandial BG -Older first generation SUs: chlorpropamide, tolazamide, tolbutamide (NO longer used from prolonged hypoglycemia risk)* Effects: *decrease A1c by 1-2%*, decreased efficacy over time (as pancreatitic beta-cell function declines) *Administration:* -Glipizide IR: take 30 minutes before meal (all others: taken w/ breakfast or first meal of day, may hold dose if NPO) -Glucotrol XL: OROS formulation and can leave ghost tablet AVEs: *weight gain, nausea* Warnings: *hypoglycemia (decreased w/ short-risk with short-acting drugs: glipizide) -Glimepiride, glyburide: NOT preferred in elderly (Beers Criteria)* -G6PD deficiency: increased risk fo hemolytic anemia CIs: *sulfa allergy* (not likely to cross-react), T1DM, DKA DDIs: -*Hypoglycemia with meglitinides or insulin* -CYP2C9 substrates (caution w/ inducers or inhibitors) -Alcohol can increase risk of delayed hypoglycemia

Question 86

Dipeptidyl Peptidase-4 Inhibitors (DPP-4is): -Drugs/Brands -MOA -ROA -Administration considerations -Effects on glucose -AVEs -Warnings -DDIs

Answer 86

Drugs: *sitagliptin (Januvia), linagliptin (Tradjenta)*, saxagliptin (Onglyza), alopgliptin (Nesina) MOA: *prevents enzyme, DPP-4, from breaking down incretin hormones, GLP-1 and GIP, which increase glucose-dependent insulin-secretion from pancreatic beta-cells and decrease glucagon secretion* ROA: PO Administration *(linagliptin): only one NOT renally adjusted* Effects: decrease A1c by 0.5-0.8%, weight neutral, low hypoglycemia risk AVEs: generally well tolerated (nasopharyngitis, URTIs, HA, rash) Warnings: -*Pancreatitis, severe arthralgia, AKI*, bullous pemphigioid (blisters/erosions requiring hospitalizations) -*Risk of HF w/ saxagliptin and alogliptin, but warning for class* -Aloglpitin: hepatotoxicity DDIs: -*do NOT use w/ GLP-1 agonists due to overlapping MOA* -Saxagliptin: major substrate of CYP3A4 and P-gp (limit dose w/ strong inhibitors to 2.5mg) -Linagliptin: major substrate of CYP3A4 and P-gp

Question 87

Pioglitazone: -Brand -MOA -ROA -Effects on glucose -AVEs -Warnings -BBW -DDIs

Answer 87

Brand: *Actos* MOA: *thiazolidinediones (TZDs) - peroxisome proliferator-activated receptor gamma (PRAPy) agonists that increase peripheral insulin sensitivity (increase uptake and utilization of peripheral tissues - insulin sensitizer)* ROA: PO Effects: lower A1c by 0.5-1.4%, low risk of hypoglycemia (unless w/ insulin) AVEs: *peripheral edema, weight gain*, URTIs, myalgia Warnings: *edema* (including macular edema), *fracture risk* (gene targeted expressed in bones), hepatic failure, *can stimulate ovulation (unintended pregnancy)*, increase risk of bladder cancer (do NOT use in hx) BBW: *cause or exacerbate HF --> do NOT use in NYHA Class III/IV HF* DDIs: major substrate of CYP3C8 (caution w/ inducers - rifampin or inhibitors - gemfibrozil)

Question 88

Explain the other medications used in T2DM: -Alpha-glucosidase inhibitors -Colesevelam -Bromocriptine -Pramlinitide

Answer 88

Alpha-glucosidase inhbitors: acarbose, miglitol (Glyset) -MOA: inhibit metabolism of complex carbohydrates and disaccharides (ex. sucrose) which delays glucose absorption -*Does NOT cause hypoglycemia, BUT if added w/ drug that does, hypoglycemia cannot be trated with sucrose (ex. fruit juice, table sugar, candy) --> glucose tablets or gels can be used -Each dose should be taken w/ first bite of meal -GI AVEs common (flatulence, diarrhea, abdominal pain)* Colesevalam: bile acid binding resin to decrease absorption --> *constipation most common AVE* Bromocriptine: DA agonist (should NOT use w/ metoclopramide or other DA agonists) -CI: syncopal migraines (hypotension and orthostasis), postpartum/breastfeeding Pramlinitidine: amayln analog that controls postprandial glucose by slowing gastric emptying and suppressing glucagon secretion following meal -Can be used in T2DM or T1DM -*Administered SC* pior to each meal (skip if no meal) -*Significant hypoglycemia risk: reduce mealtime insulin by 50% when starting* -CI: gastroparesis (common GI AVEs)

Question 89

*Diabetes Brand Name Combinations:* 1. Actoplus = _________ + ___________ 2. Janumet = _________ + ____________ 3. Invokamet = _________ + ___________

Answer 89

1. Pioglitazone + Metformin 2. Sitagliptin + Metformin 3. Canagliflozin + Metformin

Question 90

*Insulin: types and properties (onset, peak, duration, use) of types* -Basal -Intermediate-acting -Rapid-acting -Short-acting -Regular U-500 -Inhaled insulin

Answer 90

Basal insulin (ex, glargine, determir, and degludec): "peakless" insulins with onset of 3-4 hours and duration of >/=24 hours; mainly impact fasting glucose Intermediate-acting insulin - insulin NPH -Can be used as basal insulin with onset of 1-2 hours and peak of 4-12 hours -Variable unpredictable duration of 14-24 hours (can cause hypoglycemia) -P in NPH = protamine which delays absorption and extends effects of insulin Rapid-acting insulin (ex. aspart, lispro, glulisine) - bolus dose with onset of 15 minutes, peak at 1-2 hours, and duration of 3-5 hours (gone by next meal) Short-acting insulin (ex. regular) - bolus insulin with onset of 30 minutes, peak at 2 hours, and duration of 6-10 hours Regular U-500: concentrated insulin with same onset as regular insulin, but can last up to 24 hours (often dosed BID or TID before meals) Inhaled: NOT used commonly, but mealtime insulin with fast absorption through lungs

Question 91

Insulin: Storage and administration 1. Most vials are _____mL while most pens are ___mL except for _______ which comes as ____mL and ___mL. Pens also require _________. 2. Insulin concentrations are _______ units/mL. What are the insulins available with higher concentrations? 3. How to prepare suspensions (ex. NPH, protamine mixes) 4. Where to store

Answer 91

1. 10mL; 3mL; Toujeo; 1.5mL; 3mL; pen needles 2. 100 units/mL -Humalog KwikPen, Lyumjev KwikPen (lispro): 200units/mL -Humulin R U-500 KwikPen and vial: 500 units/mL -Tresiba FlexTouch pen: 200 units/mL -Toujeo SoloStar, Toujeo Max SoloStar pens: 300 units/mL 3. Regular insulin (clear) is drawn and added first before NPH (cloudly -Do NOT shake -Turn suspension up and down slowly or roll in hands 4. -Unopened vials: refrigerator, do NOT freeze -Opened vials: can be kept at room temp (more comfortable for injection)

Question 92

*Insulin:* -Whay is it considered a high-alert medication? -AVEs, Warnings, CIs

Answer 92

High-alert: due to human errors (ex. misreading measurements, wrong insulin type/strength/dose/frequency, and skipping meals) AVEs: weight gain (from excess glucose moving into adipose), lipoatrophy (loss of SC fat from injection site), lipohypertophy (accumulation of fat lumps from under injection site) -Avoid lipoatrophy and lipohypertrophy by rotating injection sites and using analog insulins (lower risk than older insulins) Warnings: hypoglycemia, hypokalemia CIs: do NOT administer w/ episodes of hypoglycemia

Question 93

Rapid-Acting Insulins: Drugs/Brands, Appearance, and Administration

Answer 93

Drugs: *insulin aspart (Novolog*, Fiasp), *insulin lispro (Humalog*, Admelog, Lyumjev), lispro U-200 (Humalog U-200), insulin glulisine (Apidra) Appearance: *clear and colorless* Dosing: *inject SC 5-15 minutes before meals* -Lispo: can be administered right after eating -Fiasp and Lyumjev: can be given with first bite or within 20 minutes of starting meal (Fiasp: formulated w/ niacinamide or B3 and Lyumjev formulated w/ treprostinil and citrate to increase absorption rate) Use: *prandial insulin to prevent high BG after meals and correction doses (often w/ sliding scale)* -Preferred type: insulin pump Other one: inhaled insulin (Afrezza) -Requires lung monitoring w/ pulmonary function tests (FEV1) -Replace inhaler Q15 days -*CI in lung disease (asthma and COPD)*, avoid in smokers --> causes acute bronchospasms

Question 94

Short-Acting Insulins: Drugs/Brands, Appearance, and Administration

Answer 94

Drugs: *regular (Humulin R, Novolin R*, Novolin R ReliOn), concentrated Regular U-500 (Humulin R U-500) Appearance: *clear and colorless* *Administation:* -Regular insulin: inject SC 30 minutes before meals (NPH: often BID -Regular insulin preferred for IV infusion including in parenteral nutrition (less expensive, intermediate onset as infusion) --> prepare in a non-PVC container -Regular U-500: five times as concentrated, recommend only when pts using >200 U/day, directions should always be expressed in units, use U-500 syringes to avoid dosing errors, do NOT mix with other insulins Use: *prandial insulin and for correction doses (often as sliding scale)*

Question 95

Intermediate-Acting Insulins: Drugs/Brands, Appearance, and Administration

Answer 95

Drugs: neutral protamine hagedorn - *NPH (Humulin N, Novolin N*, Novolin N ReliOn) Appearance: *cloudy* *Administration:* basal insulin -Typically dosed twice daily as add-on to oral drugs -Can be less expensive, but more hypoglycemia (if nocturnal hypoglycemia w/ QHS, split dose - ex. 2/3 Qam and 1/3 Qpm)

Question 96

Long-Acting/Ultra-Long Acting Insulins: Drugs/Brands, Appearance, and Administration

Answer 96

Long-acting: *insulin detemir (Levemir), insulin glargine (Lantus, Toujeo*, Basaglar) -Interchangeable biosilimars of Lantus: Rezvoglar, Semglee Ultra-long acting: insulin degludec (Tresiba) Appearance: *clear and colorless* Administration: basal insulin -*Injected once daily usually (detemir: may need to give BID) -Lantus: 100units/mL, Toujeo has concentrated of 300units/mL (when >20U/day needed)* -Toujeo: max effect by 5th day (coverage may NOT be adequate initially) -Do NOT mix with other insulins -*Tresiba: comes as vial (100 units/mL) or FlexTouch pen (100 units/mL or 200 units/mL*); can be useful when long-acting insulin causes nocturnal hypogylcemia

Question 97

Premixed Insulins: Drugs/Brands, Appearance, and Administration

Answer 97

Drugs: -*70/30 (70% NPH, 30% regular): Humulin 70/30, Novolin 70/30* -70% aspartate protamine/30% aspart: Novolog Mix 70/30 -75/25 (75% lispro protamine/25% lispro): Humalog Mix 75/25 -50/50 (50% lispro protamine/50% lispro): Humalog Mix 50/50 Appearance: *NPH or protamine will both be cloudy in mixture* *Administration:* -Give BID or sometimes TID (w/ rapid-acting insulins) -Give 15 minutes (rapid-acting) or 30 minutes (regular insulin) before meals -In premixed, percentage of protamine or NPH listed first

Question 98

Which insulins are available OTC? DDIs for insulin?

Answer 98

*OTC:* 1. Humulin R, Novolin R 2. Humulin N, Novolin N 3. Humulin 70/30, Novolin 70/30 DDIs: -*Hypogylcemia with any drug that lowers BG, but especially sulfonylureas or meglitinides -Pramlinitde: reduce mealtime insulin by 50% when starting pramlinitide to avoid severe hypoglycemia* -Reduce insulin dose when starting direct acting antivirals (DAAs) for HpeC (hypoglycemia)

Question 99

*Starting Insulin in T2DM*

Answer 99

1. Consider additon of GLP-1a first except when A1c >10% or BG >/=300mg/dL or symptoms of catabolism present (ex. DKA) 2. Add basal insulin: 10 units SC QD or 0.1-0.2 units/kg/day SC --> titrate based on fasting plasma glucose (FPG) 3. If FPG NOT at goal or signs that prandial insulin needed, add: 4 units or 10% of basal dose SC QD prior to largest meal --> titrate based on prandial blood glucose and add doses prior to other meals if needed 4. If A1c NOT at goal, can give pt full basal/bolus regimen (basal + prandial before each meal) or mixed insulin regimen (BID NPH + short/rapid self-mixed or premixed)

Question 100

*Starting insulin in T1DM -Who is a candidate for insulin pump?*

Answer 100

ALL pts require insulin --> rapid-acting injectable and long-acting basal insulin preferred over short- and intermediate-acting (less hypoglycemia since better mimic body's natural secretion of insulin) 1. Calculate TDD: 0.5 units/kg/day using TBW 2. Divide TDD into 50% for basal and 50% for prandial. 3. Divide the 50% of prandial dose into thirds for each meal. **NPH: given BID with 30% of the TDD in the morning and 20% in the evening Insulin pump: motivated, test BG frequently, understand how to use, and prior experience w/ multiple daily injections

Question 101

*Adjusting Insulin in DM:* 1. When should BG be checked? 2. When to adjust different types of insulin? 3, What are the different mealtime insulin dosing options? 4. How to convert to different insulins?

Answer 101

1. When on insulin or T1DM: before breakfast (FBG), lunch, dinner, and at bedtime 2. -Low FBG: decrease basal or NPH dose -High FBG: increase basal or NPH dose -High or low BG following same meal or preprandial BG on most days: adjust regular or rapid-acting insulin (when adjusting for meals, adjust backwards...ex. if lunch BG high, then adjust breakfast dose) 3. -Use same insulin dose everytime: assumes the grams of carbohydrates eaten at same meal is the same -Calculate insulin dose at each meal: bolus dose is calculate with insulin-to-carbohydrate ratio (ICR) which indicates the grams of carbohydrates covered by 1 unit of insulin (Rule of 450 for regular insulin: 450/TDD of insulin = ICR; Rule of 500 for rapid-acting: 500/TDD = ICR) OR -Carbohydrate correction method: calculate correction factor (how much BG will be lowered by 1 unit of insulin --> 1500 rule for regular insulin: 1500/TDD; 1800 rule for rapid-acting: 1800/TDD) -FOR both calculations: Correction dose = [blood glucose now - target blood glucose] / correction factor **TDD includes BOTH basal and bolus insulin dose 4. Majority are a 1:1 ratio EXCEPT: -NPH dose BID to insulin glargine --> use 80% of NPH dose -Toujeo to insulin glargine or detemir--> use 80% of Toujeo dose

Question 102

*Insulin: Stability at room temperature*

Answer 102

Majority: 28 days 10 days: Humalog Mix 50/50 and 75/25 pens, HUmulin 70/30 pen 14 days: Humulin N pen, Novolog Mix 70/30 pen 28 days: -Apidra, Humalog, Novolog, Admelog, Lyumjev, Fiasp vials and pens -Humalog Mix 75/25 vial -Novolog Mix 70/30 vial -Novolin R U-100, N, and 70/30 pens -Humulin 5 U-500 pen -Lantus, Basaglar, Semglee vials and pens -Humulin R U-100, N, and 70/30 vials 40 days: Humulin R U-500 42 days: Novolin R U-100, N, and 70/30 vials, Levemir vial and pen 56 days: Tresiba pen, Toujeo pen

Question 103

*Insulin: selecting syringes and needles*

Answer 103

Insulin syringes: -0.3mL syringe: for less than 30 units -0.5mL syringe: for 30-50 units -1mL syringe: for 51-100 units -Humulin R U-500 insulin vials should ONLY be dispensed with U-500 syringes (have dark green cap and green needle covers whereas insulin syringe shave orange caps) Insulin pen needles: -Higher the guage, thinner the needle (shorter needle + higher guage = less pain) -Shortest: 4mm and 5mm in legnth and preferred for most pens --> do NOT require skin to be pinched -8mm needles are long enough for most patients --> pinch skin before injection -12.7mm (1/2 inch) needles may be needed for obese patients --> pinch skin before injection

Question 104

*Insulin: administration counseling*

Answer 104

1. Get supplies. Wash hands. 2. Check insulin for discoloration and particles. Discard if present. Check expiration date. 3. If insulin contains NPH or protamine, suspension --> vials can be rolled between hands gently and pens can be inverted 4-5 times -DO NOT SHAKE 4. Clean injection site area with alcohol swab. If vial, wipe top of cap after removing plastic cover with alcohol swab. 5. -Pens: Use NEW needle for each injection. Prior to EACH injection, prime the needle by turning the knob to 2 units, face needle away from you and press injection button. Turn dosing knob to correct number of units, then inject -Vials: Use new syringe for each injection. Inject equal volume of air into vial before withdrawing insulin, limit bubbles in syringe -If mixing NPH and regular/rapid-acting insulin in the same syringe, clear insulin should be drawn from syringe first then cloudy. Inject air into cloudy insulin then inject air into clear insulin before withdrawing out. 6. Insulin best absorbed in abdomen. Alternative sites: posterior upper arm, superior buttocks, lateral thigh area -With needles >5mm, pinch a 2-inch portion with thumb and first finger. -Insert needle all the way (pens: 90 degree angle, syringes: 90 degrees or 45 degrees if thin skin). Press injection button or plunger all the way down and count 5-10 seconds before removing. -Rotate injection sites 7. Dispose of needles, syringes, single-dose pens (with needles attached), and lancets should be placed in sharps container (alternatively: heavy plastic milk bottle - NOT glass, or metal coffee can)

Question 105

*Blood glucose monitoring: how to prepare, test with a glucose meter, and alternative site testing*

Answer 105

Prepare: -If meter requires recalibration, recalibrate each time a new canister of test strips opened. If meter left in extreme cold or heat, dropped, of BG does NOT mach what pt feeling, then recalibrate -Keep test strips in original container with cap close. Check expiration date. -Wash hands vigorously using warm water. Dry hand thoroughly (water can dilute sample). -Allow arm to hang down for 30 seconds so blood can pool into fingertips. Do NOT squeeze the finger. Using glucose meter: -Insert test strip into meter -Prick side of fingertips (side is less painful) with lancet -Apply drop of blood to test strip and discard lancet in sharps container -Record results in logbook or meter might store the results Alternative site testing: -Some meters approved to test blood from forearm, palm, or thigh -Alternative testing ONLY useful when BG is steady --> do NOT use when BG is changing (ex. after eating, after exercise, hypoglycemia) -Lancing device may have special cap screweed onto tip to use on alternative site

Question 106

Hypoglycemia: 1. Defined as a BG <____mg/dL. What some severe consequences of low BG? 2. Symptoms of hypoglycemia 3. TX in conscious patient 4. TX in unconscious patient

Answer 106

1. *70; falls, motor vehicle accidents, seizures, coma, death -Each episode contributes to irreversible cognitive impairment* 2. Dizziness, *anxiety/irritability, shakiness*, HA, *diaprhoresis (sweating), hunger, confusion*, nausea, ataxia, *tremors, palpitations*/tachycardia, blurred vision 3. *Rule of 15* 1. Ingest 15-20 grams of glucose (ex. 4oz or 1/2 cup juice, 8oz or 1 cup milk, 4oz regular soda NOT diet, 1 tbsp honey or corn syrup, or 3-4 glucose tablets or 1 serving glucose gel 2. Recheck BG after 15 minutes 3. If hypoglycemia continues, repeat steps 1 and 2. 4. Once BG is normal, eat small meal or snack, 4. *IV dextrose or *glucagon (glucagon 1mg SC injection*, dasiglucagon injection, or *glucagon nasal spray*) -*If using glucagon, place pt in lateral recumebent position (on side) to protect airway and prevent choking when consciousness returns*

Question 107

*Drugs that cause hypogylcemia*

Answer 107

-Primary cause = insulin -High-risk: SUs, meglitnides, pramlitinide -Other DM agents (low risk): GLP1a, DDP-4is, SGLT2is, TZDs when alone -Alcohol: especially OES -Caution w/ beta-blockers: enhance hypoglycemic effects of insulin and SUs and may mask some symptoms (ex. shakiness, palpitations, anxiety) --> sweating and possibly hunger still present -Others: quinolones, tramadol

Question 108

*Drugs that cause hyperglycemia*

Answer 108

-Thiazide/loop diuretics -Tacrolimus, cyclosporine -PIs -Quinolones -Antipsychotics: quetiapine, olanzapine -Statins -Steroids (systemic) -Cough syrups -Niacin

Question 109

*Inpatient glucose control*: 1. TX should be initiated in persistent BG of ________ or greater and maintained between a range of ___-___ for noncritically ill pts and _____-____ for critically ill pts (ICU). 2. What is the preferred TX? 3. S/Sx of DKA and HHS 4. TX of DKA and HHS

Answer 109

1. 180; 100-180; 140-180 2. Insulin - if oral adequate intake, basal, bolus, and correction doses (based on pt's insulin sensitivity) -Rapid acting insulin preferred for correction doses -If oral intake poor: basal + correction doses 3. Diabetic Ketoacidosis (DKA) - often caused by insufficient insulin; signs: BG > 250, ketones in urine and serum (fruity breath), abdominal pain, N/V, dehydration, anion gap acidosis (pH <7.35, anion gap >12) Hyperosmolar Hyperglycemic State (HHS) - more common in T2DM from illness leading to severe dehydration and altered consciousness (ketones NOT present due to insulin still being made); signs: confusin, delirium, BG >600, high mOsm/L >320 serum osmolality, extreme dehydration, pH > 7.3, bicarbonate > 15 4. Treatment: -FIRST: fluids --> start w/ NS then when BG reaches 200, change to D5W1/2NS -Regular insulin infusion: 0.1 units/kg bolus then 0.1 units/kg/hr CIV OR 0.14 units/kg/hr CIV (prevent hyperkalemia and maintain range between 4-5 mEq/L -Trea acidosis if pH < 6.9 --> give sodium bicarbonate if needed

Question 110

*DM Medications: For the following conditions, state what medication to AVOID:* 1. Thyroid cancer, including medullary thyroid carcinoma 2. Gastroparesis, GI disorders 3. Genital infection/UTI 4. Heart failure

Answer 110

1. GLP-1a or GIP/GLP-1a 2. GLP-1a or GIP/GLP-1a, pramlintide 3. SGLT2is 4. TZDs, alogliptin, saxagliptin

Question 111

*DM Medications: For the following conditions, state what medication to AVOID:* 1. Hypoglycemia 2. Hypotension/dehydration 3. Hypokalemia

Answer 111

1. Insulin, SUs, meglitinides, pramlintide 2. SGLT2is 3. Insulin

Question 112

*DM Medications: For the following conditions, state what medication to AVOID:* 1. Ketoacidosis 2. Lactic acidosis 3. Osteopenia/osteoporosis 4. Pancreatitis

Answer 112

1. SGLT2is (can occur when BG <250) 2. Metformin (increased risk w/ alcoholism or renal impairment) 3. TZDs (fractures), canagliflozin and bexagliflozin (decreased BMD, fractures) 4. GLP1a, GLP1a/GIPa, and DPP-4is

Question 113

*DM Medications: For the following conditions, state what medication to AVOID:* 1. Peripheral neuropathy, PAD, foot ulcers 2. Sulfa allergy (severe) 3. Renal insufficiency (eGFR or CrCl <30) 4. Weight gain/obesity

Answer 113

1. Canagliflozin and bexagliflozin 2. SUs (or use cautiouslessly) 3. Metformin, exanatide, glyburide, may need to start insulin at lower dose 4. SUs, meglitinides, TZDs, insulin