502 meds review

Levothyroxine

severe symptoms: 50-125mcg/day

older, smaller, more risk for hyperthyroid: 12.5-25 mcg/day

weight based dosing: 1mcg/kg/day

recheck every 4-8 weeks: adjust by 12.525mcg based on TSH rechecks

maintenance dose (Young adults): 130mcg/day

elderly: 110mcg/day

Levothyroxine

100mcg

Liothyronine Sodium

25 mcg

Liotrix

50 mcg/12.5 mcg

Thyroglobulin

65 mg

Desiccated thyroid

60-65 mg

Hypercortisolism (Ketoconazole)

600-800mg/day

-strong CYP3A4, 2C9, P-gp inhibitor

Hypercortisolism (Metyrapone)

750-1000mg/day BID or QID

-not mono therapy, used in combination with other inhibitors

-quick onset

Hypercortisolism (Mitotane)

1-2g/day BID or QID

-monitor urinary free cortisol, adjust as needed

Hypercortisolism (Pasireotide)

600-900mcg SUBQ BID

-50% see reduction of urinary free cortisol at 6 months

Hypercortisolism (Mifepristone)

300-1200mg daily

-symptomatic treatment only

Hyperaldosteronism (Spironolactone)

Initial: 25mg/day

Max: 400mg

--sex steroid effects; gynecomastia, impotence, menstrual irregularities

Hyperaldosteronism (Eplerenone)

initial: 50mg/day

max: 300 mg

Hyperaldosteronism (Amiloride)

Initial: 5mg BID

Max: 15 mg

-less effective than spironolactone/epleronone for BP control

Adrenal Insufficiency (Fludrocortisone acetate)

0.05mg-2mg daily

-for 1st degree adrenal insufficiency

-adjust dose q6-8 weeks based on BP, peripheral edema, electrolyte levels

Adrenal Insufficiency (hydrocortisone)

15-25 mg daily

-give 2/3 dose in AM, 1/3 6-8hrs later

-also tid dosing (wake,bkfst, evening meal)

Adrenal Insufficiency (Cortisone acetate)

20-35 mg daily

-give 2/3 dose in AM, 1/3 6-8hrs later

Adrenal Insufficiency (Prednisolone)

-alt for hydrocortisone or cortisone acetate only when once daily dosing is needed

Fast acting Insulin

-Insulin Aspart (Fiasap)

-Insulin Lispro (Lyumjev)

Onset: 15 min

Peak: 60 min

duration: 3-5 hrs

Dosed at the beginning of meal or within 20 mins after starting meal

Rapid Acting Insulin

Aspart (Novolog)

Glulisine (Apidra)

Lispro (Humalog/Admelog)

Onset: 15 min

Peak: 30-90 min

Duration: 3-5hrs

-admin immediately prior to meals

-minimize PP hyperglycemia and allow for rapid correction

-mealtime coverage insulins

Short Acting Insulins

Regular (Humulin R or Novolin R)

Onset: 30-60 min

Peak: 2-4 hrs

Duration: 5-8hrs

Humulin R U-500

Onset: 15 mins

Peak: 4-8hrs

Duration: 21 hrs

-used BID/TID, 30 mins before meals

-more concentrated insulin for patients requiring 200+u/day

Intermediate Acting insulin

NPH (Humulin N or Novolin N)

onset: 1-3hrs

peak: 8 hrs (4-10hrs)

Duration: 12-16 hrs

-background option, dose BID

-Can be mixed with regular/rapid in same syringe

Long/Basal Insulin

Insulin Detemir (Levemir)

Onset: 3-8hrs

Peak: flat

Duration: 20-26 hrs

-dosed qd or bid if elevated pre-dinner BG

-mimics normal pancreatic basal insulin secretion

-reduce risk of nocturnal hypoglycemia

Long/Basal Insulin

Insulin Glargine (Lantus)

(Basaglar, Semglee, Rezvoglar)

onset: 2-4hrs

peak: none

duration: 24 hrs

-QD injection at same time

-basaglar same protien sequence+similar glucose lowering effects

-do not mix with other insulin in same syringe

MOA: injection of acidic solution and precipitation of glargine in SC tissue—>slow dissolution of precipitates prolong action

Ultra Long insulin

Insulin Glargine (Toujeo)

onset: 6hrs

peak: none

duration: 36 hrs

-small injection volume compared to lantus

-duration is >24 h when taken at same time

-do not mix with other insulin in same syringe

Ultra Long acting insulin

Insulin Degludec (Tresbia)

onset: 90 mins

peak: none

duration: up to 42 hrs

-lower risk of hypoglycemia, allows for flexibility in dosing (true 24hr insulin)

-MOA: slows release from SC depot

-do not mix with other insulin in same syringe

Mixed Insulin

50% lispro protamine/ 50% insulin lispro (HumaLOG Mix 50/50)

75% lispro protamine/25% insulin lispro (HumaLOG Mix 75/25)

70% aspart protamine /30% insulin aspart (NovoLog Mix 70/30)

onset: 5-15 mins

peak: 1-2 hrs

duration: 10-16 hrs

Premixed cont

70% NPH/ 30% Regular (HumuLIN 70/30)

70% NPH/ 30% Regular (Novolin 70/30)

onset: 30-60 mins

peak: 2-10 hrs

duration: 10-16hrs

Premixed Insulin effects

AM: short-acting bolus, regular—>reflected in pre-lunch BG (11A)

AM: intermediate-acting basal, NPH—>reflected in pre-din BG (5P)

PM: short-acting bolus, regular—>reflected in bedtime BG (10P)

PM: intermediate-acting basal, NPH—>reflected in FBG (6A)

GLP-1 Receptor Agonists

-used for weight loss

-pts with established or increased risk of CV or renal complications

-can be used for pts who need lower glucose effects—>GLP 1s preferred prior to insulin

-MOA: delay gastric emptying, enhance glucose-dependent insulin secretion by pancreatic B cells

-SC injection except oral semaglutide (Oral: 3mg/day, 30 min before first meal/beverage with no more than 4 oz of water)

AE: n/v, diarrhea, constipation, injection site reactions, dizziness, hypoglycemia

-precautions: pancreatitis

GLP-1 Receptor Agonists Meds

Short Acting

-Exenatide (Byetta): 5-10 mcg BID

-Lixisenatide (Adlyxin): 10-20 mcg/day

(avoid in very low GFR, no CV benefit)

Long Acting

Exenatide XR (Bydureon): 2mg/week

Liraglutide (Victoza): 0.6-1.8 mg/day (CV indication)

Dulaglutide (trulicity): 0.75-4.5mg/week (CV indication)

Semaglutide (Ozempic): 0.25-1mg/week (CV indication)

Amylin Analogs

-reduce PP glucagon secretion—>suppression hepatic glucose output

-regulation gastric emptying—>control rate of nutrient delivery to SI

-reduction in food intake which controls reduction of exogenous glucose entering circulation

-may delay absorption of oral meds due to slow gastric emptying (admin 1hr prior or 2hrs after)

-do not mix with insulin

Amylin meds

Pramlintide

T2DM: reduce mealtime insulin by 50%, start 60 mcg SC ASAP before meals

increase dose from 60mcg to 120 mcg if no nausea for 3 days

T1DM: reduce mealtime insulin dose 50% start 15 mcg before meals

titrate up in 15mcg increments to max 60mcg if tolerated

Metformin (Buguanide)

-insulin sensitizer: improves target cell response to liver and peripheral tissues (pushes out more insulin)

-AMPK activators

-best candiate for newly diagnosed hyperglycemia without contraindications

-reduces A1C 1-2% and reduces FBG 50-70mg/dL

AE: diarrhea, N/V, flatulence, malabsorption, heartburn, taste distrubance, lack of energy, LACTIC ACIDOSIS (RARE)

Metformin Dosing

start 500mg once daily w/food

-adjustment: may be titrated weekly as tolerable—>titrate to BID or TID

MAX doses:

10-16yo: 2000mg/day

IR: 2550/day, XR: 2000mg/day

if eGFR 45-60: 1500mg/day

-not rec for moderate to severe renal impairment (eGFR<45), unstable/acute CHF, liver disease

SGLT-2 Inhibitors (gliflozin)

-blocks reabsorption of glucose in kidney

-best used for people who have CV risks

-not for people who have renal impairment, severe hepatic impairment, pt with recurrent genital fungal infections or UTIs, pregnant in 2nd/3rd trimester

-can be used for weight loss

AEs: UTIs, bladder cancer, dehydration, increased urination, Fourniers Gangrene, ketoacidosis, lower limb amputation

SGLT2-Inhibitor meds

Canagliflozin (Invokana): 100mg/day—>not for ESRD (1)

Dapagliflozin (Farxiga): 5mg/day—>used in HF, not for ESRD (2)

Empagliflozin(Jardiance): 10mg/day—>used in HF(1)

Etrugliflozin (Steglatro): 5mg/day

DPP4i (glipton)

MOA: enhances incretin system by inhibiting DPP4 (inactivates the incretin hormone)

-Best used for ESRD and renal insufficiency

-not for pts with HF, pts at risk for pancreatitis, pts on antivirals

-reduces A1C by .5-1%, FBG 20-40mg/dL, PPg 40-50 mg/dL

-AE: HA, upper respiratory infection, nasopharyngitis, immune defects with long term use

DPP4i meds

sitagliptin (Januvia): 100mg/day

saxagliptin (Onglyza): 2.5-5mg/day—>increase in HF risk

linaglipton (Tradjenta): 5mg/day—>no dose adjustment needed

alogliptin (Nesina): 25mg/day—>increase in HF risk

(for all dosing, reduce dose by ½ based on eGFR)

TZDs (glitazone)

MOA: enhance glucose uptake, insulin sensitizer (acts on fat and liver cells)→full effect seen in 12 weeks, PPARy agonist: active of PPARy to activate insulin-responsive genes that regulate carb and lipid metabolism

-Medchem: liver toxicity may be associated with reactive quinone metabolite oxdizied by CYP2C8 and CYP3A4

-best used for pts who have A1C less than 8% (need for combination)

-not for pts who have HF, liver disease/hepatic impairment, pregnancy

-reduce A1C by .5-1%, FBG 30-60mg/dL

AE: edema, weight gain, increase in bone fracture risk, bladder cancer, delayed clinical onset (2-4 weeks, full effect at 12 wks)

TZD meds

pioglitazone (Actos): 15-45mg/day

rosiglitazone(Avandia): 4mg/day

Sulfonylureas

-MOA: stimulate insulin secretion, need existing B cells→reduce glucose output from liver and improve insulin sensitivity

-K ATP channel modulators:block ATP sensitive channel on B cells by binding to SURI→membrane depolarization and opening of Ca channel to promote insulin secretion

-best used for recent diagnosis, added to metformin, awareness of hypoglycemia symptoms

-not for pts who have renal/aderenal/pituitary insufficiency (same meglitinides)

-can use glipizide 1mg for renal insufficiency

AE:hypoglycemia, dizziness, GI upset\

-can cause weight gain for both insulin secretagogues

Sulfonylurea meds

QD-BID with breakfest

glipizide (Glucotrol): 5mg→IR: 30m b4 food

glyburide: 1.5-5mg→NR renal impairment

glimepiride (Amaryl): 1-2mg

Meglitinides

TID 30 min before meals

-Repaglinide (Prandin): 0.5-2mg

-Nateglinide (Starlix): 60-120 mg

-not for severe renal/hepatic impairment, can be used in mild/moderate renal insufficiency

Alpha glucosidase Inhibitors

MOA: delayed absorption of glucose

-best used for pts with high PPG

-not for pts with GI disease, liver/hepatic disease

-reduce A1C 0.5-1%, FBG 20-40mg/dL, PPG 40-70mg/dL

-AE: GI upset

cons: TID dosing, slow titration

increase hypoglycemia: glyburide, glipizide

Alpha glucosidase Inhibitors meds

Acarbose (Precose): 25-50mg

Miglitol (Glyset): 25-50 mg

slow titration due to GI SE

Semaglutide (Rybelsus) GLP1 receptor agonist

Dose: 3mg QD for 30 days→increase to 7mg QD (Max: 14 mg/day)

counseling: admin 30 min before first meal/beverage with no more than 4oz of water, swallow tablets whole

AE: GI upset

Methimazole

-more potent than PTU, longer ½ life preferred

-PTU preferred in 1st trimester of pregnancy

Dose: 15-60 mg/day divided TID (initial), 5-15mg/day divided 1-3xday

HYPERTHYROIDISM

PTU

MOA: inhibits peripheral T4→T3 conversion

-half life is only an 1hr, preferred in 1st trimester of pregnancy

Dosage: 100-200mg TID (initial), 50-100mg TID (maintence)

HYPERTHYROIDISM

-inhibit type I5’ deiodinase (catalyzes T4→T3)

Complex Anions

Perchlorate (CLO4-) and Pertechentate (TcO4-)

-compete with I- for symporter→inhibit I- uptake

-used as prep for surgery

Lamivudine

-reverse transcriptase inhibitor

-HBV DNA polymerase has reverse transcriptase activity

Entecavir

-originally developed for treatment of herpes simplex

-inhibits three distinct phases of HBV DNA polymerase: HBV DNA polymerase priming, reverse transcription, synthesis of the positive stranded HBV DNA

Tenofovir alafenamide

-has a bulky group attached to protect the phosphate, it is eventually cleaved off to protect the phosphate group

-the phosphate group then becomes active and is very potent (ProDrug like)

-the dose is 25mg in comparison to tenofovir disproxil fumarate dose of 300mg

-lowers serum con which results in fewer SE

NS3/4A Protease Inhibitor

-previr

NS5A Complex Inhibitor

-asvir

NS5B Polymerase Inhibitor

-buvir

Sofosbuvir

-HCV NS5B polymerase inhibitor

-uridine nucleotide analogue, alternative substrate inhibitor

-uses protide technology→prodrug to deliver a nucleotide phosphate into the liver

-active metabolite→triphosphate made by nucleoside kinases in liver

Bulk Laxatives

-increase in bowel content volume triggers stretch receptors in the intestinal wall

-causes reflex contraction (peristalsis) that propels the bowel content forward

-soaks up water in gut, makes poop softer, helps push it out easier

Psyllium (Metamucil)

Saline and Osmotic Laxatives

-effective in 1-3 hours

-used to purge intestine

-fluid is drawn into the bowel by osmotic force, increasing volume and triggering peristalsis

Salts: Milk of Magnesia

Polyethylene glycol

Non-digestible sugars and alcohols: Lactulose

Osmotic Laxatives

-nonabsorabable sugars:sorbital and and mannitol

-PEG

MOA:accumulate water in fluid

AR: flatulence and cramps, N/V

Emollient Laxatives

-Docusate sodium (Colace)

-MOA: stool softener by incorporating water into fatty fecal matter, softens feces in 1-3days

AR: Nausea and abdominal cramping

Irritant/Stimulant laxatives

-increase GI motility

-irritate the GI mucosa and pull water into lumen

-indicated for severe constipation

Castor oil

Senna

Bisacodyl (Dulcolax)

Lubiprostone-PGE1 derivative that stimulates chloride channels, producing chloride rich secretions

What are first line laxative treatments?

-Osmotic or stimulant

Lubiprostone (Amitiza)

-chloride channel activator

MOA:activates Cl- channels in gut, increases liquid secretion into intestines, shortens intestinal transit time

-used for chronic constipation

Linaclotide (Linzess)

MOA: binds to guanylate cyclase C receptor on intestinal enterocytes in gut, activates cystic fibrosis transmembrane conductance channel, stimulates intestinal fluid secretion

-used for chronic constipation

Anti-motility agents

-reduce peristalsis by stimulating opioid receptors in the bowel

-allows for more water to be absorbed by the gut

Loperamide

-peripherally acting opioid, first line therapy

-non sedating, non addictive

-safe to use when pregnant and lactation

-taken prn, 1-2mg after bowel movement up to 16mg/day

Bismuth subsalicylate

Pepto-Bismol

Bismuth subcarbonate

MOA: antibacterial, bismuth subsalicylate inhibits formation of prostaglandins producing diarrhea (anti-diarrheal drug)

AR: Nausea, bitter taste, black hairy tongue/ dark stool

Contraindications for antidiarrheals

-dont take when sick

-dont give Imodium to pts who have hypersensitivity to loperamide hydrochloride or other excipients

-dont give imodium to pts with abdominal pain in absence of diarrhea

-dont give imodium to infants below 24 months

-dont overuse as it can cause fast/irregular heartbeat or death

Clostridium difficile

-The major cause of diarrhea and colitis in patients exposed to antibiotics

Clostridium difficile treatment

-discontinue offending antibiotic

-fecal transfer

-metronidazole (dont give in pts with liver or renal impairment)

-vancomycin (contraindicated in pts with renal impairment)

Antiemetic Therapeutics

Musarinic M1 receptor antagonist: Scopolamine

MOA: blocks acetylcholine receptor (transdermal patch)

SE: dry mouth, dizziness, restlessness, allergic rxn, delirium at high doses

Contraindications: kidney or liver disease, enlarged prostate, difficulty in urination, heart disease, glaucoma

Phenothiazines

promethazine (Phenergan-antihistamine)

prochlorperazine (Compazine-D2 blocker)

dimenhydrinate (Dramamine-antihistamine)

SE: typical antipsychotics, blurred vision, dry mouth, dizziness, seizures

Contraindications: allergy to phenthiazines, glaucoma, liver disease, prostate/bladder problems

-histamine H1/Dopamine D2 receptor agonist

-these meds can help inhibit vomiting

Serotonin 5-HT3 receptor agonist

Ondansetron

Granisetron

-great for chemotherapy induced n/v (can be given before chemo)

SE: usually well tolerated, headache, constipation

End stage liver disease

decompensated cirrhosis: jaundice, ascites, encephalopathy, variceal bleeding

ESLD lab values

-high INR

-thrombocytopenia

-low albumin

Portal hypertension

when cirrhosis destroys the liver, pressure builds up

portal vein: collects blood from GI tract and sends it to the liver

When are there risks for variceal hemorrhaging?

when HVPG is greater than or equal to 12 mm Hg

Varices prevention

non selective beta blockers (first line)

Propranolol (Inderal) 20 mg twice daily

Nadolol (Corgard) 40 mg at bedtime

Carvedilol (Coreg) 3.125 mg twice daily

-B2 blockade results in splanchnic vasoconstriction, decreasing portal blood flow and pressure

Acute variceal bleeding signs and symptoms

weakness/fatigue

decreased Hgb

hematemesis: blood in vomit

melena: dark, tarry stools

Variceal bleeding treatment

band ligation (put rubber band around bleeding vessicle and stop bleed)

scierotherapy

ballon tamponade

Octreotide (Sandostatin) for variceal bleeding

-start immediately and continue for 72 hrs

-50 mcg IV loading dose, then IV drip at 50 mcg/hr

-monitor for hypo-hyperglycemia, bradycardia

Antibiotics for variceal bleeds

-Ceftriaxone 1g IV daily

or

-Levofloxacin 500 mg daily (IV or PO)

-5 to 7 days for treatment

Shunting

TIPS

-stunt creates a shunt between portal and hepatic veins

-salvage therapy

Ascites treatment

Albumin infusion: 6-8 g per liter is removed, replaces missing albumin and adds fluid into the intravenous space

Ascites pharm treatment

Spironolactone (Aldactone)

-inhibits aldosterone

-potassium sparing diuretic

-initial dose is 100 mg (max 400 mg/day)

SE: elevated K+, hyponatremia gynecomastia

Loop diuretics for ascites

Furosemide (Lasix): 40 mg/day initial dose

Bumetanide (Bumex)

Toresemide (Soaanz)

Amiloride (Midamor)

-potassium sparing diuretic (allows for more fluid to be excreted in the urine)

-10 mg amiloride can be used to replace 100mg of spironolactone (keeps K+ in check)

-non first line therapy

Diuretic AE

-volume depletion

-renal impairment

-potassium imbalance

-hyponatremia

-hypotension

-alkalosis

Spontaneous bacterial peritonitis (SBP) cause

-bacterial overgrowth in gut due to poor immune system

-bacteria translocate across intestinal cell wall

-escaped bacteria enter ascites fluid

SBP diagnosis

PMN greater than or equal to 250/mm3 in the ascites fluid

-if the count is high, automatically diagnosed with peritonitis

Antibiotics for SBP

Cefotaxime: 2g IV q8h

Ceftriaxone: 2g IV q24h

-Levofloxacin: 500 mg IV q24h for 5 days (for true penicillin allergy)

Hepatic encephalopathy

-altered mental status caused by cirrhosis

-toxins build up and cause worsening symptoms

-liver can metabolize toxins

Lactulose (Enulose, Generalc, Constulose, Kristalose)

-no fixed dose

-titrate dose to maintain 2-4 soft stools/day

-requries 15-30 mL one to five times a day

MOA: metabolized by gut bacteria to lactic, acetic, and formic acid (decreases toxin load)

-first line therapy

SE: diarrhea, flatuelence, abdominal cramping/bloating, dehydration, excessive sweet taste

HE antibiotics

Rifaximin (Xifaxan) 550 mg po BID

MOA: decrease toxin load in colon

-second line therapy

HE prevention

sedating drugs can worsen HE

-avoid benzodiazepines

-avoid hypnotics

-caution with narcotics

Treatment of HRS-AKI

Octreotide +Midodrine or Telipressin

HCV symptoms

fever

fatigue

loss of appetite

jaundice

Invasive vs Non invasive tests

NI: APRI, FIB-4, Fibrosure/Fibrotest

NI procedures: fibroscan, ultrasound elastography, magnetic resonance elastography (MRE)

Invasive: liver biopsy

Ribavirin

-HCV treatment, dont use as monotherapy

-weight based dosing

<75 kg, 1000mg/day

>75 kg, 1200mg/day

ADR: hemolytic anemia, fatigue, dyspnea, chest pain, n/v/d/c

-pregnancy→teratogenic (can cause mental abnormalities in fetus)

-need to use 2 forms of contraception during treatment and 6 months after