PHARMIII EX. 1 GI / Diabetes

Aminosalicylates used for MILD GI

Sulfasalazine

Mesalamine

Balsalazide

Olsalazine

GI drugs used for MODERATE Acute/Active problems

Corticosteroids

GI Drugs used for SEVERE/CHRONIC

Methotrexate

Cyclosporin

Thiopurines (Azathioprine, 6-Mercaptopurine)

Used IV for SEVERE/CHRONIC GI, as well as Fistulizing Crohn’s Disease

Infliximab (Anti - TNF-a)

Ulcerative Colitis

• Diffuse mucosal inflammation limited to the colon

• Bloody diarrhea, colicky pain, urgency, tenesmus

Crohn’s Disease

• Patchy transmural inflammation

• May affect any part of GI tract

• Abdominal pain, diarrhea, weight loss, intestinal obstruction

Corticosteroids MOA

Forms GC-GR complex - transport to nucleus of cells

• Transactivation: binds to GRE & induces up-regulation of lipocortin

• Transrepression: creates a complex with NF-KB resulting in down-regulation of IL-2

Thiopurines MOA (6-thioguanine nucleotides active metabolite)

Active incorporation into replicating DNA of T-cells , HALTING cell Replication and Transcription – reducing inflammation 🙂

(6-thioguanine nucleotides active metabolite)**

Methotrexate MOA

• Inhibits dihydrofolate reductase

• Inhibition of T-cell proliferation and cytokine / eicosanoid (PG, LT)

synthesis

Cyclosporin MOA

• Inhibition of the production of cytokines involved in the regulation of T-cells activation

• NFAT proteins controlled by Calcineurium (Ca2+ dep. - phosphatase)

Bulk Agents

Metamucil (psyllium based)

Citrucel (methylcellulose)
Fibercon (non-absorbable starch)

Salt / Osmotic Laxatives

o Polyethylene Glycol (MiraLax)

Salts:
o Milk of Magnesia (Mg(OH)2)

o Epsom Salt (MgSO4)

o Glauber’s Salt (Na2SO4)

o Sodium Phosphates (used as enema)

o Sodium Citrate (used as enema)

Stool Softeners

• Docusate sodium (surfactant/stimulant)

• Glycerin suppositories

Irritant / Stimulant Laxatives

• Senna (plant-based)

• Bisacodyl ** (1ry one)

• Lubiprostone - PGE1 (stimulates Cl- channels; mucosal hydration/watery stool)

 Enteral loss of water and salts causes release of:

Aldosterone

• stimulates reabsorp. in intestine, but increases excretion of K+ !!

• Can result in Hypokalemia (reduces peristalsis)

Anti-Diarrheals (anti-motility agents)

• Diphenoxylate/Atropine (Lomotil); stimulates opioid receptors in the bowel and slows intestinal contractions.

• Loperamide; binds to opioid receptors in intestinal wall, reduces peristalsis and increases tone of anal sphincter.

• Gram (+) anaerobe m.o. that prod. exotoxins A and B

• Loc. @ Distal colon

• Can lead to colitis and toxic megacolon (~20%)

C. Difficile

Anti-Flatulence drugs

Simethicone (detergent)

• alters elasticity of mucus-coated bubbles, causing them to break.

Chemoreceptor trigger for EMESIS on Dorsal surface of Medulla Oblongata

Area Postrema :) 

Anti-Emetics

• Scopolamine (M1 Antagonist)

• Promethazine, Prochlorperazine (D2 Antagonist / H1 Blocker)

• Metoclopramide (D2 Antagonist/Blocker)

• Meclizine (H1 Blocker)

• ONDANSETRON (Zofran) **best overall

  • Serotonin (5-HT3) Antagonist 

Chronic systemic disease characterized by metabolic and vascular abnormalities.

Disorder of carb. metabolism.

Fasting of blood glucose is >126.

Diabetes Mellitus

• When secreted it is cleavage into insulin and

protein C (both are secreted)

• Glucose is the major stimulus of secretion.

• Lipogenic

Insulin (Endogenous)

Diabetes types

• Type 1(10%)

→ patient secretes no insulin, needs exogenous insulin to live.

→ Destroys B cells of pancreas.

→ Sudden onset.

• Type 2 (90%)

→ patient secretes insufficient amounts of insulin and receptors are resist. to existent circulating insulin.

→ may require exogenous insulin to control hyperglycemia.

→ Can occur at any age / Easier to control. 

Rapid-acting Insulin analogs (SC)

Humalog (insulin lispro)

Novolog (insulin aspart)

*Effective in decreasing Post-prandial Hyperglycemia*

Must NOT be diluted/mixed w/ any other solution

Short-Acting Regular Insulin Analogs (SC / IV cont. drip)

Humulin R

Novolin R

Onset is ½-1 hour

Peak is 2-3 hours

Duration is 5-7 hours

Intermediate-acting

• Neutral Protamine Hagedorm (NPH) aka Isophane insulin suspension

• Humulin N / Novolin N

Onset is 1-1.5 hours

Peaks in 8-12 hours

Duration is 18-24hrs

Long-Acting Insulin Analogs

Lantus *most common*

Levemir

Tresiba

Onset is 4-8 hours

Peaks in 10-30 hours

Duration is 36+ hrs

Combos / Mixtures

• Humulin 70/30 NPH + R

• Novolin NPH + R

• Humalog Lispro protamine / Lispro

Intensive Tx 

• Multiple Daily Injections

• Tight glycemic control

Goal is to achieve glucose levels of 175 mg/dl with total HbA1c of 7% of total hemoglobin.

Standard Tx

• Insulin injections 2x a day

• Looser glycemic control

Maintains glucose levels 225 – 275 mg/dl. with total HbA1c of 8 - 9% of total hemoglobin.

Oral Diabetic Drugs

• Sulfonyureas

• Alpha Glucosidase Inhibitors

• Biguanides

• Glitazones

• DPP-4 Inhibitors

• GLP-Agonists

• SGLT2 Inhibitors

Sulfonyureas

Glipizide (Glucotrol)

Glyburide (Diabeta)

Glimepiride (Amaryl)

1ry side effect of Sulfonyureas

Hypoglycemia

**Only use if pt has functioning B cells**

(Not for renal/kidney comp. pts or pregnancy; careful w/ sulfa allergies)

Sulfonyureas MOA

Increase the number of insulin receptors and increase peripheral use of glucose.

→ increase release of insulin and decrease prod. of glucose.

Sulfonyureas can be used with

Metformin, Glitazones, Insulin, Acarboses

ALPHA Glucosidase Inhibitors

• Acarbose (Precose)

• Miglitol (Glyset)

*Taken @ beggining of each meal*

(NOT pts w/ liver/kidney impairment, malabsorption, etc.)

ALPHA Glucosidase Inhibitors MOA

→ Delay absorption of CHO and simple sugars

→ Inhibit a-glucosidase enzymes (maltase, amylase, sucrase) in GI tract.

Biguanides

• Metformin (Glucophage)

(NOT for pts w/ liver/kidney problems)

Can be used alone or combo

Biguanides

Does NOT cause Hypoglycemia

Has been associated with Lactic acidosis (parenteral radiographic contrast media)

Biguanides MOA

→ Increase use of glucose by muscle and fat cells

→ Decreases hepatric glucose production / intestinal absorption

Glitazones (TZDs)

• Pioglitazone (Actos)

• Rosiglitazone (Avandia)

Glitazones (TZDs)

Are insulin sensitizers.

Decrease insulin resistance.

*Caution in pts w/ Heart Failure* !!

(NOT for pts w/ liver disease / high ALT lvls)

Glitazones (TZDs)

• Stimulate receptors on muscle, fat, and liver cells

• Results in increased uptake of glucose in periphery and decreased production by the liver.

DPP -4 Inhibitors (dipeptidyl

peptidase-4 inhibitors)

• Sitagliptin (Januvia)

• Saxagliptin (Onglyza)

• Linagliptin (Tradjenta)

DPP-4 Inhibitors / GLP-1 Agonists SE

Side effects

o Nausea, diarrhea, or abdominal pain

o URI - sinusitis /pharyngitis

o Pancreatitis

o Joint Pain (not for 2nd)

DPP-4 Inhibitors MOA

Blocks DPP-4 receptors

DPP-4 enzyme inactivates incretins (GLP, GIP)

Stimulates Insulin release / Inhibits Glucagon release

Lowering Blood sugar

GLP-1 Agonists

• Liraglutide (Victoza)

• Exenatide (Byetta)

• Dulaglutide (TRULICITY)

• Semaglutide (OZEMPIC)

GLP-1 Agonists MOA

→  Increase insulin secretion / Decreased glucagon secretion.

→ Slow gastric emptying (reduce the rate of glucose absorption

from the intestines)

→ Increased satiety (acting on centers in

the brain that regulate appetite)

GLP-1-Agonists (Liraglutide / Semaglutide)

Associated with THYROID TUMORS & Medullary Cancers

(Thyroid Calcium cell tumors in rodents)

SGLT2 Inhibitors (Sodium-Glucose Co-transporters)

• Canagliflozin (Invokana)

• Dapaglifozin (Farxiga)

• Empagliflozin (Jardiance)

• Ertugliflozin (Steglatro)

SGLT2 Inhibitors

• Prevent the reabsorption of glucose in the

kidneys, leading to increased glucose excretion in

urine.

SGLT2 Inhibitors SE

Genital / Urinary tract infections (bc of inc. glucose)

Dehydration / Hypotension

Pt w/ Type 2 Diabetes and HbA1c > 7%

• Metformin (unless contraindications/intolerance)

  • If after 3mo does not get < 7%, add an oral agent or add basal insulin.