05 GI

Antiemetics

• Solitary track runner: the nucleus tractus solitarius (NTS, or vomiting center) located in the medulla, receives inputs from the GI tract, vestibular system, and area postrema
• Vomit on track: the NTS projects neurons to other medullary nuclei to coordinate the vomiting response
• Stomach hammer throw area: the GI tract communicates directly with the NTS (via CN X)
• Vegas sign at the stomach area: vagal afferents from the GI tract communicate with the NTS
• Smiley hammer at the stomach area: GI irritation (due to infection, chemotherapy, distention) causes mucosal serotonin release
• “1-2-3 Hammer Throw!”: serotonin activates 5HT-3 receptors on the vagal afferents
• Semicircular canal: the vestibular system communicates directly with the NTS (via CN VIII)
• Vests at the semicircular canal: the vestibulocochlear nerve (CN VIII) from the vestibular system communicates with the NTS
• Seasick at the canal: the vestibular system cis responsible for vertigo and motion sickness (vestibular nausea)
• Extreme postures next to the track: the area postrema (chemoreceptor trigger zone) is located adjacent to the NTS (outside the BBB in the 4th ventricle) and responds to emetogenic substances (e.g. chemotherapeutic agents)

• Ribbon dancer blocking the Hammer Throw: ondansetron antagonizes 5HT-3 receptor on vagal afferents in the GI tract (treats chemo-induced or post-op vomiting)
• Hammer tightening gut: ondansetron can cause constipation
• Hammer hitting head: ondansetron can cause headache and dizziness
• Twisted torsades streamer: ondansetron can prolong the QT interval and induce torsades
• Pile of smiley faces: ondansetron can cause serotonin syndrome (symptoms include rigidity, tremor, hyperthermia, confusion)

• Allergy inducing, Q shaped dandelions: the vestibular system contains H1 histamine receptors (coupled to Gq)
• Bee swatters: 1st generation H1 receptor blockers (e.g. diphenhydramine, meclizine) treat vestibular nausea (motion sickness)
• M1 motorcycle parking: the vestibular system contains M1 muscarinic receptors
• Telescope: scopolamine (muscarinic antagonist) treats vestibular nausea (motions sickness)
• Seasick sailor outfits: motion sickness (vestibular nausea) is treated with 1st generation H1 antagonists (e.g. diphenhydramine) and scopolamine (muscarinic antagonist)

• 2 D-ring ropes: the area postrema contains D2 receptors
• Tickler blocking the D-rings: metoclopramide antagonizes D2 receptors in the area postrema (treats chemotherapy induced vomiting)
• Contracted stomach: metoclopramide has upper GI prokinetic effects (useful for treatment of delayed gastric emptying due to post-surgical disorders and diabetic gastroparesis)
• “Do not obstruct”: metoclopramide (D2 antagonist) is contraindicated in small bowel obstruction
• Mud puddle: metoclopramide can cause diarrhea (prokinetic effect)
• Sleeping judge: metoclopramide can cause drowsiness (central D2 blockade)
• Crying coach: metoclopramide can cause depression (central D2 blockade)
• EXTRA pyramidal newspaper hat: metoclopramide can cause extrapyramidal effects due to central D2 blockade (e.g. dystonia, akathisia, parkinsonian features)
• Sticking out tongue: metoclopramide can cause tardive dyskinesia with chronic use (central D2 blockade)
• Now More Spicy chicken: metoclopramide (D2 antagonist) can cause neuroleptic malignant syndrome (symptoms include fever, rigidity, mental status changes, autonomic instability, rhabdomyolysis)
• Elevated milk release: metoclopramide can cause elevated prolactin levels (central D2 blockade)
• Twisted torsades streamer: metoclopramide can cause QT prolongation and induce torsades

• PlaNK 1: the area postrema contains neurokinin 1 (NK1) receptors (activated by substance P)
• “Substance pee check”: substance P binds NK1 receptors in the area postrema
• “Participants”: aprepitant antagonizes the NK1 receptors in the area postrema (treats chemotherapy induced vomiting)

GERD

• “Pour-it-all” table: parietal cells in the gastric mucosa are responsible for acid secretion
• Battery powered puree pump: H+/K+ ATPase (proton pump) on the luminal membrane pumps H+ into the lumen
• Banana into the pump, lemons out: the H+/K+ ATPase exchanges one K+ for one H+ at the luminal membrane
• Three P batteries: ATPase
• Sidewalk: lumen of the stomach

Histamine

• “Enter CarefulLy”: enterochromaffin-like (ECL) cells
• Bees released from ECL tree: the ECL cell releases histamine (activates the parietal cells)
• Bees swarming honey pot: histamine (released by the ECL cell) activates H2 receptors on the parietal cell
• Honey pot with 2 “S” handles: H2 histamine receptors (coupled to Gs) on the basolateral membrane
• Honey pot kid knocking over acid pitcher: activation of H2 receptors upregulates the H+/K+ ATPase → increased acid secretion

Gastrin

• Gas truck releasing gas tanks: G-cells release gastrin (which stimulates ECL and parietal cells)
• Vegas sticker: vagal stimulation stimulates the G cell to release gastrin (via GRP)
• Gate release pull: gastrin releasing peptide (GRP) from the vagus nerve activates G cells
• Gas powered blower releasing bees from ECL tree: gastrin (released by G cells) stimulates the ECL cell to release histamine (CCK receptor)
• Gas powered acid pump: gastrin (released by G cells) stimulates the parietal cell to secrete H+ (minor effect)

Vagal

• Motorcycle attached to stand in M3: M3 acetylcholine receptors are located on the parietal cell
• Vegas sticker: vagal stimulation stimulates the parietal cell to secrete acid (via M3 receptors)

• 2 bee swatters: H2 histamine receptor antagonists (e.g. ranitidine, cimetidine) inhibit acid secretion by parietal cells
• Tie-dye: “-tidine” suffix of the H2 receptor antagonists (e.g. ranitidine, cimetidine, famotidine, nizatidine))
• Gargling: H2 blockers (e.g. ranitidine, cimetidine) treat GERD (PPIs are first line)
• Ulcerated sidewalk: H2 blockers (e.g. ranitidine, cimetidine) treat gastric and duodenal ulcers (PPIs are first line)
• Tie-dye kid on the cement: cimetidine (H2 blocker with antiandrogenic side effects)
• Dented chrome bumper: cimetidine inhibits cytochrome P-450
• Pot lids on chest: cimetidine can cause gynecomastia
• Droopy honey wand: cimetidine can cause impotence
• Milk shooting from nose: cimetidine can cause elevated prolactin levels

• Girl scout blocking puree pump: proton pump inhibitors (PPIs) irreversibly inhibit the H+/K+ ATPase (the final common pathway for H+ secretion)
• PRIZE: “-prazole” suffix of PPIs (e.g. omeprazole, lansoprazole, rabeprazole)
• Jumbo gas tank: gastrinoma causing hypersecretion of gastric acid (Zollinger-Ellison syndrome - treat with PPIs)
• Helicopter hat: PPIs treat Helicobacter pylori infection
• Chocolate fondue fountain: PPIs increase the risk of Clostridium difficile infection (gastric acid important for bacteria proliferation)
• Dirty lung spots: PPIs increase the risk of respiratory infections (e.g. pneumonia)
• Medals bound to wagon: PPIs decrease the absorption of Ca2+, Mg2+, and Fe2+ (requires acidic environment)
• Fractured axel: PPIs may increase the risk of osteoporotic hip fractures (due to decreased Ca2+ absorption)
• Porous wood: PPIs may worsen osteoporosis (due to decreased Ca2+ absorption)
• Falling magnets: PPIs can cause hypomagnesemia

• Stop sign: somatostatin (SST) inhibits the release of histamine by ECL cells
• Stop sign: somatostatin (SST) inhibits the release of gastrin by G cells (and SST receptor positive gastrinomas)
• Octagon: octreotide (a long acting SST analog) inhibits ECL cells
• Octagon: octreotide (a long acting SST analog) inhibits G cells (useful in the treatment of gastrinoma/Zollinger-Ellison syndrome)

Laxatives

• not direct stimulation of GI motility (prokinetics, muscarinic agonists)
• changes consistency

• Spa water: osmotic laxatives (e.g. magnesium compounds, lactulose, polyethylene glycol) are nonabsorbable substances that draw water into the intestinal lumen → distention → peristalsis. Rapid action. Rapidly decompressing
• Magnets over water: magnesium compounds (e.g. magnesium hydroxide, magnesium citrate) are osmotic laxatives
• Peg drain cover: polyethylene glycol (PEG) is an osmotic laxative (nonabsorbable sugar), electrolyte balanced and used for preendoscopic prep
• Relaxulose: lactulose is an osmotic laxative (nonabsorbable sugar)
• Cirrhotic liver and brain coral: hepatic encephalopathy (a neurologic complication of cirrhosis due to the buildup of ammonia and other toxins)
• Relaxulose into the liver and brain coral tank: lactulose is useful in the treatment of hepatic encephalopathy
• Fish eating lactulose: intestinal bacteria metabolize lactulose into acidic metabolites
• Acidic pH meter: acidic metabolites decrease the pH of the intestinal lumen
• NH4+ release valve: ammonia (NH3) is trapped as ammonium (NH4+) in the acidic intestinal lumen and excreted
• Fisherman removing fish: rifaximin (a poorly absorbed antibiotic) eradicates ammonia producing intestinal bacteria (treats hepatic encephalopathy)

• Spilling mud bath: laxatives can cause diarrhea and dehydration

• Bulky seaweed: psyllium is a bulk-forming laxative (indigestible hydrophilic colloid → absorbs water → distention → peristalsis)

• Water penetrating canoe at the DOCK: docusate is a stool softener (surfactant agent that facilitates penetration of stool by water and lipids)

• Stimulating suntan lotion: senna is a stimulant laxative a.k.a cathartic (stimulation of enteric nervous system and colonic secretions)
• Brown gut: chronic use of senna causes melanosis coli (brown pigmentation of the colon)

• Muddy slippers left outside: antidiarrheal agents (featured in massage room)
• Utopia: opioid agonists (e.g. diphenoxylate, loperamide) treat diarrhea
• μssage: opioids treat diarrhea by activating μ-opioid receptors in the GI tract
• Lop-eared rabbit: loperamide treats diarrhea (μ-opioid agonist that does not cross the BBB → no analgesia or potential for addiction)
• Lop-eared rabbit hopping back and forth: opioid agonists (e.g. loperamide) increase colonic phasic segmenting activity → increased colonic transit time
• Dolphins: diphenoxylate treats diarrhea (μ-opioid agonist with some ability to cross the BBB → combined with atropine to prevent abuse)

• Red stool and inflammatory candles outside door: antidiarrheal agents are contraindicated in patients with bloody diarrhea or fever
• Clogged: opioids can cause constipation

• VIP CUSTOMERS only crab: VIPoma and carcinoid tumor cause secretory diarrhea
• Octagon stop sign: octreotide (a somatostatin "stop" analog) treats the symptoms of VIPoma and carcinoid syndrome (e.g. secretory diarrhea)

Diabetes

• Welcome INSIDE mat: insulin (the storage and anabolic hormone of the body)
• LangerHansel: islets of Langerhans in the pancreas (the site of beta cells that produce insulin)
• Beta-2 tuba: pancreatic beta cells produce insulin (stimulated by many factors including glucose and sympathetic activation of beta-2 receptors)
• LangerHansel’s candy: glucose - the most potent stimulant of insulin secretion

• Closed gate around banana candy flowers: glucose increases ATP levels in the beta cell → ATP dependent K+ channels CLOSE
• Gretel rushing in on calci-yum icecream flower: closing the ATP dependent K+ channels causes the beta cell to depolarize → voltage gated Ca2+ channels open → Ca2+ INFLUX → insulin secretion
• C wrapper: C-peptide (cleaved from proinsulin in the secretory granule) is released with endogenous secretion of insulin

• Tyrosine tire swing: the insulin receptor contains an intracellular tyrosine kinase domain
• 4 on open door: insulin inserts glucose transporter type 4 (GLUT4) into the membrane of peripheral tissues (primarily adipose and muscle)
• Full liver candy jar: insulin increases hepatic glycogen stores (increased glycogenensis, decreased glycogenolysis)
• Glycogen glazed ham: insulin increases glycogen storage and protein synthesis in muscle
• Full fatty donut jar: insulin increases triglyceride storage in adipocytes
• Eaten banana candy: insulin decreases serum K+ (increased Na+/K+ATPase in skeletal muscle drives K+ into the cells)

• Girls And Lads: insulin Glulisine, Aspart, Lispro (rapid acting, short duration)
• Tall immediate peak: insulin glulisine, aspart, and lispro have a rapid onset and short duration of action
• Birds nibbling the peak: insulin glulisine, aspart, and lispro control the postprandial glucose spike

• Rest Now: Regular insulin, NPH insulin (Neutral Protamine Hagedorn) (intermediate acting)
• Delayed peak: regular and NPH insulin have a delayed onset and intermediate duration of action (NPH is more delayed)
• Ivy under “R”: regular insulin can be administered IV
• Ivy next to eaten banana: IV regular insulin is useful in the management of hyperkalemia (administer with glucose!)
• Candy key: diabetic ketoacidosis (DKA - presents with vomiting, fatigue, polyuria)
• Ivy next to candy key: IV regular insulin is useful in the management of DKA (watch K+ levels!)

• Don’t Go: insulin Detemir, Glargine (long acting)
• Flat roof: insulin detemir and glargine have long durations of action and provide a steady background level of insulin (glargine has no peak)

• Falling candy: insulin therapy can cause hypoglycemia (presents with tachycardia, palpitations, sweating, nausea)

• Sulfa egg laying swan: sulfonylureas (e.g. glyburide, glipizide) are sulfa drugs
• Sulfa swan lake behind CLOSED banana gate: sulfonylureas bind the ATP-dependent K+ channels on beta cells → release of endogenous insulin
• Mother swan in a maid outfit: “-amide” suffix of 1st generation sulfonylureas (e.g. tolbutamide, chlorpropamide) (long duration of action, rarely used)
• Goslings riding on mother’s back: “-ride” suffix of 2nd generation sulfonylureas (e.g. glyburide, glimepiride (smaller dosing, long duration of action)
• Short zig-zagging gosling: glipizide (2nd generation sulfonylurea) has the shortest duration of action (less risk of hypoglycemia)

• Gliding: “-glinide” suffix of the meglitinides (e.g repaglinide, nateglinide)
• Gliding goose behind CLOSED banana gate: meglitinides (glinides) bind the ATP- dependent K+ channels on beta cells → release of endogenous insulin

• 2 fingers: sulfonylureas and meglitinides (glinides) are oral agents used in the treatment of TYPE 2 diabetes (require functional beta cells for endogenous insulin release)
• C wrapper: sulfonylureas and meglitinides (glinides) increase endogenous insulin release and C-peptide levels
• Father gliding goose can’t lay eggs: meglitinides (glinides) are NOT sulfa drugs (can be used in patients with an allergy to sulfonylureas)
• Falling candy: sulfonylureas and meglitinides (glinides) can cause hypoglycemia
• Fat old hag: sulfonylureas and meglitinides (glinides) can cause weight gain
• “Do not drink” next to mother sulfonylurea swan: some 1st generation sulfonylureas (e.g. chlorpropamide) cause a disulfiram-like reaction with ingestion of alcohol
• Chlorpropamide: SIADH

• 2 fingers: GLP-1 agonists and DPP-4 inhibitors are oral agents used in the treatment of TYPE 2 diabetes (require functional beta cells for endogenous insulin release)

• ExenaTIDE detergent: “-tide” suffix of GLP-1 agonists (e.g. exenatide, liraglutide)
• Gulp activated by hag: GLP-1 agonists (e.g. exenatide) activate the glucagon-like peptide-1 (GLP-1) receptor (increased insulin release and satiety, decreased glucagon release and gastric emptying)
• Gs protein AC

• 4 DRIPPING laundry items: dipeptidyl peptidase-4 (DPP-4) inhibitors (gliptins) prevent the breakdown of GLP-1
• Clipped in clothespins: “-gliptin” suffix of the DPP-4 inhibitors (e.g. sitagliptin, saxagliptin, linagliptin)
• Endogenous gulps: DPP-4 inhibitors (gliptins) increase levels of endogenously secreted GLP-1 (increased insulin release and satiety, decreased glucagon release and gastric emptying)

• Falling empty glucagon packets: GLP-1 agonists and DPP-4 inhibitors decrease glucagon secretion
• Sealed gastric container: GLP-1 agonists and DPP-4 inhibitors decrease gastric emptying
• Clothespin clipping nose: DPP-4 inhibitors (gliptins) can increase the risk of nasopharyngitis and upper respiratory tract infections
• Squeezing pancreas sponge: GLP-1 agonists (e.g. exenatide) can cause pancreatitis
• Candies NOT falling: GLP-1 agonists and DPP-4 inhibitors do NOT cause hypoglycemia
• C wrapper: GLP-1 agonists and DPP-4 inhibitors increase endogenous insulin release and C-peptide levels

Diabetes 2

• 2nd grade: these agents are used in the treatment of TYPE 2 diabetes (require functional beta cells for endogenous insulin release)
• Metaphor: metformin (a biguanide) is the first line oral agent for the management of type 2 diabetes
• Bitten mitochondrial candy: metformin inhibits mitochondrial enzyme glycerophosphate dehydrogenase (mGDP)
• AMPKandy: metformin activates the enzyme AMP-activated protein kinase (AMPK) → decreased gluconeogenesis, increased insulin sensitivity
• Stopping candy release from liver bag: metformin modulates enzyme function to decrease hepatic gluconeogenesis
• INSIDE open candy box: metformin increases insulin sensitivity

• Spilled sour milk: metformin can cause lactic acidosis
• Cracked kidney tray: renal insufficiency increases the risk of metformin induced lactic acidosis. Excreted by kidney
• Nauseated: metformin can cause GI side effects (e.g. anorexia, nausea, vomiting, diarrhea)
• Skinny kid: metformin can cause modest weight reduction

• Glitter: “-glitazone” suffix of the thiazolidinediones (glitazones- e.g. rosiglitazone, pioglitazone)
• PPARy in circle: thiazolidinediones (glitazones) are ligands of peroxisome proliferator- activated receptor gamma (PPAR-γ) (an intranuclear receptor that regulates gene transcription)
• Turtle neck: PPAR-γ upregulates adiponectin (increased insulin sensitivity and fatty acid oxidation). Adiponectin low in diabetes pts
• Elevated fatty donut jar: thiazolidinediones (glitazones) increase the differentiation and number of adipocytes
• Eating fatty donut: thiazolidinediones (glitazones) increase triglyceride storage and fatty acid oxidation → decreased serum triglycerides
• 4 on open door: thiazolidinediones (glitazones) upregulate GLUT4 in peripheral tissues (increased glucose uptake)
• INSIDE open candy box: thiazolidinediones (glitazones) increase insulin sensitivity

• Fat belly: thiazolidinediones (glitazones) can cause weight gain
• Baggy pants: thiazolidinediones (glitazones) can cause fluid retention and peripheral edema in renal tubules
• Crushed failing heart balloon: thiazolidinedione (glitazones) induced fluid retention can exacerbate heart failure
• Fractured chair leg: thiazolidinediones (glitazones) can increase the risk of atypical extremity fractures in women (due to decreased bone mineral density)

• Amy and Lynn: amylin (islet amyloid polypeptide) analogues (e.g. pramlintide) (decreased glucagon, gastric emptying, and appetite)
• Falling candy: amylin analogues (e.g. pramlintide) can cause hypoglycemia
• Closed gastric water cooler: amylin analogues (e.g. pramlintide) decrease gastric emptying
• Falling empty glucagon packets: amylin analogues (e.g. pramlintide) decrease glucagon secretion
• 1 and 2: amylin analogues (e.g. pramlintide) can be useful in the management of type 1 and type 2 diabetes
• Eaten cupcake: amylin analogues (e.g. pramlintide) can be used to control the postprandial glucose spike
• Nauseated: pramlintide can cause GI side effects (e.g. nausea, vomiting, anorexia)

• A-Carb wigglers: acarbose and miglitol (alpha-glucosidase inhibitors)
• “Monosaccharide free”: inhibition of alpha-glucosidase enzymes decreases the conversion of disaccharides into absorbable monosaccharides
• Brush border flags: alpha-glucosidase inhibitors decrease the activity of disaccharidases on the intestinal brush border
• Delayed bag opening: alpha-glucosidase inhibitors delay carbohydrate absorption
• Eaten cupcake: alpha-glucosidase inhibitors (e.g. acarbose, miglitol) can be used to control the postprandial glucose spike
• Leaky bathroom puddle: alpha-glucosidase inhibitors can cause GI side effects (e.g. diarrhea, flatulence, abdominal pain) due to fermentation of the undigested carbohydrates by gut bacteria

• Flossing: “-flozin” suffix of the SGLT2 inhibitors (e.g. canagliflozin, dapagliflozin)
• Salty Glucose Co.: sodium-glucose cotransporter 2 (SGLT2) reabsorbs glucose in the proximal tubule (inhibition leads to urinary glucose loss)
• Pro Cart Track: proximal convoluted tubule of the nephron (site of action of SGLT2 inhibitors)
• Bladder cup: SGLT2 inhibitors (e.g. canagliflozin, dapagliflozin can increase the risk of UTI (due to increased urine glucose concentration)
• Snow hitting crotch: SGLT2 inhibitors (e.g. canagliflozin, dapagliflozin) can increase the risk of vaginal candidiasis
• Canada: Candida albicans
• Fainting: SGLT2 inhibitors (e.g. canagliflozin, dapagliflozin) can cause hypotension (due to osmotic diuresis)
• Cracked kidney tray: SGLT2 inhibitors are contraindicated in renal insufficiency

Thyroid

PTU

• Evil follicu-LAIR: thyroid follicular cell (site of iodine uptake and thyroid hormone production)
• Salty sodium peanuts entering lair: sodium enters thyroid follicular cell through the sodium-iodide symporter
• Iodide vial smuggled in with salty peanuts: the sodium-iodide symporter concentrates iodide in the follicular cell
• Follicu-LAIR truck lumen: thyroid follicle lumen (site of iodide storage as thyroglobulin)
• TransPOrter: thyroid peroxidase (TPO - enzyme involved in iodide oxidation and organification)
• Rusty oxidized transport truck: TPO oxidizes iodide into iodine
• “Thyro-global” truck: thyroglobulin (tyrosine rich protein precursor to thyroid hormones located in the follicular lumen)
• Organic foods transporter truck: TPO facilitates iodine organification (iodination of tyrosine residues on thyroglobulin)
• Coupled tyres of transport truck: TPO facilitates coupling of iodinated tyrosine residues
• Time bomb prep table in the follicu-LAIR: thyroid hormones (T4 and T3) are cleaved from thyroglobulin in the follicular cell (T4 in greater quantities)
• T4 time bomb: tetraiodothyronine (thyroxine, T4)
• T3 time bomb: triiodothyronine (T3) is the more potent form of thyroid hormone
• T4 detonator in the periphery: 5’ deiodinase in the peripheral tissues converts T4 to T3

• Sensitive to catfish: thyroid hormone increases the sensitivity of peripheral tissues to catecholamines (increased number of beta-adrenergic receptors)
• Anxious henchman with big bowtie: hyperthyroidism is associated with hypermetabolic and hyperadrenergic symptoms (e.g. tachycardia, palpitations, insomnia, anxiety, tremor, heat intolerance, weight loss)
• Bulging infrared goggles: Grave’s ophthalmopathy (increased volume of retroorbital connective tissue, due to cellular proliferation, inflammation, and the accumulation of glycosaminoglycans) → exophthalmos

• Radioactive vial: hyperthyroidism due to Graves' disease can be treated with ablating doses of radioactive iodine (131-I)
• Bulging radioactive goggles: radioactive iodine treatment can exacerbate Grave’s ophthalmopathy
• “PTU!” agent firing at the transporter: propylthiouracil (PTU - a thionamide) treats hyperthyroidism by inhibiting TPO
• Evil math equations striking transporter: methimazole (thionamide) treats hyperthyroidism by inhibiting TPO
• “PTU!” agent firing at the bomb trigger: PTU treats hyperthyroidism by inhibiting 5’ deiodinase → decreased conversion of T4 into T3
• Silenced bugle gun pointed at catfish tank: beta blockers treat the hyperadrenergic symptoms of hyperthyroidism
• Silenced bugle gun pointed at trigger: beta blockers treat hyperthyroidism by inhibiting 5’ deiodinase → decreased conversion of T4 into T3
• Moon face death coaster blocking trigger: glucocorticoids treats hyperthyroidism by inhibiting 5’ deiodinase → decreased conversion of T4 into T3
• Moon face death coaster hitting goggles: glucocorticoids treat Grave’s ophthalmopathy
• Thwarted Dr. Storm: treat thyroid storm by 1) blocking sympathetic effects (beta blockers); 2) blocking thyroid hormone synthesis (PTU); and blocking conversion of T3 to T4 (beta blockers, PTU, glucocorticoids)

• Undone bowtie: radioactive iodine treatment can cause hypothyroidism
• Anxious radioactive henchman: radioactive iodine treatment can exacerbate HYPERthyroidism
• Broken liver beaker: PTU can cause severe hepatotoxicity
• Chemical spots: PTU can cause a maculopapular rash
• Self destruct sand timer: PTU and methimazole can cause agranulocytosis. Risk of infection
• Plastic chew bones: PTU and methimazole can cause aplastic anemia
• Guard wolf: PTU and methimazole can cause drug induced lupus
• Inflamed leash: PTU can cause ANCA-associated vasculitis
• Tarantula: methimazole is a first trimester teratogen

• Fat, cold, fatigued mixologist: hypothyroidism is associated with dry brittle hair, lethargy, fatigue, weakness, decreased BMR, cold intolerance, and myxedema
• Mixing cold drinks: untreated hypothyroidism can lead to myxedema coma (progressive weakness, stupor, hypothermia, hypoventilation, hypoglycemia, hyponatremia, death)
• Synthetic T4 time bombs: levothyroxine (synthetic T4) treats hypothyroidism
• Anxious agent taking cover: levothyroxine therapy can cause HYPERthyroidism

• Obstructive box of anions: anions such as perchlorate, pertechnetate, and thiocyanate competitively inhibit the sodium-iodide transporter (treat accidental radioactive iodine exposure). Decreased reduction of iodide uptake

Bisphosphonate

• Osteo-builders: osteoblasts
• Destructive class: osteoclasts
• DONATE: “-dronate” suffix of bisphosphonates (e.g alendronate, pamidronate, zoledronate), the first line treatment for osteoporosis
• Two P coins: bisphosphonates have a chemical structure similar to pyrophosphate
• Large T-rex appetite: bisphosphonates attach to hydroxyapatite in bone
• Classmate stuck in donation box: osteoclasts bind to the bisphosphonate, inhibiting their adherence to the bony surface
• Class waiting to enter: osteoclast precursors
• Preventing class from entering: bisphosphonates decrease the development and recruitment of osteoclast precursors
• Classmate’s popping balloon: bisphosphonates induce osteoclast apoptosis

• Elevated calci-yum icecream: bisphosphonates are useful in the acute treatment of hypercalcemia
• Massive calcified rock with metastatic crab fossils: hypercalcemia of malignancy is a common cause of severe hypercalcemia requiring acute treatment (with bisphosphonates and calcitonin)
• Disorganized bone display: bisphosphonates and calcitonin are useful in the management of Paget disease (uncontrolled osteoclast resorption with secondary disorganized bone formation)
• Corroded neck: bisphosphonates can cause upper GI side effects (e.g. acid reflux, esophagitis, esophageal ulcers)
• Crumbling jaw bone: bisphosphonates can cause osteonecrosis of the jaw (rare)
• Falling calci-yum icecream: bisphosphonates can cause hypocalcemia

• Female symbol: estrogen therapy can treat and prevent postmenopausal osteoporosis (not recommended due to increased risk of breast cancer and other side effects)
• Female guarding class entrance: estrogen inhibits differentiation of osteoclast precursors
• Relax: raloxifene (a selective estrogen receptor modulator - SERM) is useful in the treatment and prevention of postmenopausal osteoporosis
• Relaxing the waiting classmates: raloxifene has estrogen agonist activity in bone (inhibits osteoclast differentiation) and estrogen antagonist activity in breast and uterus (reduced risk of breast cancer)

• PthD: parathyroid hormone (PTH)
• Convincing osteo-builder to give crank-drill: PTH stimulates osteoblasts to express RANKL
• Crank-drill: receptor activator of nuclear factor kappaB ligand (RANKL)
• Active classmate with crank-drill: RANKL binds to RANK on the osteoclast, increasing its activity

• Dino suit man grabbing crank-drill: denosumab (monoclonal antibody against RANKL) is useful in the treatment of osteoporosis
• Antibody spikes: denosumab is a monoclonal antibody

• Curator toning it down: calcitonin (“tones down calcium”) has some utility in the treatment of osteoporosis
• Curator grabbing classmate: calcitonin directly inhibits osteoclasts → decreased bone resorption
• Calci-yum ice cream pouring down flank: calcitonin promotes Ca2+ excretion by the kidney
• Falling calci-yum icecream: calcitonin can cause hypocalcemia

PTH

• Osteo-builders: osteoblasts (activated by teriparatide and vitamin D → increase bone mineral density)
• Destructive classmates: osteoclasts (indirectly activated by teriparatide and vitamin D → increase bone resorption/turnover)
• Released calcified bones: osteoclasts release calcium from bone
• Released P fossil: osteoclasts release phosphate from bone

• PthD paleontologist: parathyroid hormone (PTH)
• PthD lab: parathyroid gland
• Calcified bone receiving: calcium-sensing receptor on the parathyroid gland (senses increased serum calcium)
• PthD stuck behind bones: high serum calcium levels inhibit PTH production and secretion
• PthD convincing osteo-builder to give up crank-drill: PTH stimulates osteoblasts to release receptor activator of nuclear factor kappa-B ligand (RANKL) → activates osteoclasts
• Classmate receiving crank-drill: RANKL binds to RANK on the osteoclast surface → increased differentiation and activity → increased bone resorption
• PthD teaching osteo-builders: PTH stimulates maturation of osteoblasts → increased bone formation (net effect of PTH)
• PthD gathering bones and dropping P fossils: PTH increases calcium resorption by the kidney (and increases phosphate excretion)
• 1-head added to Calci-TRON: 1-alpha-hydroxylase in the kidney converts 25-hydroxyvitamin D into 1,25-dihydroxyvitamin D
• PthD adding final piece to Calci-TRON: PTH increases activity of 1-alpha-hydroxylase in the kidney → increased production of 1,25-dihydroxyvitamin D (calcitriol)

• PthD teaching assistant (TA): teriparatide (recombinant PTH)
• TA teaching osteo-builders: intermittent doses of teriparatide stimulates maturation of osteoblasts → increased bone formation. No osteoclast activity
• Fresh piece of calcified chalk: teriparatide can be used to treat osteoporosis (increase bone density)
• TA gathering bones and dropping P fossils: teriparatide increases calcium resorption by the kidney (and increases phosphate excretion)
• TA adding final piece to Calci-TRON: teriparatide increases activity of 1-alpha-hydroxylase in the kidney → increased production of 1,25-dihydroxyvitamin D (calcitriol)

• Solar D3 battery: vitamin D3 (cholecalciferol) is obtained via dairy products or UVB radiation in sunlight
• Earth-friendly D2 battery: vitamin D2 (ergocalciferol) is obtained via plants
• Robot body added to D battery in liver-barrow: 25-hydroxylase in the liver converts vitamin D to 25-hydroxyvitamin D
• Calci-TRON gathering bones and fossils from dump site: calcitriol stimulates reabsorption of calcium AND phosphate by the kidney
• Calci-TRON gathering bones and fossils from GI truck: calcitriol stimulates intestinal absorption of calcium AND phosphate

• Calci-TRONl delivering crank-drills: calcitriol stimulates osteoblasts to release RANKL → activates osteoclasts
• Calci-TRON collapsing PthD lab: calcitriol inhibits PTH production by the parathyroid gland
• Calci-TRON teaching osteo-builders: calcitriol stimulates maturation of osteoblasts → increased bone formation
• Fresh piece of calcified chalk: calcitriol can be used to treat osteoporosis (increase bone density)
• Calci-TRON stabilizing rickety tower: vitamin D (e.g. calcitriol) can be used to treat osteoporosis (increase bone density)
• Calci-TRON stabilizing broken kidney: calcitriol can be useful in chronic kidney disease (prevent hypocalcemia)
• Scaly knee and elbow pads: topical vitamin D can be used to treat psoriasis
• Calci-TRON saving falling calcified bones: calcitriol is useful in the long term management of hypocalcemia (e.g. hypothyroidism)
• Falling PthD: hypocalcemia is commonly caused by hypoparathyroidism (decreased production of calcitriol by the kidney)
• Undone bowtie on PthD: thyroid surgery can cause hypoparathyroidism and hypocalcemia
• Shaking structure: hypocalcemia can cause seizure
• Tense fist: hypocalcemia can cause paresthesias, muscle cramps, trismus, and tetany

• Raised calci-yum ice cream: teriparatide and vitamin D therapy can cause hypercalcemia

• Calculator at the calcified bone receptor: cinacalcet (a calcimimetic) activates the calcium sensing receptor on the parathyroid gland → decreased production of PTH
• Calculating pile of calcified bones: cinacalcet is useful in the treatment of hypercalcemia due to hyperparathyroidism

• Shoveling fossils in the GI truck: sevelamer (a phosphate binding polymer) decreases absorption of phosphate in the GI tract
• Shoveling pile of fossils: sevelamer is useful in the treatment of hyperphosphatemia due to chronic kidney disease

Glucocorticoids

• Stone: “-sone” suffix of glucocorticoids (e.g. dexamethasone, fludrocortisone, prednisone)
• Adrenal cap: cortisol (an endogenous glucocorticoid) is released from the adrenal cortex
• Moon face: glucocorticoids
• Moon scepter in outer circle: the glucocorticoid receptor is located in the cytoplasm
• Activated scepter in inner circle: the activated glucocorticoid receptor enters the nucleus and regulates gene transcription
• Inhibited cataPuLt A2: glucocorticoids inhibit phospholipase A2 (PLA2 - the first step in the arachidonic acid inflammatory pathway)
• AA frame of catapult A2: glucocorticoids prevent production of arachidonic acid (AA) by inhibiting PLA2
• Inhibited pro-slugger bat: glucocorticoids prevent production of inflammatory prostaglandins by COX
• Inhibited lacrosse stick: glucocorticoids prevent production of inflammatory leukotrienes by LOX
• Inhibited N-Flame Krossbow: glucocorticoids inhibit NF-KB (transcription factor for pro-inflammatory cytokines, e.g. IL-2, TNF-alpha)
• Inhibited T-kight and antibody archer: glucocorticoids prevent activation of T-cells and B-cells (by inhibiting production of proinflammatory cytokines)
• Blocked adhesion of first responders: glucocorticoids prevent production of neutrophil adhesion molecules → demargination and decreased migration
• Crowded first responders: demargination of neutrophils causes neutrophilia
• Falling T-knight, helper T-squire, and antibody archer: glucocorticoids reduce T-cell and B-cell counts
• Helper T-squire lowest: glucocorticoids are most effective at reducing helper T-cell counts
• Falling eo-slingshot: glucocorticoids reduce peripheral eosinophil counts
• Eclipsed inflammatory sun: glucocorticoids are useful for treating inflammatory disorders (e.g. gout, rheumatoid arthritis, asthma, IBD)
• Cracked antibodies: glucocorticoids are useful for immunosuppressive therapy (e.g. transplant rejection prevention, treatment of autoimmune disorders)
• Locked welcome inside mat: glucocorticoids cause insulin resistance
• Liver bag producing candy: glucocorticoids stimulate gluconeogenesis
• Sugar-filled liver jar: glucocorticoids increase hepatic glycogen storage
• Cracked moon: adrenal insufficiency (can be due to Addison’s disease - primary adrenal insufficiency)
• Fainted druid: acute adrenal insufficiency can manifest as circulatory shock and death
• Falling candy: acute adrenal insufficiency can manifest as hypoglycemia
• Exogenous moon face: exogenous glucocorticoids treat/prevent acute adrenal insufficiency
• Shriveled adrenal hat: chronic exogenous glucocorticoid use causes adrenal cortical atrophy (secondary adrenal insufficiency)
• Falling meat: glucocorticoids promote proteolysis
• Falling fatty donut jar: glucocorticoids promote lipolysis
• Cushion: Cushing’s syndrome (due to chronic glucocorticoid use - fat redistribution, muscle weakness, skin thinning, osteoporosis, immunosuppression)
• Moon face: moon facies (due to fat deposition)
• Fat belly: fat redistribution → central adiposity
• Thin arms: myopathy, muscle wasting, proximal weakness
• Thin striped fabric: glucocorticoids inhibit fibroblast proliferation → skin thinning, striae, impaired wound healing
• Fractured osteoporotic altar: glucocorticoids decrease bone mass → osteoporosis, fractures
• Cracked head: glucocorticoid induced psychosis (hypomania, confusion, hallucinations)
• Banana peel: glucocorticoids can cause hypoglycemia (due to mineralocorticoid effects)
• Cane: glucocorticoids can cause immuno-suppression
• Pulmonary cacti: glucocorticoids can cause reactivation of latent infections (e.g. TB)

Hypothalamic

ADH

• Collecting duct (CD) - the site of action of antidiuretic hormone (ADH, vasopressin)
• Hydrating waterboy: antidiuretic hormone (ADH, vasopressin)
• Posterior water jug: ADH is released from the posterior pituitary
• V1 hole on the Q shaped green: ADH activates V1 receptors coupled to Gq (activates PLC → IP3 + DAG → increased intracellular Ca2+)
• Constricted golfclub: ADH activation of V1 on vascular smooth muscle causes vasoconstriction and increased BP
• V2 hole on the S shaped green: ADH activates V2 receptors coupled to Gs (activates adenylyl cyclase → increased cAMP)
• Green on basolateral side and translocation of pure water: ADH activation of V2 on the basolateral membrane of the CD causes translocation of aquaporin 2 to the apical membrane and reabsorption of free water
• Endothelial tile: extrarenal V2 receptors are located on the vascular endothelium
• von Wille brand pool table: ADH activation of V2 on vascular endothelium causes release of von Willebrand factor (vWF)
• 8-ball: ADH activation of V2 on vascular endothelium causes release of factor VIII

• Insipidus fountain: polyuria diabetes insipidus (DI)
• Dehydrating kidney sand trap: nephrogenic DI
• Ignoring water boy: nephrogenic DI occurs when the nephron does not respond appropriately to ADH
• Lift-ium balloons: lithium can cause drug-induced nephrogenic DI
• Chloro-thighs: thiazide diuretics treat nephrogenic DI
• Almond cart: amiloride (a K+ sparing diuretic) treats nephrogenic DI
• Falling lift-ium balloon man: amiloride treats lithium induced DI (blocks Li+ entry into collecting duct cells → increased Li+ clearance)
• Fire extinguisher: NSAIDs (e.g. indomethacin) treat nephrogenic diabetes insipidus

• Dehydrating brain sand trap: central DI
• Absent waterboys: central DI occurs when the pituitary does not release adequate amounts of ADH
• Waterboy entering exogenously: exogenous administration of ADH treats central DI
• Desert-mobile: Desmopressin acetate (DDAVP - a long acting synthetic analog of ADH) treats central DI
• V-2 engine: DDAVP has high specificity for the V2 receptor

• Scratched von Wille brand felt: DDAVP treats von Willebrand deficiency (releases vWF from vascular endothelium)
• Bruised with mucosal bleeding: von Willebrand disease (vWD - deficient vWF) can be associated with increased bruisability and mucosal bleeding (dental procedures, menstrual period)
• Missing 8-ball in “A” frame: DDAVP treats hemophilia A (releases factor VIII from vascular endothelium)
• Bleeding knee joint: hemophilia A (X-linked deficiency of factor VIII) can be associated with hemarthrosis and prolonged bleeding after minor procedures
• Wet mattress: DDAVP treats night enuresis (decreased urine production)

• Falling salty peanut shells: DDAVP can cause hyponatremia)

• Bulging venous golf clubs: ADH is useful in the management of esophageal variceal bleeding (constricts mesenteric arterioles → reduced portal pressure)

• Brain shaped water hazard: syndrome of inappropriate ADH (SIADH)
• Over-hydrating waterboy: SIADH is caused by the overproduction of ADH
• Vaporizer: “-vaptan” suffix of V2 ADH receptor antagonists (e.g. conivaptan, tolvaptan) used to treat SIADH
• Wet pants: vaptans promote free water excretion (correcting hyponatremia)
• Elevated peanuts hitting head: vaptans may cause hypernatremia or central pontine myelinolysis (osmotic demyelination syndrome - due to overly rapid correction of Na+)
• Bicycle: demeclocycline treats SIADH (vaptans are first line)

GH

• Magic growing beans: growth hormone (GH, somatotropin)
• Front of pituitary sack: GH is secreted from the anterior pituitary
• Big "welcome INSIDE" mat: octreotide treats insulinoma
• Sprouting from liver rock: GH stimulates the liver to produce IGF-1
• Tire swing: the GH receptor is associated with JAK tyrosine kinase. JAK STAT
• Striated muscle leaf: GH has anabolic effects in muscle
• Falling fatty donut jar: GH has catabolic effects in adipose tissue
• Growing “welcome INSIDE” mat: insulin-like growth factor 1 (IGF-1) (mediates the growth promoting effects of GH)
• Tall growing vine: IGF-1 is responsible for long bone growth (pubertal growth spurt)

• Short kid: GH therapy is useful in GH deficiency and idiopathic short stature (controversial)
• Turning “X” girl: GH therapy is useful for increasing growth in Turner syndrome (XO)
• Fadre Willi: GH therapy is useful for increasing growth in Prader Willi syndrome (growth failure, obesity, carbohydrate intolerance). Missing piece of chromosome donated by father

• Sermon: mecasermin (recombinant IGF-1) treats growth failure due to severe IGF-1 deficiency
• Falling candy: mecasermin (recombinant IGF-1) can cause hypoglycemia

• Giant: GH secreting pituitary adenoma causes acromegaly (in adults) or gigantism (in children)
• Octagon stop sign: octreotide (somatostatin analog) treats acromegaly and gigantism (inhibit secretion of GH)
• VIP only: octreotide treats VIPoma (neuroendocrine tumor secreting vasoactive intestinal peptide)
• Customers only: octreotide treats carcinoid tumor (ileal tumor with hepatic mets secreting serotonin)
• Giant glucagon packet: octreotide treats glucagonoma
• Giant gas tank: octreotide treats gastrinoma (Zollinger-Ellison syndrome)
• Exposed variceal pipes: octreotide can control bleeding of esophageal varices (decreased portal blood flow and variceal pressure)

• Nauseated: octreotide can cause GI side effects (e.g. nausea , vomiting, abdominal pain)
• Yellow stool: octreotide can cause steatorrhea (decreased pancreatic secretions and gallbladder contractility)

• Burglar with broomstick: cabergoline and bromocriptine (D2 receptor agonist) treat acromegaly (inhibit secretion of GH from pituitary). Also treats hyperprolactinemia
• Double rope ladder: D2 dopamine receptor (activated by cabergoline and bromocriptine)

• ANTS on the tire swing: pegvisomant (a GH receptor antagonist) treats acromegaly. Receptor activation not GH secretion