Study your flashcards anywhere!

Download the official Cram app for free >

  • Shuffle
    Toggle On
    Toggle Off
  • Alphabetize
    Toggle On
    Toggle Off
  • Front First
    Toggle On
    Toggle Off
  • Both Sides
    Toggle On
    Toggle Off
  • Read
    Toggle On
    Toggle Off

How to study your flashcards.

Right/Left arrow keys: Navigate between flashcards.right arrow keyleft arrow key

Up/Down arrow keys: Flip the card between the front and back.down keyup key

H key: Show hint (3rd side).h key

A key: Read text to speech.a key


Play button


Play button




Click to flip

182 Cards in this Set

  • Front
  • Back
5-HT is involved in…?

What are the symptoms of carcinoid syndrome?
Caused by tumor that releases serotonin.

-- bronchospasm
-- GI cramping and diarrhea
-- "odd" flushing of the skin
-- hypotension and
-- increased urinary excretion of 5-HIAA (5-hydroxyindoleacetic acid)
How do we treat carcinoid syndrome?
-- blocks 5-HT1 and 5-HT2 receptors


2. somatostatin analog OCTREOTIDE
-- inhibits the release of 5-HT from the tumor.
Metacloprimide MOA?
1. Blocks D2-receptors in CTZ –S/E’s = EPS, hyperprolactinemia

2. Blocks 5-HT3 receptors in CTZ and at vagal afferents

3. Stimulates 5-HT4 receptors on prejunctional cholinergic neurons to amplify the release of ACh, ACh stimulates muscarinic receptors in the GI tract
Metacloprimide effects?
1. prevents nausea
-- via D2 block in CTZ

2. prevents nausea/emesis
-- via 5-HT3 block in CTZ and at vagal afferents

3. stimulates muscarinic receptors in the GI tract
-- via 5-HT4 receptors on prejxnal cholinergic neurons
-- ↑gastric emptying
-- tightens LES
Metocloprimide S/E’s?
causes EPS, hyperprolactinemia due to Dopa blockade
Metacloprimide therapeutic use?
1. treat esophageal reflux (GERD)

2. Empty the stomach prior to emergency surgery, etc.
antiemetic drug which blocks 5-HT3 receptors in CTZ and at vagal afferent fibers
agonist at 5-HT4 receptors on prejxnal cholinergic neurons
-- amplifies the release of ACh to increase tone in the LES
Cisapride therapeutic use?
1. treat GERD

2. empty the stomach prior to emergency surgery
agonist at 5-HT1B and 5-HT1D receptors to inhibit the release of inflammatory peptides
Sumatriptan therapeutic use?
1. migraine headache

2. cluster headache
1. partial agonist at 5-HT1A receptors

2. opens K+ channels to hyperpolarize neurons
Buspirone therapeutic use?
anxiety treatment
-- slow onset of action
-- no drug dependence
What occurs when you activate Histamine H1 receptors?
1. dilate arterioles

2. contract vascular endothelial cells to ↑ cap permeability

3. contract GI smooth muscle – diarrhea

4. contracts bronchial smoth muscle – asthma

5. stimulates afferent pain receptors – pain/itch
What occurs when you activate Histamine H2 receptors?
1. dilate arterioles

2. ↑ gastric H+ secretion
CLINICAL: A patient has allergy induced hypotension. How do you reverse the hypotension?
Epi + H1 blocker AND H2 blocker
-- need both H blockers to fully reverse the hypotension because the BOTH cause vasodilation of arterioles
Cromolyn sodium?
inhibits mast cell degranulation by preventing ↑ in intracellular Ca++
1. inhibits mast cell degranulation

2. blocks histamine H1-receptors
Olopatidine therapeutic use?
used to tx conjunctivitis assoc w/ seasonal allergy
What are the sedating antihistamines?

What are the NONsedating antihistamines?


How do we prophylactically treat motion sickness?
Need to block central muscarinic ACh receptors



What is Meclizine the DOC for?
Tx of Meniere’s disease
-- hearing loss
-- vertigo
-- tinnitus
from nonsuppurative disease of the labyrinth
What are the H2 receptor blockers? And what do they do?



-- block gastric acid secretion
-- also block allergic responses in the skin
CLINICAL: A patient exposed to poison oak, give him…?
both diphenhydramine (H1-blocker) and cimetidine (H2-blocker) to prevent itching and pain
CLINICAL: A patient w GERD is being treated with cimetidine requires allergen testing by a dermatologist. What must you do?
Must d/c cimetidine to ensure accuracy of skin tests.

Tx GERD w/ omeprazole during allergy testing.
CLINICAL: Patient has insomnia from depression and you tx with a TCA but patient still has insomnia. What can you do next? What complication might you expect?
Give an antihistamine (e.g., diphenhydramine) to induce sleep,

Patient gets urinary retention from combined atropine-like effect of the drug combination
Name some important GI drugs.
Docusate Sodium
Al and Mg hydroxides
induces vomiting by an action at the CTZ and by an irritant action in the stomach which is not blocked by antihistamines
CLINICAL: Which drug induces emesis by stimulating D2-receptors in the CTZ?
synthetic disaccharide

Slow-acting laxative which is converted to small organic acids in the bowel
-- these acids exert an osmotic effect to slowly draw water into the feces.
CLINICAL: A patient with S/S (confusion/coma) of hepatic portal encephalopathy needs treatment. What is the best choice?
LACTULOSE which acidifies the bowel to trap ammonia as ammonium ion
-- ammonium lost in feces
-- plasma [ammonia] falls
-- coma and confusion disappear
Docusate sodium?
a stool softener

an anionic surfactant
-- detergent action allows water to enter feces
-- softens the stool w/o increasing its bulk
How do we treat diarrhea?
loperamide or diphenoxylate which stimulate mu opiate receptors
-- decreased motiility
-- longer time for water absorption
Different choices to treat ulcer symptoms?
1. H2-receptor blockers
-- cimetidine

2. antacids
-- Al and/or Mg hydroxide

3. PGE-receptor agonists
-- misoprostol

4. proton pump inhibitors
-- omeprazole

5. sucralfate
-- mixture of AlOH and sucrose whichs forms a viscous gel at acidic pH
-- gel coats ulcerated tissue
How do we get rid of H.pylori?
Causes ulceration

Triple Antibiotic Therapy
1. clarithromycin
2. amoxicillin
3. omeprazole

“CiAO!” to H. pylori
CLINICAL: Which antiulcer drug does not alter stomach pH?
CLINICAL: Patient on propranolol takes cimetidine for heartburn and develops severe bradycardia. Why?
Cimetidine inhibits CYP450 and thus blocks the metabolism of propranolol
CLINICAL: Pat being tx w doxycycline. Which drug is contraindicated?
Al/Mg antacids
CLINICAL: Patient needs emergency surgery and you need to empty stomach/prevent reflux. Drug?
-- prokinetic in stomach
-- tightens LES
CLINICAL: Cancer chemo patient has n/v and noctural acid reflux. Treat with?
CLINICAL: Patient treated with drug for Crohn’s disease or ulcerative colitis develops hepatic damage or bone marrow depression. What is the drug?
sulfasalazine -->patient is a slow acetylator.

Sulfasalazine consists of sulfapyridine conjugated to 5-aminosalicyclic acid.

Bacterial E's in the large bowel hydrolyze sulfasalazine to free sulfapyridine and free 5-aminosalicyclic acid.

The 5-aminosalicyclic acid is an NSAID, and the sulafapyridine, which is metabolized by acetylation, suppresses the bone marrow.
CLINICAL: s/s of laxative abuse w castor oil or bisacodyl?
muscle weakness
abnormal architecture inner GI wall
1. Inhibits platelet aggregation by irreversibly inhibiting the COX-1 in platelets via acetylation to prevent the synthesis of thromboxane A2 (TXA2);
-- ↑ bleeding time

2. Aspirin blocks platelet aggregation caused by arachidonic acid but not the aggregation caused by PGG2 and PGH2 (cyclic endoperoxides)
Therapeutic use of ASA?
1. Inhibition of platelet aggregation relieves chest pain in unstable angina
-- platelet count is normal, but bleeding time is increased

2. prophylactic for MI, stroke
ASA kinetics?
1. Aspirin converted to salicylate during first-pass metabolism in the liver

2. Large doses exhibit nonlinear kinetics - how to recognize non-linear kinetics? The disappearance of plasma salicylate
-- plasma [salicylate] falls by CONSTANT amount during zero order elimination b/c the enzymes responsible for hepatic clearance are saturated w/ substrate
-- plasma [salicylate] falls by 50% during first-order elimination (hepatic enzymes are no longer saturated)
The appearance of plasma salicylate during p.o. dosing…?
When the dose is doubled, the plasma concentration should double.

If the doubling of the dose causes [salicylate] to increase more than two-fold, the hepatic enzymes have become saturated and elimination has changed from first-order to zero-order
-- the ↓ in Cl will cause the half life to ↑
Signs/symptoms of ASA OD?
1. n/v, tinnitus

2. respiratory alkalosis
-- aspirin uncouples oxidative phosphorylation in skeletal muscle
-- increases pCO2 --> increases respiration

3. metabolic acidosis
-- as CO2 production increases, a metabolic acidosis develops

4. children skip the alkalosis step and go directly to acidosis w low blood pH and low bicarbonate
Treatment of ASA OD?
1. make urine alkaline to enhance the renal clearance of salicylate
-- acetazolamide or NaHCO3

2. infuse bicarbonate to correct acidosis
an inhibitor of PDEase in platelets which potentiates the antiplatelet effect of aspirin and prostacyclin (PGI2)
CLINICAL: half-life of aspirin as only 1 h, why does it inhibit platelet inhibition for a longer period?
Aspirin irreversibly acetylates active site of COX-1 in platelets
CLINICAL: How does aspirin prevent platelet aggregation when it is not taken in doses large enough to maintain a steady-state plasma concentration?
Aspirin irreversibly acetylates active site of COX-1 in platelets
CLINICAL: patient has intermittent episodes of hemiplegia which resolve spontaneously; would like to treat with aspirin, but patient has aspirin “hypersensitivity.” Treat with?
CLINICAL: What is the causative compound in aspirin hypersensitivity?
CLINICAL: DOC for menstrual cramps
CLINICAL: Baby has patent ductus arteriosus. Close with?
CLINICAL: Want to keep a patent ductus open prior to surgery. What drug will do this ?
-- PGE1 analog dilates the ductus arteriosus
CLINICAL: Pt treated w/ NSAID develops GI ulceration. MOA?
inhibition of gastric PG synthesis
CLINICAL: A patient with nasal polyps who has wheezing with aspirin needs a antipyretic drug. What do you use?
CLINICAL: Acetominophen is _______, but not ______.
IS antipyretic

NOT anti-inflammatory
CLINICAL: Drug OD; initially blood chemistries normal, but 36 h later see increase in AST and ALT. What is the drug? Treatment?

treat with n-acetylcysteine to replenish glutathione
What are the adverse effects of NSAIDs?
1. gastric ulceration
-- results from decreased PG synthesis in stomach
-- prevent or tx with misoprostol (methyl-PGE1 analog)

2. interstitial nephritis
-- hematuria, proteinuria, flank pain
-- decreased RBF and GFR causing oliguria
CLINICAL: Patient on NSAID for tendonitis for 2 weeks develops fever and hematuria. Dx?
acute interstitial nephritis from NSAID use
CLINICAL: histologic photo of kidney tissue with lots of lymphocytes: diagnosis?
Interstitial nephritis caused by ASA or other NSAID
CLINICAL: Patient with CHF takes ibuprofen. Effect on kidneys?
Constriction of afferent arteriole lowers RBF and GFR to cause salt\water retention

No PG's to partially inhibit the effects of ADH in the collecting duct = water retention.
CLINICAL: Patient tx with NSAID for arthritis exhibits ↓ [Hb] and Hct and has occult blood in his stool. Which drug could be addded to tx to reverse this pathology?
Name the drugs to treat gout.


Colchicine MOA?
binds to tubulin to block the formation of microtubules
-- thus inhibits phagocytosis of urate crystals by WBC’s
Colchicine therapeutic use?
Tx the pain of acute attacks
Allopurinol MOA?
Inhibits xanthine oxidase to block the synthesis of uric acid from purines
CLINICAL: Patient with a renal transplant is taking the immunosuppressant drug azathioprine. Patient develops gout. Which gout drug is contraindicated?
-- azathioprine is converted to the cytotoxic agent 6-mercaptopurine (6-MP) which kills antigen presenting cells and T- and B-lymphocytes
-- 6-MP is inactivated (metabolized) by xanthine oxidase

(xanthing oxidase is inhibited by allopurinol)
CLINICAL: Patient with lymphoma is treated w/ chemo. Which drug will prevent ↓ in renal function?

Chemo kills lymphoma cells which release nucleic acids which are converted to urate
-- excessive urate in urine crystalizes to occlude the collecting ducts, pelvis and ureters
-- rapid, progressive renal dysfunction develops
-- allopurinol prevents the formation of urate
Probenacid MOA?
Enhances renal clearance of urate (uricosuric)
-- urate stones may form, so keep the urine alkaline w/ sodium citrate

(Probenacid + large doses ASA)
CLINICAL: Which gout drugs are not uricosuric?
allopurinol and colchicine
CLINICAL: DOC for severe hyperuricemia?
CLINICAL: Patient with gout treated w probenecid gets remineralization of bone. Why?
increased urinary excretion of urate
CLINICAL: Patient takiing a small daily dose of aspirin may develop gout whereas a large daily dose of aspirin is used to treat gout. Why the discrepancy?
Small doses of aspirin enhance urate reabsorption in the renal tubule

Large doses of aspirin are uricosuric
CLINICAL: Patient being tx for gouty arthritic develops leukopenia. Which drug?
S/S hypothyroidism?
1. ↓HR, SV, CO, PP, BP; ↑TPR, low output HF
2. ↓ DTRs, stiffness and muscle fatigue
3. pale, cool, puffy skin, hypohydrosis
4. puffy face, large tongue, drooping eyelids, periorbital edema
5. ↓appetite, weight fain, constipation, lethargic
6. water retention, hyponatremia, pleural/peritoneal/pericardial effusions
7.↓ erythropoiesis, anemia
8. hyperprolactinemia, amenorrhea, galactorrhea, menorrhagia
9. ↓ metabolic rate, ↑ cholesterol/TGs
10. ↓ drug metabolism
S/S hyperthyroidism?
1. ↑HR, SV, CO, PP; ↓TPR, angina, high-outpt HF, atrial fibrillation
2. ↑DTRs, weakness and muscle fatigue
3. warm, moist skin, heat intolerance, pretibial dermopathy, hyperhydrosis
4. lid lag, diplopia, exopthalmos (proptosis)
5. ↑appetite, diarrhea, weight loss
6. nervous, emotionally labile
7. mild polyuria, pedal edema
8. ↑ erythropoiesis, anemia
9. amenorrhea
10. ↑ metabolic rate, ↓cholesterol/TG’s
11. ↑drug metabolism
What medication can we use to control the symptoms of hyperthyroidism?

Controls autonomic symptoms
-- tachycardia
-- palpitations
-- fatigue
-- weight loss
-- diaphoresis
-- heat intolerance
-- tremor and anxiety

DOES NOT alter the underlying excessive production of T4
What else is special about prolanolol?
It also blocks the peripheral conversion of T4 to T3 by blocking the 5-diodinase
****(no other beta blocker does this, thus this is the DOC)
Propanolol dosing?
Metabolism is very rapid in hyperthyroidism, so LARGE doses may be required initially
What is the MAIN drugs in treating hyperthyroidism?
1. Prevents iodide organification by inhibiting the enzyme THYROID PEROXIDASE which converts iodide (I-) to iodine (Io)

2. Blocks coupling of MIT and DIT which are req’d for formation of T3 and T4

**Both cause decreases synthesis but NOT release of T4 and T3. Thus, their onset of action is slow

3. PTU also blocks the peripheral conversion of T4 to T3 (methimazole does not)
Therapeutic effects of PTU?
1. depletion of T4 stores takes 3-4 wks, so rate of onset is slow

2. No “escape” phenomenon occurs

3. After the production of a euthyroid state w/ this drug, 20-40% of pts go into remission w/in 1 month – 2yrs. However, eventual relapse rate is 60-80%

4. If cessation of therapy results in reappearance of hyperthyroidism, patients are treated w/ reactive iodine (131I)
PTU toxicity?
1. reversible agranulocytosis in <1% of pts

2. PTU has antivitamin K activity and potentiates the effects of warfarin

3. skin rash w/ itching – treat w/ histamine

4. Use PTU instead of methimazle in pregnant women
-- PTU highly bound to plasma proteins and less likely to cross the placenta as compared to methimazole
-- use minimally effective doses and shortest treatment periods possible
-- about 10% of neonates will have goiter if exposed to PTU in utero
What is the first-line treatment for hyperthyroidism?
Propanolol + PTU
CLINICAL: What are the usual causes of hyperprolactinemia and their treatment?
blockade of D2-dopamine receptors and increased TRH in hypothyroidism cause hyperprolactinemia.

In hypothyroidism, tx w thyroxine to suppress plasma [prolactin]
CLINICAL: Pregnant woman develops hyperthyroidism. How to treat?
CLINICAL: Patient w recurrent V. tach/V. fib. develops hyper- or hypothyroidism while taking amiodarone. Why?
Amiodarone is 37% iodide by weight.

This iodide can either prevent the conversion of T4 to T3 (hypothyroidism), or it can serve as a substrate for the synthesis of T3 by thyroid peroxidase (hyperthyroidism)

A 21y.o. man who is a farmer comes to see you b/c he has recently developed
-- extreme thirst, polydipsia, polyuria
-- excreting 10-12L of clear urine/day and has to get out of bed 3-4 times a night to urinate
-- heavy exercise in hot weather causes him to feel faint and produces even greater thirsl

PE reveals
-- healthy young male w/ normal neuro tests and BP
-- Serum Na concentration and osmolalaity are at a high end of the normal range
-- serum glucose conc is 108mg.dL (not hyperglycemic)
-- urinalysis is NEG for glucose and yields osmolality of 178mOsm
-- treatment w/ desmopressin by nasal spray increases urinary osmolality to 226mOsm after one hour.
-- Radio exam of pituitary is negative

What is the Dx?
Central (neurogenic) diabetes insipidus (DI)

Characterized by the lack of release of sufficient ADH from the posterior pituitary
-- may be idiopathic of caysed by trauma, malignancy, granulomas, sarcoidosis and infections

Dissection of the pituitary stalk by head trauma causes a transient DI
-- DI disappears b/c AVP is actually synthesized in the hypothalamus and eventually normal osmotic stimuli elicits the release of AVP from the hypothalamus

Normal physiological stimuli to ADH release (↑serum osmolality, volume depletion and hypotension) either do not cause the release of ADH or cause only a small increase in plasma ADH concentration
Central DI treatment?
-- long t1/2 bx it is resistant to degradation by peptidases
-- very selective for renal V2-receptors
CASE 4 (continued)

Suppose that treatment w/ desmopressin did not cause urinary concentration in this patient.

What is the dx?
Nephrogenic diabetis insipidus (NDI)

1. Plasma ADH rises in response to an increase in plasma osmolality

2. Renal tubule is unresponsive to ADH (complete NDI) or a larger conc of ADH is req’d to produce antidiuresis (partial NDI)
Tx for Nephrogenic DI?

2. if that doesn’t work, try indomethacin
Li-induced DI: treatment?
1. amiloride
-- prevents entry of Li+ into principal cells of LDT/CD



Male pt w/ pulmonary small (oat) cell carcinoma has
-- serum [Na] of 132mEq/L (↓)
-- serum osmolality of 266 mOsm (↓)
-- urinary osmolality of 418 mOsm (↑)
-- serum uric acid is less than 2mg/dl (nl = 2-8)
-- BUN is less than 8mg/dl (nl = 8-20)
-- Hct is 33 (nl = 44-54)
-- No peripheral edema or evidence of abnormal adrenal or thyroid fxn is detected

What is the most likely cause of the hyponatremia and abnormalities of serum and urinary osmolality?
Syndrome of inappropriate ADH release (SIADH)

1. Secretion of ADH is autonomous and independent of serum osmolality

2. Excessive retention of water causes hypervolemia and dilutional hyponatremia which is usually asymptomatic as long as serum conc falls slowly or does not fall below 120mEq/L
-- NB: recall that furosemide and HCTZ can cause dilutional hyponatremia by a direct renal effect which is independent of AVP)
What are the causes of SIADH?
1. nonendocrine neoplasms, esp small cell lung cancer

2. CNS disorders
-- trauma
-- CVA
-- TB
-- acute encephalitis

3. pulmonary infections
-- TB
-- abscess

4. adrenal insufficiency or hypothyroidism (hypotension induces AVP release through baroreflex)
How do we treat hyponatremia assoc w/ SIADH?
1. Restrict water intake to 800-1000ml/day
-- urine output will exceed this value and plasma Na conc will rise as water is lost

2. Infusion of 3% NaCl
-- used to raise serum Na conc in SEVERE symptomatic hyponatremia
-- do NOT increase serum Na conc faster than 2mEq/L/h to avoid pontine melinosis

3. Furosimide
-- action in the ascending L of H decreases the concentrating capacity of the kidney
-- usually give K supplements to prevent hypokalemia

4. Demeclocycline (a tetracycline antibiotic)***
-- inhibits antidiuretic action of AVP in the collecting duct
-- used to treat SIADH when serum Na < 120mEq/L and the pt has severe neuro symptoms
Overview of treatment of DI…
Complete Central DI
-- desmopressin

Partial Central DI
-- desmopressin

Partial Nephrogenic DI
-- HCTZ or large doses of desmopressin

Complete Nephrogenic DI
-- HCTZ or indomethacin

Li induced DI
-- amiloride (doesn’t alter Li clearance)

-- demeclocycline
Review diagram in respiratory lecture that shows the different sites where bronchodilators can act. (pg 182 in respiratory syllabus)
Epi site of action? Produces bronchodilation via direct stimulation of 2 adrenoceptors (2 > 1> )
-- rapid onset of action
-- emergency relief
Theophylline site of action?
Inhibits phosphodiesterase which degrades cyclic AMP

A specific adenosine receptor antagonist

Dose-related bronchodilation
Cromolyn sodium site of action?
Prevents immediate and delayed Ag-induced degranulation of mast cells
-- prevents increase in intracellular Ca concentration induced by formation of IgE cross-bridges on cell surface

Must be used prophylactically
Ipratropium site of action?
Muscarinic receptor blockade in smooth muscle of large and small airways
-- prevents vagally induced bronchoconstriction
-- no antihistaminic or antiinflamm effects
Beclomethasone site of action?
Corticosteroid which
1. inhibits recruitment of leukocytes and macrophages into affected areas and prevents autocoid release from these cells

2. prevents and reverses early inflamm process

3. prevents and reverses late inflamm process

4. inhib synth and release of inflamm PGs and LTs, PAF, TNF, IL-1, and plasminogen activator
Albuterol site of action?
B1-adrenoceptor stimulation
-- bronchodilation
-- preferentially dilates smaller and more peripheral airways
-- inhib release of imflamm cmpds in mast cells
-- indirectly inhib accum of eosinophils
-- improves mucociliary transport
Terbutaline site of action?
Same as albuterol
Zafirlukast site of action?
Competitive antagonist of receptors for LTC4 and LTD4 (SRS-A cmpds)
-- decrease in late bronchoconstriction caused by challenge w/ allergens
-- max therapeutic effect after one wk therapy
CLINICAL: Patient treated with propranolol; which drug will still bronchodilate?
theophylline or aminophylline act via intracellular inhibition of PDEase
CLINICAL: Asthmatic patient treated with theophylline develops a sinus infection which requires tx w an antibiotic. Which antibiotic would require adjustment of the daily dose of theophylline?
Erythromycin because it inhibits CYP450 which is the enzyme that metabolizes theophylline
CLINICAL: Asthmatic patient taking theophylline develops seizures after taking an OTC drug for heartburn. What heartburn drug are they using?
-- blocks the CYP450 which metabolizes theophylline
CLINICAL: Which drug causes the greatest increase in FEV1 with the smallest increase in HR?
CLINICAL: patient w/ exercise-induced asthma uses cromolyn prophylactically. MOA ?
cromolyn prevents Ca++ influx into mast cells when IgE bridges form
-- no mast cell degranulation
Glucocorticoid MOA?
1. Inhibit the production of Il-1 and IL-6 by macrophages and monocytes
2. Inhibit antibody synthesis by B-cells
3. Prevent the functions of cytotoxic T-cells
4. NO bone marrow depression
CLINICAL: Which drug suppresses cellular immunity, blocks the synthesis of PG’s and LT’s and increases neutrophil count in blood?
A Glucocorticoid

NB: Glucocortiocoids decrease the number of B & T lymphocytes, monocytes, eosinophils and basophils by stimulating their movement from the blood into lymphoid tissue.
-- However, glucocorticoids acutely increase the release of neutrophils from bone marrow and prevent their migration out of the blood into tissues
Cyclosporin MOA?
inhibits calcineurin to prevent the production of IL-2 by helper T-cells
Mycophenolate MOA?
Inhibits inosine monophosphate dehydrogenase which prevents the synthesis of purines in T & B lymphocytes.

Unlike other cells from the bone marrow, T & B lymphocytes lack the enzyme HGPRTase for purine synthesis
What are the cytotoxic immunosuppressants?

Azathioprine MOA?
converted to 6-mercaptopurine (purine analog = antimetabolite) which interferes with the nucleic acid synthesis that is needed for proliferation of B- and T-cells
Cyclophosphamide MOA?
alkylates DNA

S/E = hemorrhagic cystitis
Vitamin D acts via…?
gene transcription and ion channels in the GI brush border
Osteocalcin reflects activity of the…?
CLINICAL: Patient with vitamin D toxicity exhibits…?
hypercalcemia with hypercalcinuria


anorexia, nausea, weight loss


dehydration (hypercalcemia impairs renal concentrating ability of kidney)
CLINICAL: Treatment of Vit D toxicity?
1. aggressive hydration w isotonic saline

2. furosemide to enhance urinary Ca++ excretion

3. plicamycin (mithramycin)
-- a cytotoxic antibiotic drug that inhibits bone resorption
CLINICAL: Patient w renal failure has low plasma Ca++ Tx w ?
1,23diOH-Vitamin D
CLINICAL: Patient w Paget’s disease
-- a localized bone dz w uncontrolled osteoclastic bone resorption and secondary in the formation of poorly organized bone
-- exhibits hearing loss, bone pain, bone deformity,
-- increased serum alkaline phosphatase
-- increased urinary hydroxyproline
-- high output HF
-- immobilization hypercalcemia

Treat with?
-- decrease bone pain, bone deformity, hearing loss and hypercalcemia.

Calcitonin will decrease serum Ca++ and PO4- by inhibition of osteoclastic bone resorption and decreasing the reabsorption of Ca++ and PO4- by the kidney.
Alendronate ad etidronate?

1. inhibit the resorption of bone by inhibiting the ability of osteoclasts to dissolve hydroxyapatite crystals.

2. Increase bone mass and decrease fractures.
Therapeutic use of bisphosphonates?
1. prevent glucocorticoid-induced osteoporosis
2. used with calcitonin to treat Paget’s dx

3. used an alternative to HRT to prevent post-menopausal bone loss
CLINICAL: A post-menopausal woman requires tx to maintain bone mass, but cannot take estrogen b/c her mother and sister had breast cancer. Tx with ?
Alendronate or Etindronate
CLINICAL: A patient tx with steroids develops hypocalcemia. Why?
Steroids antagonize the effects of vitamin D on the GI absorption of Ca++ ;

Less Ca++ absoprtion --> ↑ [PTH] --> ↑ bone resorption --> ↑ renal excretion of Ca++ --> hypocalcemia and osteoporosis
Hypochromic, microcytic anemia?
Fe-deficiency anemia caused by:
1. increased Fe requirement
2. decreased absorption of Fe
3. blood loss
S/S hypochromic, microcytic anemia?
feel light-headed
pica = craving for clay, laundry starch, ice
Labs for hypochromic, microcytic anemia?
↓ serum [ferritin]
Tx for hypochromic, microcytic anemia?
ferrous iron

Vitamin C enhances GI absorption of ferrous iron
Normochromic, Macrocytic anemia?
Megaloblastic anemia caused by deficiency of:
1. folate (lack of intake)
2. Vitamin B12 (no GI absorption)
Blood cells in Normochromic, Macrocytic anemia?
ALL cells affected
-- large RBCs
-- segmented PMNs
-- abnormal platelets
S/S of folate deficiency?
sore tongue
S/S of B12 deficiency?
same as for folate plus a neurological syndrome =
1. paresthesias of distal extremities
2. sensory disturbances which may progress to spastic ataxia

caused by demyelination of nerves fibers in the dorsolateral spinal column
-- vitamin B12 is necessary for the conversion of methylmalonyl CoA to succinyl CoA which is needed for the synthesis of myelin
-- no vitamin B12 = demyelination
Can peripheral blood smears be used to determine what the deficiency is in megaloblastic anemia?
Folate intake is gauged by measuring…?
RBC [folate] which reflects dietary intake over the past 2-3 months.
B12 deficiency usually results from______. What test is used to determine cause of deficiency?
Usually results from lack of GI absorption

Schilling’s test used to measure efficiency of B12 absorption
How do we treat folate deficiency?
p.o. folate.

Some patients cannot absorb folate from the GI tract and must be treated with folate i.m.
How do we treat B12 deficiency?
i.m. injection of cyanocobalamin or hydroxycobalamin
-- tx must be continued for life.
CLINICAL: A patient with normochromic, macrocytic anemia has distal paresthesias. The patient is treated with p.o. folate and the anemia disappears, but the neurological S/S worsens. What happened?
Folate will correct the megaloblastic anemia, but the neurological syndrome results from B12 deficiency because B12 is needed for the synthesis of myelin
CLINICAL: A patient being treated with phenytoin, isoniazid, pyrimethamine, trimethoprim or methotrexate develops normochromic, macrocytic anemia. Why?
Phenytoin and isoniazid
-- interfere with the GI absorption of folate.
-- phenytoin --> epilepsu
-- isoniazid --> TB

Pyrimethamine, trimethoprim and methotrexate
-- inhibit DHF reductase
-- pyrimethamine --> FQ resistant malaria
-- trimethoprim --> w/ sulfa as antibiotic
-- methotrexate --> cancer treatment and in small doses for intractable arthritis
CLINICAL: A patient on hemodialysis develops normochromic, macrocytic anemia. Why and what to do about it?
Hemodialysis removes plasma folate.

Patients on hemodialysis must be treated with
1. erythropoetin (EPO)
-- b/c kidneys not working

2. folate and ferrous iron
-- “building blocks” for RBC production
CLINICAL: A patients with a Hct. 24 is started on hemodialysis. After tx with EPO, folate and ferrous iron, the patient develops HT. Why?
As the Hct is increased by increased production of RBC's, the viscosity of blood rises.

According to Poiseuille's law, resistance is directly related to viscosity.

The increase in Hct increases the resistance to flow, so BP increases.
CLINICAL: Which drug could be used for "blood doping" (i.e., increased Hct) in competitive cycling?
EPO, epoetin alfa, darbepoetin
CLINICAL: A patient is given a PPI for gastric ulcers and develops B12 deficiency. Why?
PPIs decrease release of intrinsic factor necessary for B12 absorption
Glucocorticoid MOA?
1. Inhibit the production of Il-1 and IL-6 by macrophages and monocytes
2. Inhibit antibody synthesis by B-cells
3. Prevent the functions of cytotoxic T-cells
4. NO bone marrow depression
Glucocorticoid effects?
1. ↑ blood glucose via ↑ gluconeogenesis & glycogenolysis
2. ↓ protein synth, ↓ bone formation, ↓ wound healing
3. ↑ lipolysis --> ↑ serum lipids
4. ↓ inflammation and ↓ cell-mediated immunity via variety of mechanisms
Glucocorticoid adverse effects?


GI ulcers (from decreased gastric PG synthesis)


Cushing’ s syndrome

Adrenal insufficiency w/ sudden w/d
Signs and Symptoms of Cushing’s Disease?
buffalo hump

Moon facies

Abdominal striae

centripetal obesity

NB: DO NOT CONFUSE 17-OH-steroids from the cortisol pathway with 17-ketosteroids from the testosterone pathway.
CLINICAL: Patient with malar (buterfly) rash, arthritis, polyserositis: urine shows proteinuria and microscopic hematuria. Dx? Tx with?

prednisone or any other –sone or –lone drug
CLINICAL: Which synthetic glucocorticoid is used to differentiate bilateral adrenal hyperplasia from adrenal carcinoma?

-- will depress serum cortisol by 50% in adrenal hyperplasia caused by a pituitary adenoma (Cushing’s dx)

-- have no effect on serum cortisol in adrenal carcinoma.
CLINICAL: Which drug will increase the urinary excretion of 17-ketosteroids (testosterone) in a patient with bilateral adrenal hyperplasia (i.e., Cushing’s dx) w/o affecting urinary 17-OH-steroids (cortisol) in a patient with adrenal carcinoma?

Blocks the CYP45011 that converts 11-deoxycortisol ( a 17-OH-steroid) to cortisol so there is no cortisol to feedback inhibit the pituitary.
-- ACTH rises and stimulates adrenal steroid synthesis causing even more 11-deoxycortisol to be produced.
-- This generalized increase in adrenal steroid synthesis also increases the synthesis of testosterone which is metabolized to 17-ketosteroids
-- So the urinary excretion of 17-ketosteroids also increases.

In a patient with adrenal carcinoma, cortisol produced by the tumor suppresses ACTH release so the normal adrneal cortex atrophies and thus cannot respond to the increase in ACTH secretion caused by metyrapone
CLINICAL: Which drug will suppress plasma cortisol in a patient with normal pituitary/adrenal function
ketoconazole blocks the CYP450scc
CLINICAL: Which drug can cause a “medical adrenalectomy”?

-- blocks alladrenal and extra-adrenal steroid synthesis b/c it prevents the conversion of cholesterol to pregnenolone

-- it can be used to tx Cushing's syndrome
CLINICAL: A patient tx wih steroids develops a GI ulcer. MOA?
inhibition of gastric PG synthesis
S/E’s of estrogens?
thromboembolic disease
CLINICAL: A patient with S/S of hyperestrogenism (breast tenderness) is on a drug to enhance fertility. What is the drug?

Blocks CNS estrogen receptors causing increased putsatile release of GnRH which enhances the secretion of FSH – ovulation.
CLINICAL: Estradiol contraindicated in a patient w a history of thromboembolic dx (DVT's). Why?
estradiol increases the synthesis of clotting factors
CLINICAL: Patient has breast cancer. TX?
-- blocks estrogen receptors
CLINICAL: Why do OCP's which contain an estrogen also contain a progestin?
progestin prevents the endometrial hyperplasia caused by the estrogen
CLINICAL: Which compound can be used to maintain bone mass in a postmenopausal woman who has had breast cancer?


-- bisphosphonate
CLINICAL: Tx with an estrogen decreases the risk of…?
osteoporosis and colorectal cancer
Fluoxymesterone and nandrolone?
androgens which are used for their anabolic effects.

1. prevent the catabolic action of cortisol.

2. stimulate protein synthesis and erythropoiesis
CLINICAL: A body builder treats himself w / fluoxymesterone (an anabolic steroid). How his spermatogenesis be affected?
Spermatogenesis is suppressed
-- fluoxymesterone stimulates hypothalamic androgen receptors which inhibit the release of GnRH
-- so no FSH is secreted by the pituitary
CLINICAL: A body builder has an enlarged heart and spleen, borderline DM and mild HT, but androgenic steroids are not present in his urine. What drug is he abusing?
growth hormone
-- increases the production of insulin-like growth factors (IGF's)
CLINICAL: Older man has arthralgia, fluid retention and hyperglycemia. What drug has the effect?
Growth hormone
CLINICAL: What drug will suppress the secretion of GH hormone in a patient with acromegaly?
bromocriptine or octreotide
CLINICAL: Patient with BPH or hair loss. Tx w ?
Finasteride blocks the synthesis of dihydrotestosterone (DHT) by inhibiting 5-reductase
CLINICAL: Which drug is an androgen receptor antagonists?
CLINICAL: How to tx a young boy w cryptorchidism?
human chorionic gonadotropin (hCG)
Leuprolide, goserelin and nafarelin therapeutic use? MOA?
1. prostatic cancer

2. endometriosis

3. leiomyomas (uterine fibroid tumors)

4. In protocols for in vitro fertilization, they are used to suppress ovarian activity followed by tx with exogenous gonadotrophins (hCG) to achieve synchronous follicular development

Continuous administration via i.m. depot injection desensitizes the GnRH receptors of the pituitary and thus shuts off the release of LH and FSH.
Glucagon is synthesized by?
Pancreatic  cells

It is a 29a.a. polypeptide
Metabolic effects of glucagon?
1. increase in plasma glucose at the expense of liver glycogen stores

2. increases hepatic CAMP to activate phosphorylase a activity and the enzymes of gluconeogenesis.

3. NO effect on glycogen stores in skeletal muscle.
Cardiac effects of glucagon?
increased dp/dt and HR via increased CAMP
Medical uses of glucagon?
1. tx of severe hypoglycemia

2. tx of poisoning w -blocker
-- increases dp/dt independent of -receptors

3. diagnosis of type 1 DM
-- large doses of glucagon increase insulin and C-peptide release from -islet cells
-- no C-peptide released in type 1 DM
CLINICAL: Patient with diabetic ketoacidosis. Tx with?
1. lispro or regular insulin i.v.

2. i.v. fluids for rehydration

3. potassium to prevent hypokalemia as insulin drives glucose into liver, skeletal muscle and fat cells.
CLINICAL: Which drug decreases hepatic glucose production in a type 2 diabetic patient without enhancing the pancreatic secretion of insulin?