Diuretic, Autocoid, Gout, Nsaid Drugs

Front 1

Acetazolamide

Back 1

Carbonic Anhydrase Inhibitor

Inhibits bicarbonate reabsorption in the proximal tubule.

Produces a mild diuresis by inhibiting Na reabsorption via antiport with H+. (no H+ because no CA). This is a mild diuresis because Na is also reabsorbed from other areas .

USE:
* Mountain Sickness
* Glaucoma
* Tx Metabolic Alkalosis
* Can potentiate the efficacy of loop diuretics

SE:
* Contrainidicated with Sulfonamide Allergies.
* Metabolic Acidosis
* Hypokalemia (negative lumen potential increases K secretion).

INTERACTIONS
* Potentiates Loop Diuretics

Front 2

Furosemide

Back 2

Loop Diuretic

Block the Na/Cl/K coporter in the thick ascending limb of the LOH.

An accumulation of K into the cell leads to a back diffusion of K into the tubular lumen.
This leads to the development of a lumen postive potential…which ist he driving force of K and Ca reabsorption via paracellular pathways. (This is normal physiology). Na reabsorption here allows for a hypertonic medullarry interstitium.

So they lead to diuresis in two places:
1) Thick Ascending limb of the loop of henley - increases urine flow
2) Collecting Duct: Less concentrated medullary interstitium and excessive Na in the tubule...cannot concentrate urine

*LOOP DIURETICS SECRETE ISO- OSMOTIC URINE!! (not diluted or concentrated.) (300 mosm/kg H2O).

* LOOP DIURETICS increase renal and vascular Prostaglandin production...causing VD of vasculature and renal arteries.

USE:
* Edema
* In combo with antihypertensive drugs to reduce intravascular volume.
* Emergency situations : Acute pulmonary edema.
* Tx Hypercalcemia

SE:
* Hypokalemia
* Hypocalcemia
* Hypomagnesemia
* Hyponatremia
* Metabolic alkalosis (Inc Na delivery to principal cell of CD cause neg lumen pot. Proton pump in the intercalculated cells is stim by a more negative lumen environment)
* Hyperuricemia (Gout)..compete at OAT transporters b/c protein bound)
* Hyperglycemia (Bind to ATP dep K channel in pancreatic beta cells stay in the open state...this decreases insulin release.)
* Ototoxicity - REVERSIBLE

CONTRAINDICATIONS
* Sulfonamide allergies

DRUG INTERACTIONS
* Potentiate the effects of Digoxin and Lithium
---> A decrease in K level in the body will potentiate Digoxin's effect at the Na/K ATPase, potentiating it's action.
---> A decrease in Na reaborption will DECREASE lithium clearance.
* Probenecid has decreased activity d/t competition at OATs

Front 3

Ethacrynic Acid

Back 3

Loop Diuretic

Block the Na/Cl/K coporter in the thick ascending limb of the LOH.

NORMAL PHYSIOLOGY: An accumulation of K into the cell leads to a back diffusion of K into the tubular lumen.
This leads to the development of a lumen postive potential…which ist he driving force of Mg and Ca reabsorption via paracellular pathways. (This is normal physiology). Na reabsorption here allows for a hypertonic medullarry interstitium.

So they lead to diuresis in two places:
1) Thick Ascending limb of the loop of henley - increases urine flow
2) Collecting Duct: Less concentrated medullary interstitium and excessive Na in the tubule...cannot concentrate urine

*LOOP DIURETICS SECRETE ISO- OSMOTIC URINE!! (not diluted or concentrated.) (300 mosm/kg H2O).

* LOOP DIURETICS increase renal and vascular Prostaglandin production...causing VD of vasculature and renal arteries.

USE:
* Edema
* In combo with antihypertensive drugs to reduce intravascular volume.
* Emergency situations : Acute pulmonary edema.
* Tx Hypercalcemia

SE:
* Hypokalemia
* Hypocalcemia
* Hypomagnesemia
* Hyponatremia
* Metabolic alkalosis (Inc Na delivery to principal cell of CD cause neg lumen pot. Proton pump in the intercalculated cells is stim by a more negative lumen environment)
* Hyperuricemia (Gout)..compete at OAT transporters b/c protein bound)
* Hyperglycemia (Bind to ATP dep Na/K channel in pancreatic beta cells stay in the open state...this decreases insulin release.)
* Ototoxicity - IRREVERSIBLE!!

CONTRAINDICATIONS
* NONE - not a sulfonamimetic

DRUG INTERACTIONS
* Potentiate the effects of Digoxin and Lithium
---> A decrease in K level in the body will potentiate Digoxin's effect at the Na/K ATPase, potentiating it's action.
---> A decrease in Na reaborption will DECREASE lithium clearance.
* Probenecid has decreased activity d/t competition at OATs

Front 4

Indapamide

Back 4

Thiazide Diuretic ( not as powerful b/c only 5% of your Na is reaborbed in the DCT)

Blocks the active Na/Cl coporter on the lumenal membrane of the distal convoluted tublule (where 5% of Na is reabsorbed). This stimulates the Na/Ca antiporter on the basolateral membrane...increasing Ca reabsorption.

USE:
* Edema
* Nephroliathsis kidney stones (caused by hypercalcuria)
* Nephrogenic diabetes insipidous: incr sensitivty of V2 receptors. Decr UO by 50%.
* HTN: Decreased SVR: Increase renal/ vascular prostaglandin production, causing VD.

SE:
* Hypercalcemia (stim reabsorption of Ca that is independent of PTH!!!)
* Hypokalemia
* Hyponatremia
* Hyperuricemia: some of them are protein bound and some of them are not. The Protein bound ones can cause gout by competing at OAT transporters.
* Hyperglycemia: Bind to ATP dep K channel on the pancreatic beta cells, leaving it in the open state. This suppresss insulin release.
* Diuretic efficacy is limited in pts with GFR < 50 ml/min.
* The ONLY thiazide diuretic that does not cause incr triglycerides, LDL, decr HDL. The only thiazide that is good! for pts with CV disease.
* Reversible sexual dysfunction due to a rapid loss of water volume.

DRUG INTERACTIONS:
* Potentiate the activity of digoxin, lithium (can cause nephrogenic DI), and loop diuretics.
----> Decreased Na reabsorption decreases lithium clearance
---> Hypokalemia potentiates Na/K ATPase on heart cells..increase digoxin's effects.
* Attenuate the activity of Probenecid (d/t comp at OATS) AND diabetic meds
* The activity of thiazides may be attenuated by NSAIDs (d/t blocked effects of prostaglandins..pvt VD). (Except for Sulindac.)

CONTRAINDICATION
* Pts with hypersensitivity to Sulfonamides
* Cannot use thiazide diuretics to tx Nephrogentic DI that has been caused by Lithium becasue it potentiates lithium. Have to use amilioride. Lithium gains access to the intracellular environment of principal cells of the CD via the Na channels and disrupts the activity of vaspression, causing nephrogenic DI. Amiloride counteracts this by blocking the Na channels in the principal cells, pvt lithium from getting in.

Front 5

Spirinolactone

Back 5

Aldosterone Antagonist (K-sparing diuretic)

* Blocks aldosterone receptors on the BASOLATERAL MEMBRANE of the principal cells of the CD, preventing induction of Aldosterone Induced Proteins (AIP).
* Natriuresis is limited since only 2-3% of filtered load is reabsorbed in the CD. Their real effect is preventing K and H secretion.

MOA:
Decreased Na reabsorption means no neg lumen potential, no K secretion and no stimulation of the proton pump...H+ is not secreted.

USE:
* Main use is to pvt Hypokalemia when used in combo with loop or thiazides.
* CHF (counteracts stim of RAAS and Aldos and REDUCES FIBROSIS.)
* Female Hirsutism (has antiandrogen activity)
* Primary or secondary Hyperaldosteronism.

SE:
* Hyperkalemia (esp in renal pts, DM)
* Metabolic Acidosis (especially with cirrhosis).
* Anti-androgen effects: Impotence, menstrual irregularities, Gynecomastia, galactorrhea (d/t no androgens and decrease prolactin inhibition).

INTERACTIONS:
* Interacts with ACEI's, and ARBs. ...too much!!

Front 6

Amiloride

Back 6

Cortical Tubule of the Collecting Duct K-Sparing Diuretic

MOA:
* Block Na channels on the LUMENAL side of the principal cells in the late distal tubule and the collecting duct. This pvts a neg lumen potential, which decreases K and H+ secretion.

USE
* Lithium- induced nephrogenic diabetes insipidous
---> Lithium gains access to the intracellular environment of principal cells of the CD via the Na channels and disrupts the activity of vaspression, causing nephrogenic DI. Amiloride counteracts this by blocking the Na channels in the principal cells, pvt lithium from getting in. (Can't use thiazides here because they potentiate lithium).
* Given with loops/thiazides to pvt their SE's.

SE:
* Hyperkalemia (esp in renal pts, DM)
* Metabolic Acidosis (especially with cirrhosis).

Front 7

Triamterene

Back 7

Cortical Tubule of the Collecting Duct K-Sparing Diuretic

MOA:
* Block Na channels on the LUMENAL side of the principal cells in the late distal tubule and the collecting duct. This pvts a neg lumen potential, which pvts K and H+ secretion.

SE:
* Hyperkalemia (esp in renal pts, DM)
* Metabolic Acidosis (especially with cirrhosis).

* Also tx lithium induced nephrogenic DI.

Front 8

Mannitol

Back 8

Osmotic Diuretic.

* Acts at the segments of the renal tubule that are most permeable to water:
-->Proximal Tuble
-->Descending Limb of the LOH
-->Collecting Duct.

MOA:
*Freely filtered by the glomerulus but is poorly reabsorbed. (pharmacologically inert).
* Decreases PASSIVE reabsorption of water in the PT and DLOH, increased water retention in the tubular lumen, resulting in MILD diuresis.
* Increases extracellular fluid, decreases intracellular fluid volume.

USES:
* Reduction in IOP in ACUTE angle glaucoma, pre and post op for ocular sx.
* Cerebral edema (trauma) or pre or post op for neurosx.
* Potentiates urine flow during potentially nephrotoxic situations to pvt tubular necrosis.
* Given prior to renal shutdown to maintain renal perfusion pressure.

CONTRAINDICATIONS:
* CHF/ Pulmonary congestion
* Severe renal disease/ Anuria (will cause hyponatremia...mannitol would only make this worse!!)
* Impaired liver function

Front 9

Nesiritide

Back 9

Recombinant Human Brain-type Natriuretic Peptide (BNP).

Natriuretic peptide receptor is coupled directly to the particulate isoform of guanylate cyclase. So it INCREASES cGMP!! This causes vasodilation.

EFFECTS
* Decreased GFR 2ndary to decr renal perfusion via decr SVR
* Decreased Na reabsorption d/t increased filtrate
* Natriuresis

USE:
* CHF

SE:
* Dose dependent HOTN
 

 

Front 10

Desmopressin

Back 10

Synthetic Vasopressin - a Vasopressin Analogue.

V2 Agonist: Selective for V2 receptors. * Possesses 3000 to 1 times the antidiuretic activity over VC activity. B/c it is diuretic activity only...is NOT used for esophageal varices like vasopressin.

USE:
* Tx of NEUROGENIC DI (low ADH levels).
* Von willebrand's disease (causes factor release at V2 receptors.)
* Primary nocturnal enuresis (bed wetting...but controversial d/t seizure risk in kids).

SE
* Hyponatremia
* Seizures

Front 11

Indomethacin

Back 11

NSAID: COX1 and 2 inhibitor. Pvts prostaglandin synthesis.

USE:
* DRUG OF CHOICE TO TX ACUTE ATTACK OF GOUTY ARTHRITIS!!
* DRUG OF CHOICE FOR CLOSURE OF THE DUCTUS ARTERIOSUS!
* Antipyretic
* Analgesic (50x more potent than ASA).

SE
* Gastric Ulcers
* Decrease lithium excretion by the kidneys...can cause lithium toxicity.

CONTRAINDICATIONS
* Long-term use d/t GI side effects

Front 12

Sulindac

Back 12

NSAID: COX1 and 2 inhibitor. Pvts prostaglandin synthesis.

USE: Tx of Acute gouty arthritis

BENEFITS: No active metabolites reach the kidney.
* Good to use with renal pts and pts on loop/ thiazide diuretics d/t no renal effects.

Front 13

Naproxen

Back 13

NSAID: COX1 and 2 inhibitor. Pvts prostaglandin synthesis.
* Propionic Acid Derivative
* Inhibition is reversible (weaker than ASA).

USE:
* Tx of Acute gouty arthritis (decrease inflammation)
* Antipyretic, Analgesic, Antiinflammatory.
* Rheumatoid Arthritis, Osteoarthritis
* Acute Tendonitis

SE
* GI disturbances: less severe than with ASA
* Hypersensitivity rxns (shift towards leukotrienes).
* CNS effects: Dizziness, drowsiness
* Decreased renal fxn
* Inhibit plt aggregation (inhibit thromboxane)-->Bleeding Disorders.

CONTRAINDICATION
* Pts who have had a hypersensitivity rxn to ASA (bronchoconstriction , HOTN, edema, Urticaria). Astma pts are more sensitive to these d/t a shift toward leukotriene synthesis by blocking cyclooxygenase.
* Pregnancy and breast feeding (can cause premature labor and premature closure of ductus arteriosus). .
* Renal failure (ischemia to kidneys via VC of renal arteries).

Front 14

Colchicine

Back 14

Anti-inflammatory med.

USE:
* Tx of ACUTE Gouty Arthritis.
* Prophylactic tx of Gouty Arthritis when chronic tx is initiated to pvt an acute gout attack from mobilzation of UA.
* IV Drug

MOA: Tubulin causes mitotic spindle function, depolymerization/ disappearance of micotubule networks, and granulocyte migration that cause an inflammatory response. Colchicine binds to tubulin. This inhibits granulocyte migration and the release of inflammatory mediators.

SE:
* Arrests cell division: Attacks the most rapidly proliferating cells in the body: GI TRACT CELLS, BONE MARROW CELLS that are hematopoetic, HAIR CELLS. ---->This can cause Alopecia, Agranulocytosis, aplastic anemia, and N/V, diarrhea, abdominal pain.
* Can also precipitate a Gouty Attack when used prophylactically due to an immobilization of UA from joints and cartiledge.

Front 15

Probenecid

Back 15

Uricosuric Agents

MOA:
* Competitively inhibit OATs on the LUMENAL SIDE, pvting reabsorption of uric acid. This causes excretion of UA.

USE
* Chronic tx of gouty arthritis...especially for under excretors of UA (renal issue).

SE
* GI disturbances

INTERACTIONS
* ASA inhibits action of uricosuric agents (competes at the OAT site).
* Prolongs action of PCN (decrease the therapeutic dose).
* Diuretics compete at OATs and decr effectiveness.

Front 16

Sulfinpyrazone

Back 16

Uricosuric Agents

MOA:
* Competitively inhibit OATs on the LUMENAL SIDE, pvting reabsorption of uric acid. This causes excretion of UA.

USE
* Chronic tx of gouty arthritis...especially for under excretors of UA (renal issue).

SE
* GI disturbances

INTERACTIONS
* ASA inhibits action of uricosuric agents (competes at the OAT site).
* Prolongs action of PCN (decrease the therapeutic dose).
* Diuretics decr the effectiveness via competition at OATs.

Front 17

Allopurinol

Back 17

Xanthine Oxidase Inhibitor

MOA: Xanthine Oxidase makes Uric Acid out of Xanthine. Inhibiting this decreases uric acid levels.

USE:
* Over-producers of UA: metabolic primary disorder or Lesch-Nhyan Syndrome
* Hyperuricemia (UA > 7 mg/dl in men, > 6 mg/dL in women)
* Urolithiasis: Kidneys stones created by uric acid in the urine.
* Severe, topheceous gout (urate crystal deposits everywhere).

SE
* GI disturbances
* Type 4 Hypersensitivity Reactions (rare)
----> Fever, rash, renal insufficiency..can cause DEATH d/t sepsis. Can appear weeks after taking allopurinol.
* Xanthine renal stones (to tx alkalinize the urine with bicarb, and give IVF).

INTERACTIONS
* Decr metabolism of mercaptopurines by xanthine oxidase, requires that doses be reduced by 75%. This is an obvious drug drug interaction because cancer pts get tumor lysis syndrome which can cause gout...so they might be taking both of these drugs at the same time.

Front 18

Cromolyn Sodium

Back 18

Mast cell membrane stabilizer

* Inhibits degranulation of mast cells by Ca. This pvts histamine release.

USE
* Prophylactic Asthma Tx
* Prophylactic Tx of Allergic Rhinitis

CANNOT be used for an asthma attack...histmaine has already been released.

Front 19

Nedocromil

Back 19

Mast cell membrane stabilizer

* Inhibits degranulation of mast cells by Ca. This pvts histamine release.

USE
* Prophylactic Asthma Tx
* Prophylactic Tx of Allergic Rhinitis

CONTRAINDICATIONS:
* CANNOT be used for an asthma attack...histmaine has already been released.

Front 20

Diphenhydramine

Back 20

H1 Receptor Antagonist.
Muscarinic Receptor Antagonist

Work in th periphery AND the CNS to block histamine's actions.

USE:
* Allergic Disorders
* Seasonal rhinitis, conjunctivitis (Rhinitis is caused by separation of endothelial cells by histamine).
* Dermatological Flares: severe urticaria, atopic and contact dermatitis
* Sedation/ sleeping aids
* Motion sickness Prophylaxis (d/t antimuscarinic effects).
* Tx acute extrapyramidal effected induced by anti-psychotic drugs (d/t antimusc effects)

INEFFECTIVE IN TX OF:
* Bronchial asthma
* Systemic Anaphylaxis
* Angioedema
(because other autocoids like leukotrienes and cytokines are causing the bronchoconstriction).

SE
* CNS sedation
* Anti- muscarinic effects: dry mouth

Front 21

Fexofenadine (Allegra)

Back 21

Allegra

Selective H1 Receptor Antagonist.
(Higher affinity than Benedryl)
End in "-adine"

* Work in the PERIPHERY ONLY! Do not cross the BBB. Do not cause sedation.
* NO anti-muscarinic effects.
* Avaliable over the counter.

USE:
* Allergic Disorders
* Seasonal rhinitis, conjunctivitis (Rhinitis is caused by separation of endothelial cells by histamine).
* Dermatological Flares: severe urticaria, atopic and contact dermatitis

INEFFECTIVE IN TX OF:
* Bronchial asthma
* Systemic Anaphylaxis
* Angioedema
(because other autocoids like leukotrienes and cytokines are causing the bronchoconstriction).

Front 22

Loratadine (Claritin)

Back 22

Selective H1 Receptor Antagonist.
(Higher affinity than Benedryl)
End in "-adine"

* Work in the PERIPHERY ONLY! Do not cross the BBB. Do not cause sedation.
* NO anti-muscarinic effects.
* Avaliable over the counter.

USE:
* Allergic Disorders
* Seasonal rhinitis, conjunctivitis (Rhinitis is caused by separation of endothelial cells by histamine).
* Dermatological Flares: severe urticaria, atopic and contact dermatitis

INEFFECTIVE IN TX OF:
* Bronchial asthma
* Systemic Anaphylaxis
* Angioedema
(because other autocoids like leukotrienes and cytokines are causing the bronchoconstriction).

Front 23

Cimetidine

Back 23

H2 Receptor Antagonist
End in -"idine"

MOA:
* Block H2 receptors on Parietal cells in the stomach, preventing cAMP dependent stimulation of H/K proton pump. This inihibits gastric acid secretion.

USE
* Gastric Ulcers (via H. pylori or long term NSAIDS)
* Duodenal Ulcers
* GERD (not extreme cases)
* Acute Stress Ulcers
* Zollinger-Ellison Syndrome (incr gastrin release from tumors).
* H. Pylori tx when used in combo with antibiotics (tetracycline, amoxicillin, clarithromycin), and bismuth subsalicylate (peptoBismol).

SE
* Inhibits CYP450s. This can increase the duration of Warfarin, Phenytoin, and Theophylline (give a smaller dose).
* Anti-androgenic effects: Decr sperm count, Gynecomastia, Decr fertility in women.

Front 24

Ergotamine/ Methylergotamine

Back 24

Ergot Alkaloid
-> Parital serotonin agonist
-> Also Alpha and Dopamine receptor agonists.

MOA
* Produce a POTENT VC!!
* Produce strong uterine contactions

USE
* Management of acute migraine attacks
* Tx of frequent, moderate migraine episodes
* Tx of infrequent, severe migraine attacks.

ADMINISTRATION
* Should be given AS SOON AS SYMPTOMS APPEAR!!
* Drug has an extensive 1st pass effect: Caffeine may be co-administered to improve absorption and augment the VC.
* Give with reglan to pvt N/V

SE:
* Potent VC can lead to gangrene adn mumified limbs that will fall off w/o the loss of blood.
* Ergot alkaloids are called "Holy Fire" or "St Anthony's Fire" b/c of an intense burning sensation that occurs with toxicity.
* Can cause Coronary Vasospasm that is refractory to ALL VDr's EXCEPT NITROGLYCERIN!!.
* N/V d/t CTZ activation. (Give reglan (D2 Antagnonist) to stop.

CONTRAINDICATIONS
* Pregnancy d/t uterine contractions.
* CV Disease, HTN, PVD, CAD d/t risk of vasospasm

Front 25

Ergonovine/ Methylergonovine

Back 25

Ergot Alkaloid
-> Partial Serotonin Agonist
-> Also alpha and dopamine receptor agonists.

MOA:
* Produce a POTENT VC!!
* Produce strong uterine contraction

USE
* Postpartum Hemorrhage - control bleeding by maintaining uterine contractions (METHYLERGONOVINE IS THE DOC!!)
* (might also be used for migraines...but ergotamine is the main one).

ADMINISTRATION
* Should be given AS SOON AS SYMPTOMS APPEAR
* Can be coadministered with caffeine to increase absorption. (poorly absorbed).
* Give with reglan to pvt N/V.

SE:
* Ergot alkaloids are called "Holy Fire" or "St Anthony's Fire" b/c of an intense burning sensation that occurs with toxicity.
* Can cause coronary vasospasm that is refractory to ALL VDrs EXCEPT NITROGLYCERIN.
* N/V d/t CTZ activation. (Give reglan (D2 antagonist) to stop).

CONTRAINDICATIONS
* Pregnancy d/t uterine contractions.
* CV Disease, HTN, PVD, CAD d/t risk of vasospasm

Front 26

Propanolol

Back 26

Non-selective Beta Blocker

USE
* Drug of choice for prophylactic tx of migraines.
* THYROID STORM/ HYPERTHYROIDISM: Deiodinase Inhibitor: Blocks the conversion of T4 to T3 in the periphery.

Front 27

Sumatriptan
Zolmitriptan
Naratriptan
Rizatriptan

Back 27

5-HT1b and 5-HT1d receptor Agonists
End in "triptan".

MOA: These are g-coupled receptors for serotonin. They block the cerebral VD AND the proinflammatory mediators that cause migraines.

USE:
* Tx of ACUTE Migraine Attacks.

BENEFITS OVER ERGOTAMINE
* Efficacius at any point of the migraine attack (unlike ergots, which must be given as soon as the migraine symps appear).
* Decreased N/V!!! :) (Not 5HT3).
* Nasal formulations (Sumatriptan, Zolmitriptan) provides MORE RAPID RELIEF (5 min). (Oral takes 30 min).


SE
* Pressure
* Dizziness
* Drowsiness
* Sweating
* Coronary Artery VC!!

CONTRAINDICATIONS
* CV dysfunction d/t constriction of CA arteries.

Front 28

Ondansetron

Back 28

5-HT3 receptor Antagonist

MOA: blocks ligand gated serotonin receptors in the GI tract and in the CTZ of the CNS.

USE
* Anti-emetic tx for CA chemo pts
* Post-op N/V

SE
* HOTN
* Prolonged QT interval.

Front 29

Alosetron

Back 29

5-HT3 receptor Antagonist

MOA: blocks serotonin receptors in the GI tract and in the CTZ of the CNS.

USE
* Tx of Diarrhea predominant IBS in females.
* Also an antiemetic

SE
* PULLED IN 2002 B/C CAUSED ISCHEMIC COLITIS AND DEATH.

Front 30

Carboprost
(Hemabate)

Back 30

15- methyl PGF2a analog

EFFECT
* Strong contraction of uterine smooth muscle
* Induction of 1st or 2nd trimester abortions. (GIVE HIGH MX DOSES)
* Inhibition of postpartum bleeding (when oxytocin and ergonovine are ineffective).

SE
* GI disturbances: N.V, Diarrhea

Front 31

Dinoprostone

Back 31

PGE2 analog

EFFECT
* Strong contraction of uterine smooth muscle.

USE
* Induction of 1st or 2nd trimester abortions. (GIVE HIGH MX DOSES!)
* Promotion of ripening and dilation of the cervix for induction of labor. (GIVE A SMALL SINGLE DOSE!)

SE
* GI Disturbances: N/V, Diarrhea

Front 32

Alprostadil

Back 32

PGE1 Analog

MOA
* Causes vasodilation locally

USE
* Maintains a patent ductus arteriosus in neonates with congenital heart disease
* Tx impotence via VD.

Front 33

Misoprostol

Back 33

PGE1 Analog

MOA
* Causes cytoprotection in the GI tract: incr blood flow, incr mucus secretion, incr bicarb secretion
* Contracts the uterus.

USE
* Prevention of NSAID-induced gastric ulcers.
* Induce abortion in combination with mifepristone and methotrexate d/t uterine contraction.

SE
* Diarrhea
* Can cause spontaneous abortion in pregnancy (Contrainidicated!!)

Front 34

Epoprostenol

Back 34

Prostacyclin (PGI2) Analogue

MOA
* Causes Vasodilation and decr plt aggregation

USES
* Tx of Primary Pulmonary HTN (IV infusion via a central line. May eliminate the need for a heart/ lung transplant).

SE
* Systemic HOTN

Front 35

Zafirlukast

Back 35

Leukotriene Receptor Antagonist

USE
* Chronic Asthma (in combo w/ glucocorticoids). Reduces dependence on B2 agonists.

Front 36

Montelukast

Back 36

Leukotriene Receptor Antagonist

USE
* Tx of seasonal rhinitis - not sure if this is any better than H1 receptor antags (benedryl, etc).
* Chronic Asthma (in combo w/ glucocorticoids). Reduces dependence on B2 agonists.

Front 37

Zileuton

Back 37

5-Lipoxygenase Inhibitor

MOA: pvts leukotriene synthesis from arachadonic acid by inhibiting this enzyme.

USE
* Chronic Asthma (in combo w/ glucocorticoids). Reduces dependence on B2 agonists.

Front 38

Non-selective COX inihibitors

Back 38

Aspirin
Idomethacin
Ibuprofen/ naproxen

Front 39

Selective COX-2 Inhibitors

Back 39

Celecoxib

Front 40

Sulindac

Back 40

Sulindac

Pro-drug NSAID.

USE
* Gouty arthritis
* Renal ischemia NSAID of choice.

When it reaches the kidney, it is reoxidized back to the prodrug. This means that active metabolites of this drug do not reach the kidney. So you still have the production of renal prostaglandins. So this drug would be good for pts with gouty arthritis or with renal ischemia. Active metabs don’t’ reach the kidney.

(Can reclaim this drug from the urine of people that took it.)

Front 41

Acetaminophen

Back 41

Para-aminophenol Derivative.
Selective Brain Cyclooxygenase Inhibitor (non-NSAID)

* In the periphery, COX 1,2 are normally expressed in areas where peroxide levels are high. But peroxide levels in the brain are low.

USE:
* Analgesia (mild/moderate)
---> Can treat Osteoarthritis (DOC) b/c does not involve inflammation.
* Antipyretic
(NO anti-inflammatory activity)
* Preferred in kids with fevers because it has no link to Reye syndrome like ASA.

ADVANTAGES OVER ASA
* Reduced occurrence of hypersensitivity rxns.
* Children - no reyes syndrome
* No GI Effects! :)
* No effect on plt aggregation, uric acid excretion, and respiratory systems! :)
* None of the peripheral complications assoc with NSAIDS b/c Tylenol does not work in the periphery.

SE
* Hepatic Necrosis with overdose (> 10g): CYP450 metabolism leads to highly reactive intermediates that can react with sulfhydryl grps on proteins, decreasing their activity and damaging the liver. Oxidative stress and free radical formation. These are usually glucuronidated by phase II rxns and then excreted, but with overdose, they damage the liver. Tx with N-acetylcystine (mucomyst).
S/S of Tylenol OD: N/V, Abdominal pain initally. Then 2-4 days later, hepatic necrosis and hepatic coma.
* Skin Rash and Allergic rxns

CONTRAINDICATIONS
* Patients with impaired liver function (cirrhosis).
* Alcoholics: Alcoholism decreases liver glutathione levels and induces the cytochrome p450’s..this will makes acetaminophen toxicity more magnified. ….more intermediates produced.

Front 42

Ketoralac

Back 42

NSAID

COX 1 and 2 Inhibitor

Great analgesic properties. Given IV in the hospital. (ST therapy ONLY.)

Front 43

Aspirin

Back 43

IRREVERSIBLE Non-selective COX1 and COX2 Inhibitor.

MOA:
* Irreversibly covalently modifies COX-1 and 2. Duration of action is long in plts, require new protein synthesis.

DOSE DEPENDENT EFFECTS:
---> LOW DOSES: < 10 mg/dl: Antipyretic, Analgesia
---> MEDIUM DOSES: Anti-Inflammatory: Decreased Prostaglandins.
* Decreased thromboxane...decreased plt aggregation (not sure if at low or high doses).

USES
* Antipyresis
* Analgesia (mild/moderate pain) (Osteoarthritis) (Dysmennorhea)
* Anti-inflammatory (Rheumatoid Arthritis)
* Inhibits plt aggregation: - inhibits formation of soft clot.
---> Prophylaxis in CAD, TIA's, MI
---> Post-op DVT tx
* Closure of the ductus arteriosis in neonates (but the DOC is Indomethecin).
* External uses: ASA for tx of warts, corns, fungal infections, dermatitis: Destroys epithelial cells--> "Keratalitic".

BENEFITS
* No resp depression or addictive properties like with opiods! :)

SIDE EFFECTS:
* Blocked GI prostaglandins - loss of cytoprotective effects. Can lead to gastric ulcers, N/V via activation of CTZ. Pts at risk are MI pts, OA or RA pts. Mesoprostol can help to pvt this effect with ASA.
* Activation of CTZ can cause N/V, Tinnitus ("Salicylism")
* COMPENSATED RESPIRATORY ALKALOSIS: Increased CO2 production IN THE THERAPEUTIC DOSE RANGE, causing hyperventilation and kidneys dump bicarb to compensate.
* RESPIRATORY FAILURE AND ACIDOSIS with TOXIC DOSES (medical emergency!!) . Resp alkalosis occurs 1st, followed by metabolic decompensation. Hypoglycemia and decr renal function leads to organic acid accumulation and METABOLIC ACIDOSIS. Depression of medullary resp center then causes hypoventilation and RESPIRATORY ACIDOSIS. Clinical manifesations:
--> Hyperprexia
--> Water loss via sweating (dehydration)
--> Ketosis (organic acid breakdown)
--> Coma--> Convulsions --> death
TX: Cool pt with ice. Give CV and Resp support, Correct pH, Activated charcoal, give IVF for dehydration.
* Uricosuria: dose dependent effect at OATS.
---> LOW DOSE: Block OATS on BASOLATERAL side to decr UA secretion. Incr plasma levels of UA.
---> HIGH DOSE: Block OATS on LUMENAL side to decr UA reabsorption. Decr plasma levels of UA.
* Bleeding disorders (no thromboxane)
* Impaired renal function (no prostaglandins, blocked OATS).

CONTRAINDICATIONS
* Febrile Viral Illness - ASA can cause Reye's syndrome in these pts (no definitive link)
* Gout - low dose ASA can compete with UA at OATS and worsen gout. (High dose ASA can help but you still don't use it.).
* Be careful in asthma and nasal polyp pts. They have a shift to leukotriene synthesis with blocked COX and can have bronchoconstriction with ASA. (hypersensitivity rxn).
* Pregnancy and breast feeding pts:
---> Inhibits labor induction
---> Increased risk of postpartum and neonatal hemmorrhage!!
---> Premature closure of the ductus arteriosus in neonates!!!
* Renal pts: Can cause ischemia to the kidneys...no prostaglandins.

INTERACTIONS
* Decreases tubular secretion of thiazide and loop diuretics via competition at OATS. This decreases GFR (no prostaglandins) and diuretic activity of these agents.
* Displaces other drugs that are protein bound: (Warfarin, Sulfonureas), will inc their plasma levels!
* Decreased Uricosuric activity of Probenecid d/t competition at OATS.

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Salsalate
Sodium Salicylate

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SALSALATE & SODIUM SALICYLATE

Non-acetylated Salicylate. Cox 1,2 Inhibitor.

* Weaker than ASA...inhibition is reversible.

BENEFITS
* The ONLY NSAIDs that can be used in pts with hypersensitivity rxns to ASA safely! :) This is d/t weaker effects...not as much as a shift toward leukotriene synthesis.
* Good for pts with asthma and nasal polyps.

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Ibuprofen

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NSAID: COX1 and 2 inhibitor. Pvts prostaglandin synthesis.
* Propionic Acid Derivative
* Inhibition is reversible (weaker than ASA).

USE:
* Antipyretic, Analgesic, Antiinflammatory.
* Rheumatoid Arthritis, Osteoarthritis
* Acute Tendonitis

SE
* GI disturbances: less severe than with ASA
* Hypersensitivity rxns (shift towards leukotrienes).
* CNS effects: Dizziness, drowsiness
* Decreased renal fxn
* Inhibit plt aggregation (inhibit thromboxane)-->Bleeding Disorders.

CONTRAINDICATION
* Pts who have had a hypersensitivity rxn to ASA (bronchoconstriction , HOTN, edema, Urticaria). Astma pts are more sensitive to these d/t a shift toward leukotriene synthesis by blocking cyclooxygenase.
* Pregnancy and breast feeding (can cause premature labor and patent DA in neonates).
* Renal failure (ischemia to kidneys via VC of renal arteries).

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Celecoxib (Celebrex)

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Selective Cox-2 Inhibitor

COX2 is an enzyme that is inducible by cytokines. It is responsible for the prostaglandins that are released only in pain and inflammation. So targeting COX2 provides a clear clinical advantage.

ADVANTAGES OVER ASA AND IBUPROFEN
* No GI side effects!!! :)

USE
* Osteoarthritis/ Rheumatoid Arthritis
* Acute Pain
* Dysmenorrhea (treats the painful period).
* Prophylactic Tx and Acute Tx of Familial Adenomatous Polyposis (FAP). ---> COX2 has increased expression and activity in colon CA.

SE:
* Renal ischemia risk (blocks renal prostaglandins)
* Long term increased risk of cardiovascular disease d/t thromboxane production unopposed. (COX2 synthesizes ProstacyclinPGI2). Can cause increased plt aggregation and clots....not as bad as Viox (which caused stroke) was because Celecoxib maintains some small level of COX 1 inhibition.
* Premature closure of the DA in neonates with congenital heart disease if breast-feeding mom takes this.


CONTRAINDICATION
* Pts who have had a hypersensitivity rxn to ASA (bronchoconstriction , HOTN, edema, Urticaria). Astma pts are more sensitive to these d/t a shift toward leukotriene synthesis by blocking cyclooxygenase.
* Renal patients: The prostaglandins that are synthesized by COX2 cause renal VD...so inhibition can still cause renal ischemia.
* Pts with a known hypersensitivity to sulfonamides (based on a sulfonamide structure).

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Methylsalicylate

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Cox 1 and 2 Inhibitor.

The active ingredient in Gold-bond powder.

Methylsalicylate acts as a counter-irritant. Irritation/ inflammation leads to the sensitization of pain receptors and fibers. This drug decreases inflammation and sensitization.

CONTRAINDICATION
* Pts who have had a hypersensitivity rxn to ASA (bronchoconstriction , HOTN, edema, Urticaria). Astma pts are more sensitive to these d/t a shift toward leukotriene synthesis by blocking cyclooxygenase.

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DMARDs

Disease Modifying Anti-arthritic drugs

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Slow acting anti-arthritic drugs.
Goal is to tx the CAUSE of Rheumatoid Arthritis. To halt its progression.

It may take several weeks or months to see improvement.