MoA: carbonic anhydrase inhibitor

Secreted through organic acid (anion) in proximal tubule of kidney. Inhibits NaHCO3 reabsorption, can cause mild hyperchloremia, metabolic acidosis

decreases production of aqueous humor in eye, cerebral spinal fluid 

Effects limited: Loop of Henle enhances reabsorption of NaCl, decreased bicarb means metabolic acidosis 

USE: glaucoma, urinary alkalinzation, tx epilepsy, mountain sickness

ADR: allergic hypersensitivity (sulfonamide derivative), metabolic acidosis (bicarb wasting), hypokalemia, urinary alkalinzation (ppt of CaPO4)

MoA: osmotic diuretic, does not cross BBB

filtered by glomeruli, minimal tubular reabsorption

increases osmotic pressure means dec. reabsorption of water in  nephron segments (freely permeable to water) and solutes 

USE:  oliguric acute renal failure (induce diuresis), reduction of intraocular and intracranial pressure (increasing plasma osmotic pressure, decreases eye pressure), urinary excretion of toxins/ OD  tx/prevention of renal toxicity, edema

ADR: inc. extracellular fluid volume. for pt with pulmonary congetsion: pulmonary edema, hyponatremia

C/I: severe renal disease, cranial bleeding

MoA: loop diuretic (high ceiling--> high reabsorptive capacity , inhibitor of Na/K/2Cl symport). secreted by proximal tubule via organic acid secretion (acids such as uric acid can build up), act in thick ascending limb of Henle's loop, increase renal blood flow, inc systemic venous capacitance (dec left ventricular filling pressure)

USE: congestive HF, acute pulmonary edema, HTN, hypercalcemia 

ADR: hypotension, hypovolemia, hyponatremia, hypochloremic meteabolic alkalosis and hypokalemia, gout, ototoxicity, sulfonamide allergic reactions, hyperglycemia 

MoA: phenoxyacetic acid derivative, loop/high ceiling diuretic, inhibits apical Na/K/2Cl symport, secreted by proximal tubule via organic acid secretion (uric acid competes), acts in thick ascending limb of Henle's loop, high ceiling because high reabsorptive capacity of thick ascending limb, via PG inc renal blood flow, inc systemic venous capacitance which dec left ventricular filling pressure

USE: congestive HF, acute pulmonary edema, HTN, hypercalcemia

ADR: hypotension, hypovolemia, hyponatremia, hypochloremic metabolic alkalosis and hypokalemia, out, ototoxicity (more common than furosemide), hyperglycemia 

MoA: thiazide diuretic, inhibitor of Na/Cl symport (promotes NaCl excretion, water diuresis), induce natriuresis which reduces CO, activates RAAS, fall in peripheral vascular resistance (continued anti-HTN effect) have unsubstituted sulfonamide group, secreted by organic acid secretory system in proximal tubule, action independent of patient acid/base balance 

USE: edema of HF, anti-HTN (effective diminished when GFR is below 30-40 mL/min, primary HTN for initial therapy, flat dose-response (higher doses does not provide better lowering of BP)), tx "volume dependent" HTN (black, elderly pt) decrease excretion of Ca (enhanced reabsorption: prevents calcium nephrolithiasis, osteoporosis, nephrogenic diabetes insipidus (paradoxical antidiuretic effect)

ADR: hypokalemia, metabolic alkalosis (inc secretion of K/H), ventricular ectopic activity, gout, sulfonamide hypersensitivity (SJS), hyperglycemia, increase plasmas LDL/total cholesterol, total triglycerides), fatal hyponatremia, poor response to drug can be due to overwhelming load of dietary Na intake, impaired renal capacity to excrete Na. with severe HTN pt, other diuretics (vasodilators) can lead to intense Na retention 

MoA: contain unsubstitued sulfonamide group, secreted by organic acid secretory s ystem in proximal tubule (uric acid competes), inhibit Na/Cl symport (distal convoluted tubule, promoting NaCl excretion, water diuresis), diuretic action indepdnent of pt acid/base balance

USE: edema of HF, anti-HTN (effectiveess diminished when GFR is below 30-40 mL/min), decrease Ca excretion: prevent calcium nephrolithiasis, osteoporosis, nephrogenic diabetes insipidus (paradoxicial antidiuretic effect)

ADR: hypokalemia, metabolic alkalosis (inc excretion of K/H), gout, sulfonamide hypersensitivity (SJS), hyperglycemia, increase plasmas LDL cholesterol, total cholesterol, total triglycerides, fatal hyponatremia 

MoA: thiazide-like diuretic, inhibitor of apical Na/Cl symport (promotes NaCl excretion and water diuresis), has unsubstituted sulfonamide group, secreted by organic acid secretory system in proximal tubule (competes with uric acid) , induce natriuresis (reduces CO) then causes fall in peripheral vascular resistance (CO goes to normal) for continued effect on BP

USE: edema of HF, anti-HTN (initial therapy) (effectiveness diminished when GFR is < 30-40 mL/min) (flat dose-response curve-- higher doses not more effective) for pt with "volume dependent" HTN (black, elderly pt), decrease excretion of Ca: prevent calcium nephrolithiasis, osteoporosis, nephrogenic diabetes insipidus

ADR: hypokalemia (ventricular ectopic activity and sudden cardiac death), metabolic alkalosis (inc excretion of K/H), gout, sulfonamide hypersensitivity (SJS), hyperglycemia, increase plasma LDL cholesterol, total cholesterol, total triglycerides, fatal hyponatremia, poor response from either overload of dietary Na or impaired renal capacity to excrete Na, overly rigorous tx may activate RAAS excessively, when combined with other vasodilators (diuretics) can lead to intesne Na retention

MoA: thiaizde-like diuretic, inhibition of Na/Cl symport (promotes NaCl secretion, water diuresis), unsubstitued sulfaonmide group, secreted by organic acid secretory system in proximal tubule (competes with uric acid),  diuretic action independent of pt acid/base balance, intially induces natriuesis (reduces CO) then causes fall in peripheral vascular resistance (as CO goes normal)

USE: edema of HF, anti-HTN (initial therapy) (effectiveness diminished when GFR < 30-40 mL/min) (flat dose-response curve for BP), effective for "volume dependent" HTN-- black, elderly pt , decreases excretion of Ca: prevents calcium nephrolithasis and osteoporosis, nephrogenic diabetes insipidus

ADR: hypokalemia (ventricular ectopic activity, sudden cardiac death), metabolic alkalosis (inc decrease of K/H), gout, sulfonamide hypersensitivity (SJS),  hyperglycemia, does NOT increase cholesterol (useful for pt with high LDL cholesterol), fatal hyponatremia, poor response from overwhelming dietary Na intake, impaired renal capacity to excrete Na. over-vigorous therapy may activate RAAS extensively, with other vasodilators (diuretics) leads to intense Na retention

MoA: K sparing diuretic inhibits renal Na channels, secreted in proximal tubule by organic base secretory system, block luminal Na channels in principal cells (prevent K secretion b/c dec K entering cell for secretion, decrease electronegativity of lumen), decreased H secretion by intercalated cell, NOT powerful diuretic (late distal tubule only reabsorbs 3%)

USE: used in combination with other diuretics to treat edema, HTN, used to counterbalance hypokalemia by thiazide/loop diuretics, Liddle's Syndrome (blocks sodium channels), cystic fibrosis 

ADR: life-threatening hyperkalemia (C/I for hyperkalemia pt), do NOT administer with spironolactone (life-threatening hyperkalemia), n/v, leg cramps, dizziness, used with caution with ACE-I (hyperkalemia), poorly soluble: ppt kidney stones 

MoA: K sparing diuretic (inhibition of renal Na channel), secreted in proximal tubule by organic base secretory system, block luminal Na channels in principle cells in late distal tubule/collecting duct (prevent K secretion means less K entering cell for secretion, less electronegativity of lumen), decrease H secretion by intercalated cell, NOT powerful diuretic (late distal tubule only reabsorbs 3%) 

USE: in combination with other diuretics to treat edema, HTN, counterbalance hypokalemia caused by thiazide/loop diuretics, Liddle's Syndrome (blocks sodium channels), cystic fibrosis

ADR: life-threatening hyperkalemia (C/I in hyperkalemic pt), do NOT admin with spironolactone (hyperkalemia), n/v/d, HA , do NOT use with ACE-I (hyperkalemia)

MoA: diuretic (aldosterone receptor antagonist), maximal diuretic effect seen on 3rd day of therapy, diuresis persists for 2-3 days. antagonizes mineralcorticoid receptor, binds to receptor to prevent aldosterone-induced gene transcription , dependent on levels of endogenous aldosterone, aldosterone: increases Na conductance, inc basolateral Na/K ATPase, inc secretion of K/H (drug blocks all of these things)

USE: combination with loop/thiaizide to treat edema, HTN (especially resistant HTN), reduces edema fluid/prevent hypokalemia, tx hyperaldosteronism

ADR: life-threatening hyperkalemia (C/I in hyperkalemia pt), do not use with another K sparing diuretic, antiandrogen effects (interacts with other steroid hormone receptors), use with caution with ACE-I (hyperkalemia)

MoA: diuretic: aldosterone receptor antagonist, maximal diuretic effect seen on 3rd day of therapy, diuresis persists 2-3 days, antagonist at mineralcorticoid receptor, binding prevents aldosterone induced gene transcription, clinical efficacy dependnet on levels of endogenous aldosterone. Aldosterone: inc luminal Na conductance, inc basolateral Na/K ATPase activity, inc secretion of K/H (inc lumen electronegativity) (drugs block this)

USE: combined with loop/thiaizde diuretic for edema, HTN, reduces edema fluid and prevents hypokalemia, tx hyperaldosteronism 

ADR: life-threatening hyperkalemia (C/I in hyperkalemic pt), does NOT interact with androgen receptors like spironolactone (more selective), use with caution with ACE-I (hyperkalemia) 

MoA:  K sparing diuretic: aldosterone receptor antagonist, maximal diuretic effect seen on 3rd day of therapy, diuresis persists for 2-3 days, antagonize mineralcorticoid receptors which prevents aldosterone-induced gene transcription, clinical efficay dependent on levels of endogenous aldsterone. Aldosterone: inc luminal Na conductance, inc basolateral Na/K ATPase (inc lumen electronegativity) (drugs block this). combination with ethinyl estradiol to make yasmin: progestin (from spironolactone), retains aldosterone receptor antagonist, has diuretic effect (couterbalance fluid retaining effect of ethinyl estradiol) 

ADR:  lifte-threatening hyperkalemia (C/I in pt with hyperkalemia), use with another K sparing diuretic C/I, use with caution with ACE-I (hyperkalemia) 

MoA: similar to vasopressin (anti-diuretic hormone), increases water reabsorption by collecting ducts in kidney, greater anti-diuretic effect than ADH, reduced CV vasopressor activity to ADR

USE: nocturnal enuresis, central (pituitary) diabetes insipidus

ADR: water intoxication 

MoA:  peripheral neuronal inhibition of adrenergic neurons depletes storage of NE, decreases CO, peripheral resistance (not rapid acting) 

ADR: sedation, mental depression, ppt migraine, postural hypotensive symptoms, bradycardia, systemic fluid retention

USE: HTN

MoA: centrally acting adrenergic neuron inhibition, act as alpha-2 receptor agonist in vasomotor centers, decreases sympathetic outflow (renal renin release decreases, CO may or may not dec), fall in peripheral resistance , prodrug that is converted to methylnorepinephrine, accumulates in NE storage vesicles, dampening sympathetic neural outflow

USE: HTN during pregnancy

ADR: pierpheral fluid retention, centrally-mediated dry mouth, sedation, "autoimmune" disorders like Parkinsonian signs (accumulation of methyldopamine in CNS dopamine receptors), no rebound HTN

MoA: alpha-2 receptor agonist (centrally acting adrenergic enuron inhibition), decreases sympathetic outflow from CNS (dec renal renin release, CO may or may not dec), fall in peripheral resistance

USE: in patch form for primary HTN pt, smoother BP control with fewer side effects

ADR: skin reactions from patch, rebound HTN when stopped quickly (less with patch than PO), fluid retention

MoA: alpha 1 receptor blocker, blockade of arterial vascular alph1 inhibits binding of NE, decreasing BP by decreasing TPR. Effects veins and arteries (initial drop in BP due to dilation of resistance and capacitiance vessels)

USE: primary HTN, long acting (PO daily)

ADR: intial dose causes severe postural hypotension (especially if already on diuretic): minimize by giving low dose, telling pt to take it easy first day, less severe because it is longer acting, stop diuretic 2 days before starting and then re-starting diuretic

OTHER: improves glucose tolerance, cholesterol/triglyceride levels may be lowered, HDL may be reaised 

MoA:  blockade of arterial vascular alpha-1 recetpors inhibits binding of NE, decreasing BP by decreasing TPR. effects veins and arteries: initial reduction in BP from dilation of both resistance and capacitance vessels)

USE: primary HTN (3x a day, PO)

ADR:  severe postural hypotension with first dose (minimize by starting low, patient taking it easy first day, stopping diuretic 2 days before, then re-starting, more severe because shorter acting)

OTHER: improve glucose tolerance, cholesterol/triglyceride levels may be lowered, HDL raised 

MoA:  blockade of arterial vascular alpha-1 receptors competitively inhibits binding of NE, causes decreased BP from decreased TPR. Same effect in veins and arteries: initial reduction in BP from dilation of both resistance and capacitance vessels

USE: primary HTN (PO daily)

ADR: severe postural hypotension (minimize by starting low, pt taking it easy first day, less severe bc longer acting, stopping diuretic 2 days before and then re-starting)

OTHER: improve glucose tolerance, cholesterol/triglyceride levels lowered, HDL raised

MoA: beta 1/2 receptor blocker (nonselective). No ISA. high lipid solubility means it can cross BBB, metabolized by liver. Reduces CO, inhibits release of renin (decreases contractility, maybe dec HR). removes normal physiologic level of beta2 mediated vasodilation (offset decrease in TPR, limits effectiveness for HTN)

USE: HTN (less effective in black, elderly pt chinese pt more sensitive), angina, arrhythmias 

ADR: bradycardia, reduced exercise ability/easier fatigue, slow AV conduction/suppress ventricular contractility too much, rebound HTN with sudden withdrawal, bronchoconstriction, masks insulin-induced hypoglycemic signs (tachycardia) in diabetics (diabetics given with great caution) and hypoglycemia more severe/longer in duration, insulin resistance with glucose intolerance, hypertrigyceridemia and fall in HDL, bad dreams, hallucinations

MoA: beta 1/2 receptor blocker (nonselective). No ISA. lowlipid solubility means it canNOT cross BBB, metabolized by kidney. Reduces CO, inhibits release of renin (decreases contractility, maybe dec HR). removes normal physiologic level of beta2 mediated vasodilation (offset decrease in TPR, limits effectiveness for HTN), dec HR, contractility, arterial BP (reduces O2 demand)

MoA: beta 1 receptor blocker (cardioselective). No ISA. Low lipid solubility (does not cross BBB, excreted by kidney). Reduces CO (decrease contractility, maybe HR), inhibits release of renin, decrease O2 demand in heart

USE: HTN (less effective in black, elderly pt, chinese more sensitive) , preventative tx ofangina, preventing exercise-induced angina, tx "silent" ischemia, arrhythmias, tx reflex ADR of nitrates (i.e. tachycardia)

ADR: bradycardia, reduced exercise ability/easier fatigue, slow AV conduction, suppress ventricular contractility, rebound HTN/angina with sudden withdrawal, mask warning sign of insulin-induced hypoglycemia (tachycardia), sweating is not diminished, insulin resistance with glucose intolerance, hypertriglycerideia, fall in HDL-cholesterol

MoA: combined alpha1 and beta 1/2 receptor blocker (competitive). decreases TPR (alpha1 block) but some dec in CO/renin

USE: PO for more severe primary HTN, IV for hypertensive crisis

ADR: from alpha blockade: postural dizziness

from beta blockade: bradycardia, A/V block at high doses

MoA: selective competitive beta-1 blocker, increases production/release of NO, decreases NO degradation. beta-1 decreases renin release, HR, contractility, NO dilates vascular smooth muscle (dec TPR and CO)

USE: mild-moderate primary HTN

ADR: similar to other beta1 blockers, headache, fatigue 

MoA: decrease TPR through dilating arterioles, release of NO, "rapid" acetylators have smaller drug effects, dilate resistance arterioles (inc filtration--> edema), inc renal retention of Na/water, activates sympathetic, renal compensatory rxns (release of catecholamines/renin)

USE: with beta blocker/diuretic to have BP fall efficaciously (loss of edema, tachycardia ADR also), third drug of choice for those not responding

ADR: compensatory mechanisms, lupus-like reaction, not as much postural hypotension (does NOT act on veins) 

MoA: calcium channel blocker that suppresses CO by reducing ventricular contractility (decrease Ca entry through L-type calcium channels), some dec in HR/arterial tone

USE: available in slow release (safer), for all types of primary systemic HTN (work well in elderly, black pt), work well regardless of high Na intake, irrespective of degree of Na sensitivity 

ADR: directly suppressed HR/AV conduction, nausea, headache, short acting preps cause MI

MoA: dihydropyridine, lowers BP by reducing Ca entry into arterial vascular smooth muscle cells through arterial L-type calcium channels, decrease in Ca reduces arterial vascular tone (TPR, BP fall), little suppresssive effect on contractility, intrinsic natriuretic capacility (inhibit Na/water retention) 

USE: available in slow-release, for all types of primary HTN (work well in elderly, black pt), work well regardless of sodium intake or degree of Na sensitivity 

ADR: inc HR (from peripheral vasodilation), nausea, HA, slight postural dizziness, ankle edema, tachycardia (edema so bad, may preclude use of drug), short acting can cause MI

MoA: ACE-I (prototype), eliminated by kidneys. Prevents conversion of angiotensin I to angiotensin II (active), overcome TPR, BP falls, synthesis of aldosterone also inhibitied, inactivates bradykinin (increase availability of bradykinin and related PG vasodilators), inhibit release of NE

USE: primary HTN pt with normal/high renin, secondary HTN for diabetic nephropathy, start low for pt with high renin primary HTN (first-dose hypotension ADR), not recommended for pt with established bilateral renovascular HTN (more loss of GFR) 

ADR:  hyperkaleia, too much hypotension, higher bradykinin (nonproductive cough), angioedema (uncommon, but serious--fatal rxn), harm fetal development

Drug interactions:  hyperkalemia worsesn with K sparing diuretic/K supplements, NSAIDs block bradykini-mediated vasodilation

MoA:  competitive antagonist of angiotensin II at its main receptor (subtype I), has active metabolite, angiotensin II mediated vasoconstriction is overcome and TPR, BP fall, A-II mediated synthesis of aldosterone inhibited

USE: primary HTN, for HTN pt secondary to diabetic nephropathy, small doses for intiail therapy (for those with "high renin primary HTN"-- lead to first-dose hypotension), not recommended for pt with fully established bilateral renovascular HTN (more loss of GFR)

ADR: hyperkalemia, too much hypotension, harm fetal development

Drug interactions: hyperkalemia worsened with K sparing diueretic/K supplement

MoA: renin inhibitor, eliminated unchanged, PO QD, indirectly block synthesis of Angiotensin II (A-II vasoconstriction overcome, TPR/BP falls), A-II mediated synthesis of aldosterone is inhibited

USE: primary HTN, for HTN pt secondary to diabetic nephropathy, small doses for initial therapy (for those with "high renin primary HTN"-- lead to first-dose hypotension), not recommended for pt with fully established bilateral renovascular HTN (more loss of GFR)

MoA: wide range of duration of preps (minutes--SL to hours--transdermal), denitrated in liver (first pass effect high), rapidly become NO: venous smooth muscle more sensitive than arteria, smooth muscle relaxation leads to extensive peripheral vascular dilation: reduced CO (reduced preload at low doses) (and reduced afterload, high doses only), reduction in cardiac oxygen demand (not an increase in coronary flow), inhibit platelet aggregation

USE: tx 3 major times of angina, tx of acute anginal pain after it starts (SL), prevenative (SR), transdermal

ADR: orthostatic (postural) hypotensive sx, headache, reflex inc in HR/contractility, sodium/water retention, tolerance (with continuous exposure), rebound angina, hypotensive interaction with phosphodiesterase-5- inhibitors (i.e. viagra) 

MoA: shifting source of fuel in myocardium from fatty acid to glucose (demands less O2, increased efficiency), inhibition of increased "late" inward-directed sodium current (more likely)

USE: chronic stable angina (in monotherapy or added to other agents if angina not controlled)

ADR: dizziness, HA, nausea, constipation, high doses prolong QT interval in heart

MoA: selective inhibits absorption of dietary/biliary cholesterol, inhibits specific protein-mediated transport system (less cholesterol delivered)

USE: alone or in combination with other drugs (i.e. statins) to treat high LDL type of hyperlipoproteinemias

Pharmacokinetics: PO, converted to active metabolite, enterhepatic recirculation presents more active metabolite 

ADR: when used alone, less ADR, inc liver enzymes when combined with statins

MoA: large copolymers that have ion-exchange capacity (bile acid binding resin/sequestrants), resins exchange Cl for bile acid in intestine: bile acid-resin complex cannot be reabsorbed so body makes more cholesterol thru increase in hepatic LDL receptor numbers (gets LDL to go down). VLDL synthesis/release is increased (can be prolonged in pt with already high VLDL)

USE: used with diet/other drugs to treat high LDL type hyperlipoproteinemia, no benefit for other types (and may actually aggravate other types by raising VLDL), used PO

ADR: resins are not absorbed (NO systemic toxicity), GI rxns are common: bloating/nausea/constipation, etc. not very palatable

Drug interactions: can inhibit absorption of thiazide diuretics, antibiotics, barbitrates, ezetibe, statins (use separate administration time), interference with fat souble vitamin/iron absorption, causes weight loss by malabsorption of other nutrients

MoA: prodrug (require activation) inhibit HMG-CoA reductase in liver (early rate limiting step in the biosynthesis of cholesterol), reduces overall systemic availability of choleseterol, indirectly induce liver/peripheral tissues to increase LDL receptors (more reduction of LDL cholesterol), MOST POWERFUL LDL-cholesterol (non-HDL cholesterol lowering agent)

USE: more effective than other drugs at reducing LDL, indicated alone or as adjunct to diet and other drugs to reduce elevated LDL, taken PO (extensive first pass metabolism), excreted in feces by secretion of bile

ADR: generally well-tolerated, mild/transient ADR, liver dysfunction (inc in serum transaminase in a small amount of pt, recommended LFT), myopathy (increase in plasma creatine kinase levels, monitor for muscle weakness/pain)

C/I: actie liver disease, pregnancy/lactation

MoA:  increased clearance of VLDL (increased lipoprotein lipase activity), increased activity of PPAR-alpha OR PPAR-alpha mechanism: increased enzymes for oxidation of FFA in liver, less FFA available for VLDL production/secretion, may also increase heaptic LDL receptors (dec plasma LDL), dec VLDL more than LDL (may be most effective drug to reduce VLDL), may also increase HDL thru PPAR-a

USE: primary hyperlipidemias with high VLDL, hypertriglyceridemia secondary to some defect in apolipoprotein E (form of dysbetalipoproteinemia) PO

ADR: gallstone formation (rare but serious), most common is GI upset/nausea, risk of myopathy (especially when combined with statins)

MoA: inhibits intracellular lipolysis in fat cells by presumably inhibiting intracellular lipase actiivty in adipocytes. reduces plasma VLDL by indirectly inhibiting VLDL synthesis (may also inhibit VLDL secretion), increases VLDL catabolism by enhancing activity of extracellular lipoprotein lipase (decreases VLDL), increases HDL (most effective drug for this)

USE:  treatment of all primary types of hyperlipidemias (least expensive of lipid lowering drugs), decreaes VLDL and LDL (increases HDL), PO, metabolized to vitamin which has no lipid lowering activity

ADR: flushing/itching, burning feeling of skin (mediated by PG release from immune cells-- diminish effect by taking aspirin 30 minutes prior to niacin), hypotension for pt already on anti-HTN drugs, increases liver enzymes (LFT recommended), mild hyperglycemia, glucose intolerance especially in diabetics, GI disturbances, peptic ulcer (gastric acidity) except when combined with bile acid binding resin, elevated plasma uric acid

MoA: inhibit hepatic synthesis of triglycerides from endogenous FFA through increased beta-oxidation of endogenous FFA, decreased delivery of endogenous FFA to the liver, decreased syntheiss of endogenous FFA, decreased acitivty of triglyceride-syntehsizing enzymes, may also increase HDL but only slightly

USE: adjunct to diet to reduce high plasma triglyceride levels (decreases VLDL, LDL not effected), used with statins for pt with both LDL and VLDL (less risk of myopathy than cobinations like fibrates with statins)

ADR:  flu/infection sx, mild GI distress, "fishy" belching, inhibit platelet aggregatation too much/cause bleeding (monitor if pt is on anticoagulants)