Alteplase

Abciximab

(Activase
(ReoPro) )

Anistreplase
Amino Caproic Acid

(Eminase
(Amicar) )

Aprotinin
(FDA has suspended marketing) Ardeparin

(Trasylol
)

Aspirin
Argatroban

(Acetylsalicylic
(Acova) acid)

Clopidogrel
Bivalirudin

(Plavix
(Angiomax) )
 Fibrinolytic (Thrombolytic)
Antiplatelet Agent – GPIIb/IIIa Antagonist
tPA (tissue plasminogen activator) that is produced by
Fab fragment of a monoclonal antibody that prevents platelet
recombinant DNA technology & has ½ life of 4-8 min
aggregation by binding to the platelet glycoprotein IIb/IIIa
Requires fibrin for activity so may only activate
receptor, which prevents binding of adhesive glycoproteins
plasminogen in situ so it should cause less random
(fibrinogen, von Willebrand factor, etc) to surface of activated
proteolytic destruction of blood clotting factors (lytic
platelets (This is the Final Common Pathway of Platelet
state), which occurs when plasminogen is activated in the
Aggregation); Not Specific for GPIIb/IIIa; Rapid onset;
blood; May have ability to lyse more highly cross-linked
Activity lasts for 24-48hrs; Elimination by platelet binding;
fibrin, which is a consideration for pts who have had
Hospital use only; Antibody response possible
symptoms of longer duration; Approved in acute ischemic
Adverse effects: bleeding (usu at site of arterial access),
stroke (w/in 3hrs onset & after exclusion of intracranial
thrombocytopenia (more than other GPIIb/IIIa antagonists)
hemorrhage)

Hemostatic
Fibrinolytic (Thrombolytic) - Anisoylated Plasminogen
Streptokinase Activator complex (known as APSAC)
Binds reversibly to plasminogen and thereby blocks the
An acylated inactive complex of streptokinase and human lys-
binding of plasminogen to fibrin & its activation and
plasminogen with a ½ Life of 70-120 minutes
transformation to plasmin
Upon injection, the acyl group is hydrolyzed slowly to
produce an activator that converts plasminogen to plasmin
Useful in enhancing hemostatic when fibrinolysis contributes
Can cause proteolytic destruction of blood clotting factors
to bleeding, but not FDA approved for bleeding
(lytic state), which occurs when plasminogen is activated in
accompanying fibrinolytic use
the blood stream b/c it does not require fibrin for activity
Contraindicated in patients with DIC

Broad spectrum polypeptide serine protease inhibitor, isolated

from bovine lung; forms complex w/ plasmin, kallikreins, &
other factors to block kinin & fibrinolytic systems; Admin iv
to modulate systemic inflam response (SIR) & risk of stroke
Low Molecular Weight Heparin assoc w/ high risk coronary artery bypass grafting (CABG);
Attenuates inflam resp, fibrinolysis, & thrombin generation;
Not on market preserves platelet function bleeding & need for
transfusions; can be given w/ heparin to prevent thrombosis;
Allergic/anaphylactoid rxn may occur, assoc. w/ serious
organ damage (2-3X risk of renal failure req dialysis, risk
of MI or heart failure & risk of stroke or encephalopathy

Salicylate -Analgesic, antipyretic & anti-inflammatory

Uses: Juvenile RA, MI & colon cancer prevention Direct reversible thrombin inhibitor, including clot-bound
CI: asthma, gout, ulcer, influenza thrombin
Inhibits PG biosynthesis (irreversible acetylation of COX); Synthetic
blocks platelet aggregation for life of platelets (8-10d); Oral Admin iv (infusion); ½ life is short (40-50min)
well absorbed ½ t 15-30 min., Mainly excreted as salicyluric Hepatic eliminated so not affected by renal impairment
acid by kidney; NSAIDS prior to ASA may protect COX so (unlike lepirudin)
take ASA 2h before NSAID (acetaminophen doesn’t do this) Not immunogenic
Side effects: Tinnitus/deafness (early tox), GI intol., trans. Monitored by aPTT (1.-3.0 times baseline)
renal fxn., hepatotoxicity, respiratory alkalosis-metabolic No known antidote
acidosis, headache, confusion, drowsiness & sweating

Oral Prodrug Antiplatelet Agent – ADP Pathway Inhibitor Direct Reversible Thrombin Inhibitor
Irreversibly blocks purinergic receptor (P2Y12 coupled to inhib Synthetic 20-amino acid derivative of hirudin (anti-coag in
G proteins) for ADP indirectly inhibits binding of leeches) that can inactivate platelet bound Xa & clot bound
fibrinogen to platelet receptor GPIIb/IIIa; Better bioavail w/ thrombin (unlike heparin); ½ life in nl renal fxn pts is 25 min;
food); metabolized to active form in liver; std dose (75mg/d), dose reductions recommended in pts w/ renal impairment;
max inhibition of platelet fxn 3-5 days; loading dose of 300- Approved as iv anticoagulant to be used (w/ aspirin,
600mg, accelerates effect to w/in 4-6h; takes ~5d after clopidogrel, & provisional GPI) instead of heparin in pts w/
cessation for plt fxn to return to nl; Adverse effects: diarrhea, unstable angina undergoing PCI; Activity can be monitored by
rash (> ASA), abd pain, dyspepsia, GI bleeding (< ASA); activated clotting time (ACT) or aPTT; Doesn’t cause immune
bleeding in pts. on anti-coag; may cause bone marrow thrombocytopenia; major adverse effect is bleeding (< than
suppression & thrombotic thrombocytopenic purpura heparin); appears to be at least as effective as high-dose UFH
 Dalteparin Dipyridamole

(Fragmin (Aggrenox – dipyridamole

) +aspirin)

Enoxaparin
Eptifibatide

(Lovenox
) (Integrilin)

Fondaparinux
Heparins

(Arixtra
)

Lepirudin
Phytonadione (Vit K1)

(Refluda
n)

Protamine sulfate Reteplase

(Retavase)
 Low Molecular Weight Heparin w/ Anti-Xa:Anti-IIa ratio
of 2.7 (UFH undergone enzymatic or chem depolymerization)
Antiplatelet Agent – PDE/Adenosine Uptake Inhibitor
MW 5.8kDa; Only ~15-25% has pentasaccharide seq
necessary for activity; Excreted primarily by kidneys
Adjunct in prevention of prosthetic valve thromboembolism
Produces more predictable response than UFH b/c better
when used with warfarin
bioavail, longer ½ life, & dose-indep cl; used w/out
monitoring, for long-term prophylaxis in certain pts
Adjunct in prevention of transient ischemia of the brain or
Adverse effects: Major bleeding,, HIT (less common than
complete ischemic stroke caused by thrombosis in patients
UFH); Rx of OD: protamine (neutralizes anti-IIa completely
who already had TIA or ischemic stroke.
& Xa partially) & Withdrawal of drug
NOT INTERCHANGEABLE w/ other LMWHs or UFH

Antiplatelet Agent – GPIIb/IIIa Antagonist
Cyclic peptide that prevents platelet aggregation by binding to of 3.8 (UFH undergone enzymatic or chem depolymerization)
the platelet glycoprotein IIb/IIIa receptor, which prevents
binding of adhesive glycoproteins (fibrinogen, von Willebrand
factor, etc) to surface of activated platelets (This is the Final
Common Pathway of Platelet Aggregation); Specific for
GPIIb/IIIa; no antibody response; used only in hospital
Rapid onset; Activity lasts for ~4h; elimination by renal
primarily
Adverse effects: bleeding (usu at site of arterial access),
thrombocytopenia
Low Molecular Weight Heparin w/ Anti-Xa:Anti-IIa ratio
MW 5.8kDa; Only ~15-25% has pentasaccharide seq
necessary for activity; Excreted primarily by kidneys
More predictable response than UFH b/c better bioavail,
longer ½ life, & dose-indep cl; can be used w/out monitoring,
for long-term prophylaxis in certain pts
Adverse effects: Major bleeding,, HIT (less common than
UFH); Rx of OD: protamine (neutralizes anti-IIa completely
& Xa partially) & Withdrawal of drug
NOT INTERCHANGEABLE w/ other LMWHs or UFH

Anticoagulant
Anticoagulant – Inhibits Xa only
Inhibits Xa & IIa (thrombin) & most proteolytic coag
Synthetic pentasaccharide binding sequence
enzymes, but different types have different specificity;
Excreted primarily by kidneys; once a day dosing
Enhances activity of tissue factor pathway inhibitor (TFPI)
Produces more predictable response than UFH b/c better
Found normally in mast cells & CT; has high density of “-“
bioavail, longer ½ life, & dose-indep cl; can be used w/out
charges; effective both in vivo (esp venous clots) & in vitro;
monitoring, for long-term prophylaxis in certain pts
Needs pentasaccharide seq & antithrombin present for activity
Adverse effects: Major bleeding,, heparin-induced
Parenteral b/c enteral sulfatases remove “-“ charges
thrombocytopenia (rare)
Onset immediate (iv) or 1-3h (UFH), 3-6h (LMWH) or 17-21
Rx of OD: Withdrawal of drug (Protamine does not
h (Fondaparinux) when SC; never IM (hematoma results)
reverse)
TRANSFUSIONS NOT EFFECTIVE IN RX OF OD!!

Warfarin antagonist Direct irreversible inhibitor of thrombin, including clot

Active form of Vit K that can be used by vit K-dependent bound thrombin (doesn’t req antithrombin)
Substitute for Heparin when HIT is present
enzyme γ-carboxylase to convert glutamic acid residues on II,
Recombinant derivative of hirudin (anti-coag in leeches)
VII, IX, X, Protein C & S by γ -carboxylation to Gla (γ Admin iv (0.4mg/kg bolus followed by 0.15mg/kg/hour
-carboxyGlu) form, enabling the clotting factors to bind to Ca, infusion aimed at achieving aPTT ratio of 1.5-2.5
which forms the bridge to platelets, anchoring them to the site No effective antidote but has short ½ life; cleared by renal
of injury; acts only in vivo not in vitro excretion (t 1/2 ~1.3 h) (so affected by renal impairment
Used to treat OD of warfarin, but if therapy is too vigorous, unlike argatroban)
this may complicate re-establishment of warfarin therapy Immunogenic - Anaphylaxis has been observed in pts treated
since K1 has a long duration of action again w/in 3 months of previous exposure

Heparin Antagonist
Fibrinolytic (Thrombolytic)
Used to treat overdose of UFH (completely reverses) &
neutralizes the anti-IIa activity of LMWH (such as
Non-glycosylated deletion mutant of wild type tPA
enoxaparin, dalteparin, tinzaparin), but only partially reverses
Developed to have a longer half-life and to act faster &
the anti-Xa activity
better penetrate a thrombus than Alteplase
Anaphylactoid rxns are possible, so infuse slowly
Bolus 2X 30 min apart; ½ life of 13-16 min
DOES NOT REVERSE FONDAPARINUX
 Streptokinase Tenecteplase

(Streptase, Kabikinase) (TNKase)

Ticlopidine Tinzaparin

(Ticlid (Innohep
) )

Tirofiban
Tranexamic Acid

(Aggrasta
t) (Cyklokapron)

Urokinase Warfarin sodium

(Breokinase, Abbokinase) (Coumadin)

Unfractionated Heparin
UFH vs LMWH & Fondaparinux
(UFH)
 Fibrinolytic (Thrombolytic)
6 amino acids substituted at 3 sites compared to wild type tPA
These mutations prolong plasma ½ life & increases fibrin
specificity & resistance to plasminogen activator
inhibitor-1
Less non-intracranial major bleeding episodes than accelerated tPA;
not antigenic; results in more patency at 90 min than streptokinase; Can cause proteolytic destruction of blood clotting factors (lytic
direct plasminogen activation
Single bolus administration; ½ life of 20-24 min
Low Molecular Weight Heparin w/ Anti-Xa:Anti-IIa ratio of
1.9(UFH undergone enzymatic or chem depolymerization)
MW 5.8kDa; Only ~15-25% has pentasaccharide seq necessary for
activity; Excreted primarily by kidneys
Produces more predictable response than UFH b/c better bioavail,
longer ½ life, & dose-indep cl; can be used w/out monitoring, for
long-term prophylaxis in certain pts
Adverse effects: Major bleeding,, HIT (less common than UFH);
Rx of OD: protamine (neutralizes anti-IIa completely & Xa
partially) & Withdrawal of drug
NOT INTERCHANGEABLE w/ other LMWHs or UFH
Hemostatic
Binds reversibly to plasminogen and thereby blocks the binding of
plasminogen to fibrin & its activation and transformation to plasmin
Useful in enhancing hemostatic when fibrinolysis contributes to
bleeding, but not FDA approved for bleeding accompanying
fibrinolytic use
Contraindicated in patients with DIC
Oral & Parenteral Anticoagulant ; formation of clotting factors
II,VII, IX, X, protein C & S b/c require Vit K (drug inhibits KO
reductase (major effect) & K reductase, which converts vit K to
active form); Prevents γ -carboxyglutamic acid residues (Ca binding
sites) from being added, so can’t bind to platelets; Major disadv:
latent period (long onset & peak effect); Not used in HIT b/c assoc Can cause proteolytic destruction of blood clotting factors (lytic
w/ venous limb gangrene or multicentric skin necrosis (def protein C state), which occurs when plasminogen is activated in the blood
which is thrombotic); Adverse effects: bleeding (risk h esp if hx of
GI bleeding); recurrent skin necrosis (thrombosis of venules/
capillaries of SC fat); OD Rx: plasma transfusion & Vit K1
LMWH & Fondaparinux has a more predictable anti-coag response
( binding to plasma proteins & proteins released from activated
platelets & endothelial cells); better bioavail at low doses ( binding
to endothelium); dose-indep clearance mech & half-life ( binding
to macrophages)
None of them need monitoring when used prophylactically (except in
pts w/ renal insuff & pts weighing <50kg or >80kg), but UFH needs
aPTT (1.5-2.5 aPTT) or plasma heparin concentrations (via anti-
factor Xa assay w/ TI levels .3-/7IU/mL or protamine titration)
during treatment
Fibrinolytic (Thrombolytic)
Binds to plasminogen thereby converting plasminogen into a
plasmin-like molecule capable of converting plasminogen to plasmin
(i.e. indirect plasminogen activation)
iv or ic infusion; ½ life of 23-29 min; antigenic; results in less
patency at 90 min than alteplase, reteplase, or tenecteplase
state), which occurs when plasminogen is activated in the blood
stream b/c it does not require fibrin for activity
Antiplatelet Agent – ADP Pathway Inhibitor
Irreversibly blocks purinergic receptor (P2Y12 )for ADP, so indirectly
inhibits the binding of fibrinogen to platelet receptor GPIIb/IIIa ;
Well absorbed from GI (better bioavail w/ food); metabolized to
active form in liver; std dose (250mg/BID), max inhibition of platelet
fxn 3-5 days; takes ~5d after cessation for plt fxn to return to nl;
Adverse: diarrhea, rash (> ASA), abd pain, dyspepsia, GI bleeding (<
ASA); bleeding in pts. on anti-coag; bone marrow suppression
(neutropenia ~1%, aplastic anemia), thrombotic thrombocytopenic
purpura; Antacids absorption & cimetidine metabolism
Antiplatelet Agent – GPIIb/IIIa Antagonist
Tyrosine derivative (non-peptide) that prevents platelet aggregation
by binding to the platelet glycoprotein IIb/IIIa receptor, which
prevents binding of adhesive glycoproteins (fibrinogen, von
Willebrand factor, etc) to surface of activated platelets (This is the
Final Common Pathway of Platelet Aggregation); Specific for
GPIIb/IIIa; No antibody response; only used in hospital; Rapid
onset; Activity lasts for ~4-8h; Elimination renal ; Adverse effects:
bleeding (usu at site of arterial access), thrombocytopenia
Fibrinolytic (Thrombolytic)
Proteolytic enzyme that converts plasminogen to plasmin directly
Has a half-life of 14-20 minutes
stream b/c it does not require fibrin for activity
Anticoagulant - Inhibits Xa & IIa –thrombin equally
GAG from bovine lung or porcine gastric mucosa; Variable MW;
must be standardized (unit base dosing); Only ~1/3 has necessary
pentasaccharide seq for activity; Endothelial cells & macrophages
clear (rapid & dose depend) & much slower renal 1st order mech;
binds to several plasma proteins (makes inactive) = nonlinear resp
(both intensity & duration disproportionally w/ dose); ½ life
dose depend
Adverse effects: major bleeding, osteoporosis (prolonged use, preg
women), heparin-induced thrombocytopenia (HIT)
Treatment of OD: withdrawal (usu sufficient), protamine
Heparin-induced thrombocytopenia (HIT)
(Note: Type 1: Benign transient, so
Citrate
information is for Type 2, which is more
severe)

Recombinant activated coagulation factor

Oxalate VII
(rFVIIa)

(NovoSeven)

Treatment of venous thromboembolism Treatment of unstable angina

Anticoagulant prophylaxis in moderate-risk Indicated in Heparin-induced

or high risk patients thrombocytopenia with thrombosis

Factors that determine pt’s response to oral

Used in angioplasty
anticoagulants
 Occurs when pts dev antibodies (IgG) against complexes of UFH
& platelet factor 4 that activates platelet FcγRIIa receptors & plt
Chelating Agent count 50% or more; Occurs 5-10dys after 1st exposure or w/in
24hrs of admin if prior exposure, esp if prior exposure w/in the past
Binds Calcium 100dys; Occurs w/ bovine lung > porcine mucosal heparin; iv> SC;
UFH > LMWH >> Fondaparinux; Pt w/ highest risk are
Used in vitro only (blood storage) to prevent clotting postoperative orthopedic, cardiac & vascular surgery pts getting
UFH for 1-2 wks; danger is b/c assoc w/ DVT, DIC, PE, cerebral
thrombosis, MI & ischemic injury to legs or arms (White Clot
Syn); Rx: Change therapy to lepirudin or argatroban

Hemostatic
Treatment of bleeding episodes in hemophilia patients with inhibitors
(antibodies) to factor VIII or IX Chelating Agent
Currently being used “off-label” to stop bleeding in pts w.
intracerebral hemorrhage (hemorrhagic stroke) & other instances of Binds Calcium
uncontrolled bleeding (major trauma)
Used in vitro only (blood storage) to prevent clotting
Use in intracerebral hemorrhage has been assoc. w/ serious
thromboembolic adverse events (myocardial or cerebral infarction)

UFH (when rapid reversal is important) UFH (when rapid reversal is important)

Enoxaparin Enoxaparin

Dalteparin Dalteparin

Bivalirudin Tinzaparin

Enoxaparin – moderate or high risk

Dalteparin – moderate or high risk
Lepirudin Tinzaparin – moderate or high risk

Argatroban Fondaparinux – high risk only

Warfarin

Vitamin K levels ( intake= warfarin effect) – inadequate diet,

fat malabsorption = vit K; lots of green veggies & supplements w/
high K = vit K
Liver dz , Elderly, Congestive heart failure (results in hepatic
congestion) or Slow metabolizers due to CYP2C9 & VKORC1
(vit K epoxide reductase complex subunit 1) – metabolism = Bivalirudin
warfarin effect
Infection, following surgery, hypermetabolism – increases
sensitivity to warfarin
Significant interactions can occur when any drug is added or
removed
 Drugs/foods that will inhibit warfarin
Drugs that will potentiate warfarin effects
effects
(These are the specific ones Dr. Benz said to know)
(These are the specific ones Dr. Benz said to know)

Contraindications to Anticoagulant,
Therapy Recommendations for Treatment of
Fibrinolytic Therapy, & Glycoprotein
DVT
IIb/IIIa Antagonists

Therapeutic Uses of Fibrinolytic Agents Adverse effects of Fibrinolytic Therapy

Aspirin Doses Indications for Clopidogrel & Ticlopidine

Indication for Glycoprotein IIb/IIIa

Antagonists (GPIs)
(Abciximab, Eptifibatide, Tirofiban)
 Barbiturates
Cholestyramine
High Vitamin K content of foods/enteral feeds
1) Use heparins immediately b/c they have rapid onset of
Active bleeding; Severe bleeding diathesis or platelet count
action
<20,000/mm3; Neurosurgery, ocular surgery, or intracranial
2) Administer warfarin at same time as heparin
3) Do not discontinue heparin until the INR indicates that
warfarin is effective (~5days usually)
brain metastases, recent major trauma, major abd surgery w/in
INR necessary for most conditions is 2.0-3.0 EXCEPT for
mechanical prosthetic heart valves, which are high risk, has a
endocarditis, severe HTN (SBP>200, DBP>120 or both) at
recommended INR of 2.5-3.5
Bleeding (esp intracranial hemorrhage (streptokinase
<alteplase, reteplase, & tenecteplase)
Arrhythmias (may occur on reperfusion)
Fever and allergic reactions (streptokinase only)
Prophylaxis before (300-600mg, 4-6h) and after (75mg.d, 9-
12months) for percutaneous coronary intervention (PCI) in
combination w/ aspirin
Also used in acute coronary syndrome (ACS-unstable angina
or non-ST segment elevation MI or non-Q wave MI), post MI
prophylaxis, & for stroke prevention in pts w/ transient
ischemic attacks (TIA) or previous thrombotic stroke
(Pts on clopidogrel+ASA & scheduled for CABG should d/c
the clopidogrel 5-7 days before surgery otherwise at increased
risk for major bleeding)
Amiodarone (nonselective for enantiomer)
Fluconazole (selective for S enantiomer)
Omeprazole (selective for R enantiomer
Absolute:
bleeding w/in past 10 days; pregnancy
Relative:
Mild-to-moderate bleeding diathesis or thrombocytopenia,
past 2 days; GI or GU bleeding w/in past 14 days,
presentation
Acute myocardial infarction (primary angioplasty is better if
available), clots of PE & DVT, acute peripheral artery
thrombosis, acute ischemic stroke (alteplase)
Can reduce mortality significantly, most effective when used
shortly after thrombus formation since recently formed
thrombi are easier to lyse than aged (cross-linked thrombi);
Venous thrombi easier to lyse than arterial thrombi;
Concomitant admin of ASA & iv UFH can be used; bolus
agents permit admin by emergency personnel outside of
hospital
Prevention of recurrent MI, MI in pts w/ unstable
angina, or MI & death in pts. w/ stable angina: 75-
235 mg Qday; Prevention of vascular mortality in
suspected MI: 160-162.5 mg ASAP, continued for 30 days
then consider continued use; Post-revascularization w/
CABG: 325mg starting 6hrs post-procedure & cont 1 yr;
PTCA: 325mg 2hrs pre-surgery, then 160-325mg daily;
Carotid endarterectomy: 80mg Qday to 650mg BID
pre-surgery & cont indef; Prevention of death &
recurrent stroke following TIA or ischemic stroke:
50-325 mg Qday; Analgesic & antipyretic: 650mg;
Anti-inflammatory: Up to 4g/d
Adjunct in pts w/ ischemic heart dz undergoing or abt to
undergo PCI w/ or w/out stenting or thrombolysis
In low to intermediate risk pts, who have previously received
aspirin & clopidogrel, GPI’s appear to offer no additional
benefit
In high risk pts (those w/ ACS, recent MI, bypass-graft
stenosis, chronically occluded coronary arteries, or
angiographically visible intracoronary thrombus), aspirin,
clopidogrel and GPI’s are indicated.
 Beta blockers Angiotension Converting Enzyme Inhibitors

Loop Diuretics Sodium nitroprusside

Spironolactone
Angiotensin Receptor Blockers

(Aldactone
)

Hydralazine

Eplerenone
(BiDil – hydralazine +Isosorbide
dinitrate)
(Apresoline
) (Inspra)

Carvedilol Thiazide Diuretics

(Coreg)
 Antihypertensive & for Heart Failure
Most are prodrugs that inhibit conversion of angiotensin I to
angiotensin II
Increases plasma renin activity, but decreased angiotensin II levels (
vasoconstriction & aldosterone)
Decreases PVR, no change in HR, decreases preload and afterload
Decreases symptoms of heart failure & increased survival
Arterial & venous dilator
Stim. guanylyl cyclase cGMP either release of
NO or by direct stimulation of the enzyme
Continuous iv infusion; rapid onset & offset of
action = close monitoring necessary
Aq. solution photosensitive
Elimination: Na2Fe(CN)5NO CN SCN urine
Adverse effects: Hypotension, Cyanide & thiocyanate toxicity
Used in hypertensive emergencies (caution in pts w/ intracranial
pressure or azotemia) and in heart failure ( preload & afterload)
Inhibits type 1 angiotensin II receptors (AT1)
pressor response to infused angiotensin I & II; plasma renin
activity & plasma angiotensin II levels
Adverse effects: Hypotension (esp if vol depleted), dizziness (low hyperaldosteronism), nephrotic syndrome, heart failure (low dose
incidence), K+ can occur, angioedema (less freq than w/ ACE
inhibitors), BUN & Cr in pts w/ bilateral RAS (same as ACE
inhib), fetal toxicity & birth defects (same as ACE inhib), less likely
to cause cough
K-Sparing Diuretic - Mineralocorticoid Receptor Antagonist
Selective synthetic steroid binds to cytoplasmic aldo receptor,
preventing binding of aldo which Na reabsorption & K & H
secretion in late distal tubule & collecting duct
Used to treat dz states assoc. w/ plasma aldo levels (1º & 2 º
hyperaldosteronism) & in combo w/ thiazide or loop diuretics in pts
w/ edema & hypertension; recently approved for heart failure
following acute MI in certain cases
Adverse effects: Hyperkalemia, metabolic acidosis (possible)
Blocks salt reabsorption in distal convoluted tubule (DCT) inhibiting
NaCl symporter in luminal membrane PVR & often reduces
urinary calcium excretion
Rx: HTN, idiopathic hypercalciuria, heart failure (effect on survival
unk, preload, congestive symptoms)
Unlikely to be effective if GFR <30mL/min
Adverse: Hypokalemia, metabolic alkalosis, hyperuricemia,
hyperglycemia, some lipid , vol depletion, hyponatremia, allergic
rxn., NOT assoc. w/ ototoxicity
Less effect than loop diuretics but greater than K-sparing
β receptor adrenergic antagonists
Rx: antihypertensive, antianginal & heart failure
O2 demand effects: decreased - HR, systemic BP, &
contractility, increased by LVEDV; O2 delivery effects: some
redistrib blood flow to ischemic areas
Sudden withdrawal – exacerbation of angina MI possible
May worsen heart failure initially & improvement may take months
DO NOT USE IN VASOSPASTIC ANGINA
Blocks NaCL reabsorp in TAL by inhibiting Na-K-2Cl symporter;
In pts. w/ heart failure, preload. & improvement in pulmonary
congestion –beneficial in acute pulm but effects on survival unk.
Edema; urinary Ca excretion ( Ca reabsorption in ascending limb)
Rx for HTN, hypercalcemia, heart failure
Adverse effects: hypokalemia (cardiac arrhythmias, potentiates
effects of digitalis), metabolic alkalosis, hyperuricemia,
hyperglycemia, some lipid h, volume depletion, hyponatremia,
ototoxicity, allergic rxn.
K-Sparing Diuretic - Mineralocorticoid Receptor Antagonist
Synthetic steroid that binds to cytoplasmic aldo receptor, preventing
binding of aldo which Na reabsorption and K & H secretion in
late DT & CD
Rx: dz states assoc. w/ plasma aldo levels (1º & 2 º
freq of hospitalization & mortality – must monitor serum K &
renal fxn), cirrhosis w/ ascites & in combo w/ thiazide or loop
diuretics in pts w/ edema & hypertension
Adverse effects: Hyperkalemia, metabolic acidosis (possible),
other endocrine effects (gynecomastia in males)
Arterial vasodilator via direct relaxation
PVR ( afterload) & lowers BP, but activates compens. resp.
(sympathetic stim, salt & water retention)
Can use w/ β-blocker & diuretic, or w/ organic nitrate in African-
American pts w/ heart failure
Oral & iv administration, but metabolized partly by acetylation
Adverse effects: Palpitations, angina, headache, drug-induced lupus
(greatest in slow acetylators), fluid retention
Mixed β>α1 receptor antagonist & Antihypertensive agent
High lipid solubility & metabolized by liver & kidneys
Rx: HTN & heart failure in certain pts ( freq of hospitalizations &
mortality)
Adverse effects: myocardial contractility, bradyarrhythmias,
bronchospasms, prolong hypoglycemia in pts taking insulin,
triglycerides, HDL-cholesterol, fatigue, sleep disturbance,
depression, hypertensive response in some situations
(pheochromocytoma), sudden withdrawal – exacerbation of
angina esp if MI has occurred
NSAIDS may reduce BP lowering effect
 Dopamine
Dobutamine

(Dobutrex)

Calcium channel blockers

Metoprolol

(Lopressor, Toprol XL)

Nifedipine
Propranolol

(Inderal)

Diltiazem Nitroglycerin

(Nitrostat, Nitrodur)

Isosorbide dinitrate Isosorbide-5-mononitrate

(BiDil – hydralazine +Isosorbide dinitrate)

(Isordil Titradose, Dilatrate-SR, Isochron) (Imdur, Monoket)

DAergic neurotransmitter
Can produce renal vasodilation due to presence of DA receptors in
kidney vessels
Does not cross BBB
Controls motor activity in caudate-putamen area of brain
Associated w/ positive reinforcement in limbic area of brain
Used parenteral in heart failure b/c positive inotrope
β1 receptor antagonist - Cardioselective (β 1>>> β 2)
Produces local anesthetic effect, has moderate lipid solubility, &
metabolized by liver
Rx: HTN & heart failure ( freq of hospitalizations & mortality)
Adverse effects: contractility, bradyarrhythmias, prolong
hypoglycemia in pts taking insulin, bronchospasms, sleep disturb,
triglycerides, HDL-cholesterol, fatigue, depression, hypertensive Vasodilation (mainly arterial), some classes HR via sinus node
response w/pheochromocytoma, sudden withdrawal – exacerb of
angina esp if MI has occurred
NSAIDS may reduce BP lowering effect
1,4-Dihydropyridine Ca Channel Blocker w/ Oral admin
High vascular selectivity (ratio of vasc to cardiac effects) =
sympathetic reflex & contractility but vasodilation & SNS
activation tends to counter this results in BP, PVR
Rx: HTN, angina (atherosclerotic & vasospastic)
Adverse effects: dizziness, hypotension, headache, flushing,
constipation, peripheral edema, aggravation of ischemia, MI w/
immed release due to SNS reflex. Rare: bradycardia, AV block,
cardiac arrest, heart failure
Organic Nitrate - Releases NO endothelium cGMP prod
Available as short-acting (sublingual– rapid onset) & long-acting
(oral– sign. 1st pass metabolism, ointment, patch, buccal); also
available in a lingual spray & iv
Relaxes veins, some arterial, & other smooth muscles (esophageal,
biliary tract) and has an antiplatelet effect
Rx: relieve acute attacks (sublingual tabs) & prophylaxis of chronic
effort-assoc angina and effective in vasospastic angina
Adverse effects: headaches, orthostatic hypotension, rashes
occasionally. Sildenafil, tadalafil, & vardenafil worsens hypotensive
effects
Organic Nitrate - Releases NO endothelium cGMP prod
st Available as short-acting (sublingual) & long-acting (oral – ~100
Available as long-acting (oral– sign. 1 pass metabolism)
Relaxes veins, some arterial, & other smooth muscles (esophageal,
Relaxes veins, some arterial, & other smooth muscles (esophageal,
biliary tract) and has an antiplatelet effect
Rx: Prophylaxis of chronic effort-assoc angina &
Rx: chronic effort-assoc angina (acute & prophylaxis) & vasospastic
effective in vasospastic angina
Adverse effects: headaches, orthostatic hypotension,
rashes occasionally. Sildenafil, tadalafil, & vardenafil worsens
occasionally. Sildenafil, tadalafil, & vardenafil worsens hypotensive
hypotensive effects
Selective β1 receptor agonist
May increase cardiac output with less reflex tachycardia than occurs
with nonselective β agonists such as isoproterenol
Short term iv infusion w/ rapid onset & ½ life ~2 minutes
Used parenteral in heart failure b/c positive inotrope
Adverse effects: Excessive increase in heart rate, arrhythmias, &
other
Interacts with L-type Ca channels to cellular uptake of Ca2+.
Some also block other cardiac ion channels
Decreases O2 demand ( HR, & mycoardial work) and increases O2
supply (vasodilate coronary a)
Classes: phenylalkylamine, dihydropyridine, & Benzothiazepines
Rx: HTN, angina, certain cardiac arrhythmias
pacemaker rate, some classes AV conduction, all classes
contractility
All classes have large 1st pass effect
Nonselective β blocker & Antiarrhythmic Class II
HR & contractility CO; mb stabilization; renal renin release;
CNS effects not major (although used for stage fright) Produces local
anesthetic, high lipid sol., & metabol by liver
Adverse effects: myocardial contractility, bradyarrhythmias,
bronchospasms, prolong hypoglycemia in pts taking insulin,
Triglycerides, HDL-cholesterol, fatigue, sleep disturbance,
depression, hypertensive response in some situations
(pheochromocytoma), sudden withdrawal –exacerbation of angina
esp if MI has occurred
NSAIDS may BP lowering effect
Benzothiazepine Ca Channel Blocker w/ Oral or iv admin
Lower vascular selectivity (ratio of vasc to cardiac effect) than
diphydropyridines (=less sympathetic reflex), AV conduction,
sinus node pacemaker rate HR & contractility results in
BP, PVR, HR
Rx: HTN, Angina (atherosclerotic & vasospastic), supraventricular
tachyarrhythmias
Adverse effects: dizziness, hypotension, headache, flushing,
constipation, peripheral edema. Rare: aggravation of ischemia,
bradycardia, AV block, cardiac arrest, heart failure
CAN INCREASE PLASMA DIGOXIN LEVELS
Organic Nitrate - Releases NO endothelium cGMP prod
bioavailability, chewable oral, sublingual)
biliary tract), preload, antiplatelet effect
angina, heart failure w/ hydralazine in Afircan-Americans
Adverse effects: headaches, orthostatic hypotension, rashes
effects
 Ranolazine
Digoxin immune fab (ovine)

(Ranex
a)

1,4-Dihydropyridines Nesiritide

Adverse effects of Digitalis Digoxin

Factors that increase risk of digitalis toxicity Quinidine

Cardiac glycosides Milrinone


Fab Antibody Fragment derived from sheep that binds to digoxin
Used in overdose of digoxin to reverse toxicity effects
Recombinant human B-type natriuretic peptide (hBNP)
Approved for use in certain pts w/ acute decompensated heart failure
Decreases pulmonary capillary wedge pressure & dyspnea
Mech involves action on particulate guanylate cyclase receptor
increased cGMP smooth muscle relaxation
Iv admin (pharmacokinetic ½ life ~18 min but pharmacodynamic ½
life longer than this would predict – hypotension may last hrs),
clearance receptors on cells
Adverse effects: Hypotension, significant renal damage & deaths
Rx: heart failure ( symptoms, hospitalizations) &
supraventricular tachyarrhythmias (atrial fib & flutter) Cardiac arrhythmias such as: atrial tachycardia w/ AV block, AV
Inhibits Na,K-ATPase pump in heart to contractility b/c Ca block (1st, 2nd, or 3rd degree), AV junctional rhythm, vent premature
inside cell; Vagal efferent act, HR, atria ERP & contractility,
& AV conduction ( ERP and conduct vel.)
OD Rx: Stop drug, serum K management, arrhythmia & heart block
management, & role of digoxin immune fab (ovine)
Admin oral or iv. Cl reduced in renal insufficiency
DI: thiazide or loop diuretics (hypokalemia binding); quinidine, Delayed afterdepolarizations, arrhythmias, heart block possible;
verapamil or amiodarone ( concentration), antacids, kaolin-pectin,
cholestyramine ( concentration)
Antiarrhythmic Class IA
Rx: Atrial fib & flutter, serious vent arrhythmias
Blocks activated Na channels ( conduction velocity) & K
channels ( AP duration ERP). Also α blockade, antimuscarinic
& antivagal (may cause paradoxical vent rate in pts w/ atrial
flutter). Hepatic & some kidney metabolism
Adverse effects: torsades de pointes ( QT interval) (even at TI
dose), diarrhea, cinchonism (headache, tinnitus), hypersensitivity (
platelets, hepatotoxicity)
DI: phenytoin or phenobarbital ( quinidine), digoxin level, can
inhibit CYP2D6
Inhibits cAMP phosphodiesterase (rel selective for type III) g cAMP
g h contractility & vasodilation (arterial & venous)
Effects in pts w/ heart failure: pulmonary capillary wedge
pressure, PVR, cardiac output
Used only intravenously & only for acute heart failure or for severe
exacerbation of chronic heart failure
Adverse effects: arrhythmias, other
New oral drug for chronic angina – Mech of action unknown
Reserved for pts who have not achieved an adequate response w/
other antianginal drugs and should be used in combo w/ amlodipine,
beta-blockers or nitrates
Little effect on HR or BP, effects less in women
Extens metabolized mainly by CYP3A; also P-glycoprotein substrate
Adverse effects: dizziness, headache, constipation, nausea, Prolong
QT interval
Class of Ca Channel Blocker - Ex) Nifedipine, Amlodipine,
Felodipine, Isradipine, Nicardipine, Nimodipine, Nisoldipine
High vascular selectivity (ratio of vasc to cardiac effects) =
sympathetic reflex & contractility but vasodilation & SNS
activation tends to counter this results in BP, PVR
Rx: THN, angina (atherosclerotic & vasospastic)
contractions (ex bigeminy), vent tachycardia, vent fibrillation
Other: anorexia, nausea & vomiting, diarrhea, blurred vision,
abnormal color vision (yellow/green halos), confusion, other
mental disturbances (These may be warning signs of toxicity
before arrhythmias)
SNS outflow may occur
Hypokalemia (enhances binding of digitalis to Na,K-ATPase pump)
Hypercalcemia
Hypomagnesemia
Renal insufficiency (most drug is cleared unchanged by kidneys)
Drugs: thiazide or loop diuretics, quinidine, verapamil, or
amiodarone, nitroglycerin
Class of drug used in treating heart failure & supraventricular
tachyarrhythmias such as atrial fib & flutter
Digoxin = only one avail in US
Inhibits Na,K-ATPase pump in heart to contractility
Binding to Na, K-ATPase is enhanced by low extracellular K and
results in avail of Ca at level of contractile element
Vagal efferent activity, which tends to HR & AV conduction and
Decreases SNS activity
 Lidocaine
Disopyramide

(Xylocain
(Norpace) e)

Mexiletine Flecainide

(Mexitil) (Tambocor)

Bretylium
Propafenone

(Bretylol
(Rythmol) )

Sotalol Dofetilide

(Betapace) (Tikosyn)

Ibutilide Adenosine

(Corvert)
 Antiarrhythmic Class IA
Amide anesthetic (most common in US) & Antiarrhythmic Class IB
Use: Serious ventricular arrhythmias
Uses: Topical, IV regional, Spinal, & Epidural anesthesia, serious
Blocks activated Na channels ( conduction velocity) & K
ventricular arrhythmias
channels ( AP duration ERP, assoc w/ QT interval). Also
Blocks activated & inactivated Na channels ( effect in
blockade of antimuscarinic & antivagal (may cause paradoxical
depolar/ischemic cells) – conduction velocity
ventricular rate in pts w/ atrial flutter effects) & neg inotropic effect
pKa 7.7, pH sol 5.6 (w/out Epi) w/ Rapid onset, intermed duration,
( contractility)
intermediate toxicity Not used orally b/c 1st pass; clearance by liver
Oral admin, hepatic metabolism, urinary excretion
dz, heart failure, propranolol
Adverse effects: ventricular tachycardia, torsades de pointes,
Least cardiotoxic of current Na channel blockers, but adverse effects
decreased myocardial contractility can precipitate or worsen heart
inc. tremor, altered consciousness, seizures (above TI)
failure, constipation, anticholinergic effects

Antiarrhythmic Class IC
Use: Maintenance of sinus rhythm in certain supravent arrhythmias
Antiarrhythmic Class IB
in pts w/out structural heart dz
Use: Serious ventricular arrhythmias
Blocks Na & K channels (doesn’t prolong AP b/c AP shortened in
Orally effective lidocaine analog
Purkinje cells & lengthened in vent cells), myocardial
Blocks activated & inactivated Na channels ( effect in
contractility
depolar/ischemic cells) – conduction velocity
Oral admin, elim. by renal excretion & hep metabolism
Adverse effects: tremor, nausea, other
Adverse effects: blurred vision, can worsen heart failure, can cause
or exacerbate potentially fatal arrhythmias (cause heart block),
Low association w/ causing antiarrhythmias
CAST experiment found h mortality in post-MI pts w/ premature
vent contractions

Antiarrhythmic Class III Antiarrhythmic Class IC

Use: Refractory life-threatening ventricular arrhythmias
AP duration & ERP in ventricle by blocking K channels; interferes
w/ NOR release (initially releases NOR)
Iv admin
Adverse effects: hypotension, orthostatic hypotension, arrhythmias
Use: supraventricular arrhythmias
Blocks Na channels and β channels, myocardial contractility,
HR
Adverse effects: Can exacerbate arrhythmias & cause some non-
cardiac effects

Antiarrhythmic Class III

Antiarrhythmic Class III
Use: Maintenance of nl sinus rhythm in pts w/ atrial fib/flutter;
Use: serious vent arrhythmias, maintenance of sinus rhythm in pts
conversion of atrial fib
w/ atrial fib/flutter who are currently in sinus rhythm
AP duration (blocks K channel), blocks rapid component of the
D & L isomers both AP duration (block of K channels); QT
delayed rectifier K current; QT interval
interval.; L isomers HR, conduction velocity AV node, &
Oral admin & renal>hepatic metabolism; renal secretion by organic
refractoriness of AV node
cation system
Oral admin & renal excretion
Adverse effects: torsades de pointes, hospital & prescribers must
Adverse effects: adv effects of beta blockade ( HR, myocardial
participate in education programs in order for drug to be
contractility), torsades de pointes
available; drug interactions

Use: Conversion of paroxysmal supraventricular tachycardia

(PSVT) to sinus rhythm
Acts on adenosine receptors (effects similar to stimulation of ACh
receptors); AV conduction; ERP in AV node
½ life <10sec, rapidly taken up & metabolized; rapid iv admin
Adverse effects (usu transient due to short ½ life): facial flushing,
headache, hypotension, arrhythmias, heart block, asystole
(transient or prolonged), dyspnea, chest discomfort
DI: methylxanthines (caffeine, theophylline)- inhib receptors (
effect); dipyridamole- adenosine uptake inhib ( effect)
Antiarrhythmic Class III
Use: Rapid conversion of atrial fib or flutter to sinus rhythm
AP duration (blocks K channel), blocks rapid component of the
delayed rectifier K current; delays repolarization by inward Na
current (Na agonist), QT interval
Admin iv & hepatic metabolism
Adverse effects: torsades de pointes
 Esmolol Classic Angina

Amiodarone
Variant Angina

(Cordaron
e)

Sildenafil
Organic Nitrates (Not bolded in notes)

(Viagra)

Vardenafil
(Not bolded in notes)
Procainamide

(Levitr
a)

Tadalafil
(Not bolded in notes)
Drugs you give to decrease AV conduction
to slow ventricular rate

(Ciali
s)
 AKA Atherosclerotic Angina, Effort-Associated Angina β blocker & Antiarrhythmic Class II

Use beta blockers, Ca channel blockers & organic nitrates to treat Cardioselective drug w/ short ½ life; used iv

Antiarrhythmic Class III

Use: Serious vent arrhythmias, effective in certain supravent
arrhythmias; iv form for acute (vasodilation freq)
AP duration (blockade of K+; ERP; QT interval), Na & Ca
channel block; antiadrenergic & anticholinergic effects; AKA Vasospastic angina
Oral (bioavail 35-65%), elim by liver (½ life = weeks)
Adverse: HR , AV block (pts w/ nodal dz), pulmonary fibrosis, Use Ca channel blockers & organic nitrates to treat
hypo or hyperthyroidism, corneal microdeposits, visual acuity, skin
blue-gray discoloration, AST/ALT, peripheral neuropathy, can
worsen arrhythmias (torsades de pointes rel uncommon), DI w/
warfarin & digoxin

O2 demand effects: LVEDV, systemic BP, HR & contractility

via sympathetic reflex
Phosphodiesterase 5 inhibitor
O2 delivery effects: some coronary a. dilation, some redistrib blood
Inhibition of phosphodiesterase 5 inhibitor prevents breakdown of
flow to ischemic areas, LVEDV may subendocard perfusion,
cGMP into GMP, so cGMP
relieves coronary spasms
Adverse effects: Headaches, Orthostatic hypotension, sildenafil,
Rx: Erectile dysfunction
tadalafil, & vardenafil increases hypotensive effect so CI, rashes
occasionally
CI: in pts using organic nitrates (increases hypotensive effect)
Tolerance dev to effects if continuous expos – provide drug free
period of min of 8 hrs every day

Antiarrhythmic Class IA
Rx: Serious ventricular arrhythmias
Phosphodiesterase 5 inhibitor Blocks activated Na channels ( conduction velocity) & K
Inhibition of phosphodiesterase 5 inhibitor prevents breakdown of channels ( AP duration ERP, assoc w/ QT interval).
cGMP into GMP, so cGMP Oral or iv admin. Urinary excretion & hepatic metabolism (major
metabolite is N-acetylprocainamide (NAPA) can also h AP duration
Rx: Erectile dysfunction & excreted in urine)
Adverse effects: New arrhythmias (inc. torsades de pointes) can
CI: in pts using organic nitrates (increases hypotensive effect) occur, hypotension (ganglionic blockade), marked slowing of
conduction, nausea, drug-induced lupus (lg. % dev +ANA w/ long
term use, but not all dev lupus), agranulocytosis

Phosphodiesterase 5 inhibitor
Digoxin Inhibition of phosphodiesterase 5 inhibitor prevents breakdown of
cGMP into GMP, so cGMP
Beta blocker
Rx: Erectile dysfunction
Ca channel blocker
CI: in pts using organic nitrates (increases hypotensive effect)
Benzothiazepines Phenylalkylamine

Atorvastatin Verapamil

(Lipitor)

Orlistat
Fenofibrate

(Xenic
(Tricor) al)

Cholestyramine Fluvastatin

(Questran) (Lescol)

Pravastatin
Clofibrate

(Pravacho
l) (Atromid-S)
 Class of Ca Channel Blocker - Ex) Verapamil
Class of Ca Channel Blocker - Ex) Diltiazem
Lower vascular selectivity (ratio of vasc to cardiac effect) than
Lower vascular selectivity (ratio of vasc to cardiac effect) than
diphydropyridines (=less sympathetic reflex), AV conduction,
diphydropyridines (=less sympathetic reflex), AV conduction,
sinus node pacemaker rate HR & contractility results in
sinus node pacemaker rate HR & contractility results in
BP, PVR, HR
BP, PVR, HR
Rx: Angina, supraventricular tachyarrhythmias (ex atrial fibrillation)
Rx: Angina, supraventricular tachyarrhythmias (ex atrial fibrillation)

Phenylalkylamine Ca Channel Blocker w/ Oral or iv admin

Competitive inhibitor of HMG CoA reductase
Lower vascular selectivity (ratio of vasc to cardiac effect) than
liver cholesterol synthesis, which liver LDL receptor production,
diphydropyridines (=less sympathetic reflex), AV conduction,
which plasma LDL clearance – Major use LDL cholesterol &
ERP of Av node, sinus node pacemaker rate HR &
Reduces risk for CHD & stroke
contractility results in BP, PVR, HR
LDL by 18-55%, HDL 5-15%, Triglycerides 7-30%
Rx: HTN, angina (atherosclerotic & vasospastic), supraventricular
Adverse effects: Myopathy, AST& ALT (both dose-related
tachyarrhythmias
Absolute CI: active or chronic liver dz, pregnancy
Adverse effects: dizziness, hypotension, headache, flushing,
Relative CI: Concomitant use of cyclosporine, macrolide
constipation, peripheral edema. Rare: aggravation of ischemia,
antibiotics, various anti-fungal agents, & CP450 inhibitors (fibrates
bradycardia, AV block, cardiac arrest, heart failure
& nicotinic acid should be used w/ appropriate caution)
CAN INCREASE PLASMA DIGOXIN LEVELS

Weight loss medication that is inhibitor of gastric & pancreatic
lipases in stomach & small intestine TG absorbed 30%
Weight loss in obese pts serum cholesterol, risk factors & co- levels of plasminogen activator inhibitor type 1, Apo AI & Apo AII
morbidities such as Type 2 DM, impaired glucose tolerance,
hyperinsulinemia, hypercholesterolemia, & HTN
Adverse effects: Oily spotting, flatus w/ discharge, fecal urgency,
fatty/oily stool, oily evacuation, defecation & fecal incontinence (
if fat of diet >30%), i vit ADEK & β-carotene
CI: chronic malabsorption syn, cholestasis, or allergic
DI: possibly need to change dose of warfarin (b/c i vit K) & oral
hypoglycemics, cyclosporine levels
Fibric Acid Derivate (Fibrate)
Activates PPARα size of LDL particles, removal of LDL,
( HDL), Apo CIII ( lipoprotein lipase) & Enhances
oxidation of FA in liver & muscle and reduce lipogenesis in liver
hepatic secretion of VLDL = LDL 5-20%, HDL 10-35%,
TG 20-50%
Rx: hyperTG (1º use ) & atherogenic dyslipidemia
Adverse effects: Dyspepsia, chol gallstones, myopathy
CI: severe hepatic or renal insufficiency, gallbladder dz
May enhance action of warfarin

Bile Acid Sequestrant –“+” charged anion exchange resins

Competitive inhibitor of HMG CoA reductase
Not absorbed in GI tract but binds bile acids & bile acid excretion;
liver cholesterol syn liver LDL receptor syn plasma LDL Cl
cholesterol absorp liver chole. syn ( HMG CoA reductase)
= LDL 18-55%, HDL 5-15%, TG 7-30%
plasma TG; LDL catabolism/Cl ( LDL receptor syn) =
Reduces risk for CHD & stroke
LDL, HDL, no change TG
Adverse effects: Myopathy, AST& ALT (both dose-related
Adverse effects: Upper & lower GI complaints; absorption of
Absolute CI: active or chronic liver dz, pregnancy
other drugs (warfarin, digoxin, thiazide diuretics, statins, vitamins
Relative CI: Concomitant use of cyclosporine, macrolide
A,D, E, K) (take drugs 1h before or 4h after resin)
antibiotics, various anti-fungal agents, & CP450 inhibitors (fibrates
Absolute CI: Familial dysbetalipoproteinemia & TG >400mg/dL;
& nicotinic acid use w/ appropriate caution)
Relative CI: TG >200 mg/dL
Can use w/ resins or ezetimibe
Can use w/ statins (but risk of rhabdomyolysis)

Fibric Acid Derivate (Fibrate) (not used due to gallstones)

Competitive inhibitor of HMG CoA reductase
Activates PPARα size of LDL particles, removal of LDL,
liver cholesterol syn liver LDL receptor syn plasma LDL Cl
levels of plasminogen activator inhibitor type 1, Apo AI & Apo AII
= LDL 18-55%, HDL 5-15%, TG 7-30%
( HDL), Apo CIII ( lipoprotein lipase) & Enhances
Reduces risk for CHD & stroke
oxidation of FA in liver & muscle and reduce lipogenesis in liver
Adverse effects: Myopathy, AST& ALT (both dose-related
hepatic secretion of VLDL = LDL 5-20%, HDL 10-35%,
Absolute CI: active or chronic liver dz, pregnancy
TG 20-50%
Relative CI: Concomitant use of cyclosporine, various anti-fungal
Rx: hyperTG (1º use ) & atherogenic dyslipidemia
agents, & CP450 inhibitors (fibrates & nicotinic acid use w/
Adverse effects: Dyspepsia, chol gallstones, myopathy appropriate caution)
CI: severe hepatic or renal insufficiency, gallbladder dz Can use w/ resins or ezetimibe
May enhance action of warfarin
 Rosuvastatin
Gemfibrozil

(Crestor
(Lopid) )

Colesevelam
Lovastatin

(Welchol
) (Mevacor)

Simvastatin Colestipol

(Zoc (Colestid
or) )

Nicotinic acid
Omega-3 PUFA

(Niaci
n) (Lovaza – formerly Omacor)

Vytorin
Ezetimibe
(Ezetimibe/Simvastatin)

(Zetia)
 Fibric Acid Derivate (Fibrate)
Competitive inhibitor of HMG CoA reductase
Activates PPARα size of LDL particles, removal of LDL,
liver cholesterol syn liver LDL receptor syn plasma LDL Cl
levels of plasminogen activator inhibitor type 1, Apo AI & Apo AII
= LDL 18-55%, HDL 5-15%, TG 7-30%
( HDL), Apo CIII ( lipoprotein lipase) & Enhances
Reduces risk for CHD & stroke
oxidation of FA in liver & muscle and reduce lipogenesis in liver
Adverse effects: Myopathy, AST& ALT (both dose-related
hepatic secretion of VLDL = LDL 5-20%, HDL 10-35%,
Absolute CI: active or chronic liver dz, pregnancy
TG 20-50%
Relative CI: Concomitant use of cyclosporine, macrolide antibiotics,
Rx: hyperTG (1º use ) & atherogenic dyslipidemia
various anti-fungal agents, & CP450 inhibitors (fibrates & nicotinic
acid use w/ appropriate caution) Adverse effects: Dyspepsia, chol gallstones, myopathy
Can use w/ resins or ezetimibe CI: severe hepatic or renal insufficiency, gallbladder dz
May enhance action of warfarin

Bile Acid Sequestrant - Polymeric hydrophilic gel

Competitive inhibitor of HMG CoA reductase
Not absorbed in GI tract but binds bile acids & bile acid excretion;
liver cholesterol syn liver LDL receptor syn plasma LDL Cl
cholesterol absorp liver chole. syn ( HMG CoA reductase)
= LDL 18-55%, HDL 5-15%, TG 7-30%
plasma TG; LDL catabolism/Cl ( LDL receptor syn) =
Reduces risk for CHD & stroke
LDL, HDL, no change TG
Adverse effects: Myopathy, AST& ALT (both dose-related
Adverse effects: Upper & lower GI complaints; absorption of
Absolute CI: active or chronic liver dz, pregnancy
other drugs (warfarin, digoxin, thiazide diuretics, statins, vitamins
Relative CI: Concomitant use of cyclosporine, macrolide antibiotics,
A,D, E, K) (take drugs 1h before or 4h after resin)
various anti-fungal agents, & CP450 inhibitors (fibrates & nicotinic
Absolute CI: Familial dysbetalipoproteinemia & TG >400mg/dL;
acid use w/ appropriate caution)
Relative CI: TG >200 mg/dL
Can use w/ resins or ezetimibe
Can use w/ statins (but risk of rhabdomyolysis)

Bile Acid Sequestrant – “+” charged anion exchange resins

Competitive inhibitor of HMG CoA reductase
Not absorbed in GI tract but binds bile acids & bile acid excretion;
liver cholesterol syn liver LDL receptor syn plasma LDL Cl
cholesterol absorp liver chole. syn ( HMG CoA reductase)
= LDL 18-55%, HDL 5-15%, TG 7-30%
plasma TG; LDL catabolism/Cl ( LDL receptor syn) =
Reduces risk for CHD & stroke
LDL, HDL, no change TG
Adverse effects: Myopathy, AST& ALT (both dose-related
Adverse effects: Upper & lower GI complaints; absorption of
Absolute CI: active or chronic liver dz, pregnancy
other drugs (warfarin, digoxin, thiazide diuretics, statins, vitamins
Relative CI: Concomitant use of cyclosporine, macrolide antibiotics,
A,D, E, K) (take drugs 1h before or 4h after resin)
various anti-fungal agents, & CP450 inhibitors (fibrates & nicotinic
Absolute CI: Familial dysbetalipoproteinemia & TG >400mg/dL;
acid use w/ appropriate caution)
Relative CI: TG >200 mg/dL
Can use w/ resins or ezetimibe
Can use w/ statins (but risk of rhabdomyolysis)

EPA & DHA (PUFAs)
syn of TG & VLDL; LDL but size changes larger, more
buoyant particles (less atherogenic); minimal effects on HDL
4g/qday or 2gBID w/ meals = TG 20-50% & VLDL 30-40%;
HDL 6-13% & LDL 15-30%; low doses (1g/day) which has modest
effect on TG, reduces coronary heart dz & mortality (prob due to
inhibition of platelet aggregation)
Adjunct to diet for rx of very high TG (>500mg/dL)
Adverse effects: belching, dyspepsia, taste perversion, glycemic release), hyperglycemia, hyperuricemia/gout, worsens peptic ulcer
control in diabetics, impaired hemostasis
Does not risk of rhabdomyolysis when comb w/ statins
Antidyslipidemic drug (Useful most lipid & lipoprotein abnl)
lipolysis by adenylyl cyclase activity FFA levels VLDL
syn TAG &VLDL LDL; HDL; Lp(a); arachidonic acid
cascade (Langerhans cells) PGD2 flushing = LDL 5-25%,
HDL 15-35%, TG 20-50%
Absolute CI: Chronic liver dz, severe gout; Relative CI:
hyperuricemia & high doses in Type 2 DM
Adverse effects: hepatotoxicity (esp w/ crystalline & sustained/time
dz. risk of rhabdomyolysis w/ statins
Need 1-3 g /day (Vit dose 20mg/day) Max 2-4.5g/day

Cholesterol Absorption Blocker

Fixed dose-dose combination of ezetimibe 10mg and simvastatin cholesterol to liver
(10, 20, 40, or 80 mg)
Decreases LDL greater than can be achieved by doubling the statin
dose if only a statin is used
Increased risk of rhabdomyolysis
Inhibits absor of cholesterol & related phytosterols intestinal
cholesterol stores Cl cholesterol = Alone:
Total-Cl ~13%, LDL 18%, Apo B 16%, TG 8% & HDL 1%.
w/ statin: Total-Chol 17%, LDL 25%, Apo B 19%, TG 14%, &
HDL 3%
Rx: 1º & homo familial hypercholesterolemia, homo sitosterolemia
(phytosterolemia) (only med approved)
Adverse Effects: myalgia-Rhabdomyolysis, diarrhea, h liver
enzymes esp when used w/ statins
CI: liver dz; DI: Fibrates bioavail & cholestyramine
 Adivor Simcor
(Niaspan + Lovastatin) (Niaspan + Simvastatin)
(Not in notes, but was in ppt) (Not in notes, but was in ppt)

Bile acid sequestrants

HMG CoA Reductase Inhibitor
(AKA resins)

Cholesterol Absorption Blocker Fibric Acid Derivates (Fibrates)

Iron Vitamin B12

Folic Acid Erythropoietin

 Extended release Nicotinic acid plus lovastatin Extended release Nicotinic acid plus simvastatin

Increased risk of rhabdomyolysis Increased risk of rhabdomyolysis

Decreases LDL, Increases HDL, Decreases TG

Decreases LDL, Increases HDL minimally, no change in TG
Increases # LDL receptors
Increases Bile acid excretion
Decreases cholesterol synthesis
Decreases dietary cholesterol absorption
Increase risk of rhabdomyolysis (rare)
Increases # LDL receptors
Ex) Lovastatin, Pravastatin, Fluvastatin, Simvastatin, Atorvastatin,
Ex) Cholestyramine, colestipol, colesevelam
Rosuvastatin

Decreases LDL (in hyperTG, may raise LDL), Increass HDL,

Decreases TG
Decreases Total Cholesterol, Decreases LDL, Decreases Apo B,
Decreases Apo CIII (reduces inhibition of lipoprotein lipase (LPL))
Decreases TG, Increases HDL
Increases Apo AI & Apo AII
Increases oxidation of Fatty acids
Decreases dietary cholesterol & related phytosterols absorption
Decreases lipogenesis
Decreases VLDL secretion
Ex) Ezetimibe
Ex) Fenofibrate, Gemfibrozil, Clofibrate

Best absorbed in ferric form in the duodenum & prox jejunum (distal
sm intestine can absorb if necess); amt absorbed depends on need:
pregnant > nl menstruating women> post-menopausal & males
Iron storage controlled by absorption & serum ferritin levels
estimate iron stores; Serum transferrin in iron deficiency
200-400mg elemental iron/day for 3-6 mths after correction to
replenish stores; Parenteral therapy: iron dextran (IM or iv), iron-
sucrose complex (iv), iron sodium gluconate complex (iv)
Toxicity: Whole bowel irrigation & deferoxamine (iron chelator) for stores. Maintenance 100-1000mcg IM once a mth. High dose of oral
acute; intermittent phlebotomy for chronic
Cofactor for several essential biochemical rxn
Deficiency leads to megaloblastic (B12 def) or pernicious anemia
(B12 due to intrinsic factor def), GI symptoms, & neuro
abnormalities; Takes abt 5 yrs for store to be depleted
Causes: IF def, partial or total gastrectomy, malabsorption syn,
inflammatory bowel dz or sm bowel resection
Parenteral or IM of B12 (hydroxocobalamin (preferred) or
cyanocobalamin) daily or every other day every 1-2 wks to replace
B12 if pt refuses or can’t do shots

Hematopoietic growth factor w/ ½ life of 4-13

Used in pts w/ anemia of chronic renal failure, primary bone marrow Reduced form required for rxns that provide precursors for syn of
disorders (aplastic anemia, myeloproliferative & myelodysplastic amino acids, purines, & DNA
dz, multiple myeloma) & secondary anemias (chronic inflammation, Body stores are relatively low & daily requirements are high def &
AIDS, cancer & anemia from zidovudine treatment in HIV pts & megaloblastic anemia can occur w/in 1-6mths (RBC levels of folate
anemia of prematurity) more dx value than serum)
Normally, except in renal dz (b/c kidneys can’t make it), as Deficiency often b/c poor diet, but also caused by methotrexate,
hematocrit & Hb falls, serum EPO rises exponentially b/c it trimethoprim, pyrimethamine, phenytoin & other anticonvulsants
erythroid proliferation & differentiation (won’t cause megaloblastic anemia usually). No neuro symptoms.
Failure to respond = concurrent iron def Oral folate supplements (1mg/day) until def cause fixed
Toxicity = HTN & thrombotic complications
Darbepoetin alfa Pegfilgrastim

Sargramostim Filgrastim
(rHuGM-CSF) (rHuG-CSF)

Oprelvekin Thrombopoietin
Myeloid Growth Factor – covalent conjugation product of filgrastim Glycosylated form of erythropoietin
& a form of polyethylene glycol
Longer ½ life of filgrastim Functionally the same as erythropoietin except it has a twofold to
Injected once per myelosuppressive chemotherapy cycle threefold longer half-life

Myeloid Growth Factor w/ ½ life 2-7 hrs after iv or SQ Myeloid Growth Factor w/ ½ life 2-7 hrs after iv or SQ
Injected daily for several days for each chemotherapy cycle Multipotential hematopoietic growth factor that proliferation &
prolife & differentiation of progenitors already committed to differentiation of early & late granulocytic progenitor cells and
neutrophil lineage; phagocytic activity of mature neutrophils & erythroid & megakaryocyte progenitors; fxn of mature neutrophils;
prolongs their survival; mobilizes hematopoietic stem cells acts w/ IL-2 to T-cell proliferation; mobilizes peripheral blood
For: peripheral blood stem cell transplantation, cyclic neutropenia, stem cells (but not as well as G-CSF)
cancer chemotherapy-induced neutropenia (inc. acute myeloid For: cyclic neutropenia, cancer chemotherapy-induced neutropenia
leukemia), congenital neutropenia, myelodysplasia, & aplastic (inc. acute myeloid leukemia), congenital neutropenia,
anemia myelodysplasia, & aplastic anemia
Toxicity: well tolerated – may cause bone pain but clears when drug Toxicity: fever, malaise, arthralgias, myalgias, cap leak syn, splenic
is stopped rupture (rare)

Used in pts w/ thrombocytopenia, 2º prevention in pts getting

cytotoxic chemo for nonmyeloid cancers
Still an investigational agent, but so far well tolerated Recombinant form of IL-11 w/ ½ life of 7-8 hrs
Stimulates growth of multiple lymphoid & myeloid cells; acts
Low in pts w/ cirrhosis (b/c it is made in the liver normally) & synergistically w/ other growth factors to growth of primitive
thrombocytopenia (w/out anemia or leukopenia if no other growth
megakaryocytic progenitors & number of peripheral platelets &
factor is missing)
neutrophils
Stimulates growth of primitive megakaryocytic progenitors;
50mcg/kg/day SQ 6-24 hrs after completion of chemo & continued
stimulates mature megakaryocytes & even activates mature platelets
to respond to aggregation-inducing stimuli for 14-21 dys or until platelet # >50,000/µL
Adverse effects: fatigue, headache, dizziness, anemia, dyspnea,
transient atrial arrhythmias, hypokalemia