Cardiovascular pharmacology

Primary hemostasis

Secondary hemostasis

Thrombi that form in arteries (high flow conditions)

Thrombi that form in veins (slow flow conditions)

2 types of antithrombotic drugs

Interfere with platelet plug formation
Effectiveness may be measured by a test known as a bleeding time

Platelet plug formation consists of 3 processes

Responsible for platelet adhesion

Two pathways - extrinsic and intrinsic converge on _

Measures the integrity of the extrinsic (tissue factor) and common pathways

Measures the integrity of the intrinsic (contact activation) and common pathways

Test for low-molecular- weight heparin

Test for unfractionated heparin

Test for warfarin

Interfere with fibrin formation

Irreversibly acetylates cyclooxygenase, thus inhibiting production of thromboxane A2 (TXA2) from arachidonic acid

Aspirin should be avoided in which conditions?

Inhibit ADP-mediated platelet activation

Side effects characteristic of ticlopidine

-Proven to be slightly superior to ASA for secondary prevention following MI
-Also used following coronary stenting, and in combination with ASA in treating non-ST-elevation acute coronary syndromes
-Superior side effect profile (over ticlopidine)
-Once daily dosing
-Expensive (>$3.00 per 75 mg tablet)

-Worse side effect profile than clopidogrel
-Severe neutropenia
-Thrombotic thrombocytopenic purpura
-Twice daily dosing

Most effective antiplatelet drugs

Bind to receptors preventing fibrinogen-mediated platelet aggregation

Monoclonal antibody against receptors
Extended duration of antiplatelet action – bad if need to go to OR

GP IIb/IIIa inhibitors side effects

-Increases platelet cAMP levels
-Lowers cytosolic Ca++ concentration
-Reduces platelet aggregation
-Weak antiplatelet effect
-No proven clinical benefit as an antithrombotic when used alone
-May enhance effect of some other antithrombotics

Combine with antithrombin III, allowing to inhibit factor Xa

Selectively inactivates factor Xa (not thrombin)

Side effects heparin

Immediately reverses the anticoagulation effect of heparin

- Binds to anti thrombin III
-Specifically inhibits factor Xa
-Does not inactivate formed thrombin
-Does not interfere with platelet function
-Does not cause HIT
-No known antidote – protamine wont work

Anticoagulant used for:

-Deep venous thrombosis (DVT) prophylaxis for hip and knee orthopedic surgery
-Treatment of DVT and pulmonary embolism

-Inhibit thrombin activity independently of antithrombin III
-Effective against circulating and clot-bound thrombin
-Do not cause heparin-induced thrombocytopenia (HIT)
-Primary indication is anticoagulation in patients with HIT, or a history of HIT

Main adverse effect of direct thrombin inhibitors

Inhibits formation of the reduced form of vitamin K (inhibits epoxide reductase)

Reduced form of vitamin K is necessary for conversion of coagulation factors _ into functional forms

has the shortest half-life of all of the vitamin K-dependent proteins

Adverse effects warfarin

Reverses warfarin’s effect within hours

For emergencies/serious bleeding caused by warfarin

Patient w/out "compelling indications" with HTN

Previous MI + HTN

Exertional angina + HTN

Prinzmetal variant angina + HTN

CHF + HTN

Dyslipidemia + HTN

Diabetes + HTN

Chronic kidney disease + HTN

Osteoporosis + HTN

BPH + HTN

Migraine cephalgia + HTN

Avoid in gout + HTN

Avoid in asthma and severe COPD + HTN

Avoid in depression + HTN

Pregnancy + HTN

Avoid in pregnancy + HTN

Caution in physical active athletes + HTN

Caution in sexually active men + HTN

Avoid in truck drivers + HTN

African American + HTN

Elderly with isolated systolic HTN

Avoid in elderly with orthostatic HTN

Side effects Ca channel blockers

Indication: LVH, diastolic dysfunction and/or arrhythmias

MOA: Negative inotropic, chronotropic, decreased AV node conduction

DI: reduce therapeutic dose of cyclosporine

Indication: Ca channel blocker of choice in CHF

MOA: Smooth muscle SELECTIVE, adjunct to beta blocker or ACE inhibitor

SE: Acute MI - reflex sympathetic activation

DI: GRAPEFRUIT JUICE --> increases bioavailability of the drug, less first pass effect

Indication: LVH, diastolic dysfunction and/or arrhythmias

MOA: Negative inotropic, chronotropic, decreased AV node conduction

SE: Constipation, DO NOT give to patients with heart block or CHF

Indication: PREGNANCY INDUCED HTN and HF with ACE inhibitors intolerance, severe HTN

SE: Headache, nausea,anorexia, palpitation, sweating, flushing and SLE LIKE FEVER

Indication: REFRACTORY HTN

MOA: Opens K channels in smooth muscle membrane - inhibits contractions by hyperpolarization

SE: HIRSUTISM

Indication: PHEOCHROMOCYTOMA (in operation)

MOA: Direct and indirect stimulation of cGMP -relaxation of smooth muscle in both arterioles and veins, increase CO in patients with HF

SE: CYANIDE ACCUMULATION, hypotension, metabolic acidosis, arrhythmia (reflex sympathetic activation)

Note: LIGHT SENSITIVITY - decomposes with light

Indication: Occasionaly hypertensive emergencies, HYPOGLYCEMIA

MOA: Increase K conductance in smooth muscle

SE: EXCESSIVE HTN, renal salt and water retention

Indication: POST OP HTN + HTN emergencies

MOA: D1 agonist - DOPAMINE - relaxation of smooth muscle

C/I: DO NOT give in glaucoma

Indications: CONCOMITANT BPH, adjunct to Ca channel blockers or ACE inhibitors for resistant HTN

MOA: Decrease TPR, less tachycardia than phentolamine or phenoxybenzamine

SE: Fluid retention, tachycardia, fatigue, ORTHOSTATIC HYPOTENSION

Indication: Pheochromocytoma

SE: Tachycardia and postural hypotension

Indication: Mild to moderate HTN

MOA: Decrease TPR and decrease in renal vascular resistance

SE/CI: DO NOT give in mental depression. Sedation, nightmares, mental depression, vertigo, LACTATION (in MEN)

Indication: LABILE HTN needing multiple drugs, MAINSTAY in HTN urgencies


SE: Dry mouth and WITHDRAWAL SYNDROME- DO NOT discontinue abruptly

Indication: Mild to moderate HTN

MOA: Inhibits VMAT - catecholamine depletion

SE: Sedation, nightmares and severe mental depression, diarrhea, GI cramps

Indication: Outpatient SEVERE HTN - long T 1/2

MOA: Displaces NE at the nerve ending

SE: Postural hypotension, delayed or RETROGRADE EJACULATION

Indication: PRE OP MANAGEMENT OF PHEOCHROMOCYTOMA, chronic kidney disease, HTN emergencies, clonidine withdrawal


SE/CI: DO NOT give in people with asthma, COPD. Postural HTN, bronchospasm, heart block and heart failure

Indications: 2nd or 3d line, concomitant HF or angina, HIGH RENIN HTN


MOA: Decrease CO --> decrease BP, inhibit renin production


SE: DO NOT give in patients with asthma or insulin dependent diabetes. Bradycardia, asthma, increased TG and decreased HDL

Indications: CONCOMITANT ASTHMA, ISCHEMIC HEART DISEASE, CARDIAC ARRHYTHMIAS

SE: Bradycardia, heart block and asthma at high doses

Indication: CONCOMITANT MIGRAINES, essential tremors and adjunct for reflex tachycardia

SE: Bronchospasm, heart block. DO NOT give in patients with bronchospastic pulmonary disease and insulin dependent diabetes

Indication: First or 2nd line drugs. Concomitant HF, KIDNEY DISEASE, diabetes, adjunct in resistant HTN


MOA: Decrease TPR, no reflex sympathetic activation and save in ischemic heart diseases


SE: DO NOT give in 2nd/3d semesters of pregnancy. Initial dose hypotension, dry cough, angioedema, developmental defects and renal insufficiency.

Indication: HTN

MOA: INHIBITS RENIN - similar to ACE inhibitors

Indication: Resusciation from cardiac arrest, restoration of spontaneous circulatory function, ANAPHYLACTIC SHOCK

MOA: Increased inotropic and chronotropic effects + alpha mediated vasoconstriction --> raise BP, relax smooth muscle

SE: TACHYCARDIA, HTN crisis, CNS stimulation, angina pectoris, hyperglycemia

DI: Effects increased by cocaine, TCA's, MAO inhibitors, thyroid hormones

Indication: CARDIAC ARREST, hypotension

MOA: Acts on ALPHA1, ALPHA2, BETA1 receptors

Indication: AV block, bradycardia, in emergency situations in anticipation of insertion of artificial pacemaker

MOA: Acts on BETA 1 and BETA2 receptors

Indication: Increase GFR, sodium diuresis

MOA: Dose dependent receptor specificity --> D1 >BETA1>ALPHA1, rapid metabolism by MAO/COMT

Indication: Severe HTN

MOA: D1 agonist

Indication: HEART FAILURE (IV)

MOA: Synthetic beta 1 agonist, can activate alpha 1 receptors, increases CO w/out effect on heart

Indication: Postural hypotension

MOA: Stim alpha 1 - cause vasoconstriction - increase BP

Indication: hypotensive emergencies

MOA: Stim alpha 1 - cause vasoconstriction - increase BP

Indication: Hypertension

MOA: Stimulate alpha 2 in CV control centers of CNS, decrease sympathetic outflow

SE: Sedation, sex dysfunction, DO NOT withdraw suddenly - REBOUND HTN

Indication: Pregnancy related HTN


MOA: Stimulation of alpha 2 receptors


SE: HEPATOTOXICITY, + COOMBS TEST - problem matching blood if need transfusion, hemolytic anemia

Indication: HTN

MOA: Decrease TPR

SE: 1st DOSE HYPOTENSION, tachycardia, Na/H2O retention

Indication: Pheochromocytoma

MOA: IRREVERSIBLE BLOCKADE

SE: Reflex tachycardia, GI

Indication: Prevent HTN when removing pheochromocytoma, diagnostic

MOA: REVERSIBLE BLOCKADE

SE: Reflex tachycardia, GI