Flashcards in Review - CVS/Renal Agents Deck (307):
Fast response fibers - phase 0?
Na ion channels open (inward) which leads to membrane depolarization.
Fast response fibers - phase I?
Na channels are inactivated.
K channels (outward) are activated.
Cl channels (inward) are activated.
Fast response fibers - phase II?
Slow influx of Ca balanced by OUTWARD K current (delayed rectifier current Ik).
Fast response fibers - phase III?
Outward K current increases.
Inward Ca current decreases.
Fast response fibers - phase IV?
Membrane returns to resting potential.
On what phase(s) of the cardiac AP do amiodarone and sotalol work?
Phase 0 and III.
On what phase of the cardiac AP do lidocaine + flecainide + quinidine work?
Beta blockers - what phase(s) of cardiac AP?
II and IV
Responsible for maintaining electrochemical gradient?
Ion current responsible for depolarization of SA and AV nodal fibers?
Ion current responsible for REpolarization of SA and AV nodal fibers?
Phase IV of AP in SLOW-response fibers (SA/AV node) - difference from phase IV in fast?
Slow --> Automaticity - ability to depolarize spontaneously.
Rising phase IV slope of the action potential = pacemaker potential.
Ion current responsible for the "pacemaker" current - rising slope of phase IV?
Pacemaker of the heart has fastest uprising phase IV slope - where is this pacemaker in healthy individuals?
Effective refractory period vs Relative refractory period - difference?
No stimulus, no matter the strength, can elicit a response with fibers in the ERP - a strong one can elicit stimulus in the RRR.
Three states of voltage-gated Na channel?
Two types of GATES of voltage-gated Na channel?
1. M (activating)
2. H (inactivating)
Why is the rate of recovery from an AP slower in ischemic tissue?
Cells are already partly depolarized at rest.
Antiarrhythmics with membrane-stabilizing effects?
Antiarrhythmic are grouped into 4 classes according to what classification system?
Class I antiarrhythmics - mechanism?
Class II antiarrhythmics - mechanism?
Class III antiarrhythmics - mechanism?
Class IV antiarrhythmics - mechanism?
Class I - further subdivisions?
Class Ia antiarrhtyhmics?
1. Quinidine (antimalarial/antiprotozoal agent)
Class Ib antiarrhythmics?
Class Ic antiarrhythmics?
Class II antiarrhythmics?
Class III antiarrhythmics?
Class IV antiarrhythmics?
3 antiarrhythmics that do NOT fit in the Vaughn-Williams classification system?
Mg is used to treat what specific type of arrhythmia?
Torsades de pointes - polymorphic ventricular tachycardia.
Adenosine - what types of arrhythmia?
1. Paroxysmal supraventricular tachycardia (PSVT)
2. Specifically narrow complex tachycardia or supraventricular tachycardia (SVT) with aberrancy.
3. AV nodal arrhythmias - adenosine causes transient V block.
Symptomatic patients or unstable tachycardia with pulses - adenosine or cardioversion?
Where anatomically should the IV be placed to administer adenosine?
As close to the heart as possible, that is, the antecubital fossa since adenosine has extremely short half-life.
Adenosine rapid IV push - followed by?
5-10cc flush of saline to facilitate its delivery to the heart.
Mechanism of action of adenosine?
Stimulates A receptors --> decr. in cAMP (via Gi).
+ incr. K efflux leading to increased hyperpolarization
+ incr. refractory period in AV node.
Adenosine - side effects?
2. Chest pain
2 drugs that antagonize adenosine?
How is adenosine dosed?
1. 6mg initially by rapid IV push.
2. If NOT effective within 1-2min, give 12mg repeat dose.
3. Follow each bolus of adenosine with normal saline flush.
4. 12mg dose may be repeated once.
Most deadly ion that can be administered?
HYPERkalemia - ECG?
1. Flattened P waves
2. Widened QRS
3. Peaked T waves
4. Sine waves
HYPOkalemia - ECG?
1. Flattened or inverted T wave
2. U waves
3. ST-segment depression
Ia antiarrhythmics - effect on AP duration?
Ia antiarrhythmics - effect on ERP?
Ia antiarrhythmics - effect on conduction velocity?
Ia antiarrhythmics - effect on phase IV slope?
Ib antiarrhythmics - effect on AP duration?
Ib antiarrhythmics - effect on ERP?
Little or no change.
Ib antiarrhythmics - effect on conduction velocity?
Decrease (primarily in ischemic tissue).
Ib antiarrhythmics - phase IV slope?
Ic antiarrhythmics - AP?
Little or no change
Ic antiarrhythmics - ERP?
Little or no change
Ic antiarrhythmics - conduction velocity?
Ic antiarrhythmics - Phase IV slope?
Drugs that affect AV conduction velocity.
QT interval prolongation, and therefore torsades, is more likely to occur with what 2 classes of antiarrhythmics?
Ia and III
Class Ia antiarrhythmic that also blocks α receptors + muscarinic receptors --> potentially leading to incr. HR and AV conduction?
Side effects of quinidine?
3. Incr. digoxin levels via protein-binding displacement
Syndrome that may include:
2. High-frequency hearing loss
5. Blurred vision
Procainamide - side effects?
1. Drug-induced lupus (25-30% of patients)
Drug-induced lupus - drugs?
11. Valproic acid
Ia antiarrhythmic - peripheral vasoconstriction?
Disopyramide - side effects?
Anticholinergic side effects:
1. Urinary retention
2. Dry mouth
3. Dry eyes
4. Blurred vision
Lidocaine is useful in the treatment of ventricular arrhythmias. True or false?
Lidocaine is useful in the treatment of atrial arrhythmias. True or false?
Lidocaine is useful in the treatment of AV junctional arrhythmias. True or false?
Lidocaine - side effects?
Ib antiarrhythmic structurally related to lidocaine?
Ib antiarrhythmic - pulmonary fibrosis?
Propafenone - Ic antiarrhythmic - other type of antiarrhythmic activity?
Encaine + flecainide increase what IMPORTANT risk?
Increase sudden cardiac death in post-MI patients with arrhythmias!!!
Cardiac Arrhythmia Suppression Trial (CAST).
Sotalol - Class III - other antiarrhythmic activity?
Antiarrhythmic with class I, II, III, IV activity?
Amiodarone side effects?
1. Pulmonary fibrosis
5. HYPER + HYPOthyroidism
8. Blue skin discoloration (!)
10. Muscle weakness
12. Corneal deposits
13. Lipid abnormalities
17. Optic neuritis
19. Abnormal taste
20. Abnormal smell
Amiodarone - patient monitoring?
2. Thyroid function tests
3. Pulmonary function tests
4. Liver function tests
6. Ophthalmology examination
Verapamil - DO NOT give in what arrhythmias?
1. Wolff-Parkinson-White (WPW) syndrome
2. Ventricular tachycardia
Verapamil side effects?
1. Drug interactions
4. AV block
Digoxin - what arrhythmias?
Digoxin-INDUCED arrhythmias - what give?
How is QTc calculated?
QT/(square root of R to R interval).
Why must QT be corrected?
QT depends on HR, so higher HR will display shorter QT on ECG.
It is corrected to remove the variable of HR.
Normal value for QTc?
Less than 440msec.
Long QT - risk for?
Torsades - Ventricular arrhythmia that can degenerate into v-fib.
3 compensatory physiologic responses in CHF?
1. Fluid retention
2. Incr. sympathetic drive
3. Hypertrophy of cardiac muscle
The pressure stretching the ventricular walls at the onset of ventricular contraction - related to LVEDV/P.
The load or force developed by the ventricle during systole.
Drugs to DECREASE PRELOAD?
Drugs to DECREASE AFTERLOAD?
Drugs to increase CONTRACTILITY?
2. Phosphodiesterase inhibitors - amrinone, milrinone
3. Beta agonists
Digoxin side effects?
6. Blurred vision
7. Visual disturbances, such as YELLOW HALOS around light sources.
Electrolyte abnormalities that predispose to digoxin toxicity?
1. Supraventricular tachycardias
2. AV nodal tachycardias
3. AV block
6. Complete heart block
Digoxin - use in WPW syndrome?
No - Since digoxin slows conduction through the AV node, the accessory pathway present in WPW is left UNOPPOSED --> SVT and A-arrhythmias.
Digoxin toxicity - treat?
1. Correction of electrolyte disturbances
3. Anti-digoxin Fab antibody (Digibind)
Drugs that INCREASE digoxin concentrations?
Drugs that DECREASE digoxin concentration?
1. Loop diuretics
2. Thiazide diuretics
Does digoxin therapy in CHF lead to prolonged survival?
No - It is of symptomatic benefit only, improving quality, but not necessarily duration of life.
Classes of medications that have been shown to increases survival in CHF patients?
How does dobutamine work in CHF?
1. Incr. CONTRACTILITY
2. Incr. vasodilation
via UP cAMP.
Amrinone + milrinone mechanism?
Inhibits phosphodiesterase --> UP cAMP --> UP intracell. Ca --> UP contractility + VASODILATION.
PDEIs side effects?
1. Milrinone --> may decr. survival in CHF.
2. Amrinone --> may cause thrombocytopenia.
How do diuretics work in CHF?
Decr. in intravascular volume - thereby DECREASE in preload.
Reduce pulmonary and peripheral edema - often seen in CHF patients.
2 beta blockers with specific indications for treatment of CHF?
2. Carvedilol (mixed alpha-/beta-blocker)
Nesiritide - mechanism?
Recombinant BNP --> UP cGMP in vascular smooth muscle + endothelial cells.
ACEIs effect on CHF?
Inhibition of AT-II production --> Decr. TPR --> Decr. AFTERLOAD.
+ Prevents LV remodeling.
2 strategies in treatment of angina?
1. Incr. O2 supply
2. Decr. O2 demand
Drugs that increase O2 supply?
Drugs that decrease O2 demand?
Drugs of choice for immediate relief of anginal symptoms?
Sublingual nitroglycerin (NGT).
Mechanism of action of nitrates?
Nitrates form NITRITES --> Nitrites form NO --> NO incr. cGMP --> Incr. cGMP leads to incr. relaxation of vascular smooth muscle.
How does cGMP leads to relaxation of vascular smooth muscle?
Causes DEPHOSPHORYLATION of myosin light chains.
How do nitrates incr. O2 supply?
Dilation of coronary vessels --> incr. blood supply.
How do nitrates DECREASE O2 demand?
1. Dilation of large veins --> PRELOAD reduction.
2. Decr. preload --> reduced work of heart.
3. Decr. work of heart --> decr. O2 demand.
Nitrates side effects?
3. Reflex tachycardia
4. Facial flushing
Why must patients have at least a 10- to 12- hour "nitrate-free" interval every day?
Tolerance (tachyphylaxis) develops to nitrates if given on a continuous (around-the-clock) basis.
Nitrates contraindicated in patients taking any of which 3 drugs?
Methemoglobin formation, specifically by amyl nitrite, can be used to treat what type of poisoning?
Common formulations of nitrates?
4. Isosorbide dinitrate
Time for peak effect of sublingual NTG?
Dosing frequency of sublingual NTG during an anginal episode?
Every 5 minutes for a maximum of 3 doses.
How do beta-blockers work in angina?
Block of beta-1 --> Decr. CO, HR, Contractility --> reducing workload of the heart + O2 demand.
Do beta-blockers increase O2 supply?
Verapamil - effect on the myocardium or peripheral vasculature?
Myocardium - greater negative inotropic effects.
Dihydropyridines - effect on myocardium or peripheral vasculature?
Peripheral vasculature - more potent vasodilators.
Diltiazem - effect on myocardium or peripheral vasculature?
CCBs in the treatment of angina?
Block vascular L-type calcium channels which leads to decreased heart contractility + incr. vasodilation.
Goal BP in patients without DM or chronic kidney disease?
Goal BP in patients with DM or chronic kidney disease?
Kidney responds to reduced BP by releasing what peptidase?
Renin is responsible for what enzymatic reaction?
Angiotensinogen --> AT-I.
Where is ACE found?
Immediate/acute effects of thiazide diuretics?
1. Incr. Na
2. Incr. Cl
3. Incr. H2O exertion
--> Decr. blood volume.
Chronic effects of thiazide diuretics?
Thiazides - site of action?
Disstal convoluted tubule of nephron.
Thiazides - inhibit what transporter?
Examples of thiazides?
Thiazide diuretics may be ineffective in patients with creatinine clearances of less than what?
Thiazides - Serum Ca?
Thiazides - Serum Mg?
Thiazides - Serum K?
Thiazides - Serum Na?
Thiazides for Ca stones in the urine?
Yes - Incr. Ca reabsorption.
Side effects of HCTZ?
7. Metabolic ALKALOSIS
Patients allergic to what class of antimicrobials may also be sensitive to thiazides?
Which loop can be given safely to patients with allergy to sulfonamides?
Loops increase Ca exertion?
Side effects of loops?
5. Met alkalosis
Loop that is MOST OTOTOXIC?
Mannitol - mechanism of action?
Osmotic diuretic - thereby drawing water via increased osmolality into the PCT, LOH (thin descending) + collecting ducts.
Mannitol - used for?
1. Decr. in INTRAOCULAR + INTRACRANIAL pressure.
2. Prevents ANURIA in hemolysis + rhabdomyolysis.
Carbonic anhydrase (CA) inhibitors?
CA inhibitors - mechanism?
Incr. EXCRETION of Na + HCO3.
CA inhibitors - metabolic disturbance?
CA inhibitors used for?
1. Altitude sickness (decr. cerebreal and pulmonary edema).
2. Glaucoma - decr. aqueous humor formation thereby decreasing intraocular pressure.
3. Metabolic alkalosis
4. Enhance RENAL EXCRETION of acidic drugs.
3 K-sparing diuretics?
Spironolactone - mechanism?
Aldosterone receptor blocker.
Where in the kidney is the aldosterone receptor found?
Basolateral membrane of the principal cell in the collecting duct.
Where in the kidney does triamterene and amiloride work?
Na ion channel on the luminal side of the principal cell in the collecting duct.
Spironolactone - side effects?
2. Metabolic acidosis
Triamterene often used with?
Spironolactone - used for?
Amiloride is used to treat what conditions?
3. Li-induced diabetes insipidus
2 Cardioselective beta blockers that are widely used?
Patients with what specific disease states should not receive nonselective beta-antagonists?
1. Asthma (incr. risk of bronchospasm).
3. Peripheral vascular disease
Beta blockers action on the kidney?
DECREASE RENIN RELEASE --> Prevent renin stimulation by catecholamines + likely DIRECT depression of the RAA system.
Beta blockers side effects?
2. Lipid abnormalities
3. Rebound HTN with abrupt withdrawal
6. Sexual dysfunction
Beta blocker with shortest half-life?
Esmolol (9min) - usually administered as a continuous drip.
In addition to conversion of AT-I to AT-II, what other reaction does ACE catalyze?
The breakdown of bradykinin. ACE is also known as kininase.
Action of bradykinin on vascular smooth muscle?
Increased bradykinin levels may lead to what adverse reaction experienced by patients who take ACEIs?
ACEIs - side effects?
2. Dry cough
6. Altered taste
ACEIs - 2 contraindications?
1. Pregnancy (teratogenic)
2. Bilateral renal artery stenosis
Specific receptor type that ARBs antagonize?
AT-II type 1 receptor.
Do ARBs cause dry cough?
No - ARBs do not inhibit the breakdown of bradykinin.
Is there a pregnancy contraindication for ARBs?
Yes - pregnancy category C for the 1st semester and pregnancy category D for the 2nd and 3rd.
How do CCBs work in the treatment of HTN?
Block vascular L-type calcium channels which leads to decreased heart contractility and increased vasodilation of coronary and peripheral vasculature.
DHP CCBs side effects?
1. Peripheral edema
3. Reflex tachycardia
6. Gingival hyperplasia
Verapamil - side effects?
1. Drug-drug interactions
3. AV block
CCB action on the kidney?
CCB that is used in subarachnoid hemorrhages to prevent vasospasm?
T-type CCB used in absence seizures?
Name 3 alpha-1 blockers used for HTN?
2 main side effects of alpha-1 blockers?
1. 1st dose syncope
2. Reflex tachycardia
What class of drugs can be used to block the reflex tachycardia caused by alpha-1 blockers?
Alpha-1 blockers are most commonly used for what condition other than hypotension?
Clonidine mechanism as antihypertensive?
Central alpha-2 agonist --> Decr. sympathetic outflow from the CNS, producing a decrease in TPR, HR, and BP.
Why are diuretics often given to patients on clonidine therapy?
Clonidine causes Na/H2O retention.
Other than HTN, what is clonidine used for?
1. Nicotine withdrawal
2. Heroin withdrawal
3. Alcohol dependance
4. Migraine prophylaxis
5. Severe pain
6. Clozapine-induced sialorrhea
Clonidine side effects?
3. Dry mouth
4. Rebound HTN with ABRUPT withdrawal (must taper down dose when discontinuing therapy)
Can clonidine be used in patients with renal dysfunction?
Yes, because renal blood flow and GFR are not compromised with clonidine therapy.
Alpha-methyldopa is converted to what active metabolite?
Mechanism of action of alpha-methyldopa?
Central alpha-2 agonist.
Can alpha-methyldopa be used in patients with renal dysfunction?
Is alpha-methyldopa contraindicated in pregnancy?
NO - It is one of the antihypertensive drugs of choice in pregnant women.
Side effects of alpha-methyldopa?
2. Hemolytic anemia
3. Drug-induced lupus
6. Dry mouth
Name the drug:
1. Decreases TPR
2. Ofter requires beta-blocker to counteract subsequent tachycardia.
3. May cause drug-induced lupus
What class of drugs are used to counteract the fluid retention caused by hydralazine?
Side effects of hydralazine?
1. Reflex tachycardia
2. Fluid retention
3. Drug-induced lupus
Enzyme responsible for the metabolism of hydralazine?
Minoxidil - mechanism?
Opens K channels which leads to membrane hyperpolarization and subsequent arterial vasodilation.
Minoxidil is a prodrug that is activated by what mechanism?
Common side effect of minoxidil?
Hypertrichosis - used in treatment of alopecia.
Name the drug:
1. Direct acting vasodilator, used in hypertensive emergencies
2. Can be used to prevent hypoglycemia in patients with insulinoma
How does diazoxide work to prevent hypoglycemia in patients with insulinoma?
It decreases insulin release.
Name the drug:
1. Used in hypertensive emergenies.
2. Acts via incr. cGMP through NO mechanisms
3. Forms thiocyanate and cyanide metabolites
What class of antihypertensives may help prevent left ventricula remodeling seen in patients with CHF?
What class of antihypertensives may improve patient's lipid profiles?
What 2 classes of antihypertensives may protect renal function in patients with DM?
ACEIs and ARBs --> DECREASE MICROALBUMINURIA.
Statins - how do they affect the lipid profile?
1. Mainly reduces LDL
2. Moderate reduction of TGs
3. Moderate elevation of HDLs
Statins - side effects?
1. Incr. LFTs
2. Dose-dependent rhabdomyolysis
7. Drug-drug interaction
8. Contra in pregnancy - Category X
Lab tests for monitoring statin toxicity?
Most potent antihyperlipidemic agent to elevate HDL?
Another name for niacin?
B3, nicotinic acid.
Niacin - mech of action?
1. High-dose niacin INHIBITS VLDL and apoprotein synthesis in liver.
2. Incr. t-PA
3. Decr. fibrinogen
How does niacin affect the lipid profile?
1. Elevation of HDL
2. Reduction of LDL
3. Reduction of VLDL
4. Reduction of TGs
Niacin - side effects?
1. Facial flushing
7. Abdominal pain
How is facial flushing counteracted in patients on niacin therapy?
Pretreatment with aspirin to counteract PG release.
What new antihyperlipidemic agent works by inhibiting absorption of cholesterol at the brush border in the small intestine?
Side effects of ezetimibe?
2. Abdominal pain
Which antihyperlipidemic drug class decreases VLDL, LDL, TGs and increases HDL, by activating lipoprotein lipase?
Mention some fibrates?
Major effect that fibrates have on the lipid profile?
Reduction of TGs.
Side effects of gemfibrozil?
4. Abdominal pain
7. Incr. levels of warfarin + sulfonylureas via protein-binding displacement.
Mechanism of action of bile acid sequestrants?
Anion exchange resins that bind bile acids/salts in the small intestine, thereby preventing their reabsorption; decr. bile acids results in incr. plasma cholesterol uptake by hepatocytes to replenish bile acid levels, thereby decreasing plasma LDL levels.
Give examples of bile acid sequestrants?
Side effects of bile acid sequestrants?
5. Impaired absorption of fat-soluble vitamins
6. Impaired absorption of warfarin
What OTC medication, naturally found in certain fish, can decrease TG levels and be useful in the prevention of coronary heart disease (CHD)?
Omega-3 fatty acids.
Where is PGI2 made?
Vascular endothelial cells
Where is TXA2 made?
Incr. PGI2 leads to an increase of what 2nd messenger?
cAMP does what to platelets?
Inhibits platelet activation and release of platelet aggregating factors.
How does ASA work as a platelet aggregation inhibitor?
Irreversible inhibition, via ACETYLATION of COX --> reducing TXA2 levels.
What 2 drugs inhibit platelet aggregation + platelet fibrinogen interaction by blocking ADP receptors?
Ticlopidine - side effects?
How should patients on ticlopidine therapy be monitored?
CBC with differential every 2 weeks for the first 3 months of therapy and as needed thereafter.
Dipyridamole - mechanism as a platelet aggregation inhibitor?
Inhibits phosphodiesterase (PDE) thereby incr. cAMP levels --> cAMP potentiates PGI2 + Inhibits TXA2 synthesis.
Dipyridamole - usually given with?
Another name for factor II?
Another name for factor IIa?
How does heparin work as an anticoagulant?
Complexes with antithrombin III to increase inactivation of clotting factors IIa, IXa, Xa, XIa, XIIa, and XIIIa.
Which pathway of the clotting cascade is mainly affected by heparin?
Which lab test is used to monitor heparin therapy?
PTT, therapeutic PTT levels are 1.5 to 2.5 times that of normal.
How is heparin administered?
IV or SQ
Why is intramuscular administration of heparin contraindicated?
Trerapeutic indications of heparin?
1. Prevention and treatment (by preventing expansion of the clot) of DVT and pulmonary embolism (PE).
2. Used for anticoagulation during MI.
Onset of action of heparin?
IV = Immediate onset
SQ = 20-30min
Does heparin cross the placental barrier?
No, therefore it is safe in pregnancy.
What are the adverse effects of heparin?
4. Heparin-induced thrombocytopenia (HIT)
Heparin undergoes what type of metabolism?
2. Reticuloendothelial system
What drug is used to counteract heparin OD?
Roughly, how many units of heparin are neutralized by 1mg of protamine sulfate?
Onset of action of protamine sulfate?
What paradoxical side effect can protamine cause at high doses?
Anticoagulation leading to hemorrhage.
What is the mechanism of action of enoxaparin?
LMWH that has higher ratio of antifactor Xa to antifactor IIa activity vs unfractionated heparin (UFH).
Half-life of LMWH?
2-4 times that of UFH.
Does PTT need to be monitored in patients on LMWH therapy?
What synthetic pentasaccharide causes an antithrombin-III-mediated selective inhibition of factor Xa?
Which pathway is mainly affected by warfarin?
Which lab tests are used to monitor warfarin?
PT - INR --> Therapeutic levels are between 2 and 3.
Warfarin - mechanism?
1. Inhbitis synthesis of vit-K-dependent clotting factors II, VII, IX, X via inhibition of vitK epoxide reductase.
2. Also inhibits synthesis of protein C and protein S.
Warfarin onset of action?
36-72hrs (anticoagulant action)
How long after initiation of warfarin therapy is the full therapeutic effect seen?
5-7 days (antithrombotic action).
Acute alcohol intoxication does what to warfarin metabolism?
Inhibits warfarin metabolism - thereby increasing warfarin blood levels.
Chronic alcohol use does what to warfarin metabolism?
Induces warfarin metabolism, thereby decreasing warfarin blood levels.
What happens to the INR of warfarin patients who begin thyroid replacement medication?
Thyroid hormone increases the metabolism of clotting factors, thereby potentiating the effects of warfarin.
What happens to the INR of warfarin patients who begin sulfonamides?
Sulfonamides inhibit CYP-450 2C9 --> Incr. warfarin levels.
Does warfarin cross the placenta?
YES - Contra in pregnancy - teratogenic.
Warfarin side effects?
2. Drug-drug interactions
3. Skin necrosis (seen within the first few days of warfarin therapy and is secondary to decr. protein C levels).
4. "Purple toes syndrome" --> by cholesterol microemboli!!!
What can be used to counteract the effects of warfarin?
Vit K --> SLOW onset.
Fresh frozen plasma --> Rapid onset.
The synthesis of which 2 factors is inhibited first when warfarin therapy is initiated?
1. Factor VII
2. Protein C
--> Therefore patients may INITIALLY be hypercoagulable when warfarin is first initiated.
Why are factor VII and protein C inhibited first when warfarin therapy is initiated?
These proteins have the SHORTEST half-lives when compared to the half-lives of II, IX, X, S.
Mechanism of action of abciximab, eptifibatide, tirofiban?
Blockade of the glycoprotein IIb/IIIa receptor on platelets, thereby inhibiting platelet aggregation.
What is the physiologic ligand for the glycoprotein IIb/IIIa receptor?
What is the mechanism of action thrombolytic agents?
Conversion of plasminogen to plasmin --> cleaves fibrin, thereby leading to lysis of thrombi.
What is the main side effect of thrombolytic agents?
Thrombolytic agents - contra in what settings?
1. Active internal bleeding
2. History of cerebrovascular accident
3. Recent intracranial or intraspinal surgery
4. Intracranial neoplasm
5. AV malformation
6. Severe uncontrolled HTN (SBP>185, or DBP>110).
7. Evidencce of intracranial hemorrhage
8. Suspected aortic dissection
9. Seizure at the onset of stroke
10. Current use of anticoagulants or an INR >1.7
11. Lumbar puncture within 1 week
Therapeutic indications of thrombolytic therapy?
1. Acute MI
2. Acute PE
3. Acute ischemic stroke
What is the "therapeutic time window" for administering thrombolytic agents to patients with acute ischemic stroke?
Within the first 3 hours of the onset of symptoms.
Give examples of thrombolytic agents?
What 2 drugs can counteracct thrombolytic agent therapy?
2. Tranexamic acid
--> BOTH inhibit plasminogen activation.
With regard to thrombolytic agents, what does "clot-specific" mean?
Drug specifically activates plasminogen that is bound to fibrin in a thrombus with a low affinity for free, circulating plasminogen.
Which trombolytic agent is "clot-specific"?
Alteplase is also known as?
Where does tPA come from?
Recombinant DNA tech.
What type of enzymatic activity does tPA possess?
Serine protease activity.
Where does streptokinase come from?
Group C β-hemolytic streptococci.
How does streptokinase work as a thrombolytic agent?
Forms a 1:1 complex with plasminogen; complexed plasminogen then converts free plasminogen into plasmin (active form).
Does streptokinase have any enzymatic activity?
Is streptokinase "clot-specific"?
What proteins does the streptokinase-plasminogen complex degrade?
What lab value is monitored with streptokinase therapy?
Why is streptokinase antigenic?
It is recognized as a foreign protein (antigen).
What side effects are specific to streptokinase?
Half-life of anistreplase?
How does anistreplase work as a thrombolytic?
Anisoyl group blocks the active site of plasminogen.
As complex binds to fibrin, anisoyl group is removed and the complex becomes activated.
Does urokinase have enzymatic activity?
Originally, where did urokinase come from?
Where does urokinase come from now?
Fetal renal cells (human).
Is urokinase antigenic?
No, since it is not a foreign protein.