Cardiovascular Drugs made EZ: Part 2

One subject that often confuses nursing students preparing for the NCLEX exam and
practitioners alike, is that of clotting and anticoagulants. The problem with this, is
these medications are extremely common in both inpatient and outpatient
populations, so this knowledge is imperative for those in the healthcare industry to
have. Lets take a look together and see if we can make it a bit more simple, in case
your NCLEX exam decides to drill you on this point. We will go step by step through
the clotting process, taking small sidetracks to look at specific medications.
Hemostasis
When vascular injury occurs, various mechanisms are available to stop the loss of
blood
The mechanism employed depends upon the extent of injury, but the end result of
all is to produce strands of Fibrin to patch the hole; The difference in the various
mechanisms is the speed and amount of Fibrin produced
1.Platelet Plug
2.Intrinsic Coagulation
3.Extrinsic Coagulation

Platelet Plug
When vascular endothelial tissue is damaged, a platelet plug can form, sealing the
hole. If no deeper tissues are exposed, this may be the extent of the healing
process. If damage is more extensive, platelets, as well as tissue exposure can
initiate further coagulation. Platelet plug formation occurs in 4 steps (use pic to
right of text as visual guide):

1) Adhesion: When subendothelial tissue is exposed, sticky proteins (Von

Willebrand factor) are exposed to passing blood and act as magnets to passing
platelets.
2) Aggregation: ADP, a breakdown product of ATP released from damaged cells,
stimulates the production of receptors (GPIIb) on the platelets that bind a free
floating soluble protein Fibrinogen.
Pharm Note: Plavix and Ticlid inhibit ADP, so platelets are not stimulated to
produce fibrinogen receptors and clots are more difficult to produce
Pharm Note: Abciximab (Reopro) binds to the platelet GPIIb receptor and blocks
fibrinogen from binding, and clots are more difficult to make

3) Secretion: Stimulated platelets release chemicals like Thromboxane, that

attracts other platelets. Fibrinogen can bind two platelets, thus platelets begin to
collect in mass.
4) Platelet Coagulation: Stimulated platelets now produce factor V, which leads
to fibrinogen being transformed into Fibrin threads to incase the aggregated
platelets
Pharm Note: Aspirin blocks the release ofThromboxane for the life of the
platelet, so cell aggregation is made difficult. This is why aspirin is known to make
platelets less sticky, and is so frequently given as prophylaxis against clot
formation. Since platelets are still allowed to bind Von Willebrand, there is still some
platelet plug action, meaning some bleeding is stopped. This is why Aspirin is not as
powerful an antiplatelet drug as prescription drugs like Plavix and Reopro.

(platelet aggregation)

(fibrin threads creating plug)

Intrinsic Coagulation
When the insult is deeper, collagen may be exposed, initiating the intrinsic coagul

ation cascade. Collagenactivates

factor 12 then 11 then 8 + 9 then 10. 10 converts Prothrombin into Thrombin,
which then converts Fibrinogen to Fibrin. This process is faster than a platelet
plug as you dont need to wait for platelets to collect, and it forms more
extensive Fibrin patches.
Pharm Note: Heparin inhibits the Intrinsic Factors, making them slower to
respond, which makes clotting more difficult and less extensive

Lab Note: Partial Thromboplastin Time (PTT) measures the speed of collection
of these factors, thereby measuring the effectiveness of Heparin. PTT, usually 30-40
secondsis the amount of time it takes all of the necessary factors to gather at site of
need. Heparin binds these factors, slowing their collection, and lengthening PTT.
Extrinsic Coagulation
When deep injury occurs, tissue is exposed to blood, initiating the extrinsic
coagulation cascade. Tissue factor activates factor 7 then 10. 10 then follows
same route as above. With fewer steps this cascade is faster than the intrinsic and
develops more extensive Fibrin patch. Of importance to note is just as Ca makes
muscle contract stronger, its presence also makes clots stronger.
Pharm Note: Factor 7 is made in the liver from Vitamin K. Warfarin
(Coumadin) blocks Vitamin K and thereby reduces the amount of Factor 7 made.
Now it takes longer to collect enough Factor 7 to initiate this extrinsic clotting, and
you have slower clotting that is less extensive. Since the medication effects future
Factor 7 production and not that currently present in the blood, it takes a few days
to see its effects.
Lab Note: Prothrombin Time (PT) measures the speed of collection of Factor 7,
thereby measuring theeffectiveness of Coumadin therapy. This value is converted to
the INR. Think of this value as a stopwatch that starts timing as soon as injury
occurs. PT, usually 10-12 seconds is the amount of time it takes factor 7 to reach
the area of need.

(extensive fibrin patch)

Regulation of Coagulation
To assure coagulation does not go too far, 2 specific mechanisms inhibit or reverse
the process:
1) Antithrombin III (AT III): AT III inhibits the production of Thrombin by blocking
Prothrombin, thereby reducing the amount of Fibrin formed. Healthy endothelial
cells produce this, thereby quarantining off the damaged area so clotting does not
extend beyond where it is needed.
Pharm Note: Lovenox (Enoxaparin) enhances the activity of AT III, thereby
slowing clot formation. The low molecular portion of heparin is the active part here,
so regular Heparin partially works here in addition to Intrinsic factor inhibition.
Lab Note: Partial Thromboplastin Time (PTT) is not effected by Low Molecular
weight heparins (Lovenox) because no Intrinsic factors are inhibited.
2) Tissue Plasminogen Activator (TPA): Injured cells also release TPA,
which converts free floating Plasminogen to Plasmin. Plasmin degrades Fibrin, so
clots are constantly broken down, even as they are built. The more active system
wins, depending upon how much clotting is actually needed.
Pharm Note: TPA (Alteplase) can be synthetically injected to actively break down
clots, such as in the case of a Stroke or Myocardial Infarction. Greatcaution should
be used when administering this as massive, even fatal bleeds are possible.
(Streptokinase andUrokinase are alternatives that work by same method)
Posted by Chad Reihm MSN MD at 2:17 PM 2 comments:
Labels: Cardiology, Hematology, Pharmacology
Thursday, May 15, 2008

Cardiovascular Drugs Made EZ: Part 1

Pharmacology is a key subject when studying for any healthcare board exam, such
as the NCLEX or USMLE. This word can be a simple stimulus for nightmares in many
in nursing or medical school studying for their boards. We are going to take a multipart look at this subject by looking at one of the biggest classes of drugs that you
will need to know: Drugs effecting the heart and vasculature.

This is a huge class of drugs, accounting for a huge chunk of the drugs that we
actually need to know well, and is one that the NCLEX and USMLE are going to ask
you about. Lets break this class down into smaller, more manageable chunks. We
will start with drugs used to treat Hypertension, as this class is very large and very
important. First of all, take a look at the picture below for a summary of the drugs
we will discuss.

ACE Inhibitors
Names:
Prils Think an ACE is a Pro (kinda like a pril)
Examples: Enalapril (Vasotec), Captopril, Lisinopril
Uses:
Hypertension, Heart Failure, Protection for diabetics vs nephropathy, Decrease
Mortality in post-MI patients due to afterload reduction
Action:
blocks the enzyme that converts angio I to angio II in the lungs. Angio II leads to
vasoconstriction, aldosterone release, and sodium retention: this is blocked, which

decreases blood pressure and puts less strain on heart

Common Side Effects:
Dry hacking cough; Angioedema; Hyperkalemia
Taste disturbance; Rash; Insomnia, Orthostasis
Nursing Implications:
CI: Pregnancy Category D; Bilateral Renal Stenosis
Use K supplements carefully due to hyperkalemia concerns
Stop drug if cough, angioedema
Taste of food may be diminished during first month of therapy
Angiotensin Receptor Blockers (ARBs)
Names:
Sartans
Examples: Losartan (Cozaar), Irbesartan, Valsartan (Diovan)
Uses:
Hypertension, Heart Failure
Action:
Blocks the receptor for Angiotensin II, blocking the effects of this potent
vasoconstrictor
Common Side Effects:
Hyperkalemia, Angioedema, Orthostatic hypotension
Nursing Implications:
CI: Pregnancy Category D in 2nd/3rd trimesters; Bilateral Renal Stenosis
Safer side effect profile than ACE inhibitors but less studied

To understand ACE and ARB it is vital that you have an idea of what the ReninAngiotensin-Aldosterone System (RAAS) is. Remember the purpose of RAAS is to
increase blood pressure in response to decreased renal blood flow or pressure, and
the purpose of the drugs that work here is to block this system and lower blood
pressure. Check out the pick below for a summary of the RAAS and where certain
drugs work.

Beta Blockers (or beta antagonists)

Names:
OlOls: Remember Beta video tapes? They are OLdOLd
Ex: Selective B1: Metoprolol, Atenolol (I MET A TEN last night)
Ex: B1B2: Propanolol (Inderal), Labetalol, Carvedilol (Coreg) (ilol, alol-also alpha
blocker)
Uses:
Hypertension, Angina, Arrhythmias, Glaucoma, MI prophy, Migraines
Action:
Block adrenergic Beta receptors (1 heart, 2 lungs), leading to lower sympathetic
activity = decrease in cardiac output, blood pressure and renin activity. Also some
drugs lower aqueous humor production
Common Side Effects:
Bradycardia, fatigue, insomnia, bizzare dreams, sex dysfunction, lipid dysfunction;
Respiratory distress (wheezing), Agranulocytosis, depression
Nursing Implications:
C/I in asthma, bradycardia, severe renal/hepatic disease, hyperthyroid, CVA
Signs of hypoglycemia (DM), tachycardia (hyperthyroid) may be masked
Glucagon may reverse overdose
Calcium Channel Blockers (Antagonists)
Names:
Dihydropyridines: Pines: Amlodipine (Norvasc), Nifedipine (Procardia)
Non-Dihydropines: Diltiazem (Cardizem), Verapamil
Uses:

 Angina, Arrhythmias (Non-Ds have more AV node effect)

Hypertension (Dihydros have more vasodilation effect)
HT (Pines), Dysrhythmias (Verapamil), HT/Dys (Diltiazem)
Action:
Blockade of Ca channels causes arteries to relax (vasodilate) and cardiac
conduction to slow through the AV node
Common Side Effects:
All: H/A, hypotension, dizziness, peripheral edema, Renal/Hepatic dysfunction
Dihydros: Ankle edema, flushing, tachycardia, gingival hyperplasia
Non-Ds: AV block, bradycardia, worsened systolic dysfunction
Nursing Implications:
Use very cautiously with heart failure/left ventricle inpairment, AV block
Dont abruptly stop medication; Warn patient to contact MD if irregular HR, SOB,
swelling, pronounced dizziness, constipation, nausea, hypotension

Peripheral Alpha Blockers

Names:
Mixed names: Zosins for BPH, ilol for HT;
Examples: Carvedilol (Coreg), Tamulosin (Flomax), Prazosin (Minipress)
Uses:
Hypertension, Peripheral Vascular Dz (raynaulds, phlebitis, etc), BPH
Action:
Blockade of Alpha 1 relaxes smooth muscle in arteries and prostate capsule,
leading to lower blood pressure, reduction in BPH, and increased blood in tissues
(warm/pink skin) as well as Renal arteries
Common Side Effects:
Orthostatic Hypotension (especially first dose), Reflex Tachycardia, Ejaculation
problems, nasal congestion
Nursing Implications:
Begin with small dose and give at bedtime to avoid dizziness and syncope
Change positions slowly to decrease orthostatic hypotension
Alcohol, Excessive exercise, prolonged standing, heat make S/E worse

Central Alpha Blockers

Names:
Clonidine (Catapres); Methyldopa (Aldomet)
Uses:
Hypertension

Action:
Central acting sympatholytic stimulates pre-synaptic alpha receptors to release
NE, which paradoxically reduces peripheral NE release, inhibiting vasoconstriction =
vasodilation and lower BP
Common Side Effects:
Sodium/Water retention, Dry mouth, Bradycardia, Impotence, Depression
Nursing Implications:
Advise patient not to abruptly withdrawal because significant rebound
hypertension can result
C/I in impaired liver function so monitor liver function tests occasionally
Do not confuse with the benzo Klonipin (patients have done so and taken a bunch
of Clonidine for a high, only to end up with a real lowBP that is.

Diuretics
Types:
Loop: Furosemide (Lasix), Bumetanide (Bumex), Torsemide (Demadex)
Thiazide: Hydrochlorothiazide (HCTZ)
K-sparing: Amiloride, Spironolactone
Carbonic Anhydrase Inhibitors: Acetazolamide (Diamox)
Uses: Edema associated with heart failure; Ascites with Cirrhosis; Hypertension
Action:
Loop: Inhibit Na, Cl, and H2O resorption in the loop of henle thus decreasing
blood volume; Also increase the excretion of K; Potent diuretics
Administer IV Lasix slowly because hearing loss can occur if given rapidly
Thiazide: Inhibit Na resorption and increase Cl, H2O, K, Ca, Bicarb, Mg excretion
in the urine; Also cause arterial dilatation; Moderate diuretic
While K and Na may be excreted, HyperCa is more likely to develop so never
administer to patient with hypercalcemia;
Eat foods rich in potassium, use sunscreen, and change position slowly
Caution when taking with Lithium, Digoxin, Corts, PO Diabetic meds
K-sparing: Block Na-K exchange in distal tubule causing loss of Na and water and
retention of K; Weak diuretic mostly added to preserve K
C/I in severe renal/hepatic dysfunction, hyperkalemia, Current ACE-I use
Carbonic anhydrase inhibitors:
Used to treat M.Alkalosis, Open Angle Glaucoma, Epilepsy, High altitude sickness
Inhibits the enzyme carbonic anhydrase which normally is responsible for
excreting H to combine with HCO3 for elimination of excess acidity, as well as
promoting diuresis. This drug obviously leads to an increase level of H+ in the blood
(M.Acidosis) and an increased excretion of Bicarb (HCO3)
C/I with CLOSED (narrow) angle Glaucoma
S/E i/c Renal Calculi, Hypercalcemia, and Hemolytic anemia
Common Side Effects:

 Loop/Thiazides: Hypokalemia, Hyperuricemia, Glucose intolerance, sexual

dysfunction, increase cholesterol/triglyceride levels
K-Sparing: Hyperkalemia especially when used with ACE inhibitors
Nursing Implications:
Caution for electrolyte disturbances; Watch for cramping, paresthesia
Administer in morning to avoid diuresis during night, Supplements (PhosLo)
Posted by Chad Reihm MSN MD at 1:54 PM 10 comments:
Labels: Cardiology, Pharmacology
Monday, March 10, 2008
Cardiac Output made EZ
A guaranteed subject that you will be tested on during your NCLEX or USMLE
examination is basic physiology of the heart. It is so important that we spent 2
straight weeks on this subject at my medical school during our cardiology module.
So before diving into those NCLEX and USMLE review books, check this out...
Cardiac Output

The cardiac output (CO) is the result of the stroke volume x HR/min

Stroke volume (SV) is never 100% of the volume in the ventricle at the end of
diastole, but is usually an ejection fraction of 60-80%

The stroke volume and subsequent CO depends upon four parameters

1. Preload (PL) Amount of blood in the left ventricle at the end of diastole
It is determined by the compliance of the ventricle and the amount
delivered by the venous system
Constriction of the venous system causes blood to be delivered faster,
increasing preload
When preload is higher, the ventricles get stretched more: Think of a bow
and arrow; the more you stretch the string, the more forceful the ejection of
the arrow
Thus with more stretching (preload), you get a more forceful contraction, up
until a critical point, when the heart is overstretched. Again think if you pull
the bow and arrow string too far and it breaks; no ejection of the arrow

2. Contractility
The ability of the heart to contract and the force at which it does so
The force of contraction is determined by how much Ca is stored in the SR
Contractility can be increased by flooding the cell with more Ca (beta
agonist) or by keeping more Ca in the SR and not letting it escape outside of
the cell (Digoxin)
Contractility can be decreased by the opposite effect on Ca or by damage
to the myocytes (myocardial infarction)

3. Afterload
Essentially equivalent to aortic back pressure that the heart must pump
against
Afterload is actually controlled by the resistance in the capillaries
As afterload increases it takes longer for the pressure in the ventricle to
become higher than aortic pressure, and only when this happens does the
aortic valve open and allow blood to flow out (remember things always go
from high to low pressure)
Therefore there is less time to expel blood during systole, so CO decreases
with increased afterload

4. Heart Rate
Remember CO = HR x SV
Do the math and see that an increase in HR also increases CO
Increased HR also increases amount of blood in the vasculature, which
stretches the arteries resulting in an increased BP
This increase in CO continues to a point at about 140 bpm, when diastolic
filling time gets too short and SV begins to decrease, causing an eventual
decrease in CO
Summary:
Think of a bucket with a faucet filling and a pump and hose draining
The faucet = Preload or amount filling heart
Pump = Heart contractility

 Hose = Diameter of hose is Afterload