Hematopoiesis

• The production of new blood cells

• 3 essential nutrients- Iron, Vitamin B12, Folic Acid

Anemia

A deficiency in oxygen-carrying erythrocytes

Who has a higher risk of being anemic?

• Premature Infants
• Children during rapid growth periods
• Pregnant and Lactating Women
• Those with chronic kidney disease
• Those with inabilities to absorb iron
• Blood Loss

Average diet contains 10-15mg of iron but only 5-10% absorbed

What are symptoms of anemia?

• Pallor (Pale Skin)
• Fatigue
• Dizziness
• Exertional Dyspnea (Labored Breathing)

What is a treatment for anemia?

• Oral or Parental Iron preperations are available
• Ferrous Salts are absorebed better

              Oral Preps include- ferrous sulfate, gluconate, and fumarate.

             Side Effects include- Constipation, GI Upset, and black stools

• Iron dextran is a parental iron therapy. Usually given IV after a hypersensitivity test.

             Side Effects include- Headache, light-headedness, fever

Vitamin B-12 Deficiency Anermia

• Serves as cofactor for several essential biochemical reactions in humans.- DNA synthesis, Myelin sheath protection
• Vitamin B12 is sometimes called "extrinsic factor"- Intrinsic factor protein is secreted by the stomach to help uptake dietary uptake
• Average diet contains 5-30mcg but only 1-5mcg absorbed. Sourses include liver, eggs, and dairy products.

What are some causes and symptoms of Vitamin B12 Deficiency Anemia?

Causes: Inadequate dietary intake, decreased absorbtion, and inadequate utilization

Symptoms: Pallor(Pale Skin), Icterus(Yellowing Skin), Gastric Mucosal Atrophy

What are the two forms of Vitamin B12 deficency?

- Pernicious Anemia- Lack of the ability to synthesize intrinsic factor

-Megaloblastic Anemia- Results from a deficiency of cyanocobalamine

-Treatment- Cyanocobalamine (B-12)

Folic Acid Deficiency

Role of FA: Cell growth and reproduction which helps with protein synthesis.

Folate Deficency results in megaloblastic anemia. S&Sx are similare to Vit B12 Deficency except for neuro.

Inadequate dietary intake leads to FA deficiency- ppl with liver diease or alcoholics

Pregnant women have increased FA Reqirements- Neurotubular defects can happen

Treatment is OTC Folic Acid Supplements

Coagulation

Normal blood clot formation due to local tissue injury

Liquid to a solid-- a "plug"

Platelets/Thrombocytes

Aggregation

Thrombus

Thromboembolism

1. Deep Vein Thrombosis
2. Atrial Fibrillation
3. Stroke
4. Myocardial Infarction
5. Pulmonary Embolus

• Central role in hemostasis
• Allows fibrinogen to form a fibrin clot
• Activates other clotting factors
• Platelet activator

-Used against clot formation when clot mechanism becomes too active.

-Inhibits platelet aggregation or interferes with plasma clotting factors

Indirect Thrombin Inhibitors

*HINT: 3 of them*

• Heparin
• LMWH-- Lovenox(enoxaparin)
• Atrixa(fondaparinux)

Direct Thrombin Inhibitors

*HINT: 2*

-Lepirudin

-Dabigatran

Anti-Coagulant

*HINT: 1*

Anti- Platelets

*HINT: 3*

-ASA(Asprin)

-Plavix

-Dypridamole

Given IV and Sub Q only

Never given IM or orally

Close Monitoring

Side Effects: Heparin-Induced thrombocytopenia

MOA: Interferes with platelet aggrigation

Inhibits Thromboplastin activity

Inhibits Thrombin activity

Prevents fimbrin to form clot

Lovenox(enoxaparin)

Fragments of heparin

MOA: Inhibits factor 10a

-More predictable, improves SC bioavailablility,

longer half-life, less need for monitoring

Atrixa(fondaparinux)

Dosing is qd compared to lovenox(bid)

MOA: Inhibits factor Xa which interrups the blood coagulation cascade and inhibits thrombin formation and thrombus development.

Direct thrombin Inhibitor

Recombinant formulation of hirudin, which is a thrombin inhibitor isolated form the saliva of leeches

Direct Thrombin Inhibitor

FDA approved on OCT 2010

"Prodrug"- The body has to metabolize it for it to become active.

BID dosing

Adverse reactions: Bleeding, GERD, Dyspepsia(GI upset)

Advantages: No monitoring or dose adjustments, No known food-drug interations, Pregnancy Cat C, Very little DDI's (rafampin)

Disadvantages: Lack of a way to monitor, NO reversal agent to treat overdose, Cost(very expensive)

Anti-Platelets

MOA: Irreversibly inhibits the formation of thromboxane A2--No platelet aggregation

Anti Platelets

MOA: Reversibly interferes with platelet aggregation by increasing Adenosine, an inhibitor of platelet reactivity and inhibits phosphodisterase within the platelets

Plavix (clopidigrel)

&

Effient (prasuarel)

More beneficial compaired to clopidigrel in reducing thrombic events but bleeding was seen more frequently with prasuarel

MOA: Blocks Adenosine diphosphate binding to membrane receptors and preventing ADP activation of GP Iia/IIIb in coagulation cascade

Benefits: Given PO, Less side effects, Inexpensive

MOA: Inhibits vitamin-K dependent clotting factors II, VII, IX, X. Prevents synthesis of normal clotting factors

Used in Rat Poisin

Adverse Effects: Bleeding, Skin Necrosis, Purple toe syndrome, Pregnancy Cat X

Lots of DDIs- 4Gs-- Ginkgo,Ginseng, Garlic, Green Tea

Easy Bruising

Thrombocytopenia

Prolongled Bleeding (In gums during brushing and from shaving, Hematuria in the stool, unexplained epistaxis)

Heparin- Protamine Sulfate

1mg of protamine will neutalize 90 to 120 units of heparin. It binds to heparin molecules and inhibits the anticoagulation action.

Coumadin- Vitamin K. Promotes synthesis of factors XII, IX, and X

For a Heparin Dosing: Normal is 20-35 seconds

For Coumadin dosing: use INR lab value

Normal INR is 2-3

MOA: To stimulate Plasminogen to change into plasmin to cause Fibrinolysis to occur.(Dissolves formed clots)

"clotbusters"

must be administered ASAP

Adverse effects: Hemorrage, Allergic Reactions

• Active Bleeding Tendencies
• Uncontrolled Hypertention
• Ulcers
• Recent Surgery on Brain or Spinal Cord

Vitamin K(aquamephyton)

Thrombin-Powder

• A newborn to help wih clotting
• Newborns whos mothers were on oral anti-coagulation therapy
• Control Bleeding during a sugical procedure
• Hemophiliac- missing clotting factor VIII

Right & Left Ventricle

Right & Left Atrium

-S.A. node

     -Pacemaker

     -Maintains Pumping

-A.V. node

-Bundle of His

-Purkinje Fibers

*Responsible for coordinating the contractions of the heart chambers

Myocardial Action Potential: Normal heartbeat initiated by electrical signals

Phase 0: Rapid depolarization

Phase 1: (Notch) Initial repolarization

Phase 2: AP plateau

Phase 3: Final Repolarization

Phase 4: Return to diastolic potential

P wave- reflects atrial depolarization

PR wave segments- refects how long it takes for nerve

impulses to get form the SA node to the AV node

QRS wave- reflects ventricular depolarization

ST segment- absolute refactory period, plateau phase

T wave- Ventricular Repolarization

-Phase 1,2,3

-No stimulants, no matter how strong, will excite the nerve

-End of Phase 3

-Stronger than normal stimuli can cause excitation

An abnormal in either the rate or rhythm of the heart

Vaughan Williams Classification

They work to control arrythmias by sodium blockade, blockade of sympathetic automatic effects in the heart, prolongation of the refactory period, and calcium channel blockade.

The Goal is to convert arrythmias to a normal rhythm

Blocks sodium channels

Class 1A: Quinidine, Procainamide

Class 1B: Lidocaine

Class 1C: Propafenone

MOA: Blocks conduction velocity

Beta Blockers

-Propranolol

MOA: Blocks the potassium channels that results in prolongation of AP

-Bretylium, Amiodarone

**For Amiodarone 4 baseline test are perforemd on the thyroid, pulmonary, eyes, and liver enzymes(LFT)

MOA: inhibit Calcium entry-->Slow conduction

Calcium Channel Blockers

**Nondihydropyridines**

-Verapamil

-Diltiazem

MOA: Blocks sodium channels, blocks conduction velocity, blocks the potassium channels, and inhibits calcium entry.

Competes with Amiodarone

Can cause severe liver injury, must monitor LFTs

Tachycardia

Atrial Flutter

Atrial Fibrillation

Ventricular Fibrillation

Premature Atria Contraction

Premature Ventricular Contraction

Bradycardia

Heart Failure

Edema(pulmonary or peripheral)

Abd Pain

Tachypnea(fast breathing)

Nocturnal dyspnea(difficulty breathing at night)

Exercise intolerance

Orthopnea(difficulty breathing when lying flat)

Dyspnea on exertion

Crackling sounds (rales) on auscultation

Cardiac Glycosides

Clinical Uses: Heart Failure, Arrhythmias (Afib, SVT)

Digitalizing Dose: Frequent and higher doses are given to achieve desired blood levels

Maintenance Dose: smaller regular doses given once a day to maintain blood levels

MOA: Inhibits the NA/k ATPase pump which acts to increase the intracellular NA/CA exchange to increase intracellular calcium.

Decrease heart rate

Increases force of contraction

slow conduction thru AV node

for Heart Failure: 0.5 to 0.8 ng/ml

for Arrhythmias: 0.8 to 2 ng/ml

Toxic at > 2.5 ng/ml

Must monitor Potassium and Calcium

Side Effects: N/V, HA, Visual Distubances, Rash, Slow Pulse, Irregular Pulse

Positive Inotropic- Increase FOC

ex. Cardiac Glycosides

Negative Inotropic- Decrease FOC

ex. Beta Blockers, Calcium Channel Blockers

Positive Chronotropic- Increase HR

ex. Epinephrine & Atropine

Negative Chronotropic- Decrease HR

ex. Cardiac Glycoside

Hardening or narrowing of the arteries, which results in a decrease blood flow

due to aging

Fatty deposits accumulate on the walls of the arteries, reduces the blood supply

Most common form of arteriosclerosis

Linked to high cholesterol, Increased BP, and smoking

MOA: Dilate Veins and Arteries, Decrease blood pressure, decrease work on the heart, decrease oxygen consumption

Side Effects: Flushing, HA, Faintness, Dizziness, Tachycardia, Orthostatic HYPOtension

Avoid Drugs used to treat Erectile Disfunction--Sildenafil(24 hrs), Vardenafil(24 hrs), and Tadalafil(48 hrs)

MOA: Blocks Beta 1 Receptors--- decrease oxygen consumption

ex.Propranolol, nadolol, atenolol, metoprolol

Can cause drowziness, dizzyness

Some are selective, some are non-selective

Calcium is responsible for the force of contraction, normal activity, and heart rate associated with the heart.

CCBs are divided into two subclasses because their structures and mechanism of action differ slightly.

Dihydropyridines: Nifedipine, Amlodipine, Nisoldipine

Nondihydropyridines: Verapamil, Diltiazem

Treatment for chronic angina

MOA: Exerts anti-anginal and anti-ischemic effects without changing heart rate or blood pressure.

Side effects: Dizziness, Constipation

In Treatment for MI

What does MONA Stand for?

Morphine

Oxygen

Nitrate

Aspirin

-if allergic to aspirin use plavix

Primary HTN- Cause is unknown, but several factors contribute. ex. family history, obesity, stress, smoking, diet, etc.

Secondary HTN- Caused by Renal disease, pregnancy, and drug induced (sudafed)

Top # of Blood Pressure.

Most Common Form of HTN

Rises throughout life

When Heart pumps the blood

Heart Relaxes and Fills with blood

after age of 50 levels start to drop off

Bottom # of BP

located in the internal walls of the carotid arteries and the aortic arch

if an increase in BP, receptor stimulates the vagus nerve, causing a decrease in HR, FOC, and CO which will decrease BP

Vasodialation occurs as well

Main Function: Maintains water and electrolyte balance, maintains acid-base balance

Kidney allows the blood to gain necessary nutrients, water, and electrolytes

 Where Na+ goes--- H2o follows

If NA+ goes in, K+ goes out

If H+ goes in, Na+ goes out

If Cl- goes in, Na+ follows

Hydrochlorothiazide

MOA: Inhibits Na reabsortion in the distal tubles causing an increase excreation of Na, water, K, H

Side Effects: Photosensitivity, Sulfa Allergy (has sulfa in it) HYPOkalemia, hypercalcemia, hyperlipidemia, hyperglycemia, hyperuricemia

Thiazide-like diuretics: Hygroton, Lozol, Zaroxolyn

MOA: Inhibition of Na and Cl in the ascending loop of Henle and distal renal tubules(loses water, Na, Cl, Mg, and Ca)

ex. Bumex, Lasix, Ethacrynic Acid

MOA: Block the aldosterone receptor, which results in K retention

ex. Amiloride, Aldactone(also used for acne), Triamterene

A side effect for Aldactone is gynecomastia(produces breast)