HMG-CoA Reductase Inhibitors- the “statins”

MOA

• complex, blocks HMG-CoA reductase enzyme that is involved in cholesterol synthesis

• ↓ CV risk also by
• Promotes plaque stability
• ↓inflammation at plaque site
• ↓CAD progression/calcification
• • ↓ LDL
  • ↑ LDL receptors in liver
  • ↑ HDL

Indications of the “statins”

• Hypercholesterolemia
• Dyslipidemia
• Primary & Secondary prevention of CV events
• CV complication prevention for diabetes

• Oral only, well absorbed
• Metabolized by liver
• ½ excreted in bile
• ½ excreted in urine 

Adverse Effects of the “statins”

• Myopathy/Rhabdomyolysis- lysis of the muscle dut to creatine kinase build up
• Hepatoxicity- CK can cause renal failure
• Every 6 months have a lipid and liver panel!
• Drug Interactions
• Fibrates and Ezetimibe (Zetia)
• CYP3A4 inhibitors (in grapefruit) 

Nursing Implications of the “statins”

• Cholesterol management teaching
• Diet, exercise, drug therapy
• Monitor lipid panel and LFT’s 3 months after initiation of Rx and q6months thereafter
• Patient to report muscle pain/tenderness, malaise, weakness or fever immediately
• Most statins should be taken at bedtime
• Avoid grapefruit 

Nicotinic Acid (Niacin)

MOA

• ↓LDL and triglyceride levels, ↑HDL

Nicotinic Acid (Niacin)

strong adverse effects to true crystallin niacin

• Intense Flushing esp face and neck 
  • Flushing reduced by taking Aspirin 325mg 30 min prior to niacin
• Itching
• GI upset (N,V,D)Hepatotoxic
• ↑homocysteine levels

Bile-Acid Sequestrants

MOA

Reduces LDL cholesterol by preventing reabsorption of bile acids and increasing excretion

Bile-Acid Sequestrants

Adverse Effects

limited to GI tract: constipation, bloaing, indigestion, nausea, decrease absorption of fat-soluble vitamins

Bile-Acid Sequestrants

• Cholestyramine (Questran)
• Colestipol (Colestid)

Bile-Acid Sequestrants

Drug interactions

• bind with many drugs to reduce absorption of drugs; avoid giving any other drugs within I hour before or 4 hours after the bile sequestrant

Bile-Acid Sequestrants

Nursing Implications

• watch timing of med; monitor for constipation and encourage fluids; mix with juice or fluid well

Fibrates/Fibric Acid Derivatives

MOA 

• Most effective for lowering triglycerides
• Also raise HDL but do not affect LDL 

Fibrates/Fibric Acid Derivatives

• Gemfibrozil (Lopid)
• Fenofibrate (TriCor)

Fibrates/Fibric Acid Derivatives

adverse effects 

rashes, GI disturbances (N,V,D, Abd pain), ↑ risk GB stones, myopathy, liver injury

Fibrates/Fibric Acid Derivatives

drug interactions 

displaces warfarin from albumin- look for increased bleeding , increased PT, INR    

Cholesterol absorption inhibitor

Ezetimibe (Zetia)

Ezetimibe (Zetia)

MOA

acts on brush border of small intestines to inhibit cholesterol (dietary and bile); reduces LDL, trig, and apolipoprotein B; small increase HDL

Ezetimibe (Zetia)

drug interactions

• increase risk of liver damage with statins; monitor tranaminase levels!
• with fibrates ↑ risk GB stones; bile sequestrants will ↓ absorption of Zetia; cyclosporine ↑ levels of Zetia;        

Nitrates

Stable Angina

↓ O2 demand by dilating veins; ↓ preload

Nitrates

Variant Angina

↑ O2 supply by relaxing coronary vasopasm

Beta Blockers

Stable angina

↓ O2 demand by ↓ HR and contractility

Calcium Channel Blockers

stable angina

↓ O2 demand by dilating arterioles, ↓ afterload

Some ↓ HR and contractility (verapamil & diltiazem)

Calcium Channel Blockers

variant angina

↑ O2 supply by relaxing coronary vasopasm

Nitrates

form

• SL, translinqual spray,  oral, transdermal, IV

Nitrates

MOA

vasodilation mostly veins;  reduces preload (more blood in veins, less to the heart so the heart doesn't have to pump as hard)

Nitrates

Adverse effects

headaches; ↓ BP (vasodialted blood vessels); reflex tachycardia

Nitrates

drug interactions

antihypertensives;  Phosphodiesterase Type 5 inhibitors (Viagra); Βeta blockers, verapamil, diltiazem

Nitrates

Tolerance

Have a drug free period ; discontinue slowly

Nitrates

interventions

• transdermal-remove at night, rotate sites on upper chest, back and upper arms, monitor of skin irritation, do not put on broken skin
• Oral-do not skip, monitor BP, notify HCP if dizziness, may use Tylenol to reduce h/a initially; do not crush or chew
• SL- keep bottle tightly closed, avoid exposure to heat, moisture, replace after 6 months of opening

ANTICOAGULANTS

two types

• Parenteral
• Prevent the Conversion of Fibrinogen to Fibrin
• Oral
• Prevent the Synthesis of factors dependent on
• Vitamin K for synthesis

HEPARIN

forms

• Sub-q or IV- never IM!!

HEPARIN

uses

• keeps new clots from forming at a clot or in other places, does not break up clots

HEPARIN

uses

• Maintain patency of Venous Access Devices
• Patients with Acute Coronary Syndrome or MI- heparin drips
• Patients receiving Peritoneal Dialysis
• Patients with DVT or PE
• Patients in Disseminated Intravascular Coagulation
  (DIC)
• formation of small blood clots inside the blood vessels throughout the body. As the small clots consume coagulation proteins and platelets, normal coagulation is disrupted and abnormal bleeding occurs from the skin
• Patients with Short-term risk of Thrombus Formation
• Post- OP patients

heparin

moa

• Rapidly Promotes the inactivation of Factor X
• Prevents conversion of Prothrombin to Thrombin
• Affects Fibrin to limit Formation of a Stable Clot

heparin

pharmacokinetics

• Metabolism occurs in Liver
• Inactivated in Liver
• Excreted in Urine
• Must be administered Parenterally because destroyed in GI Tract
• Has Immediate Onset IV!!!

Heparin

o      Pharmacokinetics

• Onset 20 to 60 minutes Sub Q
• Does not cross Placenta or Breast Milk
• Safe in Pregnancy
• Heparin reaches steady state in 6-8 hrs
• Heparin has a short half life of 1-2 hr

Heparin

Adverse Effects

• Bleeding
• Antidote for Heparin
• Protamine Sulfate – 1 mg of Protamine Sulfate/100 units Heparin if Heparin given more than 30 min before Protamine Sulfate.
• Max Dose of 100mg Protamine Sulfate in a 2-hr period
• Heparin-Induced Thrombocytopenia
• Osteoporosis
• If Heparin used more than 6 months

Heparin

Contras

• Patients who are sensitive to beef and pork
• Patients with Thrombocytopenia, Bleeding Disorders, Active Bleeding (Except DIC) 

Heparin

Precautions

• Patients with potential for Hemorrhage

Heparin

Nursing implications

• High Risk Drug  requires 2 Nurses to Check before Administered
• Patients may not require Protamine Sulfate if not actively bleeding due to Heparin’s short half-life
• Teach Patients to inform you of any bleeding
• Avoid risky behaviors
• Use a soft toothbrush/electric razor during therapy
• Reason Heparin Therapy initiated and expectations

Heparin

Labs

• Therapeutic lengthening of the clotting time is 1 ½ - 2 times the control aPTT
• Check PTT q 6hrs after starting Heparin

Heparin

Drug interactions

• Nitroglycerin
• Increased Bleeding Risk
• Penicillins and Cephalosporins
• Additive effect
• Salicylates

Heparin

antidote

• Antidote for Heparin is Protamine Sulfate 

ENOXAPARIN

• Used to treat Acute Coronary Syndrome
• Prophylaxis for DVT

Lovenox

MOA

• binds to antithrombin but has less affect on thrombin
• Predictable dose response – Safer than Heparin

Lovenox

pharmacokinetics

• Prolonged half-life 3-6 hr

Lovenox

Adverse Effects

• Increased Risk of Bleeding

Lovenox

Contras

• Caution in patients with reduced Creatinine Clearance
• geriatrics       

Lovenox

nursing implications

• Self-administration of Sub Q injections (45 degree to 90)
• Same as Heparin- causes bleeding

• Prototype Warfarin (Coumadin)

warfarin

why is it administered?

• Follow-up to Heparin Therapy for 3-6 months
• Start Coumadin before Heparin discontinued to assure therapeutic levels of Coumadin reached
• Heparin is discontinued when INR is between 2 and 3 for 2 days in a row
• Why is it safe to take both drugs simultaneously?

warfarin

Prophylactically given long-term                  

• Mitral Valve Replacement
• Atrial Fibrillation

warfarin

how is dose measured?

• Measured by changes in the Prothrombin Time (PT)
• Measured against Standardized Unit of Control PT called
• International Normalized Ratio (INR) – reflects your patient’s PT compared to the Standardized PT value
• INR should be between 2 to 3 (dose is having the effect you want)
• INR range differs for Valve Replacement Patients.

warfarin

pharamokinetics

• Bound to Albumin in the Plasma
• Metabolized in Liver
• Excreted in the Bile
• Peaks in 1 to 9 hours
• Anticoagulant effect begins in 24 hours
• Max effect occurs when drug reaches steady state in 3-4 days
• Each time dose changes
• Takes 3-4 days for drug to reach full effect
• Drug persists for 4-5 days after discontinuation
• Crosses Placenta
• Does not Cross Breast Milk

warfarin

pharamocdynamics

• Blocks Vitamin K at its sites of Action
• Vitamin K is the Antidote for Coumadin
• Prevents the Activation of Factors II (Prothrombin), VII (7), IX (9), and X (10)
• Does not affects Factors already activated

warfarin 

adverse effects

• Bleeding
• GI Upset

warfarin

contras

• Patients who are Actively Bleeding
• Patients with GI tract Ulcerations or Wounds
• Bleeding Disorders
• Patients with Endocarditis, Pericarditis, or Pericardial Effusions
• Patients scheduled for Surgeries

warfarin

precautions

• Renal Patients
• Hepatic Patients

warfarin

nursing implicatons

• Monitor PT/INR 3-4 days after each change in dosing
• Discontinue Warfarin for 7 days prior to Surgery
• Monitor Patient’s Diet- Limit foods with Vitamin K
• Vitamin K competes with Warfarin
• What effect will Vitamin K levels have on Warfarin?
• Teaching Patient about Fall and Injury Precautions
• What other teaching?? GREEN LEAFY VEGGIES in moderation!!!

warfarin

drug interactions

• Additive effect with any drugs that increase risk of bleeding
• What are some of those Drugs? Aspirin, heparin, lovanox, other antiplatelets

antiplatelet drug

prototype

clopidrogrel (Plavix)

clopidrogrel (Plavix)

MOA

• Inhibits Platelet Aggregation
• Prolongs Bleeding Time
• Effect on Platelets is Irreversible
• Platelets exposed to drug are Affected for their Life Span

clopidrogrel (Plavix)

uses

• Reduces Occurrence of Artherosclerotic events
• MI, Ischemic Strokes, and TIA’s
• Prevents Reocclusion or Restenosis after Angioplasty and Bypass Surgeries
• Adjunct Therapy to Aspirin in the Treatment of Acute Coronary Syndromes with ST Elevation

clopidrogrel (Plavix)

pharmacokinetics

• Rapidly absorbed in the GI Tract
• At least 50% absorbed
• Food does not change Bioavailability
• Metabolized in the Liver
• Eliminated by the Kidneys and GI Tract
• Drug and Metabolite are highly Protein- Bound
• Steady State occurs between 3 to 7 days with Daily Dosing
• Takes about 5 days for Platelet Aggregation to Return to Baseline Levels after Antiplatelet Drug is Stopped
• Why is This Important to Know?

clopidrogrel (Plavix)

adverse effects

• GI distress and ulcers
• Bleeding
• Neutropenia

clopidrogrel (Plavix)

contras

• Active Bleeding Disorders
• Not Recommended for Children under 18, in Pregnancy, or when Lactating

clopidrogrel (Plavix)

precautions

• Patients with Hepatic Dysfunction
• Why?

clopidrogrel (Plavix)

nursing implications

• Monitor lab values
• Which ones?
• Fall and Bleeding Precautions
• Diet
• Patient Education

clopidrogrel (Plavix)

drug interactions

• Phenytoin and Warfarin
• Potential to change Drug Efficacy
• NSAID’s
• Causes additive effects

• Assist in Breaking Down Formed Blood Clots
• Prototype is Alteplase, Recombinant
• Also Known as Tissue Plasminogen Activators
• DRUGS ENDING IN -ASE

thrombolytics

uses

• Massive Pulmonary Embolism
• Unclog Central Venous Catheters
• Patients with Evolving
• MI, PE, or Acute Ischemic Stroke

thrombolytics

moa

• Accelerates Clot Lysis
• Enzyme that when Fibrin is Present, converts Plasminogen to Plasmin
• Fibrinolysis Occurs

thrombolytics

pharmacokinetics

• Rapidly Cleared from the Plasma by the Liver
• 80% of drug is cleared within 10 minutes after infusion is complete
• Onset of symptoms within 6 hours for MI and ACS
• Onset of symptoms within 3 hours for Ischemic Stroke in Adult Patients
• How do you determine type of Stroke Patient is Having?

thrombolytics

contras

• Recent trauma within 3 months
• Hemorrhagic Stroke
• Active Internal Bleeding
• Uncontrolled HTN
• Low Platelet Count/Elevated PTT
• Heparin Given within 48 hours Prior to Onset of Stroke

thrombolytics

precautions

• Recent Major Surgery within 10 days
• Bleeding
• Recent Trauma
• Pregnancy
• Liver Dysfunction
• OLDER ADULTS > 75
• Taking Oral Anticoagulants

thrombolytics

adverse effects

• Arrhythmias/ Cardiac Arrest
• Venous Thrombosis/Embolism
• Fat Embolism
• Cerebral Edema
• If administered when Onset of Symptoms > 3 hours
• Bleeding
• Internal
• Puncture Sites

thrombolytics

nursing implications

• Get thorough History of Events
• Get Accurate Medication List
• Cat Scan of Head
• Place any IV’s, Foleys, or Internal Monitoring Equipment prior to Administration of Drug
• Bleeding Precautions
• Neurological Exam Prior to Starting Drug

thrombolytics

drug interactions