-
Systolic B/P HTN
- Heart pumps blood
- Major risk factor for CVD's
- Rise in systolic B/P continues through life (compared to diastolic)
- Most common form of HTN*
-
Diastolic B/P HTN
- Heart relaxes and fills with blood
- Diastolic B/P levels of over 50 yo
-
Primary HTN
- Cause is unknown, but risk factors include:
- - family hx
- - racial predisposition
- - obesity
- - stress
- - smoking
- - sedentary lifestyle
- - high fat diet
-
Secondary HTN
- Specific etiology:
- - renal disease
- - pregnancy
- - drug induced
-
D.A.S.H.
Dietary Approaches to Stop Hypertension
-
Functions of Ion Exchange in Kidneys
- Filtration: movement of substance from blood to nephron within the glomerus
(Tubular) Reabsorption: ions go from tubules to blood/vascular system (Tubular) Secretion: ions go from the blood supply to the tubules
-
Sites of Ion Echange in Kidneys
- Proximal & Distal Tubules: sodium ions are reabsorbed in echange for hydrogen (secreted)
- Loop of Henlee: chloride ions are reabsorbed in conjunction with sodium
- Distal Tubule: Na/K (secreted) exchange occurs, controlled by aldosterone
- Collecting Duct: water is reabsorbed under the influence of ADH (antidiuretic hormone) in the proximal tubules & collecting duct
-
Drug Example of Thiazide Diuretics
Hydrochlorothiazide (HCTZ)
-
Drug Examples for Thiazide-like Diuretics
- Hygroton (chlorthalidone)
- Lozol (indapamide)
- Zaroxolyn (metolazone)
-
MOA of Thiazide Diuretics
inhibits Na reabsorptions in the distal tubules causing and increased excretion of Na, water, K, & H
-
Side Effects of Thiazide Diuretics
- Sulfa Allergy
- photosensitivity
- Hypercalcemia
- Hyperlipidemia
- Hyperglycemia
- Hyperuricemia
- Hyperkalemia (sxs: leg cramps, m. weaknedd, constipation, arrythmia, lethargy, decreased mental alertness)
-
Pt Counsling for Thiazide Diuretics
- INCREASE INTAKE OF PATASSIUM RICH FOODS:
- watermelon
- apricots
- bananas*
- nuts
- cantaloupe
- oranges
- dates
- fish
-
Drug Examples of Loop Diuretics
- Bumetanide (Bumex)
- Furosemide (Lasix)
- Ethacrynic Acid
-
MOA of Loop Diuretics
inhibition of Na & Cl in the ascending Loop pof Henlee and distal tubules --> lose water, Na, Cl, Mg, & Ca
-
Types of Duiretics
- Thiazide/Thiazide-like Diuretics
- Loop Diuretics
- Potassium-Sparing Diuretics
-
Drug Examples of Potassium Sparing Diuretics
- Amiloride
- Spironolactone (Aldactone)
- Triamtrene (Dyrenium)
-
MOA of Potassium Sparing Diuretics
block the aldosterone receptor --> results in K retention
-
(1) What is a Side Effect to the Potassium Sparing Diuretics, Spironaloactone?
(2) What is the alternative?
- (1) S.E.: causes breast development in men
- (2) alternate drug: Eperolone
-
Types of Sympatholytic Drug Classifications
- Beta Blockers
- Central Acting Alpha2 Agonists
- Peripheral Alpha1 Antagonists (blockers)
-
Name the Beta Blocker drug examples. (-olol)
Which ones are selective and non-selective?
- Tenormin (atenolol) - selective
- Inderal (propranolol) - nonselectiveLopressor (metoprolol) - selective
-
Name an additional indication for Potassium-Sparing Diuretics.
also used to clear up Acne
-
MOA for Beta Blockers
Decrease Co through negative chronotropic & inotropic effects on the heart & inhibition of renin release from the kidneys
-
Drug Example for Central Acting Alpha2 Agonists
Catapress (clonidine)
-
Side Effects of Central Acting Alpha2 Agonists
- nightmares*
- dry mouth
- constipation
-
Pt Education for of Central Acting Alpha2 Agonists
- Don't stop abruptly
- Decrease dosage slowly to prevent rebound HTN
-
Drug Examples for Peripheral Alpha1 Antagonists (blockers)
(-zosin)
- Minipress (prazosin)
- Hytrin (terazosin)
- Cardura (doxazosin)
-
Name an additional indication for Peripheral Alpha1 Antagonists (blockers)
BPH
-
Side Effects & corresponding Pt Counsling for Peripheral Alpha1 Antagonists (blockers)
- S.E.: "first dose" phenomenon"
- Counsling: take h.s.
-
Drug Examples for Vasodilators
- Apresoline (hydralazine)
- Loniten (minoxidil)
-
MOA for Vasodilators
works directly on smooth muscle to cause relaxation --> leads to vasodilation & decreased B/P
-
Side Effects for Vasodilators
- fluid retention
- tachycardia
- dizziness/lightheadedness
- syncope (fainting)
-
Name the specific Side Effect for the Vasodilator, Loniten (minoxidil).
What product uses this as the intended effect?
- S.E.: hair growth
- product: Rogain
-
Hypertension (HTN)
- defined by persistent elevation of arterial blood pressure
- -50 million Americans w/HTN (2003)
- "silent killer"
- pt is usually symptomless
- can lead to other complications (heart failure, kidney failure, stroke/cerebral hemorrhage)
-
Renin-Angiotension-Aldosterone System (RAA or RAAS)
- - decrease in renal perfusion (to kidneys) - increase of renin from Juxtaglomerular cells of kdney - angiotension - angiotension 1 (weak vasoconstriction) - combines with ACE (angiotension converting enzyme) - angiotension II (powerful vasocontrictor) - increase in Aldosterone release - increase in Na reabsorption & water - increase in blood volume
- GOAL: increase in B/P
-
Drug Examples of ACE Inhibitors
(-pril)
- Capoten (captopril)
- Vasotec (enalapril)
- Zestril/Ptinivil ( lisinopril)
- Lotensin (benzapril)
- Accupril (quinapril)
- Altace (remipril)
-
Indications of ACE Inhibitors
- No Angiotensin II produced (in plasma)
- Decrease in Aldosterone release
- Decrease in Na reabsorption & water
- Where does K go?
- "ACE" = where drug works**
K+ levels increase in blood --> Hyperkalemia - Decrease in blood volume
- GOAL: Decrease B/P
-
Side Effects of Ace inhibitors
- hyperkalemia
- hypotension
- coughing**
- angiodema
- metallic taste*
- SEVERE: swelling of face
-
Pt Cousling for ACE Inhibitors
monitor intake of sodium and/or salt substitutes
-
Drug Ecamples for Angiotensin II Receptor Antagonists (blockers) (ARBs)
(-sartan)
- Cozaar (losartan)
- Diovan (valsartan)
- Avapro (irbesartan)
- Micardis (telmisartan)
-
MOA for Angiotensin II Receptor Antagonists (blockers) (ARBs)
block the AT II receptor directly (does not inhibit ACE or renin release) --> results in a decrease in Aldosterone release --> causes vasoldiltion effect
-
What is the advantage of using Angiotensin II Receptor Antagonists (blockers) (ARBs) for HTN drug therapy?
- it has little effect on the serum potassium
- does not cause the side effect of angiodema
- very little coughing spells
-
Drug Example for Renin Inhibitors
Tekturna (aliskiren)
new tx*
-
Clinical Indication for Renin Inhibitors
tx of HTN alone OR as combination therapy
-
MOA of Renin Inhibitors
blockade of the conversion of angioteninogen to angiotensin 1
-
Side Effects of Renin Inhibitors
- Dizziness
- Rash
- Hyperkalcemia
-
Function of Calcium Channels
Calcium is responsible for the force of contraction, normal activity, & heart rate of the heart
-
2 Subclasses of Calcium Channel Blockers (CCBs)
- (1) Dihydropyridines
- (2) Non-Dihydropyridines
- Similar in first 2 MOAs
- differ in structure & 3rd MOA, with different affinities for different areas of the cardiovascular system
-
Drug Examples of Dihydropyridine CCBs
(-dipine)
- Procardia/Adalat (nifedipine)
- Norvasc (amlodipine)
- Sular (nisoldipine)
-
MOA of Dihydropyridines CCBs
- produce mainly a vasodilarion effect, but can also decrease the oxygen demand by the heart
- Block entry of the calcium in Cardiac Muscles --> allows for m. relaxation & vasodilation-->decreases ability of the heart to develop forceful contractions--> decrease O2 demand by the heart & B/P
-
Drug Examples of Non-Dihydropyridines CCBs
- Calan (verapamil)
- Cardizem/Tiazac (Diltiazem)
-
MOA of Non-Dihydropyridines CCBs
- have important effect on the pacemaker cells of the heart (SA & AV nodes), where they block Calcium Channels --> decreases rate of SA node, decreasing heart rate slightly & decreasing the conduction velocity of the AV node
- specifically affects rate - mainly treating tachyarrythmias **
-
Side Effects & Counsling of Calcium Channel Blockers (CCBs)
- HA
- Facial Fluching
- Dizziness
- Hypotension
- constipation
- Xerostoma
- Counsling: use with caution in CHF *
-
What are two side effects specifically related with Dihydropyridine CCBs?
- Reflex tachycardia - due to vasodilation effects
- Peripheral Edema
-
Combination Therapy
- Usualy add in drug from different class
- Problems occur with sensitivity to cold
-
Clinical Trials: On Target Trail
ongoing Temisartan alone & in combination with Ramipril - Global endpoint trial --> more adverse effects & no benefit when used together
-
Clinical Trials: Accomplish Trail
Avoiding Cardiovascular events through combination therapy in pts living with systolic HTN --> ACE inhibitor/Amlodipine netter than ACE inhibitor/HCTZ
-
Major Lipids in Body
- (1) Cholesterol, (2) triglycerides, & (3) phospholipids
- trasnport lipoprotein complexes
- Essential subtrates for cell membrane formation & hormone synthesis
-
3 Major Classes of Lipoproteins
- (1) LDL
- (2) VLDL (associated with TG)
- (3) HDL
-
Dyslipidemia = Hyperlipidemia
- Increase in bad cholesterol
- Decrease in good cholesterol
-
Bad Cholesterol
- TC: total cholesterol
- TG: Triglycerides
- LDL: Low density lipoproteins
-
Good Cholesterol
HFL: high density lipoproteins
-
LDL Calculation
TC (total cholesterol) - HDL (high density lipoproteins) - TG (triglycerides)/5
-
Optimal LDL Cholesterol Levels
Less than <100 (<70)
-
Atherolsclerosis (hardening)
-
Optimal HDL Cholesterol Levels
- men: above >40 mg/dl
- women: above >50 mg/dl
-
Optimal Triglyceride Cholesterol Levels
less than <150 mg/dl
-
Optimal Total Cholesterol Levels
less that <200 mg/dl
-
Risk Factors for Dyslipidemia
- AGE
- -- men: 45+ yo
- --women: 55 + yo OR premature menopause w/o estrogen replacement therapy
- Family hx of premature CHD (definite MI; sudden death before 55 yo in father OR 1st degree male relative & before 65 in mother OR 1st degree female relative)Smoking
- HTN (140/90 mmHg OR taking HTN meds)Low LDL cholesterol (<40 mg/dL)
-
10 yr risk: >20%
- Risk Category: CHD/CHD risk equivalent (DM, CHD, CVD)
- LDL goal: <100 (<70)
-
10 yr risk: 10 - 20%
- Risk Category: 2+ risk factors
- LDL Goal: <130 (<100)
-
10 yr risk: <10%
- Risk Category: 2+ risk factors
- LDL Goal: <130
-
Risk Category: 0 - 1 Risk Factors
LDL Goal: <160
-
Non-Drug Therapy for Dyslipidemia
TLC = Therpeutic Lifestyle Change:
-
"stains" = HMG-CoA Reductase Inhibitors
- 1st drug of choice for tx of most pts at risk for coronary & other artherosclerotic vascular disease - HUGE class
- These agents can decrease the incidence of major coronary events & death in such patients
- Very potent at reducing TC & LDL
- HMG-CoA = enzyme *
-
Drug Examples of "Stains" (HMG-CoA Reductase Inhibitors)
(-vastatin)
- Lipitor (atorvastatin)
- Lexol (fluvastatin)
- Mevacor (lovastatin)
- Pravachol (pravastatin)
- Crestor (rosuvastatin)
- Zocor (simvastatin)
- Livalo (pitavastatin)
-
MOA of of "Stains" (HMG-CoA Reductase Inhibitors)
- interrupt the conversion of HMG-CoA (enzyme) to mevalonate --> reduces cholesteral biosynthesis
- rate limiting step in cholesterol sythesis *
-
Side Effects of "Stains" (HMG-CoA Reductase Inhibitors)
- Mild GI distress
- Headaches
- Myalgia
- Rhabdomyolysis --> leads to renal failuer (rare)
-
Pt Counsling & Food/DDIs for "Stains" (HMG-CoA Reductase Inhibitors)
- Counsling: Need to elevate liver fxn at baseline & 2 months after starting therapy
- Food & DDI:
- --Azoles
- --CCBs
- --Grapefruit Juice
-
Drug Examples for Bile Acid Sequestrants
- Welchol (coresevelam)
- Colestid (colestipol)
- Questran (cholestyramine)
-
MOA of Bile Acid Sequestrants
- Bind to bile acids to disrupt recirculation of bile acids
- Stimulate bbile acid synthesis from cholesterol
-
Side Effects & Pt Counsling for Bile Acid Sequestrants
- S.E.: Constipation & bloating
- --Fiber suppliment may reduce GI effects
- Decrease absorptions of fat soluable vitamins
- Decrease Absorption of other drugs
- --Warfarin & Digoxin
-
-
MOA of Niacin
Reduces hepatic synthesis of VLDL (associated with triglycerides)
-
Side Effect & Pt Counsling for Niacin
- Skin Flushing & Puritis
- GI distress
- Hyperglygemia/
- Hyperuricemia/
- Hepatotoxicity
- Acanthosis Nigricans
-
Contraindications of Niacin
- PUD
- Liver disease
- Severe Gout *
-
Drug Examples of Fibric Acid Derivatives
- Lopid (gemfibrozil)
- Tricor/ Lofibra/ Trilipix (fenofibrate)
-
MOA of Fibric Acid Derivatives
Reduce the rate of lipogenesis in the liver
-
Side Effects of Fibric Acid Derivatives
- GI Distress (dyspepsia)
- Gallstones
-
DDI for Fibric Acid Derivatives
Rhabdomyolysis is increased when combined with a "-vastatin" ("stain"/HMG-CoA Reductase Inhibitor)
-
Drug Example of Cholesterol Absorption Inhibitors
Zetia (zetimibe)
-
MOA of Cholesterol Absorption Inhibitors
Decreases absorption of cholesterol from the brush border of the intestine
-
Side Effects of Cholesterol Absorption Inhibitors
Mild GI Distress
-
Drug Example of Fish Oil Supplementation
Lovaza
-
MOA of Fish Oil Supplementation
- not completely understoodactive components are DHA & EPA
-
Indications & Dosing for Fish Oil Supplementation
- Indicated for pts with increased TG (triglycerides)
- Dosing: 4 g/d
-
Side Effects of Fish Oil Supplementation
- Increase bleeding time
- Eructation (fishy)
- Dyspepsia
-
DDI of Fish Oil Supplementation
Possible DDI with anticoagulants
-
Hematopoiesis
- The production of new blood cells
- 3 essential nutrients (key players):
- (1) iron
- (2) vitamin B-12
- (3) folic acid
-
Anemia
a deficiency in O2 carrying erythrocytes (RBCs)
-
Populations with Iron Deficiency Anemia
- Premature infants
- children during rapid growth periods
- pregant/lactating women
- chronic kidney disease
- pts with certain inabilities to absord iron
- blood loss
- Avg diet contains 10-15 mg of elemental iron - only 5-10% absorbed *
-
Oral TX for Iron Deficiency Anemia
- ferrous sulfate (ferrous Salts = most efficiently absorbed) *
- gluconate
- fumarate
-
Side Effects of Oral TX for Iron Deficiency Anemia
- Constipation
- GI Upset
- Black Stools
-
Parental TX for Iron Deficiency Anemia
- Iron Dexatran
- -- IM = stains
- -- IV = hurts
-
Side Effects of Parental TX for Iron Deficiency Anemia
- HA
- light-headedness
- fever
- hypersensitivity - test dose
-
Vitamin B-12 Deficiency Anemia
- B-12 serves as cofactor for severl essential biochemical reactions
- -- DNA sythesis
- -- myelin sheath protection
"extrinsic factor": intrinsic factor is a protein secreted by the stomache to help uptake dietary Vitamin B-12
-
Etiology of Vitamin B-12 Deficiency Anemia
- inadequate dietary intake, decreased absorption, & inadequate utilization
- Avg diet contains 5-30 mcg with only 1-5 mcg absorbed *
- --sources: liver, eggs, dairy
-
Symptoms of Vitamin B-12 Deficiency Anemia
- Pallor
- Icterus
- Gastric Mucosal Atrophy
- B-12 only: Neuropsychiatric abnormalities
- -- Numbness
- -- Parethesias
- -- Irritability
-
Name & Define the 2 Forms of Vitamin B-12 Deficiency Anemia
- (1) Pernicious Anemia: lack the ability to synthesize intrinsic factor (inhibit B-12) dietary uptake)
(2) Megaloblastic Anemia: results from dificiency of cyanocobalamine
-
TX for Vitamin B-12 Deficiency Anemia
Cyanocobalamine
-
Coagulation
- Normal blood clot formation due to local tissue injury
- Liquid to solid "plug"
-
Thrombocytes
- Platelets
- cells in blood that migrate to tissue injury
- necessary for clot formation
-
Aggregation
when platelets stick to each other
-
-
Thromboembolism
- When clots are jammed in a blood vessel
- i.e. "moving clot"
-
Roles & Conditions related to Anticoagulation Therapy
- Used against Clot formation when clotting mechanism becomes too active
- Inhibit platelet aggregation OR interfere w/plasma clotting factors
- (5) Cxs treated:
- (1) Deep Vein Thrombosis
- (2) Atrial fibrillation
- (3) Stroke
- (4) MI
- (5) Pulmonary Embolus
-
"Key Players" of Anticoagulation Therapy
- (1) Adenosine diphosphate (ADP)
- (2) Thrombin
- (3) Antithrombin
-
Adenosine Diphosphate (ADP)
- Powerful inducer of platelet aggregation
- 1 of 3 "key players" in anticoagulation therapy
-
Thrombin
- Central role in hemostasis
- Allows fibrogen to form a fibrin clot
- Activator of platelets & other clotting factors
- 1 of 3 "key players" in anticoagulation therapy
-
Antithrombin
- Anticoagulant
- 1 of 3 "key players" in anticoagulation therapy
-
Drug Examples for Indirect Thrombin Inhibitors
- Heparin
- LMWH = Low Meolecule Weight Heparin:
- -- Lovenox (enoxaparin)
- Selective Anti-Xa inhibitor:
- -- Arixtra (fondaparinux)
-
Drug Examples for Direct Thrombin Inhibitors
-
Precautions for Heparin
- Administerd IV & Sub-Q
- Never give IM or Orally
- Close monitoring required
-
Side Effect of Heparin
Heparing-induced thrombocytopenia
-
MOA of Heparin
- interferes with Platelet aggregation
- Inhibits Thromboplastin activity
- Inhibits Thrombin Activity
- Prevents fibrin to form clot
- indirect thrombin inhibitor *
-
Drug Example for Low Molecular Weight Heparin (LMWH)
Lovenox (enoxaparin) - fragments of heparin
-
MOA for Low Molecular Weight Heparin (LMWH)
- Inhibits factor Xa
- Indirect thrombin inhibitor *
-
LMWH = Low Molecular Weight Heparin
- More predictable
- improved SC bioavailability
- longer half life
- less need for monitoring
-
Drug Example & dosing of Selective Anti-Xa Inhibitors
- Arixtra (fondaparinux)
- Dosing: once daily, whereas Lovenox is 1- 2 x daily
-
MOA of Selective Anti-Xa Inhibitors
- Inhibits factor Xa --> interrupts the blood coagulation cascade & inhibits thrombin formation & thrombin development
- indirect thrombin inhibitor *
-
Lepirudin
- Recombinant formulation of hirudin
Hirudin: thrombin inhibitor isolated from the saliva of leeches - Direct thrombin inhibitor *
-
Pradaxa (dabigatran)
- FDA approved on October 2010
- "Prodrug"
- BID dosing
- direct thrombin inhibitor *
-
Side Effects/Adverse Effect of Pradaxa (dabigatran)
-
Advantages of Pradaxa (dabigatran)
- no monitoring or dose adjustments
- no known food-drug interactions
- Pregnancy C
-
DDI of Pradaxa (dabigatran)
- Very little DDIs
- -- rafampin
-
Disadvantages of Pradaxa (dabigatran)
- Lack of a way to monitor
- No reversal agent to treat overdose
- Cost $$
-
Drug Examples of Anti-Platelets
- ASA (Aspirin)
- Plavix (clopidigrel)
- Effient (prasuarel)
- Dypridamole
-
Drug Example for Anticoagulants
Coumadin (Warfarin)
-
MOA of Aspirin
- Irreversibly inhibits the formation of thromboxane --> no platelet aggregation
- Anti-Platelet *
-
MOA of Plavix (clopidigrel) & Effient (prasuarel)
- Block adenosine diphosphate binding to membrane receptors & preventing ADP activation of GP IIa/IIIb in coagulation cascade
- Anti-Platelet
-
Advantage vs Disadvantage of Effient (prasuarel)
- Advantage: more beneficial compared to Plavix (clopidigrel) in reducing thrombic events
- Disadvantage:bleeding seen more frequently with Effient (prasuarel)
-
MOA of Dipyridamole
- Reversibly interferes with the platelet aggregation by increasing adenosine (inhibitor of platelet reactivity)
- Inhibits phosphodisterase within the platelets
- Anti-platelet
-
MOA of Wafarin (coumadin)
- inhibits Vitamin K dependent clotting factors II, VII, IX, X
- Prevents synthesis od normal clotting factors
- Anti-Coagulant
-
Benefits of Warfarin (coumadin)
- Orally
- Less side effects
- inexpensive
-
Side Effects/Adverse Effect of Warfarin (coumadin)
- Skin Necrosis
- Purple Toe Syndrome
- "X" - pregnancy?Easy Bruising
- Thrombocytopenia
- Bleeding/Prolonged Bleeding
- -- in gums during brushing & shaving
- -- hematuria & blood in stool
- unexplained epistaxis
-
What are some preventative measures for the adverse side effects of Warfarin (coumadin)?
- gentle blowing of the nose
- use electric razor
- soft-bristle tooth brush
- need ID card
- Get counsling before taking OTC meds
-
DDIs for Warfarin (coumadin)
- Causing Increase Response = Bleeds (4 Gs):
- -- Ginkgo
- -- Ginseng
- -- Garlic
- -- Green Tea
- Decrease Response = Clots:
- -- chronic alcohol use
- -- St. John's Wart
- -- green leafy vegetables
-
Antidote for Heparin
- Protamine Sulfate
1 mg of Protamine will neutralize: 90- 120 units of heparin, 1 mg of enoxaparin, or 100 IU of daltreparin
-
Antidote for Coumadin (warfarin)
- Vitamin KPromote synthesis of prothrombin, factors XII, IX, & X
- Phytonadione & menadione are fate soluable
- Menadiol is water soluable
-
Fibrinolytic/Thrombolytic Enzymes
- "Clot Busters"
- Must be administeres ASAP
-
Drug Example of Fibrinolytic/Thrombolytic Enzymes
Activase (alteplase-tPA)
-
MOA of Fibrinolytic/Thrombolytic Enzymes
to stimulate plasminogen to change into plasma --> causes firinolysis to occur --> dissolve preformed clots
-
Adverse Side Effects of Fibrinolytic/Thrombolytic Enzymes
- Activase (alteplase-tPA):-- hemorrhage
- -- allergic reaction
-
Contraindication for Anti-coagulants & Fibrinolytic/Thrombolytic Enzymes
- Active bleeding rendencies
- uncontrolled HTN
- Ulcers
- Recent surgery on brain &/or spinal cord
-
Drug Examples of Coagulants
- Vitamin K (Aquamephyton)
- Thrombin-powder
-
Indications for Coagulants
- neonates:
- -- to help with clotting
- -- whose mothers were on oral anti-coagulation therapy
- control bleeding during a surgical procedure
- Hemophiliac, missing clot factor VII
-
Cardiac Electrophysiology: Myocardial Action Potential
normal heart beat initiated by electrical signals
-
Cardiac Electrophysiology: Phase 0
Rapid Depolarization
-
Cardiac Electrophysiology: Phase 1
- notchinitial repolarization
-
Cardiac Electrophysiology: Phase 2
AP Plateau
-
Cardiac Electrophysiology: Phase 3
Final repolarization
-
Cardiac Electrophysiology: Phase 4
return to stable diastolic potential
-
Conduction system of the Heart
- S.A. node: "Pacemaker," maintains pumping
- A.V. node
- Bundle of His
- Purkinje Fibers
- Responsible for coordinating the contractions of the heart chambers
-
EKG/ECG: P wave
reflects atrial depolarization
-
EKG/ECG: PR wave segment
reflects how long it takes for nerve impulse to get from the S.A. node to the A.V. node
-
EKG/ECG: QRS wave
reflects ventricular depolarization
-
EKG/ECG: ST segment
- Plateau Phase
- absolute refractory period
-
EKG/ECG: T wave
ventricular repolarization
-
Absolute Refractory Period (ARP)
- Phase 1, 2, 3
- no stimulus, no matter how strong, will excite the nerve
-
Relative Refractory Period (RRP)
- End of Phase 3
- Stronger than normal stimuli can cause excitation
-
Arrythmias
- An abnormality in either the rate and/or rythm of the heart
- Loss of cardiac rythm, especially irregularity of heartbeat
-
2 Mechanisms that Result in Arrythmias
- (1) "automatic": abnormality in impulse generation
- (2) "reentrant": abnormality in impulse conduction
-
Types of Arrythmias
- Tachycardia
- Atrial Flutter
- Atrial Fibrillation (most common)Ventricular Fibrillation (worse kind)premature atria contraction
- premature ventricular contraction
- bradycardia
-
How do Anti-Arrythmics Work to control Arrythmias?
- Sodium blockade
- Blockade of sympathetic autonomic effects in the heart
- prolongationm of the refractory period
- Calcium Channel Blockers
- Goal: to convert arrythmias to a normal rhythm
-
Vaughan Williams Classification
- Class IA, IB, IC
- Class II
- Class III
- Class IV
-
MOA of Class I Anti-Arrythmics
bloack sodium channels
-
Drug Examples for Class IA Anti-Arrythmics
- Quinidine (Quinaglute)
- Procainamide (Pronestyl)
-
Drug Example for Class IB Anti-Arrythmics
Lidocaine (Xylocaine)
-
Drug Example for Class IC Anti-Arrythmics
Propafenome
-
Drug Examples for Class II Anti-Arrythmic
-
MOA of Class II Anti-Arrythmics
- Beta-Blockersblock conduction velocity
-
Drug Examples for Class III Anti-Arrythmics
- Bretylium (Bretylol)
- Amiodarone (Cardarone)
-
MOA of Class III Anti-Arrythmics
blocks the potassium channels that results in prolongation of AP
-
Drug Examples for Class IV Anti-Arrythmics
- Nondihydropyridines ***
- Verapamil
- Diltiazrm
- calcium channel blockers
-
MOA of Class IV Anti-Arrythmics
- Calcium Chyannel Blockersinhibit calcium entry --> slow conduction
-
MOA of Multaq (dronedarone)
- All 4 MOAs:
- (1) block sodium channels
- (2) beta-blocker: block conduction velocity
- (3) blocks potassium channels -->prolongation of AP
- (4) Calcium Channel Blocker: inhibit calsium entry --> slow conduction
-
Multaq (dronedarone) vs Amiodarone (Cardarone)
"anything you can do...I can do better"
-
Counsling for Multaq (dronedarone)
Severe liver injury - monitor LFTs
-
Heart Failure (HF)
- Progressive Disorder - Pathophysiological state, caused by an event, in which the heart is unable to pump blood at a rate sufficient to meet the metabolic needs of the body
- Interferes with heart's ability to contract &/or relax decreasing outputAcute onset = MI
- Chronic onset = HTN
-
Body's Compensatory Effects of Heart Failure (HF)
- increased heart rate & contractability
- vasoconstriction
- (ventricular) remodling
- increase reload --> increase cardiac output
-
Clinical Presentation of Heart Failure
- Edema - pulmonary OR peripheralTachypnea
- Nocturnal dyspnea
- exercise intolerance
- orthopnea
- dyspnea on exertion
- Rales (crackling sounds) on auscultation
-
Standard 1st Line Therapies for Heart Failure (HF)
- ACE-inhibitors
- Beta-Blockers
- Diuretics
- Digoxin
- Aldosterone antagonists/blockers
- Angiotensin II receptor Blockers (ARBs)
- Nitrates & Hydralazine
-
Indications for Cardiac Glycosides
- HF
- Arrythmias
- -- Atrial Fibrillation
- -- Supraventricular tachyarrythmias
-
Administration of Cardiac Glycosides: Digitalizing Dose
frequent & higher doses are given to acheive desired blood levels
-
Administration of Cardiac Glycosides: Maintenance Dose
Smaller regular doses given once a day to maintain blood levels
-
Drug Example of Cardiac Glycoside
Lanoxin (digoxin)
-
MOA of Lanoxin (digoxin)
- Cardiac Glycoside:Inhibition of the Na/K ATPase pump which acts to increase the intracellular Na/Ca2+ exchange -->increase intracellular Ca
- --> decrease heart rate
- -->increase force of contraction
- -->slow conduction thru AV node
-
Lanoxin (digoxin) Theraputic Serum Concentration: Heart Failure
0.5 to 0.8 ng/ml
-
Lanoxin (digoxin) Theraputic Serum Concentration: Arrythmias
0.8 to 2 ng/ml
-
Lanoxin (digoxin) Toxic Serum Concentration
>2.5 ng/ml
-
Onset of Lanoxin (digoxin)
- Enterohepatic circulation
- -- rapid
- -- long duration
-
Monitoring Parameters for Lonoxin (digoxin)
- Potassium (K)
- Calcium (Ca)
-
Side Effects of Lanoxin (digoxin)
- N & V
- HA
- visual disturbances - halos around dark objectsrash
- slow &/or irregular pulse
-
Positive Inotropic Agents
- Increase FOC
- Ex: Cardiac Glycoside
-
Negative Inotropic Agent
- Decrease FOC
- Ex:
- -- Beta-Blocker
- -- Calium Channel Blocker
-
Positive Chronotropic Agent
- Increase HR
- Ex:
- -- Epinephrine
- -- Atropine
-
Negative Chronotropic Agent
- decrease HR
- Ex: Cardiac Glycoside
-
CAD: Ischemia
decrease clood flow to heart muscle due to coronary artery blockage --> leads to O2 demand exceeding the O2 supply
-
CAD: Arteriosclerosis
- Due to aging
- Hardening & narrowing of the arteries --> results in decrease blood flow
-
CAD: Artherosclerosis
- Fatty deposits accumulate in the walls of the arteries --> reduce blood supply
- Most common form of Arteriosclerosis*
- Linked to (1) high cholesterol, (2) increased B/P, & (3) smoking
-
CAD: Angina
- Due to arteriosclerosis OR artherosclerosisChest pain
-
3 types of Angina
- (1) Stable Classic Angina
- (2) Unstable Angina
- (3) Vasospasm of coronary artery
-
Tx of Angina
- Rest
- Anti-Anginal Drug:
- -- Vasodilators (Nitrates)
- -- Beta-blockers
- -- Calcium Channel Blockers
- -- Renexa (for chronic angina)
-
Drug Examples for Nitrates
- Nitroglycerin (NTG Sublingual tabs)Isosorbide mononitrate
- Isosorbide dinitrate
-
MOA of Nitrates
- Dilate Veins & Arteries
- Cecrease B/P
- Decrease work on the heart
- Decrease Oxygen consumption
-
Side Effects of Nitrates
- Flushing
- Headaches
- Faintness
- Dizziness
- Tachycardia
- Orthostatic HTN
-
Pt Counsling (DDIs) for Nitrates
- Avoid those drugs used to treat ED:
- -- Sidenafil (24 hr)
- -- Verdenafil (24 hr)
- -- Tadalafil (48 hr)
-
Indication for Ranex (ranolazine)
tx for chronic angina
-
MOA for Ranex (ranolazine)
- Exerts anti-ischemia effects w/o changing heart rate OR B/P *
- Inhibits the late phase of the inward sodium channel in ischemia cardiac cells during repolarization --> reduces intrcellular (Na) --> reduces calcium influx via Na/Ca2+ exchange --> results in decreased ventricular tension & myocardial O2 consumption
-
Side Effects for Ranex (ranolazine)
-
Myocardial Infarction (MI)
- Results from a sudden interruption of blood supply to an area of myocardium bc of complete (or near complete) occlusion of a coronary artery
- heart cells do not receive adequate blood supply --> Necrosis (death) of the muscle cells
- = "Heart Attack"
-
What diseases can result from a Myocardial Infarction (MI)?
-
Clinical Presentation of Myocardial Infarction (MI)
- Chest pain (angina)Possible pain in arms/shoulders
- Diaphoresis
- Arm tingling/numbness
-
Tx for Myocardial Infarction (MI)
- Rest: heart healing process
- *"MONA"*: Morphine, Oxygen, Nitrate, Aspirin
- Prevention: life style modifications
- Stool Softener
- Treat Other complications: HTN
-
Acanthosis Nigricans
- skin disorder that results in velvety, light-brown-to-black markings in areas including the neck, armpits, groin, and under the breasts
- commonly associated with obesity and hyperinsulinemia, diabetics, or pts of African descent
-
Xerostomia
Dry mouth due to lack of saliva
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