Cardio 2 Exam 1.

DOAC’s in Renal Dysfunction

• Only apixaban is recommended by guidelines for CrCl < 30 mL/min; it’s least affected by renal clearance.

• Rivaroxaban may be used (10 mg daily) in severe CKD, but with caution.

• Dabigatran is 80% renally cleared — avoid if CrCl < 30 mL/min.

DOAC’s in Hepatic Dysfunction

• Mild (Child-Pugh A): No dose adjustment needed.

• Moderate (B): Avoid rivaroxaban; use caution with others.

• Severe (C): Avoid all DOACs.

DOAC’s in obesity

• no loss of efficacy up to BMI 40 or weight < 120 kg.

• Apixaban and rivaroxaban are generally preferred in obese patients.

When Warfarin is Preferred over DOAC’s:

• Mechanical heart valves
  

• Atrial fibrillation with moderate-severe mitral stenosis
  

• Rheumatic AF
  

• LVAD or antiphospholipid antibody syndrome

Antithrombotic agents prevent

clot forming and expanding

Anticoagulant medications inhibit…

Factors of the coagulation cascade

Anticoagulant medications examples

Vitamin K Antagonists (warfarin)

Unfractioned Heparin

LWHS and Fondaparinux

Direct oral anticoagulants (DOAC’s) -xaban + Dabigatran (DTI)

Antiplatelet medications inhibit…

Activation and aggregation of Platelets

Antiplatelet medications examples

Cyclooxygenase inhibitors

ADP reeptor antagonists 

Glycoprotein IIb/IIIa receptor antagonists 

Protease activated reeptor -1 anatagonists 

What do Thrombolytic agents do

Break Clots down by converting plasminogen to plasmin resulting in clot lysis 

Vitamin k antagonist 

Warfarin 

Parenteral Anticoagulants 

Unfractioned Heparin 

LMWHs (enoxaparin) and fondapurinix 

Direct thrombin Inhibitors (bivalirudin/ Argatroban)

DOAC’s

Thrombin Inhibitors ( Dabigatrin)

Factor Xa Inhibitors

• (Rivaroxaban, Apixaban, Edoxaban)

Antithrombotic and Vasoactive substances in normal blood vessels  are 

Prostacyclin and Nitric Oxide 

Steps of coagulation Cascade (Intrinsic) amplifies

12-11-9-(8)-10-(5)-2 (prothrombin)- 1(fribrinogen)

Steps of coagulation Cascade (Extrinsic) initiates

7- (3 TF)- 10 - 2 (prothrombin)- 1(fribrinogen)

Mural Thrombus

• clot attached to vessel wall/ cardiac chamber 

Streptokinase

Protein derived from Streptococci

MOA- Forms a stable complex with plasminogen → cleave to plasmin 

Streptokinase Adverse efffects

Bleeding, Anaphylaxis

Fibrin specific thrombolytics

Alteplase (t-PA), Tenecteplase (TNKase)

Alteplase t-PA MOA

Binds to fibrin and converts plasminogen to plasmin 

5 min ½ life 

Bolus to continuous 

Tenecteplase (TNKase) MOA

same as t-PA but mutations in molecular structure make it more fibrin specific 

½ half life 90-130 mins due to more resistance to PAI-1 

Single IV  bolus dose

Adverse effectsn with thrombolytic agents 

Bleeding 

Cholesterol embolization 

Angioedema 

Hypersensitivity 

(can declot an hemosttic plug resulting in bleeding)

When not to use thrombolytic agent

• Current intercranial hemorrhage 

• Subarachnoid hemmorrhage 

• Active internal bleeding 

• Recent spinal or cranial surgery/ serious head trauma 

• Severe uncontrolled HTN

Virchows Triad

Hypercoagulability- increased clotting

Vascular Wall Injury 

Venous stasis - bad blood flow (laying for long time cancauses this)

2 out of 3 indicate high possibility of thrombus formation 

Risk factors for bleeding

Previous bleeding events

old age 

Female gender

Low BW

High dosing 

Warfarin metabolism / elimination

Racemic mixture R and S enantiomers

• S isomer 2.5-3.5 times more potent metabolized by 2CYP2C9

Elim- Inactive metabolites in urine

½ life - 20-60 hrs 

2-5 days duration 

Onset 5-7 days 

Warfarin inhibition factors

2,7,9,10

Vitamin K dependent anticoagulant proteins

Proteins C and S inhibition of proteins can leadto procoagulation

Warfarin Overlap

Overlap for VTE, high risk Atrial fib, cardiac valves

Start warfarin same day as UFH or LMWH

Continue for 5 days and INR> 2.0 for 24h 

Warfarin starting dose

5-10 mg PO daily 

• 10mg PO daily x 2 days (healthy outpatients)

< 5 mg PO for elderly 65+ , impaired nutrition, liver disease, CHF, high bleed risk

INR GOALS - 2.0-3.0

Monior PT and INR

Warfarin. Colors

Please let granny brown bring peaches to your wedding

Pink lavender Green Brown Blue Peach Teal Yellow White 

INR Frequency

every 2-3 days during 1st week of therapy

Every 1-2 weeks till stable 

every 1-3 months if stable 

Warfarin Interactions Increased effect 

Binge drinking

Don quai 

Fish oil 

Garlic, Gingko 

Ginseng 

Cranberry Grapefruit mango

Warfarin Interactions decreased effect

St Johns wort

Chronic drinking 

high Vitamin K foods

Warfarin adverse effects

Easy bruising, bleeding

Do not use in pregnancy 

Purple toe syndrome  3-8 weeks 

Skin necrosis/ limb grangene (fatty areas)

Treatment of effects - DC warfarin give FFP and vit Kand anticoagulate with UFH or LMWH

Warfarin Reversal

INR > 4.5 significantly Increased Risk

Withold Warfarin

Decrease Warfarin

Phytonadione (Vitamin K1)

prothrombin complex comcentrate

Phytonadione (Vitamin k1) MOA

MOA- promotes liver synthesis of clotting factors

Onset

IV 1-2 hrs

Oral- 6-10 hours

Warfarin Reversal In INR levels

IN$ 4.5-10 No evidence of bleeding -

• hold warfarin 

INR > 10 and no bleeding

• Vitamin K PO 2.5-5 + Hold warfarin

INR raised and minor bleeding

• Vitamin K PO 2.5-5 + Hold warfarin

Major bleeding 

• Vitamin K PO 5-10mg IV + KCentra + hold warfarin

Frank- Starling Law

Relationship between ventricular end diastoliv volums (EDV), Contraction strength and stroke volume 

AS EDV increases

Myocardium 

Heart contracts more forcefully 

SV increases 

Mean arterial pressure

MAP=1/3 SBP + 2/3 DBP

Normal 80-100 mmHg

stroke volume

SV = end disatolic volume - end systolic volume

Central Venous Pressure

Pressure in throacic vena ceva near the right atrium 

marker of right ventricular end diastolic volume 

• right ventricular preload 

Pulmonary Artery Occlusion Pressure (PAOP)

Measures pressure in the pulmonary artery distal to the balloon (normal < 15mmHg)

marker of left ventricular end diastolic volume

• left ventricular preload 

Systemic Vascular resistance

AFTERLOAD 

resistance to blood flowing out of the left ventricle 

• marker of vasodilation and vasoconstriction

Arterial oxygen Saturation (SaO2)

extent to which hemoglobin is satiurated with oxygen in ARTERIES 

Central Venous Oxygen Saturation (ScvO2)

extent to which hemoglobin is saturated with oxygen in CENTRAL VEINS close to heart

Shock Definition

inadequate tissue perfusion resulting on oxygen deprivation, Ischemia and organ failure 

Shock mechanisms 

Activation of Chemo and baroreceptors resulting in Increases sympathetic response and elevated HR, SV, CO, SVR

Activation of RAAS

a1 receptor

Smooth muscle - Vasoconstriction Ca increase

a2 receptor

CNS- Inhibit NE release

B1 receptor

Heart - increased Cardiac contractility frequency and relaxation Ca increase

B2

Smooth muscle- SMC relaxation decrease Ca

Shock Stage 1

Compensated/ non pregressive

• no drop in BP 

• Increase HR, SVR

• Cool clammy skin 

Shock Stage 2

Decompensated/ Progressive

• reduced BP, perfusion 

• hypoxia

• organ failure 

Shock Stage 3

Refractory (Irreversable)

• multi organ failure/death

Hypovolemic shock

low blood volume (blood loss/ fluid loss)

Reduced Preload

(down down up)

Distributive/vasodilatory shock

increased vasodialtion

• Septic 

• Anaphylactic 

• Neurogenic 

Decreased Afterload

Pre resuscitation down down down

Post resuscitation up up down

Obstructive shock

Physical obstruction to the heart\

Decreased Cardiac output 

up down up 

Cardiogenic shock

Reduced cardiac pumping ability

Decreased cardiac output 

(up down up)

Hypovolemic shock treatment 

Stop bleeding 

Fluids

Albumin. 

packed RBC

frozen plasma 

Transfusion 

Vasopressors (replace lost fluid)

Septic shock 

Bacterial Viral or fungal infection activate wbc (profound vasodilation)

spetic shock treatment

Antiobiotics (broad spectrum) within one hour 

within 3 hours for sepsis 

Antifungals 

Blood glucose control

Increase tissue perfusion. restore BP

Isotonic fluids 

IV balanced crystalloids 30ml/kg 

Vasopressors (norepinephrine)

Target MAP is 65mmHg

monitor lactate 

septic shock diagnosis

Blood Cultures / Tissue cultures 

Signs of infection (fever, WBC)

BP

Serum lactate 

ABG 

BUN, creatinine 

C-reactive protein levels 

Vasopressors 

Dopamine 

Norepinephrine 

Epinephrine

Phenylephrine receptors

a1 +++ a2 +

Norepinephrine Receptors

a1 ++ , a2 ++ , B1 +, B2 +

Epinephrine receptors

a1, a2, B1, B2 (highest affinity)

Low does dopamine receptors

0.5-3 mg

DA ++++

Mid dose dopamine receptors

5-10 mg

B1++++, B2++, DA++++

High dose dopamine receptors

10-20 mg

a1 +++, B1++++, B2++, DA++++

Norepinephrine ADME

Brand Name Levophed

MOA

• alpha 1 AR agonist (increase SVR and BP)

• beta AR agonist

IV admin

Dose 5-20mcg/min Max 100mcg/min

Preferred for septic shock

Metabolism

• COMT / MAO

Epinephrine ADME

Continuous infusion

IV Admin 

metabolism - COMT/MAO

alpha and beta AR’s

increased SVR BP/ increased contractility, HR, CO

(bronchodialation)

NE and Epi Adverse Effects

• Arrhythmias 

• Extravasation 

• Ischemic Injury 

• lactic Acidosis 

• headaches 

• Anxiety 

• HTN

Ne and Epi drug interactions

DC any meds that lower BP

Alpha Blockers

• antagonize pressor affets

Beta Blockers

• antagonize cardiac and bronchodilatory effects 

• potentiate pressor effect 

MAO 

Seratonin/NE reuptake inhibitors/ inhaled anasthetics 

Phenylephrine ADME

Brand Name NeoSynephrine, Vazculep

MOA

• Direct acting sympathomimetic 

• a1 AR agonist 

(increased SVR BP and MAP)

IV continuous infusion 10-100 mcg/min

Metabolism- MAO

Beneficial in patients pron to arhythmias 

Phenylephrine Adverse effects

Reflex bradycardia and decreased CO

May excacerbate angina and or heart failure 

increase pulmonary arterial pressure 

Extravasation

tachyphylaxis 

HTN

Phenylephrine drug interactions

BP lowering meds

Alpha AR blockers

Beta blockers 

MAO inhibitor

Inhaled anesthetics

Dopamine ADME

used as adjunct therapy in shock

renal and mesenteric vasodilation 

D1 (Gs) postsynaptic receptors in coronary , renal , mesenteric, cerebral beds 

D2 Gi presynaptic receptors in vasculature and renal tissues promotes vasodilation and increased blood flow 

IV administration and Metabolized by COMT and MAO

Dopamine Adverse effects 

Arrhthmias

extravasation 

Ischemic injury 

HTN

Headaches 

Anxiety 

Dopamine Drug interactions

Alpha Blockers

Beta Blockers 

MAO inhibitors 

Anethetics 

Vasopressin ADME

Vasostrict

IV administration 

Metabolized in liver and kidneys

Antidiuretic hormone

V1a- constriction of vascular smooth muscle increases SVR and MAP

V2 mediates water reabsorption by enhancing renal collecting duct permeability 

Vasopressin Adverse effects/ Drug interactions 

may worsen cardiac output in patients with impaired cardiac function 

Myocardial Ischemia 

Hyponatremia 

Arrhythmias 

Interactions 

• Meds that lower BP 

• Catecholamines 

Angiotensin II ADME 

Giapreza 

IV Administration

MOA

increased vasoconstriction and SVR 

• through Gq/PLC pathway

• results in MAP

Increases aldosterone secretion

• promotes Na/ water retention

Angiotensin II adverse effects

Thromboembolic events

tachycardia

Thrombocytopenia 

Peripheral Ischemia 

Drug Interactions 

• Any med that lowers BP

• ARB’s 

• - reduce response to Giapreza 

Anaphylactic Shock

Type of distributive shock

• serious life threatening generalized or systemic hypersensitivity reaction 

• serious allergic reaction

Acute onset 

Caused by

food, medication, venom

Allergen enters and activates B cell 

IgE produced bind to mast cells 

release cytokines 

release histamine 

Reduced BP after exposure 

Anaphylactic shock treatment 

Epinephrine First

• increaseed SVR

• Promotes bronchodilation

IV fluids 

• 1-2 L rapid IV bolus 

Albuterol if necessary 

Second line therapy

• Antihistamines - combination h1 and h2 blockade more effacacious 

Corticosteroids for rebound anyphylaxis

Neurogenic shock

Spinal cord injury impairs the sympathetic nervous which results in 

• decreased SVR Co BP 

• decreased preload, HR, Cardiac contractility 

Treatments for Neurogenic shock

Vasopressors

IV fluids

Inotropes- if decreased contractility 

Atropine- if bradycardia 

Atropine

Competetive reversible antagonist of the muscarinic acetylcholine reeptors 

increases firing of pacemaker cells (SA node) conduction through the AV node which stimulates HR 

• acetylcholine is the primary neurotransmitter of the parasympathetic system 

• muscarinic receptors are found on the SA and AV nodes decrease HR 

Cardiogenic Shock Clinical Presentation

Low BP, CO

tachcardia 

Elevate CVP and PAOP >18mmHG

pulm congestion/ edema 

jugular vein distension 

cool clammy pale skin 

low urine 

Increases lactate and troponins 

Cardiogenic Shock Causes

Contraction defects

Filling defects

Arrhythmias

Structural causes aortic stenosis

Cardiogenic Shock Treatment 

Treatment of underlying cause (CABG pacemaker, valve replacement, LVAD, heart transplant)

• Inotropes 

• Vasodilaters (nitroglycerin, sodium, nitroprusside)

• O2

HFrEF

Systolic Heart failure

EF < 40

heart cannot contract (Pumping)

Causes- myocardial infarction, myocarditis, Ventricular myocardium dilated. 

HFpEF

Diastolic HF

Ejection fracture >50%
Heart can contract well but cant relax (filling problem)

Causes 

• HTN 

• Aortic stenosis 

• Ventricular myocardium hypertrophy

Diastolic HF (HFpEF) stats

End-Diastolic Volume= 70 mL

SEnd systolic volume = 30 mL

Stroke Volume= 40 mL

EF- normal 57-58%

Systolic Heart Failure HFrEF

End-Diastolic Volume= 160 mL

SEnd systolic volume =120 mL

Stroke Volume= 40 mL

EF- 25% reduced

Acute decompensated HF

Common type of cardiogenic shock

acute presentation of HFrEF

• Complex syndrome that involves both acute and chronic processes 

New onset - worsening chronic HF 

“acute on chronic”

Reasons for Acute decompensation

FAILURE

• Forgot meds 

• Arrhythmia 

• Ischemia / infarction

• Lifestyle choices 

• Upregulation Pregnany ot Hyperthyroidism 

• Renal Failure 

• Embolus pulmonary 

ADHF goals of therapy

• Relieve congestive symproms 

• Restore systemic tissue perfusion (optimize CO)

• Minimize cardiac damage and other adverse effects 

• Initiate oral guideline directed med therapy