Week 6/7: Cardiovascular System Flashcards
Hemophilia A: Definition, treatments
Factor VIII deficiency
Treatments:
- Factor VIII concentrate
- Desmopressin (DDAVP)
- Monoclonal antibody therapy
- Gene therapy
How does desmopressin treat hemophilia A?
Releases stored factor VIII form the endothelium. Used for mild hemophilia A
How does monoclonal antibody therapy treat hemophilia A?
Binds together two factors in the clotting cascade (IXa & X) that would normally be where factor VIII would work. Can’t be used for an acute bleeding episode.
How does gene therapy treat hemophilia A?
Reconstruction/repair of genetic material in patient’s body
Very expensive
Hemophilia B: Definition, treatment
Factor IX deficiency
Treatment: Factor IX concentrate
Microcytic anemia
Anemia characterized by small, abnormally shaped RBCs
Normocytic anemia
Anemia characterized by normal-shaped RBCs, but low RBC count
Macrocytic anemia
Anemia characterized by large RBCs
Nutrients/hormones essential for proper RBC formation (4)
- Iron
- Vitamin B12
- Folate
- Erythropoietin
PK/PD of iron (4 points)
- Absorbed in small intestine
- Stored as ferritin or binds transferrin for distribution
- Sent to bone marrow for use in Hgb
- Highly recycles, very minimal iron leaves the body
Iron deficiency: Cause, results, treatment
Cause: Due to uptake/demand imbalance
Results in dec. O2 carrying capacity (fatigue, pallor, tachycardia)
Treatment: PO iron supplement
PK/PD of vitamin B12 (4 points)
- Required for DNA synthesis and cell growth/division
- Catalyzes folic acid to active form, which is required for DNA synthesis
- Requires intrinsic factor from parietal cells of stomach for absorption
- Stored in liver, slow eleimination
Vitamin B12 deficiency: Cause, results, treatments
Cause: Usually due to lack of intrinsic factor
Results in the suppression of rapidly dividing cell groups (bone marrow and GI tract mucosa). Also results in neuronal demyelination of CNS
Treatments: Usually PO, IV if severe
- AE: HypoK
PK/PD of folic acid (4 points)
- Required for DNA synthesis and cell division/growth
- Must be converted into an active form (two pathways, one includes B12 and one doesn’t)
- Absorbed in small intestine
- Stored in liver
Folic acid deficiency: Cause, results, treatments
Cause: Poor diet (alcohol overconsumption) or malabsorptive disease
Results in suppression of rapidly dividing cell groups, can inc. colorectal CA + atherosclerosis risk, but no neuronal injury.
- Can cause neural tube defect in early fetus
Treatments:
- Correct underlying cause
- PO folic acid (inactive form)
- PO folinic acid (active form)
- Severe: IM folic acid and B12 injections followed by PO folic acid
PK/PD of erythropoietin (EPO) (3 points)
- Endogenous glycoprotein released by kidneys in response to hypoxia detection
- Results in stimulation of RBC production in bone marrow
- Response is limited if folate/B12/iron is low
Epoetin alpha and Darbepoetin alpha: Indications, AE
Indications: Lack of RBCs
AE:
CV events (MI, HTN, CVA)
Be careful if hemoglobin > 11 OR hemoglobin increased rapidly past 2 weeks
Darbepoetin alpha: What’s unique?
Slower clearance = longer 1/2 life, can administer less frequently
G-CSF Filgrastim: Indications, AE
Indications: Lack of WBC
AE:
Leukocytosis
Bone pain
Thrombopoietin receptor agonists: Indications
Lack of platelets – stimulate platelet production
PK/PD of cholesterol (3 points)
- Responsible for the flexibility of cell membranes and organelles
- Required for hormone synthesis
- Primarily manufactured in liver, but some dietary intake is also required
PD of lipoproteins (3 points)
- Transport cholesterol & triglycerides in the blood
- Contain apolipoproteins: recognition sites for
cell surface receptors. - Binding allows for cellular ingestion (endocytosis) & for metabolism
VLDL: Core hormone, associated apolipoproteins, actions, AE
Triglycerides as core
B-100
Actions: Delivers TGs from liver to adipose & muscle tissue
AE: Probably contributes to atherosclerosis
First line therapy for cholesterol management
Lifestyle modifications
LDL: Core hormone, associated apolipoproteins, actions, AE
Cholesterol as core
B-100
Actions: Delivers cholesterol from liver to nonhepatic
tissue
- Increased cellular demand for
cholesterol -> increased LDL receptor #
AE: GREATEST contribution to atherosclerosis
- ASCVD probability is directly correlated
w/ LDL levels
HDL: Core hormone, associated apolipoproteins, actions, AE
Cholesterol as core
A-II, A-I
Actions: Delivers cholesterol from peripheral tissues
back to liver (i.e. promote removal)
Not an AE but protects against atherosclerosis
Statins: Class, indications (1), MOA, AE (2), PK (4)
Class: HMG-CoA Reductase Inhibitors
Indications: High cholesterol blood lvl
MOA: Inhibits HMG CoA reductase → inc. LDL receptor proliferation → inc. LDL uptake into cell
AE: All rare, generally well tollerated
- Myopathy (rhabdomyolysis)
- Hepatotoxicity
PK
- PO at night
- Hepatic metabolism
- Biliary excretion
- Rosuvastatin is not well metabolized in Asian heritage
Statins and myopathies: Prevalence, symptoms, guidelines
Prevalence: Rare (5-10% of patients)
Symptoms:
- Aches
- Tenderness
- Weakness
- Can progress to myositis w/ increased creatine kinase & K+
Guidelines: Measure creatine kinase upon start of therapy and again if symptomatic. Discontinue statin if creatine kinase >10x original
Colesevelam // Colestipol // Cholestyramine: Class, indications, MOA, AE
Class: Bile acid sequestrants
Indications: High cholesterol blood lvl
MOA: Nonabsorbable from GI tract → binds to bile acid → dec. reabsorption and inc. excretion of cholesterol
- Ultimately inc.s LDL receptors in the liver
AE: GI disturbance (constipation)
Ezetimibe: Indications, MOA, AE (4), PK (3)
Indications: High cholesterol blood lvl
MOA: Act on brush border enzyme → prevents dietary cholesterol absorption and inhibits reabsorption of cholesterol secreted in the bile
AE:
- Myopathy
- Hepatitis
- Pancreatitis
- Thrombocytopenia
PK:
- PO
- Converted to active metabolite ezetimibe glucuronide
- Biliary elimination
Gemfibrozil // Fenofibrate: Class, indications, MOA, AE (4)
Class: Fibric acid derivatives (fibrates)
Indications: To lower VLDL levels
MOA: Inhibits hepatic extraction of free fatty acids → liver cannot synthesize as many triglycerides → dec. VLDL
AE: GI disturbances are most common
Gallstones
Myopathy
Hepatotoxicity
Monoclonal antibody (PCSK9) inhibitor: Indications, MOA, AE (2), PK (3)
Indications: High cholesterol blood lvl
MOA: PCSK9 is a protein that binds LDL receptors in the liver
- Inhibition of PCSK9 = freed receptors = inc. LDL uptake
AE:
Hypersensitivity
Immunogenicity
PK:
- SubQ only
- Dosing Q2 weeks
- Long half-life
Monoclonal antibody (PCSK9) inhibitor: What’s unique?
Used in combination with statins in patients with very high risk of morbidity/mortality
ACL inhibitor: Indications, MOA, AE (2), PK (3)
Indications: High cholesterol blood lvl
MOA: Inhibit ACL → dec. cholesterol synthesis → inc. LDL receptor proliferation → inc. LDL cell uptake
AE:
- Increase uric acid (gout risk)
- Increase tendon rupture risk
PK:
- PO
- Converted to active metabolite
- Excreted renally
Most effective and lease effective drugs for lowering LDL and total cholesterol
Most effective: Statins
2 general steps of blood coagulation
- Platelet plug
- Fibrin mesh production
Steps of platelet plug formation (3)
- When platelets contact surface of damaged blood vessel, they adhere
- Platelet receptors activate when exposed to an agonist
- Fibrinogen binds to activated platelet receptors ‘bridging’ between platelets
Platelet agonists (5)
- ADP
- TXA2
- Thrombin
- Collagen
- Platelet aggregation factor
Steps of fibrin mesh (2)
- Intrinsic pathway: Triggered by contact with collagen of an injured blood vessel
- Extrinsic pathway: Triggered by thromboplastin, which is released by vascular wall trauma
Coagulation factors that depend on vitamin K for synthesis (4)
II (2), VII (7), IX (9), X (10)
Degradation of clots is through _______
Plasmin (precursor: plasminogen)
Heparin // LMWH: Class, indications (5), MOA, AE (3), PK
Class: Antithrombin activator
Indications:
- DVT/PE
- Open heart surgery
- Dialysis
- Disseminated intravascular coagulation (DIC)
- Acute MI
MOA: Activate antithrombin → inhibit coagulation factors to prevent
AE:
- Hemorrhage
- Heparin-induced thrombocytopenia (HIT)
- Hypersensitivity
PK: Hepatic metabolism/renal excretion
Describe the PK difference between Heparin and LMWH
- Size
- Heparin is large & polar = no PO absorption, no placenta crossing
- LMWH is smaller - Protein binding
- Heparin: Varied protein binding -> heparin plasma concentrations require lab monitoring (PTT)
- LMWH: Dec. protein binding due to smaller size - 1/2 life
- Heparin: 1.5hrs
- LMWH: 1.5 x 6 = 9hrs (slower liver clearance) - Bleeding
- Bleeding is less common with Heparin
Describe the PD difference between Heparin and LMWH
Heparin suppresses thrombin = factor Xa
LMWH suppresses factor Xa > thrombin
Heparin-induced thrombocytopenia (HIT): Prevalence, actions, presentation, treatment/guidelines
Prevalence: Rare (0.2-5%)
Actions: The body produces antibodies against heparin-platelet protein complexes
Presentation:
- Decreased platelets via consumption & destruction (thrombocytopenia)
- Increased platelet activation (increase in thrombotic events – stroke, MI, etc.)
Treatment: Discontinue heparin & use alternatives.
- Supportive care
Warfarin: Class, indications (3), MOA, AE (3), PK (7)
Class: Vitamin K inhibitor
Indications:
- DVT/PE
- Thromboembolism in prosthetic heart valves
- MI/stroke risk
MOA: Inhibits enzyme that activates vitamin K → prevents synthesis of factors 2, 7, 9, 10 → dec. fibrin formation
AE:
- Hemorrhage
- Infant hemorrhage (caution in breastfeed)
- Fetus hemorrhage (contraindicated in pregnancy)
PK:
- PO
- 99% protein bound
- Free drug crosses membranes (placenta, breastmilk)
- CYP450 hepatic metabolism
- Renal/fecal excretion
- Peak effects take several days
- ½ life = 1.5-2 days
Warfarin: Clinical considerations
Requires lab monitoring by PT/INR
Warfarin OD: Presentation, treatment
Presentation: Anaphylactoid responses
Treatment:
- IV/slow admin
- FFP, plasma concentrates of vitamin K dependent factors
Dabigatran // Bivalirudin // Desirudin // Argatroban: Class, indications (2), MOA, AE (2), PK (5)
Class: Direct thrombin inhibitors
Indications: Prevent thrombosis
- DVT/PE
MOA: Inhibit thrombin → dec. conversion of fibrinogen to fibrin and activation of factor XIII → prevents fibrin mesh formation
AE: GI upset
- Hemorrhage
PK:
- PO
- Peak 1-3hrs (food affects absorption rate)
- Low protein binding
- Renal elimination, no liver metabolism (no interactions w/ CYP450 inducers/inhibitors)
- ½ life 13hrs (normal renal function) → 18hrs (mod renal dysfunction
Whats unique about direct thrombin inhibitors?
- Rapid onset
- No need to monitor lab values: predictable responses = reliable dosing
- Few food-drug interactions
- Lower risk of major bleeding
What’s unique about Bivalirudin?
Unique AEs: Hypotension, back pain, headache
Unique PK: continuous IV infusion
* Immediate onset
* Eliminated by renal excretion & proteolytic cleavage -> ½ life = 25mins (normal renal function)
Rivaroxaban: Class, indications (3) , MOA, AE (2), PK (3)
Class: Direct factor Xa inhibitors
Indications:
- DVT/PE
- Prevent thrombosis
- CVA
MOA: Inhibit factor 10a → prevent fibrin mesh formation
AE: Maternal hemorrhage & fetal risk (not approved in pregnancy)
PK:
- PO
- Peak 2-4hrs
- CYP450, 35% unchanged in urine
Rivaroxaban: What’s unique?
- Rapid onset
- Fixed dosage
- Lower bleeding risk
- Few drug interactions
- No lab monitoring required
Rivaroxaban OD: Treatment
No specific antidote but:
- Can give activated charcoal to avoid further absorption
- Hemorrhage = factor VIIa or factor II (prothrombin)
Asprin: Class, indications (5), MOA, AE (3), PK
Class: COX inhibitor (irreversible)
Indications:
- Acute MI
- CVA
- TIA
- Chronic stable angina
- Stents
MOA: Inhibit COX → dec. platelet activation/aggregation, dec. TXA2 mediated vasoconstriction → inhibit platelet plug
AE:
- Bleeding (general)
- GI bleed
- Hemorrhagic stroke
PK: Effects last the lifetime of platelet
Clopidogrel // Prasugrel // Ticagrelor: Class, indications, MOA, AE (2), PK (3)
Class: P2Y12 ADP receptor antagonists
Indications: Prevention of stent thrombosis & thrombotic events
MOA: Antagonize P2Y12 receptor so ADP can’t bind → dec. platelet activation/aggregation → inhibit platelet plug
AE:
- Bleeding
- TTP
PK:
- PO
- Hepatic metabolism
- Effects in 2hrs
Ticagrelor: What’s unique?
It’s reversible
Vorapaxar: Class, indications, MOA, AE, PK (5)
Class: PAR-1 antagonist
Indications: Use with aspirin/clopidogrel in reduction of thrombotic events
MOA: Reversible binding to PAR-1 receptors on platelet surface → dec. effects of thrombin → dec. platelet activation/aggregation
AE: Bleeding (general)
PK:
- PO
- Effects in 1hr
- Hepatic metabolism
- Fecal excretion
- Long ½ life
Abciximab: Class, indications, MOA, AE, PK
Class: GP IIb/IIIa receptor antagonists
Indications: Short term to prevent ischemic events in those w/ ACS or undergoing PCI
MOA: Blocks IIb/IIIa receptors on platelet inhibition of final
common step in platelet aggregation
- Inhibits aggregation from all factors (collagen, TXA2, ADP, thrombin,
platelet activation factor)
Abciximab: What’s unique?
Part of the most powerful class of anti-platelet drugs
Alteplase (tPA) // Tenecteplase // Reteplase: Class, indications, MOA, AE, PK
3 ways blood pressure is regulated
- IMMEDIATE: SNS (α1 = vasoconstriction, β1 = HR & contractility increase)
- β1 also stimulates renin release - SHORT/MEDIUM TERM: RAAS (renin release due to decreased RBF/blood volume)
- LONG TERM: Kidney (decreased GFR promotion of fluid retention)
3 ways the body tries to adapt to dec. EF
- Cardiac dilation (occurs due to increased venous pressure & decreased contractility) = increased diastolic filling
- Increased SNS tone (occurs due to baroreceptors) = increased HR/contractility/venous tone/arteriolar tone
- Retention of blood volume (due to low RBF/GFR & B1 agonism -> RAAS activation & decreased GFR) = H2O/Na+ retention
Determinants of O2 supply and demand
60
STEMI: Pathophysiology and effects
Diuretics: Mechanisms and 4 classes
Furosemide: Class, indications, MOA, AE, PK
Hydrochlorothiazide (HCTZ): Class, indications, MOA, AE, PK
Spironolactone: Class, indications, MOA, AE, PK
Mannitol: Class, indications, MOA, AE, PK
Treatment of low body fluid volume is based on whether there is… (3)
- equivalent H2O & solute loss (isotonicity is maintained)
- More H2O lost than solute lost (blood is now hypertonic)
- More solutes are lost than H2O lost (blood is now hypotonic)
Angiotensin-converting enzyme (ACE) inhibitors (-pril): Class, indications, MOA, AE, PK
Angiotensin II receptor blockers (ARBs) (-artan): Class, indications, MOA, AE, PK
Aliskiren: Class, indications, MOA, AE, PK
Aldosterone antagonists: Class, indications, MOA, AE, PK
Verapamil // Dilitiazem: Class, indications, MOA, AE, PK
Nifedipine: Class, indications, MOA, AE, PK
Hydralazine: Class, indications, MOA, AE, PK
Sodium nitroprusside: Class, indications, MOA, AE, PK
Digoxin: Class, indications, MOA, AE, PK
Nitroglycerin: Class, indications, MOA, AE, PK
Classes of antidysrhythmic medications: Class I
Classes of antidysrhythmic medications: Class II
Classes of antidysrhythmic medications: Class III
Classes of antidysrhythmic medications: Class IV
Quinidine // Procainamide: Class, indications, MOA, AE, PK
Lidocaine: Class, indications, MOA, AE, PK
Na channel blockers: Class, indications, MOA, AE, PK
Metoprolol // Esmolol: Class, indications, MOA, AE, PK
Amiodarone: Class, indications, MOA, AE, PK
Verapamil // Diltiazem: Class, indications, MOA, AE, PK
Adenosine: Class, indications, MOA, AE, PK
Digoxin: Class, indications, MOA, AE, PK
Atropine: Class, indications, MOA, AE, PK
