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
Class: Thrombolytic drugs
Indications: Remove already formed clots
- Acute MI
- Acute stroke
- Acute massive PE
MOA: Binds to plasminogen -> plasmin
- Plasmin breaks down already-formed clot
AE: Special handling
- Avoid manipulation of patient
- Avoid SQ/IV inject
- Avoid invasive procedures
- Minimize use of other blood thinners
Acute severe hemorrhage caused by thrombolytic drugs: Treatments (3)
- Whole blood replacement
- FFP (plasma with clotting factors)
- Aminocaproic acid (prevents plasminogen activation)
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 (2) and demand (3)
O2 supply: Myocardial blood flow
1. Coronary dilation
2. HR
O2 demand
1. HR
2. Contractility
3. Intramyocardial wall tension
STEMI: Pathophysiology (3) and effects (3)
Pathophysiology:
- CAD (atherosclerotic plaque) rupture
- Platelet aggregation + vasoconstriction in the area
- Cessation of blood flow to the myocardium that the vessel feeds
Effects:
- Death of cardiac myocytes = decrease contractility, release of H+/K+.
- K+ = dysrhythmia risk
- Longer term, collagen deposition & remodeling (angiotensin II & aldosterone) = increased HF & death risk
Diuretics: Mechanisms and 4 classes
Mechanism: Increase UOP and alter electrolyte excretion
4 classes: work on different areas of the nephron
* Loop
* Thiazide
* K+ sparing
* Osmotic
Furosemide: Class, indications, MOA, AE (3)
Class: Loop Diuretics
Indications: HTN
MOA: Blocks Na/Cl/K cotransporter in ascending LoH → excrete Na+/K+/2Cl- in urine followed by water
AE:
- HypoK
- HypoNa+
- HypoCl-
- Ototoxicity
- Dehydration/hypotension
- Drug interactions with other ototoxic drugs
- Drug interactions with digoxin
Hydrochlorothiazide (HCTZ): Class, indications, MOA, AE (6), PK
Class: Thiazide Diuretics
MOA: Block Na/Cl/K reabsorb @early distal convoluted tubule → these are excreted in urine followed by water
AE:
- HypoK
- HypoNa+
- HypoCl-
- Dehydration/hypotension
- Increase uric acid lvl (gout risk)
- Ineffective in kidney disease
PK: Excreted unchanged in urine
Hydrochlorothiazide (HCTZ): What’s unique? (3)
- The first line for HTN
- Much lower max diuresis than loop diuretics
- Not effective when GFR is too low
Spironolactone: Class, indications, MOA, AE (3), PK
Class: K+ Sparing Diuretics
MOA: Blocks aldosterone
- Decrease prod of Na/K exchange protein transporter
- K+ retention, Na+/H2O excretion @late distal convol tubule
- Dec. remodeling of CV system
AE:
- HyperK
- Endocrine: Menstrual irregularities, gynecomastia
PK: Onset in 48 hrs
Mannitol: Class, indications, MOA, AE (3), PK
Class: Osmotic Diuretics
MOA: Freely filtered in GFR, stays in filtrate → draw water out to be excreted in urine
AE: Fluid overload/edema
- HF
- Pulmonary edema
PK: Excreted unchanged in urine
Mannitol: What’s unique?
Strong diuresis, used for rapid excretion of volume in increased ICP/IOP
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)
HypoK: Treatment and administration guidelines
Treatment: K+ salts
ROA: IV or PO
Guidelines for IV admin:
- Dilute + infuse slowly
- Rapid infusion = cardiac arrest
- Irritating to veins
HypoMg: Treatment and administration guidelines
Treatment:
- PO for prophylaxis = Mg oxide
- IV for severe deficiency = Mg sulfate
Guidelines for IV admin:
- Dilute + infuse slowly
- Monitor for s/s hyperMg
HyperK: Treatment and guidelines
Treatment
- Avoid K+ heavy foods
- Avoid K+ sparing drugs
- May require hemodialysis (HD) or peritoneal dialysis (PD)
Guidelines:
- Protect against K+ induced cardiotoxicity
HyperMg: Treatment
Treatment: May require hemodialysis (HD) or peritoneal dialysis (PD)
Angiotensin-converting enzyme (ACE) inhibitors (-pril): Indications, MOA (5ish), AE (8), PK (3)
Indications: HTN
MOA: Inhibits ACE = Inhibition of ANG2 formation
- Inc. vasodilation
- Inc. diuresis, excrete out more Na
- Dec. SNS response = dec. myocardial O2 supply
- Prevention of CV remodeling
AE:
- HypoTN (first dose especially)
- HyperK
- Dehydration
- Cough
- Fetal injury
- Renal failure
- Rare: Angioedema, neutropenia
PK: PO (except enalapril, which is IV)
- All prodrugs (except lisinopril) that are converted in small intestine
- Long 1/2 life
Angiotensin II receptor blockers (ARBs) (-artan): Indications, MOA, AE (8), PK
Indications: HTN
MOA: Blocks the effects of ANG2 at the receptor
- Inc. vasodilation
- Inc. diuresis, excrete out more Na
- Dec. SNS response = dec. myocardial O2 supply
- Prevention of CV remodeling
AE:
- HypoTN
- HyperK
- Dehydration
- Cough
- Fetal injury
- Renal failure
- Rare: Angioedema, neutropenia
PK: All PO
Compare ACE inhibitors to ANG2 receptor blockers, how are they different? Which is preferred?
MOA:
- ACE inhibitors: Inhibits ACE = Inhibition of ANG2 formation
- ARBs: Blocks the effects of ANG2 at the receptor
Effects:
- ARBs
- Don’t block kinase 2 = lower cough/angioedema risk
- Dec. aldosterone release = lower hyperK risk
- Less evidence that they reduce CV morbidity/mortality
Preferred: ACE inhibitors
Aliskiren: Class, indications, MOA (5ish), AE (3), PK
Class: Direct renin inhibitor
Indications: HTN
MOA: Inhibit release of renin = block entire RAAS
- Inc. vasodilation
- Inc. diuresis, excrete out more Na
- Dec. SNS response = dec. myocardial O2 supply
- Prevention of CV remodeling
AE:
- HypoTN
- HyperK
- Dehydration
PK: PO, high-fat meals impact absorption
Actions of beta blockers on CV (3) and kidneys (1)
CV:
- Dec. HR
- Dec. contractillity
- Dec. AV node conduction velocity
Kidneys: Dec. renin release = dec. ANG2/aldosterone production
Actions of calcium in the cardiac system (2)
- Vascular smooth muscle + cardiac muscle
- Inc. vasoconstriction and contractility - Pacemaker cells of the heart
- Dec. action potential (SA node) and conduction velocity (AV node)
Classes of Ca2+ channel blockers (2)
- Dihydropyridines: Mainly act on vascular smooth muscle @ therapeutic doses
- Arteriole vasodilation
- Reflex tachycardia/contractility inc. - Nondihydropyridines: Act on vascular smooth muscle and the heart
- Arteriole vasodilation
- Dec. HR
- Dec. AV node conductivity
- Dec. contractility
Verapamil // Dilitiazem: Class, indications (4), MOA, AE (9)
Class: Ca channel blockers
- Non-dihydropyridines
Indications:
- HTN
- Angina
- Dysrhythmias
- SVT
MOA: Blocks Ca2+ @ vascular smooth muscle and the heart
- Dec. HR, contractility, AV node conduction
- Artery vasodilation → decrease afterload, coronary artery vasoconstriction
AE:
- Constipation
- Dizziness
- Facial flushing
- Edema
- Bradycardia
- Heart block
- Dec. contractility, dec. CO
- Hypotension
- HF
Nifedipine: Class, indications (2), MOA (3), AE (6), PK
Class: Ca channel blockers
- Dihydropyridines
Indications:
- Prinzmetal angina
- HTN
MOA: Blocks Ca2+ vascular smooth muscle
- Vasodilation of coronary arteries
- Dec. afterload
- Inc. contractility
AE:
- Reflex tachycardia
- Peripheral edema
- Flushing
- Dizziness
- Headache
- Inc. myocardial O2 demand
PK: PO
Compare the effects of vasodilation on arteries to veins
Arterioles:
- Dec. afterload = inc. CO and tissue perfusion
Veins:
- Dec. preload = dec. ventricular filling and contractility, which dec. CO and tissue perfusion
AE of vasodilation (3)
- Orthostatic hypotension (venodilation > arteriole dilation)
- Reflex tachycardia (arteriole dilation > venodilation)
- Expansion of blood volume with long term use
- Decreased BP = increased renin release = increased aldosterone = retention of Na+/H2O
Hydralazine: Class, indications, MOA, AE
Class: Vasodilator
Indications: HTN
Actions: Dec. afterload
MOA: Unknown
- Direct arteriole vasodilation
AE:
- Fluid retention with long-term use
- SLE-like syndrome
- Headache
- Dizziness
- Fatigue
- Hypotension
- Reflex tachycardia
Sodium nitroprusside: Class, indications, MOA, AE, PK
Class: Vasodilator
Actions: Dec. preload
Indications:
- Prinzmetal angina
- HTN
MOA: Vasodilate veins via NO
AE:
- Tolerance can develop rapidly
- Can’t be used with other hypotensives
- Long-term infusion can result in thiocyanate toxicity
PK:
- PO has insane first pass effect
- IV onset is immediate
Sodium nitroprusside: What’s unique?
Extremely potent and works faster than any other vasodilator, drug of choice for HTN emergencies
Digoxin: Class, indications, MOA, actions (3), AE (8)
Class: Cardiac glycoside
Indications: HTN
MOA: Selectively inhibits Na/K/ATPase pump
- Build up of Ca2+ intracellularly = inc. actin/myosin interactions
- Inc. contractility
Actions:
- Dec. HR
- Slowed AV node conduction
- Inc. electrical excitability in ventricles
AE:
- Cardiac dysrhythmias
- GI: Anorexia, nausea/vomiting
- CNS: Fatigue, visual disturbances
* GI + CNS AE precede dysrhythmias = can be a warning sign
Contraindications:
- AV heart block
- Symptomatic bradycardia
- Caution in renal impairment
- Caution in electrolyte disturbances
Nitroglycerin: Class, indications, MOA, AE, PK
Class: Organic nitrates
Indications: HTN
- Angina
MOA: Uptake into vascular smooth muscle,
conversion into NO (active form)
- NO activates guanylyl cyclase, which catalyzes cGMP formation
- cGMP = dephosphorylation of light chain myosin in vascular smooth muscle
- Thus, cannot interact w/ action = relaxation = vasodilation
AE:
- Caution with drugs that cause hypotensive effects
- Tolerance develops rapidly
- Avoid abrupt withdrawal to avoid coronary vasospasm
PK
- Highly lipid soluble
- Lots of ROA: Sublingual, buccal, transdermal, PO, IV
Treatment of HTN: Considerations, first-line therapy, HTN emergency, HTN of pregnancy
Considerations:
- Cause of HTN
- Comorbid conditions
First-line therapy: Thiazide diuretics
HTN emergency: Sodium nitroprusside or labetalol
HTN of pregnancy: Labetalol or methyldopa
Classes of antidysrhythmic medications
Class I: Na+ channel blockers
Class II: Beta blockers
Class III: K+ channel blockers
Class IV: Ca2+ channel blockers
Quinidine // Procainamide: Class, indications, MOA (3), AE
Class: IA antidysrhythmic
- Na+ channel blocker
Indications: Atrial and ventricular arrhythmias
MOA: Blocks Na+ channel
- Inc. AP
- Inc. ERP
- Inc. QT interval
AE: Anticholinergic
Lidocaine: Class, indications (2), MOA (2), AE
Class: IB antidysrhythmic
- Na+ channel blocker
Indications:
- Post MI
- Ventricular arrhythmias
MOA: Blocks Na+ channel
- Dec. AP
- Dec. ERP
AE: Toxicity at high doses
IC antidysrhythmics: Class, indications (2), MOA, AE
Class: Na+ channel blockers
Indications:
- SVTs
- Afib
MOA: Blocks Na+ channel
- Inc. ERP in AV node (but not ventricular tissue)
AE: Can induce life-threatening VT
Metoprolol // Esmolol: Class, indications (3), MOA (3), AE (3)
Class: Beta blockers
Indications:
- SVT
- VT
- Post-MI
MOA: Dec. HR, contractillity, AV node conduction
AE:
- Bradycardia
- HypoTN
- Can’t be given with CCB
Amiodarone: Class, indications, MOA (4), AE (8), PK
Class: K+ channel blocker
Indications: VT
MOA: Blocks K channel
- Delay repolarization
- Inc. AP duration
- Inc. ERP
- Prolongs QT
AE:
- Pulmonary fibrosis
- Hypothyroidism
- Hepatotoxicity
- Prodysrhythmic: torsades, bradycardia, AV block
- Corneal microdeposits
- Skin discoloration
PK: Extremely long half life (25-60 days)
Adenosine: Class, indications, MOA, AE (4), PK
Class: Class V antidysrhythmic
Indications: VT
MOA: Binds adenosine receptor in cardiac tissue → open K+ channel → hyperpolarize → prevent next contraction / temporary heart stop
AE:
- Flushing
- Transient hypotension
- Transient chest pain
- Transient flat line
PK: Extremely short half life (10 secs) → needs to be given w saline flush
Atropine: Class, indications, MOA, AE (3)
Class: Anti-cholinergic
Indications: Symptomatic bradycardia
MOA: M antagonism
- Inc. HR
AE:
- Decreased GI/GU activity
- Mydriasis
- Dry mouth
