Blocks conversion of Angiotensin I to Angiotensin II

↓ Aldosterone

↑ K

↓ breakdown of bradykinin (results in bradykinin build-up)

↓TGF-β (↓ scar tissue post MI)

Renal protective (↓ efferent arteriole constriction)

Peripheral vasoconstriction (↓ afterload)

Dry cough (bradykinin build-up)

Hyperkalemia

Angioedema (bradykinin build-up, non-allergic)

Renal insufficiency (↓ renal perfusion esp in renal stenosis

** Contraindicated in pregnancy

↓ Aldosterone

↑ K

↓ TGF-β

Peripheral vasodilation (↓ afterload)

No effect on bradykinin

Same benefits as ACE-Is but without as many side effects

Hyperkalemia

Renal insufficiency (esp. in renal artery stenosis)

** Contraindicated in pregnancy

Calcium Channel Blockers: name the 3 types and give examples

1. Dihydropyridines (Amlodipine, Nicardipine, Nifedipine, Nimodipine)

2. Phenylalkylamines (Verapamil)

3. Benzothiazepines (Diltiazem)

Act on voltage-gated channels

Block influx of Ca into cells

↓ Inotropy

↓ Chronotropy

↓ Dromotropy

Peripherally vasoconstrict (↓ afterload)

Dilate coronary vessels

Have no effect on SA node

Used for HTN, angina

HA Fatigue

Nausea

Reflex tachycardia

LE edema

Constipation

Dizziness

Significant coronary vasodilation

Significant peripheral vasodilation

↓ SA and AV node conduction

↓ Contractility

** Used for HR/BP control, angina, rhythm control

1. Atenolol

2. Esmolol

3. Metoprolol

4. Nebivolol

(no drugs are only cardioselective, all have some β₂ activity)

↓ HR

↓ BP

↓ CO

↓ Strength of contractions

↓ Conduction

↓ Renin production

↓ Free fatty acids

Bradycardia

Heart block

Hyperkalemia

Bronchospasm

Fatigue

Depression

Vivid dreams

Impotence

N/V/D/C

↓ Hypoglycemia sx 

1. Cardura

2. Minipress

3. Hytrin

Arterial and venous dilatation

↓ BP

↓ BPH

↑ Urine flow

May ↑ potency

1. Carvedilol (Coreg)

2. Labetalol

1. Methyldopa (safe in pregnancy)

2. Clonidine

↓ Sympathetic outflow

↑ Parasympathetic outflow

↓ Epi & Norepi release

↓ HR

↓ Speed of conduction

↓ Strength of contraction

Preserve CO & GFR

SedationDry Mouth

Constipation

Dizziness

Weakness

HA 

Bradycardia

** Rebound HTN if stopped abruptly (wean!!)

1. Hydralazine

2. Minoxidil

Inhibit arterial constriction by opening K channels

(↑ polarization)

↓ BP

↓ Afterload

** In long term use:

1. Consider use of Loop to prevent fluid overload

2. Consider use of βB to control/prevent HF 

Rebound tachycardia

Hirsutism (Minoxidil)

HA

Postural hypotension

Fluid retention

Angina

↑ ANA (Lupus syndrome)

Palpitations

S₃S₄

1. HCTZ

2. Metolazone

3. Chlorthiazide (Diuril)

Inhibit reabsorption of Na, Cl and H₂O from the distal convoluted tubule

Promote diuresis

↓ Na

↓ K

↓ Volume

↓ BP

↑ Tubular reabsorption of Ca

Promote vascular smooth muscle relaxation

1st line HTN mgmt

HTN 

HF

Enhances effect of some meds

Mgmt of Ca based kidney stones 

Edema

Less diuresis than Loops

** No benefit > 25mg ** only use in normal renal fx

Hyponatremia

Hypokelamia

Hypercalcemia

Hypotension

Dizziness

Weakness

↑ Uric acid retention (Gout)

Associated risk with Sulfa allergy (Stevens Johnson)

1. Furosemide

2. Bumetanide

3. Torsemide

Inhibit reabsorption of Na, K and Cl from the ascending limb of the Loop of Henle

↑ Osmolality of filtrate

↓ BP

↓ SV

↓ CO

Induce prostaglandin synthesis, causing renal vasodilation

** ok to use in impaired renal fx

HTN

Fluid overload

CHF

Hyperkalemia

Hypercalcemia

Hypotension

Hypokalemia

Hyponatremia

Hypocalcemia

↓ Renal perfusion

Ototoxicity

↑ Uric acid production (Gout)

Nephrotoxicity (if given with other renal toxic meds)

Associated with Sulfa allergy

K-Sparing Diuretics:

Name two types and their associated drugs

1. Aldosterone Inhibitors: Aldactone

2. Late distal-tubule blockers: Triamterene

↑ Na and H₂O excretion

↑ K reabsorption

Block Na and K transport proteins

↑ Na and H₂O excretion

↑ K reabsorption

** Drug is weak and rarely used

Baseline BMP (reassess in 7 days)

Yearly BMP

Stop if creatinine triples

Reassess BP in 2-4 weeks

Check serum osmolality if concern for dehydration

Carbonic Anhydrase Inhibitor (Diamox): 

What does it do?

**Not for HTN mgmt**

↓ HCO₃ reabsorption from the tubular filtrate

↑ Osmolality of tubular filtrate

1. Acute angle closure glaucoma

2. Altitude sickness

3. Pseudotumor cerebrii

4. Metabolic alkalosis

↑ Osmolality of ECF

↑ Fluid shift from ICF to ECF

↑ Osmolality of tubular filtrate

↓ H₂O reabsorption

↓ Circulating volume

↑ Diuresis

Volume overload

Pulmonary edema

Hyponatremia

Hypovolemia

Hypotension

Hypernatremia

Normal: <120/<180

Prehypertensive: 120-139/80-89

Stage 1: 140-159/90-99

Stage 2: ≥160/≥100

Lifestyle modification +

Thiazide diuretic

**May consider adding ACE-I, ARB, CCB or BB if ≥ 2 risk factors

Lifestyle modification + 

Two drug combination: Thiazide + ACE-I, ARB, CCB or BB

1. Hypertensive Urgency: >180/>110

2. Hypertensive Emergency: >180/>110 + s/s of end organ damage

Clonidine 0.3mg PO

** Goal with PO meds is to lower BP by 25%

1. Nitroprusside

2. Nitroglycerin

3. Labetalol

4. Esmolol

5. Hydralazine

6. Nicardipine

7. Phentolamine

Rapid acting

Arterial vasodilation > venous (↓afterload)

0.25-10 mcg/kg/min

RBCs metabolize it to NO and cyanide 

NO activates _cGMP → protein kinase G → smooth muscle relatation

Hypotension

Reflex tachycardia

Cyanide toxicity (parasthesias, visual Δ, acidosis, delirium, arrhythmias, increased risk with hepatic or renal insufficiency)

** Co-administration of sodium thisulfate will minimize toxicity

Converted to NO, causes vasodilation

More venous than arterial dilation

Preferred in CAD

Routes: SL, Transdermal, IV

Vasodilation

Orthostasis

HA

Reflex tachycardia

Flushing

Methemoglobinemia (treated with methylene blue)

Tolerance

β > α

↓ HR

↑ Vasodilation

Orthostasis

Heart block

Bronchospasm

N/V

β_{1 Blocker}

↓ HR

** Used for HTN emergency, Aortic dissection

Hypotension

Heart block

Bronchospasm

Arterial vasodilator

Can cause reflex tachycardia

** Indicated in eclampsia

** Do not use in aortic dissection

Preferred in Neuro events

Good cerebral and peripheral vasodilation

α and β Blocker

** Indicated in catecholamine crisis

** May be injected locally to couteract vasopressor infiltration

Potentiates the activity of antithrombin III on thrombin

Inactivates thrombin

Inactivates factors IX_a, X_a, XI_a, XII_a

Prevents development of clots and extension of existing clots

Biological half-life is dose-dependent

VTE/PE prophylaxis

VTE/PE mgmt

Peripheral arterial thrombus mgmt

ACS- STEMI

Interventional cardiology

Prevention of thrombus with venous access devices

VTE prophylaxis: 5,000u Q8-12hrs

VTE treatment:

IV: Bolus 50-100 (80) units/kg

then 15-25 (18) units/kg/hr

SQ: 10,000-20,000 units initially

then 8,000 to 10,000 units Q8hrs

Hemorrhage

Thrombocytopenia

HIT

** reveral agent: Protamine Sulfate 

May cause anaphylaxis, angioedema, bradycardia

PTT Q6-8hrs (goal 1.5-2.5x normal

Platelets

s/s of bleeding

Inactivates Factor X_a

Inhibits conversion of prothrombin to thrombin

Peaks 3-5hrs post injection

Duration: 12 hours

VTE/PE prophylaxis

VTE/PE mgmt

ACS- STEMI

Binds with protein, so more predictable

Less effect on platelets

Hemorrhage

Thrombocytopenia

Hypochromic anemia

Fever

Elevated LFTs

No need to monitor PT or PTT

Can measure anti-Factor Xa

Monitor CBC, LFTs

Inhibits vitamin K dependent clotting factors

(II, VII, IX, X)

Has no direct effect on thrombin

**100% bioavailable through ingestion

DVT treatment and prophylaxis

AFib (45-85% reduction in CVA)

Prosthetic valve replacement

** Takes 5 days to be therapeutic, start with Heparin or LMWH

Food alters metabolism

99% protein-bound

40 hour 1/2 life

Age

HF

Hepatic

Hyperthyroidism

Antibiotics

Amiodarone

Cimetedine

Fluconazole

Metronidazole

Phenytoin

Hypothyroidism

Nephrotic syndrome

Barbiturates

Griseofulvin

Carbamazepine

Nafcillin, Rifampin

Sucralfate

Diuretics

Vitamin K

Bleeding

Teratogenicity

Start 5mg PO at bedtime

Monitor Pt/INR in 24-48 hours

Adjust dose as needed (2-5mg/day)

Goal: INR 2-3

Prosthetic valve: 2.5-3.5

Once stable, monitor Q2wks

INR 2.5-3: reduce dose if needed

INR >3: stop for 24-48hrs, then lower dose

INR 6-10 and no bleeding: Vit K 0.5-1mg IV

INR 10-20 and no bleeding: Vit K 3-5mg IV

INR >20 or serious bleeding: Vit K 10mg IV and

2-4 units FFP

Direct thrombin inhibitor

Binds directly to thrombin with high affinity and specificity

Maximum benefit within 2-3 hrs of administration

12 hour 1/2 life

Non-valvular Afib, VTE prevention

** Not recommended for prosthetic valves, severe renal dz, advanced liver dz or impaired coagulation

** no lab test, no antidote, cleared by dialysis

** Can be counteracted with FFP

Dyspepsia

N/V/D

↑ risk of GIB

1. Enoxaparin (Lovenox)

2. Rivaroxaban (Xarelto)

1. Dabigatran (Pradaxa)

2. Argatroban

3. Bivalirudin (Angiomax)

Vitamin K Clotting Factor Inhibitor (1)

Which clotting factors are affected (4)?

Warfarin

1. II

  2. VII

 3. IX

4. X

1. Argatroban

2. Bivalirudin

1. ASA

2. Dipyridamole (Persantine)

3. Ticopidine (Ticlid)

4. Clopidogrel (Plavix)

5. Prasugrel (Effient)

6. Glycoprotein IIb IIIa inhibitors

(Reopro, Integrilin, Aggrastat)

Blocks cyclooxygenase (COX) which prvents the synthesis of thromboxane A₂ from arachidonic acid is platelets

Suppresses platelet aggregation

Effect is irreversible, lasts the life of the platelet

Normal aggregation returns 36 hours after discontinuation

Preferred over all NSAIDs

** stop 4-6 days prior to surgery

Inhibits ADP and ATP te reduce platelet adhesion

Causes coronary artery vasodilation

Blocks ADP-induced platelets from platelet binding

Inhibits thrombus formation

Irreversible

Avoid concurrent use with herbals

(gingko, garlic, ginger, ginseng)

Various CYP450 interactions

Same as Plavix: blocks the ADP-induced platelet binding

Inhibits thrombus formation

** No major CYP450 interactions

1. r-tPA (Alteplase, Activase)

2. Reteplase (Retavase)

3. Tenecteplase (TNKase)

Administered consurrently with anticoagulants to prevent new clots

All 3 are indicated for STEMI, line occlusion, CVA

**f-tPA is only drug approved for CVA, STEMI and PE

Used in ischemic CVA  with negative CT

Use in 3hrs of onset!

** May use intra-arterial r-tPA within 6 hour of symptom onset

1. Nitrates

2. β-Blockers

3. Calcium Channel Blockers

Metabolized to NO which causes vasodilation

Venous > arterial

↓ Myocardial O₂ demand

Vasodilates epicardial arteries

↓ Preload

↓ Afterload

NitroQuik (SL)

Nitropaste (transdermal)

Isosorbide mononitrate (PO)

Isosorbide dinitrate (PO)

Mononitrate (Imdur) is already a metabolite, so doesn't undergo hepatic first-pass

Lasts 6-10 hrs

Dinitrate (Isordil) undergoes hepatic first pass

Lasts 4-6 hrs

** Pregnancy category C

Inhibits late sodium current and reduces the calcium concentration in the myocytes

Indicated fro chronic angina not controlled by other agents

Transport trigs from the liver throughout the body to adipose tissue and muscles

Accept cholesterol from HDLs

May play a role in atherosclerosis

Unable tp measure directly, appear as a percentage

"very bad cholesterol"

Formed when VLDLs lose trigs

Converted by the liver to LDLs

Low-Density Lipoproteins (LDLs):

How do they work and what do they do?

Synthesized by the liver

Transport cholesterol throughout the body

Synthesis increases with dietary intake of cholesterol

Combination of trigs, cholesterol, phospholipids and proteins

Definitely associated with atherosclerosis

Synthesixed in the liver

Accepts free cholesterol from tissues and transports it back to the liver

Increases with estrogen, weight loss and estrogen

Decreases with obesity, elevated lipids, smoking and sedentary lifestyle

Made up of trigs, cholesterol, phospholipids and protein

Cardioprotective

Men > 40mg/dl

Women > 50mg/dl

As level increases, CV risk decreases

Goal: <120 mg/dl

High: >200 mg/dl

Very High: > 1,000 mg/dl

As level increases, risk of CV dz and pancreatitis decreases

LDL <130 and HDL >40

with < 2 risk factors

Repeat test Q5yrs

TLC education

LDL 130-159 and HDL >40

with <2 risk factors

Repeat test Q1-2yrs

TLC education

LDL >160 and/or HDL <40

with > 2 risk factors

Start medication

TLC education

Medication therapy

TLC education

Binds bile acid in the intestines and prevents their absorption

Leads to an increase in production of bile acids which consumes cholesterol and decreases LDL levels

1. Cholestyramine (Questran)

2. Colestipol (Colestid)

3. Colesevelam (Welchol)

↓ LDL, VLDL, Trigs

Inhibits adipose tissue lipolysis

↓ catabolism of HDLs

↑ HDL

Flushing

Burning/itching of upper body

Nausea

Anorexia

Dizziness

Hypotension

Hyperglycemia

Increased uric acid levels (gout)

Inhibit cholesterol synthesis in the liver

Should be taken in the evening since most cholesterol is formed at night

** contraindicated in pregnancy and lactation

Decreases total cholesterol and LDL by 40%

HDL may increase 20%

May decrease Trigs

GI: bloating, flatulence, dyspepsia

Hepatotoxicity

Myalgias and rhabdo.

** Monitor LFTs and CPK at baseline, 6wks, quarterly x 1 year then semi-annually

Cholesterol Absorption Inhibitors (Zetia):

What do they do?

Inhibit cholesterol absorption at the brush border of the small intestines

Reduce cholesterol stores, ↓ serum cholesterol levels

Beneficial if statins are not effective or well-tolerated

Often used in combination with a statin

** contraindicated in liver dz and pregnancy

Fibric Acid Derivatives (Gemfibrozil, Fenofibrate):

How do they work?

↓ lipolysis in fat tissue, which ↓ free fatty acids for hepatic trig synthesis and ↓ VLDL levels

** Useful in the patient with high trigs that do not respond to other meds

Approved for trigs >750mg/dl

GI: N/V/D/B

Hepatic: elevated LFTs

Hyperglycemia

Cholelithiasis and cholecystitis

Myalgia

Rash

Leukopenia

** Pregnancy category C

↓ Hepatic trig synthesis

Contains EPA and DHA

** Pregnancy category C