Cardio Pharm

• 1. Rate of phase 0 depolarization
• 2. Threshold potential
• 3. Resting Membran Potential

• Increase upstroke velocity in pacemakers by increase of Ca influx
• Shorten the AP duration by increasing K efflux
• Increase HR by increasing Na funny channel influx (increasing slope of phase 4)

• Sodium
• Beta blockers
• Potassium
• Calcium

• Drugs: Quinidine, Procainimide, Disopyramid
• Block fast Na channels
• prefer to be open or activated "state dependent" blockage
• increases AP duration & ERP
• Also blocks K channels (prolongs depolarization ... slows phase 4)
• Increase QT interval

• Mechanism: blocks fast Na channels, K channels, muscarinic receptors (increases HR), alpha blockade (decreases BP, reflexive tachy)
• Administration: PO
• Clinical use: a fib, need to combine with digoxin to slow AV conduction, both atrial and ventricular dysrhythmias, reentrant, ectopic SVT and ventricular tachy
• Adverse effects: cinchonism (tinnitis, blurred vision, CNS excitation, GI disturbance), QT interval increased (may lead to torsades), thrombocytopenia, hypotension
• Drug interactions: hyperK, displaces digoxin from tissue binding sites

• Mechanism: blocks fast Na channels, K channels, less muscarinic block, NO alpha block (less likely to cause a dysrhythmia)
• Clinical use: atrial and ventricular dyshrhythmias, reentrant and ectopic SVT, ventricular tachy, a fib (with digoxin)
• Metabolism: N-acetylation (genotypic variation) into N-acetyl procainamide & active metabolite (which can block K channels, prolongs repolarization, can cause Torsades)
• Adverse effects: SLE-like syndrome in slow acetylators, hematoxicity (thrombocytopenia, agranulocytosis), Torsades

• Drugs: Lidocaine Mexiletine
• Mechanism: blocks inactivated channels: prefers the tissues to be partially depolarized (slow conduction in hypoxic & ischemic tissues), increases threshold for excitation & less excitation of hypoxic tissue (accelerated phase 3)
• decreases APD: due to block of slow Na "window" currents but increases diastole & extends their time to recover
• Clinical use: acute ventricular dysrhythmias (post MI) and digitalis-induced dysrhythmias
• IB is Best for MI

• Uses: tx for: post MI, open heart surgery, digoxin therapy
• Side Effects: CNS toxicity (seizures), less cardiotoxic than conventional anti-arrhythmias
• Administration: IV (to prevent 1st pass effects)
• 'li don't know what to do, so I'll work on good and bad tissue' :)

• Clinical use: same as lidocaine
• Administration: PO

• Drugs: Flecainimide, Encainide, Propafenone
• Mechanism: blocks fast Na channels (espeically Purkinje tissue), no effect on APD, no ANS effects
• Toxicity: contraindicated post-MI, prodysrhythmic if used in prophylactic VT tx,significantly prolongs the refractory period in AV node
• IC is Contraindicated in MI, flee from using it after an MI

• Drugs: Propranolol, esmolol, metoprolol, atenolol, timolol
• Mechanism: decreases cAMP, decreases Ca++ currents (indirect Ca channel blocker), suppresses abnormal pacemakers by decreasing the slope of phase 4
• AV node is parcticularly sensitive - increases PR interval
• Clinical use: Vtach, SVT, slows ventricular rate during afib, migraines, ST thyrotoxicosis, essential, perioperative htn
• Toxicity: impotence, exacerbation of asthma, CV (bradycardia, AV block, CHF), CNS (sedation, sleep alterations), may mask signs of hypoglycemia
• OD tx: glucagon

• Mechanism: non-selective
• Clinical use: Vtach, SVT, slows ventricular rate during afib, migraines, ST thyrotoxicosis, essential, perioperative htnToxicity: impotence, exacerbation of asthma, CV (bradycardia, AV block, CHF), CNS (sedation, sleep alterations), may mask signs of hypoglycemiaOD tx: glucagon

• Mechanism: Short acting
• Clinical use: acute SVTClinical use: Vtach, SVT, slows ventricular rate during afib, migraines, ST thyrotoxicosis, essential, perioperative htnToxicity: impotence, exacerbation of asthma, CV (bradycardia, AV block, CHF), CNS (sedation, sleep alterations), may mask signs of hypoglycemia OD tx: glucagon
• Administration: IV only

• Side effect: can cause dyslipidemia
• Clinical use: Vtach, SVT, slows ventricular rate during afib, migraines, ST thyrotoxicosis, essential, perioperative htnToxicity: impotence, exacerbation of asthma, CV (bradycardia, AV block, CHF), CNS (sedation, sleep alterations), may mask signs of hypoglycemia OD tx: glucagon
• B1 selective: I met a guy, who liked B1 better than B2.... do, do, do, do

• Drugs: Amiodarone, Sotalol, ibutilide, bretylium, dofetidilide
• Mechanism: Increases AP duraction, increases ERP, last resort drugs, increases QT (torsades...except for in amiodarone)

• Characteristics: dirty drug (all classes), effects in all cardiac tissue, long t1/2 (80 days), binds excessively to tissues (large Vd), alters lipid mb
• Clinical use: all dysrhythmias
• Side effects: caused by iodine in the drug: pulmonary fibrosis, smurf skin, phototoxicity, corneal deposits, hepatic necrosis, thyroid dysfn, constipation, CV (heart block, bradycardia, CHF)
• Better replacement: Dronaderone
• Check labs: PFTs (pulmonary), LFTs (liver), TFTs (thyroid)

• Characteristics: decreases K conductance, slows phase III, Beta1 blockade (decrease HR & AV conduction)
• Clinical use: life threatening ventricular dysrrhythmia
• Side effects: torsades de points,excessive AV block

• Ibutilide: Torsades
• Bretylium: new dysrrhythmia

• Drugs: Verapamil, diltiazem
• Mechanism: moslty effects V nodes, decreases conduction velocity, increases ERP and PR interval
• Clinical use: prevention of nodal, Raynauds syndrome, dysrhythmias, SVT
• Toxicity: constipation, flushing, edema, CV effects (CHF, heart block, sinus node depression)
• Drug interaction: additive AV block w/ B blockers & digoxin, verapamil displaces digoxin from tissue binding sites

• Activates the adenosine receptors in heart & kidneys
• Gi coupled decrease in cAMP
• SHORT t1/2 (<10s)
• Clinical use: drug of choice for SVT, and AV nodal dysrrhythmias
• Administration: IV
• Antagonist: methylxanthine (theophylline and caffiene)
• Side effects: flushing, sedation, dyspnea

• quinidine
• verapamil

• class Ia: Quinidine
• all class III (except for amiodarone)

• Cardiac: T1-T5L
• Atria: T4-T6L
• Ventricles: C8-T3L]
• Ant. MI: T1-T4L
• Post/Inf. MI: C2/OA/cranial base
• Sympathetic Ganglion: C2,5,7
• Vaguse: C1 & C2
• Occiput: PNS

• Left Sympathetic Chain: AV nodes, ectopic foci & ventricular fibrillation
• Right Sympathetic Chain: SA nodes (SVT)

• Left Vagus nerve: AV node block
• Right Vagus nerve: SA node block (sinuse bradycardia)

• ACEI, ARBs
• Beta Blockers
• CCB
• Diuretics (#1 drug used) / Dilators

these are the ABCDs of hypertension

• Drug: Captopril (all other '-pril' drugs)
• Mechanism: Block formation of AngioII which prevents AT1-receptor stimulation, decreases aldosterone and VD, inhibit degredation of bradykinin (cough)
• Clinical use: mild to moderate htn, protective of diabetic nephropathy, CHF
• Side effects: dry cough, hyperK, acute renal failure in renal stenosis, angioedema
• CONTRAINDICATED IN PREGNANCY

• Drug: Losartan (all other '-sartan' drugs)
• Mechanism: blocks AT1 receptors with the same results as ACEIs on BP but the ARBs don't interfere with bradykinin degredation (don't get the cough)
• Clinical use: mild to moderate htn, protective of diabetic nephropathy, CHF
• Aliskiren does not interfere with bradykinin degredation
• Side effects: hyperK, acute renal failure in renal artery stenosis, angioedema
• CONTRAINIDCATED IN PREGNANCY

• Side effects: CV depression, fatigue, sexual dysfunction, increased LDL & TG
• Caution use with: asthma, vasospastic disorder, DM (alteration of glycemia and maksing of tachycardia when hypoglycemic)

• Drugs: Prazosin, doxazosin, terazosin
• Mechanism: decreases arteriolar and venous resistance (non selective), reflexive tachy
• Use: htn, BPH (decreases urinary sphincter tone)
• Side effects: first dose syncope (VD for the first time), orthostatic hypotension (venodilation), urinary incontinence
• Advantage: good effect on lipid profile (increase HDL and decreases LDL)
• start low and go slow

• Drugs: clonidine, methyldopa (prodrug)
• Mechanism: decreases SNS outflow, decreases TPR and HR

• Mechanism: decreases SNS outflow, decreases TPR and HR
• Use: mild/moderate htn, opiate w/drawal
• Side effects: CNS depression, edema
• Drug interactions: TCA decrease alpha 2 agonist effets

• Mechanism: decreases SNS outflow, decreases TPR and HR
• Use: mild/moderate htn, hypertensive management in pregnancy
• side effects: +ve COOMBs, CNS depression, edema
• Drug interactions: TCA decreased the effectiveness

• Destroys vesicles: decreases CO and TPR (decreases NEp in periphery) reserpinze the neuron!, decreased DA, and serotonin in CNS
• Side effects: depression (severe), edema, increased GI secretions

• Accumulated into nerve endes by reuptake
• binds vesicles
• inhibits NEp release
• Side effects: diarrhea, edema
• Drug interactions: TCA block the reuptake and action

• Drugs: verapamil, diltiazem, dihydropyridines: prototype: nifedipine (fed up with the Ca channel blockers already)
• Mechanism: blocks L-type Ca channels in heart and blood vessels,CO (diltiazem and verapamil) and all others decrease TPR
• Vascular SM: nifedipine > diltiazem > verapamil (Verapamil = ventricles)
• Heart: Verapamil > diltiazem > nifedipine
• use: hypertension (all), angina (all), antiarrhythmia (verapamil and diltiazem)
• Side effects: reflex tachy ('-dipines'), gingival hyperplasia ('-dipines'), constipation (verapamil), hypertension, angina, arrhythmias, agina, arrhythmias (not nifedipine), Prinzmetal's angina,, Raynaud's, CV depression, AV block, peripheral edema, flushing, dizziness

• CCBs (-dipines)
• phenytoin
• cyclosporin (organ transplant tx)

• Mechanism: decrease TPR arteriolar dilation (NOT VENOUS)= aferload reduction, increases cGMP = SM relaxation
• Clinical Use: moderate/severe htn, first line in PREGNANCY w/ methyldopa
• Coadministered: with beta blocker to prevent reflexive tachycardia
• Side effects: SLE-like syndrome in slow acetylators, edema, reflex tach, headache, angina
• Metabolism: phase II involving trasferases

• Mechanism: decreases TPR via dilation of both arterioles & venules
• Use: hypertensive emergencies, malignant htn
• Administration: IV
• Side effect: cyanide poisioning (which is why coadministration w/ nitrites and thiosulfate is needed)

• Mechanism: VD by releasing NO in SM = increase cGMP and SM relaxation, dilates veins >> arteries, lowers preload
• Clinical Use: angina, pulmonary edema, aprhodisiac & erection enhancer
• Toxicity: reflex tachy, hypotension, flushing, "Monday Disease" in industrial exposure - dev't of tolerance for VD action during work week and loss of tolerance over weekend = tachy, dizziness & headache on reexposure

• Mechanism: K channel opener = hyperpolarizes and relaxes vascular SM
• Clinical use: severe htn
• Toxicity: hypertrichosis (hirsuitism), pericardial effusion, reflex tachy, angina, Na retension, T wave changes on EKG

• Methylene blue
• Mechanism: causes the met-Hbg to form free Hbg again)

• Note: Endothelin (ET1) is a powerful VC thru ET-A and ET-B receptor
• Mechanism: Bosentan is an ETA receptor
• antagonist
• Administration: PO
• Side effects: anything associated with VD (headache, flushing, hypotension, etc.)
• CONTRAINDICATED IN PREGNANCY

• Mechanism: is a prostacylcine that causes VD
• Administration: infusion pumps

Mechanism: inhibits type V phosphodiesterase (PDE5 = increases cGMP = relaxes arteries) to reduce the hypertension

• beta blockers
• CCB

• ACEI (protective against diabetic nephropathy)
• ARB
• CCB
• diuretics (thiazides first line)
• Beta blockers
• Alpha blockers

• ACEI
• ARB
• Beta blockers (for compensated CHF but contraindicated in decompensated CHF)
• diuretics (K sparing)

Beta blockers

Alpha blockers

• Alpha blockers
• CCB
• ACEI
• ARBs

• Diuretics (thiazide unless contraindicated)
• ACE
• ARB
• CCB

• 1. Nitroprusside: short acting, increases cGMP = direct release of NO, CN toxicity
• 2. Fenoldopam: D1 receptor agonist - relaxes vascular SM
• 3. Diazoxide: K channel opener: hyperpolarizes and relaxes vascular SM, can cause hyperglycemia by reducing insulin release

• Characteristics: 75% bioavailability, 20-40% protein bound, t1/2=40 hours (thus need loading dose), urinary excretion
• Mechanism: direct inhibition of Na/K ATPase = inhibition of Na/Ca exchanger/antiport = increases Ca = + inotropy, also stimulates the vagus nerve
• Clinical use: CHF (increases contractility), atrial fib (decreases conduction at AV node & depression of SA node), SVT (except Wolff-Parkinson-White sydnrome)
• Toxicity:
• Cholinergic - n/v/d, blurry yellow vision (think Van Gogh)
• ECG - increase PR, decreased QT, scooping (hockey stick) depression of ST segment, T wave inversion, dysrhythmia, hyperK
• Kidneys - worsens renal failure (decreases excretion)
• Quinidine - decreases clearance, displaces digoxin from tissue binding (so does verapamil)
• Antidote: slowly normalize K, lidocaine, cardiac pacer, anti-dig Fab fragments, Mg

• 1. ACE/ARBs
• 2. Beta Blockers
• 3. Diuretics

the ABDs of heart failure

• Decreasing preload: diuretics, ACEI, ARB, venodilators
• Decreasing afterload: ACEI, ARB, arteriodilators
• Increasing contractility: digoxin (cardiac glycoside), beta agonist
• Decreasing remodeling: ACEI, ARB, sprinolactone

• Aldosterone
• Beta blockers (ie metoprolol, carvedilol)

• Digoxin
• Phosphodiesterase inhibitors: milrinone, inarinone

• Drugs: Milranone, inamrinone
• Mechanism: increases cAMP in heart muscle = increased inotropy, increases cAMP in SM = decreased TPR
• Clinical use: only acutely beneficial (increased mortality LT use)

Acute use only in heart failure

• Diuretics: Loops (backward failure), spironolactone + ACEI (to reduce remodeling)
• Metoprolol & carvedilol (decreases remodeling)
• Nesiritide: acutely
• recombinant form of human B-type nautriuretic peptide (rh BNP)
• binds to natriuretic peptide receptors = increases cGMP = VD = acutely decompensated CHF

• Nitrates
• Beta blockers
• CCB

Angina: stable/classic: occurs from xcise/effort due to coronary atherosclerotic occulsion

Goal in tx: decrease oxygen requirement by lowering TPR, CO or both

NBC for angina

• Nitrates
• CCB

Vasospastic angina: due to reversible decrease in coronary BF (vasospam)

Goal in tx: increase oxygen delivery by reducing the spasm, no beta blockers used!

• Drugs:
• isosorbide: extended release for chronic use
• Nitroglycerin: sublingual (rapidly acting, little 1st pass), transdermal (slow action), IV
• Nitrates are prodrugs of NO
• Mechanism: decreases preload = decreases cardiac work = decreases oxgen requirement, decrease the infarct size and post-MI mortality
• Side effects: flushing, headache (MC), orthostatic hypotension, reflex tachycardia, fluid retention
• Cautions/contraindications: tachyphylaxis, CV toxicity w/ sildenafil

• Mechanism: inhibits PDE5 = increases cGMP = VD = increases BF = increases erectile response
• Contraindication: cocomitant use of nitrates or other VD can cause sudden death, MI

• Use: angina of effort (classical angina), contraindicated in vasospastic angina
• Drugs: carvedilol equivalent clinically to isosorbide

• Use: vasospastic angina
• Drugs: nifedipine
• note: recurring COMLEX question: nifedipine is vasular selective- DOC for Raynauds, vasospam, cyanotic extremity

Acute: MONA: Morphine, Oxygen, Nitro, ASA

Chronically: Beta blocker, ACEI, statins

aka He'll be there even as we go through this journey of board craziness!