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Conductance in cardiac slow response tissue is dependent on what three things?
- 1. Rate of phase 0 depolarization
- 2. Threshold potential
- 3. Resting Membran Potential
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Increase in cAMP on the heart tissue will:
- 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)
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Saved By Pharm Class
- Sodium
- Beta blockers
- Potassium
- Calcium
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Antiarrhythmic Drug: Class Ia General
- 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
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Antiarrhythmic Drug: Class Ia - Quinidine
- 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
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Antiarrhythmic Drug: Class Ia- Procainamide
- 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
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Antiarrhythmic Drug: Class Ib- General
- 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
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Antiarrhythmic Drug: Class Ib- Lidocaine
- 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' :)
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Antiarrhythmic Drug: Class Ib- Mexiletine
- Clinical use: same as lidocaine
- Administration: PO
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Antiarrhythmic Drug: Class Ic- General
- 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
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Antiarrhythmic Drug: Class II - Beta Blockers (general)
- 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
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Antiarrhythmic Drug: Class II - Beta
Blocker - Propranolol
- 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
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Antiarrhythmic Drug: Class II- Beta Blocker - Esmolol
- 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
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Antiarrhythmic Drug: Class II- Beta Blocker- Metoprolol
- 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
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Antiarrhythmic Drug: Class III- K Channel Blocker (general)
- Drugs: Amiodarone, Sotalol, ibutilide, bretylium, dofetidilide
- Mechanism: Increases AP duraction, increases ERP, last resort drugs, increases QT (torsades...except for in amiodarone)
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Antiarrhythmic Drug: Class III- 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)
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Antiarrhythmic Drug: Class III: Sotalol
- 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
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Antiarrythmic Drug: Class III: Ibutilide and Bretylium side effects:
- Ibutilide: Torsades
- Bretylium: new dysrrhythmia
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Antiarrhythmic Drug: Class IV: Ca Channel Blockers
- 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
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Antiarrhythmic Drugs: Unclassified: Adenosine
- 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
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Antiarrhythmic Drugs that displace digoxin are:
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Drugs that cause long QT Syndrome (possibly Torsades) are:
- class Ia: Quinidine
- all class III (except for amiodarone)
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Viscerosomatics:
Cardiac
Atria
Ventricles
Anterior MI
Posterior/Inferior MI
Sympathetic Ganglion
Vagus
Occiput
- 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
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Sympathetic Innervation of Heart
Left Sympathetic Chain:
Right Sympathetic Chain:
- Left Sympathetic Chain: AV nodes, ectopic foci & ventricular fibrillation
- Right Sympathetic Chain: SA nodes (SVT)
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Parasympathetic Innervation of Heart
Left Vagus Nerve:
Right Vagus Nerve:
- Left Vagus nerve: AV node block
- Right Vagus nerve: SA node block (sinuse bradycardia)
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What are the 4 MC used classes of antihypertensive drugs?
- ACEI, ARBs
- Beta Blockers
- CCB
- Diuretics (#1 drug used) / Dilators
these are the ABCDs of hypertension
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Antihypertensive Drug: ACEI
- 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
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Antihypertensive Drug: ARBs
- 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
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Antihypertensive Drug (alter sympathetic activity): Beta blockers
- 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)
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Antihypertensive Drug (alter sympathetic activity): Alpha 1 Blockers
- 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
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Antihypertensive Drug (alters sympathetic activity): Alpha 2 Agonists
- Drugs: clonidine, methyldopa (prodrug)
- Mechanism: decreases SNS outflow, decreases TPR and HR
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Antihypertensive Drug (alters sympathetic activity): Alpha 2 Agonist: Clonidine
- 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
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Antihypertensive Drug (alters sympathetic activity): Alpha 2 Agonist: Methyl dopa
- 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
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Antihypertensive Drug (alters sympathetic activity): Interfering w/ storage vesicles: Reserpine
- 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
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Antihypertensive Drug (alters sympathetic activity): Interfering with storage vesicles: Guanethidine
- Accumulated into nerve endes by reuptake
- binds vesicles
- inhibits NEp release
Side effects: diarrhea, edema - Drug interactions: TCA block the reuptake and action
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Antihypertensive Drug: CCB
- 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
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Drugs that cause gingival hyperplasia
- CCBs (-dipines)
- phenytoin
- cyclosporin (organ transplant tx)
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Antihypertensive Drug: Vasodilators: Direct acting thru NO: Hydralazine
- 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
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Antihypertensive Drug: Vasodilators: Direct acting thru NO: Nitroprusside
- 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)
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Antihypertensive Drug: Vasodilator: Direct acting thru NO: Nitroglycerin, Isosorbide dinitrate
- 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
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Antihypertensive Drug: Vasodilators: Direct acting thru K channels: Minoxidil
- 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
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What is the drug of choice for methemoglobinemia?
- Methylene blue
- Mechanism: causes the met-Hbg to form free Hbg again)
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Pulmonary Hypertension:
Bosentan
- 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
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Pulmonary Hypertension: Epoprostenol
- Mechanism: is a prostacylcine that causes VD
- Administration: infusion pumps
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Pulmonary Hypertension: Sildenafil *
Mechanism: inhibits type V phosphodiesterase (PDE5 = increases cGMP = relaxes arteries) to reduce the hypertension
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What are the suitable antihypertensive drugs for a pt with angina?
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What are the suitable antihypertensive drugs for diabetic patients?
- ACEI (protective against diabetic nephropathy)
- ARB
- CCB
- diuretics (thiazides first line)
- Beta blockers
- Alpha blockers
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What are the suitable antihypertensive drugs for pts w/ heart failure?
- ACEI
- ARB
- Beta blockers (for compensated CHF but contraindicated in decompensated CHF)
- diuretics (K sparing)
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What are the suitable antihypertensive drugs post-MI?
Beta blockers
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What are the most suitable antihypertensive drugs for pts w/ BPH?
Alpha blockers
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What are the most suitable antihypertensive drugs for pts with dyslipidemia?
- Alpha blockers
- CCB
- ACEI
- ARBs
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What is the most suitable antihypertensive drug for pts with essential hypertension?
- Diuretics (thiazide unless contraindicated)
- ACE
- ARB
- CCB
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Malignant hypertension treatment includes:
- 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
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Inotropic Drug: Cardiac Glycoside: Digoxin
- 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
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What are the most common Heart Failure drug classes?
- 1. ACE/ARBs
- 2. Beta Blockers
- 3. Diuretics
the ABDs of heart failure
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Pharmacotherapy in heart failure is aimed at:
- Decreasing preload: diuretics, ACEI, ARB, venodilators
- Decreasing afterload: ACEI, ARB, arteriodilators
- Increasing contractility: digoxin (cardiac glycoside), beta agonist
- Decreasing remodeling: ACEI, ARB, sprinolactone
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What are the 2 things that cause cardiac remodeling?
- Aldosterone
- Beta blockers (ie metoprolol, carvedilol)
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Common Inotropic Drugs
(drugs that increase contractility)
- Digoxin
- Phosphodiesterase inhibitors: milrinone, inarinone
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Inotropic Drug: Phosphodiesterase Inhibitors
- 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)
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Inotropic Drug: DA / Dobutamine
Acute use only in heart failure
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Miscellaneous Drugs used 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
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What are the three main classes of drugs used in treating classic angina?
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
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What are the two main classes of drugs used in treating vasospastic (Prinzmetal) angina?
Vasospastic angina: due to reversible decrease in coronary BF (vasospam)
Goal in tx: increase oxygen delivery by reducing the spasm, no beta blockers used!
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Nitrates: Classical and Vasospastic Angina treatment
- 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
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Nitrate & phosphodiesterase drug: Sildenafil (viagra)
- Mechanism: inhibits PDE5 = increases cGMP = VD = increases BF = increases erectile response
- Contraindication: cocomitant use of nitrates or other VD can cause sudden death, MI
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Antianginal Drug: Beta Blockers + Carvedilol
- Use: angina of effort (classical angina), contraindicated in vasospastic angina
- Drugs:
carvedilol equivalent clinically to isosorbide
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Antianginal Drug: CCB
- Use: vasospastic angina
- Drugs: nifedipine
- note: recurring COMLEX question: nifedipine is vasular selective- DOC for Raynauds, vasospam, cyanotic extremity
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Treatment for an MI (acute and chronically)
Acute: MONA: Morphine, Oxygen, Nitro, ASA
Chronically: Beta blocker, ACEI, statins
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"Have I not commanded you? Be strong and courageous, do not be terrified, do not be discouraged, for the Lord God is with you wherever you go" Joshua 1:9
aka He'll be there even as we go through this journey of board craziness!
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