Cardio+renal drugs

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Cardio+renal drugs
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2011-06-19 14:44:35
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Cardio+renal drugs
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  1. Class 1A antiarrhythmic
    • Block fast Na channels (open state)
    • only fast fibers!
    • decrease slope of phase 0
    • increase APD, ERP, QT interval
    • (also block K-channels- prolong repol)

    USE- atrial AND ventricular arrhythmias, esp Re-entrant and Ectopic supraventricular and ventricular tachycardia! (Wolff-Parkinson-White syndrome!)

    SE- thrombocytopenia, torsades (inc QT)

    DRUGS: Quinidine, Procainamide, Disopyramide
  2. Quinidine
    • Class 1A antiarrhythmic
    • block fast Na channels (open) - only fast fibers!
    • M- and Alpha blocker too!
    • block K-channels (prolong repol)

    • -decrease Phase 0 (CV), increase APD, ERP, QT
    • -M2 block--> tachycardia!
    • -Alpha2 block--> reflex tachycardia!

    • USE- atrial fibrillation (give Digoxin first- slow AV) PO
    • -great for Wolff-Parkinson-White syndrome (block accessory path, increase AV node)

    • SE- Cinchonism (block both M and Alpha!)- GI distress, tinnitus, ocular dysfunction, CNS excitation. Hypotension, Torsades (incr QRS, QT),
    • hemolytic anemia, thrombocytopenia

    • NOTE- Hyperkalemia (depol cells)-->enhance chance of torsades! Quinine & Verapamil displace Digoxin--> incrs it's toxicity.
    • -Quinidine a weak base, absorption incrs w/antiacids.
  3. Procainamide
    • Class 1A antiarrhythmic
    • -block fast Na channels (open)- only fast fibers!
    • -M-blocker too (incr HR), but less than Quinidine
    • -block K-channel (prolong repol)
    • -decrease Phase 0 (CV), increase APD, ERP, QT

    • USE- atrial AND ventricular arrhythmias
    • -but monitor HR b/c M-blockade-->+AV--> QT--> torsades

    • UNIQE-metabolized by N-acetyltransferase (slow & fast acetylators)-->active metabolite.
    • -good hapten, goes everywhere

    • SE- drug induced-SLE! (anti-histone) more likely with slow acetylators. Hematotoxicity (thrombocytopenia, agranulocytosis) do reg CBC!
    • Torsades, Hypotension
  4. Disopyramide
    • Class 1A antiarrhythmic
    • Block fast Na channels (open state)only fast fibers!
    • -decrease slope of phase 0increase APD, ERP, QT interval
    • -Block M receptor!
    • -Decrease contractility!
    • -(also block K-channels- prolong repol)

    • -USE- atrial AND ventricular arrhythmias
    • -Great for Hypertrophic Cardiomyopathy (neg inotropy)

    -SE- thrombocytopenia, torsades (inc QT)
  5. Drugs that cause SLE !
    • Procainamide
    • Hydralazine
    • Isoniazid

    + anti- histone!!
  6. Class 1B antiarrhythmic
    • Block fast Na channels (inactivated!)
    • -Target ischemic/depolarized perkinje or ventricular tissue
    • -slow conduction in ischemic tissue, keep it refractory b/c that's where arrhythmias begin.
    • -decrease APD! block slow Na (window current at plateau phase), but this increase diastole, time to recover.

    • USE-acute ventricular arrhythmia (esp. post-MI)
    • -Digitalis-induced arrhythmias

    SE- local anesthetic, CNS stimulate/depress, CV depress

    DRUGS: Lidocaine, Mexiletine, Tocainide
  7. Lidocaine
    • Block fast Na channels (inactivated!)
    • -Target ischemic/depolarized perkinje or ventricular tissue
    • -slow conduction in ischemic tissue, keep it refractory b/c that's where arrhythmias begin
    • -decrease APD! block slow Na (window current at plateau phase), but this increase diastole, time to recover.

    • USE- post-MI
    • -Open heart surgery (b/c tissue depol)
    • -Digoxin toxicity (block Na/K pump-->depol cell)

    SE- CNS toxicity (seizures), Least cardiotoxic of antiarrhythmics!

    UNIQUE- only IV! so to take home, give Mexiletie or Tocainide.
  8. Mexiletine
    • Block fast Na channels (inactivated!)
    • -Target ischemic/depolarized perkinje or ventricular tissue -slow conduction in ischemic tissue, keep it refractory b/c that's where arrhythmias begin.
    • -decrease APD! block slow Na (window current at plateau phase), but this increase diastole, time to recover.

    USE-acute ventricular arrhythmia (esp. post-MI)-Digitalis-induced arrhythmias

    • SE- local anesthetic, CNS stimulate/depress, CV depress
    • UNIQUE- can take oral! so give to outpatients. b/c Lidocaine is IV only.
  9. Tocainide
    • Block fast Na channels (inactivated!)
    • -Target ischemic/depolarized perkinje or ventricular tissue -slow conduction in ischemic tissue, keep it refractory b/c that's where arrhythmias begin.
    • -decrease APD! block slow Na (window current at plateau phase), but this increase diastole, time to recover.

    USE-acute ventricular arrhythmia (esp. post-MI)-Digitalis-induced arrhythmias

    • SE- local anesthetic, CNS stimulate/depress, CV depress
    • UNIQUE- can take oral! so give to outpatients. b/c Lidocaine is IV only.
  10. Class IC
    • Block ANY fast Na channel
    • -esp. His-Punrkinje tissue
    • -No effect on APD
    • -No ANS effects

    • USE- V-tachs that --> V-fib and SVT.
    • -LAST RESORT when nothing else works!

    • SE- very proarrhythmic! esp post-MI
    • significantly prolong refractory period of AV node.

    do NOT use in post-MI

    DRUGS: Flecainide, Encainide, Propafenone
  11. Flecainide
    • Block ANY fast Na channel
    • -esp. His-Punrkinje tissue
    • -No effect on APD
    • -No ANS effects

    • USE- V-tachs that --> V-fib and SVT.
    • -LAST RESORT when nothing else works!

    • SE- very proarrhythmic! esp post-MIsignificantly prolong refractory period of AV node.
    • do NOT use in post-MI!
  12. Encainide
    • Block ANY fast Na channel
    • -esp. His-Punrkinje tissue
    • -No effect on APD
    • -No ANS effects

    • USE- V-tachs that --> V-fib and SVT.
    • -LAST RESORT when nothing else works!

    • SE-very proarrhythmic! esp post-MIsignificantly prolong refractory period of AV node.
    • do NOT use in post-MI!
  13. Propafenone
    • Block ANY fast Na channel
    • -esp. His-Punrkinje tissue
    • -No effect on APD
    • -No ANS effects

    • USE- V-tachs that --> V-fib and SVT.
    • -LAST RESORT when nothing else works!

    • SE-very proarrhythmic! esp post-MIsignificantly prolong refractory period of AV node.
    • do NOT use in post-MI!
  14. Hyperkalemia causes increased toxicity for
    ALL class I drugs!!!
  15. Class II antiarrhythmics
    • Beta blockers!
    • -work on pacemakers SA, AV!
    • -AV esp sensitive
    • -block B1-receptor--> decrease cAMP--> decrease Ca influx--> decrease slope Phase 4 (automaticity slope)
    • - increase PR!

    • USE- prophylaxis post MI (neg inotropy!)
    • -SVT, slow ventricular rate during A-fib and A-flutter. (neg chronotropy)

    SE- Impotence, Exacerbate asthma, COPD, bradycardia, AV block, CHF, Sedation, Hypoglycemia, Hyperlipidemia

    Rx overdose with Glucagon!

    • Acebutolol- no hyperlipidemia
    • Atenolol- no sedation
    • Pindolol- no hyperlipidemia, no asthma
    • Propranolol- most sedation
  16. Propranolol
    • Class II antiarrhthmic
    • nonselective beta blocker
    • -decrease cAMP at SA, AV-->dec Ca--> dec phase 4 slope--> dec HR, increaes PR

    USE- angina, MI, HTN, tachyarrhthmias (SVT),Migraine, Thyrotoxicosis, performance anxiety, essential tremor! (block deiodinase)

    UNIQUE- cause severe SEDATION!

    SE-hypotension, bradycardia, sedation, bronchospasm, vasospasm, hyperlipidemia, impotence

    DO NOT USE IN BRADYCARDIA, HEART BLOCK, SEVERE ASHMA, COPD, PRINZMETAL, COCAINE-INDUCED ANGINA! DECOMPENSATED CHF!
  17. Esmolol
    • Class II antiarrhthmic
    • beta-1 blocker
    • -decrease cAMP at SA, AV-->dec Ca--> dec phase 4 slope--> dec HR, increaes PR

    • USE-acute SVT (very short acting)
    • - IV only!

    SE-hypotension, bradycardia, sedation, bronchospasm, vasospasm, hyperlipidemia, impotence
  18. Metoprolol
    • Class II antiarrhthmic
    • beta-1 blocker
    • -decrease cAMP at SA, AV-->dec Ca--> dec phase 4 slope--> dec HR, increaes PR

    • USE- Angina, MI, CHF
    • -prophylaxis post MI
    • -SVT, slow ventricular rate during A-fib and A-flutter.

    SE-hypotension, bradycardia, sedation, bronchospasm, vasospasm, hyperlipidemia, impotence

    DO NOT USE IN BRADYCARDIA, HEART BLOCK, SEVERE ASHMA, COPD, PRINZMETAL, COCAINE-INDUCED ANGINA! DECOMPENSATED CHF!
  19. Atenolol
    • Class II antiarrhthmic
    • beta-1 blocker (longer acting)
    • -decrease cAMP at SA, AV-->dec Ca--> dec phase 4 slope--> dec HR, increaes PR

    • USE- Angina, MI, HTN
    • -prophylaxis post MI
    • - SVT, slow ventricular rate during A-fib and A-flutter.

    DOES NOT CAUSE SEDATION! (safe to use in sedated patients taking anti-depressants, BDZ, alcohol)

    • SE-hypotension, bradycardia, bronchospasm, vasospasm, hyperlipidemia
    • DO NOT USE IN BRADYCARDIA, HEART BLOCK, SEVERE ASHMA, COPD, PRINZMETAL, COCAINE-INDUCED ANGINA! DECOMPENSATED CHF!
  20. Timolol
    • Class II antiarrhthmic
    • non selective beta blocker (same as propranolol)
    • -decrease cAMP at SA, AV-->dec Ca--> dec phase 4 slope--> dec HR, increaes PR

    • USE- SVT
    • - Open angle Glaucoma! (eye drops)
    • -decrease aqeous humor formation, release intraocular pressure.
    • -mostly beta-2 receptors in ciliary body epithelium.

    SE-hypotension, bradycardia, sedation, bronchospasm, vasospasm, hyperlipidemia
  21. Class III antiarrhythmics
    • K-channel blockers (delayed rectifier)
    • -prolong repolarization--> increase APD, ERP, QT

    DRUGS: Amiodarone, Sotalol, Ibutilide, Bretylium, Dofetilide
  22. Amiodarone
    • Class III antiarrhythmic
    • K-channel blocker (delayed rectifier)
    • -prolong repolarization--> increase APD, ERP, QT!
    • -but NOT as much torsades despite QT!

    -also block Na, Ca, Beta!! (alters lipid mem)

    • USE- ANY arrhythmias!
    • but, too many SE! so use when only all else fails.
    • -can use for Wolff-Parkinson-White syndrome

    • SE- LONG HALF LIFE! (3mo) HAPTEN, STAYS IN TISSUES FOREVER (high Vd), IODINATES! (it's an iodine)
    • -pulmonary fibrosis
    • -blue pigmentation of skin (smurf skin)
    • -hypo/hyper thyroidism
    • - phototoxicity, corneal deposits
    • -hepatic necrosis
    • -CV effects
  23. Who prolongs QT?
    Class Ia and Class III!

    QT elongate--> torsades. but, NOT amiodarone!
  24. Drugs that cause Pulmonary Fibrosis!
    • Amiordarone
    • Bleomycin
  25. Sotalol
    • Class III antiarrhythmic + Beta-blocker
    • -K-channel blocker (delayed rectifier)-prolong repolarization--> increase APD, ERP, QT
    • -Beta1 block--> slow HR, AV conduc.

    USE- only life-threathening arrhythmias

    SE- Torsades (QT), exessive Beta block
  26. Ibutilide
    • Class III antiarrhythmic
    • K-channel blocker (delayed rectifier)
    • -prolong repolarization--> increase APD, ERP, QT

    USE- when all other antiarrhythmics fail.

    SE- torsades (QT)
  27. Bertylium
    • Class III antiarrhythmic
    • K-channel blocker (delayed rectifier)
    • -prolong repolarization--> increase APD, ERP, QT

    USE- when all other antiarrhythmics fail.

    SE- torsades (QT), new arrhythmias, hypotension
  28. Verapamil
    • Class IV antiarrhythmic & antihypertensitve!
    • -L-type-Ca channel blocker
    • -decr. phase 0 and phase 4 in SA, AV node
    • -decr. CV, incrs ERP, incrs PR-interval
    • -decr. CO, decr SVR (all CCBs)
    • USE- SVT, angina, prinzmetal's angina
    • - HTN (but likes heart more!), Raynaud's

    • SE-AV block, constipation,hypotension, flushing, dizziness, edema
    • -displace Digoxin from its target (like Quinidine)
    • - ADDITIVE EFFECT w/ Beta-blockers & Digoxin!!--> increase PR! monitor!
  29. Diltiazem
    • Class IV antiarrhythmic & anti-hypertensive!
    • -L-type-Ca channel blocker
    • -decr. phase 0 and phase 4 in SA, AV node
    • -decr. CV, incrs ERP, incrs PR-interval
    • -dec CO, dec SVR (all CCBs)

    • USE- SVT, angina, prinzmetal's angina
    • -HTN, Raynaud's

    • SE-AV block, constipation,hypotension, flushing, dizziness, edema
    • - ADDITIVE EFFECT w/ Beta-blockers & Digoxin!!--> increase PR! monitor!
  30. Adenosine
    • Unclassified antiarrhythimic
    • -Adenosine-R in heart-->Gi-->dec cAMP--> dec phase 4-->hyperpol--> dec HR at SA, AV (like M2)
    • -incr PR

    USE- DOC for Paroxysmal SVT!!

    • very very short acting!! (15sec)
    • antagonized by theophylline, coffee

    • SE- dyspnea!, flushing, sedation, hypotension
    • -Adenosine R-> Gq in bronchiole-->bronchoconstrict!
  31. Mg+
    • Unclassified antiarrhythmic
    • -acts to compete Ca--> decrease it's effects

    • USE- torsades!!, digoxin toxicity (like lidocaine)
    • -premature labor
    • -seizure
  32. Drugs that cause Torsades
    anything that keeps cells depol longer!

    • K-channel blockers (class IA, III)
    • Anti-muscarinic
    • Anti-psychotics
    • Anti-histamines
    • TCAs
  33. Treating Torsades
    torsades- QT increase->ventricular arrhythmia!

    • -correct hypokalemia
    • -correct hypomagnesemia
    • -stop drugs that prolong QT
    • -shorte APD with drugs (ex. isoproterenol) or electrical pacing
  34. K+
    • Unclassified antiarrhythmic
    • depress ectopic pacemakers in hypokalemia
    • ex. digoxin toxicity

    Hypekalemia--> depolarize cells!!

    BOTH HYPERkalemia and HYPOkalemia are arrhythmogenic!!!
  35. Clonidine
    • Alpha-2 agonist (anti-hypertensive!)
    • Decrease NE release (dec alpha-1, beta-1--> vasodilate, decrease HR)

    • USE-mild to moderate HTN (esp w/renal disease)
    • -Opioid withdrawl

    • SE- CNS depression (no NE), Edema (RAA),sexual dysfunction, dry mouth
    • -immediate stopping-->rebound HTN, so taper off gradually!!

    • UNIQUE- opposition with TCA! (incr NE)
    • do not give with TCA! cancel each other's effect!
    • - b/c it's indirect, NO immediate effect! it takes time to work.
    • - no need to worry about reflex tachycardia!
  36. Methyldopa
    • Alpha-2 agonist (anti-hypertensive!)
    • Decrease NE release (dec alpha-1, beta-1--> vasodilate, decrease HR)

    USE- HTN in Pregnancy (safe)! also with renal disease (b/c does NOT decrease blood flow to kidney)

    • SE- Hemolytic anemia (+ coombs), hepatotoxic, edema, impotence, sedation,dry mouth lactation (prolactin incr)
    • -safe in pregnancy b/c high plasma protein binding (why it's a good hapten-->autoimmune hemolysis!)

    - TCAs and alpha-2 agonists cancel each other's effects!!
  37. Reserpine
    • Indirect antiadrenergic (old~ antihypertensive)
    • -Block Vesicular DA-beta hydroxylase (in NE storage vesicle, marker enzyme of NE-neurons)
    • -decr release of NE, 5-HT, DA!

    USE- used to be anti-hypertensive, but removed because it causes SEVERE DEPRESSION!

    SE- suicidal! (b/c NE, 5-HT, DA all reduced in brain!) edema, incr GI secretion (PED pts hate it!)
  38. Guanethidine
    • Indirect antiadrenergic (old~ antihypertensive)
    • -enters thru NE-reuptake transporter--> block release of NE vesicles!
    • -vasodilate, decrease HR

    USE-old antihypertensive

    • SE- diarrhea, edema (RAA)
    • do not give with TCAs! useless!
    • -TCAs block NE reuptake transporter, so Guanethidine would have no entry.
  39. Prazosin
    • alpha-1 blocker, antihypertensive
    • (relax areterioles + venules)

    • USE-HTN
    • -BPH- relax sphincter so they can pee
    • -Raynaud's phenomenon

    • SE-orthostatic hypertension, urinary incontinence, sexual dysfunction, nightmare
    • -good lipid profile unlike beta-blockers! (incr HDL, dec LDL)

    alpha-1 blockers DO cause reflex tachycardia!

    similar: doxazosin, terazosin, samulosin
  40. beta blockers -as anti-HTN
    antihypertensive, post-MI, antiarrhythmic

    -block renin release! (also decr HR, CO helps too)

    SE- AV block (bradycardia), CNS depression, Dec sex arousal, hyperlipidemia (dec lipolysis B2), hypoglycemia

    • - no reflex tachycardia!
    • -watch out in use w/ Asthma, Vaspospastic dx, Diabetes!
  41. Hydralazine
    • antihypertensive
    • direct-acting vasodilator!
    • arteriole only.

    -prodrug-->met in arterioles only--incr cGMP->vasodilate-->dec SVR-->decr afterload

    • -USE- IV severe HTN (pregnancy safe!)
    • - CHF
    • -SE- SLE- in slow acetylators! edema (RAA), reflex tachycardia
    • -give with diruretics or beta blocker
  42. Nitroprusside
    • antihypertensive
    • direct acting vasodilator!
    • prodrug-->incr cGMP-->aterioles+ veins

    • USE- IV- hypertensive emergency (short term only!)
    • SE- CN-poisoning (prusside-CN)
    • -give with nitrite + thiosulfate!
  43. Cyanide poisoning
    -caused by Nitroprusside, combustion of Polyurethane (house fires!)

    • -CN--> bind Fe-containing enzymes (esp Heme in Cyt oxidase)--> inhibit ETC--> hypoxia!
    • -initial CNS and Cardio stimulation-->CNS depression, death.
    • -rapid onset flushing, tachypnea, tachycardia, headache, nausea, vomiting, severe lactic acidosis (hypoxia), High venous PO2 (tissues cannot extract)
  44. How do you treat Cyanide posioning?
    Amyl Nitrite--> induce methehmoglobin (Fe+3)-->Met-Hb bind CN, release more O2 to tissues-->thiosulfate--> SCN- + Met-Hb
  45. Minoxidil
    • anti-hypertensive
    • ATP-dep K-channel blocker
    • (arterioles , pancreas beta cells)
    • -hyperpol cells

    • USE- IV- severe HTN
    • -baldness (rogaine)

    • SE- hypertichosis, hyperglycemia (dec Insulin release), edema, reflex tachycardia
    • -use with beta blockers!
  46. Diazoxide
    • anti-hypertensive
    • ATP-dep K-channel blocker
    • (arterioles , pancreas beta cells)
    • -hyperpol SMC-->relax

    • USE- IV- hypertensive crisis
    • -insulinomas!! (b/c decr insulin release!)

    • SE- hyperglycemia (decr insulin release), Edema, Reflex tachycardia
    • -use with beta-blockers!
  47. Nifedipine
    • anti-hypertensive! direct vasodilator
    • L-type Ca-channel blocker
    • "dipines"= dihydropyridines


    • USE- HTN, Prinzmetal's angina
    • (not approved for antiarrhythmic!- only Verapamil, Diltiazem).

    • SE- reflex tachycardia, gyngival hyperplasia!
    • AV block, edema, flushing, dizziness
    • -Phenytoin also cause gyngival hyperplasia.
  48. Captopril
    • ACE inhibitor
    • block Ang-II form.
    • -arteriole + venus dilation
    • -inhibit BK breakdown!

    • USE- HTN, CHF, Diabetic nephropathy!
    • (dec afterload, dec heart remodeling)

    • SE-hyperkalemia, dry cough (BK), hypotension (esp. Na-depleted pt) ,acute renal failure in renal artery stenosis!, angioedema!
    • do NOT use in bilateral renal a. stenosis, pregnancy!!
  49. Losartan
    • ARB
    • -AngII-receptor blocker
    • -arteriole + venus dilator
    • -does NOT inhibit BK breakdown

    • USE- HTN, CHF, Diabetic nephropathy
    • (dec afterload, prevent heart remodeling)

    • SE- hyperkalemia, hypotension, acute renal failure in renal a. stenosis
    • do NOT use in bilateral renal a. stenosis, pregnancy!
  50. Aliskiren
    Block Renin

    USE- HTN

    • SE-hypotension, hyperkalemia, acute renal failure in renal a stenosis.
    • do NOT use in bilateral renal a. stenosis, pregnancy!
  51. What antihypertensive will you use?
    HTN + Angina
    • beta blockers
    • calcium channel blockers
  52. What antihypertensive will you use?
    HTN + Diabetes
    • ACE-inhibitors
    • ARB

    (improve blood supply to the hyalin-sclerosing glomeruli)
  53. What antihypertensive will you use?
    HTN + Heart failure
    • ACE-inhibitor
    • ARBs
    • beta blockers
  54. What antihypertensive will you use?
    HTN + Post-MI
    Beta blockers
  55. What antihypertensive will you use?
    HTN + BPH
    Alpha-1 blockers
  56. What antihypertensive will you use?
    HTN + hyperlipidemia
    • Alpha-1 blocker
    • Calcium channel blocker
    • ACEI, ARB

    NOT beta-blockers! (hypoglycemia, hyperlipidemia)
  57. Bosentan
    • anti-hypertension for Pulmonary HTN!
    • -inhibit Endothelin-receptorA

    • USE- Pulm HTN
    • great b/c endothelin-->vasoconstrict + endothelial hyperplasia!

    • SE-hypotension, flushing, leg edma
    • -hepatitis (high dose)
    • -induce CYP, dec warfarin (pulm HTN patienst usu on it!)
  58. Epoprostenol
    • anti-hypertensive for Pulm HTN!
    • PGI2- analog--> incr cAMP-->vasodilate

    USE- Puml HTN

    • SE- Jaw pain, headache, flusing
    • -need to infuse slowly IV (short half life)
  59. Sidenafil
    • vasodilator
    • -inhibit PDE-V--> incr cGMP--> NO--> vasodilate

    USE- erectile dysfunction, Pulm HTN!

    • SE- headache, flushing, priapism (color vision change)
    • - potentiate vasodilation of Nitroglycerin (inc cGMP)!--> severe hypotension!!
  60. Digoxin
    • + inotropic agent
    • direct-block Na/K-ATPase in heart muscle (incr Na, dec gradient for Na/Ca exchanger)-->incr Ca-->incr contractility!
    • indirect- depol all neurons-->incrs Vagal tone (node) AND Symp tone (muscle)--> dec HR, incr contractility!

    • USE- CHF (acute+chronic)
    • -A-fib (ironic, but incr vagal to AV)

    • SE-cholinergic: nausea, diarrhea, blurry vision
    • ECG- incr PR, dec QT, T-invert, sccoping, arrhythmia (depol), hyperkalemia

    • do NOT use in Hypokalemia, AV block, Wolff-Parkinson-White syndrome!!
    • -long half life-need loading dose "digitalize"
    • -cleared by kidney-->bad kidney, incr toxicity!
    • -high Vd (high tissue binding)-->displaced by Verapamil, Quinidine-->incr toxicity!
    • -Diuretics-->hypokalemia-->incr toxicity!
  61. How do I treat Digoxin toxicity?
    • slowly normalize K+ , Mg+2
    • Lidocaine (class Ib)-Rx arrythmia in digitalized (depol) area
    • anti-digoxin Fab fragment
  62. How would I treat Wolff-Parkinson-White Syndrome?
    Block fast accessory pathway, increase AV node conduction

    USE- Class Ia (Quinidine) or III (Amiodarone)

    Don't use- AV blockers! ( Digoxin, B-blocker, Ca-channel blocker, adenosine)
  63. Milrinone
    • + inotropic agent
    • -PDE-III inhibitor (heart, SM)
    • -inhibit cAMP breakdown
    • -cAMP, heart--> incrs contractiliy!
    • -cAMPT, BV--> vasodilate!

    • USE- decompensated Heart Failure!
    • increase contractiliy + decrease afterload

    SE-vent arrhythmias! hypotension, hepatotoxicity
  64. Inamrinone
    • + inotropic agent
    • -PDE-III inhibitor (heart, SM)
    • -inhibit cAMP breakdown
    • -cAMP, heart--> incrs contractiliy!
    • -cAMPT, BV--> vasodilate!

    • USE- decompensated Heart Failure!
    • increase contractiliy + decrease afterload

    SE-vent arrhythmias! hypotension, hepatotoxicity
  65. Carvedilol
    • beta blocker + alpha-1 blocker!!
    • Vasodilatory beta blocker!

    • USE- CHF!!
    • - block beta--> decrease O2 demand, decrease renin
    • - block alpha--> decrease SVR, decrease afterload, preload.

    • SE- Hypotension, Bradycardia, Bronchospasm.
    • DO NOT USE IN DECOMPENSATED HEART FAILURE!
  66. Labetolol
    • beta blocker + alpha-1 blocker + partial beta2-agonist!!
    • Vasodilatory beta blocker!

    • USE- CHF!!
    • - block beta--> decrease O2 demand, decrease renin
    • - block alpha--> decrease SVR, decrease afterload, preload.

    • SE- Hypotension, Bradycardia, Bronchospasm.
    • DO NOT USE IN DECOMPENSATED HEART FAILURE!
  67. Nesiritide
    • Vasodilator for CHF
    • recombinant BNP
    • -bind ANP, BNP receptors--> cGMP-->NO--> vasodilate, natriurisis!
    • USE- acutely decompensated CHF
    • -expensive!
    • SE- hypotension
  68. Nitroglycerin
    Isosorbide dinitrate
    • Nitrates, direct vasodilator
    • -dilate VEINS! --> decr preload--> decr MVO2
    • -prodrug--> free nitrite (need Cystein from Glutathione)--> NO--> inc cGMP
    • -decr EDV, BP,
    • -incrs HR, contractility (reflex)
    • -decr Ejection time

    • USE- ANGINA! , pulmonary edema
    • -decr infarct size, improve post-MI survival
    • -Nitroglycerin- sublingual (bc 1st pass), IV, patch
    • -Isosorbide- oral, extended release
    • -give with beta-blocker (prevent reflex)

    • SE- hypotension, reflex tachycardia (bad for MI!). flushing, headache (meningeal-a dilation), methemoglobinemia
    • - Tachyphylaxis! (acute tolerance-24hr)

    do NOT use with Sidenafil!!! (hypotensive crisis-->massive reflex tachycardia--> MVO2--> death in MI patients!!)
  69. What are the vasodilators working at NO directly?

    Tolerance?
    • Nitroprusside - arteriole + vein (CN-toxicity)
    • Hydralazine- arteriole (SLE)
    • Nitroglycerin- vein (tachyphylaxis)

    • -Patients taking daily maintenance nitrates need to have nitrate-fee period every day to avoid tolerance!!
    • -so skip a night time dose!!
  70. Calcium channel blockers for Angina?
    • all CCB can be used!
    • -Verapamil (heart)- constipation
    • -Diltiazem
    • -Nifedipine (BV-vasospastic prinzmetal)- gyngival hyperplasia
  71. Beta blockers for Angina?
    • -decr afterload!
    • -decr HR, contractility, BP, MVO2
    • -incr EDV

    • -Great for Stable angina!
    • -Shitty for Prinzmetal angina!- worsen vasospasm!
    • ex. Pindolol, Acebutolol- contraindicated in angina!!-partial agonists--> may incr MVO2

    ex. Carvedilol- beta+alpha-blocker- same efficacy as isosorbide in stable angina and decr. MI risk!!
  72. Theophylline
    • PDE inhibitor, Adenosine-R blocker
    • - incr cAMP in heart--> tachycardia
    • -incr cAMP in smooth muscle--> bronchodilate, vasodilate
    • - inhibit Adeno- R heart (Gi)--> incr cAMP

    USE- COPD, Asthma

    SE- narrow TI! tremor, agitation, arrhythmia, seizures
  73. Mannitol
    • Osmotic diuretic -increase tubular fluid osmolarity--> trap water in tubule--> increase urine volune, water loss!!
    • -think Glucose-->sorbitol--> diuresis in Diabetics!
    • -site- entire tubule,but most effect at PT

    • USE- acute narrow angle glaucoma attack
    • -decr ICP
    • -oligouria
    • -clear toxins- Rhabdomyolysis (statins!)- Mb toxic to tubules.
    • -shock

    • SE- acute hypovolemia (may incr reflex tachy, ADH, Aldosterone), pulm edema
    • - DO NOT USE IN CHF, Anuria!
  74. Acetazolamide
    • CA-inhibitor
    • NaHCO3 diuresis!
    • -decr H+ formation in PT cell-->decr Na/H antiport--> prevent reabsorption Na + HCO3---> diuresis!

    • USE- acute mountain sickness (Rx resp alkalosis + pulm edema)!
    • -metabolic alkalosis
    • -rhabdomyolysis-induced renal failure
    • -open angle glaucoma (block HCO3 form in eye, decr aqu humor)

    • SE- Hypokalemia + Acidosis!! (unique!)
    • -Hyperchloremia (b/c Na now reabsorbs with Cl-)
    • -renal stones (b/c alkalize urine!)
    • -sulfonamide hypersensitivity
    • -neuropathy, NH3 toxicity
  75. Loop diuretics- mechanism
    • 1. Block NKCC pump
    • --> decr Na, Cl, K reabsoprtion!
    • --> decr transport of K in tubule cell--> derc back diffusion--> decr + potential--> decr reabsorb Ca, Mg
    • decrease Na, Cl, K, Ca, Mg!!!!!!!

    2. Vasodilate! (incr PG!--> vasodilate afferent arteriole + others--> decr BP)
  76. Furosemide
    • Loop
    • - block NKCC--> decrease Na, Cl, K, Ca,Mg!!!!!!!
    • -eliminate + charge lumen in TAL
    • -Vasodilate by incr PGs--> decr BP

    • USE-Edema! (CHF, cirrhosis, nephroic syndrome, pulm edema)
    • -HTN!
    • -Hypercalcemia (b/c gets rid of Ca)
    • - Anion overdose

    • SE- sulfonamide hypersensitivity! (use Ethacrynic acid in sulfa-allergic pts!)
    • -Hypokalemia + Alkalosis (classic!-bc aldosterone + incr Na deliver/reabsorb at distal tubule)
    • -Hypocalcemia (opposite of TZDs)
    • -Hypomagnesemia
    • -Hyperuricemia! (weak acid drugs compete w/secretion pump in PT!)
    • -Ototoxicity- irreversible w/ ethacrynics!!
    • do NOT use with sulfa-allergic, gout patients!!

    • +Aminoglycosides enhance ototoxicity!
    • + Digoxin tocitiy enhances w/ hypokalemia!!
    • +Lithium clearnce decrease!
    • +NSAIDs cancle anti-HTN effect
  77. Ethacrynic Acid
    • Loop
    • - block NKCC--> decrease Na, Cl, K, Ca,Mg!!!!!!!
    • -eliminate + charge lumen in TAL
    • -Vasodilate by incr PGs--> decr BP

    • USE- Sulfa-allergy patients!!!
    • Edema! (CHF, cirrhosis, nephroic syndrome, pulm edema)
    • -HTN!
    • -Hypercalcemia (b/c gets rid of Ca)
    • - Anion overdose

    • SE-Hypokalemia + Alkalosis (classic!-bc aldosterone + incr Na deliver/reabsorb at distal tubule)
    • -Hypocalcemia (opposite of TZDs)
    • -Hypomagnesemia
    • -Hyperuricemia! (weak acid drugs compete w/secretion pump in PT!)
    • -Ototoxicity- irreversible w/ ethacrynics!!
    • -do NOT use w/ gout patients!!

    • +Aminoglycosides enhance ototoxicity!
    • + Digoxin tocitiy enhances w/ hypokalemia!!
    • +Lithium clearnce decrease!
    • +NSAIDs cancle anti-HTN
  78. Allergies to Sulfonamide containing drugs
    Sulfa- lipid soluble, enhance drug absorption, but binds proteins--> hapten-->hypersensitivity potential

    • cross allergy w:
    • CA inhibitors (acetazolamide)
    • All Loops!! except ethacrynic acid
    • Thiazides
    • Sulfa-antibiotics
    • Celecoxib
    • -anydrug with Sulfo- or Thio- in it!!!!
  79. hydrochlorothiazide
    • Thiazide diuretic (week bc= only 10% Na)
    • inhibit Na/Cl transporter in DCT--> NaCl Diuresis + increase Ca absorption
    • also block ATP-dependant K-channel (like Minoxidil)

    • USE- HTN, CHF
    • -kidney stones (decr Ca)
    • -Nephrogenic DM (combine free water loss with salt, induce Aldosterone)

    • SE- Sulfonamide hypersensitivity
    • Kypokalemia + alkalosis
    • Hypercalcemia, Hypeuricemia
    • Hyperglycemia + Hyperlipidemia (decr insulin release)

    • -increase Digoxin toxicity (hypokalemia)
    • -NOT good for DM!! (also b-blockers) use ACEI, ARBs!
  80. Indapamide, Metolamide
    • Thiazide diuretic (week bc= only 10% Na)
    • inhibit Na/Cl transporter in DCT--> NaCl Diuresis + increase Ca absorption
    • also block ATP-dependant K-channel (like Minoxidil)

    • USE- HTN, CHF
    • -kidney stones (decr Ca)
    • -Nephrogenic DM (combine free water loss with salt, induce Aldosterone)

    • SE- Sulfonamide hypersensitivity
    • Kypokalemia+alkalosis
    • Hypercalcemia,Hypeuricemia
    • Hyperglycemia (decr insulin release)
    • -increase Digoxin toxicity(hypokalemia)
    • -NOT good for DM!! (also b-blockers) use ACEI, ARBs!
  81. Spironolactone
    • K+ sparing diuretic
    • -block Aldosterone receptor at CD
    • -also block androgen receptor

    • USE- Hyperaldosteronic state,CHF
    • -Adjuct to K-wasting diuretics
    • -antiandrogenic uses (female hirsutism)

    • SE- Hyperkalemia, acidosis
    • -antiandrogen effects! (male gynecomastia) do NOT use in RENAL FAILURE or Rhabdomyolysis!! (can cause Hyperkalemia!)
  82. Eplerenone
    • K+ sparing diuretic
    • -block Aldosterone receptor at CD
    • -does NOT block androgen receptors like Spironolactone! (more selective)

    • USE- Hyperaldosteronic state,CHF
    • -Adjuct to K-wasting diuretics

    SE- Hyperkalemia + acidosis
  83. Triamterene
    • K+ sparing diuretic
    • -block ENAC at CD

    USE- adjuct to K+ wating diuretics

    SE-hyperkalemia + acidosis
  84. Amiloride
    • K+ sparing diuretic
    • -block ENAC at CD

    • USE- adjuct to K+ wating diuretics
    • -lithium-induced nephrogenic diabetes insipidus

    SE-hyperkalemia + acidosis
  85. lovastatin, pravastatin, simvastatin, atorvastatin, rosuvastatin
    • HMG-Coa-reductase inhibitor
    • (decr mevalonate->decr liver Xol, incr LDL-R, decr plasma LDL)
    • Block VLDL synthesis (decr TGs!)

    USE-combined hyperlipidemias!(decr Xol + TG)

    • SE- Rhabdomyolysis! (release Mb-->ATN), myalgia/myopathy (check CKMM), Hepatotoxicity (check liver enzymes!)
    • -DO NOT use with Genfibrozil (incr rhabdomyolysis! by decr statin clearance)
    • -Cyp inhibitors incr toxicity (acute alcohol, grapefruit juice..)
  86. Cholestyramine
    • Bile acid sequestrants (resin)
    • -complex w bile in gult-->decr bile salt circ-->incr syn bile, decr liver Xol-->incr LDLR-->decr blood LDL

    USE-pure high XOL (NOT high TG!)

    • SE- incre VLDL and TGs!!(b/c doesn't block VLDL syn like statins, incr precursors of LDL (VLDL, IDL)
    • -bad taste, malabsorption (steatorrhea, diarrhea), xol gallstones, decr absorption of lipid soluble drugs!(warfarin, thiazides, digoxin)
    • DO NOT use in high TG pts!!
  87. Colestipol
    • Bile acid sequestrants (resin)
    • -complex w bile in gult-->decr bile salt circ-->incr syn bile, decr liver Xol-->incr LDLR-->decr blood LDL

    USE-pure high XOL (NOT high TG!)

    • SE- incre VLDL and TGs!!(b/c doesn't block VLDL syn like statins, incr precursors of LDL (VLDL, IDL)
    • -bad taste, malabsorption (steatorrhea, diarrhea), Xol gallstones, decr absorption of lipid soluble drugs!(warfarin, thiazides, digoxin)
    • DO NOT use in high TG pts!!
  88. Niacin (vit B3) Nicotinic acid
    • VLDL synthesis blocker
    • -block lipolysis in adipose--> decr VLDL in liver,decrs LDL, incr HDL!

    USE- high XOL and high TG(?)

    • SE- flushing, pruritis, rash - PG mediated! (decr with Aspirin!)
    • Hyperglycemia (acanthosis nigricans), Hyperuricemia (worsens gout)hepatotoxicity
    • -do NOT use in DM, Gout pts!!
  89. Gemfibrozil
    • Fibrates!
    • activate Lipoprotein lipase-->decr VLDL, IDL, slight decr LDL,incrs HDL--> mostly decrs TG!!

    USE-hypertriglyceridemia!!!

    • SE-Myositis, hepatotoxicity (incr LFTs)
    • Xol gallstones
  90. clofibrate, bezafibrate, fenofibrate
    • Fibrates!
    • activate Lipoprotein lipase-->decr VLDL, IDL, slight decr LDL,incrs HDL--> mostly decrs TG!!

    USE-hypertriglyceridemia!!!

    SE-Myositis, hepatotoxicity (incr LFTs)Xol gallstones
  91. Ezetimibe
    • Prevent GI Xol absoprtion at SI!
    • --> decr LDL
    • (no effect on HDL or TG)

    USE- high Xol

    SE- not much.. GI distress
  92. Orlistat
    • Weight loss agent
    • -block Pancreatic lipase--> decr TG breakdown

    USE- weight loss (high TG)

    SE- steatorrhea, diarrhea, decr absorption of Vit ADEK!
  93. Summary of Antihyperlipidemic use
    High XOL--> Cholestyramine, Colestipol, Ezetimibe

    High TG-->Gemfibrozil, Clofibrate, Bezafibrate

    High XOL + TG--> Statins, Niacin, Ezetimibe
  94. Theophylline toxicity
    abdominal pain, vomiting, diarrhea, arrhythmias, seizures (major)
  95. beta blocker toxicity
    bradycardia, hypotension, cardiovascular collapse

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