-
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
-
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.
-
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
-
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)
-
Drugs that cause SLE !
- Procainamide
- Hydralazine
- Isoniazid
+ anti- histone!!
-
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
-
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.
-
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 depressUNIQUE- can take oral! so give to outpatients. b/c Lidocaine is IV only.
-
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.
-
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
-
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!
-
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!
-
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!
-
Hyperkalemia causes increased toxicity for
ALL class I drugs!!!
-
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
-
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!
-
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
-
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!
-
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!
-
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
-
Class III antiarrhythmics
- K-channel blockers (delayed rectifier)
- -prolong repolarization--> increase APD, ERP, QT
DRUGS: Amiodarone, Sotalol, Ibutilide, Bretylium, Dofetilide
-
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
-
-
Who prolongs QT?
Class Ia and Class III!
QT elongate--> torsades. but, NOT amiodarone!
-
Drugs that cause Pulmonary Fibrosis!
-
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
-
Ibutilide
- Class III antiarrhythmic
- K-channel blocker (delayed rectifier)
- -prolong repolarization--> increase APD, ERP, QT
USE- when all other antiarrhythmics fail.
SE- torsades (QT)
-
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
-
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!
-
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!
-
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!
-
Mg+
- Unclassified antiarrhythmic
- -acts to compete Ca--> decrease it's effects
- USE- torsades!!, digoxin toxicity (like lidocaine)
- -premature labor
- -seizure
-
Drugs that cause Torsades
anything that keeps cells depol longer!
K-channel blockers (class IA, III) - Anti-muscarinic
- Anti-psychotics
- Anti-histamines
- TCAs
-
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
-
K+
- Unclassified antiarrhythmic
- depress ectopic pacemakers in hypokalemia
- ex. digoxin toxicity
Hypekalemia--> depolarize cells!!
BOTH HYPERkalemia and HYPOkalemia are arrhythmogenic!!!
-
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!
-
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!!
-
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!)
-
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.
-
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
-
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!
-
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
-
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!
-
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)
-
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
-
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!
-
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!
-
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.
-
Captopril
- ACE inhibitorblock 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!!
-
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!
-
Aliskiren
Block Renin
USE- HTN
- SE-hypotension, hyperkalemia, acute renal failure in renal a stenosis.
- do NOT use in bilateral renal a. stenosis, pregnancy!
-
What antihypertensive will you use?
HTN + Angina
- beta blockers
- calcium channel blockers
-
What antihypertensive will you use?
HTN + Diabetes
(improve blood supply to the hyalin-sclerosing glomeruli)
-
What antihypertensive will you use?
HTN + Heart failure
- ACE-inhibitor
- ARBs
- beta blockers
-
What antihypertensive will you use?
HTN + Post-MI
Beta blockers
-
What antihypertensive will you use?
HTN + BPH
Alpha-1 blockers
-
What antihypertensive will you use?
HTN + hyperlipidemia
- Alpha-1 blocker
- Calcium channel blocker
- ACEI, ARB
NOT beta-blockers! (hypoglycemia, hyperlipidemia)
-
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!)
-
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)
-
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!!
-
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!
-
How do I treat Digoxin toxicity?
- slowly normalize K+ , Mg+2
- Lidocaine (class Ib)-Rx arrythmia in digitalized (depol) area
- anti-digoxin Fab fragment
-
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)
-
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
-
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
-
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!
-
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!
-
Nesiritide
- Vasodilator for CHF
- recombinant BNP -bind ANP, BNP receptors--> cGMP-->NO--> vasodilate, natriurisis!
- USE- acutely decompensated CHF
- -expensive!
- SE- hypotension
-
-
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!!)
-
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!!
-
Calcium channel blockers for Angina?
- all CCB can be used!
- -Verapamil (heart)- constipation
- -Diltiazem
- -Nifedipine (BV-vasospastic prinzmetal)- gyngival hyperplasia
-
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!!
-
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
-
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!
-
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
-
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)
-
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
-
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
-
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!!!!
-
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!
-
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!
-
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!)
-
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
-
Triamterene
- K+ sparing diuretic
- -block ENAC at CD
USE- adjuct to K+ wating diuretics
SE- hyperkalemia + acidosis
-
Amiloride
- K+ sparing diuretic
- -block ENAC at CD
- USE- adjuct to K+ wating diuretics
- -lithium-induced nephrogenic diabetes insipidus
SE- hyperkalemia + acidosis
-
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..)
-
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!!
-
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!!
-
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!!
-
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
-
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
-
Ezetimibe
- Prevent GI Xol absoprtion at SI!
- --> decr LDL
- (no effect on HDL or TG)
USE- high Xol
SE- not much.. GI distress
-
Orlistat
- Weight loss agent
- -block Pancreatic lipase--> decr TG breakdown
USE- weight loss (high TG)
SE- steatorrhea, diarrhea, decr absorption of Vit ADEK!
-
Summary of Antihyperlipidemic use
High XOL--> Cholestyramine, Colestipol, Ezetimibe
High TG-->Gemfibrozil, Clofibrate, Bezafibrate
High XOL + TG--> Statins, Niacin, Ezetimibe
-
Theophylline toxicity
abdominal pain, vomiting, diarrhea, arrhythmias, seizures (major)
-
beta blocker toxicity
bradycardia, hypotension, cardiovascular collapse
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