Depolymerizes microtubules.

IV or Oral

Tx acute gout attack, recurrence of gouty arthritis (not other types of arthritis) and Familial Mediterranean Fever

SE - GI disturbance, blood dyscrasias

COX inhibitor

NSAID, analgesic, antipyretic (inhbits the release of PG and inflammatory cytokines), inhibits leukocyte motility

Tx: acute gout attacks

*Must give with an antacid (prevent peptic ulcers)

Dosing: 50 mg 3x/day

SE: GI (nausea, vomiting, ulcers), severe frontal HA, hematopoietic disorders, and Indomethacin antagonizes furosemide and HCTZ (pay attn to HTN meds the pt is on when perscribing).

Structurally similar to uric acid.

A competitive/suicide inhibitor of xanthine oxidase (binds active site). Metabolized to oxypurinol (non-competitive inhibitor of XO)

↓ plasma levels and ↓ urinary levels of UA;

↑ precursors of UA (xanthine & hypoxanthine);

Helps dissolve UA crystals & prevent UA kidney stones.

Tx: Primary Gout (↑ UA due to enzyme abnormalities) and Secondary gout (due to hematologic disorders like multiple myeloma or chemo)

SE: ↑ acute gout flares, hypersensitivity rxns (dermatitis)

CI: liver failure, renal failure,

Drug Interactions:

Antibiotics (Ampicillin and related abx) and 6-mercaptopurine (chemo drug, must ↓ 6-mercap dose when on allopurinol bc 6-mercap is metabolized by XO).

Mkt as Uloric

Structurally unrelated to Uric Acid (unlike allopurinol)

Inhibitor of oxidized & reduced forms of xanthine oxidase.

↓ uric acid levels.

More potent than allopurinol with less SE.

Tx: Gout, second line (pt who don't tolorate allopurinol); useful in renal insufficiency, in place of allopurinol (which is CI in renal failure pt).

SE: transaminase elevation (mild liver damage)

Inhibits transport of organic anions across epithelia (blocks the Brush Border Transporter in the PCT) blocking UA reabsorption.

↑ UA excretion (Uricosuric); ↑ dissolution of UA crystals.

Tx: Hyperuricemia due to poor renal UA secretion (kidney is not screting enough UA daily, <1g/day)

Pt must maintain high urine volume (remain hydrated) and renal function must be normal to take this drug*

SE: Salicylates (asprin) inhibit the uricosuric actions of probenecid.

A bio-uricolytic: recombinant, PEGylated (↑ half life) analog of urate oxidase;

Urate oxidase is an enzyme humans lack that degrades UA to, easily excreted (more soluble) form: Allantoin.

Pegloticase ↓ serum UA AND ↓ urinary UA

 IV Only

Tx: Severe gout and when all other meds have failed (2nd/3rd line), dissolution of trophi, ↓ kidney stones (if pt remain well hydrated).

SE: Gout flares due to rapid ↓ in UA levels (tx w/ colchicine, NSAIDs prophylactically), antibodies can develop against PEG moiety.

Non-specific: Propranolol, Pindolol, Naldolol,

Cardioselctive (β₁): Timolol, metoprolol, Atenolol, Esmolol, Acebutolol

Mixed (nonspecific β+α) : Labetolol

Nitroglycerine: sublingual, short acting

Causes venodilation (↓ preload),

coronary vasodilation (↓ afterload), ↓/reverses coronary vasospasm (tx variant angina), slight ↓ BP, slight ↑ HR,

↓ pulmonary vascular resistance

SE - hypotension (arterial vasodilation), reflex tachy, ↓ coronary perfusion, HA, rash.

CI - with Sildenifil (Viagra), profoundly potentiates its effects. Dangerous interaction.

Nitroglycerine: slow onset, medium duration of action (4-6 hrs)

Causes venodilation (↓ preload),

coronary vasodilation (tx ischemia, vasospasm),

slight ↓ BP, slight ↑ HR,

↓ pulmonary vascular resistance

SE - hypotension (arterial vasodil), reflex tachy, ↓ coronary perfusion, headache, rash.

CI- with Sildenifil (Viagra)

Nitroglycerine: Medium onset and duration of action (4-6 hrs) 

Causes venodilation (↓ preload),

coronary vasodilation (tx ischemia, vasospasm),

slight ↓ BP, slight ↑ HR,

↓ pulmonary vascular resistance

SE - hypotension (arterial vasodil), reflex tachy, dec coronary perfusion, headache, rash

CI- (potentiation) with Sildenifil (Viagra)

Nitroglycerine: medium onset, long duration (8-12 hrs)

Causes venodilation (↓ preload),

coronary vasodilation (tx ischemia, vasospasm),

slight ↓ BP, slight ↑ HR,

↓ pulmonary vascular resistance

SE - hypotension (arterial vasodil), reflex tachy, dec coronary perfusion, headache, rash

CI- Interacts (potentiation) with Sildenifil (Viagra)

L-type Calcium Channel Blocker (CCB); dihydropyridine (DHP):selective for vascular SM, not cardiac;

Short Acting

↓ O₂ demand of the heart by ↓ afterload*

Tx HTN (use w/ diuretic), angina, valvular insufficency

SE - Peripheral edema (precapillary arteriolar vasodilation), hypoT=reflex tachycardia (always use w a βB), HA, GI irritation, constipation.

Coronary Steal, a paradoxical worsening of angina DHP CCB.

*Beta blockers are better for angina* DHP CCB are used in pt unable to tolorate a BB or as an add-on*

L-type CCB; DHP: selective for vascular SM, not cardiac; short acting

↓ O₂ demand of the heart by ↓ afterload*

Tx HTN (use w/ diuretic), angina, valvular insufficency

SE - Peripheral edema (precapillary arteriolar vasodilation), hypoT=reflex tachycardia (always use w a βB), HA, GI irritation, constipation.

Coronary Steal, a paradoxical worsening of angina DHP CCB.

*Beta blockers are better for angina* DHP CCB are used in pt unable to tolorate a BB or as an add-on*

L-type CCB; DHP

↓ O₂ demand of the heart by ↓ afterload*

Tx HTN (use w/ diuretic), angina, valvular insufficency

SE - Peripheral edema, hypoT=reflex tachycardia (always use w a βB), HA, GI irritation, constipation.

Coronary Steal, a paradoxical worsening of angina w use of DHP CCB.

*Beta blockers are better for angina* DHP CCB are used in pt unable to tolorate a BB or as an add-on*

L-type CCB; DHP

↓ O₂ demand of the heart by ↓ afterload*

Tx HTN (use w/ diuretic), angina, valvular insufficency

SE - Peripheral edema (precapillary arteriolar vasodilation), hypoT=reflex tachycardia (always use w a βB), HA, GI irritation, constipation.

Coronary Steal, a paradoxical worsening of angina with use of DHP CCB.

*Beta blockers are better for angina* DHP CCB are used in pt unable to tolorate a BB or as an add-on*

L-type Calcium Channel Blocker; dihydropyridine;

long 1/2 life

↓ O₂ demand of the heart by ↓ afterload*

Tx HTN (use with diuretic), angina, arterial vasodilation,

Ok to use in pts with CHF, no neg inotropy;

selective for vascular SM, not cardiac.

SE - peripheral edema, reflex tachy (use w βB), hypotension, constipation

Class IV AA; non-DHP CCB; phenylalkylamine

Works at slow conduction tissues: SA, AVN

 Arterial vasodiltior, - ionotrope, - chronotrope, ↓ contractility, ↓ AV conduction

(↓ HR, ↑ diastole=↑ coronary perfusion)

Reverses vasospasm (varient angina)

Tx: HTN w/angina (exertional, vasospastic), Afib, Aflutter, reentry arrhythmias, PSVT (↓ contractility/AV conduction);

Asthma, COPD and DM=OK!

 Use in pts with normal LV fxn who can't tolerate BBs

SE - Peripheral edema, reflex tachy, hypoT, constipation, depression of SA/AV node+myocardial depression, nausea, HA.

CI: With BB (cardiac depression, asystole) and in pt with history of MI/CHF (causes ↑ mortality in these pt), CI with other CYP metabolized drugs*

Class IV AA, non-DHP CCB; benzothiazepine, intermediate between phenyl and DHPs

Tx angina (or HTN w angina)

(arterial vasodilator, - ionotrope, - chronotrope), Afib, Aflutter, reentry arrhythmias, PSVT.

Use in pts with normal LV function, but can't tolerate BBs

Ltd. reflex tachycardia (better at this than Verapamil but Verapamil has ↑ Ionotropic/Chronotropic effects)

SE - depression of SA/AV nodes, myocardial depression (↓ contractility), peripheral edema, hypoT, rashes, nausea, headache, bradycardia, CHF

CI- pt on BB and pt with CHF andwith other CYP metabolized drugs*

Metabolic Modulator

↑ glucose oxidation/efficiency of O₂ use in heart

Does not effect HR/BP and does not relieve acute anginal attacks.

Tx:Chronic stable angina (w/ amlodapine, BB, nitrates);for pts refractory to revascularization (4th, 5th-line tx)

OK in pregnancy (Class C)

SE - Dizziness, syncope, HA, nausea, constapation, asthenia (weakness).

CI- w/ CYP3A4 inhibitors (nonDHP CCBs, some abx, grapefruit juice),

 Preexisting long QT or use of class 1A/III AAs, or Digoxin, use of TCA.

Liver or renal impairment.

Class 1A - (intermed. dissociation rate) antiarrhythmic;

 Orphan Drug* (rarely used in modern practice)

↓ membrane responsiveness by binding to Na channels (also has action as an alpha-blocker and a vagolytic)

↓ conduction velocity, ↓ effective refractory period

Tx atrial and ventricular arrhythmias

SE - hypoT Torsades, syncope, diarrhea, autoimmune thrombocytopenia

CI- Pt with A-fib (causes paradoxical acceleration of AV nodal conduction due to vagolytic activity)

Class 1A prototype- intermed. dissociation rate (2 sec);

↓ membrane responsiveness by binding to Na channels O and C states and preventing reversion to R, has some K+ blocking properties (see QT prologation below),

↓ conduction velocity, ↑ effective refractory period;

IV only

Tx-Short-term, acute control of atrial and ventricular arrhythmias (ex: post-op A-fib)

SE - High prevalence of SE incl (+)FANA, drug induced lupus, GI intolerance, bone marrow aplasia, QT prolongation, Torsades.

Watch dosing in slow acetylators*

Class 1A- intermed. dissociation rate;

Decreases membrane responsiveness by binding to Na channels, dec conduction velocity, dec effective refractory period

Tx atrial and ventricular arrhythmias (autonomic anticholinergic effects) and urinary retention

SE - Torsades

Class 1B prototype - rapid dissociation rate (< 1 sec);

↓ membrane responsivity by binding to Na channels, ↓ conduction velocity, ↓ ERP

Short half-life, extensive first pass metabolism, req loading IV bolus or 2.

Tx - Ventricular arrhythmias, short-term suppression of VPBs, V tach; suppression of automaticity, interruption of ventricular reentry.

Specifically able to ↓ membrane responsivity in ischemic and partially depolarized tissues=esp good at preventing V-fib*

SE - CNS, agitation, confusion, seizures

Often missed, these symptoms=those of CCU Psychosis

Elimination is by hepatic biotransformation which is altered in CHF pt who are prone to lidocaine toxicity.

CI- as MI prophylaxis, shows ↑ mortality

Class 1B - rapid dissociation rate;

↓ membrane responsiveness by binding to Na channels, ↓ conduction velocity, ↓ effective refractory period

 Orally-effective analog of Lidocaine

Tx- Vent arrhythmias, suppression of VPBs, V tach; suppresses automaticity, interrupts ventricular reentry;

SE - CNS, agitation, confusion, seizures, GI distress- (limiting factor to the use of this drug)

Note that in general the use of class IB agents is ↓ in favor of using class III agents

Class 1C prototype - SLOW dissociation rate (>10 sec);

Prolongs QRS; ↓ membrane responsiveness by binding to Na channels with high affinity, ↓ conduction velocity, ↓ automaticity, ↑ ERP in atria, vent, AVN

Tx: supraventricular arrhythmias, WPW, A fib, A flutter;

SE - pro-arrhythmic effect; contraindicated in pts with structural heart disease (incl. necrotic infarcts) - inc mortality post-MI;

Class 1C - SLOW dissocaition rate;

↓ membrane responsiveness by binding to Na channels, has some B-blocker activity, ↓ conduction velocity, ↑ effective refractory period

Tx supraventricular arrhythmias, WPW, A fib, A flutter;

SE - Pro-arrhythmic effect (strictly CI in pt w/ structural heart disease, incl. necrotic infarcts),

↑ mortality post-MI

Beta-blockers, know them

• ↓ automaticity related to catecholamine acvitity and ischemia (effective anti-anginals).
• ↓ AVN conduction velocity.
• ↓ atrial and ventricular arrhythmias post-MI and ↑ survival in these pt.
• Interrupts reentry in the AV node to halt PVST
• ↓ AV nodal conuction in supraventricular arrhythmias.
• Prevents EAD and Toursades in pt with prolonged QT intervals.
• Blocks the symptoms mediated by hyperadrenergic states (chest pain, arrhythmias etc...)
• Tx HTN, angina, acute and prophylactic MI, CHF (off label for arrhythmias).
• IV or PO

Class III - K+ channel blocker;

also blocks Na (class I), Ca (IV), and BB (class II);

Interacts with TH (thyroid) receptors; prolongs AP, ↑ effective refractory period*; inhibits abnormal automaticity, ↑ fibrillation threshold, prevents cell-cell coupling (key in preventing fibrillation).

Tx: Vtach, Vfib, A-fib, IV for cardiac rescuscitation, PO for chronic atrial, vent, AVN arrhythmias (Most effective drug at preventing Afib and Vent tachycardia).

Effective: See prolonged PR, QRS and QT intervals + bradycardia (unique EKG)

PO or IV, slow elimination (req loading dose)

SE - pulmonary fibrosis, hypo- hyper-thyroid, blindness, hepatitis, corneal microdeposits, photosensitivity dermatitis(grey-blue skin), muscle weakness

(Torsades is rare!)

CI- Metabolized by/inhibits CYP3A4 (CI with other drugs that use or block 3A4).

Class III - K channel blocker (D and L isomers, prolongs AP); non-selective beta-blocker (L-isomer only, 1/3 the potency of propanolol)

Tx - Atrial, Vent, AVN reentrant arrhythmias incl V-tach

CI - long QT, COPD/Asthma, CHF, AV block, sinus bradycardia, as MI prophylaxis (↑ mortality), excreted in kidney, adjust dosing for renal failure pt.

SE - Torsades

Class III prototype - K channel blocker;

Prolong repolarization therefore ↑ effective refractory period; interrupts reentry, 

↑ fibrillation threshold (↓ fib's)

Tx: IV for acute atrial arrhythmias (Afib, Aflutter)

SE - Torsades

Class III - K channel blocker;

Prolong repolarization therefore ↑ effective refractory period and ↑ duration of the AP

Has significant pro-arrhythmic SE and is rarely used.

Class III - K channel blocker;

inhibits NE release from presynaptic neurons

Tx - IV for emergency Vfib or Vtach

SE - orthostatic Hypotension

AA (no class)

Terminates acute PSVT by blocking the AV node;

short half-life, IV only

Tx: PVST*

SE - tight chest, flushing, bronchospasm, transient asystole, and recurrence of PSVT (*Must follow with another antiarrhythmic to prevent this).

Contraindications - methylxanthines (caffeine), Dypyridamole (potentiation, is an anticoag that causes vasodilation when used chronically),

WPW

AA (no class), Digitalis glycoside;

↑ intracell [Ca] by blocking the Na/K-ATPase, ↑ intracellular Na, ↑ activity Na/Ca exchanger;

↑ Ca = ↑ contractility;

AA - vagal nerve activity, ↓ SA automaticity, ↓ AVN conduction

Arrhythmogenic - direct effect due to Na/K ATPase activity (source of most SE).

Paradoxical effect, ↑ normal automaticity; ↓ in AV conduction velocity (↑ PR interval);

SE: ↑ automaticity causing DAD leading to premature atrial and vent contractions and v tach.

CI: interactions with diuretics, warfarin, in WPW pt.

Anginal Rebound

If the angina in the pt is unstable interruption of the dose can cause vasospasm which can worsen angina or result in MI.

DO: blunt/↓ HR, ↓ contractility, ↓ afterload (CNS effects)

Tx: Unstable angina (with nitrates, asprin, and heparin) Exertional angina (↓ HR and contractility) Very good*

MI; acute and prophylaxis:↓ chest pain/angina, ↓ ST elevation, ↓ cardiac enzymes, ↓ ventricular ectopy/fibrillation, ↓ reinfarction and ischemic episodes, ↓ mortality!

BB do NOT: ↓ preload, or prevent coronary vasospasm.

CI: Sinus bradycardia, SA/AV block, decompensated CHF, asthma (bronchospasm), DM (hypoglycemia), or with non-DHP CCB.

Do not withdraw BB abruptly in an angina/MI pt = Severe reflex tachycardia.

BB+Nitrates: ↓ LVEDP, LV volume, dilates coronary arteries. Tx angina (unstable and exertional).

BB+DHP-CCB: prevents coronary vasospasm, ↓ systemic vascular resistance. Tx angina (vasospastic and unstable)

Procanamide (Class IA antiarrhythmic)

Is metabolized by the liver: Acetylated so it can be excreted by the kidneys.

Half of thepopulation are slow acetylators and these individuals have a higher incidence of +FANA and other SE of this drug.

Also, in renal failure pt who are also poor acetylators, the metabolites of this drug accumulate in the body.

Distinguish structural from non-structural heart disease.

Why is this significant in tx arrhythmias?

Structural Heart Dz: Coronary Dz w/ ischemia, LV dysfunction, CHF, sustained ventricular tachycardia.

Non-Structural Heart Dz: Supraventricular arrhythmias incl atrial flutter, A-fib, and SVT.

Important because Class IC agents (Flecainide, Propfenone) are strictly CI in pt with structural heart dz but ok to use in those with non-structural heart dz*

An important SE of Amniodarone (Class III AA) use.

Helpful to do a baseline CXR to detect, esp if pt has preexisting pulm dz (higher incidence in this group)

2 types of toxicity:

Interstitial pneumonitis is slow onset with intersitial shadows on CXR.

Acute Respiratory Distress Syndrome (ARDS) is rapid onset and CXR shows alveolar shadows.

Presents with dyspnea, a non-productive cough, pleuritic chest pain, weight loss and crepitations*

CXR shows bilateral diffuse changes + ↓ pulmonary fxn.

Stop the drug if this happens.

If you must continue the drug ↓ dosage bc risk is dose-related.