Action: an organic nitrate that activates the cGMP pathway → incr cGMP → activates cGK-Iα → activates Ca-dependent K+ channel → hyperpolarizes membrane → Ca taken into SR, decr intracellular Ca → smooth muscle relaxation
Clinical use: ischemic heart disease

Problems: orthostatic hypotension, tachycardia, headache, tolerance, dizziness, flushing, syncope

Contraindications:

Proprietary names:

Action:
Clinical use: 

Problems:

Contraindications:

Proprietary names:

Action: Class IV antiarrhythmic; Ca channel blocker, vasodilation of peripheral, coronary, cerebral vessels; decrease HR, SA node, AV node, contractility.
Clinical use: SVT

Problems: cardiodepression (decr contractility), hypotension, AV block, periph edema, headache, constipation; possible reflex tachycardia

Contraindications: pts with CHF

Proprietary names:

See Diltiazem

Action: Class IV antiarrhythmic, Ca channel blocker, vasodilates coronary arteries well, dilates peripheral and coronary arteries; decr HR,decr SA/AV conduction, decr contractility. USE DEPENDANT.
Clinical use: vasodilation, SVT

Metabolism: hepatic, t1/2=4 hrs

Problems: Hypotension, periph edmea, AV block, cardiodepression; vascular relaxation and decr in BP may cause baroreflex tachycardia (smaller effect than other Ca channel blockers)

Contraindications: pts with CHF (decr contractility)

Proprietary names:

Action: Ca channel blocker, vasodilates peripheral and coronary vessels better than Verapamil, dilates cerebral vessels. Incr HR and contractility, no effect on SA and AV node.
Clinical use:

Problems: hypotension, headache, periph edema

Contraindications:

Proprietary names:

Action: cardioselective beta blocker. Decreases myocardial oxygen demand by decreasing HR and contractility.
Clinical use: HTN, angina, arrhythmia, ischemic heart dz, CHF

Problems: pharmacokinetic (t_1/2 = 3-4 hrs in most individuals)

Contraindications: not for pts who are "slow hydroxylators," due to 2xF and 1/2xCl (4x steady state concentration!)

Proprietary names: Lopressor, Toprol

Action: vasodilator, phosphodiesterase type 5 inhibitor (prolong the action of cGMP in vascular smooth muscle)
Clinical use: potentiate the physiological response to sexual arousal causing penile erection

Problems: low oral bioavailability, hepatic metabolism (CYP3A4), active metabolite, renal excretion <15%; flushing, dyspepsia, dose-related transient abnl vision

Contraindications: nitrates (may cause potentially fatal reductions of MAP in pts taking nitrates for angina), inhibition or induction of CYP3A4

Proprietary names: Viagra

note the last name "-afil" are all PDE5 inhibitors

• Ischemic heart disease
• Heart failure
• Hypertension
• Erectile dysfunction

EC50: The term half maximal effective concentration (EC₅₀) refers to the concentration of a drug which induces a response halfway between the baseline and maximum after some specified exposure time. It is commonly used as a measure of drug's potency.

ED50: The dosage that produces a desired effect in half the test population.

Action: conversion into NO activates guanylate cyclase and increases intracellular cGMP. cGK-Iα activates the KCa channel, which hyperpolarizes the cell g Ca channels close g intracellular Ca drops g vascular smooth muscle relaxes. End result is EDP is markedly reduced in LV g aortic pressure falls. Activity increases with dose.

Indications: for vasodilation

Problems: reflex tachycardia (give with β blockers), tolerance, orthostatic hypotension, headache, dizziness, flushing, syncope

Contraindications:

Trade name:

Action: Organic nitrate.

Sublingual: onset 2-4 min, duration 30-60 min

Oral: onset 10-20 min, duration 2-3 hr, first past effect

IV: immediate onset

Transdermal: slow onset, duration 10-24 hr, nocturnal angina

Aerosol: rapid onset, difficult to control

Half life of 1.5-4.5 min, metabolites are inactive.

Indications: for vasodilation

Problems: reflex tachycardia (give with β blockers), tolerance, orthostatic hypotension, headache, dizziness, flushing, syncope

Contraindications:

Trade name:

Action: Organic nitrate.

Sublingual: onset 2-4 min, duration 2-4 hrs

Oral: onset 10-20 min, duration 4-8 hrs
Half-life of 1.2 hrs, metabolites are active and have halflife 1.8-5 hrs.

Metabolite Isosorbide-5-monohydrate is more bioavailable, has 5 hr halflife.

Indications: for vasodilation

Problems: reflex tachycardia (give with β blockers), tolerance, orthostatic hypotension, headache, dizziness, flushing, syncope

Contraindications:

Trade name:

Tolerance: continuous or frequent exposure to organic nitrates may lead to the development of tolerance.

Avoidance: nitrate-free periods of at least 8 hours (eg overnight)

Mechanisms:

-          Decreased ability to convert nitrate to NO

-          Diminished release of NO due to depletion of endogenous sulfhydryl compounds

Changes in guanylate cyclase activation (upregulation of cGK-Iβ, which is less effective at activating Ca spark than cGK-Iα, which is downregulated)

Action: voltage gated calcium channel antagonists

Types:

-          I: Balanced myocardial, electrophys, and vascular effects

-          II: Vascular effects

-          III: “Markedly selective” vascular effects

Indications: improves oxygen delivery to ischemic myocardium by vasodilating coronary arteries; reduce myocardial oxygen consumption by reducing afterload, heart rate, and contractility

Smooth muscle cells are typically at -50mV, and cardiac myocytes are at -90mV. Ca channel antagonists have higher affinity (lower K_d by 10^-3) at the potential typical of SMC than at the potential of cardiac myocytes.

Action: class IA; fast Na+ channel blocker → slows conduction. Also blocks K+ channels → incr AP duration & effective refractory period; anti-cholinergic effects → INCR AV conduction velocity
Clinical use: antiarrhythmic 

Metabolism: hepatic

Problems: anti-muscarinic and alpha blockade, N&V, diarrhea, slightly depressed cardiac contractility, hypotension (due to alpha blockade), thrombocytopenia, hypersensitivity rxns, cinchonism, "quinidine syncope"

Contraindications: doubles plasma digoxin levels

Proprietary names:

Action: class IA; fast Na+ channel blocker → slows conduction. Also blocks K+ channels → incr AP duration & effective refractory period; anti-cholinergic effects → INCR AV conduction velocity
Clinical use: antiarrhythmic 

Metabolism: hepatic, renal, t1/2 = 3-4 hrs

Problems: anti-muscarinic (less than quinidine), N&V,  hypersensitivity rxns, lupus-like immune syndrome, proarrhythmia (torsades) caused by metabolite NAPA (has class III drug properties - blocks K+ channels)

Contraindications:

Proprietary names:

Action: class IB; fast Na+ channel blocker → slow conductance; effects at FAST HEART RATE (use dependant); decr AP duration and effective refractory period (contrast to IA drugs)
Clinical use: short-term management of life-threatening ventricular arrhythmias

Metabolism: rapid hepatic, t1/2=1.5 hr

Problems: must be given IV without epi for antiarrhythmic therapy; drowsiness, tremor, convulsion

Contraindications:

Proprietary names:

Action: class IC; fast Na+ channel blocker → slow conduction w/o effects on refractoriness + incr AP duration in ventricles (K+ channel block); effects at normal heart rates (not use dependant)
Clinical use:

Problems: antiarrhythmic

Contraindications: proarrhythmia after MI or if any structural abnl's in heart

Proprietary names:

Action: Class III; K+ channel blocker → prolong AP duration (refractory period).

• Class I properties: decreases Vmax of fast response APs
• Class II properties: some non-competitive alpha and beta block
• Class IV properties: decreases slope of phase 4 depol in SA node, and decreases AV conduction

Clinical use: life-threatening v-tach (resistant to other tx); SVT's (a-fib)

Metabolism: hepatic, t1/2 = 20-100 days, highly lipophilic (concentrates in tissues)

Problems: with long term therapy: potentially fatal pulmonary fibrosis, photosensitivity, corneal deposits, hypo/hyperthyroidism, may produce torsades

Contraindications:

Proprietary names:

Action: Class III; K+ channel blocker → prolongation of AP duration. Reduces heterogeneity of repolarization times by prolonging action potential duration more in normal tissue than in tissue damaged by ischemic insult (where AP duration is already increased). May cause transient incr in SA automaticity and in AV conduction by initial release of catecholamines. Then, it interferes with catecholamine storage in sympathetic nerve terminals, and prevents release of NE by nerve impulses.
Clinical use: emergency treatment of sustained v-fib

Problems: IV only, hypotension, rarely initial HTN and exacerbation of arrhythmia (from initial release of catecholamines)

Metabolism: none

Contraindications:

Proprietary names:

Action: a cardiac glycoside

1. blocks Na+/K+ ATPase in AV node → relative depol → slowed conduction & prolonged refractory period
2. depol baroreceptor nerve endings → sensitization → incr BR firing → decr sympathetic tone → incr parasymp tone → slow AV conduction

Clinical use: a-fib, CHF

Problems: narrow therapeutic index; DADs, complete heart block, ventricular arrhythmia, etc.

Contraindications:

Proprietary names:

Action: acts thru G-protein coupled adenosine receptors - "vagomimetic" - decr automaticity and inhibits sympathetic effects; slows AV conduction and inhibits DADs, usually causes transient asystole. Must be given by rapid IV bolus.
Clinical use: conversion of paroxysmal SVT to sinus rhythm

Metabolism: ultra short acting with t1/2=seconds

Problems:

Contraindications:

Proprietary names:

Effect of beta blockade:

1. Decrease rate of phase 4 depol in automatic cells (decr HR and ectopic automaticity)
2. Slow conduction thru AV node (blocks SNS enhancement of slow Ca channela activity) → enhances AV block
3. Reduce myocardial contractility and oxygen demand

Sympathetic activity may contribute to many forms of arrhythmia. Stimulation of beta receptors leads to incr cAMP in myocardial cells →  promotes phosphorylation of Ca channels and Ca influx. Blocking this action produces the above effects.

1. Decrease rate of phase 4 depol in automatic cells (decr HR and ectopic automaticity)
2. Slow conduction thru AV node (blocks SNS enhancement of slow Ca channela activity) → enhances AV block
3. Reduce myocardial contractility and oxygen demand

Potential to block Na+ channels at high concentrations

Use: SVT (decr ventricular rate by slowing AV conduction & blocking impulses in AV node), various atrial/ventricular arrhythmias, prevention of sudden cardiac death in post-MI pts

IV only for rapid control of ventricular rate in a-fib/flutter in emergent circumstances where short term control of ventricular rate with a short-acting agent is desireable

T1/2 = 10 minutes

Class I: block fast Na+ channels

Class II: block beta-adrenergic receptors

Class III: block K+ channels

Class IV: block Ca++ channels