Pathways

This pathway illustrates the procainamide targets involved in antiarrhythmic therapy. Contractile activity of cardiac myocytes is elicited via action potentials mediated by a number of ion channel proteins. During rest, or diastole, cells maintain a negative membrane potential; i.e. the inside the cell is negatively charged relative to the cells’ extracellular environment. Membrane ion pumps, such as the sodium-potassium ATPase and sodium-calcium exchanger (NCX), maintain low intracellular sodium (5 mM) and calcium (100 nM) concentrations and high intracellular potassium (140 mM) concentrations. Conversely, extracellular concentrations of sodium (140 mM) and calcium (1.8 mM) are relatively high and extracellular potassium concentrations are low (5 mM). At rest, the cardiac cell membrane is impermeable to sodium and calcium ions, but is permeable to potassium ions via inward rectifier potassium channels (I-K1), which allow an outward flow of potassium ions down their concentration gradient. The positive outflow of potassium ions aids in maintaining the negative intracellular electric potential. When cells reach a critical threshold potential, voltage-gated sodium channels (I-Na) open and the rapid influx of positive sodium ions into the cell occurs as the ions travel down their electrochemical gradient. This is known as the rapid depolarization or upstroke phase of the cardiac action potential. Sodium channels then close and rapidly activated potassium channels such as the voltage-gated transient outward delayed rectifying potassium channel (I-Kto) and the voltage-gated ultra rapid delayed rectifying potassium channel (I-Kur) open. These events make up the early repolarization phase during which potassium ions flow out of the cell and sodium ions are continually pumped out. During the next phase, known as the plateau phase, calcium L-type channels (I-CaL) open and the resulting influx of calcium ions roughly balances the outward flow of potassium channels. During the final repolarization phase, the voltage-gated rapid (I-Kr) and slow (I-Ks) delayed rectifying potassium channels open increasing the outflow of potassium ions and repolarizing the cell. The extra sodium and calcium ions that entered the cell during the action potential are extruded via sodium-potassium ATPases and NCX and intra- and extracellular ion concentrations are restored. In specialized pacemaker cells, gradual depolarization to threshold occurs via funny channels (I-f). Procainamide, an analogue of the local anesthetic procaine, is a Class 1A antiarrhythmic drug. It has similar effects to quinidine, but lacks the antimuscarinic and antiadrenergic effects of quinidine. Like other Class 1A drugs, procainamide blocks open sodium channels leading to an increased threshold of excitability. Voltage-gated sodium channels (I-Na) are responsible for the rapid depolarization seen during cardiac contractile cell action potentials. I-Na block results in delayed excitability of the cells. Procainamide also prolongs action potential duration, likely by slowing the final repolarization phase via potassium channel blocking. This drug may be administered intravenously to treat supraventricular and ventricular arrhythmias. It is better tolerated intravenously than quinidine. Oral administration is poorly tolerated long term.

Procainamide is a class 1A antidysrythmIc as well as an anesthetic that is used to treat ventricular dysrhythmias, tachycardia and atrial fibrillation. Procainamide mainly inhibits sodium channels protein type 5 subunit alpha but also inhibits the potassium voltage gated channel subfamily H member 2. The main antidysrythmIc effect is mediated through the sodium channel blockage though. Phenytoin slows the rate of rise in the pacemaker potential and shortens the plateau phase of atrial and ventricular myocytes as well as purkinje fibre cells as they have 'fast' action potential. This converts a one way block into a two block effectively stopping the circus rhythm irregularity. Procainamide works through use-dependent blockage meaning that it preferentially binds to the inactivate state of the sodium channel. The more active the channel the more chances procainamide can bind to the channel and block it. Procainamide can be administered through either oral or intravenous routes with both having a relatively short half-life of 2.5 to 4.5 hours. Some side effects of using procainamide may include cardiac toxicity, bradycardia, hypotension, drug-induced lupus erythematosus-like syndrome, and blood dyscrasias.

Procainamide is a class 1A antidysrythmIc as well as an anesthetic that is used to treat ventricular dysrhythmias, tachycardia and atrial fibrillation. Procainamide mainly inhibits sodium channels protein type 5 subunit alpha but also inhibits the potassium voltage gated channel subfamily H member 2. The main antidysrythmIc effect is mediated through the sodium channel blockage though. Phenytoin slows the rate of rise in the pacemaker potential and shortens the plateau phase of atrial and ventricular myocytes as well as purkinje fibre cells as they have 'fast' action potential. This converts a one way block into a two block effectively stopping the circus rhythm irregularity. Procainamide works through use-dependent blockage meaning that it preferentially binds to the inactivate state of the sodium channel. The more active the channel the more chances procainamide can bind to the channel and block it. Procainamide can be administered through either oral or intravenous routes with both having a relatively short half-life of 2.5 to 4.5 hours

Procaine is an anesthetic used mainly for peripheral and spinal nerve block, it is an ester with slow onset and short duration of action, used mainly for oral surgery. Procaine has the additional effect of constricting blood vessels to reduce bleeding. It is metabolized in the plasma by pseudocholinesterase by the process of hydrolysis into para-aminobenzoic acid (PABA) when is excreted through the process of diuresis. It's mechanism of action in mainly by inhibiting sodium flux through voltage gated sodium channels, due to this an action potential cannot be conducted. It binds to the receptor site in the cytoplasmic portion of the sodium channel, it also antagonizes N-methyl-D-aspartate (NMDA), nicotinic acetylcholine and serotonin receptors.

Procaine exerts its local anaesthetic effect by blocking voltage-gated sodium channels in peripheral neurons. Procaine diffuses across the neuronal plasma membrane in its uncharged base form. Once inside the cytoplasm, it is protonated and this protonated form enters and blocks the pore of the voltage-gated sodium channel from the cytoplasmic side. For this to happen, the sodium channel must first become active so that so that gating mechanism is in the open state. Therefore procaine preferentially inhibits neurons that are actively firing.

Procaine benzylpenicillin is a drug that is not metabolized by the human body as determined by current research and biotransformer analysis. Procaine benzylpenicillin passes through the liver and is then excreted from the body mainly through the kidney.

Procaine merethoxylline is a drug that is not metabolized by the human body as determined by current research and biotransformer analysis. Procaine merethoxylline passes through the liver and is then excreted from the body mainly through the kidney.