Pathways

Buprenorphine, trade name subutex, suboxone, zubsolv and bunavail, is a partial agonist of mu-opioid receptors and a kappa-opioid receptor antagonist and is prescribed for opioid addiction to prevent cravings and symptoms of withdrawal. The binding of these receptors causes hyperpolarization and decreased neuronal excitability. Buprenorphine has a longer duration of action due to its slow dissociation from the receptor. This long rate of action causes a long clinical effect and decreases physical dependence. Buprenorphine can also prevent opioid use by inhibiting exogenous opioid effects. This elimination of the rush from the opioid can block the reinforcing behaviour of the drug and may treat opioid addiction. Buprenorphine is available on its own or in combination with naloxone.

Bupranolol is a non cardioselective beta blocker similar to propranolol. It can be administered orally, where it passes through hepatic portal circulation, and enters the bloodstream and travels to act on cardiomyocytes. In bronchial and vascular smooth muscle, bupranolol can compete with epinephrine for beta-2 adrenergic receptors. By competing with catecholamines for adrenergic receptors, it inhibits sympathetic stimulation of the heart. The reduction of neurotransmitters binding to beta receptor proteins in the heart inhibits adenylate cyclase type 1. Because adenylate cyclase type 1 typically activates cAMP synthesis, which in turn activates PKA production, which then activates SRC and nitric oxide synthase, its inhibition causes the inhibition of cAMP, PKA, SRC and nitric oxide synthase signaling. Following this chain of reactions, we see that the inhibition of nitric oxide synthase reduces nitric oxide production outside the cell which results in vasoconstriction. On a different end of this reaction chain, the inhibition of SRC in essence causes the activation of Caspase 3 and Caspase 9. This Caspase cascade leads to cell apoptosis. The net result of all these reactions is a decreased sympathetic effect on cardiac cells, causing the heart rate to slow and arterial blood pressure to lower; thus, bupranolol administration and binding reduces resting heart rate, cardiac output, afterload, blood pressure and orthostatic hypotension. By prolonging diastolic time, it can prevent re-infarction. One potentially less than desirable effect of non-selective beta blockers like bupranolol is the bronchoconstrictive effect exerted by antagonizing beta-2 adrenergic receptors in the lungs. Clinically, it is used to increase atrioventricular block to treat supraventricular dysrhythmias. Bupranolol also reduce sympathetic activity and is used to treat hypertension, angina, migraine headaches, and hypertrophic subaortic stenosis.

Bupranolol is a nonselective beta-blocker with structural similarity to propanolol. Both drugs do not have intrinsic sympathomimetic activity. It competes with catecholamines for binding beta-1 adrenergic receptors in the heart to inhibit sympathetic activation. This inhibition causes decreased heart rate, cardiac output, blood pressure

Bupivacaine exerts its local anaesthetic effect by blocking voltage-gated sodium channels in peripheral neurons. Bupivacaine 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 bupivacaine preferentially inhibits neurons that are actively firing.

Bupivacaine is a local anesthetic for surgery, most commonly for oral or obstetrical procedures. It is adminstered via intrathecal injection or directly to the wound site. Bupivacaine does this through blocking the generation of action potential through increasing the threshold for activation. This in turn slows the propagation of the nerve impulse prevents the depolarization by binding to the intracellular portion of the sodium channels and blocking the ions influx into the neurons. Bupivacaine can also potentially bind to prostaglandin E2 receptors, subtype EP1 that stops the production of prostaglandins, reduce fever, inflammation and hyperalgesia. It is metabolized by the liver via glucuronic acid into the metabolite of 2,6-pipecoloxylidine by cytochrome P450 3A4. It is excreted via urine mainly unchanged.

Metabolites of Bumetanide are predicted with biotransformer.

Bumetanide is a loop diuretic drug, administered orally or intravenously the treatment of edema associated with congestive heart failure, hepatic and renal disease including the nephrotic syndrome. It targets the nephrons of the kidney, mainly the ascending limb of the loop of henle. The basolateral membrane of the ascending loop of henle contains the Na+/K+ ATPase, Cl- channel and K+/Cl- co-transporter which are essential for the function for ion and water reabsorption. The Na+/K+ ATPase pumps Na+ from the cell into the peritubular fluid and K+ from the peritubular fluid into the cell. The K+/Cl- co-transporter moves K+ and Cl- from the cell into the peritubular fluid and the Cl- channel transports Cl- from the cell into the peritubular fluid. The apical membrane contains the Na+/K+/2Cl- co-transporter (NKCC2) and the K+ channel. The NCKCC2 is responsible for reabsorption Na+, K+ and Cl- from the lumen into the cells of the loop of henle. The K+ channel transports K+ from the cells back into the lumen. Bumetanide is transported from the capillaries into the cells of the loop of henle then transported from the cell into the lumen. Bumetanide binds to NKCC2 transporter and inhibits it, preventing Na+, K+ and Cl- reabsorption from the lumen. The concentration of these ions builds up in the lumen, decreasing the slope of the concentration gradient between the cells and the lumen. Since water reabsorption is linked to ion reabsorption, water reabsorption is also decreased, resulting in a greater volume of water being excreted in urine. This is relieves symptoms such as swelling/ edema in patients. Side effects such as peeing more than normal, feeling thirsty and dry mouth, losing a bit of weight (as your body loses water), headaches, feeling confused or dizzy, muscle cramps or weak muscles may occur when taking bumetanide.

Bumetanide, trade name Bumex, is a loop diuretic that increases urine production by inhibiting the reabsorption of water in the nephron. In the thick ascending limb of the loop of Henle, the sodium-potassium-chloride cotransporter (NKCC2) is competitively inhibited at the chloride binding site blocking sodium transport from the lumen to the interstitium. This results in the lumen becoming hypertonic and a decreased osmotic gradient thereby reducing the water reabsorption. In the nephron, the think ascending limb reabsorbs 25% of sodium and is a good target for diuretics.