Пропранолол: Бета-блокатор для лечения и потенциала в психотерапии.

Beta blocker drug

Propranolol, sold under the brand name Inderal among others, is a medication of the beta blocker class. as well to prevent migraine headaches, and to prevent further heart problems in those with angina or previous heart attacks. It can be taken orally (by mouth) or by intravenous injection (injection into a vein). Common side effects include nausea, abdominal pain, and constipation. Its use during breastfeeding is probably safe. It is a non selective beta blocker which works by blocking β adrenergic receptors. It is on the World Health Organization's List of Essential Medicines. Propranolol is available as a generic medication.

Propranolol is being investigated as a potential treatment for PTSD. Propranolol works to inhibit the actions of norepinephrine (noradrenaline), a neurotransmitter that enhances memory consolidation. In one small study, individuals given propranolol immediately after trauma experienced fewer stress related symptoms and lower rates of PTSD than respective control groups who did not receive the drug. Due to the fact that memories and their emotional content are reconsolidated in the hours after they are recalled/re experienced, propranolol can also diminish the emotional impact of already formed memories; for this reason, it is also being studied in the treatment of specific phobias, such as arachnophobia, dental fear, and social phobia. Ethical and legal questions have been raised surrounding the use of propranolol based medications for use as a "memory damper", including: altering memory recalled evidence during an investigation, modifying behavioral response to past (albeit traumatic) experiences, the regulation of these drugs, and others. However, Hall and Carter have argued that many such objections are "based on wildly exaggerated and unrealistic scenarios that ignore the limited action of propranolol in affecting memory, underplay the debilitating impact that PTSD has on those who suffer from it, and fail to acknowledge the extent to which drugs like alcohol are already used for this purpose".

Propranolol, like other beta blockers, is classified as pregnancy category C in the United States and ADEC category C in Australia. β blocking agents in general reduce perfusion of the placenta, which may lead to adverse outcomes for the neonate, including lung or heart complications, or premature birth. The newborn may experience additional adverse effects such as low blood sugar and a slower than normal heart rate. Most β blocking agents appear in the milk of lactating women. However, propranolol is highly bound to proteins in the bloodstream and is distributed into breast milk at very low levels. These low levels are not expected to pose any risk to the breastfeeding infant, and the American Academy of Pediatrics considers propranolol therapy "generally compatible with breastfeeding".

In overdose propranolol is associated with seizures. Cardiac arrest may occur in propranolol overdose due to sudden ventricular arrhythmias, or cardiogenic shock which may ultimately culminate in bradycardic PEA.

Since beta blockers are known to relax the cardiac muscle and to constrict the smooth muscle, beta adrenergic antagonists, including propranolol, have an additive effect with other drugs which decrease blood pressure, or which decrease cardiac contractility or conductivity. Clinically significant interactions particularly occur with:

+ Propranolol Site Ki (nM) Species Ref 5 HT1A 55–272 Human 5 HT1B 56–85 Rat 5 HT1D 4,070 Pig 5 HT2A 4,280 Human 5 HT2B 457–513 (+ ((+) propranolol))166–316 (– ((–) propranolol)) Human 5 HT2C 61,700 (+ ((+) propranolol)) 5,010 (– ((–) propranolol))736–2,457 HumanHumanRodent α1 ND (No data) ND (No data) ND (No data) α2 1,297–2,789 Rat β1 0.02–2.69 Human β2 0.01–0.61 Human D1 >10,000 Human 3,700 Rat 5,000 Rat 29,000 (IC50 (Half maximal inhibitory concentration)) Rat Values are Ki (nM), unless otherwise noted. The smaller the value, the more strongly the drug binds to the site. Propranolol is classified as a competitive non cardioselective sympatholytic beta blocker that crosses the blood–brain barrier. It is lipid soluble and also has sodium channel blocking effects. Propranolol is a non selective β adrenergic receptor antagonist, or beta blocker; that is, it blocks the action of epinephrine (adrenaline) and norepinephrine (noradrenaline) at both β1 and β2 adrenergic receptors. It has little intrinsic sympathomimetic activity, but has strong membrane stabilizing activity (only at high blood concentrations, e. g. overdose). Propranolol is able to cross the blood–brain barrier and exert effects in the central nervous system in addition to its peripheral activity.

Propranolol is a non selective beta receptor antagonist. Despite complete absorption, propranolol has a variable bioavailability due to extensive first pass metabolism. Hepatic impairment therefore increases its bioavailability. The main metabolite 4 hydroxypropranolol, with a longer half life (5.2–7.5 hours) than the parent compound (3–4 hours), is also pharmacologically active. Most of the metabolites are excreted in the urine. Propranolol is a highly lipophilic drug achieving high concentrations in the brain. The duration of action of a single oral dose is longer than the half life and may be up to 12 hours, if the single dose is high enough (e. g., 80 mg). Effective plasma concentrations are between 10 and 100 mg/L. Toxic levels are associated with plasma concentrations above 2000 mg/L.

Scottish scientist James W. Black developed propranolol in the 1960s. It was the first beta blocker effectively used in the treatment of coronary artery disease and hypertension. In 1988, Black was awarded the Nobel Prize in Medicine for this discovery. Propranolol was inspired by the early β adrenergic antagonists dichloroisoprenaline and pronethalol. The key difference, which was carried through to essentially all subsequent beta blockers, was the inclusion of an oxymethylene group ( O CH2 ) between the aryl and ethanolamine moieties of pronethalol, greatly increasing the potency of the compound. This also apparently eliminated the carcinogenicity found with pronethalol in animal models. Newer, more cardio selective beta blockers (such as bisoprolol, nebivolol, carvedilol, or metoprolol) are now used preferentially in the treatment of hypertension. For about 10–16% of performers, their degree of stage fright is considered pathological. Propranolol is used by musicians, actors, and public speakers for its ability to treat anxiety symptoms activated by the sympathetic nervous system. It has also been used as a performance enhancing drug in sports where high accuracy is required, including archery, shooting, golf, and snooker.

Propranolol was first marketed under the brand name Inderal, manufactured by ICI Pharmaceuticals (now AstraZeneca), in 1965. "Inderal" is a quasi anagram of "Alderlin", the trade name of pronethalol (which propranolol replaced); both names are an homage to Alderley Park, the ICI headquarters where the drugs were first developed. Propranolol is also marketed under brand names Avlocardyl, Deralin, Dociton, Inderalici, InnoPran XL, Indoblok, Sumial, Anaprilin, and Bedranol SR (Sandoz). In India it is marketed under brand names such as Ciplar and Ciplar LA by Cipla. Hemangeol, a 4.28 mg/mL solution of propranolol, is indicated for the treatment of proliferating infantile hemangioma.