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Propranolol
Systematic (IUPAC) name
1-(isopropylamino)-
3-(naphthalen-1-yloxy)propan-2-ol
Identifiers
CAS number 525-66-6
ATC code C07AA05
PubChem 4946
DrugBank APRD00194
Chemical data
Formula C16H21NO2 
Mol. mass 259. IUPAC Nomenclature is a system of naming Chemical compounds and of describing the science of Chemistry in general CAS registry numbers are unique numerical identifiers for Chemical compounds Polymers biological sequences mixtures and Alloys They are also referred to The Anatomical Therapeutic Chemical Classification System is used for the classification of drugs It is controlled by the WHO Collaborating Centre for Drug A section of the Anatomical Therapeutic Chemical Classification System. PubChem is a Database of chemical Molecules The system is maintained by the National Center for Biotechnology Information (NCBI a component The DrugBank database available at the University of Alberta is a unique Bioinformatics and Cheminformatics resource that combines detailed drug (i A chemical formula is a way of expressing information about the Atoms that constitute a particular Chemical compound, and how the relationship between those atoms changes Carbon (kɑɹbən is a Chemical element with the symbol C and its Atomic number is 6 Hydrogen (ˈhaɪdrədʒən is the Chemical element with Atomic number 1 Nitrogen (ˈnaɪtɹəʤɪn is a Chemical element that has the symbol N and Atomic number 7 and Atomic weight 14 Oxygen (from the Greek roots ὀξύς (oxys (acid literally "sharp" from the taste of acids and -γενής (-genēs (producer literally begetteris the The molecular mass (abbreviated m of a substance, more commonly referred to as molecular weight and abbreviated as MW, is the Mass of one 34 g/mol
Pharmacokinetic data
Bioavailability 26%
Metabolism hepatic (extensive)
Half life 4-5 hours
Excretion renal <1%
Therapeutic considerations
Pregnancy cat.

C(AU) C(US)
Legal status

Prescription Only (S4)(AU) POM(UK) ℞-only(US)
Routes oral, iv

Propranolol (INN) is a non-selective beta blocker mainly used in the treatment of hypertension. In Pharmacology, bioavailability is used to describe the fraction of an administered Dose of unchanged drug that reaches the Systemic circulation, one of Drug metabolism is the Metabolism of drugs, their Biochemical modification or degradation usually through specialized enzymatic systems The liver is a vital organ in the human body and is present in Vertebrates and some other animals The biological half-life of a substance is the time it takes for a substance (drug radioactive nuclide or other to lose half of its pharmacologic physiologic or radiologic activity Excretion is the process of eliminating waste products of Metabolism and other non-useful materials The kidneys are complicated organs that have numerous biological roles The pregnancy category of a pharmaceutical agent is an assessment of the risk of fetal injury due to the pharmaceutical if it is used as directed by the mother during For a topic outline on this subject see List of basic Australia topics. The United States of America —commonly referred to as the The regulation of therapeutic goods, that is drugs and therapeutic devices, varies by jurisdiction The Standard for the Uniform Scheduling of Drugs and Poisons, abbreviated SUSDP, is a document used in the regulation of drugs and poisons in Australia. For a topic outline on this subject see List of basic Australia topics. A prescription drug is a licensed medicine that is regulated by legislation to require a prescription before it can be obtained The United Kingdom of Great Britain and Northern Ireland, commonly known as the United Kingdom, the UK or Britain,is a Sovereign state located A prescription drug is a licensed medicine that is regulated by legislation to require a prescription before it can be obtained The United States of America —commonly referred to as the In Pharmacology and Toxicology, a route Intravenous therapy or IV therapy is the giving of Liquid substances directly into a Vein. An International Nonproprietary Name ( INN; also known as rINN, for recommended International Nonproprietary Name or pINN for proposed Beta blockers (sometimes written as β-blocker) are a class of drugs used for various indications but particularly for the management of Cardiac arrhythmias Hypertension, also referred to as high blood pressure, HTN or HPN, is a medical condition in which the Blood pressure is chronically elevated It was the first successful beta blocker developed. It is the only drug proven effective for the prophylaxis of migraines in children. Prophylaxis ( Greek "προφυλάσσω" to guard or prevent beforehand) is any medical or Public health procedure whose purpose Propranolol is available in generic form as propranolol hydrochloride, as well as an AstraZeneca product under the trade names Inderal, Inderal LA, Avlocardyl, Avlocardyl, Deralin, Dociton, Inderalici, InnoPran XL, Sumial (depending on marketplace and release rate). AstraZeneca PLC (,) is a large Anglo-Swedish Pharmaceutical company formed on 6 April 1999 by the remerger of Swedish Astra AB A trade name, also known as a trading name or a business name, is the name which a Business trades under for commercial purposes although its registered It is also marketed by Wyeth. Wyeth, formerly known as American Home Products (AHP is one of the largest pharmaceutical companies in the world

Contents

History and development

Scottish scientist and St. Scotland ( Gaelic: Alba) is a Country in northwest Europethat occupies the northern third of the island of Great Britain. Andrews graduate James W. Black successfully developed propranolol in the late 1950s. Sir James Whyte Black, OM, FRS, FRSE, FRCP (born 14 July 1924) is a Scottish doctor and pharmacologist The 1950s Decade refers to the years of 1950 to 1959 inclusive He was awarded the Nobel Prize in Medicine for this discovery in 1988. The Nobel Prize in Physiology or Medicine (Nobelpriset i fysiologi eller medicin is awarded once a year by the Swedish Karolinska Institute. Year 1988 ( MCMLXXXVIII) was a Leap year starting on Friday (link displays 1988 Gregorian calendar) Black discovered it quite accidentally after doing research with topical antifungal ointments on rats. A similar drug, liasinol had been used for years as antifungal, and he found that all rats with the AB8 recessive gene for vascular constriction died when exposed to liasinol. In spring of 1959, Black discovered that, after twice phosphoralating it (thus, developing propranolol ) the rats with the AB8 gene survived. He used the new drug as an antifungal for several months before discovering its use as a beta blocker.

Propranolol developed from the early β-adrenergic antagonists dichloroisoprenaline and pronethalol. Dichloroisoprenaline, also known as dichlorosisoproterenol or DCI, was the first compound developed that exhibited &beta- Adrenergic receptor antagonist The key structural modification, which was carried through to essentially all subsequent beta blockers, was the insertion of an oxymethylene bridge into the arylethanolamine structure of pronethalol thus greatly increasing the potency of the compound. This also apparently eliminated the carcinogenicity found with pronethalol in animal models. The term carcinogen refers to any substance Radionuclide or radiation that is an agent directly involved in the promotion of Cancer or in the fatation of its propagation

Pharmacology

Main article: Beta blocker

Propranolol is a non-selective beta blocker, that is, it blocks the action of epinephrine on both β1- and β2-adrenergic receptors. Beta blockers (sometimes written as β-blocker) are a class of drugs used for various indications but particularly for the management of Cardiac arrhythmias Beta blockers (sometimes written as β-blocker) are a class of drugs used for various indications but particularly for the management of Cardiac arrhythmias The adrenergic receptors (or adrenoceptors) are a class of G protein-coupled receptors that are targets of the Catecholamines Adrenergic receptors It has little intrinsic sympathomimetic activity (ISA) but has strong membrane stabilizing activity (only at high blood concentrations, eg overdosage). Only L-propranolol is a powerful adrenoceptor antagonist, whereas D-propranolol is not. The adrenergic receptors (or adrenoceptors) are a class of G protein-coupled receptors that are targets of the Catecholamines Adrenergic receptors However, both have local anesthetic effect. A local anesthetic is a drug that causes reversible Local anesthesia and a loss of Nociception.

Pharmacokinetics

Propranolol is rapidly and completely absorbed, with peak plasma levels achieved approximately 1–3 hours after ingestion. Co-administration with food appears to enhance bioavailability. Despite complete absorption, propranolol has a variable bioavailability due to extensive first-pass metabolism. In Pharmacology, bioavailability is used to describe the fraction of an administered Dose of unchanged drug that reaches the Systemic circulation, one of The first-pass effect (also known as first-pass metabolism or presystemic metabolism) is a phenomenon of Drug metabolism whereby the Concentration Hepatic impairment will therefore increase its bioavailability. The liver is a vital organ in the human body and is present in Vertebrates and some other animals The main metabolite 4-hydroxypropranolol, with a longer half-life (5. Half-Life (computer-game page here It's already listed in the disambiguation page 2–7. 5 hours) than the parent compound (3–4 hours), is also pharmacologically active.

Propranolol is a highly lipophilic drug achieving high concentrations in the brain. Lipophilicity, fat-liking, refers to the ability of a Chemical compound to dissolve in fats oils lipids and non-polar solvents such as Hexane or 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 10–100 ng/mL.

Toxic levels are associated with plasma concentrations above 2000 ng/ml

Clinical use

An 80mg capsule of Propranolol.
An 80mg capsule of Propranolol.
Main article: Beta blocker

Indications

Propranolol is indicated for the management of various conditions including:[1]

While once first-line treatment for hypertension, the role for beta-blockers was downgraded in June 2006 in the United Kingdom to fourth-line as they perform less well than other drugs, particularly in the elderly, and evidence is increasing that the most frequently used beta-blockers at usual doses carry an unacceptable risk of provoking type 2 diabetes. Beta blockers (sometimes written as β-blocker) are a class of drugs used for various indications but particularly for the management of Cardiac arrhythmias Hypertension, also referred to as high blood pressure, HTN or HPN, is a medical condition in which the Blood pressure is chronically elevated Angina pectoris, commonly known as angina, is severe Chest pain due to Ischemia (a lack of blood and hence Oxygen supply of the heart Dysrhythmia redirects here For the American band see Dysrhythmia (band. Myocardial infarction ( MI or AMI for acute myocardial infarction) also known as a heart attack, occurs when the blood supply Anxiety is a physiological and psychological state characterized by Cognitive, Somatic, Emotional and Behavioral components Hyperthyroidism is the term for overactive tissue within the Thyroid gland resulting in overproduction and thus an excess of circulating free thyroid hormones Thyroxine Lithium in pharmacology refers to use of the Lithium Ion, Li+ as a drug Essential tremor ( ET) is a progressive Neurological disease whose most recognizable feature is a tremor of the Arms that is apparent during voluntary movements Migraine is a neurological Syndrome characterized by altered bodily experiences painful headaches and nausea Tetralogy of Fallot (TOF is a Congenital heart defect which is classically understood to involve four anatomical abnormalities (although only three of them are always present A phaeochromocytoma ( pheochromocytoma in the US is a Neuroendocrine tumor of the medulla of the Adrenal glands (originating in the Chromaffin Alpha blockers (or adrenergic alpha-antagonists) are agents that act as antagonists of alpha adrenergic receptors Classification They can be divided Post traumatic stress disorder It is a severe and ongoing emotional reaction to Hypertension, also referred to as high blood pressure, HTN or HPN, is a medical condition in which the Blood pressure is chronically elevated Year 2006 ( MMVI) was a Common year starting on Sunday of the Gregorian calendar. The United Kingdom of Great Britain and Northern Ireland, commonly known as the United Kingdom, the UK or Britain,is a Sovereign state located Diabetes mellitus type 2 or Type 2 Diabetes (formerly called non - Insulin -dependent Diabetes mellitus (NIDDM or adult-onset diabetes is a metabolic [2]

Propranolol is also used to lower portal vein pressure in portal hypertension and prevent oesophageal variceal bleeding. The hepatic portal vein (often portal vein for short is a Portal vein in the human body that drains blood from the Digestive system and its associated In Medicine, portal hypertension is Hypertension (high blood pressure in the Portal vein and its branches In Medicine ( Gastroenterology) esophageal varices are extremely dilated sub-mucosal Veins in the Esophagus.

Propranolol is often used by musicians and other performers to prevent stage fright. Stage fright or performance anxiety refers to an Anxiety, Fear or persistent Phobia related to Performance in front of

Propranolol is currently being investigated as a potential treatment for post-traumatic stress disorder. Post traumatic stress disorder It is a severe and ongoing emotional reaction to [3][4][5]

Precautions/contraindications

Propranolol should be used with caution in patients with:[1]

Propranolol is contraindicated in patients with:[1]

Adverse effects

Adverse drug reactions (ADRs) associated with propranolol therapy are similar to other lipophilic beta blockers (see beta blocker). Peripheral vascular disease (PVD also known as peripheral artery disease (PAD or peripheral artery occlusive disease (PAOD is a collator for all Diseases Raynaud's phenomenon (reɪˈnoʊz (rāy-NŌZ in Medicine, is a vasospastic disorder causing discoloration of the Fingers Toes and occasionally A phaeochromocytoma ( pheochromocytoma in the US is a Neuroendocrine tumor of the medulla of the Adrenal glands (originating in the Chromaffin Hypertension, also referred to as high blood pressure, HTN or HPN, is a medical condition in which the Blood pressure is chronically elevated Alpha blockers (or adrenergic alpha-antagonists) are agents that act as antagonists of alpha adrenergic receptors Classification They can be divided Myasthenia gravis (literally "serious muscle-weakness" from Greek μύς "muscle" "weakness" and Latin gravis Bradycardia, as applied to adult medicine is defined as a resting Heart rate of under 60 beats per minute though it is seldom symptomatic until the rate drops below 50 beat/min Asthma is a chronic Condition involving the Respiratory system in which the airways occasionally constrict become inflamed, and are Chronic obstructive pulmonary disease ( COPD) is a Disease of the lungs in which the Airways become narrowed Bradycardia, as applied to adult medicine is defined as a resting Heart rate of under 60 beats per minute though it is seldom symptomatic until the rate drops below 50 beat/min Sick sinus syndrome, also called Sinus node dysfunction, is a group of abnormal heart rhythms ( Arrhythmias presumably caused by a malfunction of the Sinus An atrioventricular block (or AV block) is a type of Heart block involving impairment of the conduction between the atria and ventricles of the heart In Physiology and Medicine, hypotension refers to an abnormally low Blood pressure. Heart failure is a Cardiac condition that occurs when a problem with the structure or function of the Heart impairs its ability to supply An adverse drug reaction (abbreviated ADR) or adverse drug event (abbreviated ADE) is an expression that describes the unwanted negative consequences Beta blockers (sometimes written as β-blocker) are a class of drugs used for various indications but particularly for the management of Cardiac arrhythmias

Pregnancy and lactation

Propranolol, like other beta blockers, is classified as Pregnancy category C in the United States and ADEC Category C in Australia. The pregnancy category of a pharmaceutical agent is an assessment of the risk of fetal injury due to the pharmaceutical if it is used as directed by the mother during The Australian Drug Evaluation Committee or ADEC, is a Committee that provides independent scientific advice to the Australian Government regarding therapeutic Beta-blocking agents in general reduce perfusion of the placenta which may lead to adverse outcomes for the neonate, including pulmonary or cardiac complications, or premature birth. lung is the essential Respiration organ in air-breathing Animals including most Tetrapods a few Fish and a few Snails The most primitive The heart is a muscular organ in all Vertebrates responsible for pumping Blood through the Blood vessels by repeated rhythmic The newborn may experience additional adverse effects such as hypoglycemia and bradycardia. Hypoglycemia or hypoglycaemia is the medical term for a pathologic state produced by a lower than normal level of Glucose ( sugar) in the blood Bradycardia, as applied to adult medicine is defined as a resting Heart rate of under 60 beats per minute though it is seldom symptomatic until the rate drops below 50 beat/min

Most beta-blocking agents appear in the milk of lactating women. Lactation describes the secretion of Milk from the Mammary glands the process of providing that milk to the young and the period of time that a Mother This is especially the case for a lipophilic drug like propranolol. Lipophilicity, fat-liking, refers to the ability of a Chemical compound to dissolve in fats oils lipids and non-polar solvents such as Hexane or Breastfeeding is not recommended in patients receiving propranolol therapy.

Interactions

Beta blockers, 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:[1]

Dosage

The usual maintenance dose ranges for oral propranolol therapy vary by indication:

Intravenous (IV) propranolol may be used in acute arrhythmia or thyrotoxic crisis. Intravenous therapy or IV therapy is the giving of Liquid substances directly into a Vein. Dysrhythmia redirects here For the American band see Dysrhythmia (band. Hyperthyroidism is the term for overactive tissue within the Thyroid gland resulting in overproduction and thus an excess of circulating free thyroid hormones Thyroxine [6]

Research into propranolol and epilepsy

Alexander Massey in the UK, is currently researching the theoretical use of propranolol as an anticonvulsant, and also the benefits of use against myoclonic and partial seizure brain activity is being explored.

Edited Version of an article resleased by A. Massey some months ago. . .

The drug propranolol has, over the past few years, has been subject to many tests attempting to establish a use in treatment of post traumatic stress disorder. However one area that I believe has gone untested is the use in epilepsy. For those unfamiliar with the chemical make up of the drug, propranolol contains C16H21NO2. This key construction binds with beta receptors in the heart, slowing beat rate, but more importantly, propranolol blocks the β1- and β2-adrenergic receptors for epinephrine (formerly known as Adrenaline). We will return to the effects of epinephrine in a moment. - Propranolol also acts as Topical anaesthesia, or a local antithetic effect. This property, combined with adequate perfusion to the brain tissues, provides the basic ‘numbing’ of the overactive/oversensitive synapses that antiepileptic drugs achieve. But to fully understand the benefits and possible problems the propranolol could hold for epileptics we have to take a deeper look at one the key ‘ingredients’ – hydrochloride. The hydrochloric salt aids and is part of the freezer cells that prevent neurotransmitters in the brain from becoming too active, and likewise hydrochloride prevents the receptors from receiving the action potentials If the message has already been sent and received by the brain once before. An example of freezer cells in use would be to place your hand on the desk. You feel the initial impact but then your hand is pretty much sense free. Without freezer cells you would repeatedly feel your hand hitting the desk. We now look at the similarity to photo-sensitive epilepsy. A repeating pattern can trigger a seizure because the synapses do not slow the rate of neurotransmissions caused by a pattern, a high contrast white, or strobe light information in the brain. A use in epilepsy would therefore have to be considered BUT a problem exists. A moment ago we read the propranolol blocks epinephrine receptors. This could be a big problem in terms of seizure prevention. According to the research of Drs. V. A. Karlov and M. A. Gleiser at the Department of Nervous Diseases of the Medical Faculty, Moscow Medical Stomatological Institute: epinephrine repolarization is important to prevent low blood sugars and other related effects that cause seizures. Propranolol as we discussed, prevents epinephrine binding to sites in the brain and also so some extent the release of epinephrine. It would seem then that the drug’s positives and negatives would both cancel themselves out in terms of theoretical effects. But early tests reveal that this is not the case. Very simple UNOFFICIAL early tests cave been carried out and patients suffering with partial seizures with some secondary generalization have shown an improvement (shortening) in the frequency and length of the partial seizures, the secondary generalization rate also appeared to drop. It would seem that the combined effect of calming of the heart and presence of hydrochloride in the brain has beneficial effects for epileptics. . . .


Research into propranolol, memory, conscience, and PTSD

Recent research suggests that propranolol has effects in the brain with regard to emotional processing. Some experiments suggest that emotional memories are recalled and restored every time they are relived, and that propranolol inhibits the restorage of bad memories and so can be used as a treatment for post-traumatic stress disorder (PTSD). Post traumatic stress disorder It is a severe and ongoing emotional reaction to There is also evidence that it inhibits the storing of emotional memories in the first place, so that propranolol administered before action in battle can prevent post traumatic stress. In a report in 2001, the President's Council on Bioethics warned that such use as a 'memory-blunter' could endanger society, because "blocking emotional memories risks falsifying our perception and understanding of the world. It risks making shameful acts seem less shameful, or terrible acts less terrible, than they really are"[1]. This has implications for the many patients on beta blockers in society who are not warned that one side effect is an alteration in personality that might only be noticed by those around them[2].

Research into role against malaria

Propranolol along with a number of other membrane-acting drugs have been investigated for possible effects on P. falciparum and so the treatment of malaria. Plasmodium falciparum is a Protozoan Parasite, one of the species of Plasmodium that cause Malaria in humans Malaria is a vector -borne Infectious disease caused by Protozoan Parasites It is widespread in tropical and subtropical regions including In vitro positive effects until recently had not been matched by useful in vivo anti-parasite activity against P. vinckei,[7] or P. yoelii nigeriensis. Plasmodium achiotense is a parasite of the genus Plasmodium subgenus Vinckeia. [8] However a single study from 2006 has suggested that propranolol may reduce the dosages required for existing drugs to be effective against P. falciparum by 5- to 10-fold, suggesting a role for combination therapies. [9]

Media

References

  1. ^ a b c d Rossi S, editor. Australian Medicines Handbook 2006. The Australian Medicines Handbook or AMH is a medical reference text commonly used in practice by health professionals (particularly General practitioners Adelaide: Australian Medicines Handbook; 2006.
  2. ^ Sheetal Ladva (28/06/2006). NICE and BHS launch updated hypertension guideline. National Institute for Health and Clinical Excellence. Retrieved on 2006-09-30. Year 2006 ( MMVI) was a Common year starting on Sunday of the Gregorian calendar. Events 1399 - Henry IV is proclaimed King of England. 1744 - France and Spain defeat the
  3. ^ Doctors test a drug to ease traumatic memories - Mental Health - MSNBC.com. Retrieved on 2007-06-30. Year 2007 ( MMVII) was a Common year starting on Monday of the Gregorian calendar in the 21st century. Events 350 - Roman usurper Nepotianus, of the Constantinian dynasty, is defeated and killed by troops of the Usurper
  4. ^ Brunet A, Orr SP, Tremblay J, Robertson K, Nader K, Pitman RK (2007). "Effect of post-retrieval propranolol on psychophysiologic responding during subsequent script-driven traumatic imagery in post-traumatic stress disorder": 503. doi:10.1016/j.jpsychires.2007.05.006. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 17588604.  
  5. ^ Effect of post-retrieval propranolol on psychophysiologic responding during subsequent script-driven traumatic imagery in post-traumatic stress disorder.
  6. ^ *Joint Formulary Committee. British National Formulary, 47th edition. The British National Formulary (BNF contains a wide spectrum of information on prescribing and Pharmacology, among others indications Side effects and London: British Medical Association and Royal Pharmaceutical Society of Great Britain; 2004.
  7. ^ Ohnishi S, Sadanaga K, Katsuoka M, Weidanz W (1990). "Effects of membrane acting-drugs on plasmodium species and sickle cell erythrocytes". Mol Cell Biochem 91 (1-2): 159-65. PMID 2695829.  
  8. ^ Singh N, Puri S (2000). "Interaction between chloroquine and diverse pharmacological agents in chloroquine resistant Plasmodium yoelii nigeriensis". Acta Trop 77 (2): 185-93. doi:10.1016/S0001-706X(00)00133-9. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 11080509.  
  9. ^ Murphy S, Harrison T, Hamm H, Lomasney J, Mohandas N, Haldar K (Dec 2006). "Erythrocyte G protein as a novel target for malarial chemotherapy". PLoS Med 3 (12): e528. doi:10.1371/journal.pmed.0030528. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 17194200.  

External links

Dictionary

propranolol

-noun

  1. A non-selective beta blocker mainly used in the treatment of hypertension.
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