CORTICOTROPHIN-RELEASING FACTOR RECEPTOR ANTAGONISTS

CORTICOTROPHIN-RELEASING FACTOR RECEPTOR ANTAGONISTS inhibit the actions of agents related to corticotrophin-releasing factor (CRF). Two subtypes of receptor, CRF, and CRF2, have recently been identified and cloned, and there is interest in these as therapeutic targets. See CORTICOTROPHIN-RELEASING FACTOR RECEPTOR AGONISTS. Some peptide antagonists that have some affinity for both CRF, and CRF2 receptors have been developed by making modifications of the CRF sequence, and these include; a-helicalCRE9-41,DPhe-CRF12-41 and the peptide astressm. Recently, some related non-peptides that act selectively at CRF, receptors have been developed including CP 154526, NB 127914 and antalarmin. A number of other agents are currently the subject of patent applications. Some possibly clinical applications of CRF receptor ligands are discussed in relation to evidence about the role of CFG; see corticotrophin-releasing factor receptor agonists. It might be hypothesized that corticotrophin-releasing factor antagonists could be used clinically to treat panic and generalized anxiety disorders, and possibly also to treat clinical depression and anorexia. Similarly, there is some evidence suggesting that stroke might be treatable with Read more […]

Herb-Drug Interactions: St John’s wort

Hypericum perforatum L. (Clusiaceae) Synonym(s) and related species Hypericum, Millepertuis. Hypericum noeanum Boiss., Hypericum veronense Schrank. Pharmacopoeias St John’s Wort (British Ph 2009, European Ph 2008, US Ph 32); St John’s Wort Dry Extract, Quantified (British Ph 2009, European Ph, 6th ed., 2008 and Supplements 6.1, 6.2, 6.3 and 6.4). Constituents The main groups of active constituents of St John’s wort are thought to be the anthraquinones, including hypericin, isohypericin, pseudohypericin, protohypericin, protopseudohypericin and cyclopseudohypericin, and the prenylated phloroglucinols, including hyperforin and adhyperforin. Flavonoids, which include kaempferol, quercetin, luteolin, hyperoside, isoquercitrin, quercitrin and rutin; biflavonoids, which include biapigenin and amentoflavone, and catechins are also present. Other polyphenolic constituents include caffeic and chlorogenic acids, and a volatile oil containing methyl-2-octane. Most St John’s wort products are standardised at least for their hypericin content (British Pharmacopoeia 2009), even though hyperforin is known to be a more relevant therapeutic constituent, and some preparations are now standardised for both (The United Read more […]

Herb-Drug Interactions: Kudzu

Pueraria montana (Lour.) Merr. (Fabaceae) Synonym(s) and related species Ge Gen. Pueraria hirsuta (Thunb.) C. Schneider, Pueraria lobata (Willd.) Ohwi, Pueraria lobata (Willd.) Ohwi var. thomsonii (Benth.) Maesen, Pueraria thunbergiana (Sieb. & Zucc.) Benth., Dolichos lobatus Willd. Other species used include Pueraria mirifica Airy Shaw & Suvatabandhu (Thai kudzu, Kwao Kreu Kao) and Pueraria phaseoloides (Roxb.) Benth. (Puero, Tropical kudzu). Constituents The major isoflavone constituent of the root of Pueraria lobata is puerarin, which is the 8-C-glucoside of daidzein, but there are many others, such as puerarin hydroxy- and methoxy- derivatives and their glycosides, daidzein and its O-glycoside daidzin, biochanin A, genistein and formononetin derivatives. Pterocarpans are also present, including medicarpin glycinol and tuberosin. The flowers contain the phytoestrogens kakkalide and tectoridin. Pueraria mirifica root contains similar constituents to Pueraria lobata, the major difference being lower amounts of daidzein. Much of the research carried out on kudzu has been on the effects of isolated puerarin. Use and indications Kudzu contains isoflavones and is used as a phytoestrogen for Read more […]

Herb-Drug Interactions: Guggul

Commiphora wightii (Am.) Bhandari (Burseraceae) Synonym(s) and related species Mukul myrrh. Commiphora mukul Engl., Balsamodendrum wightii. Constituents The resinous sap, harvested from the tree bark by tapping, is extracted to produce guggul. Gugulipid is the purified standardised extract of crude gum guggul, and contains the active guggulsterone components Z-guggulsterone and E-guggulsterone, with cembrenoids, myrrhanone and myrrhanol derivatives. Use and indications Guggul is used mainly in Ayurvedic medicine and has been traditionally used to treat hypertension, osteoporosis, epilepsy, ulcers, cancer, obesity and rheumatoid arthritis. It is now often used for hyperlipidaemia, but clinical studies have found conflicting results for its lipid-lowering effects. Pharmacokinetics An in vitro study reported that gugulipid extract and purified guggulsterones may induce the expression of the cytochrome P450 isoenzyme CYP3A4. However, the clinical significance of this is unclear and further study is needed. Interactions overview In healthy subjects, the absorption of diltiazem and propranolol was modestly reduced by gugulipid. If the mechanism is confirmed, guggul might interact with a wide range of other Read more […]

Herb-Drug Interactions: Ginger

Zingiber offidnale Roscoe (Zingiberaceae) Synonym(s) and related species Gan Jiang, Zingiber. Not to be confused with the wild gingers, which are Asarum canadense L. and Asarum europaeum L. Pharmacopoeias Ginger (British Ph 2009, European Ph 2008, US Ph 32); Ginger Capsules (US Ph 32); Ginger Tincture (US Ph 32); Powdered Ginger (The United States Ph 32). Constituents The constituents of ginger vary depending on whether fresh or dried forms are used. Generally, ginger rhizomes contain volatile oils of which zingiberene and bisabolene are major components: zingerone, zingiberol, zingiberenol, curcumene, camphene and linalool are minor components. The rhizomes also contain gingerols and their derivatives, gingerdiols, gingerdiones and dihydrogingerdiones. Sho-gaols are formed from gingerols during drying, and together these make up the pungent principles of ginger. Ginger extracts have been standardised to contain a minimum of 15mL/kg of essential oil with reference to the dried drug. Use and indications Ginger is thought to possess carminative, anti-emetic, anti-inflammatory, antispasmodic and antiplatelet properties. Both fresh and dried ginger are mainly used to settle the stomach, to alleviate Read more […]

Herb-Drug Interactions: Flaxseed

Linum usitatissimum L. (Linaceae) Synonym(s) and related species Flax, Linseed. Constituents The seeds contain a fixed oil, composed of glycerides of linoleic and linolenic acid. The seeds also contain: mucilage; the lignans secoisolariciresinol and its diglucoside; and the cyanogenetic glycosides linamarin and lotaustralin. Use and indications Flaxseed was formerly used as a demulcent and soothing emollient agent for bronchitis and coughs, and applied externally to burns. More recently, flaxseed oil has been used to lower blood-cholesterol levels, and flaxseed extract is being taken as a form of hormone replacement therapy due to its phytoestrogenic effects, thought to be due to the lignans (although note that the information available on phytoestrogenic lignans is limited). Pharmacokinetics Ingested lignans such as secoisolariciresinol have been shown to undergo bacterial hydrolysis and metabolism to produce the mammalian lignans enterolactone and enterodiol, which have oestrogenic effects. Interactions overview Flaxseed lignan supplementation appears to have no significant effect on blood-glucose levels in type 2 diabetic patients also taking oral antidiabetic drugs (not named). Limited evidence suggests Read more […]

Herb-Drug Interactions: Evening primrose oil

Oenothera biennis L. (Onagraceae) Synonym(s) and related species Common evening primrose, King’s cureall, Sun drop, Tree primrose. Oenothera lamarkiana, Onagra biennis (L.) Scop. Pharmacopoeias Evening primrose oil (British Ph 2009, European Ph, 6th ed., 2008 and Supplements 6.1, 6.2, 6.3 and 6.4). Constituents The oil from evening primrose seeds contains the essential fatty acids of the omega-6 series, linoleic acid (about 65 to 85%) and gamolenic acid (gamma-linolenic acid, about 7 to 14%). Other fatty acids include oleic acid, alpha-linolenic acid, palmitic acid and stearic acid. Use and indications Evening primrose oil is used as a food supplement to provide essential fatty acids. It is also used for atopic eczema and mastalgia; however, in the UK licences for two prescription products containing gamolenic acid derived from evening primrose oil were withdrawn in 2002, due to lack of evidence in support of efficacy. Other conditions for which it is used include rheumatoid arthritis, premenstrual syndrome, menopausal symptoms, chronic fatigue syndrome and attention deficit hyperactivity disorder. Evening primrose oil has also been used topically as a cream, for the relief of dry or inflamed skin. Read more […]

ANTIDOTES

ANTIDOTES are agents used to counteract the effects of toxic substances or overdose with drugs. They are used in a wide variety of circumstances and can work in many ways. First, where the poison works by stimulating, or over-stimulating, a distinct set of pharmacological receptors, treatment is normally straightforward since the use of an appropriate receptor antagonist can be used to reduce or completely block the effects of the poison. For example, naloxone is an opioid receptor ANTAGONIST and can be used as an antidote to an overdose by a wide range of a opioid receptor agonists, including the narcotic analgesics diamorphine (heroin), morphine, methadone and pethidine. It is quick-acting and effectively reverses the respiratory depression, coma or convulsions that result from such an overdose; also, it can be used at the end of operations to reverse respiratory depression caused by narcotic analgesics and in newborn babies. Second, poisoning by some toxic substances is effectively counteracted by an antidote that binds to the poison, rendering it relatively inert and facilitating its excretion. For example, a CHELATING AGENT can be used as an antidote to metal poisoning, where it has a high affinity for those Read more […]

ANTIINFLAMMATORY AGENTS

ANTIINFLAMMATORY AGENTS are drugs that are used to reduce inflammatory responses in the body. Although inflammation is essentially a normal defensive mechanism (a reaction to tissue injury, infection, inhalation of foreign proteins), the manifestations may be so serious and inappropriate or involve such discomfort, that treatment with antiinflammatory agents is required. Inflammatory conditions can be acute (as in insect stings) or chronic (chronic asthma, dermatitis and other skin conditions, rheumatoid conditions). A wide range of drugs may be used to treat one or other inflammatory condition, and potential toxicity in relation to the medical condition is an important determinant of choice. The NSAID ANALGESIC group has the widest antiinflammatory use, and their inhibitory antiinflammatory property is due to their cyclooxygenase activity (see CYCLOOXYGENASE INHIBITORS). Here the associated relief of pain is largely attributable to some degree of correction of the underlying inflammatory condition. Some of this group are relatively non-toxic and are available without prescription for use for relatively trivial complaints, e.g. aspirin and ibuprofen. (Paracetamol has insufficient antiinflammatory action to be useful Read more […]

ANALGESICS

ANALGESICS are drugs that relieve the sensation of pain. Because pain is a subjective experience, arising from many causes, there are many ways that drugs can be used to relieve it. However, the term analgesic is best restricted, from a pharmacological point of view, to two main classes of drugs. (1) Narcotic analgesics or opioid analgesics, typified by morphine, have powerful actions on the CNS, and act to alter the perception of pain. Because of the numerous possible side-effects, crucially dependence (habituation, ‘addiction’), this class is usually used under strict medical supervision and are only available on prescription or OTC in very low doses. (2) Non-narcotic analgesics (NSAIDs), typified by aspirin, which have no tendency to produce dependence, but are by no means free of side-effects. This class is referred to by many names, most commonly non-steroidal antiinflammatory drugs (NSAIDs). The latter term refers to the valuable antiinflammatory action of some members of the class. This class is used for a variety of purposes, such as treating mild aches and pains, for fever (see ANTIPYRETICS) and rheumatoid arthritis (at higher dosages), see ANTIINFLAMMATORY AGENTS. Apart from these two main classes, there Read more […]