Category: Topics/Drug Classes (page 6 of 6)

Cromoglycate and Amiodarone

The surprising connection between cromoglycate and amiodarone

Cromoglycate is a mast cell stabiliser administered by inhalation as a preventer in the prophylactic control of asthma. It is also used for prophylactic control of allergic rhinitis and allergic conjunctivitis. Amiodarone is a  class III antiarrhythmic agent, which prolongs repolarization of the cardiac action potential thus increasing the cardiac action potential duration.

Pharmacologically there is no obvious connection between cromoglycate and amiodarone. However, both drugs were first synthesised as derivatives of khellin the active ingredient obtained from plant extracts of khella (Ammi visnaga).

Low-dose aspirin plus glycine for anti-platelet drug therapy

Why do some low-dose aspirin formulations intended for use as anti-platelet medications contain glycine?

Aspirin has a potent anti-platelet action because it is an irreversible inhibitor of cyclooxygenase (COX). COX-1 is required for synthesis of the prothrombotic factor, thromboxane A2 (TXA2), in platelets. Platelets, being fragments of megakaryocytes, do not have a nucleus and therefore cannot synthesise more COX when it is irreversibly inhibited by aspirin. Thus,  to recover from irreversible inhibition of COX-1 in the platelets, your body has to make new platelets. The average lifespan of a platelet is 8 to 9 days, so the anti-platelet effect aspirin is potent and long-lasting. However, in the stomach, inhibition of COX-1 prevents the production of protective prostaglandins and results in increased risk of gastrointestinal disturbance and peptic ulcers.

The combination of aspirin with glycine is reported to improve gastrointestinal tolerance to aspirin for anti-platelet drug therapy (1).  Glycine is also itself reported to have an anti-platelet effect (2).  The evidence to date for the efficacy of glycine both in improving gastrointestinal tolerance of aspirin and in having anti-platelet actions is limited. However, as glycine is a common dietary amino acid, there is little concern over the risk-to-benefit ratio of including glycine in aspirin formulations for use in anti-platelet drug therapy.

References:
(1) Kusche W, Paxinos R, Haselmann J, Schwantes U, Breddin HK. Acetylsalicylic acid tablets with glycine improve long-term tolerability in antiplatelet drug therapy: results of a noninterventional trial. Adv Ther. 2003 Sep-Oct;20(5):237-45.

(2) Schemmer P, Zhong Z, Galli U, Wheeler MD, Xiangli L, Bradford BU, Conzelmann LO, Forman D, Boyer J, Thurman RG. Glycine reduces platelet aggregation. Amino Acids. 2013 Mar;44(3):925-31. doi: 10.1007/s00726-012-1422-8.

Abuse potential of dextromethorphan?

When comparing dextromethorphan to the opioid antitussive (cough suppressant), codeine, it is often said that, while codeine is the more potent antitussive, the advantage of dextromethorphan is that it has no opioid-associated abuse potential. This is true but, unfortunately, detromethorphan is not completely free from potential for abuse. 

Codeine is a weak opioid agonist. Low doses of codeine are sufficient to achieve the antitussive effect. Therefore, there is relatively little risk of abuse of codeine when used as an antitussive.  However, up 15% of codeine is metabolised to morphine,  which is a much more potent opioid agonist (1).  Codeine has a well-known potential for abuse and abuse of codeine cough mixtures is a peristent problem.

Dextromethorphan is not an opioid receptor agonist and so does not have opioid-associated abuse potential. However, dextromethorphan is abused as a recreational drug. At very high doses, well above the label-specified maximum dosages for use as an antitussive, dextromethorphan acts as a dissociative anaesthetic.  Like other dissociative anaesthetics, such as ketamine and phencyclidine (PCP), dextromethorphan is abused.  The mechanisms of the dissociative anaesthetic effects of dextromethorphan are thought to involve actions as a nonselective serotonin reuptake inhibitor and an NMDA receptor antagonist.

References:

(1) “Codeine and Morphine Pathway, Pharmacokinetic”
https://www.pharmgkb.org/pathway/PA146123006 [accessed 2nd Feb 2017]

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