Codeine, CYP2D6 phenotypes and morphine

Codeine is metabolised to morphine by CYP2D6.
CYD2D6 displays huge variation in activity due to genetic polymorphism.

4 phenotypes of expression are identified depending on the level of activity

• UMs: Ultrarapid metabolisers
• EMs: Extensive metabolisers (Most Common)
• IMs: Intermediate metabolisers
• PMs: Poor metabolisers

Morphine is formed at a very fast pace in ultrarapid metabolisers.
In adults with ultra rapid metabolisation: if codeine is administered at therapeutic doses then resulting levels of morphine is unlikely to cause respiratory depression. But the possibility increases substantially in overdosage.
In lactating mothers with ultra rapid metabolisation: codeine administered at therapeutic doses may result in high levels of morphine in milk; there are case reports of respiratory depression occurring in infants of such mothers.

Rifampin vs Rifampicin: Know the difference

People often think these two molecules are different molecules. But they are the same molecule as explained below.

• Rifampin is USAN: United States Accepted Nomenclature
• Rifampicin is INN: International non-proprietary name

List of drugs with different INN and USAN

• Glibenclamide: glyburide
• Isoprenaline: isoproterenol
• Moricizine: moricizine
• Orciprenaline: metaproterenol
• Paracetamol: acetaminophen
• Pethidine: meperidine
• Rifampicin: rifampin
• Salbutamol: albuterol
• Torasemide: torsemide
• Retigabine: ezogabin

Macrolide: Brief history and timeline

Erythromycin was the first macrolide developed around 1950s and has been in human use since 1952
Erythromycin  was primarily used as an alternative to penicillin
Further macrolides were developed to improve the acid stability of erythromycin resulting in development of macrolides with differing spectrum and pharmacokinetic profiles

Subsequent macrolides

• Azithromycin
• Clarithromycin
• Roxithromycin
• Spiramycin

Factors contributing to variation in clearance of theophylline

Increased clearance

• Enzyme induction by drugs: rifampicin, ethanol, phenobarbitone
• Smoking: tobacco, marijauna
• High-protein, low-carbohydrate diet
• Childhood

Decreased clearance

• Enzyme inhibition by drugs: cimetidine, erythromycin, allopurinol, zafirlukast, ciprofloxacin
• High carbohydrate diet
• Congestive heart failure
• Liver disease
• Pneumonia
• Viral infection and vaccination
• Old age 

Look for mechanism of action of theophylline. 

Theophylline: multiple mechanism of action

• Non selective phosphodiesterase inhibition: bronchodilation primarily attributed to increase in cAMP* 
• Adenosine receptor blockade: additional bronchodilatory effect 
• Promotes apoptosis of neutrophils and eosinophils
• Activation of histone deacetylase (HDAC):

* Increase in cAMP can mediate other effects:

• Reduced expression of proinflammatory genes
• Increase in interleukin 10; a antiinflammatory cytokine levels

Long term effects of PPI

Long term PPI use is associated with the following effects. The level of evidence for such association is sparse. Clinician must be aware of the following risks and take appropriate measure if required. 

• Vitamin B12 deficiency
• Increased risk of fractures (osteoporosis)
• Hypergastrinemia
• Increased risk of infections: nosocomial pneumonia, community acquired Clostridium difficile, SBP in ascites

History of clonidine

Around 1960: Clonidine, an α2-agonist, was developed as a nasal decongestant that worked by vasoconstriction.

Administered to a secretory she developed following features along with good nasal decongestant effect at low concentration 

• Fell asleep for 24 h
• Low blood pressure
• Marked bradycardia
• Dryness of the mouth

1966: introduced in clinical practice reformulated for hypertension.

Source: Helmut Stähle,

A historical perspective: development of clonidine, Best Practice & Research Clinical Anaesthesiology, Volume 14, Issue 2, 2000, Pages 237-246, ISSN 1521-6896,

https://doi.org/10.1053/bean.2000.0079.

(http://www.sciencedirect.com/science/article/pii/S152168960090079X)