Pseudoephedrine and blood pressure: Is it risky to combine the two?

Pseudoephedrine is most commonly used as a nasal and sinus decongestant, or to address congestion in the Eustachian tubes of the ear. It also has a number of other uses, and can be administered as a stimulant or as a pharmaceutical agent that promotes wakefulness (1).

Pseudoephedrine is a sympathomimetic drug (a stimulant compound that mimics the effect of neurotransmitter substances of the sympathetic nervous system) and belongs to the phenethylamine and amphetamine class of chemical substances. It is often found in many over the counter medications either as a single agent or, more commonly, in combination with a number of other substances such as paracetomol (acetaminophen), antihistamines, codeine, dextromethropan, or a non steroidal anti-inflammatory drug (NSAID) such as aspirin or ibuprofen. Any pseudoephedrine found within these drug combinations is in its salt form of pseudoephedrine hydrocholoride or pseudoephedrine sulphate. In some cases, it is also used as by health professionals as a first line treatment of choice for priapism due to its sympathetic action, and used on an off-label basis for urinary incontinence (2).

Pseudoephedrine is primarily used as an oral decongestant, although it can also be applied topically. Oral pseudoephedrine is generally considered to be the optimal administration route, as it has been evidenced to be less likely than topical application to cause rebound congestion (otherwise known as rhinitis medicamentosa). Because it is also a stimulant, it can cause a number of known side effects including excessive sweating, insomnia, anxiety, and hypertension (3).

Pseudoephedrine misuse

Pseudoephedrine misuse has also been evidenced in a range of high profile sports, and it has been misused by a number of elite athletes for its stimulant properties. It is also commonly used as a chemical precursor in the illegal manufacturing of methamphetamines – as such, many pharmaceutical companies are in the process of reformulating many of their oral and topical decongestants to contain alternative substances such as phenyleprine, which are less effective but cannot be used for a wide range of illicit purposes. Its regular misuse has also changed the way in which the drug is regulated and prescribed in Australia, with products that contain pseudoephedrine now classified as ‘pharmacist only medicines’ during which a pharmacist must be present and directly involved in each transaction with anyone wishing to buy any pseudoephedrine related product. They must also never be sold on general sale, and must be retained on the pharmacist’s side of the counter away from public access. Because of its widespread misuse many pharmacies now stock phenyleprine based decongestants instead, yet there remains very little evidence for their effectiveness from a number of clinical trials (4,5).

Contraindications for pseudoephedrine

There are a number of medicines against which pseudoephedrine is contraindicated, many of which are taken by individuals who use medication to lower their blood pressure.

Studies have shown that pseudoephedrine interacts negatively with monoamine oxidase inhibitors (an older type of antidepressant), occasionally leading to a range of hypertensive reactions and even hypertensive crises (6). A  number of studies concerned with the role of orally administered pseudoephedrine found there to be a well established link between pseudoephedrine dosage and increased blood pressure and heart rate.

Synthesising data from a range of studies, and measuring the impact of pseudoephedrine use on systolic BP, diastolic BP and heart rate, the 2005 study found that higher dose administration and immediate-release preparations were associated with a greater increase in blood pressure (7). The review of 24 studies also revealed that shorter-term pseudoephedrine use was associated with higher systolic and diastolic blood pressure readings, even in patients with well controlled hypertension.

Pseudoephedrine and increased blood pressure

Pseudoephedrine causes an increase in blood pressure through increasing the heart rate and causing blood vessels to narrow – a process known as vasoconstriction. As decongestants tend to be immediate, fast-acting products, the effects of taking any pharmaceutical substances that contain the drug can result in symptoms being felt almost immediately. As well as pseudoephedrine, other over the counter medications that contain active ingredients such as oxymetalozine, naphazoline,and levmetamfetamine can also cause an increase in blood pressure. Although phenylephrine has largely replaced pseudoephedrine in many over the counter preparations, it is also worth noting that this drug can also cause increased blood pressure and should be administered with caution. The use of pseudoephedrine can also significantly reduce the efficacy of other pharmaceutical options that have antihypertensive properties, interacting negatively with mecamylamine, reserpine, veratrum alkaloids, and methyldopa (8). It is not recommended for use in a wide range of health conditions including diabetes mellitus, cardiovascular disease, hyperthyroidism, severe coronary heart disease, and severe hypertension.

Advice with high blood pressure and pseudoephedrine medication

In considering whether patients with hypertension take products containing pseudoephedrine, caution from a pharmaceutical perspective should always be considered. Whilst the studies highlight increased levels of BP and heart rate when pseudoephedrine is administered, there is a similar body of evidence that shows very limited effects when small doses are taken, carefully, over a clearly defined time period. As such, many pharmacists will advise their patients that pseudoephedrine may modestly increase blood pressure and heart rate, particularly when taking medication that has an immediate release formulation or is given at a high dose. Patients with stable, controlled hypertension do not generally appear to be at a significantly higher risk for blood pressure elevation compared to those without controlled hypertension, yet at the same time each individual patient must be assessed on account of their own medical history and current medication regimen. If patients insist on taking medication that includes pseudoephedrine, their pharmacist or family doctor will generally advise them to monitor their blood pressure carefully and advise the use of a sustained-release product to avoid any sudden increases in blood pressure.

References

1. Hodges K, Hancock S, Currell K, Hamilton B, Jeukendrup AE (2006) Pseudoephedrine enhances performance in 1500-m runners  US National Library of Medicine National Institutes of Health 38(2): pp329–33
2. Hatton RC, Winterstein AG, McKelvey RP, Shuster J (2007) Efficacy and safety of oral phenylephrine: systematic review and meta-analysis Ann Pharmacother 41 (3): 381–90
3. Hernández Colín D, González Díaz SN, Rodríguez Medina R et al (2004) Assessment of the clinical efficacy and safety of epinastine plus pseudoephedrine vs loratadine pluspseudoephedrine in perennial allergic rhinitis Rev Alerg Mex 51(1):23-8
4. Horak F, Zieglmayer P, Zieglmayer R et al (2009) A placebo-controlled study of the nasal decongestant effect of phenylephrine and pseudoephedrine in the Vienna Challenge Chamber  Ann all asth  102(2): 116–20
5. Eccles R (2007) Substitution of phenylephrine for pseudoephedrine as a nasal decongeststant. An illogical way to control methamphetamine abuse Bri  Jour Clin Pharm 63 (1): 10–4
6. Vidal C, Prieto A, Pérez-Carral C, Armisén M et al (1998) Nonpigmenting fixed drug eruption due to pseudoephedrine Ann. Allergy Asthma Immunol 80 (4): 309–10
7. Salerno SM, Jackson JL, Berbano EP (2005) Effect of oral pseudoephedrine on blood pressure and heart rate: a meta-analysis Arch Intern Med 165(15)1686-94
8. Neri I, Jasonni VM, Gori GF, Blasi I, Facchinetti F (2006) Effect of L-arginine on blood pressure in pregnancy-induced hypertension: a randomized placebo-controlled trial J Matern Fetal Neonatal Med 19(5):277-81