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What are the Differences Between Morphine and Fentanyl?

By John Markley
Updated Mar 03, 2024
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Morphine and fentanyl are both opioid analgesic drugs, meaning that they relieve pain by binding to structures called opioid receptors in the cells of the nervous system. Morphine is a naturally occurring opioid substance, or opiate, derived from opium poppy plants, or Papaver somniferum, while fentanyl is synthetic. Fentanyl is much more potent than morphine, and while some of their medical uses overlap, each has its own distinct applications.

Morphine (C17H19NO3) is a natural alkaloid found in the latex, a type of fluid produced in many plant species to deter herbivores, of opium poppy seeds. The latex that is extracted quickly dries up, resulting in a residue called opium. Morphine can then be extracted from it. Along with morphine, opium is also the source of another natural opiate, codeine, and a substance called thebaine that is used in the production of many semi-synthetic opioids such as oxycodone.

Fentanyl (C22H28N2O) does not occur in nature and was first synthesized in 1959. Its production begins with a chemical reaction between 4-Piperidinone (C5H9NO) and 2-Phenylethylbromide (C8H9Br) to produce the intermediate chemical N-Phenethyl-4-piperidinone (C13H17NO). This intermediate chemical then undergoes reactions with aniline (C6H5NH2), and sodium borohydride (NaBH4). The product of that reaction then reacts with propanoic anhydride ((CH3CH2CO)2O) to produce fentanyl.

Both morphine and fentanyl are used to relieve pain in trauma and surgical patients and for severe ongoing pain from injuries or from chronic illnesses such as cancer. Both drugs are also used to supplement anesthetics. Morphine can also be used for some medical purposes beyond analgesia and anesthesia, such as treating severe diarrhea and some respiratory conditions.

Fentanyl has much stronger effects than morphine. A given amount of fentanyl has about 100 times the potency of the same amount of morphine. Doses of morphine are usually measured in milligrams or tens of milligrams, while the same quantity of fentanyl would cause a lethal overdose if taken all at once. Fentanyl causes pain relief much more quickly than morphine, but its effects do not last as long. Consequently, morphine and fentanyl play different roles in pain management.

Morphine is used for ongoing pain relief in patients suffering chronic pain, while fentanyl is often reserved for so-called breakthrough pain. Breakthrough pain is a sudden, temporary increases in pain that does not respond to the patient's usual pain treatment. This often happens in people with ongoing pain caused by cancer. Fentanyl is also used for chronic pain patients who have developed a tolerance to less potent drugs such as morphine or who cannot take them due to their adverse effects.

Morphine and fentanyl can be taken in several ways. When used for surgical patients or trauma victims, they are often administered through injections. Both drugs can also be taken orally. Fentanyl taken for chronic pain management is often taken by means intended to administer the drug gradually, such as a lozenge or lollipop dissolved in the patient's mouth or a transdermal patch that slowly releases the drug into the skin. When used illegally as a recreational drug, morphine is sometimes inhaled or smoked.

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Discussion Comments
By anon994645 — On Feb 25, 2016

I had the same problem with my fentanyl patches. I found that cleaning the skin and then after applying the patch. Rub the edges outwards and remove the excess "gummed up" adhesive. This worked wonders for me I also try to put the patch on an area with little movement or bending, like my arm, abdomen, up by my collarbone even my lower back.

By the way: the best way to remove the adhesive is with Avon's Skin So Soft. Absolutely amazing.

By anon993956 — On Jan 02, 2016

@waterhopper: This was happening to several people I know. Tegaderms help enormously. Make sure the area is clean and dried thoroughly before placing the patch. The skin has natural oils and if not cleansed first, you will get the peeling problem. People just put them on without having washed the area first. Try it and see if it works for you.

By anon339702 — On Jun 26, 2013

Yes, with other patches I have had the same problem. I think it has more to do with the adhesive than the patch material or what it is delivering. For example, estrogen patches called Vivelle stay on for many days until peeled off. Clymara patch though is just like you experienced. A small sweat, or bathing of any fashion causes peeling up. This is a complaint the pharma manufacturer really needs to hear.

By alex94 — On Aug 09, 2011

@waterhopper- I am on the Fentanyl patch also. I take it due to a bad car accident that I had many years ago. I suffered several broken bones and the pain continues to this day. My doctor put me on the patch. I had the problem that you are describing the first time I put one on. A few hours after, it was already peeling at the corners.

I asked my pharmacist what I could do to prevent losing much needed medication. He suggested Tegaderm. It goes over the patch and helps to keep it on, even while bathing. I tried it and it worked very well in keeping the patch in place.

However, I was having the problem of breaking out everywhere that I had placed a patch on my body. I usually put mine on my shoulder, chest, or back area. I would have to take it off after the first day because it was burning so bad.

It turned out that I was allergic to the adhesive, not the medication. My doctor put me back on Morphine since I could not use the patch. Not quite as good, but it does control the pain better than no medicine at all.

By WaterHopper — On Aug 08, 2011

I was recently diagnosed with Fibromyalgia. I have had rheumatoid arthritis for many years, as well. My doctor and I tried several different combinations of drugs to relieve the pain before she prescribed Fentanyl.

It comes in a patch and it is to be worn for 3 days at a time. However, I have not been able to keep one on for more than a day and a half. If I even sweat, the corners of the patch start peeling back. If I take a bath, that does it in. I am very careful not to get it wet but it still comes off. It is a waste of medication and it is not cheap. Does anyone else have that problem?

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