Comparison of unusual administration methods of morphine

Morphine is a widely used analgesic. Its clinical use and the huge dependency factor (morphine and heroin include tested to be the most addictive opiates) brought up the need to investigate the typical routes of administration (oral, rectal, iv, sc) and evaluate them with some not well established routes (nebulised, intrathecal, transdermal, sublingual etc).


Morphine is a solid opioid derived from the opium poppy, Papaver somniferum1. It can be used for the control of moderate and severe pain. It acts right to central nervous program exhibiting an instant time of actions. Along with pain relief, it causes the feeling of very well being (euphoria). It can also produce a series of various other central and peripheral effects such as sedation, cough suppression, nausea, constipation and might cause histamine launch2. It is utilized during surgeries for anaesthesia and as a soreness reliever following the operation. It is just a drug of preference for terminal good care and it is really useful for pain management in cancer patients3.

Morphine is offered by several formulations and various drug administration routes. Selecting the correct administration route would depend on the level of soreness control required. For example, parenteral morphine can be used for acute severe discomfort, while oral morphine is utilized for the treating temporary pain. The location of the pain will also determine if it’s essential to apply topical preparations or certainly not.

Table 1 Pharmacokinetic Properties of three opioid analgesics

Pharmacokinetic Parameters

Half life

Volume of Distribution


Morphine (iv)

2-3 hours

3-5 litre/kg

15 -20ml/min/kg

Fentanyl (iv)

3. 5-3. 8 hours

5-6 litre/kg



2-3 minutes


Use morphine values

Source: Clarke’s examination of prescription drugs and poisons4

Moreover, pharmacokinetic parameters such as bioavailability, half life and clearance and different characteristics of the medicine (table 1) like side effects, ADRs and interactions should be considered before choosing the appropriate drug route. Patient’s inclination (or fear) for a particular drug route and different psychosocial factors might also affect the choice of the formulation and patient’s compliance and finally medicine’s effectiveness.


Oral route

Regarding oral path, morphine comes as a remedy and as quick or controlled (systained) launch tablets and capsules(fig 2).

Fig 2. Oral formulations of morphine

Oral Suspension

Morphine solutions come in different strengths. Oral solutions could be prescribed by writing the formula Morphine HCl 5mg and Chloroform drinking water to 5ml but the proportion could be altered. Morphine Sulphate alternatives (Oramorph) can be found at 10mg/5ml and as concentrated alternatives of 100mg/5ml3.

Other excipients contain: ethanol (96%- morphine is somewhat soluble in ethanol), corn syrup, sucrose, methyl parahydroxybenzoate (E218), propyl parahydroxybenzoate (E216) and purified water. As a result of high content of alcohol this drug isn’t recommended to liquor misusers.

Normal adult dose is 10-20mg every four hours although when approved in palliative care dosage varies more significant or lower based on the severity of the soreness and kidney function respectively3.

As this formulation isn’t readily absorbed from GI system, to be able to produce same results as iv medication dosage a 50%-100% increase in dose should be considered. Overdose risk is certainly high and may cause hypotension, respiratory depressive disorder and sometimes death. Naloxone which can be an opiate antagonist is the first line treatment in the event of overdosing5.

Tablets and Capsules

Solid dosage varieties contain morphine in sort of salt e. g Morphine Sulphate and Morphine hydrochlorate. Theses salts within the body will be available as morphine bases.

Tablets can be purchased in two preparations immediate let go and modified discharge. The short acting tablets come in 10mg, 20mg and 50mg3. They receive every 2-4 hours to regulate and stabilise breakthrough pain. These tablets are a way of determining the volume of morphine had a need to manage pain.

Once the amount of morphine is established the individual can take slow-launch tablets and capsules. These formulations consist of enough morphine to control discomfort for 12 or a day. In the throws of the epidemic question why do cockroaches die on their backs; The starting medication dosage varies and from 10-20mg every 12hours if the patient hasn’t taken any other painkiller previously, to 20-30 mg every 12 hours in cases of replacement weak analgesics3. Note just the dose can maximize whereas the rate of recurrence must remain the same we. e. every 12 time. It can take up to 48 time for the morphine to attain the required plasma levels and therefore it is vital to be taken regularly in any other case they lose their effectiveness5. If the patience encounter pain between doses yet another dose must be given and the GP should determine if it’s necessary to raise the daily dose.

Oral morphine is definitely a more developed drug delivery method however; problems such as the first pass metabolism, the slow onset and the chance of overdose have elevated questions on whether various other novel administration routes can be utilized.


This route is employed just in hospitals and in managing emergency soreness symptoms. The bolus administration provides almost instant onset with a short effect. Iv morphine is utilized when sc route isn’t tolerated. A favorite application of the method is in Person Controlled analgesia (PCA) where the opioid is delivered by using a Hospiral infusion device. The individual can control the morphine consumption and establish a satisfactory degree of analgesia6. Morphine is available in 50 and 100ml vials with strength 1mg/ml3. It is used post operatively specifically after transplants surgeries and in the supervision of chronic pain of malignancy. Although this method pays to for the management of severe pain there are lots of drawbacks. First of all, almost all of the pumps are bulky and invasive. Their unit installation is complicated because they require mains attachment and the patient has limited mobility. There is a risky of overdose therefore supervision is necessary. Side effects such as hypotension and respiratory major depression might develop while convulsions because of high dosage are likely to occur.

fig3. PCA infusion unit vs syringe driver


Subcutaneous method is a great option to oral administration method. It is safe and effective method which is trusted both in palliative attention and extreme pain management. It is utilized for clients that present conditions such as for example gastrointestinal disturbances incorporating indigestion, palindromic motility and obstruction5. A prime characteristic of the sc method may be the syringe driver. The driver employs simple syringes and bears a move rate setting option generally ml/hr which enables accurate dosing over a specific time frame. Unlike PCA infusion products, it is battery powered, so patient’s mobility is not a concern (fig 3). The chance of overdose is lower compared to iv route as there exists a constant stable administration schedule6. There is no need for continuous strict supervision as the driver can be simple to use.

Often, the subcutaneous route could cause some skin site complications. Irritation might appear particularly when there are great concentrations of morphine or when it’s coupled with other drugs which are not fully compatible3. This issue can be cured either by diluting the dosage or by choosing option more compatible drugs.

Also some sufferers might experience needle allergic reactions and action must be used e. g introduce an alternative solution Teflon cannula. Sufferers might feel discomfort, especially those who insufficient subcutaneous tissue16. Sometimes, possible leakage of subcutaneous blog might be noticed. Finally, the sc approach is not recommended for palliative attention patients with acute vascular conditions.


This drug administration way is pretty popular and is utilized for short-term management of acute agony. Also in terminal malignancy patients modified let go morphine sulphate is administered via this way6. Although the absorption rate varies for each and every individual, it’s estimated that around 300-330 mg of morphine happen to be absorbed rectally every four time, indicating a sufficient analgesic effect.

Studies have proven that for the people who have never taken morphine, rectal morphine is more effective compared to the oral administered one5.

Rectal morphine comes in the form of suppositories at distinct strengths (10, 15, 20 and 30 mg) 3. Prescribers must specify both the strength and the morphine salt (morphine hydrochloride or morphine sulphate) that suppositories should consist of.

Evidence displays two deaths15 after consequent dosages of rectal morphine should raise awareness and the need of monitoring the dosing routine and frequency.

Rectal route isn’t avoiding completely the earliest pass metabolism; which means bioavailability could possibly be influenced.

Non conventional routes

Apart from the conventional drug routes discussed earlier, it is necessary to consider other not so popular ones such as the transmucosal, transdermal, sublingual, intrathecal and nebulised routes of administration and make an effort to compare them.

Transdermal- Transmucosal

Transdermal route is a comparatively painless method. The medication absorption is rapidly. Patches are easy to use and not quite expensive. Although this method is often tolerated from the clients skin discomfort and rashes might appear.

Transdermal morphine isn’t popular as there are problems about the efficacy of the method. On the other hand, fentanyl another opioid may be the drug of preference. More particularly, fentanyl patches are more effective in managing chronic pain compared to modified launching oral morphine9. Likewise, transdermal fentanyl causes decreased constipation and drowsiness14.

Another administration route which fentanyl is once again preferred than morphine is the transmucosal route by a buccal tablet. The main reason is that fentanyl is definitely a lipophilic medication while morphine has a limited lipid solubility. More especially, when fentanyl is located in saliva it is 80% non-ionized and it often takes 20-30 minutes for the analgesic result to reach its peak14. Note transmucosal morphine can be available however the bioavailability is certainly low and analgesic impact is not significant.

Sublingual route

This route utilises soluble immediate discharge tablets in fact it is recommended to patients which have swallowing troubles. Morphine enters into bloodstream via sublingual mucosa. Investigations possess demonstrated that the absorption of morphine may be the same (and in a few cases faster) compared with the oral way7. Same studies have displayed that there is no significant difference in the degree and duration of analgesic impact when is weighed against oral administered morphine3.

Nebulised morphine

Nebulised morphine utilises the airways to provide the drug into pulmonary circulation. It works extremely well for COPD patients in the control of acute thoracic soreness11. Through this route, the effect of hepatic fat burning capacity is avoided and an instant absorption is noted. Even so, the plasma drug amounts are unpredictable indicating the need of further clinical investigations. Studies confirmed that inhaled morphine was as effectual as intravenous PCA morphine without causing strong sedating symptoms8. Although nebulised morphine is well accepted, patients who are not used to opioids might encounter nausea and vomiting and in rare circumstances respiratory depression. Other prevalent side effects incorporate constipation and histamine induced broncho-constriction.

Another drawback of nebulised morphine may be the high cost of the equipment (nebuliser, injectable vials, etc). It is not a simple method and some patients might find it difficult to use the nebuliser. Studies show a wide selection of bioavailability in subjects; relating the bioavailability of the drug with the patient’s ability to utilize the nebuliser in the proper way10.


Both epidural and intrathecal routes are used mostly in a healthcare facility clinical environment. The bioavailability is definitely substantial so spinal administered morphine can provide extended analgesic result at lower doses (compared to the conventional drug routes)12. Although epidural and intrathecal morphine can alleviate both severe and chronic pain; analyses recommend that these routes should be used only for pain which can’t be controlled by the basic established methods13. For example, these routes work in managing lower torso pain. Note that just 1% of the daily iv dose must be used intrathecally and only 10% epidurally5. An implanted infusion pump may be used to deliver intrathecal morphine at a continuous rate.

A disadvantage of the methods is the risky of contamination and overdose as the personnel should be trained and mindful when dosing for breakthrough pains. Studies have reported several patients experiencing unwanted effects such as for example sedation, dyspnoea, nausea and vomiting after spinal administration12.

Spinal morphine is not usually desired while diamorphine is the drug of choice because of its high solubility manner.


As it was mentioned before, morphine can be administered via distinct routes. However, it really is vital every time to consider the risk- benefit ratio for every single method and opt for the most effective and safe one. In addition, before establishing unconventional strategies such as nebulised and spinal morphine it is necessary to help expand investigate their suitability and methods to improve the medicine delivery and minimise side effects. .