According to a study by Gagliese and Melzack, about 60-80% of the people, age between 60 and 89 years, suffer from chronic pain. More than three quarters of the people living in their own quarters either not at all or only insufficiently supplied regarding pain therapy. Pain in an older age can have many reasons: Degenerative skeleton diseases, osteoporosis, and sequels of a fall, poly-neuropathies, zoster complications, tumors and metastases. Problems often start with the diagnosis. It is hardly possible to measure the pain of persons with dementia since they are not able to express themselves targeted. Quite frequently in these cases, aggression is the only way to react to situations causing or increasing pain like washing or getting dressed. Aggressions decrease with an adequate analgesia.
Old patients are pharmacologically different
The general presumption that resorption of drugs in older age is getting worse, cannot be confirmed across the board. For most of the examined drugs, no clinically relevant changes of resorption kinetics were found. Perhaps some of the changes due to age in the gastrointestinal tract equalize each other regarding their effect. For example the resorption rate is getting lower with sour antiphlogistics caused by the low acidity of the stomach. But at the same time it is improved due to the slowed down stomach-intestine passage. But there are a large number of extrinsic factors influencing the resorption kinetics.
The share of total body water plays an important role in pharmacokinetics. This parameter decreases by 10 to 20% in the years between 20 and 80. The relative share of fat increases from 18 to 36% in men, in women it increases from 33 to 45%. This means that the same dose of a primarily water soluble medication leads to a higher plasma concentration. For fat soluble drugs, this circumstance leads to a longer biological halftime.
The liver gets older as well
The liver as a metabolizing organ gets changes as well the older it gets. And a change of liver function automatically leads to a change of pharmacokinetics of most of the drugs. The relative liver weight decreases from 2.5 to 1.5%. But compared to the influence of extrinsic factors like alcohol, nicotine and liver-toxic drugs, the age-related physiological changes of the live are rather small. The function of the kidneys decreases as well, the glomerular filtration rate decreases by 35% in the age between 20 and 90. This results in an extension of the halftime with drugs eliminated primarily renal.
The pharmacokinetic changes caused by the physiological aging process have to be taken into account in an analgesic pharmacotherapy. Thus, side effects and interactions of drugs can be avoided respectively reduced. Older people consider pain rather restrained, they accept the pain as an expression of the aging process or their disorders, other again are afraid of the meaning of the pain or do not believe in a chance of an analgesic treatment. Already many years ago, McMillan examined tumor-accompanying symptoms and reported that older patients state a lower intensity of pain in the course of their disease. There is no indication for therapeutic minimalism or polypragmatic procedure in the treatment of an old patient. Drugs have to be selected carefully, administered targeted and dosed accordingly in order to achieve a use for the older patient, preferably free of side effects.
A study of the Arbeitskreis Schmerz im Alter (working group pain in older age) displayed problematic tendencies in pain therapy:
- 51 percent of the examined patients with an average age of 76 years received solely drugs against pain level 1of the WHO-recommendation, i. e. “simple” analgesics (non-opioids)
- 25 percent received a therapy level 2, i. e. a combination of simple pain killers and weak opioids, only 18 percent were treated with drugs level 3, i. e. strong opioids.
- 6 percent did not get any pain therapy.
- In 50 percent of the patients, the researchers found a depressive symptomatic.
In comparison, NSAR is a lot more risky in a permanent therapy of the older patient. This applies especially fort he following concomitant diseases:
- Loss of fluid caused by diuretics
- Cardiac insufficiency in connection with congestion lung
- Renal insufficiency
- Liver cirrhosis
The most frequent reason for older patients being treated in a hospital due to side effects are non-steroidal antirheumatic drugs. The risk of ulcer bleeding with a lethal end is increased by factor 4. Increased as well is – according to a study by Buffum et al – the danger of acute renal failure in older age during high-dosed therapy with diuretics during NSAR administration.
“Compared to acetylsalicylic acid and NSAR including the selective COX-2 NSAR, preference should be given to Paracetamol due to the side effects feared in gerontology”, thus the recommendation of the Gerontological Society of America. Since inflammatory rheumatic diseases quite frequently require therapy with analgesics, the patient does not get around “sour” pharmaceuticals. It is possible to mitigate gastrointestinal side effects with proton pump inhibitors or antacids. In addition, a restricted liver- and/or kidney function might be a contra-indication.
Some of the features of non-opioid analgesics in older patients:
- Paracetamol does not make sense in cases of restricted liver- and kidney function and inflammatory pain.
- Acetylsalicylic acid not in cases of asthma, gout and application of anticoagulants. The age-related physiological decrease of kidney function causes an increased risk for NSAR induced sodium- and/or water retention, hyperkalemia as well as a decline of the glomerular filtration rate all the way to acute renal failure.
- Ibuprofen and ASS should be taken at different times during coagulation therapy since it might revoke the inhibiting effect on thrombocytes-aggregation.
- Metamizol could make sense against colicky pains, but regarding an intravenous application you have to take hypotensive and allergen components into consideration.
- Coxibes have advantages regarding the missing effect on platelet aggregation. The US-American FDA though published intensified warnings (“black box warnings”) in April 2005 concerning the cardiovascular risks of Celecoxibe and the common NSAR.
Opioid analgesics – beware of the metabolites
Instead of high doses of level 2 analgesics, a change to strongly effective opioids (WHO-level III) often is more advantageous for old patients. Under no circumstances you should combine opiates of varying potency. The more potent opioid will force out the less potent from its binding site. Potency 0.2 (for example Tramadol) combined with potency 1 (morphine) results mathematically in 1.2, but pharmacologically in 1. Even is the desired effect is not increased, it might lead to increased undesirable side effects like nausea and constipation. Prior to a (permanent) therapy with opioids, you certainly should take other preferable curative steps.
Basics of pain therapy
Five key sentences summarize the concept of the WHO-level scheme:
1. by the mouth,
2. by the clock,
3. by the ladder,
4. for individual,
5. attention to detail
1. pain killers should be taken orally (or non-invasive),
2. in accordance with a fixed schedule,
3. in accordance with a fixed level “ladder”,
4. in individual dosage,
5. specialties have to be taken into consideration and paid attention to.
For a permanent medication of geriatric patients, retarded or long-term effective opioids should be applied (e. g. Buprenorphine). They grant adequate intervals for taking the medication and at the same time a continuous sleep at night not interrupted by taking analgesics which also takes part in a patient’s compliance. If it is necessary to administer the analgesics through a tube, many of the retard preparations are not suitable. Here Buprenorphine is a sensible alternative since it can be taken sublingually.
The ideal analgesic for an old person should:
- Be rather lipophilic than hydrophilic
- Have a sufficiently long (compliance-promoting) effectiveness
- It also should be applicable in cases of swallowing disorders and
- display kinetics adjusted to the older patient, i. e. the metabolites should not cumulate in case of a minor function of the excretory organs
- In particular, the opioid should not generate the metabolite Morphine-6-Glucuronid which, among other things, increases sedation and leads to confusion.
Opioid analgesics for the geriatric patient should have a “kidney-friendly” metabolism. A cumulation of the degradation product Morphine-6-Glucuronid entails side effects which might show only days later as delirious states. Especially in cases of a restricted renal function due to age, the metabolite might cumulate. Thus is seems to make sense to prefer such opioids not generating them for patients in an older age. This applies for:
- Hydromorphone and
Morphines on the other hand generate Morphine-3-Glucuronid. Also the opioid-analgesic Pethidin seems not suitable for geriatric patients. It might cause an increasing number of the anticholinergic syndrome. Thus the application of hydrophilic analgesics like morphine will lead to a higher analgesic effectiveness in younger patients. In addition, morphines generate metabolites with side effects which might cumulate with renal insufficiency. Although the relative gain of body fatty tissue might lead to a delayed effect when lipophilic analgesics like Buprenorphine are administered but a cumulation will not happen. Thus the dose to be given has to be adjusted carefully with increasing age and according to individual effect and side effects.
Buprenorphine – strong effect, no respiratory depression
Buprenorphine sublingual pills can be applied for older, cachectic pain patients with swallowing disorders, the dose can be adjusted very well to the individual pain intensity. The substance is active as a partial agonist at the Mµ-receptor. This special mechanism of effectiveness increases the application safety considerably. Even if massively overdosed, a respiratory depression is nearly impossible. The antagonistic effect at the kappa-receptor might have a positive effect on older pain patients, especially those with depressive symptoms. The patients are hardly influenced by Buprenorphine in their vigilance. In particular for patients with respiratory diseases like for example COPD, the non-relevant influence of the breath-minute-volume is of advantage. In multimorbid patients with a large number of accompanying medications, the therapy with this opioids partial agonist remains more manageable due to its low range of interactions. Buprenorphine has no immunosuppressive effects – a fact, especially older pain patients with a weaker immune system profit from. Compared to morphine (level 1), the analgesic potency is 100. Another advantage is the long period of effect despite the low elimination halftime and the low binding to proteins relevant for other pharmaceuticals.
Hydromorphone – old substance revamped
The semi-synthetic dihydromorphine-derivate is member of the substance class of the morphinane and is applied all over the world since 1926. It is a lot more lipophilic than morphine and crosses the blood-brain border accordingly fast. The manufacturer states the analgesic potency with factor 7.5, other authors (M. Kloke, Deutsche Gesellschaft für Hämatologie und Onkologie/German society for hematology and oncology) with factor 5. Hydromorphone has very low plasma protein binding which benefits the low potential for interactions. Especially for geriatric or multimorbid patients this is of great relevance. Myoclonia which might occur with other opioids, were not observed during oral application. Although the active ingredient is more than 80 years old, it was further developed galenically several times. The OROS® (ORal OSmotic system)-technology for example makes use of the osmosis principle. The active ingredient hydromorphone is set free steadily and nearly independent from food by a push-pull-mechanism. After taking the osmotic tablet, water enters from the gastro-intestinal tract into the inner (pull component), the swelling body expands and pumps hydromorphone slowly but steadily through a small laser-drilled opening in its cover to the outside (push component). Pharmacokinetics is proportional to the dose in all offered potencies. After 24 hours, the setting free of hydromorphone is completed.
Oxycodone – double the power of morphine
Oxycodone is a semi-synthetic opioid agonist which originally was applied for postoperative analgesia. It is member of the opioid-analgesics of level III of the WHO level scheme, working medium- to strongly effective. Oxycodone has affinities to kappa-, my- and delta-receptors in brain and spinal marrow. The bio-availability of the pharmacon is nearly double of the one of morphine. Compared with morphine, the dose can be nearly cut half with the same effectiveness. And it works faster. Oxycodone causes the usual effects and side effects of opiates but supposedly causes less central nervous side effects like hallucinations and lower release o histamine with the result that less itching, drop o blood pressure and fatigue occur.
Several studies are available comparing the effectiveness and tolerance of Tramadol. Oxycodone is up to 20 times more potent than Tramadol, but causes significantly less nausea and muscle cramps. Controlled studies with persons age 65 plus have shown that, compared to younger adults, the clearance of oxycodone is only slightly decreased. In cases of a not manifested liver- or renal functional disorder, an adjustment of dosage is not necessary. A newer galenic variation is the combination of oxycodone with naloxone. Thus the risk of constipation is supposed to be lower; in addition an abuse outside pain therapy as a drug replacement is prevented. One thing all opioids have in common: The patients should preventively be treated against constipation. Macrogol seems to be better than lactulose. The latter might lead to heavy gases.
Transdermal systems not always remedy of first choice
Not only the active ingredient, but also the type of application is of relevance. Transdermal therapeutic systems are applied over-proportionally often in geriatrics. Especially in old patients, resorption and effectiveness are subject to strong fluctuations and hardly predictable. Transdermally applied lipophilic opioids like Buprenorphine and Fentanyl are resorbed very badly by cachectic old people as lipophilic substances due to the lack of a subcutaneous fat layer. In addition skin folds lead to a reduced contact area.
Dose reduction when taking anti-hypertensives
A reduction of the opioids dose for older patients should always be aimed for if they take additional drugs like for example anti-hypertensives and/or calcium-antagonists. Although opioids attack other transmitter systems like the monaminergic (dopamine, serotonin), the GABA, the histaminergic and/or the cholinergic system, it might lead to drug interactions with anti-hypertensives and/or calcium-antagonists. The reason is a hyperpolarization of the cells on a membrane level. Opioids enhance the cellular release of K+ ions and reduce the Ca2+ influx into the cell.
Since calcium-antagonists primarily work through inhibiting calcium-reuptake, a combination with any opioids leads to a potentialization of effectiveness (synergistic effect). Thus everyone applying such pharmaceuticals or pharmaco-groups as a permanent medication for older people should keep this enhancement of effectiveness in mind, especially since the desirable enhancement (analgesia) as well as the respiratory depression and sedation are stronger and/or the effect lasts longer.
If you are interested in learning more about this topic, you will find an overview of the potentially inadequate medication for older people in the so-called PRISCUS-list.