Hydromorphone tolerance

Patients who are considered opioid-tolerant are those who have been taking, for a week or longer, morphine 60 mg/day or more, or oral oxycodone 30 mg/day or more, or oral hydromorphone 8 mg/day or more, or an equianalgesic dose of another opioid. 

High potency (HP) injection - HP injection is a highly concentrated solution of hydromorphone intended for use in opioid-tolerant patients. Do not confuse HP injection with standard parenteral formulations of injection or other opioids. Overdose and death could result. 

Seizures Seizures may be aggravated or may occur in individuals with or without a history of convulsive disorders if dosage is substantially increased above recommended levels because of tolerance. Observe patients with known seizure disorders closely for hydromorphone-, meperidine-, morphine-, or tramadol-induced seizure activity. 

The patient who uses hydromorphone repeatedly may develop a tolerance to the drug s analgesic effect as well as physical dependence. 

The levels of hydromorphone usually peak in the body about 45 minutes after oral administration of the drug. Injections into muscle produce effects within 15 to 30 minutes and reach peak levels between one-half to one and one-half hours later. The duration of effect usually lasts four to five hours. The actual amount of hydromorphone prescribed or administered depends on a variety of factors, including age, the degree of pain, the amount of opioid tolerance, and the body mass of the patient. 

Individuals who have developed tolerance to opioids and who have overdosed on hydromorphone are not likely to develop the serious depression of the respiratory system that occurs in individuals with no such tolerance who have overdosed on hydromorphone. The typical treatment of narcotic overdoses with narcotic... 

Hydromorphone has the potential for abuse. Chronic users may develop tolerance, thus necessitating larger doses for the desired effect. Abrupt cessation can cause withdrawal, yielding restlessness, insomnia, hypertension, tachycardia, tachypnea, vomiting, and diarrhea. 

Hydromorphone PO 2-4 mg q 3-6 h IM 1-4 mg q 3-6 h IV 0.1-0.5 mg q 5 min prn Rectal 3 mg q 6-8 h Use in severe pain More potent than morphine otherwise, no advantages Use immediate-release product with sustained-release product to control "breakthrough" pain in cancer patients Use sustained-release product only in those patients who have demonstrated opioid tolerance 12-mg, 16-mg, 24-mg, and 32-mg sustained-release capsules are available and should be dosed every 24 hours... 

As an oral drug, codeine is much less effective as an analgesic due to its large first-pass hepatic metabolism compared to morphine, hydrocodone and oxycodone. The plasma half-life of codeine is also shorter than many other orally available opiates such as morphine, hydromorphone, and oxymorphone. Like all opioids, continued use of codeine may result in tolerance development and physical dependence. However, when compared to potent mu agonists, codeine is less addictive and is associated with mild withdrawal symptoms. 

Hydromorphone binds to mu and delta opiod receptors in the central nervous system. It has no effect at the kappa, sigma, or epsilon opioid receptors. Activity at the mu receptors causes analgesia, but also miosis, urinary retention, constipation, hyperthermia, and euphoria. Other side effects such as respiratory depression, pruritus, nausea, vomiting, and development of tolerance are due to binding at both mu and delta receptors. Hydromorphone, unlike other opioids, also has a direct depressant effect on the respiratory brainstem center and the cough center in the medulla. 

The intramuscular route for chronic cancer pain based on a timed regimen is given at a dose of 3-4 mg every 3-4 hours. Terminal cancer patients may have much higher requirements, and, as with all opioids, there is no ceiling effect. The dose for the acute treatment of pain is 1-2 mg IM every 4-6 hours. Tolerance to fhis regimen is typically evidenced by a reduction in duration of pain relief A reduction in the duration of action indicates a developing tolerance to hydromorphone... 

Hydromorphone 0.2 mg/mL intravenously is used extensively for patient-controlled analgesia (PCA) in the treatment of acute pain. A typical bolus dose is 0.2 mg with a lock-out period of 6 minutes. When used on an as-needed basis hydromorphone is given at a dose of 1-2 mg every 4-6 hours. A lower initial dose should be used in opiate-naive patients. Doses can be escalated in refractory pain. Again, a decrease in the duration of pain-free periods suggests the development of tolerance to the analgesic effects of hydromorphone. Intravenous administration of hydromorphone should be slow over 2-3 minutes. 

Hydromorphone is easily available and titrateable, inexpensive (except extended release), and well tolerated. It causes less pruritus than morphine. It is equivocal whether it causes less nausea in cases where substantial doses are administered. Hydromorphone can be used in a multimodal approach to treat both acute and chronic pain. It carries less risk of toxic metabolites when compared to morphine and meperidine in patients with renal disease. Overdoses are readily treated with the antagonist naloxone. 

The Exalgo formulation of hydromorphone ER is proceeding toward FDA approval for the treatment of moderate to severe chronic pain in opioid-tolerant... 

A search of completed studies also reveals the following effectiveness and tolerability of OROS Hydromorphone and Hydromorphone IR in chronic pain, safety and tolerahihty of OROS Hydromorphone in long-term use for cancer pain, effectiveness versus placebo for chronic low hack pain, in chronic non-malignant pain, safety and impact on quahty of life, randomized open-label for safety and effectiveness in short-term use for post-operative pain, dose proportionality studies, OROS Hydromorphone versus morphine in cancer patients, and safety and effectiveness in patients with osteoarthritis. 

Common/serious adverse events for hydromorphone respiratory depression, dependence, tolerance, nau-sea/vomiting, constipation, sedation, primitus. 

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