Ch26

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Propoxyphene (dextropropoxyphene; Darvon) is struc-
most often cut, or diluted, with substances such as qui-
turally related to methadone but is much less potent as
nine, which contribute to the flash, or high. Injection of
an analgesic. Compared with codeine, propoxyphene is
the drug leads to the eventual collapse of the vessels
approximately half as potent and is indicated for the
into which it is injected, leading to the appearance of
treatment of mild pain. It is not antipyretic or antiin-
track marks under the skin. Heroin passes rapidly into
flammatory like aspirin and is less useful than aspirin in
the brain and thus has a rapid onset of action. It is then
most cases of mild pain. Toxicity from propoxyphene,
metabolized to morphine. The rapid onset contributes
especially in combination with other sedatives, such as
to the abuse liability of the drug. Heroin use in pregnant
alcohol, has led to a decrease in its use. Death following
women can lead to low-birth-weight babies, babies born
ingestion of alcohol in combination with propoxyphene
addicted to heroin, immunosuppression, and an in-
can occur rapidly (within 20 minutes to 1 hour). The
creased incidence of infections in both the mother and
drug is not indicated for those with histories of suicide
newborn; an increased incidence of AIDS also occurs.
or depressive illnesses.
Like meperidine, propoxyphene has an active
Mixed Opioid Agonist Antagonists
metabolite, norpropoxyphene, that is not analgesic but
or Partial Agonists
has excitatory and local anesthetic effects on the heart
similar to those of quinidine. Use of the drug during The mixed opioid agonist antagonists are potent anal-
pregnancy is not safe. Teratogenic effects have been ob- gesics in opioid-naive patients but precipitate with-
served in newborns, as have withdrawal signs at birth. drawal in patients who are physically dependent on opi-
As with morphine, propoxyphene requires adequate he- oids. They are useful for the treatment of mild to
patic and renal clearance to prevent toxicity and drug moderate pain. They were developed to reduce the ad-
accumulation. It is thus contraindicated in the elderly diction potential of the opioids while retaining the anal-
patient and those with renal or liver disease. gesic potency of the drugs. Their analgesic effect is gen-
Propoxyphene interacts with several drugs. The use erally attributed to an interaction at the - and to a
of sedatives in combination with propoxyphene can be lesser extent the -opioid receptor.
fatal. In addition, the metabolism of the drug is in- Interaction at the -receptor increases the sedative
creased in smokers due to induction of liver enzymes. effects of the drugs. The euphoric effects are due to in-
Thus, smokers may require a higher dose of the drug for teraction with the -receptor. The dysphoric and psy-
pain relief. Propoxyphene enhances the effects of both chotomimetic side effects of the drugs are attributed to
warfarin and carbamazepine and may increase the tox- interaction at the -receptor.
icity associated with both drugs, such as bleeding and se- The mixed agonist antagonists and partial agonists
dation, respectively. differ from morphine in that they (1) produce excita-
26 Opioid and Nonopioid Analgesics 325
tory and hallucinogenic effects, (2) produce a low de- Contraindications
gree of physical dependence, (3) induce withdrawal Most of the contraindications specific to penta-
signs that differ from those of morphine, and (4) pro- zocine stem from its excitatory effects. Other con-
duce excitatory effects related to the sympathetic dis- traindications are similar to those for morphine.
charge of norepinephrine and therefore are positive in- Pentazocine is contraindicated in patients with myo-
otropic agents in the heart. cardial infarction because it increases heart rate and
cardiac load. Similarly, it is contraindicated in epileptic
Pentazocine patients because it decreases seizure threshold. In addi-
Pharmacological Effects tion, in head trauma patients, it can increase intracranial
Pentazocine (Talwin) is a potent analgesic with an- pressure and brain injury. Pentazocine use in patients
tagonistic activity in opioid-addicted patients. It incom- with psychoses is contraindicated because of its psy-
pletely blocks the effects of morphine in such patients chotomimetic side effects.
but will precipitate withdrawal. To eliminate abuse of
the drug via IV administration, pentazocine is com-
Drug Interactions
bined with naloxone (Talwin-NX). IV administration of
The combination of pentazocine with the antihista-
Talwin-NX will produce no analgesic or euphoric ef-
mine tripelennamine results in a combination known to
fects because naloxone blocks the pentazocine moiety.
drug abusers as T s and blues. This combination pro-
However, the drug will retain its analgesic potency
duces heroinlike subjective effects, and heroin addicts
when administered orally, since naloxone is not active
use it in the absence of heroin. In addition, the use of
orally. Pentazocine produces as much respiratory de-
pentazocine in combination with alcohol or barbitu-
pression as morphine but does not produce the same
rates greatly enhances its sedative and respiratory de-
degree of constipation or the biliary constriction ob-
pressant effects.
served with morphine. Pentazocine may increase GI
motility if used in high doses. Unlike morphine, penta-
Tolerance and Dependence
zocine increases heart rate and blood pressure by re-
Tolerance to the analgesic effects of pentazocine de-
leasing norepinephrine. Pentazocine also may increase
velops.Withdrawal signs are milder than those seen with
uterine contractions in pregnancy.
morphine, and they produce more excitatory effects.
Pharmacokinetics
Butorphanol
Absorption of pentazocine following oral administra-
tion is rapid. The onset of action occurs within approxi- Butorphanol (Stadol) is chemically related to levor-
mately 15 minutes, and the half-life is 2 to 3 hours. phanol but pharmacologically similar in action to pen-
Pentazocine is extensively metabolized in the liver and tazocine. As an opioid antagonist it is nearly 30 times as
thus has a high first-pass effect following oral administra- potent as pentazocine and has one-fortieth the potency
tion; its half-life differs considerably from patient to pa- of naloxone. It is a potent opioid analgesic indicated for [ Pobierz całość w formacie PDF ]

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