Opioid+Analgesics+&+Anatagonists

= Opioid Analgesics and Anatagonists =

Elle and Elina will work together on this page (This is week #7 readings. Deadline is April 25th)
What are opioids analgesics? Opioids are drugs that are primarily used to relieve pain and are often used in dentistry for this purpose.

Opioids have different groups and structures: · Morphine/Codeine · Methadone · Morphinan · Meperidine

Action of opioids: -Opioids bind to receptors in the CNS, peripheral sites, and the spinal cord.

There are 3 different receptors which have different responses: · mu: Produce analgesia (pain reduction). Morphine and other similar agonist have the greatest attraction for this receptor in the CNS and peripheral nervous system. · kappa: Produces analgesia and sedation. It is a non-preferred binding site for opioid agonist, but preferred site for mixed agonist-antagonist opioids. · delta: Produces analgesia, sedation, dysphoria (sadness), micturition and diuresis.

There are 4 classifications of opioids: 1.) Complete agonist: Have affinity to mu and kappa receptors. Agonists such as morphine bind to the receptor to produce analgesia  2.) Partial Agonist: Partial agonists may cause some of the agonist effects when binding to a receptor, but not all. For example Buprenorphine, which produces a strong analgesic effect when binding with the mu receptor, but has less psychotomimetic effects than many other agonist opioids. 3.) Agonist-antagonist: Some opioids can be both an agonist and antagonist. Sometimes binding to the kappa receptor, instead of the mu receptor, is desirable since the mu receptor affects respiratory depression. Some opioids that are antagonists for the mu receptor while being agonists for the kappa receptor can cause the same analgesia as morphine but without the associated respiratory depression. 4.) Antagonist: Antagonists bind to the receptor to prevent the binding of other opioids but have no analgesic or other agonist effects. These can be useful for reversing intoxication or overdoses of opioid agonists such as heroine or morphine.

Pharmacokinetics: Absorption- Opioids can be taken orally and are absorbed by the small intestine. Metabolized- Undergo the first pass effect in the liver, and then bind to plasma proteins. Distributed- Through the blood stream Excretion- Through the kidneys

Pharmacologic Effects: · Pain- suppression (Morphine has the strongest effect) (Codeine has the weakest effect) · Cough- suppression · Respiratory- depression · Gastrointestinal effects- increase smooth muscle tone; some drugs such as Lomotil can help control diarrhea.

Adverse Reactions: · physical dependence (addiction) · respiratory depression · constipation · nausea/vomiting

Addiction: -Can be addictive due to its euphoric effects. (mu opioid agonist may be more psychologically addictive.) -Addiction to opioids can be treated with substitutions such as Methadone and Buprenorphine or by gradually reducing the dosage. Overdose Symptoms: -coma, respiratory depression, pinpoint pupils, hypoxemia, cyanosis, and acute pulmonary edema

Withdrawal Symptoms: -perspiration, irritability, nausea, vomiting, tachycardia, tremors/chills

Treatment of overdose: -Use of an antagonist such as Naxoloxone

Drug Interactions: -Opioids can be given in addition to anti-inflammatory drugs to treat pain and inflammation.

Uses in Dentistry: -Common opioids used in dentistry are codeine, hydrocodone, oxycodone, and pentazocine. -The use of opioids in the use of dentistry are used only for the relief of pain. -Because dental pain is frequently associated with inflammation, non-opioid analgesic drugs with anti-inflammatory efficacy are often the first choice for use. ex. aspirin, ibuprofen -Combinations of opioids with acetaminophen, aspirin, or ibuprofen are often used because different complementary central and peripheral mechanisms of pain relief are invoked. -Acetaminophen is NOT a good choice for the reduction of inflammation becasue it does not have an anti-inflammatory efficacy.

Implications for Dentistry: -Opioid analgesics have the potential to be abused and physical and psychological dependence can develop. -The interaction of opioids and CNS depressants can produce a greater than expected depression. -The interaction of opioids and phenothiazines are known to produce additive CNS depression and respiratory depression, and may also produce a greater incidence of orthostatic hypotension. -Greater incidence of orthostatic hypotension is also seen with the combination of opioids and tricyclic antidepressants. -Opioids and CNS depressants, when used in combination, should have a sufficient margin of safety to avoid dose-dependent toxicity. -Large doses of local anesthetics and the use of opioids display supra-additive toxicity and is likely that respiratory acidosis caused by an opioid can increase the entry of LA into the CNS. -Interactions of opioids and oral anticoagulants result in an enhanced response. -The interaction of meperidine and monoamine oxidase inhibitors results in severe and immediate reactions that include excitation, rigidity, hypertension, and sometimes death.