• High affinity for μ receptors and lower affinity for δ and κ receptors.
• Morphine remains the standard against which the new analgesics are measured.
-is primarily conjugated to morphine-3-glucuronide (M3G), a compound with NEUROEXCITATORY PROPERITES
- the neuroexcitatory effects of M3G are NOT mediated by opioid receptors
-10% of morphine is metabolized to MORPHINE-6-GLUCURONIDE (M6G)
- M6G is an active metabolite with analgesic potency 4-6 x the potency than morphine itself!
-M3G and M6G are POLAR METABOLITES with limited ability to cross the BBB
- probably do NOT contribute significantly to the CNS effects of morphine, however the effects of these metabolites should be considered in patients with RENAL IMPAIRMENT
--> need to MORPH into another ONE b/c the pain is sooooo bad
-useful in treating SEVERE PAIN
HEROIN GOES INTO YOUR HEAD --> it's only 6-MAM!!! LEAVE ME ALONE, GET OUTA MY HEAD!!!
-RAPIDLY HYDROLYZED TO 6-MAM which is then hydrolyzed to MORPHINE
-BOTH HEROIN + 6-MAM --> are MORE LIPOSOLUBLE than morphine and enter the brain more readily (know this)
Note: morphine + 6-MAM are responsible for the pharmacological actions of heroin
"MY PAIR-IDINE" --> it's his metabolite that causes the problems --> normeperidine has a long half life, can get SEROTONIN SYNDROME, and also CONTRAINDICTD with a MAOI
- μ receptor agonist.
- No longer recommended for treatment of chronic pain d/t concerns over metabolite toxicity.
- LARGE DOSES repeated at SHORT INTERVALS produce TREMORS, MUSCLE TWITCHES, DILATED PUPILS, HYPERACTIVE REFLEXES, and CONVULSIONS
--> these symptoms are d/t the accumulation of the metabolite NORMEPERIDINE****, which has a 1/2 life of 15-20 hours compared with 3 hours for meperidine
DRUG INTERACTIONS: SEROTONIN SYNDROME = d/t ability of meperidine to block reuptake of serotonin
--> is an excitatory reaction with delium, hyperthermia, headache, hyper or hypotensoin, rigidity, convulsions, coma, and death
CONTRAINDICATIONS: should not be used in patients taking other serotonergic agents such as MAO INHIBITORS
MEPERIDINE (STRONG AGONIST)
can occur when taken with a MAO INHIBITOR
SYMPTOMS: excitatory reaction ("serotonin syndrome") with delirium, hyperthermia, headache, hyper- or hypotension, rigidity, convulsions, coma, and death.
Due to the ability of meperidine to block reuptake of serotonin.
FENTENYL IS FAST + FUROCIOUS (VERY potent)
- RAPID ONSET and SHORT DURATION OF ACTION (15-30 mins)
-the fentanyl subgroup also includes SUFENTANIL, ALFENTANIL, and REMIFENTANIL
-fentanyl is 100x MORE POTENT than MORPHINE, and sufentanil is 1000x more potent than morphine
-alfentanil is seldum used
"METH has been DONE" in this person's life... they need help coming off of their drug (HEROIN) problem
-approx equal in potency to morphine
-induces LESS EUPHORIA and has a LONGER DURATION OF ACTION
μ receptor agonist
NMDA receptor ANTAGONIST
SEROTONIN + NE REUPTAKE INHIBITOR
-these multiple mechanisms of action make methadone an interesting choice for chronic pain
--> is the preferred method of MANAGING OPIOID WITHDRAWAL for addicted patients because it has a long-half-life and less profound sedation + euphoria
--> d/t the long 1/2 life of methadone, the abstinence syndrome is prolonged but less severe than that from a shorter-acting opiate such as heroin
--> these properties make methadone a useful drug for detox and for maintencnce of the chronic relapsing HEROIN ADDICT
AE: QT PROLONGATION, TORSADES DE POINTES, DEATH have all been reported
ALL HAVE "COD" in their name, you never play cod alone (usually combined), and is used as an anti-tussive (don't cough when playing) --> gives you that MORPHINE HIGH b/c converted to morphone by CYP2D6
-don't confuse with hydromorphone or oxymorphone
-are LESS EFFICACIOUS than morphine
-are RARELY USED ALONE --> usually combined with aspirin, acetaminophen, or other drugs
-codeine has LOW AFFINITY for opioid receptors
-the analgesic effect of codeine is d/t its conversion to MORPHINE by CYP2D6 (metabolites have greater potency)
HOWEVER: it's ANTITUSSIVE ACTIONS may invovle distinct receptors that bind codeine itself
MILD TO MODERATE AGONIST
TRAM A DOLL --> tram tracks --> inhibit reuptake of people that miss the tram. NO SER, you cant get on the tram. People only use the tram if they have NEUROPATHIC PAIN, ie they can't walk themselves
--> starts and stops fast, so people on the tram have an increased risk for SEIZURES, SEROTONIN SYNDROME
-NEED to know this one
- 1) Weak μ agonist and
- 2) norepinephrine and serotonin reuptake inhibitor.
USES: for NEUROPATHIC PAIN
1) increased risk of seizures in patients with a seizure disorder and those taking medications that lower seizure threshold.
2) Use of tramadol with other serotonergic drugs should be avoided because it may precipitate a serotonin syndrome.
-the mixed opioid agonist-antagonist are POTENT ANALGESICS in opioid-naive patients
-they PRECIPITATE WITHDRAWAL in aptients who are physcially dependent on opioids
-useful in MILD-MODERATE PAIN
-they were developed to REDUCE the addiction potential of the opioids
PENTAZOCINE, BUTORPHANOL, NALBUPHINE = κ agonist and a μ antagonist
---> PENTA BUTS "N AL B PHINE" (and i'll be fine) Say K to 5 girls, Say No to U
BUPRENORPHINE = partial μ agonist and a κ antagonist.
--> "burp en phine" = burping fine... think g/f is burping, so only partially attracted to the "U"
--> is a loyal dude, so is a K antagonist
partial μ agonist and a κ antagonist
-is approved for the management of OPIOID ADDICTION
Mixed agonist-antagonists are not recommended as routine analgesics, because they have CEILING EFFECT
Also, pentazocine, butorphanol and nalbuphine may cause psychotomimetic effects.***
• Psychotomimetic effects are uncommon with buprenorphine.
Antagonists at μ, δ and κ receptors
"NIL-OXONE" --> in an opioid overdose it NIL's the ozone outta there
-is used in the treatment of ACUTE OPIOID OVERDOSE
Antagonists at μ, δ and κ receptors
NIL-TREX-ONE --> get the fuck outta the REX man, you need some help to "nil" your alcohol problem
-is used for OPIOID ADDICTION
--> it DECREASES CRAVING FOR ALCOHOL in CHRONIC ALCOHOLICS and is approved for this purpose
DEX PHAN --> dexter needs to take the anti-cough medication because he cna't get caught while he's killing people
--> he needs the CODE to get IN
-are among the MOST EFFECTIVE drugs available for suppression of cough
-this effect is often acheived at doses below those necessary to produce analgesia
-the receptors involved in the antitussive effect appear to DIFFER from those associated with other actions of opioids
--> diphenoxylate makes you DIP LATE (ie makes you not go to the bathroom), it makes you LOOP BACK and hold back your poop
-widely used in the Tx of DIARRHEA
-they act by several different mechanisms, mediated principally through either
- μ or δ receptors on enteric nerves, epithelial cells, and muscle.
At the usual doses, diphenoxylate and loperamide lack analgesic effects