1. Analgesia
2. Anesthesia

3. Antitussive

4. Antidiarrheal 

Opiate: A natural compound present in opium

Opioid:any drug, natural or synthetic, with morphine-like actions;
opioids are the most effective analgesics available

Analgesic: drug that relieves pain without causing loss of consciousness 

endogenous opioid peptides

3 familes of peptides and how long are each of them?

1. Enkephalins: brief

2. Endorphins: longer duration

3. Dynorphins: longer duration 

Mu: most important. mediate analgesia, respiratory depression, sedation, euphoria, physical dependence, decrease GI motility

Kappa: analgesia, sedation, decr GI motility, dysphoria, psychotomimetic effects

Delta: not directly activated by most opioid analgesics. The enkephalins are endogenous ligands 

Gi: inhibits adenylyl cyclase which decreases cAMP.

presynaptic; closes Ca++ channel so decreases neurotransmitter release

postsynatpic: opens K+ channel cuasing hyperpolarization and inhibition of inhibitory neurons 

-Classified by how they affect funcion of receptor; agonist, partial agonist, antagonist

-Pure opioid agonists:

-Agonist-Antagonists opioids:

-Pure opioid Antagonists 

Pure Agonists

What is prototype in this group?

-What does this group cause in the body?

-MOA?
-Components of Pain?

-Morphine

-analgesia, sedation, and euphoria

- mimicks actions of endogenous opioid peptides at primarily mu and partially kappa receptors
-Relieves both components, Sensation and Suffering

-Respiratory depression, Antitussive, sedation, miosis, n/v, convulsant/excitation, hypothermic, neuroendocrine, euphoria/dysphoria (dysphoria if taken in absence of pain), Constipation, Urinary retention, Biliary colic, orthostatic hypotension, decrease renal function, elevation of intracranial pressure, release histamine, prolon labor.

-Naloxone

-faster if parenteral

 
-oral b/c high 1st pass metabolism.

-No, it rapidly leaves the blood and localizes in tissues with high blood flow and perfusion. Slow penetration into the BBB

Metabolism

-active metabolite?

-inactive metabolite?
-Does it go through enterohepatic recirculation?

-Morphine 6-glucoronide

-Morphine 3-glucoronide

-yes it does go through enterohepatic recirc. 

Tolerance develops to which of the following when taking Opioids?
a.analgesia

b.euphoria

c.sedation

d.miosis

e.convulsions

f.constipation

-Can be cross tolerant with other opioids

-Cannot be cross tolerant with other CNS depressants 

PHYSICAL DEPENDENCE

-should you stop abrubtly?

-more at risk of dependence, for acute pain or chronic?
-pregenant, what's special about dependency?

-should you withhold rx from patient in pain if you think they are addicted? 

-no withdraw gradually or else withdrawal symptoms will occur.

-chronic

-the fetus can be dependent on the drug

-absolutley not! 

D/I

-what other drugs can have drug interactions? 

-CNS depressnats: additive effects

-Anticholinergics: increase constipation and urinary retention

-Antihypertensives: increase hypotension

-MAOI's: excitation, delirium, convulsions, hyperpyrexia, sever resp depress. death!
-Agonist-antagonist opioids:

Acute Toxicity

-symptoms?

-dosage?

-treatment? 

-coma, resp depression, pinpoint pupils

-greater then 120 mg

-support respiration and give opioid antagonist (naloxone!) 

Dosing Considerations

-Can everyone have the same typical dose?

-what is better for chronic and acute pain? prn or atc? 

- no highly individualized. lower dose for elderly and children.

-for chronic, use long acting for atc pain and Imediate release if needed.  For acute, use on fixed schedule q4h rather then prn. 

-Oral

-Parenteral- for acute pain

-Recatal 

Heroin

-schedule?

-how related to morphine

-cross BBB? why?

- 

-SCHEDULE 1

-prodrug of morphine 

-Rapidly crosses BBB b/c greater lipid solubility

Meperidine

-why is this preferred to morphine in some cases?

-slow or fast onset and duration?

-what else is it used for besides obstetrical analgesia? 

-b/c it does not decrease uterine contractions and has minimal respiratory depression. less constipation too

-slightly faster onset and shorter duration

-also used as preop medication and during anesthesia 

METHADONE
-duration of action?

-clinical uses? 

-long duration fo action

 -relieve of severe pain, detox and maintenance treatment of opioid addicts

Levomethadyl (ORLAAM)

-used for?

-long short acting?

-how is it available? 

-treating opioid addicts

-long acting

-only available through federally-approved programs for addiction treatment 

FENTANYL

-how is it used?

-onset and duration?

-lipophobic or philic?
-what was it developed for, what pain?

-parenterally(inducing and maintaing anesthesia)  or transdermally(chronic pain) or oral (lollipop)

-short duration rapid onset

-lipophilic 

-for breakthrough cancer pain 

Codeine

-low or high oral:parenteral potency?

-schedule?

-a lot of a little is changed to morphine?

-effects of medication? 

-highest oral:parenteral potency

-schedule 2 by itself

-a little bit is demethylated to morphine ~10%

-antitussive, analgesia

Nalxone(Narcan)

-used for?

-how does it work?

-how can you take it? 

-DOC for overdose of pure opioid agonist, to reversepostopopioid resp, cns depress, and to reverse neonatal resp depression.

-competitive antagonist of opioid receptors (highest affinity for mu)

-only parenteral