Pharmacology Strong Analgesic Drugs

Front 1

What are two distinctive characteristiccs of opioid induced analgesia?

Back 1

-Very effective without loss of consciousness
-Reduction in suffering disproportionate to reduction in pain perception

Front 2

What is an opiate?

Back 2

Any of several analgesic alkaloids (or semisynthetic drugs derived from them) found in opium, which is the dried joice of the poppy, Papavver somniferum; morphine and codeine are the two most prominent examples

Front 3

What is an opioid?

Back 3

All agonists and antagonists which have morphine-like effects, or which act predominantly at opioid receptors; includes opiates, endogenous neurotransmitters like beta-endorphin, and synthetic drugs like meperidine

Front 4

Explain the ascending pathway for pain

Back 4

-Adelta (fast pain) and C (slow pain) primary sensory fibers synapse on projection neurons in the spinal cord. These project to the thalamus and in regions involved in processing of emotional information and regulating autonomic responses.

Front 5

Explain the descending pathway for pain

Back 5

1. Periaqueductal gray receives inputs from spinal cord, prefrontal cerebral cortex, hypothalamus and amygdala.
2. Projects to the rostral ventral medulla (RVM)
3. This inhibits spinal cord projection neurons via local inhibitory interneurons that use an opioid transmitter, enkephalin

Front 6

Endorphins

Back 6

-Beta-endorphin
-mu +++
-delta +++
-kappa -
-Derived by proteolytic processing from proopiomelanocortin (POMC)
-Major location in arcuate nucleus of hypothalamus, which projects to periaqueductal gray

Front 7

Enkephaloins

Back 7

1. Leu and met0enkephalin
2. Derived from proenkephalin
3. mu ++ delta +++
4. Important location in inhibitory interneurons in dorsal horn of the spinal cord; also in periaqueductal gray

Front 8

Dynorphins

Back 8

1. Dynorphins A and B, alpha-neoendorphin
2. Derived from prodynorphin
3. Dynorphins: mu ++ kappa +++
alpha-neoendorphin kappa +++
4. In spinal cord and periaqueductal gray

Front 9

Describe the analgesic effect of morphine

Back 9

-More of a reduction in the suffering associated with pain than in the pain perception itself
-Dull pain blocked more effectively than sharp pain

Front 10

What are the side effects of morphine?

Back 10

-Nausea
-Drowsiness, lethargy, inability to concentrate
-Euphoria
-Depressed resiration
-Pinpoint pupils (miosis)
-Increases GI tone, reduced pulsitile waves
-Reduced biliary and pancreatic secretions
-Flushed, warm skin

Front 11

Describe the absorption, distribution, metabolism, and excretion of morphine

Back 11

-Well absorbed through all routes
-Does not penetrate BBB
-Considerable first pass effect
-Hepatic glucuronidation is a major metabolic pathway
-Morphine conjugates excreted mainly by kidney

Front 12

Describe tolerance and dependence of morphine

Back 12

-These develop with repeated use, but are not necessarily predictors of abuse
-Withdrawal symptoms not difficult to avoid

Front 13

Describe codeine

Back 13

-Lower affinity for mu receptor than morphine
-Less first-pass effect than morphine
-Often used with non-opioid analgesic to increase analgesic potency without side effects
-Antitussive action through both mu receptor and non-opioid receptor

Front 14

Dextromethorphan

Back 14

Structurally related to codein but has no analgesic activity and suppresses cough by binding to non-opioid receptors

Front 15

Methadone

Back 15

-Similar to morphine in receptor binding and effects
-Good choice for treatment of severe chronic pain and opioid addiction
-Oral potency: ease of admin, decrease threat of infectious disease because needles not used
-Slow onset and long duration of action: no rush, little high, less intense withdrawal symptoms

Front 16

Meperidine

Back 16

-Similar to morphine in receptor binding and effects, including non-analgesic effects
-More rapid onset and shorter duration of action than morphine
-Good analgesic during labor because produces less fetal respiratory depression than morphine
-Should not be taken w MAOI
-Not recommended for long-term use because of toxicity

Front 17

Fentanyl

Back 17

-Structurally related to meperidine
-Similar to morphine in receptor binding and effects
-Rapid, brief action make it favored for anesthesias
-Used in general anesthesia and for postoperative pain
-Less constipation than morphine
-Does not cause histamine release, so less cardiovascular effect

Front 18

Pentazocine

Back 18

-Synthesized in an effort to develop an effective analgesic with little abuse potential
-Produces analgesia by binding to kappa receptor
-Partial agonist at mu receptor, so produces less respiratory depression than morphine at high doses
-Dysphoria and psychotomimesis possible at high doses

Front 19

Buprenorphrine

Back 19

Mixed agonist/antagonist
-Derived from thebaine
-Considerably more potent than morphine at mu receptor, but only a partial agonist
-Antagonist at kappa receptor
-Potent partial agonist so can reduce effects of more efficacious agonists at mu receptor.

Front 20

Naloxone

Back 20

-Competitive blocker at mu and kappa receptors
-Used to diagnose and treat opioid overdose, as it has rapid effect
-Administered parenterally

Front 21

Maltrexone

Back 21

-Competitive blocker at mu and kappa receptors
-Higher oral efficacy and longer lasting than naloxone
-Used to treat addiction