Opiates Option D, Section 3

Morphine Naturally occurring in the poppy - only needs to be isolated Belong to group of alkaloids Very strong pain reliever but also very addictive (2nd to heroin) Usually injected but can be smoked, sniffed, or swallowed Commonly used in hospitals Large illegal street culture

Strong Analgesics Morphine and its derivatives (opiates) Known as narcotic analgesics Used to relieve severe pain associated with injuries, heart attacks, or chronic diseases such as cancer Most strong analgesics are derived from the opium poppy or synthetically produced

Mechanism of Strong Analgesics The human body contains “natural opiates” in the brain called endorphins These are produced in the body during extreme conditions such as “running high” and extreme injuries. When these are absorbed by receptors in the brain the body feels analgesia and the pain is reduced.

Mechanism of Strong Analgesics Opiates derived from the poppy act in the same way as endorphins but are not natural to the human body. The “high” is produced because of the absorption of opiates is quicker than endorphins Drugs such as naloxone act to fill the receptors in the brain but are not analgesics and thus are used to prevent overdoses on analgesics. Endorphins are not used as analgesics because they cannot be stored and are unstable.

Mechanism of Strong Analgesics Temporarily bind to opioid receptors in the brain to depress the central nervous system (CNS)

Side Effects of Strong Analgesics Short term Dulling of Pain Euphoria Slow Nervous system Slowed heart rate Loss of cough reflex Nausea Overdoses can lead to death Possibility of stroke Overall slowdown of biological systems Long Term Addiction and very strong withdrawal effects Constipation Loss of libido Disruptions in menstruation “Cross-tolerance” Loss of appetite Problems associated with buying street drugs i.e. sharing needles AIDS and prostitution.

Crossing the blood-brain barrier Activity of opiates depends on ability to cross blood-brain barrier – a series of lipophilic cell membranes that cover the blood vessels and prevent polar molecules from entering the CNS. Lipophilic – dissolves in fats (lipids) Presence of one amino and two hydroxyl groups makes it polar enough to be soluble, but reduces the ability to reach the opioid receptors in the brain.

Codeine Derivative of morphine Modify one phenolic group to ether group Can cross the blood brain barrier, but does not bind to opioid receptor because of steric hindrance of ether group. Metabolized into morphine which can bind opioid receptor. 10x less potent than morphine Commonly used with Tylenol as a more mild analgesic Low activity, wide therapeutic window, and limited potential for abuse makes it the most widely used opiate in the world. Steric hindrance: stopping of a reaction because of shape of molecule (wrong or too bulky to fit receptor).

Heroin (diamorphine) Derivative of morphine – both hydroxyl groups substituted with ester groups. Prepared from reacting morphine with ethanoic anhydride (?) Soluble in lipids (crosses blood-brain barrier) and is quickly metabolized into morphine. 5 times more potent than morphine, but has more severe side effects Most dangerous substances of abuse. Responsible for nearly 50% of all drug-related deaths around the world. Banned or restricted to terminally ill patients with certain forms of cancer or CNS disorders.

Heroin (diamorphine) Originally sold as cough suppressant and a pain killer

Methadone Compared to most strong analgesics it is weaker. Has been synthesized to not have euphoric properties and mild withdrawal effects but is still addictive. Used as an analgesic but most commonly to help in the withdrawal for heroin addicts.

Other Synthetic Strong Analgesics Vicodin Is solution of acetaminophen and hydrocodone (the latter being the stronger) Hydrocodone is addictive and can cause highs. Usually taken orally Stronger than codeine but not as strong than Morphine

Demerol Demerol (Meperidine) Used for moderate to severe pain and to stop muscle spasms. Usually injected or taken orally.