However, CYP2D6 has been implicated in the toxicity and death of neonates when codeine is administered to lactating mothers, particularly those with increased enzyme activity ("ultra-rapid" metabolizers). Pharmacology
Pharmacodynamics
Codeine is a nonsynthetic opioid. It is a selective agonist of the μ-opioid receptor (MOR). Codeine itself has relatively weak affinity for the MOR. Instead of acting directly on the MOR, codeine functions as a prodrug of its major active metabolites morphine and codeine-6-glucuronide, which are far more potent MOR agonists in comparison.Codeine has been found as an endogenous compound, along with morphine, in the brains of nonhuman primates with depolarized neurons, indicating that codeine may function as a neurotransmitter or neuromodulator in the central nervous system. Like morphine, codeine causes TLR4 signaling which causes allodynia and hyperalgesia. It doesnt need to be converted to morphine to increase pain sensitivity. Mechanism of action
Codeine is an opioid and an agonist of the mu opioid receptor (MOR). It acts on the central nervous system to have an analgesic effect. It is metabolised in the liver to produce morphine which is ten times more potent against the mu receptor. Opioid receptors are G protein-coupled receptors that positively and negatively regulate synaptic transmission through downstream signalling. Binding of codeine or morphine to the mu opioid receptor results in hyperpolarization of the neuron leading to the inhibition of release of nociceptive neurotransmitters, causing an analgesic effect and increased pain tolerance due to reduced neuronal excitability. Pharmacokinetics
The conversion of codeine to morphine occurs in the liver and is catalyzed by the cytochrome P450 enzyme CYP2D6.
These can have an indirect effect on appetite by a number of means, including peripheral afferents from their sites of production in the body, by enhancing production of leptin from fat stores. Inflammatory cytokines can also signal to the central nervous system more directly by specialized transport mechanisms through the blood–brain barrier, via circumventricular organs (which are outside the barrier), or by triggering production of eicosanoids in the endothelial cells of the brain vasculature. Ultimately, the control of appetite by this mechanism is thought to be mediated by the same factors normally controlling appetite, such as neurotransmitters (serotonin, dopamine, histamine, norepinephrine, corticotropin releasing factor, neuropeptide Y, and α-melanocyte-stimulating hormone). Drugs
Stimulants, such as ephedrine, amphetamine, methamphetamine, MDMA, cathinone, methylphenidate, nicotine, cocaine, caffeine, etc. Narcotics, such as heroin, morphine, codeine, hydrocodone, oxycodone, etc. Antidepressants can have anorexia as a side effect, primarily selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine. Byetta, a type II diabetes drug, will cause moderate nausea and loss of appetite. Abruptly stopping appetite-increasing drugs, such as cannabis and corticosteroids. Chemicals that are members of the phenethylamine group. (Individuals with anorexia nervosa may seek them to suppress appetite.) Topiramate may cause anorexia as a side effect. Other drugs may be used to intentionally cause anorexia in order to help a patient preoperative fasting prior to general anesthesia. It is important to avoid food before surgery to mitigate the risk of pulmonary aspiration, which can be fatal.