GABA (γ-aminobutyric acid). major inhibitory neurotransmitter in CNS synthesized from glutamate GABAa receptor protein is the site of action of benzodiazepines.

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Presentation transcript:

GABA (γ-aminobutyric acid)

major inhibitory neurotransmitter in CNS synthesized from glutamate GABAa receptor protein is the site of action of benzodiazepines and barbituates (synthetic anti-seizure medications and sedatives)

GABA Antagonist: Anamirta cocculus fish-berry or Indian berry in Indomalaysia in Indomalaysia, fruit is used as a fish poison, insecticide, and treatment for head lice active compound: Picrotoxin stimulates CNS by inhibiting a ction of GABA modern therapeutic uses: treats barbituate poisoning CNS stimulant schizophrenia

GABA Enhancer: Areca catechu nipecotic acid in Areca catechu is precursor of chemical derivative, gabitril Gabitril blocks the re-uptake of GABA and increases its concentration at receptors

Betel Nut Main part used is leaves &may be used seeds. the betel nuts, which are chewed for their stimulatory effects. The nuts contain arecoline, a strong stimulant. Chewing of the nuts releases brightly yellow colored keratin medicinally,the betel nut is used to treat intestinal worms

Cont… seizures occur when too many impulses generated in brain since gabitril enhances GABA levels and GABA has an inhibitory effect on neurotransmitters, gabitril is used to treat seizures

GABA Enhancer: Valeriana officinalis Valerian native to Europe root traditionally used as sedative and sleep enhancer active chemicals: valepotriates, enhance GABA levels in CNS used as a sedative and sleep enhancer

Endorphins bind to opiate receptors in brain and have analgesic (pain reducing) effects

Opiate receptor agonists: Papaver somniferum opium, opium poppy originated in western Mediterranean & Near East dried latex from immature fruit capsules traditionally used as an analgesic, inebriant, hypnotic, and treatment for diarrhea

History 3000 BC – first records of use; 2500 BC – Sumerian “joy plant” Romans/Greeks – familiar with opium Europe – 1525, rediscovery of solution of opium in alcohol = laudanum (Paracelsus) Chinese – first introduced in 7th century AD by Arab traders Banned by government British trade policies  forced Chinese to trade for opium 1803 – morphine purified  able to deliver it in defined doses Potent painkiller, but problem – addictive

narcotics The term "narcotic" is believed to have been coined by the Greek physician Galen to refer to agents that numb or deaden, causing loss of feeling or paralysis. It is based on the Greek word (ναρκωσις =narcosis), the term used by Hippocrates for the process of numbing or the numbed state.Galen Hippocrates Narcotics refer to opium, opium derivatives, and their semi-synthetic or fully synthetic substitutes. Typical classes of narcotics include morphine, opium, and heroine.

Papaver Alkaloids- Opiates Fig. 11.6, p. 279

Opiate receptor agonists: Papaver somniferum opium contains 20 alkaloids, including: morphine (  heroin) codeine papaverine thebaine noscapine

Opiate receptor agonists: Papaver somniferum Therapeutic uses: morphine = analgesic codeine = analgesic, antitussive noscapine (narcotine) = antitussive Mechanism of analgesis: stimulation of opiate receptors inhibits the release of substance P, the neurotransmitter responsible for inflammatory responses and pain

Administration Narcotics can be administered in a variety of ways. In a medical context, they are taken orally, transdermally (skin patches), injected, or administered as suppositories. As recreational drugs, they may be used orally, but are also commonly smoked, snorted, or self-administered by the more direct routes of subcutaneous ("skin popping") and intravenous ("mainlining") injection.

Effects Drug effects depend heavily on the dose, route of administration, previous exposure to the drug, and the expectation of the user. Aside from their clinical use in the treatment of pain, cough, and acute diarrhea, narcotics produce a general sense of well-being, known as euphoria, and reduce tension, anxiety, and aggression. These effects are helpful in a therapeutic setting and contribute to their popularity as recreational drugs, as well as helping to produce dependency.

Side Effects Narcotic use is associated with a variety of side effects, including drowsiness, itching, sleeplessness, inability to concentrate, apathy, lessened physical activity, constriction of the pupils, dilation of the subcutaneous blood vessels causing flushing of the face and neck, constipation, nausea, vomiting and, most significantly, respiratory depression. As the dose is increased, the subjective, analgesic, and toxic effects become more pronounced. Except in cases of acute intoxication, there is no loss of motor coordination or slurred speech, as occurs with many depressants such as alcohol or barbiturates. Among the hazards of careless or excessive drug use are the increasing risk of infection, disease and overdose. Medical complications common among recreational narcotic users arise primarily from the non-sterile practices of injecting.barbiturates

Narcotics and addiction It is the neurological effects of narcotic drugs that make them addictive. Narcotics bind to painkilling sites throughout the brain, known as opioid-u receptors, or the "reward pathway. " This leads to slower uptake of neurotransmitters such as dopamine between neurons. Immediate effects include cessation of pain, drowsiness, and a feeling of well-being associated with pain reduction. Addiction occurs when the brain stops producing its own natural painkilling chemicals, called endorphins, and depends on the narcotics instead.neurologicalneurons

Dependence With repeated use of narcotics, tolerance and dependence develop. The development of tolerance is characterized by a shortened duration and a decreased intensity of analgesia, euphoria and sedation, which creates the need to administer progressively larger doses to attain the desired effect. Tolerance does not develop uniformly for all actions of these drugs, giving rise to a number of toxic effects. Although the lethal dose is increased significantly in tolerant users, there is always a dose at which death can occur from respiratory depression. Physical dependence refers to an alteration of normal body functions that necessitates the continued presence of a drug in order to prevent the withdrawal or abstinence syndrome.dependencewithdrawal

Withdrawal Symptoms The withdrawal symptoms experienced from opioid addiction are usually first felt shortly before the time of the next scheduled dose. Early symptoms include watery eyes, runny nose, yawning and sweating. Restlessness, irritability, loss of appetite, tremors and severe sneezing appear as the syndrome progresses. Severe depression and vomiting are not uncommon. The heart rate and blood pressure are elevated. Chills alternating with flushing and excessive sweating are also characteristic symptoms.

Psychological Dependence The psychological dependence that is associated with narcotic addiction is complex and protracted. Long after the physical need for the drug has passed, the addict may continue to think and talk about the use of drugs. There is a high probability that relapse will occur after narcotic withdrawal when neither the physical environment nor the behavioral motivators that contributed to the abuse have been altered.think