Saturday 16 June 2012

Psychotomimetic Agents


Psychotomimetic drugs
Also referred as hallucinogens which affect thought, perception and mood without causing marked psychomotor stimulation or depression
Psychotomimetic drugs fall broadly into 2 groups:
o    Drugs that act on 5-HT transporter or receptors
§  agonist at 5-HT2 receptors (LSD, psilocybin, mescaline)
§  inhibitor of 5-HT uptake (MDMA)
o    Antagonists at NMDA-type glutamate receptors (PCP)

Toxicity/overdose
Depends on the individual drugs
1 Tissue toxicity - some are neurotoxic
2 Psychic toxicity - acute transient psychosis, flash backs
3 Behaviour toxicity - distorted behaviour, aggressive, violent

Hallucinogens withdrawal
These drugs do not cause physical dependence, but they have tremendous abuse potential (psychological dependence).

LSD, Psilocybin & Mescaline
They are exceptionally potent psychotomimetic drug
Lysergic acid diethylamide (LSD) occurs in the fungus ergot
Mescaline is derived form Mexican cactus while Psilocybin is obtained from fungus, similar properties to LSD
Their main effects are on mental function (most notably alteration of perception in such a way that sights and sounds appear distorted and fantastic)
Hallucinations which include visual, auditory, tactile and olfactory aspect also occur.
Sensory modalities may become confused - that sounds are perceived as visions
Thought processes tend to become illogical and disconnected.

LSD appears to act as an agnoist at 5-HT2 receptors and suppresses electrical activity in 5-HT raphe nuclei.
LSD is exceptionally potent, producing a long-lasting sense of dissociation and disordered thoguht, sometimes with frightening hallucinations and paranoid delusions (bad trip) which can lead to violence
Hallucinatory epsiodes can recur even after a long interval
Activation of the sympathetic nervous system causes pupillary dilation, hypertension, piloerection and hyperthermia
LSD may precipitate schizophrenic attacks in suspetible patients

MDMA
MDMA is an amphetamine derivate which is a powerful psychomotor stimulant & psychotomimetic
MDMA works by inhibiting monoamine transporter especially the serotonin transporter, which bring the net effect of large increase in free serotonin in certain brain regions.
Research in animals links MDMA exposure to long-term damage to neurons that are involved in mood, thinking, and judgement.

MDMA effects
They have many effects similar to amphetamines.
Chronic users of MDMA are found to perform more poorly than nonusers on certain types of cognitive or memory tasks.
The after effect of MDMA persist for few days and comprise depression, anxiety, irritability, increased aggression - also kown as 'midweeek blues'
At high doses, MDMA can interfere with one body's ability to regulate temperatue leading to hyperthermia which results in kidney, liver and cardivascular system failure)
MDMA is able to  interfere with its own metabolism, potentially harmful levels can be reached by repeated drug use within short intervals.

Phencyclidine
Phencyclidine is also known as PCP or 'angel dust'. Its effect resemble other psychotomimetic drugs but also include analgesia.
Phencyclidine main pharmacological action is to block the NMDA receptor channel in cortex and limbic system. It produces hallucinations which is the desired effect, however, detachment, disorientation and violent behavior may occur. Phencyclidine can be fatal in overdose.

PCP effects
At low dose, it can cause dreamlike, carefree state, mood elevation, heightened or altered perception.
Adverse effects are impaired judgment, mood swings and partial amnesia

At moderate dose, it induces inebriation, dissociation, depersonalization, perceptual distortion, diminished pain sensitivit.
Adverse effects are ataxia, motor impairment, confusion, disorientatoin, abnormal body sensations, amnesia, exaggerated mood swings, panic

At high dose, it may cause all of the above effect mentioned plus hallucinations
Adverse effects are catatonia, 'blank' stare, delirium, severe motor impairment, psychotic behavior, hypertensive crisis.

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