With drug means any substance that affect the functioning of the SN. In addition to NT, several other psychotropic substances that act on the SN. Among the endogenous substances include the NT, neuromodulators, hormones, II messengers that are created by the body to alter the functioning of the synapse. However, there are exogenous substances that interfere with the functioning of the synapse, including animal and plant poisons and psychoactive substances such as drugs and drugs (drug abuse). The pharmacodynamic
concern the way drugs act on the body. A drug can have two effects on synaptic transmission.
L ' of a NT agonist is a substance that increases the effects.
can act at pre-synaptic synthesis or by increasing the release of NT (poisons) or by increasing the permanence of the NT in the synaptic cleft by inhibiting the reuptake or by inhibiting the enzyme inactivation (drugs).
at post-synaptic site binds to the NT with similar or more intense activity, increases the affinity for NT, enhances the effects of NT.
L ' of NT antagonist reduces or blocks the effect.
The antagonist may act at pre-synaptic inhibition of synthesis by inhibiting the release of NT or NT. A post-synaptic
decreases the affinity of receptor for NT or occupies the active site but not showing effects.
Both agonists antagonists that can bind to the active site of the NT receptor or of the active sites of the receptor sensitive to other endogenous molecules. In many cases it is not yet known endogenous substance that is to interact with these sites. The opiate morphine
was discovered before payment endogenous' s endorphin. More recently have been discovered endogenous substances that bind to the active site of cannabinols , the ' anandamide and 2-AG these endocannabinoids . The
benzodiazepines (anxiolytics) act subclass of GABAA channels selectively.
L ' alcohol increases the action of GABA and inhibits NMDA channels.
L-dopa (parkinson therapy) increases the synthesis of dopamine. The
curare blocks the nicotinic receptors. The
nicotine stimulates nicotinic receptors.
Cocaine and amphetamine block the reuptake of norepinephrine and dopamine. Cocaine in particular the dopamine system and lead to a strong dependency because the dopamine system is linked to pleasure and positive reinforcement. The
cannabinols act on pre-synaptic autoreceptors inhibiting the release of NT. Act on glutammaergico and GABAergic system. The
caffeine increases the release of glutamate. The antidepressants I
generation MAO inhibitors which inactivate the catecholamines in the synaptic cleft. The second generation antidepressants
(Prozac) block the reuptake of serotonin. Some
local anesthetics (eg lidocaine ) act by binding to voltage-gated ion channels of the SNP by limiting the action potential. The pharmacokinetics
is the process by which drugs are absorbed, distributed in the body, metabolized and excreted. 99% of psychoactive substances CNS-active so it must cross the blood-brain barrier and penetrate into the nervous tissue. The exogenous substances are continuously removed by enzyme systems present in blood and especially in the liver and excretion via the urine.
The pharmacokinetics of a substance is highly dependent mode of administration (intravenous, smoked, oral, intranasal, etc.).. Among the factors that determine the speed at which a drug reaches the site of action is the ability to cross the blood-brain barrier and this depends greatly on the lipid solubility of the molecule, because the water-soluble molecules are retained. For example, morphine and heroin within the brain have the same effectiveness of action, however, heroin is much more soluble and has a more rapid and intense.
Regarding the effectiveness of a drug, some drugs are active in small doses, others only at high concentrations. To assess the effectiveness of a drug is administered to different subjects (correcting for body weight) and measuring objectively the effects. This will produce a dose-response curve . This is usually a sigmoid in which there is a minimum to detect the effect, then increases linearly until a dose escalation does not increase the effect.
Most of the drugs has more of an effect. Some are harmful side effects, such as morphine and high doses depresses the respiratory system and causes death by asphyxiation. A good product should have a good therapeutic index, ie the ratio between the dose-response for the desired dose-response for side effects. The distance between the two dose-response is said margin of safety. Technically, the therapeutic index is the ratio of the dose that produces the toxic effect on 50% of the subjects and the dose that produces the desired effect in 50% of subjects. For example, the index is between 2 and 3 for barbiturates and is about 100 for benzodiazepines (valium). This means that is very easy to accidentally make mistakes with fatal consequences dose in the first case in the second.
If a drug is normally administered repeatedly changing its pharmacokinetics.
The most frequent is that of tolerance . With prolonged use its effects are less and less effective and increasing doses. Tolerance is the body's attempt to offset the effects of the drug in order to obtain an optimal level of functioning. In general, the tolerance may depend on many factors, such as the increased capacity of the liver and other mechanisms to metabolize the drug. At the neural level depends on induced changes in the level of synapses. Can be produced channels that have reduced affinity with the drug, may be reduced on the membrane channels, can change the production and inactivation of the second messengers. For all intents and different tolerances occur. For instance, for benzodiazepines, tolerance to the hypnotic effect is very rapid, while the anxiolytic effect tolerance occurs in a minor.
A secondary aspect of the phenomenon of tolerance are the symptoms of withdrawal , ie, effects opposite to those induced by the drug. In fact, the metabolism may have been set for the arrival of a given drug agonist of NT and by the time the pre-synapse always produces less NT.
The effect is the opposite of tolerance awareness, so the drug at doses similar effects increasing. For example, the euphoric effects of cocaine develop tolerance, while the secondary symptoms such as disturbance in the movement undergoes sensitization.
Levin (1979) studied the biological basis of ' placebo effect, ie a dose of a drug is not active but produces measurable effects in the subject.
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