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- 1. Influence of Drugs NoorUl Ain Basit
- 2. - Psychopharmacology isthe study of how drugs affect the nervous system and behavior - A drug is a chemical compound that is administered to bring about some desired change in the body. - Psychoactive drugs—substances that act to alter mood, thought, or behavior and are used to manage neuropsychological illness. Many psychoactive drugs are also substances of abuse.
- 3. Drug Intake - Theway in which a drug enters and passes through the body to reach that target is called its route of administration - Drugs can also be inhaled, administered through rectal suppositories, absorbed from patches applied to the skin, or injected into the bloodstream, into a muscle, or even into the brain - Drug absorption is affected by drugs properties
- 5. Drug Removal - Drugsare metabolized throughout the body, but particularly in the kidneys, liver, and bile. They are excreted in urine, feces, sweat, breast milk, and exhaled air. - Drugs manufactured for therapeutic purposes are usually designed to optimize their chances of reaching their targets and to prolong their survival in the body. - The body has trouble removing some substances, however, and these substances are potentially dangerous because, with repeated exposure, they can build up in the body and become poisonous
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- 7. Blood Brain Barrier Afew brain regions lack tight junctions between the cells of capillary walls and so lack a blood–brain barrier. These regions are shown in Figure 7.3. The pituitary gland of the hypothalamus is a source of many hormones that are secreted into the blood, and their release is triggered in part by other hormones carried to the pituitary gland by the blood. The absence of a blood–brain barrier at the area postrema of the lower brainstem allows toxic substances in the blood to trigger a vomiting response. The pineal gland also lacks a blood– brain barrier and is therefore open to the hormones that modulate the day– night cycles controlled by this structure
- 8. Drug Dosage - Themost effective consist of molecules that are small in size, weakly acidic, water or fat soluble, potent in small amounts, and not easily degraded - With each obstacle eliminated on the route to the brain, the dosage of a drug can be reduced by a factor of 10 and the drug will still have the same effects. - 1 milligram (1000 lg) of amphetamine, a psychomotor stimulant, produces a noticeable behavioral change when ingested orally. If inhaled into the lungs or injected into the blood, thereby circumventing the stomach, 100 lg of the drug (1000 lg 10) produces the same results. Similarly, if amphetamine is injected into the cerebrospinal fluid, thereby bypassing both the stomach and the blood, 10 lg is enough to produce an identical outcome, as is 1 lg if dilution in the CSF also is skirted and the drug is injected directly onto target neurons.
- 9. Drug Actions inSynapses - Each component of neurotransmission entails one or more chemical reactions that drugs can potentially influence. Drugs that increase the effectiveness of neurotransmission are called agonists, whereas those that decrease its effectiveness are called antagonists. - For example, all drugs that stimulate the release of the neurotransmitter dopamine or block the reuptake of dopamine or block dopamine’s inactivation are considered dopamine agonists, because they increase the amount of dopamine available in the synapse. Conversely, all drugs that block the synthesis of dopamine or its release from the presynaptic membrane or that block dopamine receptors or speed up dopamine’s inactivation are considered dopamine antagonists, because they decrease the biochemical effect of this transmitter in the synapse.
- 11. Drug Classification 1- Sedative-hypnotics and antianxiety: “sedative,” to calm or moderate nervousness or excitement, and “hypnotic,” sleep inducing At low doses, they reduce anxiety; at medium doses, they have a tranquilizing effect; and, at successively higher doses, they anesthetize, induce coma, and kill E.g alcohol, barbiturates and benzodiazepine All sedative-hypnotic drugs may act by influencing the GABA receptor dissociative anesthetics developed as anesthetic agents receive restricted use because they also produce altered states of consciousness and hallucinations e.g ketamine
- 13. Antipsychotic Psychosis: hallucinations (falsesensory perceptions) or delusions (false beliefs) Treatment drugs are known as major tranquilizers and neuroleptics. They include the phenothiazines( chlorpromazine) and butyrophenones (haloperido) Reduction of motor activity but prolonged use can be to produce symptoms reminiscent of Parkinson’s disease and dyskinesia (involuntary movements) Blocks D2 receptors: led to the dopamine hypothesis of schizophrenia schizophrenia-like symptoms of chronic users of amphetamine
- 14. Antidepressants monoamine oxidase inhibitors(MAO inhibitors), tricyclic antidepressants, and second-generation antidepressants, sometimes called atypical antidepressants, which include fluoxetine (Prozac) act by improving chemical transmission in serotonin, noradrenaline, histamine, and acetylcholine synapses and perhaps in dopamine synapses
- 15. MAO inhibitors stopsbreakdown of serotonin, Tricyclic blocks transporter to take serotonin back into axon, SGA more selective in blocking transporters thus keeping serotonin in the cleft for longer (SSRIs) Side effects include increased anxiety, sexual dysfunction, sedation, dry mouth, blurred vision, and memory impairment
- 16. Mood Stabilizers Treatment formanic depressive illness such as bipolar Include salt lithium and a variety of other drugs including valproate, which is also used to treat epilepsy lithium may increase the synaptic release of serotonin, and valproate may stimulate GABA activity. Typically, mood stabilizers mute the intensity of one pole of the disorder, thus making the other pole less likely to reoccur.
- 17. Narcotic Analgesic sleep-inducing (narcotic)and painrelieving (analgesic) properties derived from opium, an extract of the seeds of the opium poppy, Papaver somniferum Friedrich Sertürner synthesized two pure substances from the poppy plant—codeine and morphine. Codeine: cough medicine and in pain relievers such as aspirin. Morphin: very powerful pain reliever. Heroin, another opiate drug, is synthesized from morphine. It is more fat soluble than is morphine and so penetrates the blood–brain barrier more quickly. methadone, a drug widely used to treat addiction by acting as a substitute for heroin.
- 18. Morphine is similarto endorphins and can mimic their action in brain Opium antagonists such as nalorphine and naloxone block the action of morphine by blocking endorphin receptors thus are useful in reversing opioid overdoses. Endorphins are peptides and can be ingested to relieve pain, but they do not easily cross the blood–brain barrier so morphine is preferred for treatment
- 19. Psychomotor stimulants Behavioural: suchas cocaine and amphetamine increase motor behavior as well as elevating a person’s mood and level of alertness. Act as dopamine agonists. Cocaine derived from plants whereas amphetamine is synthetic compound discovered in attempts to synthesize epinephrine. Dextroamphetamine and methamphetamine (crystal meth) General: 1) . Caffeine inhibits an enzyme that breaks down the cyclic adenosine monophosphate (cyclic AMP). The resulting increase in cyclic AMP leads to an increase in glucose production within cells, thus making available more energy 2) Nicotine: increase in neuronal activity in (A), amygdala (B), and cingulate gyrus and frontal lobes (C). All these structures are the targets of dopamine projections
- 20. Hallucinogens Primary effect isto trigger non-ordinary mental states (known as psychedelic experiences or "trips") and a perceived "expansion of consciousness" e.g LSD, peyote, PCP, psilocybin, cannabis Act on serotonin altering appetite, sensory perception and glutamate altering emotions Drugs such as LSD result in vivid mental imagery, loss of sense of self, altered perception of time. They are not addictive as they dont cause uncontrollable drug-seeking behavior but dependance can still develop
- 21. Dopamine theory ofdrug abuse - Animals trained to perform actions through conditioning stop learned behaviour when dopamine channels are blocked - Drugs increases or prolongs availability of dopamine in synaptic cleft - Drugs blocking dopamine channels are not abused e.g psychosis drugs
- 22. Drug Abuse - DependenceHypothesis: Concept: Habitual drug users experience psychological or physiological withdrawal symptoms when the drug's effects wear off. Symptoms: Anxiety, insecurity, sickness. Behavior: Users take the drug again to alleviate these symptoms. Shortcomings of the Dependence Hypothesis: Long-term Abstinence: Addicts may return to drug use even after months of abstinence, long after withdrawal symptoms have disappeared. Selective Abuse: Some drugs, like tricyclic antidepressants, cause withdrawal symptoms but are not typically abused.
- 23. Cont. - Hedonic Hypothesis: Concept:People take drugs because they produce pleasure. Weakness: Addicted individuals often report that the drugs they take give them little pleasure. - Incentive-Sensitization Theory (Terry Robinson and Kent Berridge): Concept: Addiction is acquired unconsciously through conditioned learning, developing in stages.
- 24. Cont. Stages of AddictionDevelopment: Stage 1: Activation of pleasure as a consequence of drug taking; the user likes the experience. Stage 2: Pleasure becomes linked to objects, acts, places, and events connected to drug use through associative learning (classical conditioning). The drug-taking context and related cues are repeatedly paired with the drug, producing a pleasurable reaction. Stage 3: Attribution of incentive salience to drug-associated cues. These cues become highly desired and sought-after incentives. Acts leading to drug use become attractive, as do new acts predicted to lead to the drug.
- 25. Cont. Wanting-and-Liking Theory: Concept: Wanting(craving) and liking (pleasure) a drug are affected differently in addiction. Wanting: Increases in addiction; equivalent to craving a drug. Liking: Decreases in addiction; defined as the pleasure produced by drug taking. Liking: Activity of opioid neurons (endorphins) associated with early drug use pleasure. Wanting: Activity in the mesolimbic dopamine system, consisting of dopamine neurons in the midbrain projecting to the nucleus accumbens, frontal cortex, and limbic system.
- 26. Cues and Craving: Mechanism:Cues associated with drug taking activate the mesolimbic dopamine system, producing the experience of wanting. Unconscious Process: Desire for the drug is awakened by unconsciously acquired associations between drug taking and related cues. Persistence: Even long after drug use ends, cues can elicit craving by activating the mesolimbic dopamine system.
- 27. Drug induced behaviour -Disinhibition Theory: Concept: Alcohol selectively depresses the neocortex (responsible for judgment) while sparing subcortical structures (primitive instincts). Result: Alcohol reduces learned inhibitions based on reasoning and judgment, "releasing the beast within." - Learned-Behavior Theory (Craig MacAndrew and Robert Edgerton): Challenge to Disinhibition Theory: Behavior under the influence of alcohol varies widely depending on context. Some cultures show disinhibited behavior when sober and inhibited behavior after drinking, others are inhibited when sober and become more inhibited after drinking. Conclusion: Alcohol-related behavior is learned and specific to the drug, culture, group, and setting. It often represents a "time-out" from normal rules.
- 28. Cont. - Alcohol Myopia(Tara MacDonald and Coworkers): Concept: Alcohol causes people to focus on a limited set of prominent cues, ignoring more distant cues and potential consequences. Examples: In a fight, a person with alcohol myopia may quickly resort to aggression. They might quickly respond to complaints or join in happiness if others are happy. Application: Explains risky behavior like aggression, date rape, and reckless driving under the influence of alcohol.
- 29. Harmfulness of recreationaldrugs How harmful are drugs for the brain? Complexities in answering this question: 1) Effects of the Drug vs. Related Factors: Example: Chronic alcohol use is associated with damage to the thalamus and limbic system, resulting in severe memory disorders. Complications: The damage is often due to vitamin deficiencies (e.g., thiamine) caused by poor diet, compounded by alcohol interfering with thiamine absorption, rather than the alcohol itself. 2) Psychiatric Disorders Post-Drug Use: Challenge: Differentiating whether drugs initiate psychiatric conditions or simply exacerbate pre-existing issues is difficult. Many reports exist of severe psychiatric disorders following drug abuse.
- 30. 3) Contaminants inDrugs: Example: Synthetic heroin users developed Parkinson’s disease due to contamination with MPTP, not the heroin itself. Contaminants can produce harmful outcomes, complicating assessments of the drug's direct effects. 4) Polydrug Use: Example: Marijuana (Cannabis sativa) contains over 400 chemicals, with 60+ related to its active ingredient, tetrahydrocannabinol (THC). Psychotic attacks linked to chronic marijuana use may be due to THC or other ingredients, making it hard to determine the exact cause.
- 31. 5) Conditions ofDrug Use: Example: MDMA (Ecstasy), amphetamines, and methamphetamines show evidence of causing brain damage but since its taken in hot, noisy settings typical of party environments the extent of damage by either drug or temperature is hard to determine Research: Animal studies show MDMA can cause degeneration of serotonergic neurons. In rodents, neurons regrow within months, but in monkeys, the damage can be permanent. Cognitive declines in MDMA users have been reported, but researchers are still investigating if the same neuronal loss occurs in humans.
- 32. 6) Detection Methods: Example:Phencyclidine (PCP), initially developed as an anesthetic, was discontinued due to its psychotic effects. It blocks NMDA receptors, causing perceptual changes, slurred speech, and hallucinations in users. Animal Studies: PCP toxicity reduces synapse numbers in rats, with some symptoms lasting weeks. This decrease in synapses is proposed as an animal model for schizophrenia.