Influence of Drugs.pdf..................

Influence of drugs

1. Influence of Drugs
Noor Ul Ain Basit

2. -Psychopharmacology is the 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
-The way 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
-Drugs are 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

6. Blood Brain Barrier

7. Blood Brain Barrier
A few 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
-The most 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 in Synapses
-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 (false sensory 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 stops breakdown
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 for manic 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 similar to 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: such as 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 is to 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 of drug 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
-Dependence Hypothesis:
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 Addiction Development:
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 recreational drugs
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 in Drugs:
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 of Drug 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.