Many drugs -human beings consume -they choose to, and not because they are advised by doctors.

Society in general disapproves, Because there is a social cost Use is banned in many countries. 3 most commonly used nontherapeutic drugs are caffeine, nicotine and ethanol-legally and freely available. Many other drugs are widely used

Psychotropic drugs-Those affect brain Used by Physician-Psychiatric diseases-can be misused or abused Non-prescription psychotropic drugs- legal or illegal Psychopharmacology explains how these drugs affect brain

They dominates the lifestyle of the individual and damages his or her quality of life Habit itself causes actual harm to the individual or the community. [HIV,

Addiction[Substance abuse] = Physiologic+ Psychologic dependence Psychologic =Compulsive drug seeking, craving Physiologic = symptoms and signs opposite to drug Tolerance-PK, PD DIAGNOSTIC and STATISTICAL

Reinforcement:Tendency of a pleasureproducing drug to lead to repeated self administration Withdrawal-Drug is suddenly stopped— develop a withdrawal syndrome characterized by craving, dysphoria, signs of sympathetic overactivity. Rebound -Drug (usually for a medically sanctioned use)- suddenly stopped— their symptoms come back in an exaggerated fashion. Eg. BZDP for panic attacks suddenly stop panic attack[Rebound panic attack].

Detoxification: Tapering of a drug that has caused dependence and would cause withdrawal if stopped suddenly. Detoxification accomplished slowly withdrawing the drug itself or by substitution of a cross-dependent drug that has a similar pharmacological mechanism of action. Prevents withdrawal symptoms.

Mesolimbic Dopamine Pathway and the Psychopharmacology of Reward[Reinforcement] •Pleasure center •Pleasure Neurotransmitter. [DA]

Natural High ntellectual accomplishments Athletic accomplishments Enjoying a symphony Experiencing an orgasm Less intense Natural High Brain’s own!!!

Drug induced high

•Brain’s own!!! •Endorphins[Morph ine!] •Marijuana (anandamide), •Nicotine •(acetylcholine) •Cocaine and • amphetamine (dopamine itself)

•Alcohol, opiates, •Stimulants, •Marijuana, •Benzodiazepines, •Hallucinogens •‘HIGH ON’ DEMAND •Unfortunately at a PRICE

Drug-induced reward Feeding of dopamine to postsynaptic limbic (D2) sites -furiously crave more drug to replenish dopamine Drug stopped Individual becomes preoccupied with finding more drug and thus beginning a vicious circle.

Few receptors High risk for ultimate abuse Low initial response to a drug High initial response Many receptors

Aversion to drug

Stimulants: Cocaine and Amphetamine

Cocaine

•Cocaine powerful inhibitor -dopamine transporter. •Blocking this transporter acutely causes dopamine to accumulate, •Produces euphoria, •Reduces fatigue,

•Cocaine has similar but less important actions at the NE and 5HT transporters. Local anesthetic Freud and tongue Ca

•Repeated intoxication with cocaine • Sensitization or "reverse

•Cocaine releases more and more dopamine.
•Doses of cocaine that previously only induced euphoria •Now create an acute paranoid psychosis virtually indistinguishable from

tolerance.“

•The clinical effects of amphetamine Derivatives are similar to those of cocaine •Euphoria - less intense •Last longer than that due to cocaine

The hallucinogens are a group of agents that produce intoxication, sometimes called a "trip,“ With changes in sensory experiences, including visual illusions and hallucinations, Enhanced awareness of external stimuli Enhanced awareness of internal thoughts and stimuli.

These hallucinations are produced with a clear level of consciousness and a lack of confusion Psychedelic is the term for the subjective experience, due to Heightened sensory awareness, that one's mind is being expanded or that one is in unison with mankind or the universe and having some sort of a religious experience. Psychotomimetic means that the experience mimics a state of psychosis

•Hallucinogens such as Lysergic acid diethylamide (LSD),Mescaline, Psyloscibin, and 3,4methylenedioxymethamphetamine (MDMA)

Phenylcyclidine (PCP) developed as an anesthetic Not used- psychotomimetic hallucinatory experience. Its structurally related and mechanism-related analogue Ketamine –Used Phenylcyclidine causes intense Analgesia, amnesia, delirium, stimulant as well as depressant effects, Staggering gait, slurred speech, and a unique form of nystagmus (i.e., vertical nystagmus). Catatonia (excitement alternating with stupor and catalepsy), Hallucinations, delusions, paranoia,

Cannabis preparations are smoked THC delta-9-tetrahydrocannabinol (THC) Interact with brain's cannabinoid receptors Triggers dopamine release from the mesolimbic reward system Cannabinoid receptors, CB1 - brain CB2 - immune system Anandamide –endo genous

ne-Cigarette smoking is a nicotine delivery sy

•Nicotine acts directly on nicotinic cholinergic receptors, • which are located in part on mesolimbic dopamine neurons

Reinforcing actions of nicotine similar cocaine and Amphetamine-But SUBTLE Nicotine shuts down receptor shortly after binding to it Neither it nor Ach can stimulate for a while [longer and much more intense euphoria with cocaine] Pleasure of nicotine is a desirable but small boost in the sensation of pleasure ("minirush"), → decline until the smoker takes the next puff or smokes the next cigarette. Somewhat self-regulating – Behavioral effects less severe thancocaine

Over time, upregulation Of receptors

Nicotine and DA release

No Nicotine and No DA release CRAVING

Cigarette smoking is a pulsatile nicotine delivery system withdrawal from nicotine is characterized by craving and agitation,

Nicotine →nAChRsα4β2 Produces inhibitory and excitatory effects Shows reinforcing properties Peripheral effects → Ganglionic stimulation: tachycardia,↑ BP,and ↓GI motility. Tolerance develops rapidly Metabolised, mainly in the liver, within 1-2 hours.

The inactive metabolite, cotinine, has a long plasma half-life -used as a measure of smoking habits Tolerance, physical dependence and psychological dependence (craving), and is highly addictive. Long-term cessation succeed -20% of cases The life expectancy of

Cancer, particularly of the lung and upper respiratory tract but also of the oesophagus, pancreas and bladder CAD and other forms of PVD Chronic bronchitis Harmful effects in pregnancy-Birth wt., physical and mental development↓[7yrs] Parkinson's disease is

Motivation Psychological help Transdermal patch Nicotine gum Bupropion

“Brain's own morphine-like molecules."

Opiate drugs act on a variety of receptors,

Pain relievers, -Codeine or Morphine, Drugs of abuse, -Heroin, Euphoria, -reinforcing property. Withdrawal syndrome Dysphoria, craving for another dose of opiate, irritability, and signs of autonomic hyperactivity, such as tachycardia, tremor,

Piloerection ("goose bumps") associated with opiate withdrawal, Symptoms subjectively so horrible Opiate abuser will often stop at nothing in order to obtain another dose of opiate to relieve symptoms of withdrawal. What may have begun as a

Alcohol acts by enhancing inhibitory neurotransmission at GABA-A receptors Reducing excitatory neurotransmission at the (NMDA) subtype of glutamate receptors So alcohol enhances inhibition and reduces excitation,

Alcohol

Decreases the actions of the excitatory NMDA receptor complex —that is, it

•Enhancie GABA inhibition •Reduces glutamate excitation, •Enhances euphoric effects •by releasing •Opiates and

Naltrexone Blocks opiate receptors Decreases craving -increases abstinence rates. If one drinks when taking Naltrexone, the opiates released do not lead to pleasure, so why bother drinking? Some patients may also say, why bother taking Naltrexone?

•Acamprosate, a derivative of the amino acid taurine, •Interacts with the NMDA receptor •Substitute s for this effect of alcohol during abstinence •Thus, when alcohol is withdrawn and the mesolimbic D2 receptors are whining for dopamine because of too much glutamate, •Alcamprosate substitution reduces neuronal hyperexcitability of alcohol withdrawal, Reduced withdrawal distress and craving. Treatment alcohol abuse and
dependence 12-step programs

Benzodiazepine

Modulators of GABA-A •Benzodiazepine -drug-naive patient, •Acute benzodiazepine effect, •Opening the Cl- channel maximallyEnhancing inhibitory neurotransmission Anxiolytic actions. Psychopharmacological mechanism of euphoria,

•Chronic administration of a benzodiazepine •Tolerance and dependence •Cl- channel to open less than before •But still enough to give an anxiolytic Euphoric and drug-reinforcing effect. •Less than before •Brain gets used to too much benzodiazepine at its receptors

BZDP-ACUTE ADMN.

BZDP-SUDDEN WITHDRAWAL [REVERSE OF BENZODIAZEPINE INTOXICATION]

•These actions continue until benzodiazepine is replaced •Alternatively BZDP can be tapered •So that the receptors have time to readapt withdrawal symptoms are prevented.

Euphoria Tranquility and lack of anxiety Sedation and sleep Muscle relaxation Anticonvulsant effects.

Dysphoria and depression Anxiety and agitation Insomnia Muscle tension Seizures

Has the clinical condition benefitted? If ‘Yes” is he stable? Has the pt. limited the use within prescribed limits? BZDP tapering programme

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