2.
<ul><li>Many drugs -human beings consume -they choose to, and not because they are advised by doctors. </li></ul><ul><li>Society in general disapproves, </li></ul><ul><li>Because there is a social cost </li></ul><ul><li>Use is banned in many countries. </li></ul><ul><li>3 most commonly used non-therapeutic drugs are caffeine, nicotine and ethanol- legally and freely available. </li></ul><ul><li>Many other drugs are widely used </li></ul><ul><li>Others -'sport' drugs </li></ul>

3.
<ul><li>Psychotropic drugs-Those affect brain </li></ul><ul><li>Used by Physician-Psychiatric diseases-can be misused or abused </li></ul><ul><li>Non-prescription psychotropic drugs- legal or illegal </li></ul><ul><li>Psychopharmacology explains how these drugs affect brain when misused or abused </li></ul>

5.
<ul><li>They dominates the lifestyle of the individual and damages his or her quality of life </li></ul><ul><li>Habit itself causes actual harm to the individual or the community. [HIV, Criminal behaviour] </li></ul>

6.
<ul><li>Addiction[Substance abuse] </li></ul><ul><li>= Physiologic+ Psychologic dependence </li></ul><ul><li>Psychologic =Compulsive drug seeking, craving </li></ul><ul><li>Physiologic = symptoms and signs opposite to drug </li></ul><ul><li>Tolerance-PK, PD </li></ul><ul><li>D IAGNOSTIC and S TATISTICAL MANUAL OF M ENTAL DISEASES- DSM IV </li></ul>

7.
<ul><li>Reinforcement:T endency of a pleasure-producing drug to lead to repeated self administration </li></ul><ul><li>Withdrawal -D rug is suddenly stopped— develop a withdrawal syndrome characterized by craving, dysphoria, signs of sympathetic overactivity. </li></ul><ul><li>Rebound -D rug (usually for a medically sanctioned use)- suddenly stopped— their symptoms come back in an exaggerated fashion. </li></ul><ul><li>Eg. BZDP for panic attacks suddenly stop panic attack[Rebound panic attack]. </li></ul>

8.
<ul><li>Detoxification: Tapering of a drug that has caused dependence and would cause withdrawal if stopped suddenly. </li></ul><ul><li>Detoxification accomplished slowly withdrawing the drug itself or by substitution of a cross-dependent drug that has a similar pharmacological mechanism of action. </li></ul><ul><li>Prevents withdrawal symptoms. </li></ul><ul><li>Tapered discontinuation.[Glucocorticoids, Anti HTN] </li></ul>

9.
Mesolimbic Dopamine Pathway and the Psychopharmacology of Reward[R einforcement] <ul><li>Natural High </li></ul><ul><li>Intellectual accomplishments </li></ul><ul><li>Athletic accomplishments </li></ul><ul><li>Enjoying a symphony </li></ul><ul><li>Experiencing an orgasm </li></ul><ul><li>Less intense </li></ul><ul><li>Brain’s own!!! </li></ul><ul><li>Pleasure center </li></ul><ul><li>Pleasure Neurotransmitter. [DA] </li></ul>Drug induced high Natural High

10.
<ul><li>Brain’s own!!! </li></ul><ul><li>Endorphins[Morphine!] </li></ul><ul><li>Marijuana </li></ul><ul><li>(anandamide), </li></ul><ul><li>Nicotine </li></ul><ul><li>(acetylcholine) </li></ul><ul><li>Cocaine and </li></ul><ul><li>amphetamine </li></ul><ul><li>(dopamine itself) </li></ul><ul><li>Alcohol, opiates, </li></ul><ul><li>Stimulants, </li></ul><ul><li>Marijuana, </li></ul><ul><li>Benzodiazepines, </li></ul><ul><li>Hallucinogens </li></ul><ul><li>‘ HIGH ON’ DEMAND! </li></ul><ul><li>Unfortunately at a </li></ul><ul><li>PRICE </li></ul>

11.
<ul><li>Drug-induced reward </li></ul><ul><li>Feeding of dopamine to postsynaptic limbic (D2) sites -furiously crave more drug to replenish dopamine </li></ul><ul><li>Drug stopped </li></ul><ul><li>Individual becomes preoccupied with finding more drug and thus beginning a vicious circle. </li></ul>

12.
<ul><li>Few receptors </li></ul><ul><li>Low initial response to a drug </li></ul><ul><li>High initial response </li></ul><ul><li>Many receptors </li></ul>High risk for ultimate abus e Aversion to drug

13.
Stimulants: Cocaine and Amphetamine

14.
Cocaine <ul><li>Cocaine powerful inhibitor -dopamine transporter. </li></ul><ul><li>Blocking this transporter acutely causes dopamine to accumulate, </li></ul><ul><li>Produces euphoria, </li></ul><ul><li>Reduces fatigue, </li></ul><ul><li>Cocaine has similar but less important actions at the NE and 5HT transporters. </li></ul>Local anesthetic Freud and tongue Ca

15.
<ul><li>Repeated intoxication with cocaine </li></ul><ul><li>Sensitization or &quot; reverse </li></ul><ul><li>tolerance.“ </li></ul><ul><li>Cocaine releases more and </li></ul><ul><li>more dopamine . </li></ul><ul><li>Doses of cocaine that previously only induced euphoria </li></ul><ul><li>Now create an acute paranoid psychosis virtually indistinguishable from paranoid schizophrenia. </li></ul>

16.
<ul><li>The clinical effects of amphetamine </li></ul><ul><li>Derivatives are similar to those </li></ul><ul><li>of cocaine </li></ul><ul><li>Euphoria - less intense </li></ul><ul><li>Last longer than that due to cocaine </li></ul>

17.
<ul><li>The hallucinogens are a group of agents that produce intoxication, sometimes called </li></ul><ul><li>a &quot;trip,“ </li></ul><ul><li>With changes in sensory experiences, including visual illusions and hallucinations, </li></ul><ul><li>Enhanced awareness of external stimuli </li></ul><ul><li>Enhanced awareness of internal thoughts and stimuli. </li></ul>

18.
<ul><li>These hallucinations are produced with a clear level of consciousness and a lack of confusion </li></ul><ul><li>Psychedelic is the term for the subjective experience, due to </li></ul><ul><li>Heightened sensory awareness, that one's mind is being expanded or </li></ul><ul><li>that one is in unison with mankind or the universe and having some sort of a religious experience. </li></ul><ul><li>Psychotomimetic means that the experience mimics a state of psychosis </li></ul>

19.
<ul><li>Hallucinogens such as Lysergic acid diethylamide (LSD),Mescaline, Psyloscibin, and 3,4-methylenedioxymethamphetamine (MDMA) </li></ul><ul><li>Partial agonists at 5HT2A receptors. </li></ul>

20.
<ul><li>Phenylcyclidine (PCP) developed as an anesthetic </li></ul><ul><li>Not used- psychotomimetic hallucinatory experience. </li></ul><ul><li>Its structurally related and mechanism-related analogue </li></ul><ul><li>Ketamine –Used </li></ul><ul><li>Phenylcyclidine causes intense </li></ul><ul><li>Analgesia, amnesia, delirium, stimulant as well as depressant effects, </li></ul><ul><li>Staggering gait, slurred speech, and a unique form of nystagmus (i.e., vertical nystagmus). Catatonia (excitement alternating with stupor and catalepsy), </li></ul><ul><li>Hallucinations, delusions, paranoia, disorientation, and lack of judgment </li></ul><ul><li>Neuroprotective </li></ul>

21.
<ul><li>Cannabis preparations are smoked </li></ul><ul><li>THC delta-9-tetrahydrocannabinol (THC) </li></ul><ul><li>Interact with brain's cannabinoid receptors </li></ul><ul><li>Triggers dopamine release from the mesolimbic reward system </li></ul><ul><li>Cannabinoid receptors, </li></ul><ul><li>CB1 - brain </li></ul><ul><li>CB2 - immune system </li></ul><ul><li>Anandamide –endo genous cannabinoids </li></ul><ul><li>Receptor antagonists and analogues-????? </li></ul>

22.
Nicotine-Cigarette smoking is a nicotine delivery system <ul><li>Nicotine acts directly on nicotinic cholinergic </li></ul><ul><li>receptors, </li></ul><ul><li>which are located in part on mesolimbic dopamine neurons </li></ul>

23.
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 (&quot;minirush&quot;), -> decline until the smoker takes the next puff or smokes the next cigarette. Somewhat self-regulating – Behavioral effects less severe thancocaine

24.
Over time, up-regulation Of receptors

25.
Nicotine and DA release No Nicotine and No DA release CRAVING

26.
Cigarette smoking is a pulsatile nicotine delivery system withdrawal from nicotine is characterized by craving and agitation,

27.
<ul><li>Nicotine ->nAChRs- α 4 β 2 </li></ul><ul><li>Produces inhibitory and excitatory effects </li></ul><ul><li>Shows reinforcing properties </li></ul><ul><li>Peripheral effects -> Ganglionic stimulation: tachycardia,↑ BP,and ↓GI motility. </li></ul><ul><li>Tolerance develops rapidly </li></ul><ul><li>Metabolised, mainly in the liver, within 1-2 hours. </li></ul><ul><li>The inactive metabolite, cotinine, has a long plasma half-life -used as a measure of smoking habits </li></ul><ul><li>Tolerance, physical dependence and psychological dependence (craving), and is highly addictive. </li></ul><ul><li>Long-term cessation succeed -20% of cases </li></ul><ul><li>The life expectancy of smokers is shorter than that of non-smokers </li></ul>

28.
<ul><li>Cancer, particularly of the lung and upper respiratory tract but also of the oesophagus, pancreas and bladder </li></ul><ul><li>CAD and other forms of PVD </li></ul><ul><li>Chronic bronchitis </li></ul><ul><li>Harmful effects in pregnancy-Birth wt., physical and mental development↓[7yrs] </li></ul><ul><li>Parkinson's disease is approximately twice as common in non-smokers as in smokers </li></ul>

29.
<ul><li>Motivation </li></ul><ul><li>Psychological help </li></ul><ul><li>Transdermal patch </li></ul><ul><li>Nicotine gum </li></ul><ul><li>Bupropion </li></ul>

30.
Opiate drugs act on a variety of receptors, “ Brain's own morphine-like molecules.&quot;

32.
<ul><li>Pain relievers, -Codeine or Morphine, </li></ul><ul><li>Drugs of abuse, -Heroin, </li></ul><ul><li>Euphoria, -reinforcing property. </li></ul><ul><li>Withdrawal syndrome </li></ul><ul><li>Dysphoria, craving for another dose of opiate, irritability, and signs of autonomic hyperactivity, such as tachycardia, tremor, sweating. </li></ul><ul><li>Piloerection (&quot;goose bumps&quot;) associated with opiate withdrawal, </li></ul><ul><li>Symptoms subjectively so horrible </li></ul><ul><li>Opiate abuser will often stop at nothing in order to obtain another dose of opiate to relieve symptoms of withdrawal. </li></ul><ul><li>What may have begun as a </li></ul><ul><li>Quest for euphoria may </li></ul><ul><li>End up as a </li></ul><ul><li>Quest to avoid withdrawal. </li></ul>

33.
<ul><li>Alcohol acts by enhancing inhibitory </li></ul><ul><li>neurotransmission at GABA-A receptors </li></ul><ul><li>Reducing excitatory neurotransmission at the (NMDA) subtype of glutamate receptors </li></ul><ul><li>So alcohol enhances inhibition and reduces </li></ul><ul><li>excitation, </li></ul>

34.
Alcohol Decreases the actions of the excitatory NMDA receptor complex — that is, it diminishes excitation. <ul><li>Enhancie GABA inhibition </li></ul><ul><li>Reduces glutamate excitation, </li></ul><ul><li>Enhances euphoric effects </li></ul><ul><li>by releasing </li></ul><ul><li>Opiates and endocannabinoids, </li></ul><ul><li>Thereby mediating its &quot;high.&quot; </li></ul>

35.
<ul><li>Naltrexone Blocks opiate receptors </li></ul><ul><li>Decreases craving -increases abstinence rates. </li></ul><ul><li>If one drinks when taking Naltrexone, the opiates released do not lead to pleasure, so why bother drinking? </li></ul><ul><li>Some patients may also say, why bother taking Naltrexone? </li></ul>

36.
<ul><li>Acamprosate, a derivative of the amino acid taurine, </li></ul><ul><li>Interacts with the NMDA receptor </li></ul><ul><li>Substitute s for this effect of alcohol during abstinence </li></ul><ul><li>Thus, when alcohol is withdrawn and the mesolimbic D2 receptors are whining for dopamine because of too much glutamate, </li></ul><ul><li>Alcamprosate substitution reduces </li></ul><ul><li>neuronal hyperexcitability of alcohol withdrawal, </li></ul><ul><li>Reduced withdrawal distress and craving. </li></ul>Treatment alcohol abuse and dependence 12-step programs

38.
Benzodiazepine Modulators of GABA-A <ul><li>Benzodiazepine -drug-naive patient, </li></ul><ul><li>Acute benzodiazepine effect, </li></ul><ul><li>Opening the Cl - channel maximally-Enhancing inhibitory neurotransmission </li></ul><ul><li>Anxiolytic actions. </li></ul><ul><li>Psychopharmacological mechanism of euphoria, </li></ul><ul><li>Drug reinforcement </li></ul>

39.
<ul><li>Chronic administration of a benzodiazepine </li></ul><ul><li>Tolerance and dependence </li></ul><ul><li>Cl - channel to open less than before </li></ul><ul><li>But still enough to give an anxiolytic Euphoric and drug-reinforcing effect . </li></ul><ul><li>Less than before </li></ul><ul><li>Brain gets used to too much </li></ul><ul><li>benzodiazepine at its receptors </li></ul>

40.
<ul><li>BZDP-ACUTE ADMN. </li></ul><ul><li>BZDP-SUDDEN WITHDRAWAL </li></ul><ul><li>[REVERSE OF BENZODIAZEPINE INTOXICATION] </li></ul><ul><li>Euphoria </li></ul><ul><li>Tranquility and lack of anxiety </li></ul><ul><li>Sedation and sleep </li></ul><ul><li>Muscle relaxation </li></ul><ul><li>Anticonvulsant effects. </li></ul><ul><li>Dysphoria and depression </li></ul><ul><li>Anxiety and agitation </li></ul><ul><li>Insomnia </li></ul><ul><li>Muscle tension </li></ul><ul><li>Seizures </li></ul><ul><li>These actions continue until benzodiazepine is replaced </li></ul><ul><li>Alternatively BZDP can be tapered </li></ul><ul><li>So that the receptors have time to readapt </li></ul><ul><li>withdrawal symptoms are prevented. </li></ul>

41.
<ul><li>Has the clinical condition benefitted? </li></ul><ul><li>If ‘Yes” is he stable? </li></ul><ul><li>Has the pt. limited the use within prescribed limits? </li></ul><ul><li>BZDP tapering programme </li></ul>