A PRESENTATION ON DRUG DEPENDENCE AND ABUSEBY AKSHAY ANAND

DRUG DEPENDENCEDRUG ABUSEAND

AKSHAY ANAND A PRESENTATION BY

III YEAR B.PHARM. PHARMACOLOGY

DR. S. RADHAKRISHNA SEMINAR HALLSREE SIDDAGANGA COLLEGE OF PHARMACY, TUMKUR

People take drugs because they want to change something about their lives.

Here are some of the reasons young people have given for taking drugs:

To fit in

To escape or relax

To relieve boredom

To seem grown up

To rebel

To experiment

They think drugs are a solution. But eventually, the drugs become the problem.

Difficult as it may be to face one’s problems, the consequences of drug use are always worse than the problem one is trying to solve with them. The real answer is to get the facts and not to take drugs in the first place.

WHY DO PEOPLE 1ABUSEANDGET ADDICTED

DRUGS

TO THEM?

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TERMINOLOGIES2

Indiscriminate usage of drugs (except for CNS Stimulants and Depressants) is

termed as Misuse.MISUSE

Examples : Misuse of Purgatives, Laxatives, Antibiotics, etc.

It is defined as usage of drugs for non-therapeutic purpose (for individual pleasure), using a drug for altered mood, consciousness and physical development such as misuse of CNS Stimulants and Depressant. The term abuse also represents certain drugs used by people which are not approved or accepted by the society.

ABUSE

Abused Drugs and Abused Substances are known to enhance CNS

effects and an increased demand for the drug. The enhanced drug seeking property of a drug is Reinforcing Property.

DRUG SEEKING BEHAVIOUR

TERMINOLOGIES3

Increased drug seeking property or wanting of drug or desire to procure the

drugCRAVING

Primary reinforcing property of the drug, referred to as ‘Positive Effective State’ and characterized by pleasant experience on usage of a particular drug because of excitation related to orgasmic pleasures.It is medically recognized as a mental and emotional condition in which a person experiences intense feelings of well-being, elation, happiness, excitement, and joy.

EU

PH

OR

IA

A negative reinforcing property where an individual derives relief from unwanted effects. It is a state of feeling unwell or unhappy; a feeling of emotional and mental discomfort as a symptom of discontentment, restlessness, dissatisfaction, malaise, depression, anxiety or indifference.

DYS

PH

OR

IA

TERMINOLOGIES4

The recurrence of symptoms of a disease due to sudden cessation of the drug. Symptoms are vivid

and appear to a greater extent.REBOUND

Examples : Recurrence of Hypertension immediately after discontinuation of Clonidine, a β-blocker

The recurrence of disease which has been successfully treated earlier. This may occur with similar symptoms of

the disease after a gap of certain period due to discontinuation of treatment.

RELAPSE

It is one of the process of drug dependence treatment. It involves administration of abused drug in reduced doses so that slow

withdrawal is possible.

DETOXIFICATION

TERMINOLOGIES5

ADDICTIONChronic use of drug leads to drug addiction. Drug addiction is characterized by the following:

The person aims to consume the drug at any circumstances.

Procurement of the drug becomes a must for the person.

Drug addiction leads to the development of tolerance.

Tolerance development increases the effective dose requirement production of normal therapeutic effect.

Addicted people must use the drugs regularly to avoid abstinence (self-denial) syndrome.

Discontinuation of cessation of the drug leads to relapse.

Examples : The drugs like Amphetamines, Lysergic Acid Diethylamide,

Cocaine, Cannabis and others are liable for addiction. These drugs produce addiction without physical dependence.

TERMINOLOGIES6

HABITUATIONIt is a state of mind of a drug abuser characterized by the following features:

There is no compulsion to consume the drug.

Tolerance, withdrawal symptoms are developed to a maximum extent.

Habituation is not harmful to society but is problematic for an individual.

It is closely related to addiction.

Examples: Addiction to Tea, Coffee and other beverages, Alcoholism,

consumption of Soft Drinks, Cool Drinks, Energy Drinks, etc., Addiction to Tobacco in the form of Smoking Cigarettes,

Chewing, etc.

Substance or Drug Dependence, commonly called as Drug Addiction, is a compulsive need to use drugs in order to function normally.

When such substances are unobtainable, the user suffers from withdrawal.

DRUG DEPENDENCE 7OR SUBSTANCE DEPENDENCE

DRUG DEPENDENCE 8ACCORDING TO DSM-IV-TR-2000DIAGNOSTIC AND STATISTICAL MANUAL OF MENTAL DISORDERS

“When an individual persists in use of alcohol or other drugs despite problems related to use of the substance, Substance (Drug) Dependence may be diagnosed. Compulsive and repetitive use may result in tolerance to the effect of the drug and withdrawal symptoms when use is reduced or stopped. This, along with Substance (Drug) Abuse are considered Substance (Drug) Use Disorders.”

Substance abuse, also known as drug abuse, is a patterned use of a substance (drug) in which the user consumes the substance in amounts or with methods neither approved nor advised by medical professionals.

Substance/Drug abuse is not limited to mood-altering or psycho-active drugs. If an activity is performed using the objects against the rules and policies of the matter (as in steroids for performance enhancement in sports), it is also called substance abuse.

DRUG ABUSE 9OR SUBSTANCE ABUSE

The mood-altering and psychoactive substances are not the only types of drugs abused. Using illicit drugs – narcotics, stimulants, depressants (sedatives), hallucinogens, cannabis (marijuana), even glues, paints, lacquer paint solvents, turpentine, nail polish removers, petrol, LPG are also considered to be classified as drug/substance abuse.

Substance abuse or Drug abuse often includes problems with impulse control and impulsive behaviour.

DRUG ABUSE 10OR SUBSTANCE ABUSE

The DSM-IV-TR identifies two different severities of Substance Use Disorders. These are Substance Abuse and Substance Dependence.

DEPENDENCE AND ABUSE 11THE DIFFERENTIATION

Substance Abuse is the less severe diagnosis. It includes these symptoms:

The repeated and continued use of a substance despite negative consequences (within a 12-month period).

"Negative consequences" includes four primary types.

DRUG ABUSE

1. One negative consequence is continued use despite problems with work, school or family/social obligations. This might include repeated work absences, poor school performance, neglect of children, or failure to meet household responsibilities. 

2. Another negative consequence occurs when a person becomes involved in legal difficulties related to their substance use (e.g. DUI, assault, theft).

3. A third type of negative consequence is repeatedly using substances in physically dangerous situations. For instance, using alcohol or other drugs while operating machinery or driving a car.

4. Abuse may also be indicated when someone continues substance use despite having interpersonal problems because of the substance use. This could include arguments with family members about the substance use; or, losing important friendships because of continued use.

NEGATIVE CONSEQUENES 12

13

Substance Dependence, as compared to Substance Abuse, is the more severe diagnosis. Substance Dependence requires at least three of the following seven symptoms (within a 12-month period)

DRUG DEPENDENCE

1. Tolerance 2. Withdrawal symptoms 3. Using for longer periods of time than

intended, or using larger amounts than intended;

4. Wanting to reduce use, yet being unsuccessful doing so;

5. Spending excessive time getting/using/recovering from the drug use;

6. Isolated Behaviour : Giving up social or occupational activities due to use;

7. Continuing to use despite knowing about physical/psychological problems related to use.

VARIOUS FACTORS 14FOR DRUG ADDICTION AND ABUSE

1 DRUG RELATED FACTORSDrugs possess different abilities to produce

reinforcement in an individual. Drug variables play major role in the development of drug abuse and drug addiction.

Examples: Availability of the drug, Cost of the drug, Potency,

Route of administration, Speed of action, etc. are the important drug related factors.

2 HOST RELATED FACTORS

Every individual has a different mechanism of action for drug absorption, metabolism and other pharmacokinetic & pharmacodynamic properties.

Genetic factors of an individual closely control the various activities. Almost 60% people are genetically addicted to drugs. Alcohol abuse may also be due to genetic factor.

Apart from genetic factors, other factors related to the host that control drug abuse and addiction include development of tolerance, euphoria, intoxication, psychiatric symptoms, metabolism etc.

15

3 ENVIRONMENTAL FACTORSThese factors are closely related to the society and

surroundings in which the person lives.

People living in underdeveloped areas where job opportunities and educational exposure is less are more susceptible to drug abuse and addiction. Drug abusers, dealers influence the local people to consume the drugs.

The consumption of abused drugs lead to reinforcement and increased craving for the drug.

16

Examples: Substances like Cannabis, Cocaine, Heroine, Marijuana, Nicotine, Alcohol are abused

intentionally.

REWARD-REINFORCEMENT PATHWAY 17OR MESOLIMBIC DOPAMINERGIC PATHWAY

Drugs which are prone to dependence induce the Reward-Reinforcement Pathway. Sometimes this pathway is considered as pleasure center of the brain while Dopamine is considered as the pleasure neurotransmitter.

Drugs we know to produce dependence act at various sites with different mechanisms in order to produce relative effects. However, the ultimate action of these drugs is to enhance Dopamine levels in nucleus accumbens by stimulating the release of dopamine or by inhibiting the reuptake of dopamine.

The dopaminergic pathway is responsible for the positive reward but is not responsible for the negative withdrawal effects.

DRUGS OF ABUSE 18

DRUGS SITE OF ACTION

Opioids μ, κ, δ receptors

Cannabinoids CB1 (cannabinoid1) receptors

Amphetamine Dopamine, Norepinephrine, Serotonin, Vesicular Monoamine Transporters

Benzodiazepines, Barbiturates

GABAA (gamma-aminobutyric acidA) receptors

Alcohol GABAA, 5-HT3, nACH, NMDA receptors

Nicotine Na+ channel associated nACH

LSD, Mescaline, Psilocybin 5-HT2 (5-hydroxytryptamine2)

DRUGS OF ABUSE

NICOTINE

ALCOHOL

OPIOIDS BARBITURATES

BENZODIAZEPINES

DRUGS OF ABUSE 19

NICOTINE Nicotine is obtained from

Nicotiana tobaccum to a maximum extent and is potent, toxic substance that exists in tobacco and is responsible for drug dependence.

Addiction to nicotine has been increasing over the past few years.

It is globally consumed in various forms; smoked as cigars, cigarettes, beedi, hooka; inhaled as snuff; chewed as jarda, khaini, gutka etc. Apart from nicotine, smoke is known to possess various irritant substances like pyridine, ammonia, hydrogen cyanide, carbon monoxide, carbon dioxide, furfural, nitrosamine etc.

NICOTINE PRODUCTS

CIGARETTE

CIGAR BEEDI

SNUFF JARDA GUTKA

NICOTINE 20

Nicotine acts on the acetylcholine receptors which are present in cortex and hippocampus regions of the brain at the presynaptic and postsynaptic areas.

Nicotine is involved in stimulation and desensitization of acetylcholine.

Stimulation of acetylcholine causes excitation of neurons, which leads to rapid neuronal transmissions.

Chronic administration of nicotine desensitizes acetylcholine receptors.

MECHANISM OF ACTION

NICOTINE 21

PHARMACOLOGICAL ACTIONS

Nicotine stimulates CNS by stimulating acetylcholine receptors and the resultant effect includes alertness, attention, decreased depression, anorexia and improved memory. Stimulation of supraoptic nucleus causes release of antidiuretic hormone. Apart from regions of brain, nicotine also stimulates respiratory centers and vomiting centers. It inhibits spinal reflexes which causes relaxation of skeletal muscles stimulating Renshaw cells of the spinal cord. Excess intake of nicotine causes adverse effects like seizures, coma and even death due to respiratory failure.

Nicotine stimulates autonomic ganglia and adrenal medulla which results in vasoconstriction of peripheral regions and the ultimate effect is tachycardia, increased cardiac output and arterial pressure.

ON CARDIOVASCULAR SYSTEM2

ON CENTRAL NERVOUS SYSTEM

1

Salivary secretions are increased by stimulatory effects of nicotine. Other effects on GIT include nausea, vomiting. Excess stimulation of GIT delays healing of peptic ulcers, increased motor activity and diarrhoea are noticed.

ON GASTROINTESTINAL TRACT3

NICOTINE 22

Nicotine is absorbed rapidly when it is inhaled in the form of smoke. Cigarettes possess 0.8g of tobacco and 9-17g nicotine.

Cigar or pipe smoke gets absorbed rapidly from mouth to pharynx. Absorption of nicotine from cigar occurs at slower rate and lasts for longer duration.

Consumption of one cigarette increases about 15-30mg/ml of nicotine concentration in the plasma within 10 minutes. The obtained concentration reduces to half after another 10 minutes and slowly declines within 1 to 2 hours as it gets distributed to tissues and blood.

Nicotine is metabolized by liver. Oxidation of nicotine takes place and the oxidized metabolic product is cotinine, plasma half-life of metabolic product is for longer duration.

PHARMACOKINETICS

NICOTINE 23

ADVERSE EFFECTS

Chronic smokers have high risk of cancer attack. Occurrence of cancer in lungs, upper respiratory tract, oesophagus, bronchi, larynx have been noticed. Cancer is associated with symptoms like dyspnoea, wheezing cough, chest pain, respiratory tract infections, etc. Risk of cancer is greater in smokers when compared to non-smokers.

Thrombosis induced by smoking results in coronary heart diseases. Hypertension and ischemia may also occur due to excess release of catecholamine, antidiuretic hormone and fatty substances in plasma

ON CARDIOVASCULAR SYSTEM2

RESPIRATORY DISORDERS1

Smoking may lead to several complications in pregnant women such as premature delivery, spontaneous abortion and placenta praevia. It may also show deleterious effects in the newborns such as decreased birth weight, physical and mental abnormalities. It may also lead to tachycardia in infants dependent on mother’s milk.

REPRODUCTIVE DISORDERS3

NICOTINE 24

Nicotine activates the Reward-Reinforcement pathway by increasing the dopamine levels. Prolonged use of nicotine leads to desensitization of nicotinic acetylcholine receptors.

Nicotine stimulates autonomic ganglia in order to stimulate postganglionic nerves. But higher doses of nicotine blocks the ganglionic transmission by producing depolarization.

Tolerance is rapidly developed due to desensitization of acetylcholine receptors because of chronic administration of nicotine. The desensitization of acetylcholine receptors is responsible for blockage of ganglionic stimulation.

The withdrawal symptom of nicotine is craving for cigarettes. This symptom lasts for a month. Other symptoms include anxiety, sleeplessness, restlessness, etc.

DEPENDENCE & TOLERENCE

NICOTINE 25

Nicotine dependence and withdrawal symptoms can be treated by using nicotine substitutes and other suitable antagonists for nicotinic receptors.

Nicotine Replacement Therapy is found useful in treating nicotine dependence where a substitute to nicotine is administered to the dependents which contain relatively small amounts of nicotine.

Drugs for treatment of nicotine and tobacco dependence are:

TREATMENT

Bupropion (Wellbutrin, Budeprion, Prexaton, Elontril, Aplenzin)

Rimonabant (Acomplia, Bethin, Monaslim, Remonabent, Riobant, Slimona,)

Varenicline (Chantix, Champix)

Clonidine (Kapvay, Nexiclon)

DRUGS OF ABUSE 26

ALCOHOL Alcohol beverages are

widely distributed and available globally.

Alcohol is one of the most abused drugs. People prefer alcohol for pleasure and euphoria.

The reinforcement of alcohol is high as a result several people are currently suffering from alcoholism.

Alcohol primarily acts as a CNS depressant and gradually initiates sedation.

ALCOHOL PRODUCTS

FER

MEN

TED

BEER WINE LAGER

BRANDY

VODKA

WHISKY

SCOTCH

RUM

DIS

TIL

LED

ALCOHOL 27

Chronic alcohol consumption produces various adaptive neuronal changes in order to counter attack the acute cellular effects produced by alcohol.

The density of GABAA receptors decreases upregulation of NMDA (N-methyl-D-aspartate) receptors and proliferation of Ca2+ Channels takes place.

Alcohol enhances the neurotransmitters of reward pathway. It elevates dopamine, 5-HT, acetylcholine, norepinephrine and other opioid receptors with a similar mechanism as that of opioids i.e., enhances the drug dependence activity since it produces pleasant feelings.

MECHANISM OF ACTION

ALCOHOL 28

ADVERSE EFFECTS

Initial effects include impairment of cognitive functions like ability to learn, attention, contraction, slurred speech, euphoria, highly excited nature, self confidence, sedation, ataxia. Excess alcohol results in melancholy, aggressive nature, mood disorders, impaired sensory parameters, etc.

CNS MANIFESTATIONS1

These include peripheral vasodilation, sweating, excessive sweating, increased heart rate, flushing.

CARDIOVASCULAR MANIFESTATIONS2

Alcohol enhances gastric acid secretions and results in impairment of normal functioning of GIT.

GASTROINTESTINAL MANIFESTATIONS

3

Diuresis due to inhibition of anti-diuretic hormone. Hyperuricaemia (excess uric acid in blood) due to abnormal excretion of uric acid.

RENAL MANIFESTATIONS4

ALCOHOL 29

CHRONIC TOXIC EFFECTS

Chronic alcohol consumption leads to various neurological disorders such as –

b. Polneuropathyc. Karsakoff’s Neuropathy

d. Retrobulbar Neuropathye. Marchiafava Bignami Syndrome

f. Hepatic Encephalopathy

a. Wernicke’s Encephalopathy

ALCOHOL 30

Tolerance and dependence are also major problems.

They are a result of prolonged consumption of alcohol which desensitizes and decreases GABAA receptors, increases NMDA subtype glutamate receptors.

These changes play a vital role in development of tolerance.

Cells and tissues function abnormally due to tolerance development.

Elimination of alcohol at a faster rate is also one of the reasons for tolerance development.

DEPENDENCE & TOLERENCE

ALCOHOL 31

The withdrawal symptoms include seizures, sweating, hyperthermia, delirium, hallucination, hyperexcitation and neurotoxicity.

These are due to the effect of sudden withdrawal of alcohol on Ca2+ ions. Increased Ca2+ ions cause this.

WITHDRAWAL SYMPTOMS

Cardiomyopathy, cardiac arrhythmias, abnormal metabolism, increase of catecholamine, hypertension are some of the withdrawal effects of alcohol.

CARDIOVASCULAR SYSTEM1

Some effects of alcohol withdrawal on GIT are oesophagal reflux, Barrett’s oesophagus, gastric pain, Mallory-Weiss syndrome and oesophagal cancer. Excess alcohol consumption affects gastric mucosa and causes gastric bleeding.

GASTROINTESTINAL TRACT2

ALCOHOL 32

Administration of glucose, thiamine and other electrolytes reduces metabolic alterations like hypoglycemia and ketosis, preventing respiratory depression hence treating alcohol toxicity.

Administration of sedatives and hypnotics like chlordiazepoxide and diazepam reduces withdrawal symptoms to a certain extent, preventing seizures, delirium and arrhythmias. β-Blockers like clonidine, propranolol are helpful in inhibiting neurotransmitter release and controlling sympathetic activity.

Aversion therapy is a primary approach in treating alcoholism. Disulfiram (Antabuse, Antabus) is a drug of choice used in the therapy, however it has its own set of adverse effects.

Naltrexone (Revia, Depade, Vivitrol), an opioid receptor antagonist is helpful in reducing the craving for alcohol in addicts.

Acamprosate (Campral) is another preferred drug for alcohol dependents. It has multiple effects on various receptors and neurotransmitters.

TREATMENT

DRUGS OF ABUSE 33

OPIOIDSAn opioid is any psychoactive chemical that resembles morphine in its pharmacological effects. Opioids work by binding to opioid receptors, which are found principally in the central and peripheral nervous system and the gastrointestinal tract. 

Commonly abused opioids are morphine, heroin, codeine, oxycodeine and meperidine.

OPIOID PRODUCTS

MORPHINE HEROIN CODEINE

OPIOIDS 34

Opioids act on G-protein coupled receptors μ, κ, δ which are known to inhibit adenyl cyclase, cAMP, protein kinase A, voltage gated CA2+ channels.

The inhibitory action of opioids leads to depression upon mild exposure.

Prolonged exposure of opioids exert an opposite effect on the G-protein coupled receptors resulting an increase in the compensatory response element binding [(cAMP, adenyl cyclase, protein kinase A) CREB].

The rise in CREB exert excitatory actions due to enhanced Na+ channel functions and cAMP upregulation.

All these cellular effects not only decrease the inhibitory actions of opioids but also lead to the development of tolerance, dependence and withdrawal symptoms.

MECHANISM OF ACTION

OPIOIDS 35

Physical and psychological dependence develop in opioid drug abusers.

Physical dependence develops to a greater extent that compared to psychological dependence.

Sudden withdrawal of opioids may lead to death of individuals.

The symptoms of physical dependence include dysphoria, GI upset, mydriasis, cough, hyperventilation, ocular discharge, diarrhea, yawning, hyperthermia, piloerection, aggressiveness and emesis.

Psychological dependence is characterized by craving. The enhanced dopamine levels enhance the craving effect.

Sudden withdrawal effects are termed noradrenergic storm due to increased release of norepinephrine.

DEPENDENCE

OPIOIDS 36

Desensitization of opioid receptors, increased CREB (compensatory response element binding), reduced receptor-effector coupling mechanism are the various changes produced due to chronic administration of opioids.

All these changes lead to the development of tolerance.

Tolerance is developed to euphoria, respiratory depression, sedation and emetic actions.

Tolerance to euphoria develops at a faster rate.

Cross tolerance to opioid agonists is also developed.

TOLERANCE

OPIOIDS 37

Replacement therapy is found useful in treating opioid dependence. Long acting drugs are administered in place of short acting drugs.

Methadone (Symoron, Dolophine, Amidone, Methadose, Physeptone, Heptadon), levo-α-acetyl methanol, buprenorphine are known to be potent opioid replacement agonists.

Opioid agonist like Naltrexone (Revia, Depade, Vivitrol) is effective against euphoria and withdrawal symptoms of opioids.

Lofexidine, an α-2-adrenergic receptor agonist is also effective against withdrawal effects of opioids.

TREATMENT

DRUGS OF ABUSE 38

BARBITURATES & BENZODIAZEPINESBarbiturates and

benzodiazepines are known to have similar pharmacological actions.

The use of barbiturates has decreased because more beneficial drugs with higher safety margins have been introduced.

Benzodiazepines and Barbiturates are sedative-hypnotics used in the treatment of anxiety, insomnia.

BARBITURATES & BENZODIAZEPINE PRODUCTS

MIDAZOLAM DIAZEPAM AMYL NITRATE

BARBITURATES & BENZODIAZEPINES 39

Barbiturates and benzodiazepines are known to enhance the inhibitory actions of GABAA receptors by facilitating the opening of chloride-ion channels.

MECHANISM OF ACTION

BARBITURATES & BENZODIAZEPINES

DEPENDENCE & TOLERANCE

Benzodiazepines develop little tolerance but the drug dependence and withdrawal effects are common for both barbiturates and benzodiazepines.

The abuse of benzodiazepines is mostly seen in alcohol consumers.

Tolerance is developed to sedation after prolonged use of these drugs.

Withdrawal symptoms include insomnia, irritation, depression, muscle cramps, seizures, dizziness and anxiety.

BARBITURATES & BENZODIAZEPINES 40

Replacement therapy is found useful, short acting drugs like phenobarbital are used to substitute long acting barbiturates and benzodiazepines like pentobarbital or secobarbital.

Detoxification is also useful, osmotic diuretics along with sodium bicarbonate is used for detoxification of barbiturates.

Flumazenil (Anexate, Lanexat, Mazicon, Romazicon) is an effective benzodiazepine antagonist.

Diphenhydramine (Benadryl, Dimedrol, Nytol) is suggested for habituated withdrawal symptoms.

TREATMENT

INHALANT ABUSE 41

Exposure to various volatile substances for recreational purposes is termed as Inhalant Abuse.

The volatile substances in crude chemical vapour like nitrates, kerosene, toluene, gasoline, carbon tetra cholride, nitrous oxide, amyl nitrate, aliphatic & aromatic hydrocarbons are known to produce psychological changes.

INHALANT ABUSE42

Inhalation of substances from open containers is called sniffing.SNIFFING

Inhalation of cloth or any other substance after soaking it in volatile substance.HUFFING

Inhalation of substances which are present (collected or stored) in bag or

paper.

BAGGING

The abuse of inhalants begin with sniffing, slowly progresses to huffing and bagging which results in addiction.

There is no specific treatment for inhalant abuse. Creating awareness and rehabilitation is beneficial.

REFERENCES 43

H.L.Sharma, K.K.Sharma Principles of Pharmacology – 1st EditionParas Medical Publishers, Hyderabad

K.D.TriphthiEssentials of Mediacal Pharmacology – 5th EditionJAYPEE Brothers Medical Publishers, New Delhi

en.wikipedia.orgwww.mayoclinic.comwww.psychiatry.org www.drugfreeworld.orgwww.drugabuse.comimages.google.com

THANK YOU!AKSHAY ANAND

axayanand@gmail.com

END OF SLIDESHOW