DEADDICTION

Dr. RAGHU PRASADA M SMBBS,MDASSISTANT PROFESSOR DEPT. OF PHARMACOLOGYSSIMS & RC.

1

Drug dependence ?

Taking a Drug for any reason other than a

medical one…

To get a feeling of euphoria (high)

2

dependence?

uncontrollable compulsive drug seeking and use, even in the face of negative health and social consequences.”

Results from both psychological and physical dependence on the drug

3

modalities

Treatment of withdrawal

symptoms

Aversion therapy

To reduce craving

To prevent relapse

Rehabilitation & psychosocial

intervention

4

First line treatment

SINGLE AGENT

ACAMPROSATE

NALTREXONE

DISULFIRAM

Aimed at complete abstinence , can be started at any time including withdrawal phase, may be started immediately during first consultation

Early onset with family loading, helps in heavy drinking and may be choice in which acamprosate trial has failed, Liver function test is mandatory

Patient completely motivated and with good social support, still low acceptability

Second line Drugs (based on open label trials, large case report, one or two RCTs and case report

SSRIS (FLUOXETINE, SERTRALINE, CITALOPRAM)

TOPIRAMATE

BACLOFEN

Effective with co morbid depression

Can be used as single agent, or with co morbidities like seizure, bipolar disorder.

Helpful in withdrawal management and relapse prevention in patients with cirrhosis liver. Also co morbid cannabis or solvent or benzodiazepine uses

6

Alcohol Withdrawal

General principles of treatment Careful monitoring and supportive care Ample fluids (p/o or IV fluids if

dehydrated) Correction of electrolyte imbalance Parenteral Thiamine(100 mg p.o or i.v or

i.m) daily

Restrict access to addicting substances Involve significant others in the treatment

from the initial stages Liaise with specialists as appropriate

7

Alcohol Withdrawal

Cross tolerant medications with alcohol Benzodiazepines Diazepam and Chlordiazepoxide Lorazepam and oxazepam - short acting

(patients with liver problems, in elderly)

Others (more than 150 agents, carbamazepine; valproate, ß adrenergic antagonists etc.,)

Emerging: Baclofen

8

Ethanol AcetateAcetaldehyde •Flushing

•Headache•Palpitations•Dizziness•Nausea

ADH ALDH

Disulfi

ra

m

.

.

9

Disulfiram

Prescribing Disulfiram

Main contraindications:

recent alcohol use, pregnancy,

rubber, nickel or cobalt allergy,

cognitive impairment, drug

interactions

hepatitis, neuropathy

10

Disulfiram 250 mg/d-->500 mg/dDisulfiram 250 mg/d-->500 mg/d

Main side effects:

Reduce craving

Acamprosate (calcium acetyl homo taurinate)

structure similar to GABA amino acid.

Restores the GABA activity.

reduce glutamate surges that excite NMDA- Rs.

acts as a neuro-protectant and protect neurons from damage caused by alcohol withdrawal 11

The RewardPathway

The RewardPathway

Ethanol

DopamineDopamine

Beta endorphin release potentiated

Beta endorphin release potentiated

Naltrexone-

aimed at reducing the psychological need or craving for alcohol.

prefrontal cortex

nucleus accumbens

VTA

Firing

12

Prescribing Naltrexone

▪ Main contraindication:

opiates, pregnancy

▪ Main side effects:

13

Naltrexone 12.5 mg/d-->25 mg/d-->50 mg/dNaltrexone 12.5 mg/d-->25 mg/d-->50 mg/d

Ondansetron▪ a 5-HT3 antagonist that exerts its antidrinking

effects through cortico-mesolimbic dopamine system modulation.

▪ improve drinking outcomes in patients with early-onset alcoholism.

▪ Adverse events are mild

▪ starting dosage of 4 mcg/kg twice daily should be maintained throughout treatment.

14

Opioids……..

15

Intervention

Treatment of Dependence and Abuse

Intoxication

Withdrawal

16

Antagonist therapy

Naltrexone Complete abstinence approach long term treatment helps in

maintaining complete abstinence extinction of drug seeking behavior blocking the effects of opioid over

a significant period Reduced craving

Naltrexone….

Advantage No tolerance or

withdrawal Not a schedule drug No abuse potential

Disadvantage Abstinence for 5-7

days Retention and

compliance issues Sensitivity to over

dosages

18

Agonist Therapy

Methadone

Buprenorphine

LAAM( levo Alfa acetyl methadone)

methadone

Advantages Best available

evidence Lower costs Good Retention and

abstinence rates

Disadvantages Mortality following

overdose Scheduled drug Supervised clinic Daily dosing Abuse and dependence

20

Buprenorphine

semi-synthetic opium alkaloid derivative of thebaine.

long acting, highly lipophilic opiate Mixed agonist antagonist Side effects – as in methadone elevated liver enzymes Toxicity – Less risk, none reported but if occurs, difficult to reverse and needs higher

doses of naloxone.

21

Thank you for your time, concerns and your support.

Semper Fi !!!

22