Substance Abuse

Substance abuse – Use of drug interferes with ability to function

Fails to meet work or family obligations – No physiological dependence

Substance dependence (addiction) – Involves either tolerance or withdrawal – Tolerance

Greater and greater amounts of substance are needed to produce

the desired effect – Withdrawal

Physiological and psychological consequences when individual

discontinues or reduces substance use – Restlessness, anxiety, cramps, death

Alcohol-Related Disorders Discontinuation of alcohol in heavy user: – Anxiety – Depression – Weakness – Restlessness – Difficulty sleeping – Muscle tremors • Face, fingers, eyelids, other small

musculature – Elevated BP, pulse, temperature

Management of Alcohol Withdrawal

General Measures Seizure precautions with h/o Sz

Hydration

Thiamine 100mg IM/IV prior to glucose

Correct electrolytes—Mg, Ca, K, PO4

Treat concurrent illnesses

Management of AWS

Benzodiazepines (BDZ) Treatment of choice Reduce symptoms and decrease risk of

Seizurezs Phenobarbital

Narrow therapeutic index Carbamazepine

Effective alternative, less sedation

Mayo-Smith JAMA 1997;278:144-51

Choice of Benzodiazepine All seem effective for AWS

Limited comparative data All metabolized by liver Differences

Onset of action, half life, routes 1 or 2 step metabolism; active

metabolites Long vs shorter acting

Long-acting Benzodiazepines

Chlordiazepoxide (Librium®) Oral dosing only

Intermediate onset

Long-acting parent compound and metabolites

Smoother withdrawal, less sz, better cognitive fxn

Potential accumulation in elderly and patients with liver disease

[Diazepam]

Shorter-acting BDZs

Lorazepam (Ativan®) Versatile dosing—PO, IV, IM, SL

Fast to intermediate onset

Intermediate half-life, no metabolites

Less likely to accumulate in elderly or with liver disease

Breakthrough sx, met. acidosis, delirium

[Oxazepam]

Benzodiazepines

Chlordiazepoxide generally preferred

Indications for Lorazepam Elderly Established liver disease NPO Severe w/d requiring frequent or high

doses

Benzodiazepines

Route of administration

Oral preferableEase of administrationMore consistent blood levels

Sublingual if NPO (e.g., surgical patients)

IntravenousSevere w/d requiring rapid titration or

NPO

Amphetamine Related Disorder DSM IV

Amphetamine induced Anxiety disorder Mood disorder Psychotic disorder with delusions Psychotic disorder with hallucinations Sexual dysfunction

Amphetamine Related Disorder Treatment

None established

Treat specific symptoms Comorbid conditions such as

depression may respond to antidepressants Bupropion (Wellbutrin)

Used after patients withdraw from amphetamines

Caffeine-Related Disorder Caffeine is an methylxantine More potent than other known

methylxantines Theophyline (Primatene)

Half-life- 3-10 hrs Peak 30-60 minutes Crosses BBB Adenosine-receptor antagonist

Amount of Caffeine Consumption

Beverages / Food: Cup of coffee: 65-120 mg caffeine

Espresso 1oz shot: 40 mg Cup of tea: 40-60 mg Can of soda: 30-60 mg Red Bull (8.3oz): 80 mg Hershey’s milk chocolate almond bar (6oz): 25mg

Over the counter medicines: No-Doze: 100 – 200 mg Midol: 20-100 mg Excedrin: 30-65 mgBenowitz, 1990

Total consumption of caffeine per person per day is estimated at

210 to 238 mg (Barone and Roberts, 1996)

Mechanism of Action

Three main hypotheses:1. Mobilization of intracellular calcium Biphasic effect on intracellular calcium levels *Toxic amounts of caffeine2. Inhibition of phosphodiesterase Inhibition of enzyme that breaks down cyclic adenosine

monophosphate (cAMP) *Toxic amounts of caffeine3. Antagonism of inhibitory presynaptic adenosine

receptors Caffeine blocks adenosine receptors Resulting in the inhibition of the breakdown of cAMP Blocking the inhibitory effects of adenosine

Nehlig et al., 1992

Pharmacodynamics

CaffeineCaffeineCentral Nervous SystemCentral Nervous System Enhances neurotransmitter releaseEnhances neurotransmitter release

Stimulates locomotor activityStimulates locomotor activity

Decreases cerebral blood flowDecreases cerebral blood flow

CardiovascularCardiovascular Release of epinephrine (adrenaline) Release of epinephrine (adrenaline) whichwhich

Increases heart rateIncreases heart rate

Increases blood pressureIncreases blood pressure

Increases blood flow to the musclesIncreases blood flow to the muscles

Decreases blood flow to skin and inner Decreases blood flow to skin and inner organsorgans

RenalRenal Diuresis; stimulates renal releaseDiuresis; stimulates renal release

VasculatureVasculature Peripheral: DilationPeripheral: Dilation

Central: ConstrictionCentral: Constriction

GastrointestinalGastrointestinal Increases gastric secretionsIncreases gastric secretions

RespiratoryRespiratory BronchodilationBronchodilation

Increases respiratory rateIncreases respiratory rateGarrett and Griffiths 1997Garrett and Griffiths 1997

Pharmacokinetics

Absorption Gastrointestinal tract and stomach Rapid rate, peak blood level in 30-60 min. Crosses lipid-membrane (not water soluble)

Distribution Diffuses throughout the organism and

crosses BBB Including placenta and placental BBB

Nehlig et al., 1999; Fredholm et al., 1999

Pharmacokinetics

Metabolism Metabolized through liver biotransformation initially by

demethylation into dimethylxanthines. *Dimethylxanthines are pharmacologically active and may

add to the effects of caffeine consumption in humans. This process is unique to humans, no other animal species

metabolizes caffeine in a similar way Half life of caffeine

Three to eight hours; varies with age and other external factors Newborns cannot metabolize caffeine, mainly eliminated by

excretion Half life 80 +/_ 23 hours

Smokers, half life is reduced up to 50% Pregnant women and those taking oral contraceptive, half

life up to 15 hours longer

Nehlig et al., 1999; Fredholm et al., 1999

Treatment of Caffeine-Related Disorders

Reducing or eliminating caffeine consumption

ASA Headaches, muscle aches from

withdrawal Benzodiazepines-rarely required

Cannabis-Related Disorders

Major active ingredient – THC (delta-9- tetrahydrocannabinol) • Psychological – Feelings of relaxation and sociability – Rapid shifts of emotion – Interferes with attention, memory, and thinking – Heavy doses can induce hallucinations and panic – Impairment of skills needed for driving • Impairment present for several hours after ‘high’ has worn off

Physiological – Bloodshot & itchy eyes – Dry mouth and throat – Increased appetite – Reduced pressure within the eye – Reduced BP – Abnormal heart rate • May exacerbate preexisting cardiovascular problems – Damage to lung structure and function – Tolerance may develop

Cannabis Withdrawal

No specific treatment Abstinence and support

Anxiolytics Short-term withdrawal symptoms relief If depressive disorder is present, treat

with antidepressants

Cocaine-Related Disorder

Alkaloid obtained from coca leaves – Reduces pain – Produces euphoria – Heightens sexual desire – Increases self-confidence

and indefatigability Blocks reuptake of

dopamine in mesolimbic areas of brain

Overdose – Chills, nausea, insomnia,

paranoia, hallucinations, and other psychotic symptoms

– Can cause heart attack and death because drug causes

blood vessels to narrow • Not all users develop

tolerance – Some become more sensitive

• May increase risk of OD • Usage increased in 70s and

80s – Dropped late 80s; rose mid

90s In 2003, 2.3 million users

over the age of 12 (SAMHSA, 2004)

Cocaine-Related Disorder

Crack – Form of cocaine that become popular

in the 80s

– Rock crystal that is heated, melted, & smoked

– Increased popularity because it is cheaper than cocaine

Cocaine-Related Disorder

Treatment No pharmacological treatments produce

decreases in cocaine use comparable to the decreases in opioid use when heroin users are treated with methadone, levomethadyl and buprenorphine.

Methylphenidate (Ritalin),Lithium (Eskalith) Cocaine users presumed to have preexisting

ADHD and mood disorders Those drugs are useless in patients

without the disorders

Cocaine-Related Disorder

Treatment, cont. Many different treatments have been

use with little or no effects TCAs MAOIs SSRIs Antipsychotics Etc.

Hallucinogen-Related Disorders Natural and synthetic substances

Psychedelics or psychomimetics Induce hallucinations or disconnection

with reality Schedule 1 drugs

Hallucinogen-Related Disorders Naturally occurring

Psilocybin Mushroom

Mescaline Peyote cactus

Other Harmine, harmaline, ibogaine,

dymethyltriptamine (DMT)

Hallucinogen-Related Disorders LSD

Synthesized in 1938 Classic synthetic hallucinogen MDMA- erroneously classified as a

hallucinogen, vstructirally related to amphetamines

Hallucinogen-Related Disorders Treatment

Symptom specific Psychological support Hallucinogen intoxication can be treated

with diazepam 20 mg Stops LSD effect and associated panic to a

stop within 20 minutes

Inhalants-Related Disorders Volatile hydrocarbons

Tolouene n-Hexane Methyl butyl ketone Trichloroethylane Dichloromethane Gasoline Butane

Inhalants-Related Disorders 4 commercial classes1.Solvents, glues and adhesives2.Propelants for aerosol sprays3.Thinners4.Fuels

Inhalants-Related Disorders Inhalant-induced pathological

conditions Intoxication Delirium Persisting dementia Psychotic disorder Mood and anxiety disorders Disorder not otherwise specified

Inhalants-Related Disorders Intoxication requires no medical

attention Effects of intoxication may require

attention Coma, bronchospasm, laryngospasm,

cardiac arrhythmias, or burns Sedation is contraindicated Confusion, panic or psychosis

Severe agitation Haloperidol 5mg IM/70 kg bw

Nicotine-Related Disorders One of the most highly addictive

drugs in the US.

Treatment Modalities for Substance-Related Disorders• Alcoholics Anonymous• Disulfiram (Antabuse)• Other medications for

treatment of alcoholism• Counseling• Group therapy• Alcohol

– Benzodiazepines– Anticonvulsants– Multivitamin therapy– Thiamine

• Opioids– Narcotic antagonists

• Naloxone (Narcan)• Naltrexone (ReVia)• Nalmefene (Revex)

– Methadone– Buprenorphine– Clonidine

• Stimulants– Minor tranquilizers– Major tranquilizers– Anticonvulsants– Antidepressants

• Hallucinogens and Cannabinols– Benzodiazepines– Antipsychotics