alcohol
TRANSCRIPT
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AMBO UNIVERSITYCOLLEGE OF MEDICINE AND HEALTH SCIENCES
DEPARTMENT OF PHARMACY
PPHARMACOTHERAPY IIIGROUP ASSIGNMENT
TITLE Substance-Related DisordersAlcohol
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Outline
Definition Epidemiology Pharmacology and pharmacokinetics of alcohol Alcohol Poisoning Clinical presentation of alcohol intoxication and withdrawal Treatment
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Session Objectives
• After the completion of this session you will be able to understand
• The use and effects of alcohol• Alcohol poisoning ,pharmacokinetics and its
mechanism• The treatments of alcohol withdrawal and
dependence
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Substance-Related DisordersAlcohol
• Introduction• Alcohol is a central nervous system depressant
that affects the central nervous system in a dose-dependent fashion
• Alcohol use impose enormous social and economic costs on society
• Alcohol abuse causes numerous chronic diseases and injuries with an inordinate amount of mortality
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EPIDEMIOLOGY OF ALCOHOL USE
51.8% of Americans ages 12 and older Approximately one-fifth of persons 12 years of age and older (55 million people) participated in binge drinking, defined as having five or more drinks on the same occasion, at least once in the 30 daysPossibly more damaging for womenWorldwide, alcohol abuse leads to 1.8 million deaths annuallyNationally, an estimated 100,000 U.S. citizens die each year because of alcohol-related causes, including traffic collisions and cirrhosis of the liver
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DISEASE MODEL OF ADDICTION AS APPLIED TO ALCOHOLISM
• The disease concept of addiction, using alcoholism as a model, states that addiction is a disease
• Alcoholism is heritable, as 50% to 60% of first-degree relatives of alcoholics become alcohol dependent themselves
• Diagnostic criteria for alcoholism do not specify frequency of drinking or amount of alcohol consumed. The key determinant is whether drinking is compulsive ,out of control, and consequential when one drinks
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Genotypic, Phenotypic, and Environmental Factors That Increase Alcohol Dependence Risk
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PHARMACOLOGY AND PHARMACOKINETICS OF ALCOHOL
Alcohol as drugCNS depressant that affects the CNS in a dose-dependent fashion, producing sedation that progresses to sleep, unconsciousness, coma, surgical anaesthesia, and finally fatal respiratory depression and cardiovascular collapseAlcohol affects
Endogenous opiates euphoriaSeveral neurotransmitter (GABA,glutamine, and dopamine).
Approximately 14 g of alcohol in a 12-oz can of beer (5%)The lethal dose of alcohol in humans is variable, but deaths generally occur when blood alcohol levels are greater than 400 to 500 mg/dL
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Pharmacokinetics
• Absorption of alcohol begins in the stomach within 5 to 10 minutes of oral ingestion.
• Peak serum concentrations 30 to 90 minutes after finishing the last drink, depends on type of alcohol ,what and when person ate last
• More than 90% is metabolized in the liver• The remainder is excreted by the lungs and in urine and sweat Alcohol ADH
Acetaldehyde
ALDHAcetic acid and water
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Alcohol Poisoning
• Acute alcohol poisoning after rapid consumption of large quantities of alcoholic beverages
• The person vomits to rid the stomach of its toxic reservoir
• The person may fall asleep or pass out without vomiting, allowing continued alcohol absorption from the GI tract, while the patient sleeps, until fatal BACs are achieved
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Specific Effects of Alcohol Related to BAC
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CLINICAL PRESENTATION OF ALCOHOL INTOXICATION AND WITHDRAWAL
• Acute alcohol detoxification and withdrawal after chronic alcohol abuse is a serious condition that can require hospitalization and adjunctive pharmacotherapy.
• If the BAC gets high enough, death is possible• Symptoms
– Slurred speech– Ataxia– Sedation or unconscious– BACs nausea, vomiting, and hallucinations– Delirium and seizures are the most severe symptoms
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• Signs– Nystagmus– In withdrawal tachycardia, diaphoresis, or hyperthermia.
• Laboratory Tests– In the emergency department, a BAC should be ordered
when alcohol ingestion is suspected– A whole blood alcohol level of 150 mg/dL reported in the
hospital corresponds to 0.15% BAC obtained by law enforcement
• Other Diagnostic Tests– computed tomography (CT)
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TREATMENT
Alcohol Withdrawal Goals
The prevention and treatment of withdrawal symptoms (including seizures and delirium tremens) and medical or psychiatric complications,Long-term abstinence after detoxificationEntry into ongoing medical and alcohol-dependence treatment
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PHARMACOLOGIC THERAPY Benzodiazepine is the current standard of care in alcohol
detoxification to manage and minimize symptoms and avoid progression to the more severe stages of withdrawal
Consideration in the choice of benzodiazepine is their potential for abuse during recovery.
Lorazepam is preferred by many clinicians because it can be administered intravenously, intramuscularly, or orally with predictable results
Agents with rapid onset of action, such as diazepam or alprazolam, demonstrate higher abuse potential because of their reinforcing effects
Those with slower onset of action, such as chlordiazepoxide or oxazepam, are less likely to be abused
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Pharmacologic Agents Used in the Treatment of Alcohol Withdrawal
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..cont..
Although barbiturates are used by approximately 10% of detoxification programs in the United States, there is less evidence-based support for their use versus the benzodiazepines.
carbamazepine, Clonidine, vigabatrin, valproic acid, gabapentin, and topiramate can reduce symptoms of alcohol withdrawal
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Treatment Regimens• Symptom-Triggered Therapy
medication is given only when the patient has symptoms shorter, potentially avoiding oversedation lorazepam 2 mg administered every hour as needed
• Fixed-Schedule Therapy Over the years, benzodiazepines given regularly at a fixed dosing
interval have been used for alcohol withdrawal Under dosing is the major problem with this approach cross-tolerance Current guidelines take exception with this rigid approach, urging
clinicians to allow for some degree of individualization within fixed-schedule therapy
• Patients should be monitored and given additional medication when indicated by symptoms.
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Treatment of Alcohol Withdrawal Seizures
Not require treatment with an anticonvulsant drug unless they progress to status epilepticus Because seizures usually end before diazepam or another drug can be administeredPhenytoin, which is not cross-tolerant to alcohol,does not prevent or treat withdrawal seizures, and without an intravenous loading dose, therapeutic blood levels of phenytoin are not reached until acute withdrawal is complete Patients experiencing seizures should be treated supportivelyTapering to prevent further seizure activity
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Cont...
Patients with a history of withdrawal seizures can be predicted to experience an especially severe withdrawal syndrome. In such patients, a higher initial dosage of a benzodiazepine and a slower tapering period of 7 to 10 days are advisable.
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Treatment of Nutritional Deficits and Electrolyte Abnormalities
Fluid status should be carefully assessed, and fluid, electrolyte, and vitamin abnormalities should be correctedExcessive hydration should be avoidedbecause of increased vasopressin levels.Hydration can be necessary in patients with vomiting, diarrhoea, increased body temperature, or severe agitation.Alcoholics often have electrolyte imbalances because of inadequate nutrition and fluid volume related to antidiuretic hormone inhibition
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Cont... Hypokalemia can be corrected with oral potassium supplementation as
long as renal function is adequate Hypomagnesemia is also common but routine magnesium replacement
for alcohol withdrawal is not recommended. Only if symptoms of hypomagnesemia are present should magnesium replacement be considered
Thiamine (vitamin B1) is often depleted in alcoholics, particularlythose with poor nutrition. Thiamine supplementation is standard therapy
Because it can prevent the development of the WernickeKorsikoff syndrome
An initial dose of 100 mg IV or IM is commonly used If the patient has evidence of thiamine deficiency replacement with
100 mg orally every day for 1 to 4 weeks is appropriate
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Adverse effects associated with thiamine use– hypersensitivity reactions,– cardiovascular effects, and CNS effects
• Other nutritional deficits can also occur with chronic alcoholabuse primarily caused by poor eating habits. A multivitamin isusually given once daily
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Treatment Settings
• Inpatient treatment– coexisting acute or chronic medical (including
pregnancy), surgical, or psychiatric conditions that would complicate alcohol withdrawal
– those concurrently using other drugs, and those with a history of seizures or delirium tremens
• outpatient treatment– Only patients with mild to moderate symptoms
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Non-Pharmacological Treatment of AlcoholDependence
• Psychotherapy• Behaviour therapy• Aversive therapy dislike• Relaxation Training• Skills Training
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PHARMACOLOGIC MANAGEMENT OF ALCOHOL DEPENDENCE
In the US, disulfiram, naltrexone, and acamprosate are the only three drugs that are FDA-approved for the treatment of alcohol dependence.Disulfiram acts as a deterrent to the resumption of drinkingNaltrexone is a competitive opioid antagonist that has been shown to reduce cravings for alcoholAcamprosate is aGABA-ergic agonist that modulates alcohol cravings
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Pharmacologic Agents Used in the Treatment of Alcohol Dependence
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DISULFIRAMDisulfiram deters a patient from drinking by producing an aversive reaction if the patient drinksInhibits metabolism of alcohol by blocking acetaldehyde dehydrogenaseAcetaldehyde is toxic product causing the reaction (flushed, tachycardia, diaphoresis, nausea, headache, etc.)Metronidazole and alcohol may cause disulfiram like reactionMonitor liver enzymesMay cause psychosisEvaluate need for patient to take in front of staff The prescriber shouldwait at least 24 hours after the last drink before starting disulfiram,usually at a dose of 250 mg/day
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NALTREXONE
Opiate blockerEvidence for reduced cravings and relapse ratesShort-term treatment (up to 12 weeks) with naltrexone decreases the chance of alcohol relapse by 36% versus placeboShould not be given to patients currently dependent on opiates because it can precipitate a severe withdrawal syndromeAssociated with dose-related hepatotoxicity
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• Side effect– headache,– dizziness, nervousness, fatigue, insomnia, vomiting,
anxiety, and– Somnolence--sleepy
• If dosed daily, naltrexone 50 mg per day is sufficient to effectively block μ-opioid receptors.
• The usual effective dose is 380 mg IM each month
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ACAMPROSATE
• Is a glutamate modulator at the N-methyl-D-aspartate (NMDA) receptor that reduces alcohol craving
• Patients treated with acamprosate are more successful in maintaining abstinence from alcohol versus placebo
• The combination of acamprosate and naltrexone has been shown to be more efficacious than acamprosate alone for the maintenance of abstinence from alcohol, when combined with psychosocial interventions
• Is well tolerated, with gastrointestinal adverse effects most common
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CLINICAL CONTROVERSY
The most difficult clinical problem in the treatment of alcohol related illness is helping patients remain abstinent after alcohol
detoxification. The usefulness of acamprosate, naltrexone, disulfiram remains
controversial. Acamprosate and naltrexone have been shown to be superior to
nonpharmacologic therapy alone for maintenance of abstinence from alcohol; however, relapse during naltrexone and acamprosate therapy is still common.
Disulfiram use has fallen out of favor. Studies have failed to prove it effective, and it is poorly tolerated.
For this reason, most clinicians rarely recommend the use of disulfiram.
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References
1. Pharmacotherapy 7th edition McGraw Hill Dipro
2. Applied Therapeutics:THE CLINICAL USE OF DRUGS Ninth Edition
3. www.drugabuse.gov
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Group members
Name ID1 Habtamu Abebe R/1440/042 Baredin Jemal R/1427/043 Musse Gelebo R/1451/044 Teketel Alemu R/1463/04
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Thank you