Medical Management of the Hospitalized Alcoholic Patient: Joseph S Bertino Jr., Pharm.D CPRC Goals and Objectives Understand the pathophysiology of alcohol withdrawal and treatment Discuss how to use the Signs and Symptoms Assessment (SSA) scoring system to prevent and treat alcohol withdrawal syndrome CPRC Classes of Drugs of Abuse Anticholinergic drugs Cannabinoids (marijuana) Dissociative drugs (phencyclidine, ketamine) Opiates (morphine, heroin) Hallucinogens (LSD, mescaline) Sedative-hypnotics (barbiturates, benzodiazepines, alcohol) Stimulants (amphetamine, cocaine) Volatiles (glue, gasoline, paint remover) CPRC Drugs and Neurotransmitter Actions that Cause Symptoms GABA 5-HT NE AcCH β -endorphin Dopamine Opiates Dissociatives Psychodelics Stimulants EtOH, sedatives GABA = γ-aminobutyric acid; 5-HT = 5-hydroyxtriptamine; AcCH = acetylcholine CPRC Why Are the Neurotransmitters Important? You cannot use the same strategies for treatment or withdrawal from alcohol for other drugs of abuse The primary neurotransmitter affected by chronic alcohol use is GABA You must replace GABA to treat alcohol withdrawal syndrome CPRC Etiology of Alcohol Withdrawal Syndrome The brain adapts to chronic alcohol use Alcohol potentiates the post-synaptic effect of GABA (sedation) Alcohol withdrawal causes a sudden deficiency of GABA Deficiency of GABA causes hyperactivity in a patient…A large adrenergic stimulation CPRC Etiology of Alcohol Withdrawal Alcohol stimulates norepinephrine (NE) synthesis and release receptor sensitivity to NE is reduced In acute alcohol withdrawal NE synthesis continues NE release decreases NE receptors become are very sensitive CPRC Etiology of Alcohol Withdrawal Dopamine receptor sensitivity increased by alcohol In acute alcohol withdrawal, dopamine receptors become very sensitive Kindling: repeated stimulation of brain causes increased sensitivity of neurons Repeated episodes of acute alcohol withdrawal may stimulate kindling and seizures…each time a patient has alcohol withdrawal syndrome the symptoms are worse CPRC Alcohol Withdrawal Syndrome (AWS) AWS patients have a strong adrenergic response Due to sensitivity to norepinephrine and dopamine Due to lack of GABA receptor stimulation CPRC Stages of Alcohol Withdrawal Syndrome Stage 1: Autonomic hyperactivity (100%) Occurs within hours of last use of alcohol and lasts 24-48 hours Stage 2: Hallucinations (25%): Occurs 8-48 hours after last use of alcohol Stage 3: Brain stimulation and seizures (10%): Occurs 6-48 hours after last use of alcohol Stage 4: Delirium Tremens (DTs) (5%) Occurs 2-5 days after last alcohol use, 15% die CPRC Considerations for using SSA Seizures: Do not score as number Assure patient is on seizure prophylaxis Consider need for further assessment of seizure CPRC Considerations for using SSA Blood pressure may be elevated in presence of: hypertension pain (trauma, post op, acute rhabdomyolysis) Temperature may be elevated in presence of: infection Lung disease pancreatitis Pulse may be elevated in presence of: infection pain (pancreatitis) agitation/panic/anxiety CPRC Considerations for using SSA Tremor may be present : at baseline secondary to alcoholic pseudoParkinsonism tremor, rigidity, bradykinesia intensified by agitation or activity Agitation/panic may be present with subdural hematomas other neurologic or psychiatric conditions Sleeplessness may be present with sleep apnea caused by alcoholism CPRC Considerations for using SSA Sweating may occur in presence of: infection or fever Nausea/vomiting may be present with: post operative effects of anesthesia underlying gastrointestinal problem (gastritis, GI bleeding, etc.) Delay in appearance of alcohol withdrawal signs and symptoms can occur after anesthesia CPRC Alcohol Detoxification Worksheet Standard Regimen: If SSA < give no diazepam If SSA 4-6, give diazepam 10mg po Q2H & prn If SSA 7-8, give diazepam 15mg po Q2H & prn If SSA 9-10, give diazepam 20mg po Q2H & prn If SSA 11-12, give diazepam 25mg po Q2H & prn If SSA > 12, give diazepam 30mg po Q2H & prn Prn = as needed for patient Po = by mouth CPRC Alcohol Detoxification Worksheet Standard regimen for patients who cannot use oral medications: If SSA < no drug is given If SSA 4-6, give diazepam 5mg slow IV push Q2H & prn If SSA 7-8, give diazepam 7.5mg slow IV push Q2H & prn If SSA 9-10, give diazepam 10mg slow IV push Q2H & prn If SSA 11-12, give diazepam 12.5mg slow IV push Q2H & prn If SSA > 12, give diazepam 15mg slow IV push Q2H & prn CPRC Alcohol Withdrawal Syndrome Use lorazepam instead of diazepam: for patients with impaired liver function for elderly patients who may be unable to metabolize diazepam for patients with poor venous access who cannot take oral medication (can give lorazepam IM, not give diazepam IM) CPRC Seizure Prophylaxis Recommendations for seizure prophylaxis: Recommended for patients with: • suspected or documented history of seizures • History of seizures during previous alcohol withdrawal Usual prophylaxis*: • diazepam 10mg po Q8H x doses then diazepam 10mg po BID x doses or • phenobarbital 30mg Q8H x doses then phenobarbital 30mg BID x doses *This medication is administered in addition to medication administered for SSA CPRC SSA Protocol Is the Starting Point for Treatment May increase the dose of BZD if required to control symptoms May increase the SSA score required to receive medication if necessary to account for underlying medical problems which can increase SSA score: hypertension tremor infection CPRC Benzodiazepine Dosing Patients should receive a benzodiazepine in the amounts necessary to control symptoms Patients require close monitoring until symptoms are controlled For patients with significant co-morbidities, medications should be considered even if withdrawal is mild to moderate CPRC Use of Large Doses of Benzodiazepines Large dose requirements are uncommon (< 5% of patients) Use of large doses occur (more than 1300 mg diazepam /day) Patients with large alcohol use or repeated alcohol withdrawal syndrome may require larger doses of benzodiazepines Total daily dose is determined by efficacy and toxicity CPRC Use of Large Doses of Benzodiazepines Sedation is common Respiratory depression is rare Flumazenil should almost never be used to reverse benzodiazepine side effects Assess patient frequently with SSA (as often as every 5-10 minutes) Give additional doses as needed CPRC Summary The SSA protocol is the starting point for safe and effective management of alcohol withdrawal The SSA protocol is only safe and effective if properly used and interpreted Understanding the pathophysiology of alcohol withdrawal and treatment makes treatment more effective Pharmacists can implement and direct an alcohol withdrawal syndrome treatment program CPRC Thank you Questions and Comments CPRC Summary Nurses are the key personnel for assessing the patient’s stage of withdrawal Nurses are the key personnel for assuring patient safety Early intervention is the key to prevention of medical complications of alcohol withdrawal syndrome CPRC [...]... frequent doses of benzodiazepines) cannot stop DTs once they have begun CPRC Medical Complications in Patients with Alcoholism Increased risk of all types of infections due to: decreased WBC function decrease in other immunologic factors Taking increased risks in lifestyle Increased incidence of bacterial pneumonia caused by pathogens rare in the normal population CPRC Medical Complications in Patients with... Increased risk of aspiration pneumonia Increased risk of spontaneous bacterial peritonitis (SBP) Cardiomyopathy and arrhythmias associated with alcoholism and withdrawal Hypertension is common in alcoholics CPRC Assessment and Treatment of Alcohol Withdrawal Syndrome CPRC The Problem Patients may not tell physician about alcohol use if they are not asked about it Patients usually will state they use much... active metabolite CPRC Benzodiazepines: Choice of Drug and Dose/Dose Interval May use a fixed dose schedule or Symptom triggered therapy (Therapy of choice) results in significantly less medication used results in significantly shorter hospitalization CPRC Management Goals of Alcohol Detoxification Symptomatic relief and prevention of disease progression Prevent medical complications Fluid hydration, vitamins,... Stimulation may produce seizures CPRC Hallucinations (Stage 2) Occur in 3-10 % of patients Increased risk with use of larger amounts of alcohol Are not predictive of DTs (stage 4) and are not necessarily related to DTs May be auditory (hearing), tactile (feeling), olfactory (smelling) Patients are rarely disoriented (i.e they have ego-intact hallucinations) CPRC Hallucinations (Stage 2) Hallucinations... manifestation of alcohol withdrawal Affects < 5% of patients Mortality 15%, due to: myocardial infarction respiratory arrest sepsis As age increases, risk of DTs increases Rare in patients < 30 years of age CPRC Delirium Tremens (Stage 4) Delirium tremens (DTs) Large autonomic hyperactivity gross tremor delirium (hallucinations) usually occurs after 3 days of untreated or poorly treated AWS may occur as... AWS No evidence that one BZD is more effective than another as a substitute for alcohol CPRC Benzodiazepines Advantages Good anticonvulsant properties high therapeutic to toxic ratio good pharmacokinetic profile good pharmacodynamic profile lower potential for tolerance and abuse Disadvantages no effect on hallucinations Will not stop DTs once they have started CPRC Benzodiazepine Pharmacokinetics... after the first seizure 5-15% incidence Occasionally, status epilepticus seen in < 3 % of patients CPRC Seizures (Stage 3) Seizure incidence increases with increased or repeated alcohol abuse (“kindling” phenomenon) Predisposing factors for seizures: Previous seizures for any reason head trauma previous alcohol withdrawal syndrome seizures CPRC Delirium Tremens (Stage 4) Most severe manifestation of alcohol... alcohol than they really do use Surgical patients may never be asked about alcohol use Homemade alcohol drinks may vary in alcohol content CPRC Alcohol Use in Vietnam CPRC WHO 2014 CPRC Prevalence of High Alcohol Use and Dependence in Vietnam 2010 WHO 2014 data 90 million population (2010) ~8 million individuals with alcohol related problems CPRC Vietnamese consume twice as much beer as any other SE Asian... Conc ↓ 48 hr Insomnia As EtOH conc↓ 48 hr Tremor 6-24 hr 48 hr Nausea/vomiting 6-24 hr 48 hr CPRC Physical Signs of Acute Alcohol Withdrawal (Stage 1) Autonomic nervous system hyperactivity restlessness diaphoresis (sweating) tachycardia hypertension tremors nausea/vomiting CPRC Physical Signs of Acute Alcohol Withdrawal (Stages 2 and 3) Changes in perception, sensation, and arousal may produce: hallucinations... Vietnamese consume twice as much beer as any other SE Asian country Int J Hum Med Sci 2014;4:102-107 CPRC Drugs to Treat Alcohol Withdrawal Syndrome Drug treatment of alcohol withdrawal syndrome uses benzodiazepines (BZD) BZD substitutes for alcohol at the GABA receptor and reduces symptoms CPRC Benzodiazepine (BZD) and Alcohol Withdrawal Syndrome (AWS) BZD are not useful in treating withdrawal hallucinations