What are the 3 drugs for alcohol maintenance and which one is usable for pts w/ liver damage?
3) Calcium Acetylhomotaurinate - Acomprosate - No Liver Toxicity!!!
What is Physiologic Depenedence?
State of the body as a result of ongoing exposure to a substance
Definitely Present if person displays tolerance or withdrawal but NOT synonymous with addiction
Tolerance: The need for increasing amounts of a substance for the same effects
Withdrawal: Problems (physical or psychological) that occur after the cessation of use of a substance were body has tolerance
Sensitization: Reverse Tolerance ...increased response to same amount of drug
What are the Intoxications you can die from?
Nicotine, Cocaine, Amphetamine
Benzos, Alcohol, Barbituates
Opioids, PCP, Steroids
Inhalants and designer drugs
What are the Withdrawals you can die from?
The "B.A.B."s + O
Opioids (debiltated and infants)
How is alcohol absorbed? What are factors that alter absorption?
Rapidly absorbed in GI tract and sometimes even starting in the mouth
Passive Diffusion that is concentration dependent (Rapid at 20-30% and slower above that)
Depends on stomach content!!!!!
Summary of Factors altering absorption:
- Volume and character of beverage
- fat content
- time course of ingestion
- H2 Blockers
How does alcohol distribute in the body?
EtOH is highly water soluble and therefore distributes water to all tissues and accumulates in high blood flow organs (THE BRAIN!)
Enters Fetal circulation too!!!
Alcohol moves to organs w highest water content
Describe the metabolism of Ethanol: What are the major enzymes players? What are some factors that cause differences in metabolism?
Metabolized in liver in 2 big steps controlled by 2 enzymes: 1) Alcohol Dehydrogenase to Acetaldehyde and Aldehyde Dehydrogenase
Gender Differences matter
- For any given amount, women have higher BAC and slower metabolism
Race and Ethnicity Matters:
- ADH enzyme variants matter - especially asians!!
How is alcohol eliminated? aka what are the pharmacokinetcs?
Most alcohol elimination is Zero Order elimination until at very low amounts (10mg/dl) where it is First Order
What are the important BACs to know for Alcohol?
0.02 - mood elevation and slight muscle relaxation; DUI if under 21
0.08 - DUI
[amounts are different in tolerant people]
What are effects of alcohol intoxication?
What is treatment?
BEING DRUNK!!! flushing, diuresis, warmth, nystagmus etc
Treatment supportive - protect airway, electrolytes, trauma (CHECK HEAD FOR TRAUMA), COFFEE DOESNT CUT IT!
What are the GI effects of Alcohol Intoxication?
stimulates gastric juices - high acid and low pepsin
Low amounts stimulate GI motility and high amounts depress it
can cause N/V that is both central and peripheral
How does taking ASA affect Alcohol absorpiton?
MORE alcohol is absorbed when also using ASA
ASA inhibits gastric ADH!!!!
Both are more likely to cause GI irritation and are local irritants!
What are CV effects of Alcohol?
Smaller amounts - transient increase in pulse, CO, BP and sub-cutaneous vasodilation
DANGER in cold weather!!!!
What's the more important factor in Alcohol withdrawal from chronic use?
Absolute alcohol level is less important compared to the relative decreases in that level which are important bc tolerance changes dependence on BAC
What is the staging/symptoms of Chronic alcohol withdrawal? What is the final result and what can kill you?
Stage 1 - (w/in 24 hours and ablates by 48) - Shakey/tremor, HTN, tachycardia, sweating, N, Hyperactive reflexes, Fever, anxiety, derealization, clowdy sensorium, insomnia, HA --- Hangover
Stage 2 - (w/in 48 hours) more severe Stage 1 symptoms + HALLUCINATIONS - people know that something is weird - mostly auditory and are non-life-threatening
Pts have non-threatening hallucinations but intact reality testing
Stage 3 - (w/in 72 hrs and can last 3-7 days or more!) = Delirium Tremens - Need to prevent it - MORE hallucinations that are visual/tactile/auditory/olfactory and Threatening!!!!
OR have Seizures - tonic clonic (can be seen up to 1 week later) that are self-limited and can occur depsite normal vital signs
Delirium tremens or Seizures can be lethal
What are some criteria that mandate in-patient detox?>
History of DT or Seizures when stop drinking
dehydration, malnutrition, infection
CV collapse or arrhythmias
Fever, Tremor, Tachycardia
What can you use in the treatment of Alcohol withdrawal?
correct fluid imblances
Benzos!!! Diazepam for a smoother taper
+ Beta-blocker or Anti-convulsants (carbamazepine) so you can use less BZD
What is Wernicke? Why is it dangerous? What are some signS?
Less result of EtOH and more of nutrient deficiency in Thiamine
Can progress to Alcoholic-Induced Persisting Amnestic Disorder - Korsakoff which is irreversible
Nystagmus, Lateral Gaze Palsy, Ataxia, Confusion, Diplopia
What are primary diseasesa from chronic alcohol use?
What are secondary diseases from chronic alcohol use?
Primary - Withdrawal
Cardiomyopathy!!!! Gastritis, Liver cirrhosis, neuropathy
Cancer, DB, Pancreatitis, Pneumonia/influenza/TB, malnutrition, Respiratory disease
What are some biological markers for chronic heavy drinking?
LFTs - AST/ALT
CDT and MCV
What are endocrine effects of chronic alcohol use
Decreased testosterone in men - loss of secondary sex characteristics leading to impotence and sterility + testitcular atrophy and gynecomastia
Women - disruption of ovarian function
What do you see in FAS?
Prenatal Growth deficiency
Short, palpebral fissures
What are the 3 maintenance treatments for Alcoholism and how do each of them work?
1) Disulfiram - Blocks Aldehyde Dehydrogenase so build up acid aldehyde ....N/Dizziness/HA/Flushing
2) Naltrexone - Mu Antagonist to decrease reinformcement you get when someone drinks
3) Calcium Acetylhomotaurinate (Acomprosate/Campral) - NMDA glutamate Rec modulator - decreases cravings and triggers
What are the pros and cons of disulfram?
Pros - makes you feel like shit if you drink on it = Adverse Conditioning
Cons - occasionally can cause heart problems and death if you drink on it
HAVE TO TAKE IT!!!!
Side Effects: Drowsiness, lethargy, HTN, peripheral neuropathy
What are the pros and cons of naltrexone?
Pros - decreases reinforcement you get w/ drinking
generally well tolerated
Can get long-acting injection!
Cons - occasional N/ HA sedation or anziety
Rarely - increase in LFT!
What are the pros and cons of Calcium Acetylhomotaurinate aka Acomprosate?
Pros: Decreases cravings by normalizing glutamate levels to help w craving and trigger
NO LIVER TOXICITY
Cons: FDA WARNING INCREASED SUICIDE AND VIOLENCE
Side Effects: Diarrea and nausea