Kruse DSA: Pharmacology of Alcohol Flashcards
Drugs we use for the tx of acute alcohol withdrawal syndrome
- Diazepam
- Lorazepam
- Oxazepam
- Thiamine
Drugs for the prevention of alcohol abuse
- Acmprosate
- Disulfiram
- Naltrexone
Drugs for the tx of acute methanol or ethylene glycol poisonin
- Ethanol
- Fomepizole
What is fetal alcohol syndrome
-a syndrome of craniofacial dysmorphia, heart defects, and mental retardation caused by the teratogenic effects of ethanol consumption during pregnancy
Wernicke Korsakoff syndrome
-syndrome of ataxia, confusion, and paralysis of the EO muscles that is associated with chronic alcoholism and thiamine deficiency
Where does alcohol get absorbed the most?
-the small intestine
What order kinetics does alcohol follow?
- zero order
- independent of time and concentration
What enzyme metabolizes alcohol?
- Alcohol dehydrogenase (ADH)
- aldehyde dehydrogenase (ALDH)
What does fomepizole inhibit
-alcohol dehydrogenase
What does disulfiram inhibit?
- Aldehyde dehydrogenase
- gives you a bitch of a hangover
What does ADH do?
- converts ethanol to acetaldehyde
- in the liver
What other thing is required to vonvert ethanol to acetaldehyde?
- NAD+
- so, NADH comes out of there too
What does aspirin do in this DSA?
- inhibits gastric ADH and can increase ethanol bioavailability
- Fomepizole inhibits ADH and is used in tx of acute methanol or ethylene glycol poisoning
What is acetadehyde also dependent on?
-NAD+
What does acetaldehyde get converted to?
- acetic acid
- (produces NADH)
Which drug inhibits ALDH?
-disulfiram, a drug used for the tx of alcohol abuse and dependence
does ALDH have genetic polymorphisms?
- yes
- Asians… remember Ross the boss tanaka
What is the microsomal ethanol oxidizing system (MEOS)?
- oxidases (CYP450’s) use NADPH as a cofactor in the metabolism of ethanol to acetaldehyde
- higher concentrations of alcohol
Which cyp does chronic alcoholism induce?
- CYP2E1
- enhanced activation of toxins, free radicals, and hydrogen peroxide
What big ion channel does ethanol affect?
- NMDA subtype of glutamate receptors
- glutamate= primary excitatory NT in CNS
- GABA receptor… inhibitory in CNS
- enhances effects of GABA receptor and leads to an increased depression of the CNS
What is the most common cause for both acute and chronic pancreatitis in the US?
-Alcohol
Why do alcoholics get fatty liver?
-inhibition of both the TCA cycle and the oxidation of fat…. owing to the generation of excess NADH produced
What is tolerance
-reduced behavioral or physiological response to the same dose of ethano
What is that severe sign of alcohol withdrawal?
-delirium tremens
What is Wernicke-Korsakoff syndrome?
- paralysis of the EO muscles, ataxia, and a confused state that can progress to coma and death
- Associated with thiamine deficiency and rarely seen in the absence of alcoholism
- Tx with thiamine will improve ovular problems, ataxia, and confusion, but most pts are left with a chronic disabling memory disorder known as Korsakoff’s psychosis
What did studies show about alcohol and CHD?
-moderate alcohol consumption prevents CHD and reduces mortality more than in ppl who abstain or are heavy consumers or alcohol
Why do chronic drinkers have mild anemia
-folic acid deficiency
Why the iron deficiency anemia?
-GI bleeding
What is the weird thing that happens with body temp
-due to increased cutaneous and gastric blood flow, sweating may occur while the internal body temp falls
Why would someone going through withdrawal experience hyponatremia?
-vasopressin release is increased during withdrawal… so they retain a shit ton of water
What is the leading cause of mental retardation and congenital malformation ?
-Alcohol
What all comes with the Fetal alcohol syndrome package?
- Intrauterine growth retardation
- Microcephaly
- poor coordination
- underdevelopment of midfacial region
- minor joint abnormalities
Does the fetal liver have alcohol dehydrogenase activity?
-nah
What enzyme levels are increased from chronic ethanol consumption?
- CYP450s
- particularly, CYP2E1
- acetaminophen will fuck these people up
What do we do to manage acute alcohol intoxication?
- prevent severe resp depression and aspiration of vomitus
- Glucose can tx metabolic things like hypoglycemia and ketosis
- Thiamine to protect against the Wernicke-Korsakoff syndrome
- Potassium may be needed in the event of severe vomiting
What drug can we give them if they are having a really bad withdrawal?
- long acting benzos (diazepam)
- less frequent dosing and built in tapering effect
- but watch out for pts with a compromised liver because then pharmacologically active metabolites may accumulate
What do we do for someone in withdrawal but they’re liver function sucks?
- give them a short acting benzo like lorazepam or oxazepam
- rapidly converted to inactive metabolites and are useful in pts with liver disease
What is Naltrexone?
- approved for tx of alcohol and opiate dependence
- MOA: mu opioid receptor antagonist (long acting)
- reduces craving for alcohol and the rate of relapse to either drinking or acohol dpendence for the short term
When is Naltrexone contraindicated?
-in pts with acute hepatitis or liver failure
What do we have to make sure the patient is clear of before we give them Naltrexone?
- must be opioid-free!!!!!
- Naltrexone will create an acute withdrawal syndrome
Acamprosate
- MOA: weak NMDA receptor antagonist and GABAa receptor agonist
- Reduces short-term and long-term relapse rates
- elminated in urine as an uncharged drug; use caution in patients with kidney disease
- can be used in combo with naltrexone or disulfiram
Disulfiram
- MOA: irreversibly inhibits aldehyde dehydrogenase and causes exteme discomfort in pts who drink alcoholic beverages
- Slowly absorbed from GI tract with onset of action from 3-12 hrs; effects may persist up to 14 days from previous dose
- hepatotoxic, inhibits metabolism of other therapeutic agnets
What should we not mix disulfiram with?
-other drugs that contain alcohol
What is the caveate with disulfiram?
-the pts must be highly motivated and have supportive therapy
should we give disulfiram in a state of alcohol intoxication?
-no!
What is the most common characteristic symptom in methanol poisoning ?
-blurred vision (like being in a snowstorm)
tx of methanol poisoning
- resp support
- suppression of metabolism by ADH (ethanol and fomepizole)
- Hemodialysis to enhance methanol removal
- alkalinzation to counteract the metabolic acidosis (bicarb)
Which has a higher affinity for ADH, methanol or ethanol?
- ethanol actually, that is why you give them a drink lol
- remember fomepizole inhibits ADH and is approved for the tx of methanol poisoning
What is ethylene glycol metabolized to?
-toxic aldehydes and oxalate
Tx for ethylene glycol
- hemodialysis
- ethanol infusion
- Fomepizole
