M5: Alcohols Flashcards
Chemical Structure of Alcohol & Examples (4)
CHEMICAL STRUCTURE:
- Organic compound: made of OH & C atom
OH = functional group
C atom = saturated
EXAMPLES (4):
1. Methanol: CH3OH
2. Ethanol: C2H5OH
3. Propan-2-ol (isopropyl alcohol): C3H7OH
4. Ethane-1,2-diol (ethylene glycol): C2H4(OH)2
ETHANOL (ETHYL ALCOHOL)
- Properties
- Pharmacokinetics
- Metabolic Pathways
- Mechanism of Action
PROPERTIES:
- Small molecule
- Produced by sugar fermentation
- Water–soluble
- Organic solvent
- Volatile & flammable
- Used as:
1. Recreational drug
2. Antiseptic / disinfectant
3. Chemical solvent
4. Fuel
PHARMACOKINETICS:
1. Absorption: rapidly through GIT
- Peak blood level: within 30 minutes (F>M)
- Distribution: rapid – increase in VD close to total body water (0.5-0.7 L/kg)
- Crosses membranes: e.g., BBB – placenta
- Metabolism: liver (90%) – oxidation – 2 pathways …
- Excretion:
Kidney → urine
Lungs → breath (DUI)
METABOLIC PATHWAYS:
1. MEOS: Microsomal Ethanol-Oxidizing System
- Fomepizole: treatment of methanol or ethylene glycol poisoning
- Disulfiram: treatment of alcohol dependence
- Rate:
Zero order kinetics (= independent of time & concentration) - 2 Pathways:
Alcohol dehydrogenase (primary pathway)
MEOS (chronic alcoholism) → Acetaldehyde →
Acetate → CO2 OR acetyl-CoA
Acetaldehyde accumulation →
(Facial flushing, nausea, vomiting, dizziness, headache)
MECHANISM OF ACTION:
1. Increase GABA-mediated inhibition through GABAA receptor
- Decrease glutamate-mediated excitation through NMDA receptor
- Other actions:
Increase dopamine (DA)–mediated reward processes
Increase endogenous opioid & cannabinoid pathways - High Dose:
Na channel blockade, electrical stabilization & conduction of nerve action potential (direct effect)
GLUTAMATE RECEPTORS
- NMDA receptor = N-methyl-D-aspartate receptor
- AMPA receptor = α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor
PHARMACODYNAMICS OF ACUTE CONSUMPTION
- CNS Depression:
- Chronic drinkers require higher concentrations due to tolerance
- Sedation, Coma, Emesis, Respiratory Distress. Impaired Motor Function - Heart:
- Decrease myocardial contractility
- High dose: dysrhythmia - Smooth Muscle Relaxation:
- Due to decrease in vasomotor center + acetaldehyde
- Vasodilation → hypothermia (heat loss) + hypotension
- Uterine relaxation
Drug Interactions
- Additive CNS depression with other CNS depressants
- Hepatic microsomal enzyme induction →
- Increase metabolism of drugs
- Generation of toxins, free radicles, H2O2 - Drugs with disulfiram-like reaction:
- E.g., metronidazole, trimethoprim
Long Term Effects of Alcohol Consumption
- CNS:
- Tolerance, addiction & dependence
- Neurotoxicity - Liver:
- Alcoholic fatty liver → hepatitis → cirrhosis liver failure - GI:
- Gastritis → peptic ulcer & GI bleeding
- Chronic pancreatitis
- Malabsorption - CVS:
- Cardiomyopathy & HF
- Dysrhythmias – atrial & ventricular
- Hypertension - Hematologic: Folic acid deficiency & Fe anemia
- Abnormal immune response
- Endocrine & metabolic:
-♂: Gynecomastia & testicular atrophy
- Hypoglycemia
- Lactic acidosis - Cancer:
- Mouth, pharynx, larynx, esophagus, liver
- Causes: acetaldehyde, folate metabolism changes, chronic inflammation
What is Fetal Alcohol Spectrum Disorder (FASD’s)
Fetal alcohol spectrum disorders (FASDs):
- Group of conditions in children due to chronic maternal alcohol abuse during pregnancy
- Mechanism of teratogenic effect: unknown!
- Wide Spectrum: most severe is Fetal Alcohol Syndrome (FAS)
Main Manifestations:
- Growth retardation
- Microcephaly
- Facial features
- Congenital heart defects
- CNS defects …
CNS Defects in Fas:
- Cognitive deficits:
- E.g., learning disabilities – mental retardation
- Impaired motor function:
- E.g., lack of coordination – impaired gross & fine motor skills
- Attention & hyperactivity problems (ADHD)
- Social skills problems
- Epilepsy
Tolerance
May result from:
- Ethanol–Induced up–regulation of a pathway
Results in:
- Decreased intensity
- Shortened duration of action
Cross tolerance with:
- Sedative–hypnotics
- General anesthetics
Dependence
- Psychological Dependence (Addiction):
Compulsion to:
- Experience the rewarding effect
- Avoid the withdrawal symptoms - Physical dependence: →
Withdrawal syndrome (1-3 days after stopping) :
- Mild: hyperexcitability
- Severe: seizures – psychosis – delirium tremens – coma – death
- Delirium tremens (3-9 days after stopping): Hyperadrenergic state, disorientation, tremors, diaphoresis, impaired attention/consciousness & visual & auditory hallucinations
Neurotoxicity
Peripheral neuropathy
- Wernicke-Korsakoff syndrome:
- Caused by thiamine (vitamin B1) deficiency
Manifestations:
- Extrinsic eye muscles paralysis
- Ataxia
- Confusion → encephalopathy → coma → death
Sequalae after treatment:
- Korsakoff’s psychosis – memory loss
- Impaired vision
Management of Alcohol Intoxication (3)
- Treatment of acute intoxication (overdose)
- Management of withdrawal syndrome
- Treatment of alcoholism
Treatment of Acute Intoxication
- Prevent severe respiratory depression
- Aspiration of vomitus
- Correct electrolyte imbalances
- Treatment of hypoglycemia & ketoacidosis
- Vitamin B1 (thiamine)
- No antidote
Management of Withdrawal Syndrome
Mild symptoms don’t need treatment
Prevention of seizures, delirium & dangerous dysrhythmias:
1. Vitamin B1 (thiamine)
- Correct electrolytes – e.g., K, Mg, PO4
- Benzodiazepines
- Long-acting – e.g., diazepam
- In liver disease: short acting – e.g., lorazepam
Treatment of Alcoholism (3 Drugs)
Rehabilitation & psychological therapy
- Naltrexone:
- Long-acting opioid antagonist – blocks mu () receptors - Acamprosate:
- Decrease NMDA receptor & Increase GABAA receptor - Disulfiram:
- Flushing, nausea, vomiting, dizziness, headache…
Alcoholism Drug Therapy: General Consideration
- All three drugs are administered orally
- Both Naltrexone & Acamprosate help reduce craving
- Disulfiram makes the patient hates drinking
- Precautions while using Naltrexone:
- Patient should not be opioid dependent (opioid withdrawal)
- Don’t combine with Disulfiram (both are hepatotoxic) - Acamprosate is poorly absorbed from GIT
