Alcohol MBBS 2014

 Alcohol Beer Cider Wine

Whiskey Brandy Rum Rectified spirit 26

Ethyl alcohol •  Alcohol is important important in medicine misuse/abuse • Present in beverages/used as drug •  Alcoholism is a complex complex disorder disorder with a genetic and environmental component 25

Pharmacological actions Local • Mild rubefacient - Cutaneous vasodilation • Promotes heat loss •  Astringent; antiseptic (↑20-70%=90% ↓) • Injected to nerve – nerve – permanent  permanent damage (sclerosant)

24

William Shakespeare (1564 –1616).  –1616). The Tragedy of Macbeth.

• Lechery, sir, it provokes, and unprovokes; • It provokes the desire, but it takes away the performance; performance; • It makes him, and it mars him; • It sets him on, and it takes him off; • It persuades him, and disheartens him; • Giveth redness of nose, sleep and urine 23

CNS effects •

CNS depressant

•

Inhibition is lost

•

At higher concentrations - slurred speech, ataxia, impaired judgment, motor incoordination, increased self-confidence & disinhibited behavior

•

Induces sleep-not dependable

•

Chronic: dementia, wernick’s, wernick’s , cognition disorders

•

Mechanism of CNS action involves:

•

22

 –

 potentiation of GABA receptor

 –

inhibition of Glutamate receptor neurotransmission

Enhances action at other ligand-gated ion channels like 5HT 3, NN, glycine receptors

CVS • Small doses – doses – cutaneous  cutaneous vasodilatation • Moderate dose - ↑ BP central sympathetic stimulation • High dose - ↓BP – Myocardial – Myocardial + vasomotor center depression

• Chronic alcoholism – alcoholism – cardiomyopathy,  cardiomyopathy, conduction defect, ventricular hypertrophy, atrial & ventricular ventricular arrhythmias 21

Blood • Low doses- ↑ HDL & ↓ CHD risk  •

Do not advice non drinkers to drink

Body temperature cold??—feeling of warmth • Combats cold??— • Heat loss is increased-vasodilation 20

• Gastric mucosa  – disrupt the gastric mucosal barrier and cause acute and chronic gastritis  – Promotes the release of gastrin and histamine  – ↑ gastric acid acid secretion  – act synergistically with H. pylori  to  to delay healing  – Inflammation and bleeding by ulceration of the stomach lining 

19

 Acute pancreatitis

Liver • Small to moderate-safe • Chronic-Cirrhosis

• Chronic alcohol consumption – consumption  – osteoporosis osteoporosis  –  reasons - unclear, impaired osteoblastic osteoblastic activity has been implicated

Endocrine Small doses-hyperglycemia-Adrenaline release Hypoglycemia[gluconeogenesis is  Large- Hypoglycemia[gluconeogenesis inhibited] 

18

Kidney • Diuresis - ↓ Antidiuretic hormone

Uterus • Relaxant

17

Pharmacokinetics

• Orally - rapidly absorbed from stomach and small intestine • Depends on the presence of food • Vol.of distribution wide • Metabolism-zero order [12ml/hr]

16

Ethanol Metabolism o Oxidation - Alcohol dehydrogenase (Al.DH) [F o m e p i z o l e  inhibits]  inhibits]

o Ald.DH - mainly in liver, stomach and brain [D i s u l f i r a m   inhibits]  inhibits] Sulfonylurea, cefoperazone, metronidazole] Microsomal Ethanol-Oxidizing Ethanol-Oxidizing System (MEOS) Another minor pathway of metabolism 15

Ethanol-metabolism • Genetic factors • In 50% of Asian people, an inactive genetic variant of one of the aldehyde dehydrogenase dehydrogenase isoforms (ALDH-2) is expressed; • These individuals experience a disulfiramlike reaction after alcohol, and the incidence of alcoholism in this group is extremely low 13

 Adverse health health effects • >3 drinks/day is associated with adverse health effects •

1 drink =18 ml of alcohol

•

350ml of beer or 150 ml of wine or 45 ml of spirit

1. GIT – GIT – peptic  peptic ulcer, hyperacidity, nutritional deficiency, pancreatitis 2. Lowers seizure threshold 3. Liver disease 14

 Adverse health effects •  Abuse • Fetal alcohol syndrome • HTN, cardiomyopathy cardiomyopathy • CNS – CNS – impaired  impaired mental and physical performance • Werni Wernicke cke’s ’s enceph encephalo alopat pathy, hy, Korsa Korsakof koff’s f’s psychosis 13

Teratogenic effects Fetal alcohol syndrome Characteristics of fetal alcohol syndrome include: (1) intrauterine growth retardation, (2) microcephaly, microcephaly, (3) poor coordination, (4) underdevelopment of mid-facial region (appearing as a flattened face), (5) minor joint anomalies •

12

Severe cases - congenital heart defects and mental retardation

Interactions •  Anxiolytics, antihistaminics, antihistaminics, hypnoticshypnoticsmarked CNS depression • Sulfonylurea, cefoperazone, metronidazole-Disulfiram like reaction •  Acute[Enzyme inhibitor][Chronic inhibitor][Chronic inducerinducerPmol?] 11

Therapeutic Uses TOPICAL

• • • •

Antiseptic Counterirritant Prevent bedsores To reduce body temp??? SYSTEMIC

• Trigeminal neuralgia (to destroy painful nerves) • Carminative and appetizer • Treat Methanol poisoning • Fainting hysteria

10

Contraindication • • • •

Peptic ulcer Epileptics Liver disease Pregnancya. Mode Modera rate te drin drinki kingng-fe feta tall sy synd ndro rome mes s b. Heav Heavy-m y-mis isca carri rriag age, e, stil stillb lbir irth ths s

9

 Acute Ethanol Intoxication Intoxication • Occurs from consumption of large quantities by naive individuals Degree of intoxication depends on: 1. Blood Blood ethano ethanoll concentr concentrati ation on (BAC) (BAC) 2. How fast fast the the blood blood ethanol ethanol level level rises 3. How long long the BAC BAC is is maint maintain ained ed Other factors are: Drinking patterns, Absorptive surface, other medications

8

 Acute Ethanol Ethanol Intoxication….. •  Acute Effects: Vasodilation, Tachycardia G.I. Irritation, respiratory depression • Management: Prevention of respiratory depression; aspiration of vomitus • Treatment of: Hypoglycemia & ketosis with glucose • Treatment of dehydration with electrolytes • Thiamine - to protect against Wernicke-Korsakoff syndrome. 7

 Alcoholism  Alcoholism & Treatment Treatment • Chronic alcohol use (alcoholism) results in CNS adaptations called Tolerance and Physical dependence • Withdrawal symptoms during abstinence from alcohol include delirium tremens, convulsion, seizure, tremors and nausea TREATMENT / DETOXIFICATION • Substitution of a long acting sedative/hypnotic drug for ethanol, i.e. Benzodiazepine or Oxazepam • I.V. infusion of Phenytoin to stop Seizures • Disulfiram (250 mg daily) Supplementary dietary thiamine to replace body vitamin loss

6

Treatment of alcoholism 1. Motivated alcoholic and complete abstinence 2. Disulfiram Disulfiram –  – used  used as a aversion technique in chronic alcoholics 3. Naltrexone Naltrexone –  – long  long acting opioid antagonist - ↓ craving for alcohol and prevent relapse 4. Acamprosate 4. Acamprosate ;  ; Complex receptor action[GABA & NMDA]  – decreases drinking frequency and reduces relapse in abstinent alcoholics 5

Disulfiram • Inhibits ALDH activity - blood acetaldehyde concentration rise to 5 to 10 times • Ingestion of alcohol by individuals pretreated with disulfiram - rise to marked signs and symptoms of acetaldehyde poisoning. • Face feels hot , flushing •  Throbbing ache in the head and neck, Respiratory difficulties, nausea, copious vomiting, sweating, thirst, chest pain, hypotension, marked uneasiness, weakness, vertigo, blurred vision, and confusion  A/E –  A/E – Psychosis,  Psychosis, hepatitis, rashes, metallic taste 4

Methyl alcohol (Methanol/Wood alcohol) • Metabolized to formaldehyde and formic acid • CNS depressant • Formic acid is responsible for toxic effect • Manifestation – Manifestation – vomiting,  vomiting, headache, epigastric pain, dyspnoea, hypotension, acidosis, retinal damage, damage, death

3

Leucovorin

Methanol-poisoning

Leucovorin

26

Treatment • Protect the eyes from light • Gastric lavage with sodium bicarbonate • IV sodium bicarbonate - ↓retinal damage by decreasing acidosis. • Ethanol to saturate alcohol dehydrogenase enzyme • Fomepizole – Fomepizole – specific  specific inhibitor of alcohol dehydrogenase – dehydrogenase – retards  retards methanol metabolism [Also used in ethylene glycol poisoning]

• Folinic acid [promotes oxidation of formic acid] 2

Summary •  Actions-CNS,CVS,LOC  Actions-CNS,CVS,LOCAL, AL, KIDNEY,STOMACH • PK-Zero order and metabolism •  ADEs-peptic ulcer, cirrhosis,CNS,cardiomyopathy, psychosis • DIs---Disulfiram like reactions • Uses • Methyl alcohol poisoning last