Chapter -2
Drugs Acting on CNS
1.ALCOHOL
Alcohols are hydrocarbons. They may contain one or more hydroxyl (OH) groups. Ethyl alcohol is the commonly used alcohol.
ETHYL ALCOHOL
Ethyl alcohol is the main constituent of all kinds of alcoholic beverages. It is generally obtained by fermentation of sugar by yeast.
Pharmacological actions:
External:
Externally alcohol is:
i. astringent since it precipitates proteins.
ii. refrigerentsince it produces cooling effect on the skin.
iii. rubifacient since it dilates cutaneous blood vessels.
iv. detergent since it dissolves sebaceous secretions.
v. antiseptic since it destroys micro-organisms.
2. Gastrointestinal tract : Alcohol increases gastrie acid secretion and also produces a carminative effect.
3. Liver: Produces fatty liver on chronic administration.
4. Central nervous system : Alcohol produces initial excitation (characterised by incoherent speech and gait) due to depression of higher inhibitory centres. This is followed by progressive depression, drowsiness, sleep and unconsciousness as the dose is increased.
5. Cardiovascular system : Moderate dose of alcohol produces cutaneous vasodilatation. This produces a feeling of flushing and warmth. A concentrated form of alcohol produces slight rise in blood pressure and increase in heart rate due to reflex action.
6. Respiration : Moderate doses produce slight stimulation
Drug treatment of alcohol intoxication
• Psychological and medical supportive measure are needed during withdrawal and many CNS depressant like barbiturates, phenothiazine, Chloral hydrate have been used.
Drugs
Bezodiazepam=Prevent withdrawal syndrome.
Naltrexone=Opioid antagonist, prevent relapse of alcoholic form.
Acamprosate=NMDA antagonist, used for maintenance therapy.
Ondansetron=5 HT3 antagonist, blocks action of alcohol.
Disulfiram=Inhibits aldehyde dehydrogenase
Disulfiram:
• It is used in treatment of chronic alcoholism by producing an acute sensitivity to ethanol (drinking alcohol).
• Disulfiram works by inhibiting the enzyme acetaldehyde dehydrogenase, causing many of the effects of a hangover to be felt immediately following alcohol consumption.
• Side effect of disulfiram are include metallic taste, nervousness, malaise and abdominal upset.
• It inhibit alcohol dehydrogenase, dopamine ß hydroxylase and several cytochrome P450 isoenzyme, Metalloenzymes, thus it prolong T1/2 many drugs.
Explanation
How disulfiram work
METHYLALCOHOL .
Methanol is highly toxic alcohol. . It is metabolized to formaldehyde (by alcohol dehydrogenase) and formic acid (by acetaldehyde dehydrogenase). . It is the accumulation of formic acid which causes toxic effects in methanol poisoning.
Drugs used in methanol poisoning ·
Ethanol: Competitively inhibits the conversion of methanol to formic acid
Fomepizole: Specific inhibitor of alcohol dehydroginase. .
Folicacid and Folinic acid: Responsible for conversion of formic acid to CO2.
Short Questions and Answers
1.Chronic alcoholism causes following symptoms except:
(a) Wernicke's encephalopathy
(b) Korsakoff's psychosis
(c) Myocardial infarction
(d) Cirrhosis
2. Which of the following disease contraindicated in alcohol consumption
(a) Peptic ulcer,
(b) Hyperacidity
(c) Epileptics
(d) All of the above
Explanation
Interaction:
• Alcohol synergises with anxiolytic, antidepressant, antihistamine, hypnotics opioids so that marketed CNS depression.
• Acute alcohol ingestion inhibits, while chronic intake induces CYP enzyme.
•Hypoglycemicaction of insulin and sulfonylurea is enhanced by alcohol ingestion.
• Aspirin and other NSAIDS cause more gastric bleeding when taken with alcohol.
Contraindication:
• Intake of alcohol should be avoided by Patient with peptic ulcer, hyperacidity and gastroesophageal reflux disease.
• Epileptics: Seizure may be precipitated.
3. Select the correct statement about Disulfiram:
(a) It inhibits formation of acetaldehyde from ethanol
(b) It is useful in treatment of acute ethanol poisoning
(c) It inhibits several hepatic cytochrome p450 isoenzymes
(d) It is not effective on orał adminstration
4. Disulfiram inhibits
(b) Acetaldehyde dehydrogenase
(b) Metalloenzymes
(c) Dopamine ß-hydroxylase
(d) All of the above
5. Following agents are administered in methanol poisoning except
(a) Disulfiram
(b) Fomepizole
(c) Folate
(d) Ethanol
6. Ethanol is used in methanol poisoning because it
(a) Antagonizes the actions of methanol
(b) Stimulates the metabolism of methanol and reduces its blood level
(c) Inhibits the metabolism of methanol and generation of toxic metabolite
(d) Replenishes the folate stores depleted by methanol
7. Drug of choice for methanol poisoning is:
(a) Disulfiram
(b) Fomepizole
(c) Folate
(d) Ethanol
8. The toxicity of methyl alcohol is due to:
(b) Formic acid
(b) Ethanol
(c) Methanol itself
(d) All of the above
9.The methanol is toxic to optic nerve, it is because of
(b) Methanol itself
(b) Oxidative metabolites of methanol
(c) Conjugated product of methanol
(d) Idiosyncratic reaction
10.In methyl alcohol poisoning there is CNS depression, cardiac depression and optic nerve atrophy. These effects are produced due to:
(a) Formaldehyde and formic acid
(b) Acetaldehyde
(c) Pyridine
(d) Acetic acid
11.All of the following reduce craving in alcoholics except:
(a) Acamprosate
(b) Ondansetron
(c) Nalmephene
(d) Diazepam
Explanation
Alcohol craving refer to a broad range of thoughts, physical sensations, or emotions that tempt you to drink, even though you have at least some desire not to.
12.All of the following drugs causes disulfiram like reaction except:
(a) Chlorpropamide
(b) Cefoperazone
(c) Griseofulvin
(d) Chloramphenicol
13.The drug which is a specific inhibitor of the enzyme alcohol dehydrogeņase and is useful in the treatment of methanol and ethylene glycol poisoning is:
(b) Disulfiram
(b) Ethylene glycol
(c) Calcium leucovorin
(d) Fomepizole
2.General anaesthetics
INTRODUCTION: .
General anaesthetic are drugs which produce reversible loss of all sensation and consciousness.
The features are: ·
Reversible loss of consciousness
Analgesia and amnesia Immobility and muscle relaxation .
Reversible loss of all sensation, especially pain.
Stage of Anaesthesia:
Stage I: Stage of analgesia, sedation.
Stage II: Loss of pain to unconsciousness (Delirium), Reflex action observe
Stage IlI: Stage of surgical anaesthesia
Srtage IV: Medullary Paralysis & Death
Classification
Inhalational
Gas= Nitrous oxide
Volatile Liquid= Ether, Halothane, Enflurane,
Isoflurane,
Desflurane,
Sevoflurane
Parenteral
Fast acting drugs=Thiopentone
Methohexitone
Propofol
Etomidate
Slowing acting drugs
Benzodiazepines: Diazepam, Lorazepam, Midazopam
Dissociative anaesthetic: Ketamine
Opioid analgesic: Fentanyl, Remifentanil
Minimum Alveolar Concentration (MAC)
• Minimum alveolar concentration or MAC is the concentration of a vapour in the alveoli of the lungs that is needed to prevent movement in 50% of subjects in response to surgical stimulus. Potency of general anaesthesia depicted upon its MAC value.
Nitrous oxide
• Colorless,odorless, nonirritating and noninflammable gas.
• It is also called as laughing gas.
• It has good analgesic but poor muscle relaxants activity.
• Patient maintained on (70%N2O+ 30% O2) recall .
• events during anaesthesia.
• N2O has been used with O, for dental analgesia.
• N20 cause hypoxia
SECOND GAS EFFECT:
•During induction of general anesthesia, when a large volume of a gas (e.g. nitrous oxide) is taken up from alveoli into pulmonary capillary blood, the concentration of gases remaining in the alveoli is increased. This results in effects known as the "concentration effect" and the second gas effect.
• These effects occur because of the contraction of alveolar volume associated with the uptake of the nitrous oxide
ETHER (DIETHYL ETHER) :
It is a colourless and volatile liquid with a pungent odour. Ii is highly inflammable and Explasive. It is quickly absorbed and eliminated through lungs.
Advantages:
1. It is a safe anaesthetic.
2. I produces satisfactory muscle relaxation.
3. It does not produce liver or kidney damage.
4. It does not affect uterine conractility.
5. It can be administered without complicated apparatus.
Đisadvantages:
1. Induction is slow and unpleasant.
2 It irritates mucous membranes and produces cough.
3. It increases secretions of respiratory tract.
4. Produces nausea and vomiting during recovery.
5. Recovery is slow.
HALOTHANE :
It is a fluorinated volatile annesthetic It is a heavy, colourless liquid with a characteristic sweet, fruity odour. It attacks metals like steel and brass and also rubber elements of anaesthetic equipments. Malignant hyperthermia is an important toxicity of halothane. It is due to the release of calcium from the sarcoplastic reticulum. It is treated by the administration of dantrolene (a directly acting muscle relaxant).
Advantages :
1. It is non - inflammable. It does not irritate respíratory passages.
2. Induction and recovery are quick. It does not produce bronchospasm and coughing. But it produces bronchodilatation. So it is preferred in asthmatic patients.
4. It induces controlled hypotension. So it produces bloodless field for safe plastic surgery.
Disadvantages:
1. Muscle relaxation is not adequate.
2. Respiratory depression at 2% concentration.
3. Cardiovascular depression and hypotension.
4. Arrhythmias due to sensitisation of myocardium to adrenaline:
5. Delayed recovery of mental function.
6. Increase in intracranial pressure due to cerebral vasodilatation.
7. Hepatic damage due to allergy or idiosyncrasy
ENFLURANE :
1. It is a non irritating, non inflammable liquid with a mild odour.
2. It undergoes less metabolism than halothane, so toxicity is less.
3. Faster induction and recovery than halothane.
4. Risk of epilepsy like seizures during induction or recovery.
5. Contraindications : patients with epilepsy or brain lesions.
Short Questions and Answers:
1. Which of the following is not the fast acting parenteral general anesthetics
( a ) Thiopentone
( b ) Propofol
( c ) Etomidate
( d ) Ketamine
2. Second gas effect is seen with :
( a ) Ether
( b ) Nitrous oxide
( c ) Desflurane
( d ) Sevoflurane
3. Second gas effect is exerted by which of the following gas when co administered with halothane ?
( a ) Nitrous oxide
( b ) Cyclopropane
( c ) Nitrogen
( d ) Helium
4. Laughing gas is :
( a ) Nitrous oxide
( b ) Cyclopropane
( c ) Diethyl ether
( d ) Halothane
5. The disadvantage of halothane anaesthesia is
( a ) It depresses respiration
( b ) It increases blood pressure
( c ) It decreases intracranial pressure
( d ) Induction of anaesthesia is slowly
6. Which of the following inhalational agent is the best uterine relaxant
( a ) Halothane
( b ) Isoflurane
( c ) Sevoflurane
( d ) Desflurane
7. The anaesthetic that sensitizes heart to catecholamines is
( a ) Ether
( b ) Enflurane
( c ) Sevoflurane
( d ) Halothane
8. Ketamine is useful as an anesthetic agent in
( a ) Ischemic heart disease
( b ) Intracranial hemorrhage
( c ) Hyperactive airways
( d ) Glaucoma
9. Benefit of ketamine is
( a ) Cause decrease in BP
( b ) Good analgesic action
( c ) Decrease ICT
( d ) Decrease IOP
10. Structural analogue of phencyclidine
( a ) Thiopentone
( b ) Propofol
( c ) Ether
( d ) Ketamine
11. Intravenous general anaesthetic of choice in bronchial asthma is
( a ) Thiopentone
( b ) Propofol
( c ) Etomidate
( d ) Ketamine
12. Which of the following causes dissociative anaesthesia
( a ) Ketamine
( b ) Fentanyl
( c ) Propofol
( d ) Halothane
13. Which of the following intravenous anaesthetic agents is contraindicated in epileptic patients posted for general anaesthesia
( a ) Ketamine
( b ) Thiopentone
( c ) Propofol
( d ) Nlidazolarn
14. Which of the following statement regarding isoflurane is incorrect
( a ) It is an isomer of entlurane
( b ) It produces a rapid induction of anaesthesia
( c ) it produces marked respiratory depression
( d ) It decreases secretions
15. General anaesthetic with antiemetic action is
( a ) Thiopentone
( b ) Propofol
( c ) Etomidate
( d ) Ketamine
16. Which of the following cause nephrotoxic
( a ) Halothane
( b ) Methoxyflurane
( C ) Ether
( d ) Cyclopropane
17. True statement about sevoflurane is
( a ) It can produce convulsions
( b ) It is cardiostable
( c ) It can cause hepatitis
( d ) It is neurotoxic at high doses
3. HYPNOTICS AND SEDATIVES
Hypnotics are drugs which produce sleep resembling natural sleep. Sedatives are drugs which reduce excitement without producing sleep. Qualitatively hypnotics and sedatives produce depression of central nervous system and the difference between them is mainly quantitative.
Classification of drugs:
1. Barbiturates=
Phenobarbitone (long acting)
Butobarbitione(short acting)
Pentobrabitone(short acting)
Thiopentone (ultra short acting)
Methohexitone(ultra short acting)
2. Benzodiazepines=
Diazepam
Flurazepam
Nitrazepam
Lorazepam
3. Newer non-benzo diazepines=
Zolpidem
Zopielone
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