Pharmacology-CNS Fast Track

CNS
PHARMACOLOGY
SYLLABUS
Introduction
Aliphatic Alcohols: (P. 943)
Ethanol and methanol- effects on different organ systems, acute and chronic alcoholism, methyl alcohol
poisoning (P. 945)– management
Local Anaesthetics: (P. 946)
Types of local anesthesia, classification, mechanism, uses and adverse effects
General Anaesthetics: (P. 948)
Principles, classification
Commonly used general anaesthetics
Dissociative anesthesia, neuroleptanalgesia
Preanaesthetic medication- rationale and examples
Sedatives, hypnotics: (P. 951)
Anti-Epileptic drugs: (P. 953)
VIII
Mechanism of action, indications, adverse effects and contraindication of antiepileptics
Types of epilepsies and drugs for each
Psychopharmacology: (P. 957)
Anti-psychotics (P. 957), antidepressants (P. 963) and mood stabilizers (P. 961)
Classification, mechanism, pharmacological actions, uses, adverse effects and drugs interactions.
Antianxiety drugs (P. 966): brief description.
Therapy of Parkinsonism: (P. 966)
Types, causes
Principles of drugs therapy, drugs used and the rationale of therapy.
Opioid Analgesics and Antagonists: (P. 970)
Classification, mechanism, pharmacological actions, uses, adverse effects, acute poisoning (P. 971),
management, drug dependence- management.
Therapy of insomnia.
Drug Abuse: Types and management
FAST TRACK BASIC SCIENCE MBBS -941-

Pharmacology
VIII
-942- FAST TRACK BASIC SCIENCE MBBS

CNS
PHARMACOLOGY
ALIPHATIC ALCOHOLS  Impairment of memory

Past Questions:  Alteration of perception
1. Give the pharmacological basis of use of:  Drowsiness
a. Ethanol is used in methanol poisoning [04 Dec] iii. 150-200 mg/dl
b. Ethyl alcohol is used in methyl alcohol  The person becomes sloppy, ataxic and
poisoning [03 Dec] drunk.
c. Ethyl alcohol is used in methanol poisoning iv. 200-300 mg/dl
[03 June]  Results in stupor
d. Use of Disulfiram in chronic alcoholism  Unconsciousness prevails
[01 June]  Medullary centres are paralyzed
e. Use of ethyl alcohol in methyl alcohol  Death may occur
poisoning (2) [02 Dec] - Alcohol can also act as sedative, hypnotic
f. Disulfiram in chronic alcoholism (2) [04 Dec] agent.
Ethanol and methanol - It raises pain threshold and primarily affects
reticular activating system.
 Alcohols are hydroxy derivatives of aliphatic
hydrocarbons. 3. Cardio vascular system
- Small doses: BP is not affected
Effects of alcohol on different organ
systems: - Moderate doses: Cause tachycardia and a mild
rises in BP VIII
1. Local Actions
- Large doses: Cause direct myocardial as well as
- Applied to delicate skin or mucous membranes,
vasomotor centre depression
it produces irritation and burning sensation.
 Fall in BP
- By evaporation, it produces cooling
4. Blood
- Alcohol is an astringent and acts as an
antiseptic as well. - Small to moderate amounts of alcohol raises
HDL cholesterol levels and decreases LDL
2. CNS
oxidation.
- It's action on CNS is dose dependent.
5. Body Temperature
i. 30-100 mg/dl
- It produces a sense of warmth due to
 Hesitation, caution , self-criticism and rest
cutaneous and gastric vasodilatation.
raint are lost.
6. Respiration
 Apparent excitation and euphoria are
- It depresses respiratory centre.
experienced.
7. GIT
 Mood and feelings are altered
- It's a strong stimulant of gastric secretion
 Anxiety may be allayed
whereas higher concentration inhibit gastric
ii. 100-150 mg/dl secretion.
 Mental clouding 8. Liver
 Disorganization of thought - It may cause alcoholic cirrhosis.

Pharmacology
9. Skeletal Muscle - Aspirin and other NSAIDS causes gastric

- Weakness and myopathy occurs in chronic bleeding when taken with alcohol
alcoholism. - Alcoholics are more prone to paracetamol
10. Kidney toxicity.
- It results in diuresis. Contraindication:
11. Sex - Peptic ulcer, hyperacidity and gastroesophageal
- It produces aggressive sexual behaviour. reflux patients
12. Endocrine effects - Epileptics
- Moderate amounts can cause hyperglycemia. - Severe liver disease patients
- Acute intoxication may causes hypoglycemia - Pregnancy
13. It suppresses uterine contractions at moderate Note:
blood levels. - On average 1-2 drinks per day is usually safe.
Meatabolism of alcohol - Safe limits are somewhat lower for women than
for men, because metabolism of alcohol is slower
CH3CH2OH
NAD+ Ethanol NADPH+O2 and its bioavailability is higher in women than in
men.
Alcohol
dehydrogenase MEOS
Acute Alcohol Intoxication
NADH CH3CHO NADP++H2O Characterized by:
Acetaldehyde - Hypotension, gastritis, hypoglycemia, collapse,
Fomepizole NAD+
Aldehyde respiratory depression, coma, death
dehydrogenase
NADH Treatment:
VIII - Gastric lavage if patient is brought soon after
Acetate
CH3COO- Disulfiram ingesting alcohol.
- Maintenance of patent airway and positive
Clinical uses of ethyl alcohol pressure ventilation for respiratory support
- As antiseptic - Maintenance of blood and electrolyte balance
- To prevent bed sores - Glucose infusion along with thiamine to correct
- Neuralgias, severe cancer pain [injection hypoglycemic
around nerve causes permanent loss of - Haemodialysis
transmission]
- Insulin + fructose drip to accelerate alcohol
- To treat methanol poisoning metabolism.
- Rubefacient and counterirritant for sprains
Chronic Alcoholism
- Alcoholic sponges to reduce body temperature
in fever Characterized by:
- Reflex stimulation in fainting/hysteria - Psychic and physical dependence.
- As appetite stimulant - Nutritional deficiencies, because food is
- To ward off cold neglected and malabsorption may occurs.
Interactions - Impaired mental and physical performance,
polyneuritis, pellagra, tremors, Wernicke's
- Disulfiram-like reactions occurs with
encephalopathy, Korsakoff's psychosis and
sulfonylureas (especially chlorpropamide);
megaloblastic anaemia.
cephalosporins (cefoperazone).

CNS
- Alcoholic cirrhosis of liver, HTN,  Dizziness, Visual disturbances, Mental

cardiomyopathy, arrhythmias, stroke. confusion, Postural fainting, Circulatory
- Impotence, gynaecomastia, infertility and collapse.
skeletal myopathy are complications. - Because inhibition of aldehyde dehydrogenase
Withdrawal Syndrome of Alcohol with disulfiram is irreversible, the subjects
resolve not to drink is reinforced by the
Characterized by: distressing symptoms that occur if he drink a
- Anxiety little bit.
- Sweating - Thus, it produces aversion to alcohol.
- Tremor Dose:
- Impairment of sleep - 1g on 1st day, 0.75g on 2nd day, 0.5g on 3rd
- Hallucinations day and 0.25g daily for 1-2 weeks followed by
- Delirium tremors 0.125 - 0.25g /day
- Confusion Note:
- Convulsions - Disulfiram should not be used in patients who are
physically dependent on alcohol.
- Collapse
Note: In severe alcohol intoxication, the blood Methyl Alcohol Poisoning
ethanol exceeds 300mg.  Mixing of methylated spirit with alcohol beverages
or its accidental ingestion results in methyl alcohol
Treatment:
poisoning.
- Physiological and medical supportive measures
 Methanol is metabolized to formaldehyde and
- Benzodiazepines (diazepam) are the preferred
then formic acid by alcohol and aldehyde
drugs. dehydrogenases respectively. VIII
- Naltrexone  Opioid antagonist  Helps
 Toxic effects of methanol are largely due to formic
prevent relapse of alcoholism. acid, since its further metabolism is slow and
- Acamprostate  GABA receptor agonist  For folate dependent.
maintenance therapy of alcohol abstinence.
 Manifestations of methanol poisoning are:
- Ondansetron  5HT3 antagonist
- Vomiting
Use of Disulfiram in chronic alcoholism
- Headache
[KU 99, 00, 01]
- Epigastric pain
- Disulfiram inhibits the enzyme aldehyde
dehydrogenase which helps in the conversion - Uneasiness
of acetaldehyde to acetic acid. - Dyspnea
- Thus, the concentration of acetaldehyde in - Bradycardia
tissues and blood rises and a number of highly - Hypotension
distressing symptoms so called Aldehyde - Acidosis
Syndrome are produced promptly. These - Retinal damage [specific toxicity of formic
include: acid]
 Flushing, Burning sensation, Perspiration
 Blurring of vision, congestion of optic disc
 Uneasiness, Tightness in chest followed by blindness always precede death,
 Throbbing headache, Vomiting which is due to respiratory failure.

Pharmacology
Note: LOCAL ANAESTHETICS

i. A blood level of >50mg/dl methanol is associated Past Questions:
with severe poisoning 1. Give the pharmacological basis of use of:
ii. Even 15ml of methanol has caused blindness and a. Adrenaline with lignocaine for infiltration
30ml has caused death.
anesthesia [3][11 July]
iii. Fatal dose is regarded to be 75-100 ml.
b. Lignocaine as local anaesthetic agent
iv. Methanol causes blindness due to its oxidative
[3] [06 June, 05Dec]
products.
c. Lidocaine should not be combined with
Ethanol in methyl alcohol poisoning Epinephrine during circumcision (2)[02Dec]
[KU 99, 02, 03, 04] d. Lignocaine is not combined with epinephrine
 Ethanol 100 mg/dl in blood saturates alcohol during circumcision surgical operation [10Jan]
dehydrogenase and retards methanol metabolism 2. Write short notes on pre-anaesthetic medication.
by reducing the rate of generation of toxic [3] [08 Jan, 05 June]
metabolites (formic acid)
A. Classification
 Ethanol (10% in water) is administered through a
nasogastric tube, loading does of 0.7 ml/kg is 1. Injectable Anaesthetic
followed by 0.15 ml/kg/hour drip. - Low potency , short duration
 Treatment has to be continued for several days  Procaine
because the sojourn of methanol in body is long.
 Chloroprocaine
Other treatment measures include:
- Intermediate potency and duration
- Keep the patient in a quiet, dark room; protect
 Lidocaine (Lignocaine)
VIII the eyes from light.
- Gastric lavage with sodium bicarbonate; if the  Prilocaine
patient is brought within 2 hours of ingesting - High potency, long duration
methanol.
 Tetracaine (Amethocaine)
- Supportive measures to maintain ventilation
and BP should be instituted.  Bupivacaine
- Combat acidosis by i.v. sodium bicarbonate  Ropivacaine
infusion.
 Dibucaine (Cinchocaine)
- Potassium chloride infusion is needed only
when hypokalemia occurs due to alkali 2. Surface Anaesthetic
therapy. - Soluble
- Hemodialysis to clear methanol as well as
 Cocaine
formate.
- Fomepizole (4-methyl-pyrazole), a specific  Lidocaine
inhibitor of alcohol dehydrogenase retards  Tetracaine
methanol metabolism.
 Benoxinate
 A loading dose of 15 mg/kg iv. followed by
10mg every 12 hours till serum methanol - Insoluble
falls below 20mg/dl is effective and safe.  Benzocaine
- Folate Therapy: Calcium leucovorin 50mg
 Butyl-amino-benzoate
injected 60 hourly reduce blood formate levels
by enhancing its oxidation.  Oxethazine

CNS
B. Mechanism of Action 4. Spinal Anaesthesia

- LA is injected in subarachnoid space between
L2-3 or L3-4.
- The primary site of action is the nerve root in
cauda equina rather than the spinal cord.
5. Epidural Anaesthesia
- Injection of LA in epidural space.
- Three categories depending upon site.
a. Thoracic
 The receptor of local anaesthetic (LA) is located in
intracellular half of Na+ channel. b. Lumbar
 LA first transverses the membrane in unionized c. Caudal
lipophilic form and then reionized again in 6. Intravenous regional anaesthesia
axoplasm and then binds to its receptor in cationic - Injection of LA in a vein of tourniquet occluded
form. limb such that drug diffuse retrograde from
 Receptor has higher affinity of LA in active state peripheral vascular bed to non-vascular tissue
rather than in resting state. including nerve endings.
 Binding of LA to its receptor stabilizes the channel
in inactive state.
D. Adverse Effects
 Therefore, probability of channel opening is 1. CNS: Light headedness, dizziness, auditory and
reduced. visual disturbance, mental confusion,
 This blockages of depolarization causes failure in disorientation, shivering, twitching, involuntary
initiation and propagation of action potential movements, convulsions, and respiratory VIII
 Thus, anaesthesia is maintained. arrest
C. Uses 2. CVS: Bradycardia, hypotension, cardiac

arrhythmia, vascular collapse
1. Surface Anaesthesia
3. Hypersensitivity rection: Rashes, angioedema,
- Only superficial layer is anaesthetised.
dermatitis, asthma, rarely anaphylaxis occur.
- Produced by topical application of surface
anaesthetics to mucous membrane and 4. Injection of LA is painful
abraded skin. 5. Wound healing may be delayed sometimes.
2. Infiltration anaesthesia E. Contraindications of LA
- Dilute solution of LA is infiltrated under the
 Hypotension, hypovolemia, uncooperative or
skin.
mentally ill patients, vertebral abnormalities like
- Blocks sensory nerve endings, motor function Kyphosis, lordosis, sepsis at injection site.
are not affected.
F. Individual Compounds
3. Conduction block
- LA is injected around nerve trunks so that the 1. Lidocaine (Lignocaine) [06,05]
area distal to injection is anaesthetised and - Most widely used LA
paralyzed. - Good for both surface application and injection
a. Field block - Vasodilation occurs in the injected area
b. Nerve block
Pharmacology
- It is used for surface application, infiltration, GENERAL ANAESTHETICS

nerve block, epidural spinal and intravenous Past Questions:
regional block anaesthesia.
1. List drugs used as general anaesthetics.
- Early central effects of lidocaine are (2) [10 July]
drowsiness, mental clouding, altered taste,
2. Diazepam as pre-anaesthetic agent [09July]
tinnitus
3. Atropine as pre-anaesthetic medication [03June]
- Overdose causes muscle twitching,
4. Ketamine for short surgical procedures [09Jun]
convulsions, cardiac arrhythmias, fall in BP,
5. Thiopentone sodium is used for induction of
coma, Respiratory arrest. general anaethesia
2. Bupivacaine  General anaesthetics are drugs which produce
- Potent and long-acting amide linked LA. reversible loss of all sensation and consciousness.
- Used for infiltration, nerve block, epidural and  Cardinal feature of general anaesthesia are:
spinal anaesthesia i. Loss of all sensation, especially pain
- When injected epidurally produces adequate ii. Sleep (unconsciousness) and amnesia
analgesia without significant motor blockage, iii. Immobility and muscle relaxation
so is popular in obstetrics and for iv. Abolition of somatic and autonomic reflex
postoperative pain relief. Stage of Anaesthesia
- Bupivacaine is more prone to prolong QTc i. Stage of analgesia
interval and induce ventricular tachycardia or ii. Stage of delirium
cardiac depression - so should not be used for
iii. Surgical anaesthesia
intravenous regional analgesia.
VIII iv. Medullary paralysis
Basis of combining local anaesthetic with
Classification [KU 10]
adrenaline (vasoconstrictor) [11]
1. Inhalational
- Prolongs duration of action of LAs by
a. Gas  Nitrous oxide (N2O)
decreasing their rate of removal from local site
into circulation b. Volatile liquid  Ether, Halothane, Enflurane,
Isoflurane, Desflurane, Sevoflurane
- Reduces systemic toxicity of LAs as rate of
absorption is reduced. 2. Intravenous
- Provides more bloodless field for surgery a. Inducing agent: Thiopentone sodium,
Methohexitone sodium, propofol, Etomidate
- Enhances the intensity of nerve block
b. Slower acting drugs
Epinephrine should not be given along with
i. Benzodiazepines: Diazepam, Lorazepam,
LAs during circumcision, finger or toe
Midazolam
surgery, ear surgery
ii. Dissociative anaesthesia: Ketamine
- Epinephrine produces intense vasoconstriction.
iii. Opioid analgesia: Fentanyl
- So, blood supply to these organs gets cut off
N2O - Nitrous Oxide
- Collateral supply in these organs is not so well
 Good analgesic but poor muscle relaxant.
developed.
 Quick onset and quick recovery because of its low
- Therefore, organs may suffer from ischemic
blood solubility
necrosis and damage.
CNS
Mechanism of action: Mechanism of Action:

- It selectively inhibits NMDA type of glutamate - It potentiates the action of inhibitory
receptor. -
transmitter GABA to open Cl channels.
Use: Advantages:
- Generally used as carrier and adjuvant to other - Has high therapeutic efficacy
anaesthetics. 70% N2O + 25-30% O2 + 0.2-2% - Rapid induction and rapid recovery
another potent anaesthetics.
- Its bronchodilator action makes it preferable
- As a sole agent, N2O has been used with O2 for for asthmatics.
dental and obstetric analgesia.
- It does not augment salivary or bronchial
Adverse effect: secretion.
- Can expand pneumothorax and other - Incidence of postoperative nausea and
abnormal air pockets in body. vomiting is low.
Note: Adverse effect:
- 2nd gas effect and diffusion hypoxia is found in - Myocardial depression, decreases cardiac
case of N2O. output, decreases BP, decreases GFR,
- When a potent anaesthetic is being given at the decreases urine.
same time with N2O, it will be delivered to blood at - Hepatitis due to metabolite of halothane
faster rate and induction will be faster. This is - Malignant hyperthermia  Genetically
called 2nd gas effect. determined Reaction [MCQ 2013]
- When N2O is discontinued after prolonged - Post-anaesthetic shivering can occur.
anaesthesia, N2O having low blood solubility
rapidly diffuses into alveoli and dilutes alveolar air.
Isoflurane
So partial pressure of oxygen in alveoli is reduced  Similar to halothane. But, it is good maintenance VIII
resulting into hypoxia called diffusion hypoxia. anaesthetic, not preferred for induction.
 Cardiac output is maintained but BP falls (due to
Ether
vasodilation)
 Potent anaesthetic, produces good analgesia,
 Coronary circulation is maintained; safer in
marked muscle relaxation.
patients with myocardial ischemia.
 It is highly soluble in blood. So induction and
 Renal and Hepatic toxicity don't occur
recovery is slow.
 Better adjustment of depth of anaesthesia.
 Ether causes salivation and marked respiratory
 Do not provoke seizures, so is preferred for
secretions. So, atropine must be given as
neurosurgery.
premedication to prevent patient from drowning
in his own secretions. Desflurane
 Post anaesthetic nausea, vomiting is marked with  New congener of isoflurane
ether.  Gained popularity as an anaesthetic for
outpatient surgery
Halothane
 Induction and recovery are very fast
 Potent anaesthetic but not a good analgesic or
 Depth of anaesthesia changes rapidly with change
muscle relaxant.
in inhaled concentration.
 Non-irritant, non-inflammable volatile liquid with
 Serves as good alternative for routine surgery as
reasonably quick and pleasant induction
well, especially prolonged operations.

Pharmacology
Thiopentone Sodium Ketamine [KU 09]

 Ultra-short acting thiobarbiturate  It induces "dissociative anaesthesia"
Mechanism of Action: characterized by profound analgesia, immobility,
- It potentiates the action of inhibitory amnesia with light sleep, feeling of dissociation
transmitter GABA to open Cl- channels. Cl- from one’s own body and surrounding.
channel opening is prolonged. Mechanism of Action:
- It also activates another inhibitory transmitter - It blocks NMDA receptors and thus affects
glycine to open Cl- channel. binding of excitatory neurotransmitter
glutamate.
Advantage:
- The primary site of action is in cortex and sub
- Very rapid onset of action. It produces
cortical areas; not in reticular activating
unconsciousness in 15-20 sec.
system. (Site of barbiturates)
- Pleasant and smooth indication: No
Advantages
excitement.
- Respiration is not depressed
- Conciousness is regained in 6 - 10 min as
redistribution occurs. - Airway reflexes are maintained
Disadvantages: - Produce profound analgesia (persisting for 40
minutes)
- Poor analgesic, so painful procedures could not
be carried out under its influence, unless Uses
opioid or N2O has been given. - Operation for head and neck
- It is weak muscle relaxant. - Used in asthmatics and in those who do not
- Laryngospasm occurs: Can be prevented by want to lose consciousness.
atropine premedication - Burn dressing
VIII - Patient who have bled or in shock (due to
- It can precipitate acute intermittent porphyria
in susceptibles. cardiostimulant property)
- Shivering and delirium may occur during recovery. - Angiography, cardiac catheterization, trauma
Uses: surgery.
- Induction of General anaesthesia Note:
- Anaesthesia of short duration in minor surgical - Since ketamine increases heart rate, cardiac
procedure. output, BP, it may be dangerous for hypertensive,
- Occasionally used for rapid control of convulsion. in ischemic heart disease and in those, with raised
- To facilitate verbal communication in intracranial pressure.
psychiatric patient and for narcoanalysis of Fentanyl
criminals.
 Short acting potent opioid analgesic
Propofol  Generally given intravenous at beginning of
 Unconsciousness after propofol injection occurs in painful surgical procedures.
15-45 sec and last for 5-10 minutes.  It is frequently used to supplement anaesthetics in
 It lacks airway irritancy and is particularly suited balanced anaesthesia.
for outpatient surgery because residual Pre-anaesthetic medication [09,08,05,03]
impairment is less marked and shorter lasting.
 Use of drugs before anaesthesia to make it more
 It is drug of choice for sedating intubated
pleasant and safe is pre-anaesthetic medication.
patients in ICU.

CNS
Aim: d. Benzodiazepines in therapy (3) [10 July]

- Relief of anxiety and tension pre-operatively e. Diazepam (3) [05 June]
- Amnesia for pre-post operative events. 6. Explain why thiopentone is short lived?
- To supplement analgesic action of anaesthetics (3) (05 June)
- To decrease secretion and vagal stimulation by Sedative
anaesthetics  Drug that subsides excitement and calms the
- Antiemetic effect extending to post-operative subject without inducing sleep.
period.
Hypnotic
- To decrease volume and acidity of gastric juice
 Drug that induces and/or maintains sleep, similar
to prevent gastric pneumonitis.
to normal arousal sleep.
Drug Used:
Classification [04]
- Opioids like morphine or pethidine.
1. Barbiturates
- Benzodiazepines like diazepam
- Long acting: Phenobarbitone
- Anticholinergic like Atropine or hyoscine
- Short acting: Butobarbitone, Pentobarbitone
- Antihistamine like promethazine - Ultra-short acting: Thiopentone, Methohexitone
- Neuroleptic like chlorpromazine 2. Benzodiazepines
- H2 blocker like ranitidine - Hypnotic: Diazepam, Flurazepam, Nitrazepam,
- Proton pump inhibitor like omeprazole Alprazolam, Triazolam
- Antiemetic like metoclopramide - Antianxiety: Diazepam, Oxazepam, Lorazepam,
Alprazolam
SEDATIVE - HYPNOTICS - Anticonvulsant: Diazepam, Lorazepam,
Past Questions: Clonazepam, Clobazam
1. List therapeutic use of benzodiazepines. List 3. Newer non-benzodiazepine hypnotics VIII
important adverse effect of Diazepam. - Zopiclone
(2+2=4) [06 Jan, 08 Jan] - Zolpidem
2. List drugs used as sedative-hypnotics. Mention - Zaleplon
why benzodiazepines are preferred to GABAA–Benzodiazepine Receptor-chloride channel
barbiturates. (2+3=5)[04Dec] complex
3. Give the pharmacological basis of use of:
a. Benzodiazepines as sedative-hypnotics
(3) [07July]
b. Benzodiazepines are preferred as hypnotic
over barbiturates (3) [03Dec, 03June]
c. Flumazenil in Benzodiazepine overdose
(3) [10 Jan]
4. Enumerate the difference between Diazepam and
Lorazepam (4) [01 Dec]
5. Write short notes on:
a. Limitations of use of sedative-hypnotics
(2) [11 July]
b. Indications of benzodiazepines. (3) [05 Dec]
c. Benzodiazepine (3) [05 June, 02 June]

Pharmacology
Barbiturates Benzodiazepines (BZDs) [10,07,05,02]

MOA: MOA:
-
- In GABA-BZD receptor Cl channel complex, - Acts preferentially on midbrains ascending
barbiturates probably bind to picrotoxin reticular formation and on limbic system
sensitive site. - BZDs bind on specific BZD receptor, which is an
- Binding to the site, it potentiates GABAergic integral part of GABAA receptor–Cl- channel
-
inhibition by increasing the lifetime of Cl complex.
channel opening induced by GABA. - Binding on receptor, they increase the
- At high concentrations, barbiturates directly frequency of Cl- channel opening.
increase Cl- conductance (GABA-mimetic - BZDs also enhance binding of GABA to GABAA
action) and inhibit Ca2+ dependant release of receptor.
neurotransmitter. - However, BZDs do not show GABA mimetic
- They also depress glutamate induced neuronal action.
depolarization through AMPA receptors. Superiority of BZD over Barbiturates [04,03]
- At very high concentration, barbiturates - BZDs have high therapeutic index (even 20
depress voltage sensitive Na+-K+ channels as hypnotic dose don’t endangers life)
well. - Hypnotic doses do not affect respiration or CVS
Adverse Effects: functions.
- Side effect: Hangover, mental confusion, - BZDs cause less distortion of sleep architecture
impaired performance. - BZDs have lower abuse liability, withdrawal
- Idiosyncrasy: syndrome is less marked
 In occasional patient, barbiturates produce - A specific BZD antagonist  Flumazenil is
VIII excitement available which can be used in case of
 May precipitate porphyria in susceptible poisoning.
individuals. Pharmacological actions:
- Hypersensitivity: Rashes swellings of eyes, lips. i. CNS effects:
- Tolerance and dependence: - Anxiolytic effect
 Both cellular and pharmacokinetic tolerance - Hypnotic effect
occurs. - Muscle relaxant
 Physiological as well as psychological - Anticonvulsant effect
dependence occurs. - Cause anterograde amnesia (patient does not
 Withdrawal symptoms are: Excitement, clearly recollect the events on recovery)
hallucination, delirium, convulsions, deaths ii. Other effects
have occurred.
- Decreases nocturnal gastric secretion.
Acute barbiturate Poisoning - Produce short lasting coronary dilation.
Management:
Adverse effects: [08,06]
- Gastric lavage
- Dizziness, vertigo, ataxia, disorientation,
- Supportive measures; patent airway, assisted amnesia, impaired psychomotor skill.
respiration, maintenance of blood volumes.
- BZDs can aggravate sleep apnea
- Alkaline diuresis.
- Weakness, blurring of vision, dry mouth,
- Hemodialysis and hemoperfusion. urinary incontinence
CNS
- Tolerance EPILEPSY
 Tolerance to sedative effect develops Past Questions:
 Cross tolerance to alcohol and other CNS 1. List the drugs used for epilepsy. Write the
depressant occurs. adverse effects and therapeutic uses of
- Withdrawal causes anxiety, insomnia, carbamazepine (2+2+2=6) [09July]
restlessness, malaise, loss of appetite, bad 2. List aniepileptic agents. Describe the adverse
dreams, etc. reactions and therapeutic uses of phenytoin
sodium. (2+3+2=7)[05June]
Non-benzodiazepines Hypnotics
3. List antiepileptic drugs. (2) [04June]
- These are indicated for short-term insomnia.
4. Explain the mechanism of action and adverse
- They preferentially bind on 1-subunit effects of phenytoin sodium
containing subtype of BZD receptors and (3+3=6, 3+2=5)[04June, 03 Dec]
function like BZD. 5. Give the clinical classification of drugs used in
- They do not produce disturbance in sleep epilepsy. Explain the status of carbamazepine in
architecture or produce hangover or modern therapy. (2+5=7)[02June]
withdrawal phenomena or discontinuation. 6. Describe the mechanism of action and adverse
Use of BZD [08,07,06,05] effects of carbamazepine (2)[01June]
1. As hypnotic for insomnia 7. Outline the management of status epilepticus
(3)[02Dec]
- Chronic insomnia > 3 weeks
8. Classify Antiepileptic drugs by clinical use.
- Short-term insomnia: 3-21 days.
(2) [01June]
- Transient insomnia: 1-3 days.
2. As anxiolytic and for day-time sedation. VIII
a. Phenytoin sodium in grand mal epilepsy
3. As anticonvulsant (2) [04Dec]
4. As centrally acting muscle relaxant b. Phenytoin in epilepsy [11July,09 Jun]
5. As preanaesthetic medication. c. Sodium valproate in epilepsy [10 July]
6. Before electrical cardioversion of arrhythmias, 10.Write short notes on:
cardiac catheterization, endoscopies. a. Carbamazepine (3) [07 July]
7. Alcohol withdrawal in dependant subjects b. Adverse effects of sodium valproate
8. Along with analgesics, NSAIDs, etc. (3) [06 June]
Benzodiazepine Antagonist c. Management of status epilepticus (3) [09 July]
d. Diphenylhydantoin (2) [08 July]
Flumazenil [10]
e. Phenytoin sodium [03 June]
- Is competitive antagonist at BZD site on GABA
receptor - Cl- channel complex.
Seizure
 Abnormal activity in brain resulting in motor or
- At higher dose, it has some weak BZD agonist
sensory or psychomotor experiences is called
like as well as inverse agonist-like activity.
seizure.
Uses:
Epilepsy
1. To reverse BZD anaesthesia
 Group of disorders in CNS characterized by
2. BZD overdose.
paroxysmal cerebral dysrhythmia manifesting as

Pharmacology
brief episodes (seizures) of loss or disturbance of ii. Complex partial seizure (CPS or Temporal lobe
consciousness, with or without characteristic body epilepsy)
movements, sensory or psychiatric phenomena - Impairment of consciousness
 In other words, recurrent tendency to develop - Attacks of bizarre and confused behavior
seizures is called epilepsy. and purposeless movements, emotional
Types changes lasting 1-2 minute.
1. Generalized seizure iii. Simple partial or complex seizures secondarily
generalized
I. Generalized Tonic-clonic seizure / Grand mal
- Partial seizure occurs first
Epilepsy (GTCS)
- Later it evolves into generalized tonic –
- Usual sequence: Aura  Cry 
clonic seizure with loss of consciousness.
Unconsciousness  Tonic spasm of all body
Antiepileptic drugs [10,05,02,01]
muscles  Clonic jerking followed by
prolonged sleep and depression of all CNS Classification:
functions. - Barbiturate: Phenobarbitone
II. Absence seizure / Petit mal epilepsy - Deoxybarbiturate: Primidone
- Hydantoin: Phenytoin, Fosphenytoin
- Momentary loss of consciousness
- Iminostilbene: Carbamazepine, Oxcarbazepine
- Patient apparently freezes and stares in one
- Succinimide: Ethosuximide
direction
- Aliphatic carboxylic acid: Valproic acid (Sod.
- EEG shows characteristic 3 cycle per second
valproate)
spikes and wave pattern.
- Benzodiazepine: Diazepam, Lorazepam
III. Atonic seizures
VIII - Cyclic GABA analogue: Gabapentin
- Unconsciousness with relaxation of all - Phenyltriazine: Lamotrigine
muscles due to extensive inhibitory
- Newer drugs: Vigabatrin, Topiramate,
discharges
Tiagabine, Zonisamide, Levetiracetam
- Patient may fall Phenobarbitone (GTCS, SPS, CPS)
IV. Myoclonic seizures MOA
- Shock-like momentary contraction of 1. GABA facilitatory: Potentiate action of GABA by
muscles of limb or whole body. binding on GABA-BDZ-chlorine channel
V. Infantile spasms (Hypoarrhythmia) complex.
- Seen in infants 2. GABA mimetic: At higher does, directly opens
- Intermittent muscles spasm and progressive Cl- channel.
mental deterioration. 3. Anti glutamate action: Thus, decrease Ca2+
influx.
2. Partial seizures
4. At high doses, blocks Na+ and K+ channel; raises
i. Simple partial seizures (SPS or cortical focal
seizure threshold
epilepsy)
Pharmacokinetics:
- No loss of consciousness
- Poor oral absorption, High plasma binding
- Convulsions are confined to a group of
- T1/2 80-120 hrs.
muscles or localized sensory disturbance
- Metabolized by liver.
depending on area of cortex involved.
- Excreted by kidney unchanged.
CNS
Adverse Effects: At higher doses

- Sedation - Cerebellar impairment, vestibular impairment:
- Impaired memory and learning Ataxia, vertigo, diplopia, Nystagmus.
- Decreases mental capacity - Hallucination, confusion, Behavioral
- Hyperactivity in children alterations.
- At higher doses; A/E of phenytoin like - Epigastric pain, vomiting.

Hypersensitivity, Megaloblastic anemia, - On IV: Thrombosis, vasculitis
osteomalacia. - Fall in BP, cardiac arrhythmias (only in IV)
Phenytoin [11,09,05,04,03] Carbamazepine [CPS, GTCS, SPS]

 1st line drug for epilepsy. [07,02,01]
MOA:  Chemically related to imipramine.

MOA:
- Primarily increases the inactivation state of
Na+ channel. Acts mostly on high frequency - Modifies maximum electroshock for seizure.
impulse. So, normal low frequency synaptic - Increases threshold of pentylenetetrazol (PTZ).
transmission are unblocked. - Prolongs inactivation state of voltage gated
2+
- Minor MOA: Decreases Ca influx, inhibit Na+ channel.
glutamate and potentiate GABAergic action. - Lithium-like action in cases of mania, bipolar
disorder.
Pharmacokinetics:
Pharmacokinetics:
- Poor oral absorption (Because less aqueous
solubility) - Poor oral absorption
- Metabolized in liver by hydroxylation and - 75% plasma bound.

glucuronide conjugation. - T1/2 20-40hr reduces to 10-20hr due to auto- VIII
induction of metabolism.
- High plasma bound.
- Metabolized in liver by:
- Initial half-life 12-24 hrs increases up to 60 hrs.
due to saturation of metabolic enzymes.  Oxidation  To active metabolite (10, 11–
epoxy carbamazepine)
Adverse Effects:
 Hydroxylation, conjugation  To inactive
At therapeutic does:
metabolite
- Gum hypertrophy,
- CYP3A4 inducer
- Hirsutism, acne Adverse Effects:
- Hypersensitivity; rashes - Does related neurotoxicity: Sedation,
- Lymphadenopathy dizziness, ataxia, vertigo diplopia.
- Megaloblastic anemia - Hypersensitivity: Lupus like syndrome,
- Osteomalacia photosensitivity, hepatitis
- Fetal hydantoin syndrome - Vomiting, diarrhea
- Higher doses: Cardiovascular collapse, coma
 Microcephaly
- ADH like: Water retention, hyponatremia
 Hare Lips
- 10, 11-epoxy metabolite can cause blood
 Cleft palate
dyscrasias, leucopenia and aplastic anemia.
 Hypoplastic phalanges
Pharmacology
Interactions: Pharmacokinetic:
- Carbamazepine increases metabolism of - Good oral absorption
phenytoin, phenobarbitone, valproate, etc. - 90% plasma bound.
- It decreases efficacy of Haloperidol, oral - T1/2 : 10-15 hrs.
contraceptives, lamotrigine, topiramate. - Metabolized in liver by oxidation and
- Erythromycin, Isoniazid, fluoxetine inhibit glucuronide conjugation.
metabolism of carbamazepine. - Excreted in urine.
- Carbamazepine along with valproate doubles Adverse Effects:
the teratogenic frequency.
- Anorexia, vomiting, GI tolerance
Uses:
- Drowsiness, ataxia, tremor, thrombocytopenia
- Antiepileptic
- Alopecia, curling of hair
- Trigeminal Neuralgia
- Hypersensitivity, pancreatitis, fulminant
- Mania. hepatitis (rare in children only)
Ethosuximide - Teratogenic (spina bifida)
MOA: - in serum transaminase.
- Selectively suppresses ‘T’ current Uses:
- Raises threshold seizure - DOC of Absence seizure, SPS, CPS, GCTS.
Pharmacokinetic: - Mania, bipolar disorder (substituent/
- Slowly but completely absorbed. alternative to Lithium)
- Not plasma bound. - Myoclonic and atonic seizure.
- Largely metabolized in liver (Hydroxylation, Gabapentin
VIII Glucuronidation) MOA:
- T1/2 – 48 hours (adult), 32 hours (children) - Enhances GABA release in nerve synapse
th
- Excreted in urine (1/4 unchanged)
- Thus promotes Cl- channel opening and
Adverse Effects: induces hyperpolarization.
- Gastrointestinal tolerance Uses:
Use: - 1st line drug for pain due to diabetic
- In absence seizure. neuropathy and post herpetic neuralgia
Valproic Acid [10,06] - Added with 1st line drugs to reduce seizure
 Broad spectrum Anticonvulsant frequency.
 Inhibit PIZ induced seizures. Vigabatrin
MOA: MOA:
- Phenytoin like: Prolongs inactivation state of - Inhibition of GABA transaminase. So, inhibits
Na+ channel. Thus, decreasing high frequency degradation of GABA.
impulses which inhibit transient ‘T’ current
Use:
(ethosuximide like)
- Suppresses maximal electroshock and kindled
- Inhibit degradation of GABA by blocking ‘GABA
seizures.
transaminase’. Thus, potentiate GABAergic
action. Also increases GABA synthesis from - Used in Refractory epilepsy especially partial
Glutamic acid. seizures with or without generalization.

CNS
Treatment of Epilepsy:
Types of seizure 1st choice drugs 2nd choice drugs Alternative/add-on drugs
GTCS/ SPS with or Lamotrigine, gabapentin,
without Carbamazepine, phenytoin Valproate, phenobarbitone topiramate, primidone,
generalization levetiracetam
CPS with or without Carbamazepine, valproate, Gabapentin, Lamotrigine, Clobazem, zonisamide,
generalization phenytoin levetiracetam topiramate
Absence Valproate Ethosuzimide, Lamotrigine Clobazem, clonazepam
Myoclonic Valproate Lamotrigine, topiramate Levetiracetam, clonazepam
Atonic Valproate Clonazepam, Clobazem Lamotrigine
Febrile seizures Diazepam (rectal)  
Lorazepam (i.v.), diazepam Fosphenytoin (i.v.),
Status epilepticus General anaesthetics
(i.v.) phenobarbitone (iv.,i.m.)
Status epilepticus - Once seizure is controlled, commence longer

term anticonvulsant medication with one of
 Status epilepticus is defined as a seizure or a
following:
series of seizures lasting 30 minutes without the
patient regaining awareness between attacks. • Sodium valproate 10 mg/kg i.v over 3-5
mins, then 800-2000 mg/day
 Refers to recurrent tonic clonic seizures and is a
life threatening medical emergency. • Phenytoin (if not already used) 15 mg/kg
infuse at <50 mg/min then 300 mg/day
Management
• Carbamazepine 400 mg by nasogastric tube
Initial VIII
then 400-1200 mg/day
- Ensure airway is patent, give oxygen to prevent
cerebral hypoxia and secure intravenous access ANTIPSYCHOTIC
- Draw blood for glucose, urea and electrolyte, Past Questions:
liver function
- Give diazepam 10 mg intravenous or 1. Explain the clinical importance of
lorazepam 4 mg intravenous, repeat once after phenothiazines. Mention their adverse effects
15 minutes and uses. (2+2+2=6)[04Dec]
- Transfer to ICU, monitor neurological 2. Explain how phenothiazines are effective as
condition, blood pressure, respiration and antipsychotic mention its adverse effects and
blood gases, intubate and ventilate patient if uses. (2+2+2=6) [02June]
appropriate 3. List antipsychotic drugs. Describe the mechanism
Ongoing of action and adverse effects of phenothiazines.
- If seizures continue after30 minutes infuse (with (3+3+2=8)[01Dec]
cardiac monitoring) with one of following: 4. Give the pharmacological basis of use of:
• Phenytoin: 15 mg/kg at 50 mg/min a. Antipsychotics (3) [09July]
• Fosphenytoin: 15 mg/kg at 100 mg/min b. Phenothiazines in psychosis (3) [07July]
• Phenobarbitol: 10 mg/kg at 100 mg/min c. Antipsychotics in schizophrenia (3) [05Dec]
- If seizure still continue after 30-60 min, start 6. Write short notes on:
treatment for refractory status with intubation, a. Adverse effects of anti-psychotics (2) [11 July]
ventilation, and general anaesthesia using b. Atypical antipsychotics
propofol or thiopentone. (3) [10 July, 09 July, 08 Jan]
Pharmacology
 Those drugs having primary effects on psyche Negative symptoms:

(mental process) - Negative symptoms are deficits of normal
Psychoses: emotional responses or of other thought
- Severe psychiatric illness with serious processes.
distortion of thought, behaviour, capacity to - These symptoms do not respond well to
recognize reality and of perception. medication.
i. Cognitive disorder: Confusion, - They include:
disorientation, behavior, etc. a. Blunted effect (failure to express feelings)
ii. Functional disorder: Schizophrenia (split b. Emotional withdrawal
mind), Paranoid state (false belief) c. Social withdrawal
iii. Affective disorder: d. Poor relationship
- Mania: Irritable mood e. Difficulty in abstract thinking
- Depression: Sadness, loss of pleasure f. Lack of spontaneity and flow of
- Bipolar: Manic-depressive conversation
Neuroses: g. Stereotyped thinking
- Reality is not lost. Classification of Antipsychotic [KU 01]
i. Anxiety: Worry and tension A. Typical antipsychotic (first generation)
ii. Phobic state: Fear of unknown 1. Phenothiazines
iii. Obsessive-compulsive state: Recurrent - Aliphatic side chain: Chlorpromazine,
intrusive thoughts. Triflupromazine
iv. Reactive depression - Piperidine side chain: Thioridazine
v. Post traumatic: Stress disorder.
VIII - Piperazine side chain: Trifluoperazine,
vi. Hysterical Fluphenazine
Schizophrenia 2. Butyrophenones: Haloperidol, Trifluperidol,
- Term literally means “splitting of mental Penfluridol
functions”. 3. Thioxanthenes: Flupenthixol
- It is a psychoses characterized by delusions, B. Atypical antipsychotic
hallucinations and lack of insight. - Clozapine, Risperidone, Olanzapine,
Positive symptoms: Aripiprazole, Ziprasidone, Quetiapine
- Positive symptoms are those symptoms that A. Typical antipsychotics
most individuals do not normally experience
Chlorpromazine (Prodrug)
but are present in people with schizophrenia.
MOA
- These symptoms respond well to medication.
Potent D2 receptors blocking action
- They include:
a. Delusions 
Blockage of dopaminergic transmission to
b. Conceptual disorganization
limbic system and mesocortical area
c. Hallucinations

d. Hyperactivity
Over activity of dopamine in such area is
e. Grandiosity (unrealistic sense of superiority)
controlled
f. Suspiciousness 
g. Hostility Antipsychotic action
CNS
Note: Blockage of D1, D3, D4 receptors has no Haloperidol

correlation with antipsychotic potency. - First line drug for acute schizophrenia
Adverse effect MOA
- Acts as inverse agonist to D2, D3, D4 receptors
Blockage of Adverse effects
and antagonist to D1 and D5 receptors
a. Dopaminergic - In nigrostriatal pathway:
- Reduces over activity of dopamine
receptors Extrapyramidal symptoms
Adverse effects:
- In tuberoinfundibular
pathway: Hyperprolactinemia a. Extrapyramidal symptoms
(galactorrhoea, Note: Extrapyramidal symptoms are more marked
gynaecomastia, amenorrhoea) with haloperidol because haloperidol has minimal
b. Serotonin - Weight gain, ejaculation anticholinergic activity. (Though anticholinergic effect
receptors disorders is considered side effect but it is beneficial to prevent
c. Histamine (H1) - Sedation, vertigo extrapyramidal symptoms)
receptors b. Somnolence
d. α1 and α2 - Postural hypotension, reflex c. Orthostatic hypotension
receptors tachycardia d. Few anticholinergic effects like constipation,
e. M1 and M2 - Dry mouth, blurred vision, dry mouth, blurred vision
receptors constipation, difficulty in Note: Breastfed child may sometime show
micturation extrapyramidal symptoms when given to lactating
Use: mother.
a. Psychoses: Schizophrenia, bipolar disorder, Use:
organic brain syndrome
a. Acute schizophrenia VIII
b. Antiemetic
b. Huntington’s disease
c. Anxiety
c. Gilles de la Tourette’s syndrome
d. Tetanus
d. Intractable hiccups
e. Intractable hiccough
e. Cerebral sclerosis
Contraindication:
Contraindication:
1. Absolute
a. Pre-existing coma, acute stroke
a. CNS depression
b. Alcohol intoxication
b. Coma
c. Known heart disease
c. Drug intoxication
Special cautions:
d. Bone marrow suppression
a. Pre-existing Parkinson’s disease
e. Pheochromocytoma
b. QT prolongation
f. Liver failure
c. Liver disease
2. Relative
a. Epilepsy Extrapyramidal symptoms
b. Parkinson’s disease - More prominent: Fluphenazine, haloperidol,
c. Myasthenia gravis pimozide etc.
d. Hypoparathyroidism - Least with thioridazine, clozapine and all other
atypical drugs
e. Prostatic hypertrophy

Pharmacology
a. Parkinsonism MOA
- With typical manifestations: Rigidity, - Blocks D2, D4, 5-HT2, α and H1 receptors
tremor, hypokinesia, mask like face, Note:
shuffling gait.
- It spares
- Appear 1-4 weeks of therapy
a. Nigrostriatal pathway: So no extrapyramidal
- Levodopa is not effective symptoms
- Rare form of extra-pyramidal side effect is b. Tuberoinfundibular pathway: So no rise in
‘peri-orbital tremors’ rabbit syndrome’. prolactin level
b. Acute muscular dystonia
- Inhibits both positive and negative symptoms
- Bizarre muscle spasms, mostly involving
Adverse effect
linguo-facial muscles-grimacing, tongue
a. Agranulocytosis (weekly monitoring of
thrusting, torticollis, locked jaw.
leukocyte is required)
c. Akathisia b. Sedation
- Restlessness feeling of discomfort, apparent c. Hyperlipidemia
agitation manifested as a compelling desire d. Hyperglycaemia
to move about, but without anxiety. e. Weight gain
d. Malignant neuroleptic syndrome f. Can induce seizure
- Develops marked rigidity, immobility, Use:
tremor, fever, semi-consciousness, - Reserve drug in resistant schizophrenia
fluctuating BP and heart rate.
Risperidone
- Myoglobin present in blood.
- First line of drug
e. Tardive dyskinesia
- Has no risk of agranulocytosis
VIII - It occurs late in therapy
MOA
- Purposeless involuntary facial and limb
- Blocks D2, 5-HT2, α1, α2, H1 receptors
movements like constant chewing, pouting,
puffing, lip licking, choreoathetoid - Inhibits both positive and negative symptoms
movements. Note:
- Common in elderly women. - Prolactin level rise during Risperidone therapy
Limitations of typical antipsychotics - Extrapyramidal symptoms are low (but shown at
higher dose)
a. Approximately one-third of patients with
schizophrenia fail to respond. Adverse effects:
b. Limited efficacy against - Weight gain
- Type 2 diabetes mellitus
- Negative symptoms
- Orthrostatic hypotension
- Affective symptoms
- Increased risk of stroke in elderly
- Cognitive deficits
Use:
c. High proportion of patient relapses
- Schizophrenia
d. Side effects and compliance issue - Bipolar disorder
e. Limited effect on depression and suicidality - Dementia
B. Atypical antipsychotics Olanzapine
Clozapine MOA
- First atypical antipsychotic drug - Blocks D2, 5-HT2, α1, α2, muscarinic, H1 receptors

CNS
Adverse effects ANTIMANIAC (MOOD STABILIZERS)

- Weight gain, diabetes mellitus, hyperlipidemia Past Questions:
- Can cause dry mouth and constipation
- Can precipitate seizures
a. Lithium in therapy (3)[06June]
Use:
- Schizophrenia b. Lithium in mania (3)[10 July]
- Anxiety disorder 2. Write short notes on:
- Panic disorder a. Lithium in mental disease (3) [02 June]
- Delusional disorder b. Antimanic agents (3) [02 Dec]
- Post- traumatic stress disorder
3. Explain why therapy monitoring is essential for
Note: lithium? (3) [05 June]
1. Relative adverse effect of atypical antipsychotic
a. Weight gain, diabetes: Clozapine > olanzapine > Mania
risperidone  Elation or irritable mood, reduced sleep,
b. Movement disorder: Risperidone > olanzapine > hyperactivity uncontrolled thought and speech
clozapine may be associated with reckless or violent
c. Sedation: Clozapine > olanzapine > risperidone behaviour.
d. Decrease sex drive, missed period, discharge
from breast: Risperidone > olanzapine > Classification
clozapine 1. Lithium carbonate
2. Receptor binding affinity of antipsychotics 2. Antiepileptic like
a. Chlorpormazine: 1 = 5-HT2A > D2 > D1
- Carbamazepine
b. Haloperidol: D2 > 1 > D4 > 5-HT2A > D1 > H1
c. Clozapine: D4 = 1 > 5-HT2A > D2 = D1 - Sodium valproate
VIII
d. Olanzapine: 5-HT2A > H1 > D4 > D2 > 1 > D1 - Lamotrigine
e. Aripiprazole: D2 = 5-HT2A > D4 > 1 = H1 >> D1 3. Antipsychotics like
Difference between typical and atypical - Olanzapine
antipsychotic
- Haloperidol
Typical Atypical
a. Less efficacy a. More efficacy
Lithium Carbonate [10, 06, 02]
b. Cause extrapyramidal b. Less likely to cause  A drug of its own kind to suppress mania and to
symptoms extrapyramidal exert a prophylactic effect in bipolar manic-
symptoms depressive illness (MDI)
c. More addictive, c. Less addictive,  It is neither sedative nor euphorient; but on
withdrawal symptoms withdrawal symptoms
prolonged administration, it acts as a mood
are more likely are less likely
stabilizer in bipolar disorders.
d. Faster excretion so d. Slower excretion so
chance of relapse into chance of relapse into  In acute mania, it gradually suppresses the
psychoses is minimal psychoses is greater episode taking 1-2 weeks; continued treatment
e. Cardiac effects are e. Cardiac effects are prevents cyclic mood changes.
mild. severe. Mechanism of Action:
f. Positive symptoms are f. Both positive and
- Exact mechanism is not known
corrected negative symptoms are
corrected - Proposed mechanisms are:

Pharmacology
i. Li+ partly replaces body Na+ and is nearly Adverse effects:

equally distributed inside and outside cells. Has narrow therapeutic index
 a. Nausea, vomiting and mild diarrhea
Defect in ionic gradient b. Thirst and polyuria (due to inhibition of ADH)

c. Fine tremors and rarely seizures even at
Action potential is impaired
therapeutic concentrations.
ii. Decreases the release of NA and DA in brain
d. CNS toxicity: Coarse tremors, giddiness, ataxia,
 motor incoordination, nystagmus, mental
Corrects imbalance of Neurotransmitter confusion, slurred speech, hyper-reflexia.
iii. Preferentially in hyperactive neurons Lithium
e. Foetal goiter and congenital abnormalities if
inhibits hydrolysis of Inosital-1 phosphate by
used during pregnancy.
enzyme inosital monophosphatase

Interaction:
Supply of free inositol impaired i. Diuretics: Increase plasma level of lithium.
 ii. Tetracyclines, NSAIDS and ACE inhibitors can
Regeneration of membrane phosphatidyl inositol also cause lithium retention.
can't occur iii. Lithium reduces presser response to NA.
 iv. Lithium tends to enhance
IP3 and DAG pathway is impaired insulin/sulphonylurea induced hypoglycaemia.
 v. Succinylcholine and pancuronium have
Mood stabilizes produced rolonged paralysis in lithium treated
VIII Note: It has been found that lithium ignores normally patients.
operating receptor and selectively dampens the signal Importance of monitoring of lithium
transmission of overactive receptors. therapy [05]
Pharmacological actions: - Li has narrow therapeutic index.
i. CNS - Plasma level less than 0.4 mmol/L is
- Neither sedative nor euphorient but on subtherapeutic, and level more than 1.2 mmol/L
prolonged administration it acts as a mood are toxic.
stabilizer in bipolar disorder - Lithium toxicity is serious; the clinical
ii. Other actions consequences include seizures and irreversible
- Li+ inhibits the action of ADH on distal tubules renal damage.
and causes diabetes insipidus like state. - Lithium is primarily renally excreted so any
Uses: change in renal functions, fluid balance or
i. Acute manic episode electrolyte levels can lead to lithium toxicity.
ii. Prophylaxis of MDI (maniac depressive illness) - Even when Li levels are in therapeutic range,
iii. Recurrent neuropsychiatric illness there is risk of hypothyroidism.
iv. Cancer chemotherapy induced leucopenia and - So, for lithium treatment patient should have a
agranulocytosis. plasma lithium level in the therapeutic range
v. Inappropriate ADH secretion syndrome. within the last 6 months, and renal and thyroid
function tests within the last 15 months.

CNS
ANTI-DEPRESSANTS iii. Selective serotonin reuptake inhibiters (SSRIs)

Past Questions: - Fluoxetine, Paroxetine, citalopram, Es-
citalopram, fluvoxamine, sertraline
1. List antidepressants. Describe the adverse effects
iv. Atypical antidepressants
of imipramine (2+3=5) [08 July]
- Trazodone, mianserin, mirtazapine, venlafaxine,
2. List antidepressants. Describe mechanism of
duloxetine, tianeptine, amineptine, bupropion
action and adverse effects of tricyclic
antidepressants. (7) [11 July] Moclobemide
3. List the drugs used in depression. Describe Mechanism of Action:
mechanism of action and adverse effects of - It is a reversible and selective MAO-A inhibitor
antidepressants. (2+3+2=7) [06 June] - Full MAO activity is restored within 1-2 days of
4. Give the pharmacological basis of use of: stopping the drug (because of competitive
a. Antidepressants in therapy (3) [05Dec] enzyme inhibition)
b. Tricyclics in depression (3) [10 July] Adverse effects:
5. Give the pharmacological basis of use of: - Nausea, dizziness, headache, insomnia, rarely
a. Selective serotonin re-uptake inhibitor excitement and liver damage
(3) [09 July] Uses:
6. Write short notes on: - Depression, social phobia, smoking correction
a. Antidepressant (3)[05 June, 04 June] - Lacks anticholinergic, sedative, cognitive,
psychomotor and cardio vascular adverse
b. SSRI's (3)[02 Dec]
effects. Hence, good option for elderly patient
c. Selective serotonin to uptake inhibitors
and in those with heart disease.
(3) [08 Jan]
Tricyclic Antidepressants (TCA) [11,10,08]
d. Fluoxetine (3) [07 July, 05 June, 03 June] VIII
These drugs inhibit non-epinephrine and
 Major depression is characterized by symptoms
serotonin transporters
like sad mood, loss of interest and pleasure, low
energy, worthlessness, guilt, psychomotor 
retardation or agitation, change in appetite Inhibited transporter cannot undergo reuptake
and/or sleep, melancholia, suicidal thoughts. of these biogenic amines
 Anti–depressants are drugs that can elevate mood 
in depressive illness. Reuptake inhibition results in increased
Classification [11, 08, 06] concentration of amines in the synaptic cleft
i. Reversible inhibitors of MAO-A (RIMAs) 
- Moclobemide, clorgyline. Facilitated synaptic transmission
ii. Tricyclic antidepressants (TCAs) 
a. NA + 5-HT reuptake inhibitors: Inhibition of series of time dependent changes in
- Imipramine, Trimipramine, clomipramine, synapse
amitriptyline 
- Doxepin, Dothiepin Antidepressant action
b. Predominantly NA reuptake inhibiters
Notes: TCA also inhibit dopamine reuptake. This is
- Desipramine, Nor-triptyline, Amoxapine,
the basis of stimulant action of TCA.
Reboxetine.

Pharmacology
Pharmacological Actions: ii. Sedation, mental confusion and weakness.

i. CNS iii. Increased appetite and weight gain.
a. In normal people: iv. Sweating and fine tremors
- Peculiar clumsy feeling, tiredness, v. Amoxapine, Bupropion, clomipramine,
sleepiness maprotiline precipitates seizures
- Difficulty in concentrating and thinking [Desipramine and SSRI – safe in this regard]
b. In depressed patient: vi. Postural hypotension
- Gradual mood elevation vii. Cardiac arrhythmia
- Patient become communicative and take viii. Tachycardia
interest Drug Interaction:
Note: i. Potentiate sympathomimetic amines.
ii. Potentiate CNS depressants
- Clomipramine, maprotiline, bupropion,
iii. TCA abolishes anti-hypertensive action of
Amoxapine: High seizure precipitating potential.
Guanethidine and clonidine.
- Amitriptyline and imipramine: Depress respiration iv. Phenytoin, phenylbutazone, aspirin and CPZ
in overdose - Displace TCA from protein binding site and
ii. ANS caused toxicity.
- Potentiate anti-cholinergic action v. Phenobarbitone induces as well as
competitively inhibits imipramine metabolism.
- Bad taste, blurred vision
vi. SSRIs inhibit metabolism of several drug
- Constipation including TCA, hence dangerous toxicity can
- Dry mouth occur if the two are given simultaneously.
- Epigastric distress Limitations of TCA
VIII - Palpitation - Frequent anticholinergic, CVS and neurological
side effects.
- Urinary retention
- Relatively narrow safety margin
iii. CVS - Lag time of 2-4 weeks.
- Tachycardia Acute poisoning
- Postural hypotension - It is frequent; usually self attempted by
- ECG changes and cardiac arrhythmia depressed patients and may endanger life.
Uses: - Manifestations are:
- As antidepressant Excitement, delirium, anticholinergic symptom
seen in atropine poisoning, followed by muscle
- Nocturnal enuresis
spasms, convulsions and coma, respiration
- Multiple sclerosis
depresses body temperature falls, BP low,
- Phobic anxiety syndrome (school phobia)
tachycardia, ventricular arrhythmia
Adverse effects:
- Treatment:
i. Anticholinergic
i. Gastric lavage
- Bad taste, blurred vision
ii. Respiratory support, fluid infusion,
- Constipation maintains BP and body temperature
- Dry mouth iii. Bicarbonate infusion for acidosris.
- Epigastirc distress iv. Diazepam to control convulsions and
- Palpitation delirium.
- Urinary retention v. Propranolol/lidocaine for arrhythmia.

CNS
SSRI (Selective Serotonin re-uptake - Kleptomania

Inhibitor) [09, 08, 02] - School phobias
 Currently used as first line drugs in depression due - Eating disorder
to relative safety and better acceptability. Adverse effects:
Drugs: - Nervousness, anxiety, agitation, insomnia
- Fluoxetine - Sexual dysfunction including loss of libido,
- Fluvoxamine delayed ejaculation
- Paroxetine - Nausea (due to 5-HT3 receptor stimulation)
- Sertaline - Dyskinesia
- Citalopram - Headache
Mechanism of action: - Diarrhea
- SSRIs selectively increase the levels of - Increased incidence of epistaxis and
serotonin in the synaptic cleft by blocking its ecchymosis (due to impairment in platelet
uptake by serotoninergic neurons function)
- Selectively inhibit membrane associated SERT - Weight gain (in case of Paroxetine)
i.e. serotonin transporters. Individual drugs:
- Produce little or no sedation; do not interfere Fluoxetine [07, 05, 03]
with cognitive or psychomotor function; do not - Longest acting SSRI
produce anticholinergic side effect - Approved for use in children below 7 years
- No α-adrenergic blocking action so they don’t - Only when psychotherapy fails
cause postural hypotension, hence suitable for
Fluvoxamine
use in elderly patients.
- Short acting SSRI VIII
Drug interactions:
Sertraline
- SSRIs inhibit drug metabolism by isoenzymes
CYP2D6 and CYP3A4 - Efficacy in juvenile depression
- Elevate plasma level of TCAs, haloperidol, - T1/2 = 26 hours
clozapine, terfenadine, astemizole, warfarin, - Atypical Antidepressants
blockers, some BZDs and carbamazepine.
i. Trazodone
Serotonin syndrome:
- Selectively but less efficiently block 5-HT
- Occurs when any serotonergic drug is taken by
uptake and has prominent -blocking + 5-HT2
a patient receiving SSRIs.
antagonistic action
- Clinical manifestations: Agitation, restlessness,
- Sedative but not anti-cholinergic
sweating, twitching, convulsions
- A/E: Inappropriate, prolonged and painful
- Some degree of tolerance to antidepressant
penile erection.
action of SSRIs after a few months use.
Therapeutic uses: ii. Mianserin
- Endogenous depression - Do not inhibit NA or 5-HT uptake; but blocks
- Panic disorder pre-synaptic 2 receptors
- Obsessive compulsive disorder - Increase release and turnover of NA in brain,

which may be responsible for antidepressant
- Post-traumatic stress disorder
effect.
- Premenstrual dysphoric disorder
Pharmacology
iii. Venlafaxine 2. Azapirones: Buspirone, Gepirone, Ispapirone

- Serotonin and nor-adrenaline re-uptake 3. Sedative antihistaminic: Hydroxyzine
inhibitor (SNRI) because it inhibits uptake of 4. -blocker: Propranolol
both of these amines.
Buspirone
- Does not react with cholinergic, adrenergic or
 Does not produce significant sedation or cognitive
histaminergic receptors or have sedative
or functional impairment
property.
 Does not produce tolerance or physical
- Faster onset of action.
dependence
iv. Mirtazapine
 Does not interact with BZD receptor or modify
- Blocks 2 autoreceptors and 5-HT hetero
GABAergic transmission.
receptors enhancing both NA and 5-HT release.
 Has no muscle relaxant or anticonvulsant activity
- Noradrenergic and specific serotonergic
antidepressant (NaSSA)  Relieves mild to moderate generalized anxiety but
ineffective is severe cases.
ANTIANXIETY DRUGS MOA:
Past Question: Selective partial agonistic action on 5-HT1A
1. Write short notes on anxiolytics (3) [01 Dec] receptors
 Anxiety is an emotional state, unpleasant in 
nature, associated with uneasiness, discomfort Stimulation of presynaptic 5-HT1A autoreceptors
and concern or fear about some defined or 
undefined future threat. Reduces activity of dorsal raphe serotonergic
 Anti-anxiety drugs are an ill-defined group of neurons
VIII drugs. Mostly mild CNS depressants, which are Adverse effects:
aimed to control the symptoms of anxiety, - Dizziness, nausea, headache, light-headedness,
produce a restful state of mind without interfering rarely excitement.
with normal mental or physical functions.
Features ANTI-PARKINSONIAN DRUGS
i. Have no therapeutic effects to control thought Past Questions:
disorder of schizophrenia. 1. Explain why L-dopa is used in combination with
ii. Do not produce extrapyramidal side effects. carbidopa in Parkinsonism? (3) [05 June]
iii. Have anti-convulsant property 2. Give the clinical classification of antiparkinsonian
iv. Produce physical dependence and carry abuse drugs. Explain therapeutic usefulness of Levo
liability DOPA and carbidopa in parkinsonism
v. Do not selectively block conditioned avoidance (3+4=7) [04Dec]
response in animals. 3. Classify drugs used in the treatment of
Parkinson's disease (3)[02Dec]
Classification
4. Explain the mechanism of action of Levo DOPA in
1. Benzodiazepines Parkinson's disease and its adverse effects
- Diazepam (2+2=4) [02 Dec]
- Chlordiazepoxide 5. Give the pharmacological basis of use of:
- Oxazepam a. Trihexyphenidyl is used in drug induced
- Lorazepam, Alprazolam Parkinsonism (3) [04Dec]

CNS
b. Use of benztropine in drug induced e. COMT inhibitor: Entacapone, Tolcapone

Parkinsonism (3) [04June] f. Dopamine fascilator: Amantadine
c. Long term use of chlorpromazine may cause 2. Drugs affecting brain cholinergic system
Parkinsonism (3) [04June] a. Central anticholinergics: Trihexyphenidyl,
d. Trihexyphenidyl in Parkinsonism (3) [07July] procyclidin, Biperdin
e. Carbidopa with Levo DOPA in Parkinsonism b. Antihistaminics: Orphenadrine, promethazine.
(3) [09Jun]
Levo DOPA (Dopamine precursor)
f. Carbidopa and Levo DOPA combination in
Parkinsonism (3) [01 June] MOA:
g. Carbidopa in Parkinsonism (3) [03 Dec] About 1% of Levo DOPA crosses the blood brain
barrier
Pramipexole, Bromocriptine,
ropinirole pergolide 
Dopamine Levo DOPA in brain (precursor)
receptors

Selegiline,
rasagiline Tolcapone Taken up by surviving dopaminergic neurons
(substantia nigra)

MAO-B COMT
DOPAC Dopamine 3-MT Converted into dopamine (active) by DOPA
decarboxylase
DOPA decarboxylase 
L-DOPA Dopamine released as neurotransmitter
Brain L-amino acid transporter Actions:

Blood-brain barrier a. CNS:
Periphery - Improve hypokinesia, rigidity and tremor VIII
3-OMD COMT
L-DOPA DOPA decarboxylase
Dopamine - Normalize posture, gait, handwriting, speech,
facial expression, mood, etc.
- General alerting response
Entacapone, Carbidopa - Awakening effect in hepatic coma
tolcapone Adverse effect
b. CVS:
DOPAC: Dihydroxyphenylacetic acid
- Tachycardia
3-MT: 3-Methoxytyramine.
- Postural hypotension
3-OMD: 3-O-methyldopa.
MAO: Monoamine oxidase c. CTZ: (Chemotrigger zone)
COMT: Catechol-O-methyltransferase - Elicits nausea and vomiting.
d. Endocrine:
Classification of Antiparkinsonian drugs - Inhibit prolactin release
[04,02] - Increase GH release
1. Drugs affecting brain dopaminergic system Pharmacokinetics:
a. Dopamine precursor: Levo DOPA - Rapidly absorbed in small intestine (active
b. Peripheral decarboxylase inhibitor: Carbidopa, transport)
Benserazide. - 1st pass metabolism in GI mucosa and liver.
- About 1% of administered Levo DOPA enters
c. Dopaminergic agonist: Bromocryptine,
Ropinirole, Pramipexole. brain (amino acid medicated active transport
across BBB)
d. MAO-B inhibitor: Selegiline, rasagiline
Pharmacology
Adverse Effects: Uses:

- Nausea, vomiting - In Parkinsonism: Levo DOPA (250mg) +
- Postural hypotension Carbidopa (25mg)
- Cardiac arrhythmia and Exacerbation of angina Carbidopa (Peripheral decarboxylase
 Due to -adrenergic action of Dopamine. inhibitor) [03]
- Alteration of taste sensation MOA:
- On Prolonged therapy: Behavioral effects, - DOPA carboxylase inhibitor
abnormal movements, fluctuation in motor
Note: Carbidopa do not cross BBB. Hence, conversion
performance
of Levo DOPA to dopamine in the brain is not
Note: inhibited.
- Response fluctuation on prolonged therapy of
Use:
Levo DOPA
- Combination with Levo DOPA also called ‘Co-
Example:
careldopa’ is 1st line antiparkinsonian drug.
i. End of dose akinesia
Levo DOPA must be used in combination with
ii. On off phenomena peripheral decarboxylase inhibitor [i.e. L-DOPA
Reason: (250mg) + carbidopa (25mg)]: [04]
- Levo DOPA is not curative drug for - Peripheral decarboxylase inhibitor (carbidopa,
parkinsonism i.e. inspite of administration of benserazide) inhibits the peripheral conversion
Levo DOPA, disease progresses slowly unless of Levo DOPA to dopamine and indirectly
neurodegeneration is prevented by some other increases dopamine concentration in brain.
method. - It also increases efficacy of Levo DOPA.
- No. of neurons available to store and release
VIII Dopamine continue to reduce slowly.
- Reduce toxic effort of Levo DOPA.
Benefits of Combination of Levo DOPA and
- So, in later stage, as neurons available to store Carbidopa: [04]
dopamine are less, patient show good activity - Plasma T1/2 of L-dopa prolonged and dose is
just after drug administration but in between reduced by 1/4th.
dose intervals, there is marked depression in
- Systemic concentration of DA is reduced,
activity.
nausea vomiting are not prominent.
- Patient gets 'ON' when drug is given and again
- Cardiac complications are minimized.
in between doses as plasma concentration falls,
- Pyridoxine reversal of L-dopa does not occur.
patient gets 'OFF' i.e. depressed activity.
- On-off effect minimized as cerebral DA levels
Management:
are more-sustained.
- Such condition can be managed by increasing
- Degree of improvement is higher.
overall dose and each dose being smaller and
frequent. Dopaminergic agonist
Interactions: Note:
- Pyridoxine enhances peripheral - D1, D5: Excitatory dopamine receptor
decarboxylation of Levo DOPA. Thus, less of it - D2, D3 and D4: Inhibitory dopamine receptor
available to cross the brain.
i. Bromocryptine
- Should not be given with antihypertensive drug
- MOA: Potent against on D2 but partial agonist
- Phenothiazines, butyrophenones effect. or antagonist to D1 receptor

CNS
- Adverse effects: Vomiting, hallucinations, Uses:

hypotension, nasal stiffness, conjunctival infection. - Enhance and prolong the therapeutic effect of
- Uses: Supplement to Levo DOPA to improve Levo DOPA-carbidopa in advance cases of
control and smoothen ‘on off’ fluctuation in Parkinsonism.
Parkinsonism. - Used to:
ii. Ropinirole and Premipexole a. Smoothen wearing off
- MOA: Selective D2/D3 receptor against b. Increase ‘on’ time
- A/E: Similar to bromocryptine. c. Decrease ‘off’ time
- Uses: d. Improve activities of daily living
 Both used as monotherapy for early e. Allow Levo DOPA dose to reduce.
Parkinsonism.
Central Anticholinergics
 Ropinirole is used in restless leg syndrome.
 Central cholinergics are used in drug induced
Selegiline/Deprenyl (MAO-B inhibitor) Parkinsonism as adjuvant to Levodopa.
MOA:  Certain drugs like phenothiazine groups
Selective and irreversible MAO-B inhibitor (Chlorpromazine) Reserpine, metoclopramide
 block the dopamine receptor and causes
Reduce metabolism of dopamine to dihydroxy- imbalance between dopamine and acetylcholine
phenyl-acetic acid i.e. precipitate Parkinsonism.
Adverse Effects:  Trihexyphenidyl is the most commonly used
- Postural hypotension, nausea, confusion, central anticholinergics in Parkinsonism.
psychosis  They act by reducing the unbalanced cholinergic
- Accentuation of Levo DOPA induced activity i.e. M2 blockade in the striatum of
involuntary movements. parkinsonian patients.
VIII
Uses:  They have higher central action and less
- Used with Levo DOPA. peripheral action.
- When used with L-dopa, it:  They are mainly effective in controlling
i. Prolongs L-dopa action hypokineria.
ii. Attenuate motor fluctuation. Important points to be remembered:
iii. Decreases “wearing off effects”. - The major cause for Parkinsonism is degeneration
Entacapone (COMT Inhibitor) of dopaminergic neurons in nigrostriatal pathway.
MOA: - Degeneration of dopaminergic pathway cause
Selective, potent and reversible COMT imbalance between dopaminergic (inhibitory) and
(catecholamine O- methyl transferase) inhibitor. cholinergic (excitatory) pathway giving rise to
 motor defect.
Inhibit metabolic pathway of dopamine. - Levo DOPA is first line of drug for Parkinsonism but
it must be provided with peripheral decarboxylase
Adverse Effects:
inhibitor (Carbidopa, Benserazide) to prolong it
- Diarrhea and yellow-orange discoloration of urine.
action.
- Worsening of Levo DOPA side effects like
nausea, vomiting, dyskinesia, postural - Balance between dopamine and Acetylcholine is
hypotension, etc. restored by the antiparkinsonic drugs.

Pharmacology
OPIOID ANALGESICS AND

Classification of Opioid Analgesics
ANTAGONISTS
[08,07,03]
Past Questions:
1. Opioid receptor agonist
1. a. Compare morphine and pethidine (3)
a. Natural Opium alkaloid: Morphine, Codeine
b. Mention the contraindications of morphine.
b. Semisynthetic opiates: Diacetyl morphine,
(2) [10Jan] heroine, hydromorphon
2. Classify opioid analgesics. Describe briefly their c. Synthetic opioids: Pethidine, fentanyl,
therapeutic uses adverse effects and precaution methadone, Tramadol
in their use. (3+2+2+2=9)[08July]
2. Opioid agonist-antagonist: Pentazocine, nalorphine.
3. List opioid analgesic. Describe the mechanism of
3. Partial µ receptor agonist: Buprenorphine.
action and adverse effects of pethidine.
(2+3+2=7)[08 Jan] Morphine
4. List opioid analgesics. Mention the important  It is a prototype drug and opioid receptor agonist
differences between morphine and pethidine.  It is strong analgesic that relived dull, poorly
(2+3=5) [07 July] localized and visceral pain.
5. List synthetic opioids. Enumerate important MOA:
differences between synthetic opioids. List - As morphine binds to opioid receptors,
contraindication of opioids. (2+3+2=7) [03June] molecular signaling activates the receptors to
6. Enumerate the difference between (42=8)[01Dec] mediate certain actions.
a. Morphine and Pethidine - There are three important classes of opioid
b. Nalorphine and naloxone receptors and these are: [09]
i. μ (mu) receptor:
VIII 7. Give the pharmacological basis of use of:
a. Morphine is used in cardiac asthma (acute left  Present in the brainstem and the thalamus
ventricular failure) [3] (2)[02Dec]  It is Gi protein coupled receptor. When
b. Morphine is contraindicated in head injury. stimulated it  cAMP and  K+ efflux.
[04Dec]  Activation of these receptors can result in
c. Naloxone in acute morphine poisoning [06June] pain relief, sedation and euphoria as well as
respiratory depression, constipation and
d. Morphine in acute myocardial infraction
physical dependence.
(2) [04Dec]
ii.  (kappa) receptor:
e. Contraindication of morphine in head injury
 This receptor is present in the limbic system,
[3] [04June, 01 June]
diencephalon, the brain stem and spinal cord.
8. Write short notes on:
 It is Gi protein coupled receptor. When
a. Opioid poisoning [3] [04 June]
stimulated causes  Ca++ influx.
b. Opioid receptors (2) [09 July]
 Activation of this receptor causes pain
c. Contraindications of opioid analgesics
relief, sedation, loss of breath and
[3] [05 Dec] dependence.
d. Contraindication of opioids in head injury iii. (delta) receptor:
[3] [02 Dec]  This receptor is widely distributed in the
e. Naloxone [3] [09 July, 03 Dec] brain and present in the spinal cord and
f. Pentazocine [3] [10 July, 04 Dec] digestive tract.

CNS
 It is Gi protein coupled receptors. When Adverse Effects of Morphine:

stimulated cause  cAMP and  K+ efflux. - Sedation, mental clouding, lethargy
 Stimulation of this receptor leads to - Constipation
analgesic as well as antidepressant effects - Respiratory depression
but may also cause respiratory depression. - Blurring of vision as it cause miosis
Pharmacological actions of Morphine - Urinary retention
A. CNS - BP falls
i. Sedation - Biliary colic
ii. Euphoria - Urinary urgency
iii. Respiratory centre depression - Idiosyncracy and allergy: As morphine induce
iv. Cough centre depression histamine.
v. Hypothermia - Apnoea in newborn
vi. Vasomotor centre - Acute morphine poisoning
a. CTZ: Stimulation of CTZ so vomiting and - Tolerance and dependence.
nausea occurs. Uses:
b. Edinger Westphal nucleus: Produces miosis - As analgesic
c. Vagal centre: Stimulation causes bradycardia - Preanasthetic medication
B. Neuroendocrine - Balanced anesthesia and surgical analgesia
- Hypothalamic influence on pituitary is reduced - Relief of anxiety and apprehension.
so FSH, LH and ACTH levels are reduced but
- Acute left ventricular failure.
prolactin and GH levels are raised because
- Cough
these two are under inhibitory control.
- Diarrhea VIII
C. CVS
- Causes vasodilation due to: Contraindications:
i. Histamine release - Patient with respiratory depression.
ii. Depression of vasomotor centre - Respiratory insufficient
iii. Decreases tone of blood vessels. - Bronchial asthma
D. GIT - Head injury
- Causes constipation as it: - Hypotensive states
i. Decreases GI motility - Undiagnosed acute abdominal pain
ii. Increases tone of a sphincter acting on CNS. - Elderly male
E. Smooth muscle of - Hypothyroidism, liver and kidney disease
a. Urinary bladder: Cause urinary urgency as it
increases tone of both detrusor and sphincter
Acute Morphine poisoning [04]
muscle of UB.  50mg of morphine intramuscular produces serious
b. Uterus: Prolong labour toxicity, but human lethal dose is estimated to be
c. Bronchi: Bronchoconstriction occurs as about 250mg.
morphine secretes histamine. Symptoms of Morphine poisoning:
d. Biliary tract: - Stupor or coma
- Causes spam of sphincter of Oddi - Flaccidity
- May causes biliary colic. - Shallow and occasional breathing

Pharmacology
- Cyanosis Difference between Pethidine & Morphine:

- Pinpoint pupil [10,07,01]
- Fall in BP and shock Morphine Pethidine
- Convulsion - Natural opium alkaloid - Synthetic opioid
- Death due to respiratory failure
- (1/10)th does of pethidine - Required 10 times more
Treatment: is sufficient for analgesic dose than morphine
- Respiratory support action.
- Maintenance of BP by providing - Longer duration of action - Shorter
vasoconstriction
- Spasmodic action on - Spasmodic action on
- Gastric lavage should be done with potassium smooth muscle is smooth muscle is less
permanganate to remove unabsorbed drugs. prominent so cause:
- Naloxone 0.4-0.8 mg IV repeated every 2-3 min i. Constipation
until respiratory problem subsides. ii. Biliary spasm
- Injection should be repeated every 1-4 hours iii. Urinary retention
a/c to response. iv. Miosis
Pethidine (Meperidine) [08] - Cause bradycardia - Tachycardia
 It is synthetic opioids - Higher histamine release so - Less histamine release
 Chemically unrelated to morphine and less potent shows allergic reaction.
than morphine - Suppress cough - Does not suppress
 Its action is blocked by naloxone. cough.
 Advantages over morphine are: Complex action opioids and opioid
VIII - Less spasmodic action on smooth muscle so no antagonist
miosis, no constipation and less urinary 1. Agonist-antagonist ( analgesics): Nalorphine,
retention. pentazocine, Butorphine.
- Less biliary spasm action. 2. Partial/weak μ agonist +  antagonist: Buprenosphine
- Less histamine release so also can be used in 3. Pure antagonist: Naloxone, Naltrexone,
asthmatic patient. Naimefene
MOA:
Naloxone [09,03]
- Same as that of morphine.
 It is pure opioid antagonist blocking μ receptor mainly
Adverse Effects:
but it shows action on  and δ receptor as well.
a. Atropinic side effects (as it is atropinic
 It has no any agonistic action even at higher dose.
substitute): Dry mouth, blurred vision,
tachycardia  No physical and psychological dependence occurs.
b. Tremors, hyperreflexia, delirium, convulsion  It antagonizes the action of morphine at a dose
c. Respiratory depression and 0.4-0.8mg IV but at dose 4-10 mg; it antagonizes
d. Physical dependence and tolerance. agonistic action of Nalorphine and pentazocine as
Uses: well.
a. As an analgesic (substitute of morphine) Uses:
b. In preanaesthetic medication a. Acute morphine poisoning
c. Used to control shivering during recovery from - 0.4-0.8 mg IV and repeated every 2-3 min.
anaesthetia. till respiratory symptoms subsides.

CNS
b. To reverse neonatal asphyxia due to use of Pharmacological basis for using morphine
opioid during labour. in left ventricular failure: [04,02]
c. Overdose of other opioids. - Morphine reduces preload on the heart due to
d. To reverse respiratory depression. vasodilation.
e. Reverse alcohol intoxicants.
- It also shifts blood from pulmonary to systemic
Pentazocine [10,04] circuit and
 It has both agonistic action ( receptor) and - It also reduces the cardiac work by cutting
antagonistic action (µ receptor) down sympathetic stimulation.
 It has more agonistic action than antagonistic.
Morphine is contraindicated in head injury:
Agonistic action:
[04,02,01]
- Similar to morphine but shows following
differences - Because morphine by absorbing CO2 increases
i. Analgesic effect does not increase with the intracranial pressure that exacerbates
increases in dose. headache.
ii. Less sedation and respiratory depression - Patient with head injury when use morphine
(1/3 rd – ½) as comparison to morphine. causes marked respiratory depression even in
iii. Cause tachycardia and increases BP
therapeutic use.
iv. Less severe biliary spasm and constipation
- Vomiting, miosis and altered sensation
v. Low abuse liability to tolerance and
dependence. produced by morphine interferes with
Antagonistic action: assessment of progress in head injury cases.
- 1/5th of potency of Nalorphine. Therefore, it Things to be Remember:
cannot be used as a correct antidote for - Morphine causes respiratory depression in infant
VIII
morphine poisoning.
and elderly patient
Difference between Morphine & Pentazocine
- Morphine exacerbates asthma by releasing
Morphine Pentazocine histamine
- Pure agonist - Has both agonistic and - Morphine shouldn’t be used in case of head injury
weak antagonistic
- Morphine has contracting action on all smooth
action
muscles except vascular smooth muscle
- More potent - Less potent
- Morphine can be used against diarrhea as it acts
- More sedation and - Less effects as a constipating action.
respiratory depression
- Morphine causes miosis by stimulating Edinger
effect
Westphal nucleus (III CN nuclei)
- BP is less marked - Tachycardia and
- Naloxone (0.04 -0.8 mg) is a special antidote for
increases BP markedly
morphine poisoning.
- Vomiting more frequent - Less frequent

Pharmacology
SPECIAL POINTS FOR MCQs

1. General anesthetics (GA) are drugs which produce reversible loss of all sensation and
consciousness.
2. The major target of anaesthetic action ligand gated ion channel (but not voltage sensitive ion
channels).
3. General anaesthetics appear to act by depressing synaptic transmission.
4. Local anaesthetics which act primarily by blocking the axonal conduction.
5. Nitrous oxide (N2O) is a poor muscle relaxant; neuromuscular blockers are often required.
6. N2O (50%) has been used with O2 for dental and obstetric analgesics.
7. Ether does not sensitize the heart to adrenaline and is not hepatotoxic.
8. Halothane causes the direct depression of myocardial contractility by reducing intracellular Ca2+
concentration.
9. Halothane causes the bronchodilation, hence it is preferred for asthmatics.
10. Enflurane has propensity to provoke seizures at the deeper levels of anaesthesia.
11. Isoflurane maintains the coronary circulation; hence, thin drug is safer in patients with
myocardial ischemia.
VIII 12. Isoflurane does not provoke seizures and is preferred for neurosurgery.
13. Fluorinated congener of isoflurane is desflurane.
14. Adverse effect of the thiopentone sodium is the laryngospasm which can be prevented by atropine
premedication and also by administrating the succinylcholine immediately after the thiopentone.
15. Succinylcholine and thiopentone should not mix in the same syringe because they react
chemically.
16. The anaesthetic action of Benzodiazepines can be rapidly reversed by flumazenil 0.5–2mg
intravenous.
17. Ketamine is also called as dissociative anaesthesia.
18. Heart rate, cardiac output and blood pressure are elevated due to sympathetic stimulation, by
ketamine.
19. Ketamine when combined with diazepam can be used in angiographies, cardiac catheterization
and trauma surgery.
20. When alcohol injected subcutaneously, it causes intense pain, inflammation and necrosis followed
by fibrosis.
21. Alcohol dose not kill bacterial spores.
22. Regular alcohol intake induces microsomal enzymes.

CNS
23. Megaloblastic anaemia has been seen in chronic alcoholism due to interference with folate
metabolism.
24. Alcohol induces the inhibition of ADH secretion.
25. Lower oesophageal tone is suppressed by alcohol.
26. Metabolism of alcohol follows zero order kinetics.
27. Alcohol gets distributed widely in the body i.e. volume of distribution 0.7 liter/kg and can cross
the blood brain carrier efficiently.
28. Methanol is metabolized to formaldehyde and formic acid by alcohol and aldehyde
dehydrogenase respectively.
29. Toxic effects of methanol are largely due to formic acid.
30. The specific toxicity of the formic acid is retinal damage.
31. Fomepizole (4-methylpyrazole) is a specific inhibitor of acid dehydrogenase that retains the
methanol metabolism.
32. A drug that subdues excitement and calms the subject without inducting sleep, though drowsiness
may be produced, is called as sedative drug.
33. Hypnotic drug that induces and/or maintains sleep, similar to normal arousable sleep.
34. Barbiturates have anticonvulsant property.
35. High lipid soluble barbiturates Thiopentone.
36. Less lipid soluble barbiturates Phenobarbitone.
37. Tone and motility of bowel is decreased slightly by the hypnotic does of the barbiturates. VIII
38. Barbiturates tend to reduce urine flow by decreasing blood pressure and increasing ADH release.
39. Oliguria attends barbiturate intoxication.
40. Barbiturates cross the placenta and secreted in milk, can produce effects on the fetus and suckling
infants.
41. Barbiturates induce the microsomal enzymes i.e. (–amino levulinic acid synthetase) and 
increases porphyrin synthesis.
42. Hangover, rashes, swelling of eyelids, lips etc. are the most common side effects of the
barbiturates.
43. Benzodiazepines have high therapeutic index.
44. Hypnotic does of benzodiazepines do not affect the respiration & cardiovascular function.
45. Benzodiazepines synergies with alcohol and other CNS depressant leading to excessive
impairment.
45. Zaleplon is the shortest acting of the newer non benzodiazepines hypnotics.
46. Flumazenil is the benzodiazepine antagonist.
47. Even though flumazenil is absorbed orally, it is not used orally.

Pharmacology
48. On intravenous injection, flumazenil starts in seconds and last for 1–2 hr, elimination 1/2 is 1hr,
due to rapid metabolism.
49. Ramelteon is the melatonin receptor agonist and is the novel hypnotic drug which does to produce
the Benzodiazepines like side effects.
50. Phenobarbitone is one of the cheapest and least toxic antiepileptics.
51. Phenobarbitone has broad spectrum efficacy in generalized tonic clonic (GTC), simple partial (SP)
and complex partial (CP) seizures.
52. Primidone belongs to deoxybarbiturates which is converted into phenobarbitone and phenyl-
ethyl-malonamide (PEMA) in the liver.
53. Adverse effects of the deoxybarbituratesare similar tophenobarbitone. In addition, anemia,
Leukopenia, psychotic reaction and lymph node enlargement occurs rarely.
54. Gum hypertrophy is the commonest side effect of the phenytoin.
55. Carbamazepine and phenytoin increases each other metabolism.
56. Sodium valproate displaces protein bound phenytoin and decreases its metabolism.
57. Phenytoin competitively inhibits warfarin metabolism.
58. Phenytoin induces the microsomal enzyme and increases the degradation of the steroids (failure
of oral contraceptives), digitoxin, doxycycline, and theophylline.
59. Carbamazepine is the drug of choice for the trigeminal neuralgia.
60. Carbamazepine produces the dose dependent neurotoxicity.
VIII 61. Pancreatitis, polycystic ovarian disease and menstrual irregularities mainly associated adverse
effects of valproic acid (sodium valproate).
62. Gabapentin inhibits the PTZ induced clonic seizures.
63. Lamotrigine is new anticonvulsant having carbamazepine like action profile used in the epilepsy.
64. Gabapentin is the lipophilic GABA derivatives which crosses the brain and enhances the GABA
release.
65. First choice of drug for the febrile seizures is diazepam and route of administration of the drug is
per rectal.
66. First choice of drug for the absence seizures is the sodium valproate.
67. More than 95% of an oral dose of the Levo DOPA gets decarboxylated in the peripheral tissues
(mainly gut and liver).
68. Ropinirole has recently been approved for use in "restless leg syndrome”.
69. Selegiline is a selective and irreversible Monoamino oxidase-B inhibitor.
70. Postural hypotension is one of the side effects of the selegiline.
71. COMT inhibitor preserves the dopamine formed in the stratum.
72. Amantadine developed as an antiviral drug for the prophylaxis of influenza A2, it was found
serendipitously to benefit Parkinsonism.

CNS
73. Anticholinergics are only drugs effective in drug (phenothiazine) induced Parkinsonism.
74. Misperception and misevaluation is called psychoses and the person is unable to meet the
ordinary demands of life.
75. All the antipsychoitcs (except clozopine like atypical) have potent dopamine D2 receptor blocking
action.
76. Penfluridol is the long acting neuroleptic, recommended for the chronic schizophrenia.
77. Cardiac arrhythmias and interference with the male sexual function are the most common side
effects of thiomidazine.
78. Chozapine is the atypical antipsychotics which is used as reserve drug in resistant schizophrenia.
79. Ziprasidone is the latest atypical antipsychotic drug with combined D2 + 5–HT2A/2C + H1 + 1
blocking activity.
80. Lithium carbonate is antimanic (mood stabilizing) drug.
81. Lithium causes the equal distribution of the Na+ inside and outside the cells.
82. Lithium decreases the synthesis of nor-adrenaline and dopamine without interfering with the
serotonin synthesis.
83. Lithium inhibits the action of ADH on distal tubules and causes a diabetes insipidus like state.
84. Leukocytes count is increased by lithium therapy.
85. Lithium reduces thyroxin synthesis by interfering with iodination of tyrosine.
86. Moclobemide is reversible and selective MAO-A inhibitor. VIII
87. Tricyclin antidepressant (TCAs) inhibits the monoamine uptake and interact with a variety of
receptor viz, muscarinic, -adrenergic, Histamine-H1, 5HT1, 5HT2 and occasionally dopamine D2.
88. Tricyclin antidepressant lower seizure threshold and produce convulsion in overdose.
89. Most of TCAs are potent anticholinergics and have similar side effects like anticholinergic.
91. Fluoxetine is the bicyclic compound, prototype of SSRI (selective serotonin receptor inhibitor) has
been approved for use in children 7 years or older for depression.
92. Fluoxetine has caused more agitation and dermatological reaction than other SSRIs.
93. Trazodone is the 1st atypical antidepressant, selectively but less efficiently blocks 5–HT uptake
and has prominent  blocking as well as weak 5HT2 antagonistic action.
94. Alprazolam has high potency anxiolytics benzodiazepines which in addition has some mood
elevating action in mild depression.
95. Alprazolam is particularly used for the anxiety associated depression.
96. Morphine can release ADH and reduce the urine volume.
causes
97. Morphine releases the histamine  bronchoconstriction.

Pharmacology
98. Specific antidote for morphine poisoning is naloxone 0.4–0.8mg intravenous repeated every 2–3
minute till the respiration picks up.
99. Pure opioid antagonist is naloxone.
100. Tramadol is centrally acting analgesics relieves pain by opioid as well as additional mechanism.
101. Injected intravenous 100mg tramadol is equianalgesics to 10mg intramuscular morphine.
102. Drug for producing local anesthesia Lidocaine.
103. Drug of choice for the patients with the lidocaine allergy Prilocaine.
104. Local anesthetics which is used for obstetrical procedure Bupivacaine.
105. Drug of choice (DOC) in Prilocaine induced methaemoglobinaemia  Methylene blue (vitamin
C is an alternative).
106. DOC for local anesthetic induced cardiac arrhythmias Bretylium (K+ channel blocker)
107. DOC for epidural block Bupivacaine.
108. DOC for spinal anesthesiaLidocaine.
109. DOC for local anesthesia in malignant hyperthermia  Procaine.
110. Local anesthetic of choice in hypotensive/cardiac/ epileptic patients Mepivacaine.
111. DOC for patients with psychosis and EPS is Clozapine/Thioridazine.
112. DOC for neutropenia in felty's syndrome – Lithium (monovalent ion)
VIII 113. DOC for achieving selective antianxiety effect without producing sedation is Buspirone–5H1A
partial agonist.
114. Drug for reducing preanaesthetic anxiety Lorazepam.

Pharmacology-CNS Fast Track

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CNS

FAST TRACK BASIC SCIENCE MBBS -941-

-942- FAST TRACK BASIC SCIENCE MBBS

ALIPHATIC ALCOHOLS  Impairment of memory

FAST TRACK BASIC SCIENCE MBBS -943-

9. Skeletal Muscle - Aspirin and other NSAIDS causes gastric

-944- FAST TRACK BASIC SCIENCE MBBS

- Alcoholic cirrhosis of liver, HTN,  Dizziness, Visual disturbances, Mental

FAST TRACK BASIC SCIENCE MBBS -945-

Note: LOCAL ANAESTHETICS

-946- FAST TRACK BASIC SCIENCE MBBS

B. Mechanism of Action 4. Spinal Anaesthesia

C. Uses 2. CVS: Bradycardia, hypotension, cardiac

- It is used for surface application, infiltration, GENERAL ANAESTHETICS

Mechanism of action: Mechanism of Action:

FAST TRACK BASIC SCIENCE MBBS -949-

Thiopentone Sodium Ketamine [KU 09]

-950- FAST TRACK BASIC SCIENCE MBBS

Aim: d. Benzodiazepines in therapy (3) [10 July]

FAST TRACK BASIC SCIENCE MBBS -951-

Barbiturates Benzodiazepines (BZDs) [10,07,05,02]

FAST TRACK BASIC SCIENCE MBBS -953-

Adverse Effects: At higher doses

- At higher doses; A/E of phenytoin like - Epigastric pain, vomiting.

Phenytoin [11,09,05,04,03] Carbamazepine [CPS, GTCS, SPS]

MOA:  Chemically related to imipramine.

- Metabolized in liver by hydroxylation and - 75% plasma bound.

-956- FAST TRACK BASIC SCIENCE MBBS

Status epilepticus - Once seizure is controlled, commence longer

 Those drugs having primary effects on psyche Negative symptoms:

Note: Blockage of D1, D3, D4 receptors has no Haloperidol

FAST TRACK BASIC SCIENCE MBBS -959-

-960- FAST TRACK BASIC SCIENCE MBBS

Adverse effects ANTIMANIAC (MOOD STABILIZERS)

FAST TRACK BASIC SCIENCE MBBS -961-

i. Li+ partly replaces body Na+ and is nearly Adverse effects:

-962- FAST TRACK BASIC SCIENCE MBBS

ANTI-DEPRESSANTS iii. Selective serotonin reuptake inhibiters (SSRIs)

FAST TRACK BASIC SCIENCE MBBS -963-

Pharmacological Actions: ii. Sedation, mental confusion and weakness.

-964- FAST TRACK BASIC SCIENCE MBBS

SSRI (Selective Serotonin re-uptake - Kleptomania

- Obsessive compulsive disorder - Increase release and turnover of NA in brain,

iii. Venlafaxine 2. Azapirones: Buspirone, Gepirone, Ispapirone

-966- FAST TRACK BASIC SCIENCE MBBS

b. Use of benztropine in drug induced e. COMT inhibitor: Entacapone, Tolcapone

Brain L-amino acid transporter Actions:

Adverse Effects: Uses:

-968- FAST TRACK BASIC SCIENCE MBBS

- Adverse effects: Vomiting, hallucinations, Uses:

FAST TRACK BASIC SCIENCE MBBS -969-

OPIOID ANALGESICS AND

-970- FAST TRACK BASIC SCIENCE MBBS

 It is Gi protein coupled receptors. When Adverse Effects of Morphine:

FAST TRACK BASIC SCIENCE MBBS -971-

- Cyanosis Difference between Pethidine & Morphine:

-972- FAST TRACK BASIC SCIENCE MBBS

FAST TRACK BASIC SCIENCE MBBS -973-

SPECIAL POINTS FOR MCQs

-974- FAST TRACK BASIC SCIENCE MBBS

FAST TRACK BASIC SCIENCE MBBS -975-

-976- FAST TRACK BASIC SCIENCE MBBS

FAST TRACK BASIC SCIENCE MBBS -977-