This document provides information on sedative-hypnotic-anxiolytic drugs, including benzodiazepines, barbiturates, and alcohols. It discusses the mechanisms of action, effects on sleep cycles, drug classifications and uses. Specific drugs discussed include diazepam, flurazepam, nitrazepam, phenobarbital, and ethanol. Adverse effects, drug interactions, and contraindications are also summarized.

1. CNS DRUGS

2. SEDATIVE-HYPNOTIC-ANXIOLYTIC DRUGS
Contents
 Benzodiazepines
 Barbiturates
 Alcohols

3. INTRODUCTION
 Sedation refers to decreased
responsiveness to any level of stimulation
and it is associated with some decrease in
motor activity.
 A drug that calms the subject without
inducing sleep, though drowsiness may be
produced.

4. CONTINUED
 Hypnotic is a substance that induces sleep,
similar to normal arousal sleep.
 This is not to be confused with hypnosis
meaning a trans like state in which the
subject becomes passive and highly
suggestible.

5. SLEEP CYCLES
 There are four sleep cycles:
1. Stage 0: EEG shows alpha activity when
eyes are closed and beta activity when
eyes are open. It constitutes 1-2 % of
sleep.
2. Stage 1: EEG shows interpretation of
alpha waves into theta waves, eye
movements are reduced, neck muscles

6. CONTINUED
 Stage 2: EEG shows theta waves, little eye
movement and this comprises 40-50% of
sleep time.
 Stage 3: EEG shows theta and gamma
waves, eye movements are few and it
comprises 5-8% of sleep time.

7. CONTINUED
 Stage 4: EEG shows only gamma, eyes
are practically closed, night terror may be
occur and it comprises 10-20% of sleep time.
Note
 During stage 2,3, and 4 heart rate, Bp and
respiration are steady and muscles are
relaxed.
 Stages 3 and 4 together are called slow
wave sleep.

8. BENZODIAZEPINES
 Benzodiazepines are well absorbed when given
orally.
 They bind strongly to plasma proteins, however,
many of them accumulate gradually in the body
fat (i.e. they are highly lipid soluble).
 Benzodiazepines are inactivated by the liver
and excreted in the urine.

9. CLASSIFICATION OF DRUGS
1. Short acting (triazolam),
2. Medium acting (alprazepam, lorazepam)
3. Long acting compounds (diazepam,
chlordiazepoxide, clonazepam)

10. CONTINUED
 Benzodiazepines potentiate GABA.
 Increase frequency of Cl influx.
 Act through benzodiazepine receptors.
 Bz 1 mediates sedation.
 Bz 2 mediates anti-anxiety
 Benzodiazepines cause CNS depression

11. DRUGS AND THEIR USES
 Alprazolam- anxiety, panic & phobia.
 Diazepam- anxiety, sedation, muscle
relaxation & withdrawal states.
 Lorazepam- anxiety, sedation & status
epilepticus.
 Midazolam- sedation & anesthesia IV.
 Temazepam- sleep disorders
 Oxazepam- anxiety & sleep disorders.

12. DIAZEPAM
 It is a prescription over medication drug
 Highly lipid soluble drug and long acting
agent.
 With regular use accumulation occurs and
prolonged anxiolytic effects may be obtained.
 It is available 2, 5, 10mg tabs, 10mg/2ml
inj, and 2mg/5ml syrup.

13. FLURAZEPAM
 It is a prescription over medication drug
 Highly lipid soluble drug
 It is a long acting drug
 Has a long half life
 Suitable for patients who have frequent
nocturnal awakenings and in whom some
day time sedation is acceptable.
 It is available in 15mg caps.

14. NITRAZEPAM
 It is a prescription over medication drug
 Highly lipid soluble drug
 Good for patients with frequent nocturnal
awakenings.
 It is available in 5, 10mg capsules.

15. MECHANISM OF ACTION
 They increase GABA-A activity, indirectly by
stimulating BZ receptors both in 1 & 2.
 GABA (An amino acid that is found in the central
nervous system; acts as an inhibitory
neurotransmitter)

16. THERAPEUTIC USES
 Treatment insomnia
 Anxiety
 Preoperative medication
 Acute alcohol withdrawal
 As anticonvulsants
 Chronic muscle spasm and spasticity.

17. ADVERSE EFFECTS
 Prolonged sleep
 Drowsiness
 Confusion
 Amnesia –(Partial or total loss of memory)
 Impaired motor coordination
 Tolerance and dependence

18. BARBITURATES
 They are non-selective CNS depressants,
which produce effects ranging from
sedation and reduction of anxiety, to
unconsciousness and death from
respiratory and cardiovascular failure.
 Barbiturates act by enhancing action of
GABA, but less specific than

19. CONTINUED
 They are potent inducers of hepatic drug
metabolizing enzymes, hence likely to cause
drug interaction.
 Tolerance and dependance occur, more
than benzodiazepines.

20. DRUGS
 Phenobarbitone (long acting drug)
 Butobarbitone (short acting)
 Pentobarbitone (short acting)
 Methohexitone (short acting)
 Thiopental (short acting)

21. MECHANISM OF ACTION
 They stimulate GABA-A activity, by
increasing Cl influx directly, with out going BZ
receptors.

22. WITHDRAWAL SIGNS
• Withdrawal signs of benzodiazepines:
1. Insomnia
2. Anxiety
3. Seizure
• Withdrawal signs of barbiturates:
1. Anxiety
2. Agitation- A mental state of extreme emotional
disturbance
3. Life-threatening abortion

23. DRUG INTERACTIONS
• Anesthetics
• Anti-histamines
• Opiates (A narcotic drug that contains opium or an
opium derivative)
• Beta-blockers
• Oral contraceptives
• Carbamazepine
• Phenytoin
• Warfarin

24. ALCOHOL
• All alcohols cause CNS depression, in
part through GABA mimetic activity.
• All alcohols cause metabolic acidosis.
• Alcohols are classified into:
1. Ethylene glycol
2. Methanol
3. Ethanol

25. PHARMACOLOGICAL ACTIONS
Local actions
 Ethanol is a mild superefficient and
counterirritant when rubbed on the skin.
By evaporation it produces cooling.
 Applied to delicate skin or mucous
membranes it produces irritation and
burning sensation.
 Alcohol is astringent(sour/bitter),
precipitates surface proteins in bacteria
and it acts as an antiseptic.

26. CNS
 Alcohol is a neuronal depressant since the
highest areas are mostly easily deranged
and these are primarily inhibitory apparent
excitation and euphoria are experienced at
lower plasma concentration 30-100mg/dl.
 Mood and feelings are altered, anxiety may
be allayed.

27. CVS
 The effects are dependent on dose. Small
doses produce only cutaneous and gastric
vasodilatation, skin is warm and flushed and
there my be conjuctival injection, BP is not
affected.
 Moderate doses, cause tachycardia and a
mild rise in BP due to increased muscular
activity and sympathetic stimulation.
 Large doses, cause direct myocardial as well as
vasomotor centre depression and there is fall in
BP.

28. BLOOD
 Regular intake of small to moderate
amounts of alcohol has been found to raise
HDL cholesterol levels and decrease LDL
oxidation. This may be responsible for the
15-35% lower incidence of coronary artery
disease in such individuals.
 Megaloplastic anemia has been seen in
chronic alcoholism due to interference with
folate metabolism.

29. BODY TEMPERATURE
 Alcohol is reputed to combat cold. It does
produce a sense of warmth due to cutaneous
and gastric vasodilatation, but heat loss is
actually increased in cold surrounding.
 High doses depress temperature
regulation centre.

30. RESPIRATION
 Brandy or whiskey are reputed as respiratory
stimulants in collapse. They irritate buccal
and pharyngeal mucosa, may transiently
stimulate respiration reflexly.
 However it is better not to depend on this,
because the direct action of alcohol on
respiratory centre is only a depressant
one.

31. GIT
 Alcoholic beverages have variable effect on
gastric secretion depending on the beverage it
self and whether the individual likes it.
 How ever dilute alcohol put in the stomach is a
strong stimulant of gastric stimulation.
 Higher concentrations inhibit gastric secretion,
cause vomiting, mucosal congestion, and
gastritis.
 Alcoholism is important cause of chronic
gastritis, acute pancreatitis and disorders of
bowel movements.

32. LIVER
 Neither alcohol intoxication nor chronic use of
moderate amounts cause significant liver
damage, provided adequate nutrition is
maintained.
 Chronic alcoholism subjects liver to oxidative
stress and causes cellular necrosis followed
by fibrosis.
 Acetylaldehyde produced during metabolism of
alcohol appears to damage the hepatocytes
and induce inflammation.

33. SKELETAL MUSCLE
 Alcohol produces little direct effect. Fatigue is
allayed by small doses, but muscle work is
increased or decreased depending on the
predominating central effect.
 Weakness and myopathy occurs in
chronic alcoholism.

34. KIDNEY
 Diuresis is often noticed after alcohol intake.
This is due to water ingested with drinks and
alcohol induced inhibition of ADH
secretion.
 It doesn't impaired renal function.

35. SEX
 Alcohol is reputed as an aphrodisiac.
Aggressive sexual behavior is due to loss of
restraint and inhibition. However,
performance of the sexual is often impaired.
 Chronic alcoholism can produce
impotence, testicular atrophy,
Gynecomastia and infertility.

36. ENDOCRINE EFFECTS
 Moderate amounts of alcohol increase
adrenaline release which can cause
hyperglycemia, and other sympathetic
effects.
 However, acute intoxication is often
associated with hypoglycemia and depletion
of hepatic glycogen, because
gluconeogenesis inhibited.
 Glucagon, thus fails to reverse it and glucose
must be given.

37. UTERUS
 Uterine contractions are suppressed at
moderate blood vessels.

38. 1. ETHYLENE GLYCOL
• Ethylene glycol causes:
1. CNS depression
2. Metabolic acidosis
3. Nephrotoxicty
 Ethylene glycol is converted into oxalic
acid by the help of the enzyme, alcohol
dehydrogenase.

39. 2. METHANOL
• Methanol causes:
1. Respiratory failure
2. Metabolic acidosis
3. Ocular damage
• Methanol is converted into formic acid, by
the help of the enzyme, alcohol
dehydrogenase.

40. 3.ETHANOL
• Ethanol causes:
1. CNS depression
2. Metabolic acidosis
3. Acetaldehyde toxicity
• Ethanol is converted into acetic acid, by
the help of the enzyme, of alcohol
dehydrogenase.

41. CONTRAINDICATIONS
 Peptic ulcer, and hyperacidity.
 Epileptics, seizures may be precipitated.
 Severe liver disease patients
 Unstable personalities, they are likely to abuse it
and become excessive drinkers.
 Pregnant women, even moderate drinking
during pregnancy can produce fetal alcohol
syndrome resulting from low birth weights, low
IQ, stillbirth, growth retardation, increased
susceptibility to infections.

42. SIDE EFFECTS
 Nausea
 Vomiting
 Flushing
 Hangover
 Traffic accident
 Hypotension
 Gastritis
 Respiratory depression
 Coma
 Death

43. CHRONIC ALCOHOLISM
 Hypoglycemia
 Fatty liver, lipemia
 Muscle wasting
 Gout

44. MANAGEMENT
 Keep the patient in a quit, dark room, protect
the eyes from light. Preventing retinal
damage.
 Gastric lavage with sodium bicarbonate.
 Potassium chloride infusion is needed only
when hypokalemia occurs due to alkali
therapy.
 Supportive therapy like monitoring BP and
ventilation.
 Combat acidosis by iv sodium bicarbonate

45. CONTINUED
 Disulfiram, inhibits the enzyme aldehyde
dehydrogenase.
 Hemodialysis clears methanol as well as
formate.
 Fomepizole is a speacific inhibitor of alcohol
dehydrogenase retards methanol metabolism. A
loading dose of 15mg/kg iv followed by 10mg/kg
every 12 hours till serum methanol falls below
20mg/dl has been found effective and safe.

46. ALCOHOL & PREGNANCY
 The fetal alcohol syndrome is characterized
by growth restriction, hypoplasia,
microcephally, & marked CNS dysfunction
including frequent occurrence of mental
retardation.

47. ANTICONVULSANTS
 Seizure is a brief episode of abnormal
electrical activity in the nerve cells of the
brain.
 Convulsion is a characterized by spasmodic
contractions of involuntary muscles.
 epilepsy is a chronic, recurrent pattern of
seizure.

48. GENERALIZED SEIZURE
 Generalized tonic clonic seizure: major
epilepsy (grand mal) this the commonest
lasts 1-2 minutes.
 Absence seizures: minor epilepsy (petit mal)
lasts about 30 seconds.
 Atonic seizures: unconsciousness with
relaxation of all muscles due to excessive
inhibitory discharges, patient may fall.
 Myoclonic seizures: shock like momentary
contraction of muscles of a limb or the whole
body.

49. PARTIAL SEIZURES
 Simple partial seizure; lasts 0.5-1 minutes.
 Complex partial seizure: confused behavior
and purposeless movements, emotional
changes lasts 1-2 minutes along with
impairment of consciousness.
 Simple partial or complex partial seizures
secondary generalized: the partial seizure
occurs first and evolves into generalized
tonic clonic seizures with loss of
consciousness.

50. DIAGNOSIS
 EEG (electroencephalography)
 CT (computerized tomography) scan
 MRI (magnetic resonance image)

51. CLASSIFICATION OF DRUGS
1. Barbiturates: phenobarbitone
2. Deoxybarbiturate: primidone
3. Hydantoin: phenytoin and fosphenytoin
4. Iminostilbene: carbamazepine,
oxcarbamazepine
5. Succinimide: ethosuximide
6. Aliphatic carboxylic acid: valproic acid,
divalproex.

52. CONTINUED
7. Benzodiazepines: clonazepam, diazepam,
Lorazepam, clobazam.
8. Phenyltriazine: Lamotrigine
9. Cyclic GABA analog: Gabapentin
10. Newer drugs: vigabatrin, topiramate,
tiagabine.

53. SEIZURE STATES & DRUGS OF CHOICE
 Partial-simple or complex- valproic acid,
phenytoin and Carbamazepine.
 General tonic clonic - valproic acid,
phenytoin and Carbamazepine.
 General absence- Ethosuximide
 Status epilepticus- Lorazepam, diazepam,
or phenytoin.

54. MECHANISM OF ACTIONS
 Decrease axonal conduction by preventing
sodium influx.
 Increase GABA activity
 Decrease excitatory effects of glutamic acid
 Decrease pre-synaptic calcium influx

55. PHENYTOIN
 It was synthesized in 1908 as a barbiturate
analogue.
 Its anticonvulsant activity was specifically tested
in 1938 and since then it is a major antiepileptic
drug
 Blocks axonal sodium channels
 Prevents seizure propagation
 Uses for seizure states
 It is absorption is variable
 It is inducted in cytochrome P450

56. USES
 Phenytoin is a first line antiepileptic drug for:
1. Generalized tonic clonic, simple and
complex partial seizures, dose is 100mg
BD maximum 400mg/day.
2. Status epilepticus
3. Trigeminal neuralgia, second choice drug to
carbamazepine

57. SIDE EFFECTS
 CNS depression
 Gingival hyperplasia
 Hirsutism
 Osteomalacia
 Megaloblastic anemia
 Aplastic anemia
 Teratogenicity, cleft lip.

58. CARBAMAZEPINE
 It was introduced in the 1960 for trigeminal neuralgia.
 It is now a first line antiepileptic drug.
 Blocks axonal sodium channels
 It is used for seizure
 It is a DOC for trigeminal neuralgia
 Induces cytochrome P450

59. USES
 Complex partial seizure
 Generalized tonic clonic seizure
 Simple partial seizure
 Trigeminal neuralgia
 Acute mania

60. SIDE-EFFECTS
 CNS depression
 Osteomalacia
 Megaloblastic anemia
 Aplastic anemia
 Exfoliative dermatitis
 Increase ADH secretion
 Teratogenicity, like cleft lip & spina bifida.

61. VALPROIC ACID
 Blocks axonal sodium channels
 Blocks in calcium of the thalamic region
 Inhibits cytochrome P450
 Valproic acid is used for:
1. Seizure states (DOC absence seizure)
2. Mania (as an alternative to lithium)
3. Bipolar disorders (as an alternative to
lithium)
4. Migraines (prophylactic therapy)

62. PHARMACOKINETIC PROFILE
 Oral absorption of valproic acid is good. It is
90% bound to plasma proteins, completely
metabolized in the liver.
 It is excreted in the urine. Plasma half life is
10 to 15 hours but anticonvulsant effects are
longer lasting.
 Adult dose: start with 200mg TDS, maximum
800mg TDS
 Child dose: 15-30mg/kg/day.

63. SIDE-EFFECTS
 Hepatotoxicity
 Thrombocytopenia
 Pancreatitis
 Alopecia
 Anorexia
 Drowsiness
 Tremor
 Teratogenicity, spina bifida and defects of neural
tube.

64. ETHOSUXIMIDE
 Block calcium channels in the thalamic region of the
brain.
 It also doesn't potentiate GABA at therapeutic
concentrations.
 It is used for the absence of seizure.
 The dose is 20-30mg/kg/day or 250mg/5ml syrup.

65. ADVERSE EFFECTS
 Gastrointestinal intolerance
 Tiredness
 Mood changes
 Agitation
 Headache
 Drowsiness
 Hypersensitivity

66. FELBAMATE & LAMOTRIGINE
 Block sodium channels and glutamate
receptors.
 Used in seizure states
 Side-effects are:
1. Hepatotoxicity
2. Aplastic anemia
3. Stevens- johnson syndrome

67. GABAPENTIN
 Gabapentin is a lipophilic GABA derivative
crosses to the brain and enhances GABA
release.
 It reduces seizure frequency in refractory
partial seizures with or with out
generalization.
 Though Gabapentin has been found effective
as monotherapy as well as SPS & CPS, it is
mostly employed as add on drug.

68. CONTINUED
 Gabapentin is considered to be a first line
drug for pain due to diabetic neuropathy
and neuralgia and has some prophylactic
therapy for migraine.
 Gabapentin is well absorbed orally and
excreted unchanged in urine with a half life of
6 hours.
 The dose, start with 300mg OD, increase to
300-600mg TDS are required.

69. CONTINUED
 Increase GABA activity
 Used for seizure states and neuropathic
pain.
 Side-effects include:
1. Aplastic anemia
2. Liver failure

70. TREATMENT OF EPILEPSIES
 Generalized tonic clonic or simple partial
with or without generalization
1. First line drugs: Carbamazepine, phenytoin
2. Second line drugs: valproic acid,
Phenobarbitone
3. Third choice or add up: Lamotrigine,
Gabapentin, primidone

71. CONTINUED
 Complex partial with or without
generalization
1. First line drugs: Carbamazepine, valproic
acid, phenytoin.
2. Second line drugs: Gabapentin,
Lamotrigine
3. Third choice: clobazam, tiagabine,

72. CONTINUED
 Absence
1. Firs line drug: valporate
2. Second line drugs: Ethosuximide,
Lamotrigine.
3. Third line: clonazepam, clobazam

73. CONTINUED
 Myoclonic
1. First line drug: valproic acid
2. Second line drugs: topiramate, Lamotrigine
3. Third line drugs: primidone, clonazepam

74. CONTINUED
 Atonic
1. First line drug: valproic acid
2. Second line drugs: clonazepam,
clobazam
3. Third line drug: Lamotrigine
 Febrile seizure
1. First line: Diazepam

75. CONTINUED
 Status epilepticus
1. First line drugs: diazepam iv, Lorazepam iv
2. Second line drugs: fosphenytoin iv,
Phenobarbitone iv, im.
3. Third line drugs: General anesthesia

76. GENERAL FEATURES OF ANTI-CONVULSANT
DRUGS
 Anti-convulsant are additive with other CNS
depressants.
 Avoid abrupt withdrawal, which may precipitate
seizures.
 Decrease efficacy of oral contraceptives
 Phenobarbital is considered safest during
pregnancy.

77. ANESTHESIA HISTORY
 Before the middle of 19th century a number of
agents like alcohol, opium, and cannabis
were used to obtund surgical pain but
operations were horrible.
 Horace wells, a dentist picked up the idea of
using nitrous oxide from a demonstration of
laughing gas in 1844.
 Morton, a dentist and medical student at Boston
after experimenting on animals gave a
demonstration of ether anesthesia in 1846.

78. CONTINUED
 And then chloroform was used by Simpson
in Britain for obstetrical purpose in 1847.
 Cyclopropane was introduced in 1929, but
the new generation of anaesthetics was
heralded by halothane in 1956.The first iv
anesthetic thiopentone was introduced in
1935.

79. STAGES OF ANESTHESIA
 General anesthesia cause an irregularly
descending depression of the CNS, i.e the
higher functions are lost first and
progressively lower areas of the brain are
involved but in the spinal cord lower
segments are affected somewhat earlier than
the higher segments. The vital centers
located in the medulla are paralyzed the last
as the depth of anesthesia increases.

80. CONTINUED
 There are four stages in anesthesia:
1. Stage of analgesia
2. Stage of delirium
3. Surgical anesthesia
4. Medullary paralysis

81. STAGE OF ANALGESIA
 Starts from beginning of anaesthetic
inhalation and lasts upto the loss of
consciousness. Pain is progressively
abolished. Patients remains conscious can
hear and see and feels a dream like state,
amnesia develops by the end of this stage.
Reflexes and respiration remain normal.
 Though some minor operations can be
carried out during this stage, it is rather
difficult to maintain.

82. STAGE OF DELIRIUM
 From loss of consciousness to beginning of
regular respiration. Apparent excitement is
seen patient may shout, struggle and hold
his breath, muscle tone increases, jaws are
tightly closed, breathing is jerky, vomiting,
involuntary defecation may occur. Heart rate
and BP may rise and pupils dilate due to
sympathetic stimulation.

83. STAGE OF SURGICAL ANESTHESIA
 Extends from onset of regular respiration to
cessation of spontaneous breathing. This has
been divided into 4 planes which may
distinguished:
1. Plane 1 roving eyeballs, this plane ends
when eyes become fixed.
2. Plane 2 loss of corneal and laryngeal
reflexes
3. Plane 3 pupil starts dilating and light reflex
is lost
4. Plane 4 intercostal paralysis, shallow
abdominal respiration, dilated pupil.

84. STAGE OF MEDULLARY PARALYSIS
 Cessation of breathing to failure of circulation
and death. Pupil is widely dilated, muscles
are totally flabby, pulse is thready and BP is
very low.
 Many of the above indices have been
robbed by the use of atropine and
morphine.

85. DRUGS USED IN ANESTHESIA M.O.A
 Anesthesia protocols include several agents
in combination.
 The more soluble the anesthetic in the blood,
the lower the anesthesia.
 Anesthetics with low blood gas ratios have
fast onset and recovery.

86. GENERAL ANAESTHETICS
 General anaesthetics are drugs which
produce reversible loss of all sensation and
consciousness. The cardinal features of
general anaesthetics:
1. Loss of all sensation especially in pain
2. Sleep and amnesia
3. Immobility and muscle relaxation
4. Abolition of somatic and autonomic reflexes

87. CLASSIFICATION OF DRUGS
 Inhalational
1. Gas, e.g nitrous oxide
2. Volatile liquids
a. Ether
b. Halothane
c. Enflurane
d. Isoflurane
e. Desflurane
f. Sevoflurane

88. CONTINUED
Intravenous
1. Thiopentone
2. Methohexitone sod
3. Propofol
4. Etomidate
5. Diazepam – benzodiazepine
6. Lorazepam – benzodiazepine
7. Midazolam – benzodiazepine
8. Ketamine
9. Fentanyl- opiod

89. INTRAVENOUS (GENERAL) ANESTHESIA
Thiopental
1. Barbiturate used for induction
2. Highly lipid soluble
3. Rapid onset
4. Short acting

90. MIDAZOLAM
1. It is a benzodiazepine group
2. Used for pre-operative sedation
3. Used for anterograde amnesia
4. Used for induction
5. Used for outpatient surgery
6. Depress respiratory function

91. DIAZEPAM
 It is a prescription over medication drug
 0.2- 0.5 mg/kg may slow undiluted injection
in a running i.v drip, this technique reduces
the burning sensation in the vein and
incidence of thrombophlebitis.
 It is available 10mg/2ml injection.

92. LORAZEPAM
 It is a prescription over medication drug
 Three times more potent, slower acting and
less irritating than diazepam.
 It distributes more gradually awakening may
be delayed, amnesia is more profound.
 Dose is 2-4 mg iv per ml.

93. PROPOFOL
1. Used for induction and maintenance of
anesthesia
2. It is an oily liquid employed as a 1%
emulsion. Unconsciousness after Propofol
injection occurs in 15-45 sec and lasts 5-10
minutes.
3. Propofol distributes rapidly 2-4 min and
eliminates 100 minutes
4. Anti-emetic
5. CNS depressant
6. Cardiac depressant
7. Dose is 2mg/kg iv for induction and
9mg/kg/hr for maintainence.

94. FENTANYL
1. This is short acting 30-50 minutes potent Opiod
analgesic related to pethidine is generally given
iv at the beginning of painful surgical
procedures
2. After iv Fentanyl 2-4 microgram/kg the patient
remains drowsy but conscious and his co-
operation can be commanded.
3. It is opiate used for induction of anesthesia
4. Depress respiratory function
5. Nausea, vomiting and itching often occurs
during recovery, the Opiod antagonist
Naloxone can be used to reverse the problem.

95. KETAMINE
1. Used for induction of anesthesia
2. Cause emergent delirium and hallucination
3. Cause cardiovascular stimulation
4. Increase intracranial pressure (ICP)
5. Respiration is not depressed, airway reflexes
are maintained, muscle tone increases, limb
movements occur and eyes may remain
open.
6. Dose is 1.5mg/kg for iv or 5mg/kg for im
produces the effects within a minute and
recovery starts after 10-15 min but patient
remains amnestic 1-2 hours.

96. PREANAESTHETIC MEDICATION
 Preanaesthetic medication refers to the use
of drugs before anesthesia to make it more
pleasant and safe. The aim are:
1. Relief of anxiety
2. Amnesia for pre and postoperative events
3. Supplemental analgesic action to potentiate
them so that less anaesthetic is needed.

97. CONTINUED
4. Decrease secretions and vagal stimulations
5. Antiemetic effect
6. Decrease acidity and volume of gastric juice
so that it is less damaging if aspirated.

98. DRUGS
 Diazepam
 Lorazepam
 Promethazine
 Morphine
 Pethidine
 Atropine
 H2 blockers
 Metoclopramide
 Domperidone
 Ondansetron

99. LOCAL ANESTHETICS
 Local anesthesia provide regional
anesthesia.
 Local anesthesia can be grouped into:
1. Esters
2. Amides

100. ESTERS
 Esters drugs are the following:
1. Procaine
2. Cocaine
3. Benzocaine
 Esters of local anesthesia are metabolized
by plasma.

101. AMIDES
 Amides drugs are:
1. Lidocaine
2. Pupivacaine
3. Mepivacaine
 Amides of local anesthesia are metabolized
in by liver.

102. SIDE-EFFECTS
 Neurotoxicity
 Nausea
 Vomiting
 Cardiovascular toxicity
 Allergies

103. OPIOD ANALGESICS & ANTAGONISTS
 Algesia (pain) is an ill defined, unpleasant
sensation, usually evoked by an external or
internal noxious stimulus.
 Analgesic is a drug that selectively relieves pain
by acting in the CNS or on peripheral pain
mechanisms without significantly altering
consciousness.

104. CLASSIFICATION
 Analgesics are divided into two groups:
1. Opiod/narcotic/morphine like analgesics
2. Nonopiod/non-narcotic/Aspirin like
analgesic drugs

105. OPIOD ANALGESICS
 Opium: a dark brown, resinous material
obtained from poppy (papver somniferum)
capsule.
 Opiod analgesics contains two types of
alkaloids:
1. Phenanthrene derivatives
2. Benzoisoquinoline derivatives

106. DRUG CLASSIFICATION
 Phenanthrene derivatives
1. Morphine 10% opium
2. Codeine 0.5% opium
3. Thebaine 0.2% opium
 Benzoisoquinoline derivatives
1. Papaverine 1%
2. Noscapine 6%

107. DRUG CLASSIFICATION 2
1. Natural opium alkaloids
a. Morphine
b. Codeine
2. semi-synthetic opiates
a. Diacetylmorphine (Heroin)
b. Pholcodeine
3. Synthetic opiods
a. Methadone
b. Tramadol
c. Fentanyl

108. MORPHINE
 Morphine is the principle alkaloid in opium
and still widely used, therefore, it is
described as prototype.

109. PHARMACOLOGICAL ACTIONS
1. Central nervous system
 Analgesia
 Sedation
 Mood and subjective effects
 Respiratory centre
 Cough centre
 Temperature regulating centre
 Vasomotor centre

110. CONTINUED
2. Neuro-endocrine: the sex hormones like LH,
FSH, ACTH and corticosteroids levels are
lowered while prolactin and growth hormone
levels are raised in the short term but tolerance
develops in the long term.
 Morphine can release ADH and reduce urine
volume.

111. CONTINUED
3. Cardiovascular system: morphine causes
vasodilatation due to:
a. Histamine release
b. Depression of vasomotor centre
c. Direct action decreasing tone of blood
vessels.
 Intracranial tension tends to raise as a
consequence of carbon dioxide retention
leading to cerebral vasodilation.

112. CONTINUED
4. GIT: Constipation is a prominent feature of
morphine action, decrease in all
gastrointestinal secretions and reduction in
transfer of water and electrolytes from
mucosa to the lumen, absorption of fluid is
increased.

113. CONTINUED
5. Urinary bladder: tone of both detrusor and
sphincter is increased, urinary urgency and
difficulty in micturition.
6. Uterus: the action is clinically insignificant and
may slightly prolong labour.
7. bronchi: morphine releases histamine which
can cause bronchoconstriction.

114. ADVERSE EFFECTS
 Sedation
 Nausea
 Vomiting
 Urticaria, itching
 Apnoea
 Tolerance and dependence
 Fall in Bp

115. MORPHINE POISONING
 It is an accidental, suicidal or seen in drug
abusers. In the non-tolerant adult, 50mg of
morphine i.m produces serious toxicity.
 The human lethal dose is estimated to be
about 250mg.
 Coma, shallow of breathing, cyanosis,
pinpoint pupil, fall in Bp and shock,
convulsions may be seen in few, pulmonary
edema and death is due to respiratory
failure.

116. TREATMENT
 I.v fluids
 Vasoconstrictors
 Gastric lavage with potassium permanganate
 Naloxone 0.4-0.8mg i.v repeated every 2-3
minute till the respiration picks up.

117. CODEINE
 It is a methyl morphine, occurs naturally in
opium and partly converted in the body to
morphine.
 Codeine has very slow affinity for Opiod
receptors.
 However, it is more selective cough
suppressant and has mild analgesic effect.
 Codeine has been used for diarrhea and it is
prominent side-effect is constipation.
 Dose: 10-20mg BID, TID.

118. TRAMADOL
 Tramadol is indicated for mild to moderate short
lasting pain due to injury, surgery and cancer
pain.
 Injected i.v 100mg tramadol is equianalgesic to
10mg i.m morphine.
 Tramadol causes less respiratory depression,
sedation, constipation, urinary retention than
morphine.
 Dose: available in 50mg cap, 100mg tab, 1 & 2
ampoule injection.

119. CONTINUED
 Tramadol can be used for different disorders:
1. As analgesic Opiod
2. Preanaesthetic medication
3. Relief of anxiety
4. Cough
5. Diarrhea

120. OPIOD ANTAGONISTS
 Nalorphine
 Pentazocine
 Butorphanol
 Buprenorphine
 Naloxone
 Naltrexone
 Nalmefene

121. NALOXONE
 It is a N-alylnor-oxymorphone and a
competitive antagonist on all types of opiod
receptors. It blocks mu, kappa, and delta
receptors.
 Injected intravenously 0.4-0.8mg, it promptly
antagonizes all actions of morphine.
 Naloxone is inactive orally because of high
first pass metabolism in liver.

122. CONTINUED
 Plasma half life is one hour when injected adults
and three hour when injected newborns.
 Adverse effects of naloxone are uncommon
and may include rise in Bp and pulmonary
edema.
 Dose: 0.4mg in 1ml inj (adult) & 0.04mg in 2ml
inj (infant).

123. USES OF NALOXONE
 Naloxone is the drug of choice in morphine
poisoning (04-0.8mg i.v every 2-3 minutes)
 For reversing neonatal asphyxia
 Reversing respiratory depression
 Reverse alcohol intoxication
 Elevate the blood pressure

124. ABUSE LIABILITY OF OPIOD ANALGESICS
 Tolerance
 Dependence
Withdrawal
1. Yawning
2. Lacrimation
3. Rhinorrhea
4. Salivation

125. CONTINUE
 Anxiety
 Sweating
 Muscle cramps
 Spasms
 CNS originating pain

126. MANAGEMENT WITHDRAWAL
 Supportive
 Methadone
 Clonidine

127. PARKINSONIAN DISEASE
 Parkinsonism is an extrapyramidal motor
disorder characterized y rigidity, tremor and
hypokinesia with secondary manifestations
like defective posture and gait, mask like face
and sialorrhoea and dementia may
accompany.
 If untreated the symptoms progress over
several years to end stage disease in which
the patient is rigid unable to move, unable to
breathe properly, succumbs mostly to chest
infections or embolism.

128. DRUGS USED FOR PARKINSON DISEASE
 Parkinson disease (PD) is the degeneration
of nigrostriatal dopamine tracts with
imbalance between dopamine and acetyl
choline.
 Signs & symptoms of PD:
1. Bradykinesia
2. Muscle rigidity
3. Tremor

129. CONTINUED
 Belladonna alkaloids had been empirically
used in PD. A breakthrough was made in
1967 when Levodopa was found to produce
dramatic improvement.

130. CONTINUE
 Dopamine Agonist
1. psychosis
2. Nausea
3. Vomiting
4. Dyskinesias
5. Hypoprolactemia

131. CONTINUE
 Dopamine Antagonist
1. Decrease cognitive function
2. Gynecomastia
3. Amenorrhea
4. Galactorrhoe

132. CLASSIFICATION OF DRUGS
 drugs affecting brain dopaminergic system
1. Dopamine precursor: Levodopa
2. Peripheral decarboxylase inhibitors:
Carbidopa, benserazide.
3. Dopaminergic agonists: Bromocriptine,
ropinirole, pramipexole
4. MAO-B inhibitor: Selegiline
5. COMT inhibitors: Entacapone, Tolcapone
6. Dopamine facilitator: Amantidine

133. CONTINUED
 Drugs affecting brain cholinergic system
1. Central Anticholinergic: Trihexyphenidyl
(Benzhexol), procyclidine, Biperidine.
2. Antihistamines: Promethazine,
orphenadrine.

134. MECHANISM OF ACTIONS
 Drugs increase the dopamine level.
1. Levodopa
2. Carbidopa
3. Bromocriptine
4. Pergolide
 Drugs decrease the acetylcholine level.
1. Benztropine
2. Trihexyphenidyl
3. Diphenhydramine

135. LEVODOPA
 It is a precursor converted to dopamine by
aromatic amino acid decarboxylase (AAAD).
 Usually given with Carbidopa.
 Side-effects include:
1. Dyskinesias
2. Psychosis
3. Hypotension
4. Vomiting

136. BROMOCRIPTINE
 Use in hyperprolactemia
 Side-effects are like;
1. Dyskinesias
2. Psychosis

137. AMANTIDINE
 It is an anti-viral drug, which block muscarinic
receptors and increase dopamine function.
 Side-effects is atropine like.

138. INTRODUCTION TO ANTIPSYCHOTICS
 Schizophrenia is a mental disorder
characterized by a breakdown of thought
processes and by a deficit of typical
emotional responses.
 Common symptoms include auditory
hallucinations, paranoid or bizarre
delusions, or disorganized speech and
thinking, and it is accompanied by
significant social or occupational
dysfunction.

139. MANIA
 Mania is a state of abnormally elevated or
irritable mood, arousal, and/or energy levels.
In a sense, it is the opposite of depression.
Mania is a necessary symptom for certain
psychiatric diagnoses. The word derives from
the Greek (mania), "madness.

140. DEPRESSION
 Depression is a state of low mood and
aversion to activity that can affect a person's
thoughts, behavior, feelings and sense of
well-being. Depressed people may feel
sad, anxious, empty, hopeless, worried,
helpless, worthless, guilty, irritable, hurt,
or restless.

141. CONTINUED
 They may lose interest in activities that once
were pleasurable, experience loss of appetite
or overeating, have problems concentrating,
remembering details, or making decisions,
and may contemplate or attempt suicide.
Insomnia, excessive sleeping, fatigue, loss of
energy, or aches, pains, or digestive
problems that are resistant to treatment may
also be present.

142. ANXIETY
 Anxiety is an unpleasant state of inner
turmoil and apprehension, often
accompanied by nervous behavior, such as
pacing back and forth, somatic complaints
and rumination.
 It is the subjectively unpleasant feelings of
dread over something unlikely to happen,
such as the feeling of imminent death.

143. PHOBIA
 A phobia meaning "fear" is a persistent fear
of an object or situation in which the sufferer
commits to great lengths in avoiding, typically
disproportional to the actual danger posed,
often being recognized as irrational.
 In the event the phobia cannot be avoided
entirely, the sufferer will endure the situation
or object with marked distress and significant
interference in social or occupational
activities.

144. ANTIPSYCHOTIC AND ANTIMANIC
AGENTS
 An antipsychotic (or neuroleptic) is a
psychiatric medication primarily used to
manage psychosis including:
 Delusions
 Hallucinations
 Disordered thought, particularly in
schizophrenia and bipolar disorder
 Non-psychotic disorders

145. CONTINUED
 A first generation of antipsychotics, known as
typical antipsychotics, was discovered in
the 1950s. Most of the drugs in the second
generation, known as atypical
antipsychotics, have been developed more
recently, although the first atypical
antipsychotic, clozapine, was discovered in
the 1950s and introduced clinically in the
1970s.

146. CONTINUED
 Both generations of medication tend to block
receptors in the brain's dopamine pathways,
but atypicals tend to act on serotonin as well.
 Most antipsychotic drugs are readily but
incompletely absorbed. Many of these
drugs undergo significant first-pass
metabolism.

147. DRUG CLASSIFICATION
Typical
1. Phenothiazines
 Chlorpromazine
 Triflupromazine
 Thioridazine
 Trifluoperazine
 Fluphenazine

148. CONTINUED
2. Butyrophenones
 Haloperidol
 Trifluperidol
 Penfluridol
3. Thioxanthenes
 Flupenthixol
4. Others
 Pimozide
 Loxapine

149. CONTINUED
 Atypical antipsychotics
1. Clozapine
2. Risperidone
3. Olanzapine
4. Quetiapine
5. Aripiprazole
6. Ziprasidone

150. PHARMACOLOGICAL ACTIONS
1. CNS
 Reduces irrational behavior, agitation, and
aggressiveness, disturbed thought and
behavior are gradually normalized, anxiety
is relieved. Hyperactivity, hallucination, and
delusions are suppressed.

151. CONTINUED
2. ANS
 Neuroleptics block the alpha adrenergic
receptors, and they are weak inhibitors of
acetylcholine.

152. CONTINUED
3. CVS
 Neuroleptics produce hypotension, the
hypotensive action is more marked after
parenteral administration and roughly
parallels the alpha adrenergic blocking
potency.

153. CONTINUED
4. Skeletal Muscles
 The Neuroleptics reduce certain types of
spasticity and the site action is being in the
basal ganglia or medulla oblongata.

154. CONTINUED
5. Endocrine System
 Neuroleptics consistently increase the
prolactin level, by blocking dopamine
receptors, they also reduce gonadotropin
releasing hormones and ACTH is also
reduced.

155. THERAPEUTIC USES
 Schizophrenia
 Mania
 Radiation emesis
 Anxiety
 As antiemetic
 To potentiate hypnotics, analgesics, and
anesthesia
 Tetanus
 Alcoholic hallucinosis
 Tourette syndrome

156. FLUPHENAZINE
 It is a prescription over medication drug
 It is available in 25mg/ml inj
 Fluphenazine has a minimum autonomic
action.
 Hypotension, sedation, and lowering seizure
threshold is not significant.
 It is less likely to cause jaundice and
hypersensitivty.

157. HALOPERIDOL
 It is a potent antipsychotic with
pharmacological profile resembling that of
piperazine substituted phenothiazines.
 It is the preferred drug for acute
schizophrenia and Tourette syndrome.
 It is a prescription drug
 Haloperidol half life is 24 hours.
 It is available both oral and parenteral
dosage forms.

158. RISPERIDONE
 It is an antipsychotic drug which inhibits both
dopamine and serotonin receptors
 It is a prescription drug
 It also blocks alpha 1,2 and histamine
receptors.
 Prolactin levels rise during risperidone
therapy.
 It is available both oral and parenteral
dosage forms.

159. CLOZAPINE
 It is a prescription drug
 It is an atypical anti-psychotic drug
 It suppresses both positive and negative effects
of schizophrenia
 It does not arise prolactin level
 It is a quite sedating drug
 It inhibits dopamine and serotonin receptors,
and has some inhibition of alpha receptors.
 It has average half life 12 hours

160. M.O.A
 All anti-psychotics except clozapine have
potent dopamine, D2 receptor blocking
agent.
 Blockade of dopamine and serotonin
receptors.

161. ADVERSE EFFECTS
 Akathisia (constant discomfort to a varying
degree causing restlessness),
 Tremor, and abnormal muscle contractions, an
involuntary movement disorder known as
tardive dyskinesia
 Elevations in prolactin (resulting in breast
enlargement in men, breast milk discharge, or
sexual dysfunction).
 Metabolic syndrome
 White blood cell reduction

162. DRUGS USED FOR DEPRESSION
 Depression is caused by:
1. Decrease of serotonin
2. Decrease of nor-epinephrine
3. Decrease of dopamine
 Anti-depressants are classified into:
1. mono-amine oxidase inhibitors (MAOI)
2. Tricyclic anti-depressants (TCAs)
3. Selective serotonin reuptake inhibitors
(SSRIs).

163. MONOAMINE OXIDASE INHIBITORS
 Monoamine oxidase inhibitors are:
1. Phenelzine
2. Tranylcypromine
 Mechanism of action
1. Inhibition of MAOA & MAOB.
2. Increase norepinephrine
3. Increase serotonin
 It is used for atypical depression.

164. SIDE-EFFECTS
 Increase BP, arrhythmias
 Sweating
 Rigidity
 Hyperthermia
 Seizure

165. TRICYCLIC ANTIDEPRESSANTS
 Tricyclic antidepressants are:
1. Amitriptyline
2. Imipramine
3. Clomipramine
 Mechanism of action
1. Increase serotonin
2. Increase nor-epinephrine

166. THERAPEUTIC USES
 Major depression
 Phobia
 Panic anxiety states
 Obsessive compulsive disorders (OCD)
 Neuropathic pain
 Enuresis

167. TOXICITY
 Coma
 Convulsion
 Cardiotoxicity

168. SELECTIVE SEROTONIN REUPTAKE INHIBITORS
 Selective serotonin reuptake inhibitors drugs
are the following:
1. Fluoxetine
2. Paroxetine
3. Sertraline
Mechanism of action is:
1. Decrease serotonin level

169. THERAPEUTIC USES
 Major depression
 OCD
 Bulimia
 Anxiety disorders
 Premenstrual dysphoric disorder (PMDD)

170. SIDE-EFFECTS AND TOXICITY
 Side-effects
1. Anxiety
2. Agitation
3. Bruxism
4. Sexual dysfunction
5. Weight loss
 Toxicity
1. Sweating
2. Rigidity

171. BIPOLAR DISORDERS
 Lithium
1. Remains the drug of choice of bipolar
disorders.
2. It decreases cyclic AMP.

172. SIDE-EFFECTS
 Tremor
 Flu like symptoms
 Seizure
 Hypothyroidism
 Teratogenicity

173. DRUG USED IN ATTENTION DEFICIT HYPERACTIVITY
DISORDER
 Methylphenidate: it is an amphetamine like
drug.
 Side-effects
1. Agitation
2. Restlessness
3. Insomnia
4. Cardiovascular toxicity
 Atomoxetine: selective increase in nor-
epinephrine.

174. ALCOHOL CASE STUDY
 ID/CC: A 48 year old male complains his doctor
about increasing anxiety, insomnia, irritability,
and severe cravings for alcohol.
 HPI: The patient, two bottle day drinkers for 20
years, recently quit drinking of alcohol. He
claims that he is not longer able to relax and
has been having problems with his wife
(impotence) and at work due to impulsiveness.
 Labs: hypercholestremia, hypertriglyceridemia


175. TREATMENT
 Management of alcohol withdrawal can be
pharmacological and non- pharmacological
treatment. Pharmacological, the drug of
choice is Disulfiram, non-pharmacological
treatments includes, taking more fluid,
exercise, psychological consultation.

176. DISCUSSION
 Discussion: Alcohol produces serious
addiction and long lasting cravings upon
quitting. Alcohol produces CNS depression,
metabolic acidosis, ocular damage,
respiratory depression, acetylaldehyde
toxicity.

177. IMIPRAMINE CASE STUDY
 ID/CC: A 5 year old male is rushed to the emergency
department after his mother found him playing with
her purse, where she carries her antidepressants
(Imipramine); she noticed that the boy had swallowed
a handful of pills.
 HPI: The child complained of dry mouth, blurred
vision, and hot cheeks (Anticholinergic effect); he
also complained of palpitations (due to arrhythmias).
 PE: Tachycardia, fever, patient confused, pupils
dilated skin warm and red.
 Labs: Normal

178. CONTINUE
 Discussion: Tricyclic antidepressants
(Imipramine, Amitriptyline) block the reuptake of
norepinephrine and serotonin are used for the
endogenous depression treatment. TCAs are
commonly taken by suicidal patients and are a
major cause of poisoning and death.
Intoxication or overdose may produce seizures
and myoclonic jerking with rhabdomyolsis.
Death may occur within few hours. Other side
effects are Anticholinergic (sedation, coma, and
xerostomia).

179. CONTINUE
 Treatment: Gastric lavage, activated
charcoal, Phygostigmine in selected cases.
Dialysis is not effective for TCA overdose
because TCAs have a wide volume of
distribution. Treat arrhythmias.

180. CARBAMAZEPINE CASE STUDY
 ID/CC: A 45 year old female comes to her family
physician for an evaluation of frequent upper
respiratory infections and gum bleeding; she
also complains double vision, nausea, vomiting,
sleepiness, and dry mouth as well as difficulty
walking.
 HPI: she has been suffering trigeminal neuralgia
and she has been taking by Carbamazepine for
several months.
 PE: Ataxia, mydriasis
 Labs: decreased platelet.

181. TREATMENT & DISCUSSION
 Treatment: Switch to phenytoin. Consider
alternative treatment options for trigeminal
neuralgia.
 Discussion: Trigeminal neuralgia is
sometimes seen in association with multiple
sclerosis, primarily in younger patients.
Carbamazepine is chemically similar to
Imipramine and has been used for trigeminal
neuralgia as well as for the treatment of
partial and tonic clonic seizures.

182. CAFFEINE INTOXICATION
 ID/CC: A 6 year old girl is brought to the
pediatric emergency room because she
accidentally consumed large quantities of her
sisters Vivarin stimulant pills.
 HPI: The child, a healthy girl with no previous
medical history, mistook the pills for candy, as
they were in a non-child-proof container in the
kitchen cabinet.
 PE: Tachycardia, extreme restlessness, tremors
and nausea.

183. CONTINUE
 Labs: CBC: normal
 Imaging: CXR: normal
 Discussion: Caffeine is widely used as an
appetiate and sleep suppressant and as a
diuretic. It has a wide therapeutic index;
however, serious toxicity may result from
accidental ingestion of large quantities. Beta-
blockers effectively reverse the cardiotoxic
effects of excess catecholamine release and
stimulation.

184. CONTINUE
 Treatment: Monitor patient for ECG
changes. Treat tachycardia and possible
hypotension due to excess beta1 and beta 2
stimulation with propranolol or esmolol.

185. CLOZAPINE TOXICITY
 ID/CC: A 24 year old female of Somali
background complains to her family doctor of
repeated URIs (due to Neutropenia), increasing
fatigue, muscle aches, and headaches.
 HPI: She had been showing flattening of effect,
suspiciousness, a delusional mood, and
auditory hallucinations that were diagnosed as
schizophrenia 3 years ago. She has been
receiving Clozapine treatment because other
antipsychotics were unsuccessful.
 Treatment: Discontinue Clozapine and institute
alternate pharmacotherapy.

186. /
 PE: Fever, tachycardia, patient in obvious
discomfort; pallor (due to anemia); conscious
and oriented to person, place and time;
petechiae (due to thrombocytopenia) on
chest and arms; cardiopulmonary, abdominal
and genital exams normal; no extrapyramidal
signs.
 Labs: CBC: pancytopenia
 Imaging: CXR: no signs of lung infection

187. CONTINUE
 Discussion: Clozapine is used for the
treatment of schizophrenia and psychotic
disorders that are unresponsive to other
therapy.
 It blocks D1, D2, and D4 dopamine receptors
as well as serotonin receptors. Because of it is
low affinity for D2 receptors, Clozapine causes
few extrapyramidal symptoms.
 Agranulocytosis occurs in less than 2%
patients, but all patients must receive weekly
blood counts to monitor for this potentially lethal
effect. Other side-effects include seizures,

188. CONTINUE
 Agranulocytosis occurs in less than 2%
patients, but all patients must receive weekly
blood counts to monitor for this potentially
lethal effect. Other side-effects include
seizures, sedation, and Anticholinergic
symptoms. Agranulocytosis usually reverses
with discontinuation of Clozapine.

189. CONTINUE
 Discontinue Clozapine and institute alternate
pharmacotherapy.

190. COCAINE ABUSE
 ID/CC: A 32 year old stockbroker is brought
to the ER after police find him hiding in an
alley.
 HPI: The patient had been at a party with
several friends. He admits to indulging in
cocaine from a new dealer for the past 6
hours.
 PE: Hypertension, tachycardia, restless,
malnourished, and disoriented.

191. DISCUSSION
 Cocaine is a CNS stimulant and an inhibitor of
neuronal catecholamine reuptake mechanisms;
hence, it is use results in a state of generalized
sympathetic stimulation, with typical symptoms
including euphoria, anxiety, psychosis and
hyperactivity. Severe hypertension, ventricular
tachycardia, or fibrillation may also occur.
Angina pectoris in a young, healthy person is
suggestive of cocaine use. Myocardial infarction
secondary to coronary vasospasm and
thrombosis have been described as well.

192. TREATMENT
 Monitor vital signs and ECG for several
hours. There are no speacific antidotes for
cocaine use. Propranolol may be used with a
vasodilator for treatment of hypertension and
tachyarrhythmia’s. Dialysis and
hemoperfusion are not effective.

193. LITHIUM SIDE EFFECTS
 ID/CC: A 26 year old female who models for
photography magazines is referred to the
dermatologist by her family doctor because of
persistent acne that has been unresponsive to
the usual treatment.
 HPI: She also complains of constant thirst,
dryness of the mouth, and frequent urination.
She has been diagnosed with bipolar affective
disorder with manic predominance and was
recently started on lithium therapy.

194. CONTINUE
 PE: Sensorium normal; oriented and
cooperative; mouth is dry, no signs of present
depression or mania; face shows presence
of severe cystic acne on chin, forehead, and
upper chest with folliculitis.
 Labs: CBC: leukocytosis, pregnancy test
negative. ECG: T-wave inversion.

195. CONTINUE
 Discussion: Lithium is the preferred treatment
for the manic stage of bipolar affective disorder;
however, it is mechanism of action on mood
stability is still unclear. One possibility revolves
around lithiums effects on the IP3 second
messenger system in the brain. The onset of
action may take several days, and side effects
may be very bothersome, such as persistent
Polyuria and polydipsia (ADH antagonism),
weight gain and severe acne. It is
contraindicated in pregnancy due to its
Teratogenic effect.

196. TREATMENT
 Acne treatment with isotretinoin
(Teratogenic), chronic, low dose tetracycline,
benzoyl peroxidase.

197. MAO-SSRI INTERACTION
 ID/CC: A 40 year old male was brought into
the ER by his sister, who reported that he
had dropped by her apartment acting drunk
and agitated.
 HPI: The patient was diagnosed as suffering
from major depressive disorder 1 month ago
and had been on Phenelzine (MAO inhibitor)
for 3 weeks. He was switched to Paroxetine
(SSRI) last week.

198. CONTINUE
 PE: Fever, hypertension, tachycardia,
tachypnea, disoriented, agitated, diaphoretic,
neurologic exam reveals hyperreflexia,
resting hand tremor and rigid extremities.
 Labs: ABGs: metabolic acidosis

199. CONTINUE
 Discussion: Serotonin syndrome is
characterized by an excess of serotonin in
the blood stream. The combination most
frequently leading to serotonin syndrome is a
monoamine oxidase inhibitor given with an
SSRI. Other drugs that can precipitate
serotonin syndrome in combination with an
MAO inhibitor or an SSRI include opiods
(dextromethorphan, meperidine) and street
drugs such as cocaine and LSD.

200. CONTINUE
 In severe cases, serotonin syndrome
progresses to seizures, disseminated
intravascular coagulation (DIC), renal failure,
coma, and death. Tyramine containing foods
such as cheeses and beer in combination
with an MAO inhibitor, can also cause a
hypertensive crisis. Patients should stop
using an MAO inhibitor at least 14 days
before starting SSRI therapy.

201. CONTINUE
 Treatment: External cooling; supportive
care; IV benzodiazepines for agitation and
seizures, anti-hypertensives.

202. CONTINUED
THANK YOU…