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)
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.
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.
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
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.
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
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
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.
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.
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
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.
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
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
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
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.
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.
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.
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.
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.
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.
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.
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.
