CHAPTER

4 Autacoids
These are the substances produced by wide variety of cells that act locally at the site of

Autacoids

Amine Lipid Peptide

Histamine Prostaglandins Bradykinin
Serotonin Leukotrienes Angiotensin
Platelet activating factor Kallidin

HISTAMINE

Histamine is synthesized from histidine and is stored within the storage granules of mast cells.
It acts mainly on H1 and H2 receptors. Recently H3 (presynaptic) and H4 receptors have also
Histamine is synthesized from
been isolated. histidine

ACTIONS
It causes dilation of small blood vessels and can result in . Fall
in blood pressure is mediated by both H1 as well as H2
receptors.
It through stimulation of H1 receptors.
Intradermal injection may result in consisting of red reaction (due to
Histamine induced fall in blood
(spreading redness ). It is primarily an H1 response. pressure is mediated by both H1
H1 receptor stimulation has effect (early) as well as H2 (delayed
and persistent) receptors.
whereas H2 stimulation of isolated heart. Effect on
intact heart is not prominent.
Histamine is a powerful contractor of visceral smooth muscles through H1 receptors
and results in
Histamine by stimulation of H2 receptors.
It stimulates nerve endings and may result in
Histamine synthesized within the brain
(through H1 receptors). H3 receptors are pre-synaptic in
location and inhibit the release of histamine. Inverse agonist or antagonist of these
receptors may increase histamine leading to wakefulness. Pitolisant (tiprolisant) is
such a drug approved for Narcolepsy.
Intradermal injection of histamine
It serves as a may result in triple response
Betahistine is an oral histamine analogue used in Meniere’s consisting of
disease ed reaction (due to
Some basic drugs like vasodilation).

H4 receptors are present in hematopoietic cells like eosinophils, basophils and mast to increased permeability)
cells. These promote chemotaxis. antagonists of these receptors are being developed Flare (spreading redness due
for allergic conditions. ).

H1 Anti-Histaminics
These drugs act as competitive antagonists at H1

anticholinergic properties.

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First generation anti-histaminics
are contraindicated in persons
requiring constant attention.
N
Tiprolisant is H3 inverse agonist
used for Narcolepsy
Uses of H1 blockers (First
Generation) based on anti-
cholinergic properties
Possess - Parkinsonism
Anti - Acute muscular
dystonia
Cholinergic - Common cold
Properties -P
motion sickness
Autacoids
- (dryness of mouth, blurred vision, urinary retention, constipation etc.)
pressant having most potent H1
blocking action (800 times more
potent than diphenhydramine).
Terfenadine and Astemizole
result in polymorphic ventricu-
lar tachycardia (Torsades de’
pointes) manifested as prolon-
gation of QTc interval.
112
(A) FIRST GENERATION ANTI-HISTAMINICS
These drugs and thus result in sedation and psychomotor
impairment. Therefore, these drugs are
(like truck drivers, machinery operators and swimmers).
.
This property is responsible for their wide spectrum of uses and more adverse effects than
Highly sedating Moderately sedating Mildly sedating
Diphenhydramine Pheniramine Chlorpheniramine
Dimenhydrinate Cyproheptadine Mepyramine
Promethazine Meclizine Cyclizine
Buclizine Clemastine
Cinnarizine
Uses
Based on H1 blocking action Based on anticholinergic properties Other uses
1. Allergic conditions like itch- 1. Common cold (to control rhinor- 1. Antihistaminics are
ing, urticaria, hay fever etc. rhoea) drug of choice for idi-
2. Insect bite, ivy poisoning 2. Motion sickness (as prophylactic opathic pruritis
and to prevent the adverse agents) 2. Cinnarizine is useful in
effects due to histamine re- 3. Parkinsonism (promethazine may be vertigo.
leasers. used)
4. Acute muscular dystonia
Adverse Effects
(B) SECOND GENERATION ANTI-HISTAMINICS
anticholinergic activity. Some drugs like cetirizine and azelastine possess additional anti-
allergic mechanisms. These drugs (can be used in truck drivers)
but their use is also restricted to antiallergic effects.
IMPORTANT DRUGS
Terfenadine is the fastest acting antihistaminic drug. In overdose, it blocks cardiac
+ channels and may result in polymorphic ventricular tachycardia
(torsades de’ pointes) manifested as prolongation of QTc interval. Use of this drug
with microsomal enzyme inhibitors like ketoconazole, erythromycin, clarithromycin
and itraconazole increases the risk of this arrhythmia. Terfenadine is metabolized
to an active metabolite “fexofenadine” +
channel blocking property.
astemizole is slowest and longest acting agent and possesses arrhythmogenic
property similar to terfenadine. Therefore, it should not be administered with
ketoconazole, erythromycin, clarithromycin and itraconazole.
is another second generation antihistaminic and is metabolized
to (available as a separate drug).
Cetirizine
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 Autacoids

. It possesses additional anti-allergic mechanisms like inhibition of Some authorities describe

release of cytotoxic mediators from platelets and inhibition of chemotaxis. Some the term 3rd generation
persons acquire sedative effects with cetirizine. is l-isomer of cetirizine antihistaminics for the active
that is more potent and less sedative. enantiomer (like levo-cetirizine)
or metabolite (e.g. desloratidine
possesses and can be given by nasal spray for
allergic rhinitis. generation drugs.
and are other
second generation antihistaminic agents.
Olopatadine is a recently approved topical H1-antihistaminic used as nasal spray for
seasonal allergic rhinitis.
Alcaftadine is approved as ophthalmic solution for allergic conjunctivitis.
Triphasic response of sero-
SEROTONIN tonin
5-hydroxytryptamine (serotonin) is synthesized from tryptophan. It is produced by
hydroxylation followed by decarboxylation of tryptophan; steps similar to catecholamine -
synthesis. It is similarly stored in the vesicles and its action is terminated by reuptake. It acts constriction)
by activation of several serotonin receptors (5- HT1 - HT7 receptors).
(due to arteriolar dilation)
ACTIONS
On i.v. injection, it produces . Early sharp fall

prolonged fall (due to arteriolar dilation) in blood pressure is seen.

GeneralAutacoids
Serotonin is a powerful stimulator of smooth muscles. It

It has by decreasing acid secretion and increasing mucus production.

5-HT is

Pharmacology
Serotonin increases

Receptors

5 HT1 5 HT2A/2C 5 HT3 5 HT4

5 HT1A 5 HT1B/1D
Presynaptic Cause constriction of cra- Inotropic receptor (all Present in GIT
autoreceptor nial vessels direct actions of serotonin others 5 HT receptors are
G-protein coupled receptors) increase in peristalsis

Modulates the realse Ketanserin and ritanserin

of serotonin (antagonists) are useful as and indirect actions of sero-
antihypertensive agents tonin

Partial agonist of this Agonists at this receptor Clozapine and risperidone Antagonists like ondanse- Agonists (cisapride,
receptor (buspirone, (sumatriptan, naratriptan) are atypical antipsychotic tron, grainsetron and tro- mosapride, renzapride,
isapirone, gepirone) are useful for the treat- agents that act through pisetron are the agents of tegaserod) are useful in
are useful as antian- ment of acute migraine antagonistic activity at this choice for chemotherapy the treatment of gastroe-
xiety drugs attacks receptor. induced vomiting

NON-SELECTIVE DRUGS
Cyproheptadine 2a, H1 and muscarinic receptors. It increases appetite
and can be used in children to
Methysergide: It is a 5 HT antagonist and a 5 HT1 agonist. It is indicated for the
attacks but prolonged use

LSD: It is an ergot derivative and a . It acts as an agonist at

several serotonin receptors including 5 HT1a, 5 HT and 5 HT5-7 receptors.
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can cause dry
gangrene of hand and feet and
coronary vasospasm.
Sumatriptan is the drug of choice
for aborting acute attack of
migraine.
Frovatriptan is the longest acting
and rizatriptan is the fastest
acting 5HT1B/1D agonist.
Both triptans and ergot alkaloids
can cause coronary vasospasm
and are contraindicated in
ischemic heart disease.
Autacoids
Triptans and ergotamine should
not be administered within 24
hours of each other.
Propanolol is the most com-
monly used drug for prophy-
114
ERGOT ALKALOIDS
These are derived from a fungus . Important compounds are
. These
drugs possess partial agonistic and antagonistic effect at 5HT, and dopaminergic receptors.
These drugs are only blockers that can cause vasoconstriction due to their partial agonistic
activity on and 5HT2 receptors (maximum with ergotamine). Hydrogenation of the
compound decreases agonistic activity but increases the blocking potential. Therefore
dihydroergotamine has very little vasoconstricting activity. Ergot derivatives
Ergotamine and dihydroergotamine are used for the treatment of
. These are (due to their
propensity to cause coronary vasospasm).
Dihydroergotoxine (codergocrine) is useful for the treatment of
Bromocriptine is useful in
Methysergide is useful for the
Migraine
require ergot alkaloids or triptans for termination.
Ergotamine ( ) or dihydroergotamine (parenteral) can be used to
abort acute attack of migraine. Caffeine of ergotamine and
is a . It is usually combined with ergotamine. These drugs
however,
.
It acts as a selective agonist at 5 HT receptors. It also suppresses the vomiting
of migraine. It is a short acting drug and has low oral bioavailability.
. Other drugs useful
are . all of these drugs can cause
coronary vasospasm and are . Triptans are
also contra-indicated in patients with , , ,
.
Maximum Minimum
Naratriptan Sumatriptan
Frovatriptan Sumatriptan
Frovatriptan (slowest)
Sumatriptan
binding
therefore opioids like intranasal butorphanol should be used for acute severe
migraine.
drugs useful for prophylaxis are:
Propanolol is the most commonly used drug for prophylaxis of migraine
attacks. Timolol, atenolol, metoprolol and nadolol can also be used but the
drugs with ISa (e.g. pindolol) are ineffective.
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 Autacoids

+
channels) is also
effective
Methysergide, cyproheptadine and TCAs like amitriptyline can also be used.
Clonidine can be used orally for the prophylaxis of migraine attacks.
Topiramate (anticonvulsant drug) has recently been approved for prophylaxis
of migraine Valproate and gabapentin also possess some prophylactic activity.
Onabotulinum toxin A has recently been approved for prophylaxis when
headaches occur for more than 14 days per month. It is given every 12 weeks
as multiple injections around the head and neck to try to dull future headache
symptoms.

GeneralAutacoids
Pharmacology
PROSTAGLANDINS

Prostaglandins and thromboxanes are synthesized from arachidonic acid (obtained from
Phospholipase A2 is rate limiting
membrane phospholipids due to the action of phospholipase a2 ; rate limiting enzyme) with
enzyme in synthesis of prosta-
glandins.
COX-1 COX-2 COX-3
- -
present in Cells)

keeping function and fever

e.g. gastro-protec- kidney
tion
on apoptosis, stimulation of cell migration
and invasiveness.

2 2) in all cells.
Further fate of these compounds depends on the presence of different enzymes in the cells.
2
2 Various cells contain enzyme

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 2 2 2 . Corticosteroids
inhibit the enzyme phospholipase a2 by
annexins) NSAIDs

Actions

CNS
Autacoids

1 2

PERIPHERAL NERVE ENDINGS

2 2

CVS
2 2 2 2 are vasoconstrictor agents.
2 2

2 increases capillary permeability.

2 2 keeps ductus arteriosus patent. In some congenital heart diseases (like
transposition of great vessels), it becomes essential to keep ductus arteriosus patent
before surgery. For this indication, 1) 2) can be
given intravenously. If ductus arteriosus fails to close (patent ductus arteriosus) at
birth, like aspirin and indomethacin are given to close it.

PLATELETS
2 2
2
is synthesized in platelets and its synthesis cannot be resumed, once it is inhibited
Alprostadil is used to keep by NSAIDs 2 resumes after
ductus arteriosus patent
2 synthesis and
before surgery whereas NSAIDs
like aspirin and indomethacin can be used as an drug for the prophylaxis of MI and
are used for treatment of. Patent
stroke.
ductus arteriosus
2) can be used as an -
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 Autacoids

. It can also be used for storage of platelets for transfusion.

UTERUS PGI2 Inhibits platelet aggregation

2 2 are powerful uterine stimulants (contractor). whereas TXA2 is a potent aggre-
can be used gator of platelets.
2
. Misoprostol (PGE1) along with methotrexate or mifepristone
is used
2 causes softening of cervix (cervical ripening) during labour.
intravaginally are employed for .
2 ) can be used to (contraction of uterus
leads to compression of blood vessels resulting in decreased bleeding).

are useful for relieving this pain.

Use of is associated with (abnormal
development of cranial nerves; most commonly VI and VII).

BRONCHUS
2 2 2 2 are bronchoconstrictor
agents.
aspirin acetylated COX-2 en-
2 has been used effectively
zyme can convert arachidonic
acid to 15-HETE -

asthma. 4 or 15-epi

GeneralAutacoids
4).These are called aspirin-
GIT triggered lipoxins and have
powerful bronchoconstrictor
2 2 decrease acid secretion and increase mucus production and mucosal
induction of asthma with aspirin

Pharmacology
[Remember, the drug of choice is proton pump inhibitors]
2 2 cause in the abdomen. These symptoms are
important side effects of these drugs. ?
Misoprostol is the most
drug whereas proton
pump inhibitors are drugs
KIDNEY of choice for the treatment of
peptic ulcer due to chronic
2 2 cause , and increased water clearance due
NSAID use.
.

of these drugs.
Bartter syndrome is characterized by leading to ,
. Indomethacin is used for
of this syndrome.

MALE REPRODUCTIVE SYSTEM

2 2 increases sperm motility and enhances penile erection.

EYE
2 decreases intraocular pressure
2 ) is being used as eye drops for glaucoma.

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Use of misoprostol in pregnancy
is associated with Moebius
syndrome
Most potent agent known to
cause increase in the capillary
permeability is platelet activating
facor.
Autacoids
PGF decreases intraocular
pressure by increasing the
Licofelone is combined COX-
LOX inhibitor that is being in-
vestigated as a disease modi-
fying anti-osteoarthritis drug
118
LEUKOTRIENES
These are synthesized from arachidonic acid with the help of the enzyme, 5-lipoxygenase.
This enzyme must associate with 5-lipoxygenase activating protein (FLAP) for leukotriene
4 4 or to
4 4 and E4). LTC are also known as
substance of anaphylaxis (SRS-A) due to their powerful bronchoconstricting action. LTB
Action of LTs can be inhibited by:
2)
)
)
PLATELET ACTIVATING FACTOR (PAF)
2 on cell membranes (phospholipase
a2 is also involved in the production of arachidonic acid). This substance is converted to
PAF most
.
decrease the production of PaF by inhibiting phospholipase a2
apafant and lexipafant are PaF antagonists that are being investigated for the
treatment of acute pancreatitis.
THROMBOXANE A2
2
aspirin 2
Daltroban and sultroban 2 receptor antagonists.
inhibits the enzyme thromboxane synthetase.
NON STEROIDAL ANTI INFLAMMATORY DRUGS (NSAIDS)
term use.
Classification
NON SELECTIVE COX INHIBITORS
(a) Paracetamol (Acetaminophen)
It because it is ineffective in the presence of
selective COX 3
inhibition in the brain. It produces very little GI toxicity and can be administered in patients
can combine with the enzymes and other biomolecules resulting in hepatotoxicity.
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 Autacoids

to presence of sulfur containing amino acid, cysteine) produced by the liver combines with

Paracetamol acts by inhibiting

alcohol is a powerful inducer of microsomal enzymes. It increases the production of

acetaminophen toxicity can be decreased by providing sulfhydryl donors like -

( ). acetaminophen overdose constitutes medical emergency and
N-acetylcysteine is antidote of
90% of patients will develop severe liver damage, if plasma concentration is greater than choice for paracetamol poising.
300 g/ml at 4 hours or 45 g/ml at 15 hours after ingestion.
charcoal) should be done to prevent further absorption but it is ineffective after 4 hours
of ingestion.

(b) Salicylates
aspirin is the only irreversible inhibitor

several other indications.

it acts as an and is useful in the prophylaxis
of myocardial infarction and stroke. It acts by inhibiting cyclooxygenase enzyme and
2 (platelet aggregator). However it also inhibits
2 2

2 is synthesized by and these

GeneralAutacoids
2. Very little aspirin reaches the systemic circulation to
2 synthesis.

Pharmacology
2 Paracetamol (acetaminophen)
2 generation.
and Nimesulide and nefopam
aspirin and indomethacin are useful for the closure of ductus arteriosus in children do not act by decreasing PG
with PDA (alprostadil is used to keep it patent). synthesis
aspirin is used to
It is also useful in
in
patients on long term aspirin therapy.

Adverse Effects
Salicylates can cause dose dependent effects on acid base balance. Respiratory
Aspirin is the only irreversible
(salicylism). Excessive metabolic compensation can result in inhibitor
metabolic acidosis manifested as loss of vision, hyperpyrexia, vasomotor collapse,
more in
infants because early symptoms like tinnitus and vertigo are frequently missed.
, gastric lavage, correction of
metabolic acidosis and urinary alkalinization to increase the excretion.
aspirin can prolong bleeding time and should be used cautiously with
anticoagulants.
At therapeutic doses, it can cause hyperuricemia by decreasing the excretion of
uric acid. It, therefore, should not be used in patients with gout. It also decreases the
uricosuric action of probenecid. at high doses (>5 g/d), it increases the excretion of
uric acid, but such high doses are not tolerated.
aspirin is contraindicated in children (<12 yrs old) due to increased risk of Reye’s
syndrome.

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 (c) Other Non-selective COX Inhibitors
At low doses (40-325 mg), it
acts as an antiplatelet drug Indomethacin 2 and possesses immunosuppressive properties apart

implicated in causing (analgesic causing pain) and . Treatment

with , combined with and is
associated with the symptoms and biochemical derangements of
Aspirin is contraindicated in
children (<12 yrs old) due to
increased risk of Reye’s syn-
causes agranulocytosis due to bone marrow suppression.
Propionic acid derivatives include

be used topically as eye drops. Ibuprofen has been cleared for paediatric patients.
are long acting drugs that also inhibit leucocyte
Sulindac and nabumetone are migration.
prodrugs.
Mefenamic acid 2 inhibitory
activity. It is very useful in dysmenorrhoea.
Phenacetin (prodrug of paracetamol) is implicated in causing analgesic
Ketorolac is the only NSAID nephropathy
that can be used i.v. Ketorolac

Piroxicam and tenoxicam

Piroxicam and tenoxicam are
longest acting NSAIDs due to possess potent uricosuric activity. It is indicated in conditions, in which
enterohepatic cycling.
Autacoids

PREFERENTIAL COX-2 INHIBITORS

group are nimesulide ( ), meloxicam, nabumetone ( ),

etodolac and diclofenac.
toxicity is experienced with the use of these drugs.

SELECTIVE COX-2 INHIBITORS

These drugs have advantage of very little GI toxicity. However renal toxicity is similar and
chances of thrombosis (acute MI and stroke) are increased on prolonged use.

Rofecoxib and valdecoxib were

withdrawn due to increased rash and hypersensitivity.
risk of thrombotic disorders like Etoricoxib is and monitoring of hepatic function is must during
myocardial infarction. its use.
Lumiracoxib
Parecoxib is a prodrug of valdecoxib that can be administered parenterally

Note:
except nabumetone.

(have no chiral center).

– Tolmetin is not effective in gout.

– Aspirin is less effective for ankylosing spondylitis.

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 Autacoids

Rheumatoid Arthritis

Rheumatoid arthritis (Ra) is an autoimmune multisystem disease.

A. Corticosteroids

GeneralAutacoids
B. Synthetic DMARDs

1. Methotrexate

Pharmacology
It is and is used at much lower doses (7.5 mg weekly) than required in
cancer chemotherapy (30 mg daily).

Adverse effects of methotrexate

Pancytopenia
Risk factors are:

Heavy alcohol consumption

Obesity is a prodrug (con-

verted in the body to an active
metabolite) that inhibits the en-
Interstitial pneumonitis (Hypersensitivity reaction) zyme dihydro orotate dehydro-
Teratogenicity genase.
Increased risk of B-cell lymphomas
amoxycillin and probenecid increase risk of methotrexate toxicity

2. Sulfasalazine
It is metabolized to . Former is the active moiety in
Ra and latter is useful for ulcerative colitis. It is used in patients when methotrexate is
contraindicated.
N
3. Leflunomide is dihydro-orotate
dehydrogenase inhibitor (like
It is a prodrug (converted in the body to an active metabolite) that
dihydro orotate dehydrogenase. This enzyme is required for pyrimidine synthesis and thus relapsing-remitting multiple
sclerosis.
. It is (action is manifested in 4 weeks as compared to 3 months with
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 .

4. Chloroquine and hydoxychloroquine

Hydroxychloroquine is the
chloroquine due to less chances of retinal damage by the former.

5. Minocycline

collagenase. Most common adverse effect of minocycline is dizziness.

6. Tofacitinib
It is an inhibitor of Janus kinase 3. Tofacitinib is approved for severe Ra refractory to

Tofacitinib is an inhibitor of must be done prior to receiving the drug

Janus kinase 3 and is approved
for severe rheumatoid arthritis
7. Old drugs
be given orally.

(aurothiomalate). . These

encephalopathy and bone marrow depression.

C. Biological DMARDs

1. TNF- blocking agents

Autacoids

plays a major role in the joint destruction in patients with Ra. Five drugs etanercept
(s.c.), adalimumab (s.c.), (i.v.), golimumab (s.c.) and (s.c.) act as
. These drugs can cause
is

Drug Dose Route Frequency

3–10 mg/kg Intravenous 0,2,6,10,14 weeks,
then every 8 weeks
50 mg Subcutaneous
Adalimumab 40 mg Subcutaneous
Golimumab 50 mg Subcutaneous Monthly
Certolizumab 200-400 mg Subcutaneous

2. Co-stimulation inhibitors
Abtacept and belatacept

Abatacept is a co-stimulation
inhibitor indicated for severe
refractory rheumatoid arthritis. inhibitors.

3. Tocilizumab
-
trexate.

122 4. Rituximab

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 Autacoids

It is a monoclonal antibody that depletes B-cells and is used for Ra in combination with
methotrexate
NSAIDs like indomethacin are
drug of choice for acute gout
Disease Modifying Anti-Osteoarthritis Drugs (DMAOAD)

destruction. Recently two compounds; Diacerin (IL-1 antagonist) and Licofelone (combined
Colchicine is more effective and
COX-LOX inhibitor) have been developed to slow the progression of the disease.
faster acting than NSAIDs

Gout

It is a disease characterized by elevated serum uric acid level. Uric acid has low water
solubility and gets precipitated in the joints, kidney and subcutaneous tissues. Secondary
hyperuricemia may result due to excessive production (breakdown of proteins and nucleic
acids during cancer chemotherapy) or decreased excretion (due to the use of thiazides, loop
diuret etc.) of uric acid.

Uses of Colchicine
U – U
of recurrent attacks of gouty
arthritis]
C – Cirrhosis

GeneralAutacoids
M – Mediterranean fever [Acute]
S – Sarcoid arthritis

Pharmacology
Dose of 6-Mercaptopurine
and azathioprine should be
decreased when given with
ACUTE GOUT allopurinol.

NSAIDs like indomethacin are due to better tolerability.

as it may cause hyperuricemia. Tolmetin is not effective.
Colchicine is due to Drugs decreasing uric acid
synthesis are contra-indicated in
acute gout
It (other drugs causing metaphase arrest are
). . It can also
cause

To prevent further attacks

along with urate-lowering therapy to suppress attacks precipitated by abrupt alkalinizers should be given
with probenecid to prevent
changes in serum uric acid precipitation of uric acid crystals
Intra-articular corticosteroids can be used in the refractory cases. in the kidney tubules.
anakinara, canakinumab and rilonacept

Makes
CHRONIC GOUT Xanthine
O
Strategies to decrease uric acid in the serum are to
STATic

FebuXOSTAT

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 Drugs Decreasing Synthesis
Allopurinol (hypoxanthine analog) and recently approved drug, febuxostat (a non-purine
drug) decrease the production of uric acid by . allopurinol
is metabolized by the same enzyme to alloxanthine which is a long acting inhibitor of
xanthine oxidase. These are indicated as drug of choice for chronic gout in the inter-critical
period (between two acute attacks) and also with anticancer drugs (to decrease secondary
are metabolized by xanthine oxidase;
therefore when given with allopurinol.
It is contra-indicated in
acute gout because uric acid has inhibitory effect on release of cytokines and allopurinol may

Recombinant
Bird's
Uricase
acute attack of gout.
Ras b uricase

administered without dose adjustment.

Drugs Increasing Excretion

acts as competitive inhibitors of

be given concurrently to prevent precipitation of uric acid crystals in the kidney tubules.
These drugs are . Probenecid is also used along
Autacoids

Uricosuric drugs should not be used if

History of nephrolithiasis (uric acid or calcium stones)

collection)

Drugs Increasing Metabolism

Urate oxidase (uricase) metabolizes insoluble uric acid to soluble allantoin in the birds.
This enzyme is absent in humans. rasburicase.
Pegloticase is another similiar drug that is pegylated to increase duration of action. Pegloticase
and rasburicase are administered by i.v. route and are indicated only in patients with chronic
gout refractory to other treatments.

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 Autacoids

DRUG OF CHOICE
Condition Drug of choice

– Acute-mild to modrate NSAIDs

– Acute-severe Sumatriptan
Propanolol
Mifepristone + misoprostol

Misoprostol
Proton pump inhibitors
Latanoprost
Alprostadil
Indomethacin
Indomethacin

– Pain relief NSAIDs

GeneralAutacoids
– Bridge therapy Corticosteroids

Aspirin
Aspirin

Pharmacology
N-Acetyl cysteine
Adrenaline
Colchicine
5HT3 antagonists like ondansetron

– Delayed Aprepitant

– Acute
Colchicine
– Chronic Allopurinol
– Chronic (in patient allergic to allopurinol)
Allopurinol

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 Multiple ChoiCe Questions
HISTAMINE AND SEROTONIN 8. All
through H1 receptors EXCEPT:
1. Wh -
ing in vasodilation

vasodilation
(d) Fexofenadine (c) Bronchoconstriction
(d) Release of catecholamines from adrenal medulla

(a) Histamine
(a) aspirin
(b) angiotensin II
(b) Procaine
(c) Bradykinin
(c) Morphine
(d) Renin
(d) Sulfadiazine
3. Ergometrine is commonly used for:
(a) Post Partum Hemorrhage anticholinergic property EXCEPT:
(b) To shorten 2nd stage of labour (a) Promethazine
(b) astemizole
(d) Toxemia of pregnancy
Autacoids

11. The drug possessing antagonistic action at histamine,

serotonin and muscarinic receptors is:
(a) Pheniramine (a) Promethazine
(b) Promethazine (b) Terfenadine

(d) Hydroxyzine

1
antihistaminic drug. He should be advised to avoid:

(b) Fexofenadine (c) Strenuous physical exertion

(d) all of the above
(d) acrivastine
TRUE about second
6. The H3 generation antihistaminic agents EXCEPT:
actions EXCEPT: (a) These do not impair psychomotor performance
(a) Inhibition of H1 receptor induced wakefulness (b) These possess high anti-motion sickness activity
(b) Increase in H1 mediated gastrin secretion (c) These lack anticholinergic actions
(c) Inhibition of H1 mediated bronchoconstriction (d) These may possess additional antiallergic mecha-
nisms

7. Second generation anti-histaminics used in allergic 14. This antihistaminic drug can cause cardiac arrhythmia
rhinitis are: at high dose by blocking cardiac K+ channels. It is most
(a) azelastine likely to be:
(b) Fexofenadine
(b) Fexofenadine
(c) astemizole
e
(e) Promethazine
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 Autacoids

1
and has prominent labyrinthine suppressant property
is: by antagonism of histamine EXCEPT:

(b) Insect bite

(d) Seasonal hay fever

(c) astemizole inhibits the metabolism of ketoconazole fact:

(d) astemizole antagonizes the antifungal action of ke- (a) Use of these drugs by addicts
toconazole
slowly
17. True statement about fexofenadine is:
(d) Treatment of these patients with erythromycin, a
(b) Terfenadine is an active metabolite of this drug
+ channels macrolide antibiotic

1 receptors

18. H1 antihistaminic having best topical activity is:

(a) Fexofenadine

(c) astemizole
(d) azelastine

GeneralAutacoids
19. All 5-HT receptors are heptahelical serpentine receptors
(a) 5HT1B antagonist
EXCEPT:
(b) 5HT2 antagonist
(a) 5-HT1
(c) 5HT1a agonist
(b) 5-HT2

Pharmacology
(d) 5HT antagonist
(c) 5-HT3
(d) 5-HT4 1 antihistaminic include

(b) astemizole
(a) 5-HT1a
(b) 5-HT
(c) 5-HT2a
(d) 5-HT3

induced vomiting is:

(a) Histamine H1 receptor
(c) ampicillin
(b) Serotonin 5-HT3 receptor
2 receptor
(d) Opioid receptor

4 agonist useful in gastroesophageal

(c) Methysergide
(a) Buspirone
(d) Tropisetron
(b) Sumatriptan
31. Antihistaminic used in motion sickness is:
(d) Tegaserod
(b) Meclizine

(d) Fexofenadine
(b) adrenaline
(c) Ranitidine (a) antiemetic
(d) Sumatriptan (b) anxiolytic
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 (c) analgesic 41. Selective 5-HT1B/1D receptor agonist useful in acute
(d) antidepressant migraine is:
33. Fexofenadine is metabolic product of: (a) Buspirone
(b) Ondansetron
(b) astemizole (c) Frovatriptan

(d) Terfenadine
34. Cisapride is useful in:
(a) Pulmonary hypertension

(c) Hepatotoxicity
(d) Ischemic heart disease
35. Histamine blocker in stomach act through:
43. Dihydroergotamine differs from ergotamine in the
(b) Increasing caMP in stomach
(a) It is a more potent oxytocic
(c) Increasing IP3 in stomach
stomach (b) It has antiemetic property
(c) It has high oral bioavailability
(d) It is more potent adrenergic blocker and less potent
ERGOT ALKALOIDS AND MIGRAINE
vasoconstrictor
36. After taking some drug for acute attack of migraine, a 44. Ergot alkaloid commonly used to prevent post-partum
patient developed nausea and vomiting. He also devel- hemorrhage is:
(a) Methyl ergometrine
(b) Ergotamine
Autacoids

(b) Sumatriptan
(c) aspirin 45. Choose the CORRECT statement about sumatriptan:
(d) Butorphanol (a) It activates 5-HT1a receptors
(b) It tends to suppress both pain and vomiting in mi-
(a) Propanolol graine
(b) Flunarizine (c) It does not carry risk of precipitating coronary vasos-
(c) Topiramate pasm
(d) It is combined with ergotamine for the treatment of
severe migraine
migraine except:
(a) Sumatriptan
(b) Valproate (a) Verapamil
(c) Propanolol
(d) Topiramate (c) Flunarizine
39. Drugs used for prophylaxis of migraine is/are: (d) amlodipine
(a) Flunarizine
47. Drugs used in migraine prophylaxis are all except:
(a) Flunarizine
(c) Beta blocker
(b) Propanolol
(d) Sodium valproate

(d) Sumatriptan
48. Sumatriptan is used in:
(a) Ergotamine (a) Mania
(b) Methysergide
(c) Schizophrenia
(d) Phenoxybenzamine (d) Migraine
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 Autacoids

49. Sumatriptan is: (c) Prothrombin time

(a) 5HT antagonist
(b) 5HT1a agonist 58. Misoprostol is a:
(c) 5HT agonist (a) Prostaglandin E1 analogue
(d) 5HT1a antagonist (b) Prostaglandin E2 analogue
50. Drug of choice in acute severe migraine is: (c) Prostaglandin antagonist
(a) Ergotamine (d) antiprogestin
(b) Sumatriptan EXCEPT:

(d) Propranol acid

51. Methyl ergometrine is used in the prophylaxis of II is induced by cytokines at the site of in-
(a) Migraine
(b) Postpartum hemorrhage I is an inducible enzyme
(c) PIH

(a) Phenylbutazone
(a) antagonist of serotonin (b) aspirin
(b) Interacts with alpha and beta adrenergic receptors (c) Ibuprofen
(c) Has antimigraine activity (d) Piroxicam

emergency department having consumed 10 g of par-

EICOSANOIDS AND NSAIDs
paracetamol level is reported as 400 micrograms/ml.

GeneralAutacoids
NOT TRUE about

(a) acetyl salicylic acid is an irreversible inhibitor of (b) administration of activated charcoal
(c) abnormalities of the kidney function are likely to be

Pharmacology
(b) acetylsalicylic acid reduces in vivo synthesis of present
prostaglandins. (d) Hepatotoxicity is likely to occur
(c) Its clearance is independent of plasma concentration
(d) antiplatelet effect of low dose aspirin is related to
different prostaglandins may have different effects.
NOT

blunted by NSAIDs because they: (a) The human arteriolar smooth muscle is relaxed
2 2 2 2 cause
(b) Increase the clearance of antihypertensive drugs vasoconstriction
1 2 inhibit platelet aggregation whereas
2 facilitate aggregation
2 2 has
tocolytic action
reason: 2 2 is a
(a) In diabetics because it can cause hyperglycemia bronchoconstrictor
(b) In children with viral disease, because of the risk of 63. Therapeutic uses of prostaglandin El include all of the
acute renal failure EXCEPT:
(c) In gout, because it can increase serum uric acid (a) Medical termination of pregnancy
(d) In pregnancy, because of high risk of teratogenicity (b) Impotence
(c) Primary pulmonary hypertension
(d) Maintenance of patent ductus arteriosus
64. True statements about TXA is:
(a) It is formed in platelets
2/H2
(c) It is prothrombotic
(a) Bleeding time (d) It is having platelet anti-aggregatory activity
(e) aspirin can inhibit its production
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 65. True stagements regarding aspirin toxicity are: 73. The chief advantage of ketorolac over aspirin is that the
(a) Tinnitus is an early symptom former:
(b) 10-30 g causes poisoning
(c) Hyperthermia, tachypnea are early complications codeine.

(c) Is available in a parenteral formulation that can be

used intramuscularly or intravenously.
(a) aspirin (d) Is less likely to cause acute renal failure in patients
(b) Indomethacin with pre-existing renal impairment.
(c) Betamethasone -
sible reason for the use of celecoxib in the treatment of

(a) History of severe rash after treatment with a sulfona-

inhibitors: mide antibiotic
(a) aspirin (b) History of gout
(b) Prednisolone (c) History of peptic ulcer disease
(c) Indomethacin
(d) Betamethasone
(e) Rofecoxib 75. Irreversible inhibitor of cyclooxygenase is:
(a) aspirin
(b) Phenylbutazone
(c) Indomethacin
(d) Piroxicam
2 derivative used in glaucoma
(b) It is selective 1 blocker used in benign hypertrophy 76. Prostaglandin E analogs can be used for all of the fol-
of prostate EXCEPT:
(c) It is a 5 reductase inhibitor used to reduce the size (a) Treatment of patent ductus arteriosus
of enlarged prostate gland (b) Treatment of bronchial asthma
Autacoids

2 analogue used intravaginally for cervical

priming

their inhibitors EXCEPT: of platelet cyclooxygenase because:

(a) abortion
(b) Essential hypertension
(c) Patent ductus arteriosus
(d) Transposition of the great arteries
-

(a) alprostadil (a) Prostacyclin

(b) aspirin (b) Platelet activating factor
(c) Ibuprofen 4
(d) Prednisolone 4 4

(a) Paracetamol
4 (b) Ibuprofen
4
(c) Misoprostol
(d) Prostacyclin

phospholipase A (a) It is not inhibited by indomethacin

(a) alprostadil (b) It is inducible
(b) aspirin (c) It generates cytoprotective prostaglandins in gastric
(c) Ibuprofen mucosa
(d) Prednisolone (d) It is found only in fetal tissues

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 Autacoids

of prostaglandin synthesis EXCEPT:

(a) Prolongation of bleeding time
(b) Prolongation of prothrombin time
(c) Prolongation of labour (b) Indomethacin

inhibition of prostaglandin synthesis EXCEPT: 90. Rofecoxib as compared to indomethacin is:

(a) analgesia
complications
(c) Hyperventilation
(d) Bleeding tendency
(d) all of the above
83. Use of aspirin in a diabetic patient can result in:
91. NSAID proposed to be acting via inhibition of COX-3
(a) Hyperglycemia is:
(b) Hypoglycemia
(b) Paracetamol
(d) alkalosis
84. The plasma half life of aspirin: (d) Rofecoxib
(a) Is independent of dose

that for analgesic dose (a) Indomethacin

(b) Ibuprofen
that for analgesic dose

GeneralAutacoids
(d) Piroxicam
85. TRUE statement about aspirin is: 93. Among NSAIDs aspirin is unique because it:
(a) In an afebrile patient acute overdose of aspirin pro- (a) Irreversibly inhibits its target enzyme

Pharmacology
duces hypothermia (b) Reduces the risk of colon cancer
(c) Reduces fever
dose of nicotinic acid
(c) aspirin therapy prevents granulomatous lesions and 94. Aspirin is used in the prophylaxis of myocardial infarc-
cardiac complications of acute rheumatic fever tion because it results in:
- (a) Inhibition of thromboxane synthetase
veloping colon cancer (b) Inhibition of cyclooxygenase

(a) analgesic 95. Mechanism of action of aspirin in MI is:

(b) antipyretic (a) Inhibition of thromboxane synthesis
(b) Inhibition of cyclooxygenase
(d) antiplatelet aggregatory
(d) Thrombolytic action

takes aspirin for headache, he develops severe short-

(b) It has potential to cause agranulocytosis
(c) It has weak analgesic action
(d) It alters the protein binding and metabolism of many (b) Prostaglandin E
drugs (c) Thromboxane a2
88. Analgesic that itself can cause headache as a side effect (d) Prostacyclin
is:
(a) Indomethacin
(b) Mephenamic acid because of increased risk of:
(c) Piroxicam
(d) aspirin (b) Thrombocytopenia
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 (c) Fanconi syndrome 105. Misoprostol, a prostaglandin analogue is useful as:
(d) Reye’s syndrome (a) Uterine relaxant
98. A college student is brought to emergency after taking (b) anti-ulcer
an overdose of a non-prescription drug. The patient is (c) Bronchodilator
confused and lethargic He has been hyperventilating and (d) Vasodilator
dehydrated. Arterial blood gas analysis demonstrates 106. Drug commonly causing analgesic nephropathy is:
metabolic acidosis. In the management of this patient,
(a) aspirin
(a) alkalinization of urine (b) Ibuprofen
(c) Phenacetin
(d) Phenylbutazone
(d) Treatment with acetyl cysteine
(a) Methyl salicylate
severe hepatotoxicity after doses of acetaminophen that (b) Para-aminobenzoic acid
(c) Para-aminosalicylic acid
This increased sensitivity to acetaminophen’s toxicity is (d) acetyl salicylic acid
due to:

(a) It is constitutionally expressed on some cell surfaces

on gastric mucosa
-
normality that resulted in transposition of great vessels. (d) It is utilized in generation of eicosanoids with a ring
While preparing the infant for surgery, the medical structure
team needed to keep the ducts arteriosus open. They
did this by infusing:
Autacoids

(b) Indomethacin
(c) alprostadil (b) Tenoxicam
(d) Tacrolimus
(d) Piroxicam
101. The antidote of choice in paracetamol poisoning is:
(a) Flumazenil 110. All are true about Reye’s Syndrome Except:
(b) Sodium bicarbonate (a) Hepatic encephalopathy
(b) Seen with ampicillin therapy
(d) Methylene Blue (c) Fever and rash
(d) Viral associated
ulcer is:
111. Ibuprofen acts on:
(b) Misoprostol
(c) alprostadil

(d) Serotonin system

103. Prostaglandin inhibiting action of aspirin is useful

EXCEPT:
(a) analgesia and antipyresis (a) Misoprostol

(c) Uricosuria
(c) Enprostil
(d) Rioprostil

(a) aminocaproic acid (a) aspirin

(b) aspirin (b) Warfarin
(c) aprotinin (c) Phenylbutazone
(d) alteplase

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 Autacoids

2 (d) Salicylism
2
2
2 (a) Etanercept
115. Development of hepatic central lobular necrosis
secondary to acetaminophen overdose can be prevented (c) Sulfasalazine

EXCEPT:
(a) Ethambutol
(c) Sodium nitrite (b) Pyrazinamide
(d) amyl nitrite
(d) Hydrochlorothiazide
116. For pain control in a patient having history of G I

(b) Ibuprofen (b) Indomethacin

(c) Rofecoxib (c) allopurinol
(d) Pentazocin

(a) Ischemic heart disease is:

(b) Renal complication (a) Sedation

GeneralAutacoids
(d) Muscle paralysis

but is NOT
(a) Probenecid

Pharmacology
-
(b) Phenylbutazone
erative pain
(c) Is used as preanaesthetic analgesic
(d) allopurinol
(d) It interacts with opioid receptor

EXCEPT:
(a) Metabolic acidosis (b) Hydrochlorothiazide induced hyperuricemia
(b) Reye’s syndrome (c) acute gouty arthritis
(c) Renal tubular acidosis
(d) Fixed drug eruption

RHEUMATOID ARTHRITIS AND GOUT

(b) Increasing urate oxidation

(d) Increasing renal excretion of uric acid

130. A drug that is effective for rheumatoid arthritis but is
(c) Methotrexate not appropriate for osteoarthritis is:
(d) Sulfasalazine (a) acetaminophen

(a) Hypoxanthine to xanthine

(d) Rofecoxib
(c) Hypoxanthine to I.M.P. 131. A drug X is useful in the treatment of rheumatoid
arthritis. It is available only in parenteral formulation
and its mechanism of action is antagonism of tumor
limited by its propensity to cause:
(a) Metabolic acidosis
(b) Hypersensitivity reactions (b) Penicillamine
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 (c) Phenylbutazone
(d) Etanercept
(b) arginase
pain in the knee and shoulder joint. On examination
and further investigations, a diagnosis of rheumatoid (d) Urease
-
(a) Rheumatoid arthritis
using methotrexate, recurrent episodes of arthritis con-
(c) Bony metastasis
that inhibit the pyrimidine synthesis by inhibiting (d) Postmenopausal osteoporosis
-
(a) Sulfasalazine
(a) Methotrexate

(d) abatacept
(d) anakinra

limiting is:
(b) Penicillamine
(c) Succimer

(c) Retinal damage

(a) allopurinol
(b) aspirin
MISCELLANOUS
(d) Probenecid
144. Most common cause of Mobius syndrome is use of
Autacoids

(a) Misoprostol
(a) Furosemide
(b) Thalidomide
(c) Methotrexate
(c) allopurinol
(d) Piroxicam
136. Allopurinol potentiates the action of:

(b) Probenecid 2

(c) Phenylephrine
(d) ampicillin
(d) alprostadil

(a) Streptomycin
(b) ampicillin
(c) Vancomycin (a) aspirin
(d) Erythromycin (b) Penicillin

138. Drug useful for gout: (d) Bosentan

(a) Pyrazinamide
(b) Rifampicin
(c) allopurinol

is to administer:
(a) 20 mg
(b) 10 mg (b) Epinephrine inj.
(c) 100 mg (c) High dose hydrocortisone tablet
(d) 400 mg

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 Autacoids

(a) angiotensin I
(c) Thromboxane synthase
(b) Omapatrilat
(d) Phospholipase
(c) Bosentan
3. Which drug is not included in DMARDs:
(d) Endothelin
149. The primary endogenous substrate for nitric oxide syn- (b) Vincristine
thase (NOS) is: (c) Penicillamine

(b) arginine -
(c) Heme tioins except:
(d) Methionine
(b) Post partum haemorrhage
(c) Erectile dysfunction
(d) Palliative treatment of patent ductus arteriosus
metatarsophalangeal joint. A needle aspirate of the joint
5. Allopurinol is used in the treatment of:
The physician prescribed a drug for the patient, but he (b) Hypothyroidism
(c) Hypertension
(d) Hyperlipidemia
6. Irreversible inhibition of COX is done by:
(a) allopurinol (a) aspirin

GeneralAutacoids
(c) Steroids
(d) Indomethacin
151. Nitric oxide produces its anti-aggregatory action by

Pharmacology
increasing the levels of (a) Indomethacin
(b) Paracetamol
(a) caMP
(c) Ibuprofen

3
(d) Phosphoinositol
(b) Ondansetron

2 (d) Buspirone
2
2
9. Dinoprost is
(d) all of the above 1
2
153. Bosentan is a/an: 2
(a) Serotonin uptake inhibitor 2
(b) Endothelin receptor antagonist 10. H1 antagonist has all the functions except:
(a) antipruritic
(d) Phosphodiestease inhibitor (b) Sedation

RECENT QUESTIONS ASKED BY NATIONAL BOARD (d) antivertigo

1. 5 HT 1 11. -
(a) anti anxiety drugs tions except:
(b) antipsychotic drugs

(d) For chemotherapy induced vomiting

(d) Patent ductus arteriosus

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 -
1
2
2
(c) Sulindac 2
(d) Piroxicam
-
ment is: (a) Propranalol
(b) Sumatriptan
(b) Probenecid
(c) allopurinol (d) Ergotamine

14. Alprostadil is not used for: (a) adrenaline

(a) Erectile dysfunction
(b) Pulmonary hypertension (c) antihistaminic
(c) Patent ductus arteriosus (d) Sodium cromoglycate

15. Ergometrine is not used for initiation of labour because:

(a) Slow onset of action (a) Bromocriptine
(b) Fetal hypoxia
(c) Increases blood pressure (c) Sumatriptan
(d) Ondansetron
16. NSAID given in once daily dose is:
1 histamine receptor include:
(a) Inhibition of gastric acid secretion
(b) Induction of hepatic cytochrome P450 enzymes
Autacoids

(c) Piroxicam (c) Maintenance of a wakeful state

(d) Paracetamol (d) Vasoconstriction of arterioles
17. Most commonly used drug for prophylaxis of migraine
is: in toxicity due to:
(a) Sumatriptan (a) Isoniazid
(b) Propranolol
(b) acetaminophen
(c) Valproate
(c) Halothane
(d) Flunarizine
(d) Methyldopa

1 blocker has high anti-cholin-

cyclo-oxygenase except:
ergic activity:
(b) Ibuprofen
(c) aspirin
(c) Fexofenadine
(d) Indomethacin
(d) astemizole
ferred antidote for paracetamol (acetaminophen)
poisoning is:
(a) activated charcoal
(b) aspirin
(c) Indomethacin (c) adrenaline
(d) acetaminophen (d) Magnesium hydroxide gel
alpha) is used in:
(a) Maintenace of ductus arteriosus (a) Uricase
(b) Pulmonary hypertension

(d) adenosine deaminase

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 Autacoids

(d) Ondansetron
in breathing and facial edema. What is the best

(a) IV adrenaline
(c) arachidonic acid
(c) IV antihistamine
(d) Butyric acid
(d) IV Hydrocortisone
-
tacyclin PGI :
except:
(a) Vasodilation and platelet aggregation
(a) aspirin
(b) Vasodilation and inhibition of platelet aggregation
(b) acetaminophen
(c) Vasoconstriction and platelet aggregation
(c) aminoglycosides
(d) Vasoconstriction and inhibition of platelet aggrega-
tion

derivatives: ex-
(a) Migraine cept:
(b) Hyperprolactinemia (a) It is the principal prostaglandin synthesized in the
(c) Obstructive vascular disease stomach
(d) Postpartum hemorrhage (b) Its biosynthesis is inhibited by aspirin
(c) It stimulates gastric acid secretion
33. Triptans used in migraine headaches are agonists at (d) It causes dilatation of submucosa blood vessels

(a) 5HT
(b) 5HT1a (a) Tryptophan

GeneralAutacoids
(c) 5HT3 (b) Tyrosine
(d) 5HT2a
(d) Epinephrine
41. Uricosuric drug among these is:

Pharmacology
(a) Increase in lactic acid
(b) Increase in uric acid (a) Probenecid
(c) Increase in hippuric acid
(c) allopurinol
(d) Increase in glutamic acid
(d) all of these

combination is incorrect:

(b) Terfenadine-Fexofenadine (c) Increased excretion of uric acid

43. Latanoprost is used in treatment of:

1 and 5 HT receptor is:
(a) Induction of labor
(a) Phenoxybenzamine (b) Refraction

(c) Ritanserin (d) Iridocyclitis

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 explanations

loratidine and fexofenadine are second generation drugs.

although both histamine as well as bradykinin can cause edema and increase in permeability, histamine is an amine
whereas bradykinin is a peptide.
3. Ans. (a) Post partum hemorrhage
Obstetric indications of ergometrine (Ergonovine):

To control and prevent Post partum hemorrhage. It is given at the time of delivery of anterior shoulder.

To ensure normal involution in multipara.

It is a non-sedating second generation antihistaminic agent and is preferred for the patients requiring constant attention.
It does
antihistaminics.
Autacoids

6. Ans. (b) Increase in H1 mediated gastrin release

H3 receptors act as pre-synaptic receptors and decrease the release of histamine and other neurotransmitters. These an-
tagonize H1 mediated wakefulness and bronchoconstriction. These also decrease gastrin release and produce negative
chronotropic effect. Inverse agonist of H3

8. Ans. (b) Direct action on vascular smooth muscle causing vasodilation

Both H1 and H2 receptors cause vasodilation. H1 receptors are present in the endothelium and cause vasodilation by
2 receptors are present on the smooth muscles and cause direct vasodilation.

9. Ans. (c) Morphine

to itching and hypotension.

all the drugs listed in the question are second generation anti-histaminic agents except promethazine.
11. Ans. (c) Cyproheptadine

First generation antihistaminic agents cause sedation and impairment of psychomotor function.
13. Ans. (b) These possess high anti-motion sickness activity
-
pounds whereas second generation antihistaminics lack this potential.

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 Autacoids

16. Ans. (b) Dangerous ventricular arrhythmias can occur

+ channels at high concentration. If administered along with microso-

mal enzyme inhibitors, these drugs can result in torsades de pointes, a serious polymorphic ventricular tachycardia.
17. Ans. (c) It does not block cardiac K+ channels
+ channel blocking property, therefore is devoid of ar-

rhythmogenic potential. It is available as a separate second generation H1 blocking agent.

19. Ans. (c) 5-HT3

3, which is an inotropic receptor.

1A

3 receptor
(d) Tegaserod
Both cisapride and tegaserod are selective 5HT4 +

channel blocking activity and can lead to torsades de pointes. Tegaserod is devoid of this adverse effect. However, tegas-
erod has recently been withdrawn due to increased risk of MI and stroke.

adrenaline is a physiological antagonist of histamine. It reverses bronchoconstriction caused by histamine. Raniti-

dine is an H2 antagonist that decreases gastric acid secretion but has no effect on smooth muscles.

In this condition, excessive secretions (like rhinorrhoea) are due to cholinergic overactivity. First generation antihistamin-
ics possess anticholinergic property and therefore are effective for common cold. On the other hand, second generation

GeneralAutacoids
agents (lacking anticholinergic actions) are ineffective.

astemizole and terfenadine are metabolized by microsomal enzymes. Erythromycin inhibits these enzymes and raises the
+ channels leading to arrhythmias.

Pharmacology
antagonist

30. Ans. (b) Lanreotide

31. Ans. (c) Diphenhydramine

emetic
33. Ans. (d) Terfenadine

35. Ans. (d) Decreasing IP3 in stomach

36. Ans. (a) Dihydroergotamine

peripheral vascular disease. These may also lead to development of gangrene.

37. Ans. (d) Levetiracetam

Propanolol is the most commonly used drug for prophylaxis of migraine attacks. Timolol, atenolol, metopro-
lol and nadolol can also be used but the drugs with ISa (e.g. pindolol) are ineffective.
+ channels) is also effective

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 Topiramate (anticonvulsant drug) has recently been approved for prophylaxis of migraine. Valproate and
gabapentin also possess some prophylactic activity.

38. Ans. (a) Sumatriptan

For details see text.

40. Ans. (c) Nitroprusside
This agent is a mixed dilator and is highly effective agent against ergot induced vasospasm. It is also the drug of choice for
most of the hypertensive emergencies.
41. Ans. (c) Frovatriptan

44. Ans. (a) Methylergometrine

Methylergometrine (methergin) is administered during delivery of anterior shoulder to prevent postpartum hemorrhage.
45. Ans. (b) It tends to suppress both pain and vomiting in migraine
Sumatriptan decreases whereas ergotamine aggravates the vomiting of migraine. These two agents should not be admin-
istered concomitantly due to the risk of severe coronary spasm. Triptans act as agonists at 5HT receptors.

47. Ans. (d) Sumatriptan

Autacoids

48. Ans. (d) Migraine

49. Ans. (c) 5HT1D agonist
50. Ans. (b) Sumatriptan
51. Ans. (b) Postpartum hemorrhage

53. Ans. (c) Its clearance is independent of plasma concentration

acetylsalicylic acid (aspirin) is an irreversible inhibitor of
at low doses (40-325 mg), it exerts antiplatelet action. This drug shows i.e. kinetics changes

not constant.
54. Ans. (d) Decrease the synthesis of vascular prostacyclins
2 2 cause , and increased water clearance due to inhibition of the action of

of these
drugs.
55. Ans. (c) In gout, because it can increase serum uric acid

at therapeutic doses, aspirin can cause hyperuricemia by decreasing the excretion of uric acid. It, therefore,
should not be used in patients with gout. It also decreases the uricosuric action of probenecid. at high doses
(>5 g/d), it increases the excretion of uric acid, but such high doses are not tolerated.
aspirin is contraindicated in children (<12 yrs old) due to increased risk of Reye’s syndrome, which is a type
of hepatic encephalopathy.
It should be avoided in diabetics because of risk of hypoglycemia
It should be avoided in pregnancy because it may be responsible for low birth weight babies, however, it does
not cause congenital malformations.

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 Autacoids

56. Ans. (c) Cyclooxygenase

prostaglandins.
57. Ans. (a) Bleeding time
antiplatelet drugs (like aspirin and clopidogrel) prolong the bleeding time.
anticoagulant drugs prolong the clotting time.

58. Ans. (a) Prostaglandin E1 analogue

2 1 analogs.

-1 is a constitutional (house keeping) enzyme.

60. Ans. (d) Piroxicam

61. Ans. (d) Hepatotoxicity is likely to occur

has tocolytic action

2 2 is an oxytocic agent and
can be utilized for the induction of abortion.

GeneralAutacoids
63. Ans. (c) Primary pulmonary hypertension
2 1 analogs are

Pharmacology
(alprostadil).
64. Ans. (a) (b) It is formed from PGG /H (c) -
duction
2 2 synthetase.
2/H2)
with the help of an enzyme, cyclooxygenase.
aspirin inhibits its production by irreversible inhibition of cyclooxygenase enzyme.
2 causes aggregation of platelets, therefore is prothrombotic.

65. Ans. (a) (b) 10-30 g causes poisoning

Symptoms of aspirin poisoning

-

The dose has to be titrated to one which is just below that produces these symptoms,

Metabolic acidosis, hyperthermia and acidotic breathing are seen in severe poisoning
Aspirin causes platelet dysfunction by inhibiting cyclooxygenase pathway.
Fatal dose in adult is 15-30 g but considerably lower in children.

-
indomethacin, diclofenac etc are competitive and reversible inhibitors of
COX, return of activity depends on their dissociation from the enzyme which is turn is governed by the pharmacoki-
netic characteristics of the compound.
Corticosteroids like betamethasone act by inhibiting phospholipase A .

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 68. Ans. (a) It is PGF derivative used in glaucoma
69. Ans. (b) Essential hypertension
70. Ans. (c) Ibuprofen
1) and prednisolone do not inhibit cox enzyme whereas aspirin is an irreversible inhibitor of this enzyme.

71. Ans. (a) LTC4

4 4 and E4 are known as slow reacting substance of anaphylaxis as these can cause bronchoconstriction.

(d) Prednisolone
-
lipase a2
73. Ans. (c) Is available in a parenteral formulation that can be used intramuscularly or intravenously

74. Ans. (c) History of peptic ulcer disease

75. Ans. (a) Aspirin

76. Ans. (a) Treatment of patent ductus arteriosus

2 analogues are used to maintain the patency of ductus arteriosus whereas aspirin or indomethacin are

2 is a bronchodilator and can be used to treat bronchial asthma via inhalational route.
Autacoids

2 2 level results in the anti-aggregation of platelets.

78. Ans. (d) Leuktoriene C4/D4
79. Ans. (a) Paracetamol
80. Ans. (b) It is inducible

isoforms of .
81. Ans. (b) Prolongation of prothrombin time
Prothrombin time is increased by the drugs interfering with the coagulation pathway (e.g. warfarin). as cox has no role in
-
ing with platelet function. aspirin increases BT by acting as an antiplatelet agent.

respiratory stimulation.
83. Ans. (b) Hypoglycemia

1/2
than for analgesic dose.
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 Autacoids

can cause hyperthermia in overdose. It decreases the risk of developing colon cancer.
86. Ans. (d) Antiplatelet aggregatory
87. Ans. (b) Its potential to cause agranulocytosis
88. Ans. (a) Indomethacin
89. Ans. (b) Indomethacin
Sedation caused by indomethacin can interfere with driving.
90. Ans. (a) Less likely to cause gastric ulcer and their complications
-

91. Ans. (b) Paracetamol

94. Ans. (b) Inhibition of cyclooxygenase

2. However it has
no effect on the enzyme, thromboxane synthetase. Therefore, answer here is the inhibition of cox.
95. Ans. (a) Inhibition of thromboxane synthesis

GeneralAutacoids
See the difference from the above question. Here in the question, it is written thromboxane synthesis and not synthetase.

96. Ans. (a) Leukotrienes

Pharmacology
aspirin inhibits
choconstrictor agents, these may result in the shortness of breath in patients who are susceptible. aspirin acetylated
starts producing lipoxins (known as aspirin triggered lipoxins) that also have bronchoconstrictor properties.
97. Ans. (d) Reye’s syndrome
aspirin can increase the risk of Reye’s syndrome, if used in children with viral diseases.

-
sis must be corrected by sodium bicarbonate. alkalization of urine will increase the excretion of this weakly acidic
drug. Treatment with acetylcysteine has no role in salicylate poisoning. It is the antidote of choice for paracetamol
poisoning.

99. Ans. (b) Decreased hepatocellular stores of glutathione

-

100. Ans. (c) Alprostadil

Prostaglandins (like alprostadil) are used to keep ductus arteriosus patent whereas aspirin or indomethacin are used for

101. Ans. (c) N-acetylcysteine

103. Ans. (c) Uricosuria

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 104. Ans. (b) Aspirin
105. Ans. (b) Anti-ulcer
106. Ans. (c) Phenacetin
It is a prodrug of paracetamol and is commonly implicated in the causation of analgesic nephropathy.
107. Ans. (d) Acetyl salicylic acid

in protection from gastric ulcers.

-
tion.

ring.

109. Ans. (a) Nefopam

Autacoids

113. Ans. (b) Warfarin

114. Ans. (c) PGE
115. Ans. (a) N-acetylcysteine
116. Ans. (c) Rofecoxib
117. Ans. (a) Ischemic heart disease

some situations involving mild to moderate postsurgical pain.

119. Ans. (b) Reye’s syndrome

Sulfasalazine can cause a reversible infertility in males owing to changes in sperm number and morphology.

(c)

This drug is uricosuric agent and is used in the treatment of hyperuricemia.

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 Autacoids

allopurinol is contra-indicated in acute gout. Rarely it can be used in kala azar patients.

Rasburicase and pegloticase are recombinant urate oxidase enzymes that convert insoluble uric acid to soluble allantoin.

antagonist that plays no role in osteoarthritis.

131. Ans. (d) Etanercept

For details, see text.

133. Ans. (b) Penicillamine
134. Ans. (d) Probenecid
135. Ans. (d) Piroxicam

GeneralAutacoids
chronic gout. Furosemide causes hyperuricemia and should be avoided in patients with gout.
136. Ans. (c) 6-Mercaptopurine

Pharmacology
used along with allopurinol.
137. Ans. (b) Ampicillin
Interactions of Probenecid

It competitively blocks active transport of organic acids at all sites especially renal tubules. It inhibits excre-
tion of penicillin/ampicillin and increases its blood level.
It also inhibits urinary excretion of cephalosporins, sulfonamides, methotrexate and indomethacin.
It inhibits tubular secretion of nitrofurantoin.
Salicylates, pyrazinamide and ethambutol inhibit uricosuric action of probenecid.
It inhibits biliary excretion of rifampicin.

138. Ans. (c) Allopurinol

139. Ans. (c) 100 mg
140. Ans. (a) Xanthine oxidase
141. Ans. (a) Rheumatoid arthritis

143. Ans. (a) Diarrhea

144. Ans. (a) Misoprostol

Mobius syndrome is extremely rare congenital condition characterized by facial paralysis and inability to move the

Birth trauma
Use of misoprostol in mother during pregnancy

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 Use of thalidomide in mother during pregnancy
Use of cocaine in mother during pregnancy
145. Ans. (c) Phenylephrine
Phenylephrine is an -agonist and will cause vasoconstriction therefore not used in erectile dysfunction where vaso-
dilation of penile vessels is required.
Other drugs given in the option are used for this condition
For further details, see chapter 19.
146. Ans. (a) Aspirin

147. Ans. (b) Epinephrine inj

Epinephrine (adrenaline) is the drug of choice for anaphylactic shock. It is given by s.c. or i.m. route in a concentration of

148. Ans. (c) Bosentan

a and ETB). It is useful for the treatment of pri-
mary pulmonary hypertension.

149. Ans. (b) Arginine

150. Ans. (b). Colchicine

Autacoids

effects.
151. Ans. (b) cGMP

153. Ans. (b) Endothelin receptor antagonist

ANSWERS OF RECENT QUESTIONS ASKED BY NATIONAL BOARD

1. Ans (a) Anti anxiety drugs

3. Ans (b) Vincristine

4. Ans (d) Palliative treatment of patent ductus arteriosus
5. Ans (a) Gout
6. Ans (a) Aspirin
7. Ans (b) Paracetamol
8. Ans (b) Ondansetron

10. Ans. (c) Decrease gastric acid secretion

11. Ans. (d) Patent ductus arteriosus

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 Autacoids

13. Ans. (a) Naproxen

allopurinol is drug of choice for most cases of chronic gout.

14. Ans. (c) Patent ductus arteriosus
alprostadil is used to keep the ductus open and not for already patent ductus arteriosus.

15. Ans. (b) Fetal hypoxia

16. Ans. (c) Piroxicam

17. Ans. (b) Propranolol

18. Ans. (c) Aspirin

19. Ans. (b) Aspirin

GeneralAutacoids
Pharmacology
30. Ans. (b) SC Adrenaline

31. Ans. (b) Acetaminophen

33. Ans. (a) 5HTID/IB (

34. Ans. (b) Increase in uric acid

36. Ans. (b) Cyproheptadine

37. Ans. (c) Arachidonic acid

38. Ans. (b) Vasodilation and inhibition of platelet aggregation

39. Ans. (c) It stimulates gastric acid secretion

40. Ans. (a) Tryptophan

41. Ans. (a) Probenecid

43. Ans. (c) Glaucoma

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