1 Systemic effects of histamine and serotonin .

histamine: Excess production of

histamine in the body (eg, in systemic mastocytosis) can be detected by measurement of its
major metabolite, imidazole acetic acid, in the urine. Because it is released from mast cells in
response to IgE-mediated (immediate) allergic reactions, this autacoid plays a pathophysiologic
role in seasonal rhinitis (hay fever), urticaria, and angioneurotic edema. Histamine also plays a
physiologic role in the control of acid secretion in the stomach and as a neurotransmitter. Fish
that has been stored improperly generates high concentrations of histamine; consumption of
such fish may produce severe histamine toxicity (“scombroid poisoning”). Serotonin: plays a
physiologic role as a neurotransmitter in both the CNS and the enteric nervous system and may
have a role as a local hormone that modulates gastrointestinal activity. After release from
neurons, it is partially taken back up into the nerve ending by a serotonin reuptake transporter
(SERT). Serotonin is also stored (but synthesized to only a minimal extent) in platelets.

2. Prototypes of first and second generation antihistamines, their

therapeutic and side effects Chlorpheniramine and cyclizine, dimenhydrinate, cyclizine,
meclizine, and promethazine may be considered prototypes. The second-generation H1
blockers, typified by cetirizine, fexofenadine, and loratadine, are far less lipid soluble than the
first-generation agents and have greatly reduced sedating and autonomic effects.Most are
metabolized extensively in the liver. first-generation agents have anti-motion sickness effects.
H1 blockers have major applications in allergies of the immediate type (ie, those caused by
antigens acting on IgE antibody-sensitized mast cells). These conditions include hay fever and
urticaria. Diphenhydramine, dimenhydrinate, cyclizine, meclizine, and promethazine are used as
anti-motion sickness drugs. Diphen- hydramine is also used for management of chemotherapy-
induced vomiting. Doxylamine, in combination with pyridoxine, is promoted for the prevention
of morning sickness in pregnancy.* Adverse effects of the first-generation H1 blockers are some-
times exploited therapeutically (eg, in their use as hypnotics in over-the-counter sleep aids).
Some of the more common side effects of first-generation antihistamines can include:
drowsiness. dry mouth, nose, and throat. headache.

1. 3. Mechanism of action of sumatriptan and clinical uses;

5-HT1D/1B agonists—Sumatriptan they are the first-line treatment for acute migraine and
cluster headache attacks, an observation that strengthens the association of serotonin
abnormalities with these headache syndromes. These drugs are active orally; sumatriptan is also
available for nasal and parenteral administration. Sumatriptan selectively binds to and activates
serotonin 5-HT1D receptors in the central nervous system (CNS), thereby constricting cerebral
blood vessels. This may lead to a relief in pain from vascular headaches.
 4. 5-HT2C agonists—Lorcaserin has been approved for the treatment of obesity. It activates
receptors in the CNS and appears to moderately reduce appetite. Older agonist drugs,
fenfluramine and dexfenfluramine, appear to act directly and by releasing neuronal 5-HT or
inhibiting SERT, and thereby activat- ing central 5-HT2C receptors. : Ketanserin,
phenoxybenzamine, and cyproheptadine are effec- tive 5-HT2 blockers. Ondansetron,
granisetron, dolasetron, and alosetron are 5-HT3 blockers. The ergot alkaloids are partial
agonists (and therefore have some antagonist effects) at 5-HT and other receptors (see later
discussion).

8. Mechanism of action of aspirin, its therapeutic and side effects

Cyclooxygenase has at least 2 isoforms: COX-1 and COX-2. COX-1 is primarily expressed in
noninflammatory cells, whereas COX-2 is expressed in activated lymphocytes,
polymorphonuclear cells, and other inflammatory cells. Aspirin and nonselective NSAIDs inhibit
both cyclooxygenase isoforms and thereby decrease prostaglandin and thromboxane synthesis
throughout the body. Release of prostaglandins necessary for homeostatic function is disrupted,
as is release of prostaglandins involved in inflammation. The COX-2-selective inhibitors have less
effect on the prostaglandins involved in homeostatic function, particularly those in the
gastrointestinal tract. The major difference between the mechanisms of action of aspirin and
other NSAIDs is that aspirin (but not its active metabolite, salicylate) acetylates and thereby
irreversibly inhibits cyclooxygenase, whereas the inhibition produced by other NSAIDs is
reversible. The irreversible action of aspirin results in a longer duration of its antiplatelet effect
and is the basis for its use as an antiplatelet drug Aspirin—Aspirin has 3 therapeutic dose ranges:
The low range (

Q.12 Mechanism of action of benzodiazepines, therapeutic, side effects and clinical

uses; mechanism of action of benzodiazepines : Benzodiazepines increase the frequency of
channel openings produced by GABA ,, they don’t bind to GABa receptor they increase the
affinity of GaBa which leads to increase frequency of the channel opining , they decrease the
anxiety by selectively enhancing GABAergic transmission in neurons .//and greater feeling of
calm Sedative/hypnotic because The hypnotic effects are mediated by the α1-GABAA
receptors. //+ produce mild muscle relaxation ,Anterograde amnesia, Anticonvulsant :

mediated by the α1-GABAA receptors //// Therapeutic uses Anxiety disorders, Sleep
disorders (These agents decrease the latency to sleep onset and increase stage II of non–rapid
eye movement (REM) sleep) , . Amnesia, Muscular disorders side effects the most common
due to their act on sedating and muscle relaxant ( drowsiness , dizziness , and decrease
alertness and concentration , impotent of motor coordination
Q. 13 ) Mechanism of action of barbiturates, dose-dependent effects and clinical
uses Barbiturates depress neuronal activity in the midbrain reticular formation, facilitating and
prolonging the inhibitory effects of GABA and glycine. barbiturates it binds to GABA alpha
or beta // they increase the ion channel opening duration decrease the activity of
excitor neurotransmitter / anticonvulsant and anaesthetic agents Suppression of
seizure activity occurs with high doses , much lower therapeutic index // side
effects ( dizziness tight headiness , sedation memory and attention , impairments ,
induce the formation of the liver microsomal enzymes that metabolize drugs,
precipitate acute intermittent porphyria in susceptible patients

Q. 14) Pharmacology of Flumazenil and clinical use Flumazenil: Benzodiazepine

receptor antagonist: used to reverse CNS depressant effects of benzodiazepines, zolpidem,
eszopiclone, and zaleplon , but has no beneficial actions in overdosage with other sedative-
hypnotics. to help you wake up after your medical procedure. Flumazenil is also used to treat
benzodiazepine overdose in adults

Q. 16 ) Pharmacology of Morphine - mechanism of action, therapeutic, side

effects and clinical uses Morphine 1. Mechanism of action: Morphine their major effects by
interacting stereospecifically with opioid receptors on the membranes of certain cells in the CNS
and other anatomic structures, such as the gastrointestinal (GI) tract and the urinary bladder.
Morphine also acts at κ receptors in lamina I and II of the dorsal horn of the spinal cord. It
decreases the release of substance P, which modulates pain perception in the spinal cord.
Morphine also appears to inhibit the release of many excitatory transmitters from nerve
terminals carrying nociceptive (painful) stimuli.ACTION ( CLINICAL USE) Analgesia: Morphine
cause analgesia (relief of pain without the loss of consciousness), Euphoria: Morphine produces
a powerful sense of contentment and well-being, Morphine causes respiratory depression, .
Depression of cough reflex: Both morphine and codeine have antitussive properties, GI tract:
Morphine relieves diarrhea by decreasing the motility and increasing the tone of the intestinal
circular smooth muscle Adverse effects: Many adverse effects are common across the entire
opioid, severe respiratory depression can occur and may result in death from acute opioid
overdose. Respiratory drive may be suppressed in patients with emphysema or cor pulmonale

Q.17) Pharmacology of Codein - mechanism of action, therapeutic, side effects

and clinical uses Codeine is a naturally occurring opioid that is a weak analgesic compared
to morphine. It should be used only for mild to moderate pain. The analgesic actions of codeine
are derived from its conversion to morphine by the CYP450 2D6 enzyme system CYP450 2D6
activity varies in patients, and ultrarapid metabolizers may experience higher levels of morphine,
leading to possible overdose. Drug interactions associated with the CYP450 2D6 enzyme
system may alter the efficacy of codeine or potentially lead to toxicity. Codeine is commonly
used in combination with acetaminophen for management of pain// Codeine is used to relieve
mild to moderate pain. It is also used, usually in combination with other medications, to reduce
coughing., Side effects codeine administration include drowsiness, lightheadedness, dizziness,
sedation, shortness of breath, nausea, vomiting, sweating, and constipation.
Other adverse reactions include allergic reactions, euphoria, dysphoria, abdominal pain, and
pruritis( p 259)

Q.20) The main causes for the combination of local anesthetics and
adrenomimetics and contraindications for combined use Smaller fibers are
blocked more easily than larger fibers, and myelinated fibers are blocked more
easily than unmyelinated fibers, pain sensation appears to be selectively blocked
by local anesthetics. Fibers located in the periphery of a thick nerve bundle are
blocked sooner than those in the core because they are exposed earlier to
higher concentrations of the anesthetic. Most local anesthetics also have weak
blocking effects on skeletal muscle neuromuscular transmission<//The local
anesthetics are commonly used for minor surgical procedure,ALSO used in
spinal anesthesia and to produce autonomic blockade in ischemic conditions,
reducing pain in the perioperative

Q.21 Agents of premedication and their pharmacology Epinephrine is a an

alpha-/beta-agonist that is administered as an adjuvant in local
anesthetic cartridges. Epinephrine is also used as an emergency drug for treatment of
anaphylactic reaction and a vasoconstrictor to decrease systemic absorption of local
anesthetics and to increase the duration of anesthetic action, contraindications due to risks
of irreversible vasospasm

Q22 Agent for dissociative anesthesia and its pharmacology: is Ketamine

This drug produces a state of “dissociative anesthesia” in which the patient
remains conscious but has marked catatonia, analgesia, and amnesia. Ketamine
is a chemical congener of the psychotomimetic agent, phencyclidine (PCP), and
inhibits NMDA glutamate transmission. The drug is a cardiovascular stimulant,
and this action may lead to an increase in intracranial pressure. Emergence
reactions, including disorientation, excitation, and hallucinations, which occur
during recovery from ketamine anesthesia, can be reduced by the preoperative
use of benzodiazepines