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1.) Epinephrine (also known as adrenaline) is a hormone and neurotransmitter.[1].

It increases heart rate, contracts blood vessels, dilates air passages and participates in
the fight-or-flight response of the sympathetic nervous system.[2] Chemically, epinephrine is a catecholamine, a monoamine produced only by the adrenal glands from
the amino acids phenylalanine and tyrosine.

The term adrenaline is derived from the Latin roots ad- and renes and literally means on the kidney, in reference to the adrenal gland's anatomic location on the kidney.
The Greek roots epi- and nephros have similar meanings, and give rise to epinephrine. The term epinephrine is often shortened to epi in medical jargon.[3]

Adrenal extracts containing adrenaline were first obtained by Polish physiologist Napoleon Cybulski in 1895. These extracts, which he called "nadnerczyna", contained
epinephrine and other catecholamines.[4] Japanese chemist Jokichi Takamine and his assistant Keizo Uenaka independently discovered adrenaline in 1900.[5][6] In 1901,
Takamine successfully isolated and purified the hormone from the adrenal glands of sheep and oxen.[7] Adrenaline was first synthesized in the laboratory by Friedrich
Stolz and Henry Drysdale Dakin, independently, in 1904.[6]

Actions in the body

As a hormone, epinephrine acts on nearly all body tissues. Its actions vary by tissue type and tissue expression of adrenergic receptors. For example, epinephrine causes
smooth muscle relaxation in the airways, but causes contraction of the smooth muscle that lines most arterioles.

Epinephrine acts by binding to a variety of adrenergic receptors. Adrenaline is a nonselective agonist of all adrenergic receptors, including α₁, α₂ , β₁, β₂, and β₃
receptors.[8] Epinephrine's binding to these receptors triggers a number of metabolic changes. Binding to α-adrenergic receptors inhibits insulin secretion by the
pancreas, stimulates glycogenolysis in the liver and muscle, and stimulates glycolysis in muscle.[9] β-Adrenergic receptor binding triggers glucagon secretion in the
pancreas, increased adrenocorticotropic hormone (ACTH) secretion by the pituitary gland, and increased lipolysis by adipose tissue. Together these effects lead to
increased blood glucose and fatty acids, providing substrates for energy production within cells throughout the body.[9]

In addition to these metabolic changes, epinephrine also leads to broad alterations throughout all organ systems.

Physiologic responses to epinephrine by organ


Organ Effects
Heart Increases heart rate
Lungs Increases respiratory rate
Nearly all tissues Vasoconstriction or vasodilation
Liver Stimulates glycogenolysis
N/A, systemic Triggers lipolysis
N/A, systemic Muscles contraction

Biosynthesis and regulation

Adrenaline is synthesized in the adrenal gland in an enzymatic pathway that converts the amino acid tyrosine into a series of intermediates and ultimately adrenaline.
Tyrosine is first oxidized to L-DOPA, which is subsequently decarboxylated to give dopamine. Oxidation gives norepinephrine, which is methylated to give
epinephrine.

Adrenaline is synthesized via methylation of the primary distal amine of noradrenaline by phenylethanolamine N-methyltransferase (PNMT) in the cytosol of
adrenergic neurons and cells of the adrenal medulla (so-called chromaffin cells). PNMT is only found in the cytosol of cells of adrenal medullary cells. PNMT uses S-
adenosylmethionine (SAMe) as a cofactor to donate the methyl group to noradrenaline, creating adrenaline.[citation needed]

The biosynthesis of adrenaline involves a series of enzymatic reactions.

For noradrenaline to be acted upon by PNMT in the cytosol, it must first be shipped out of granules of the chromaffin cells. This may occur via the catecholamine-H+
exchanger VMAT1. VMAT1 is also responsible for transporting newly synthesized adrenaline from the cytosol back into chromaffin granules in preparation for release.
[citation needed]

In liver cells, adrenaline binds to the β-Adrenergic receptor which changes conformation and helps Gs, a G protein, exchange GDP to GTP. This trimeric G protein
dissociates to Gs alpha and Gs beta/gamma subunits. Gs alpha binds to adenyl cyclase thus converting ATP into Cyclic AMP. Cyclic AMP binds to the regulatory
subunit of Protein Kinase A: Protein kinase A phosphorylates Phosphorylase Kinase. Meanwhile, Gs beta/gamma binds to the calcium channel and allows calcium ions
to enter the cytoplasm. Calcium ions bind to calmodulin proteins, a protein present in all eukaryotic cells, which then binds to Phosphorylase Kinase and finishes its
activation. Phosphorylase Kinase phosphorylates Glycogen phosphorylase which then phosphorylates glycogen and converts it to glucose-6-phosphate.[citation needed]

Regulation

The major physiologic triggers of adrenaline release center upon stresses such as physical threat, excitement, noise, bright lights, and high ambient temperature. All of
these stimuli are processed in the central nervous system[10].

Adrenocorticotropic hormone (ACTH) and the sympathetic nervous system stimulate the synthesis of adrenaline precursors by enhancing the activity of tyrosine
hydroxylase and dopamine-β-hydroxylase, two key enzymes involved in catecholamine synthesis.[citation needed] ACTH also stimulates the adrenal cortex to release cortisol,
which increases the expression of PNMT in chromaffin cells, enhancing adrenaline synthesis. This is most often done in response to stress.[citation needed] The sympathetic
nervous system, acting via splanchnic nerves to the adrenal medulla, stimulates the release of adrenaline. Acetylcholine released by preganglionic sympathetic fibers of
these nerves acts on nicotinic acetylcholine receptors, causing cell depolarization and an influx of calcium through voltage-gated calcium channels. Calcium triggers the
exocytosis of chromaffin granules and thus the release of adrenaline (and noradrenaline) into the bloodstream.[citation needed]

Adrenaline (as with noradrenaline) does exert negative feedback to down-regulate its own synthesis at the presynaptic alpha-2 adrenergic receptor.[citation needed]
Abnormally elevated levels of adrenaline can occur in a variety of conditions, such as surreptitious epinephrine administration, pheochromocytoma, and other tumors of
the sympathetic ganglia.

Effect of epinephrine on glucose metabolism in humans: contribution of the liver

Epinephrine causes a prompt increase in blood glucose concentration in the postabsorptive state. This effect is mediated by a transient increase in hepatic glucose
production and an inhibition of glucose disposal by insulin-dependent tissues. Epinephrine augments hepatic glucose production by stimulating glycogenolysis and
gluconeogenesis. Although its effect on glycogenolysis rapidly wanes, hyperglycemia continues because the effects of epinephrine on gluconeogenesis and glucose
disposal persist. Epinephrine-induced hyperglycemia is markedly accentuated by concomitant elevations of glucagon and cortisol or in patients with diabetes. In both
cases, the effect of epinephrine on hepatic glucose production is converted from a transient to a sustained response, thereby accounting for the exaggerated
hyperglycemia. During glucose feeding, mild elevations of epinephrine that have little effect on fasting glucose levels cause marked glucose intolerance. This exquisite
sensitivity to the diabetogenic effects of epinephrine is accounted for by its capacity to interfere with each of the components of the glucoregulatory response, i.e.,
stimulation of splanchnic and peripheral glucose uptake and suppression of hepatic glucose production. Our findings suggest that epinephrine is an important contributor
to stress-induced hyperglycemia and the susceptibility of diabetics to the adverse metabolic effects of stress.

2.)Atropine is a tropane alkaloid extracted from deadly nightshade (Atropa belladonna), jimsonweed (Datura stramonium), mandrake (Mandragora officinarum) and
other plants of the family Solanaceae. It is a secondary metabolite of these plants and serves as a drug with a wide variety of effects. It is a competitive antagonist for
the muscarinic acetylcholine receptor. It is classified as an anticholinergic drug. Being potentially deadly, it derives its name from Atropos, one of the three Fates who,
according to Greek mythology, chose how a person was to die. Atropine is a core medicine in the World Health Organization's "Essential Drugs List", which is a list of
minimum medical needs for a basic health care system.[1]

Physiological effects and uses

Atropine increases firing of the sinoatrial node (SA) and conduction through the atrioventricular node (AV) of the heart, opposes the actions of the vagus nerve, blocks
acetylcholine receptor sites, and decreases bronchial secretions.

In general, atropine lowers the parasympathetic activity of all muscles and glands regulated by the parasympathetic nervous system. This occurs because atropine is a
competitive antagonist of the muscarinic acetylcholine receptors (acetylcholine being the main neurotransmitter used by the parasympathetic nervous system).
Therefore, it may cause swallowing difficulties and reduced secretions.

Ophthalmic use

Topical atropine is used as a cycloplegic, to temporarily paralyze the accommodation reflex, and as a mydriatic, to dilate the pupils. Atropine degrades slowly, typically
wearing off in 7 to 14 days, so it is generally used as a therapeutic mydriatic, whereas tropicamide (a shorter-acting cholinergic antagonist) or phenylephrine (an α-
adrenergic agonist) is preferred as an aid to ophthalmic examination. Atropine induces mydriasis by blocking contraction of the circular pupillary sphincter muscle,
which is normally stimulated by acetylcholine release, thereby allowing the radial pupillary dilator muscle to contract and dilate the pupil. Atropine induces cycloplegia
by paralyzing the ciliary muscles, whose action inhibits accommodation to allow accurate refraction in children, helps to relieve pain associated with iridocyclitis, and
treats ciliary block (malignant) glaucoma. Atropine is contraindicated in patients pre-disposed to narrow angle glaucoma.

Atropine can be given to patients who have direct globe trauma.

Resuscitation

Injections of atropine are used in the treatment of bradycardia (an extremely low heart rate), asystole and pulseless electrical activity (PEA) in cardiac arrest. This works
because the main action of the vagus nerve of the parasympathetic system on the heart is to decrease heart rate. Atropine blocks this action and, therefore, may speed up
the heart rate. The usual dosage of atropine in bradyasystolic arrest is 0.5 to 1 mg IV push every three to five minutes, up to a maximum dose of 0.04 mg/kg. For
symptomatic bradycardia, the usual dosage is 0.5 to 1.0 mg IV push, may repeat every 3 to 5 minutes up to a maximum dose of 3.0 mg[2].

Atropine is also useful in treating second-degree heart block Mobitz Type 1 (Wenckebach block), and also third-degree heart block with a high Purkinje or AV-nodal
escape rhythm. It is usually not effective in second-degree heart block Mobitz type 2, and in third-degree heart block with a low Purkinje or ventricular escape rhythm.
Atropine is contraindicated in ischemia-induced conduction block, because the drug increases oxygen demand of the AV nodal tissue, thereby aggravating ischemia and
the resulting heart block.

One of the main actions of the parasympathetic nervous system is to stimulate the M2 muscarinic receptor in the heart, but atropine inhibits this action.

Secretions and bronchoconstriction

Atropine's actions on the parasympathetic nervous system inhibits salivary, sweat, and mucus glands. This can be useful in treating hyperhidrosis, and can prevent the
death rattle of dying patients. Even though atropine has not been officially indicated for either of these purposes by the FDA, it has been used by physicians for these
purposes.[3]

Treatment for organophosphate poisoning


Atropine is not an actual antidote for organophosphate poisoning. However, by blocking the action of acetylcholine at muscarinic receptors, atropine also serves as a
treatment for poisoning by organophosphate insecticides and nerve gases, such as Tabun (GA), Sarin (GB), Soman (GD) and VX. Troops that are likely to be attacked
with chemical weapons often carry autoinjectors with atropine and obidoxime, which can be quickly injected into the thigh. Atropine is often used in conjunction with
Pralidoxime chloride.

Atropine is given as a treatment for SLUDGE (Salivation, Lacrimation, Urination, Diaphoresis, Gastrointestinal motility, Emesis) symptoms caused by
organophosphate poisoning. Another mnemonic is DUMBBELSS, which stands for Diarrhea, Urination, Miosis, Bradycardia, Bronchoconstriction, Excitation (as of
muscle in the form of fasciculations and CNS), Lacrimation, Salivation, and Sweating (only sympathetic innervation using Musc receptors).

Some of the nerve agents attack and destroy acetylcholinesterase by phosphorylation, so the action of acetylcholine becomes prolonged, pralidoxime (2-PAM) is the
cure for organophosphate poisoning because it can cleave this phosphorylation. Atropine can be used to reduce the effect of the poisoning by blocking muscarinic
acetylcholine receptors, which would otherwise be overstimulated by excessive acetylcholine accumulation.

Optical penalisation

In refractive and accommodative amblyopia, when occlusion is not appropriate sometimes atropine is given to induce blur in the good eye.[4]

Side-effects and overdose

Adverse reactions to atropine include ventricular fibrillation, supraventricular or ventricular tachycardia, dizziness, nausea, blurred vision, loss of balance, dilated
pupils, photophobia, dry mouth and potentially extreme confusion, dissociative hallucinations and excitation especially amongst the elderly. These latter effects are
because atropine is able to cross the blood-brain barrier. Because of the hallucinogenic properties, some have used the drug recreationally, though this is potentially
dangerous and often unpleasant.

In overdoses, atropine is poisonous. Atropine is sometimes added to potentially addictive drugs, particularly anti-diarrhea opioid drugs such as diphenoxylate or
difenoxin, wherein the secretion-reducing effects of the atropine can also aid the anti-diarrhea effects.

Although atropine treats bradycardia (slow heart rate) in emergency settings, it can cause paradoxical heart rate slowing when given at very low doses, presumably as a
result of central action in the CNS.[5]

Atropine is incapacitating at doses of 10 to 20 mg per person. Its LD50 is estimated to be 453 mg per person (per oral) with a probit slope of 1.8..[6] The antidote to
atropine is physostigmine or pilocarpine.

A common mnemonic used to describe the physiologic manifestations of atropine overdose is: "hot as a hare, blind as a bat, dry as a bone, red as a beet, and mad as a
hatter".[7] These associations reflect the specific changes of warm, dry skin from decreased sweating, blurry vision, decreased sweating/lacrimation, vasodilation, and
central nervous system effects on muscarinic receptors, type 4 and 5. This set of symptoms is known as anticholinergic toxidrome, and may also be caused by other
drugs with anticholinergic effects, such as diphenhydramine, phenothiazine antipsychotics and benztropine.[8]