yuva ......vibrant

Tuesday, November 8, 2011

"The future cannot be predicted, but futures can be invented.

Friday, January 22, 2010

STEM CELLS

HOW STEM CELLS CAN SAVE YOUR LIFE

Any sufficiently advanced technology is indistinguishable from magic, Arthur. C.Clarke once wrote. So it is stem cells and their most miraculous potential to save our lives. Stem cells are so tiny that it would take a million of them clustered together to form a pin head. Yet as their name denotes all other cells ‘stem’ from them. They can divide and multiply rapidly into cells that give rise to the brain, the heart, the spine, the limbs, the muscles, the skin and everything else that constitutes the human body. Once the body is fully grown they lie dormant in the marrow of your bones, in the cavities in your eye, under the nose, in your stomach and even in your skin waiting for the signal to transform into whichever tissue or organ that is needed .they are the hidden biological repair system –the super mechanics with a warehouse stacked with everything you need to make your body new again. Now researchers are unlocking the mysteries these nanosized cells store and are ushering in a revolution in the treatment of a range of debilitating diseases.

Sunday, August 30, 2009

DRUG

Drug Listing: Autonomic Pharmacology

* Direct Muscarinic Agonists
o Choline Esters
o Alkaloids
* Direct Nicotinic Agonist
* Acetylcholinesterase Inhibitor (Reversible)
* Acetylcholinesterase Inhibitor (Irreversible)
* Muscarinic Antagonist
* 2-PAM
* Ganglionic Blockers

* Catecholamines
* Direct Adrenoceptor Agonists
* Indirect-Acting Sympathomimetics
* Alpha adrenoceptor Antagonists
* Beta-adrenoceptor Antagonists
* Adrenergic Neuron Blocking Drugs

Direct Muscarinic Agonists

Choline Esters

* Acetylcholine
* Bethanechol (Urecholine)
* Carbachol
* Methacholine (Provocholine)

Alkaloids

* Muscarine
* Pilocarpine (Pilocar)

Direct Nicotinic Agonist

Nicotine

Acetylcholinesterase Inhibitors

Acetylcholinesterase Inhibitors ("Reversible")

* Neostigmine (Prostigmin)
* Physostigmine (Antilirium)
* Edrophonium (Tensilon)

Acetylcholinesterase Inhibitors ("Irreversible")

* Soman
* Parathion
* Malathion
* Isoflurophate (Floropryl)
* (Diisopropylflurorphosphate DFP)
* Echothiophate (Phospholine)

Muscarinic Antagonists

* Atropine
* Scopolamine
* Ipratropium (Atrovent)
* Pirenzepine (M1 selective)

2-PAM: Acetylcholinesterase Reactivator

* Pralidoxime (Protopam) {2-PAM}:peripheral acetylcholinesterase reactivator for certain phosphoryl-enzyme complexes

Ganglionic Blockers

* Mecamylamine (Inversine)
* Hexamethonium
* Trimethaphan

Catecholamines

DRUG

Epinephrine

Norepinephrine (Levophed)

Isoproterenol (Isuprel)

Dobutamine (Dobutrex)

Dopamine (Intropin)

Receptor Classification

alpha-1, alpha-2, beta-1, beta-2

alpha-1, alpha-2, beta-1

beta-1, beta-2

beta-1 (alpha-1)

D-1 (alpha-1 and beta-1 at high doses)

Direct Adrenoceptor Agonists

Drug

Phenylephrine (Neo-Synephrine)

Methoxamine (Vasoxyl)

Oxymetazoline (Afrin)

Clonidine (Catapres)

Ritodrine (Yutopar)

Terbutaline (Brethine)

Albuterol (Ventolin,Proventil)

Salmeterol (Serevent)

Receptor Classification

alpha-1

alpha-1

alpha-1, alpha-2

alpha-2

beta-2

beta-2

beta-2

beta-2

Indirect-Acting Sympathomimetics

Drug

Ephedrine, Pseudoephedrine

Cocaine

Tyramine

Amphetamine

Mechanism of Action

Release & direct receptor activation

Uptake I inhibitor

Release

similar to ephedrine, but greater CNS actions

Alpha-Adrenoceptor Antagonists

Drug

Prazosin (Minipress)

Terazosin (Hytrin)

Trimazosin

Doxazosin (Cardura)

Phentolamine (Regitine)

Phenoxybenzamine (Dibenzyline)

Tolazoline (Priscoline)

Labetalol (Trandate, Normodyne)

Yohimbine (Yocon)

Receptor Selectivity(alpha1 vs. alpha2)

alpha-1

alpha-1

alpha-1

alpha-1

non-selective

only slightly selective for alpha-1 (non-competitive)

non-selective

alpha-1 (also non-selective beta-antagonist)

alpha-2

ß-Adrenoceptor antagonists

Drug

Propranolol (Inderal)

Metoprolol (Lopressor)

Esmolol (Brevibloc)

Atenolol (Tenormin)

Nadolol (Corgard)

Timolol (Blocadren)

Pindolol (Visken)

Labetalol (Trandate, Normodyne)

Butoxamine

Receptor Selectivity

non-selective

beta-1

beta-1

beta-1

non-selective

non-selective

non-selective (partial agonist)

non-selective (selective alpha-1-antagonist)

beta-2 (no clinical applications)

Adrenergic Neuron Blocking Drugs
Reserpine

Guanethidine (Ismelin)

* non-selective blockade of vesicular uptake and storage of biogenic amines

* similar to reserpine: Uptake I dependent

DRUG LISTING

DOBUTAMINE

More about dobutamine

*

Dobutamine is a racemate; the (+) isomer produces the beta-1 effect (positive-chronotropic), but minimal cardioacceleration occurs because the (-) isomer is an alpha agonist, which tends to prevent the chronotropic effect (cardioacceleration)

*

The result is that cardiac output is increased with minimal increase in heart rate.

Saturday, August 29, 2009

CATACHOLAMINE SYNTHESIS

Catecholamine Synthetic Pathway

Adrenergic Neurotransmission: Introduction to the Neurotransmitters

Norepinephrine: transmitter released at most postganglionic sympathetic terminals

Dopamine: major CNS neurotransmitter of mammalian extrapyramidal system and some mesocortical and mesolimbic neurononal pathways.
Epinephrine: most important hormone of the adrenal medulla
Catecholamine Synthesis, Storage, and Release

Aromatic L-amino acid decarboxylase (DOPA decarboxylase)

dopa leads to dopamine
methyldopa leads to a-methyldopamine (converted by dopamine ß hydroxylase to the "false transmitter" alpha-norepinephrine)
5-hydroxy-L-tryptophanleads to5-hydroxytryptamine (5-HT)
Tyrosine Hydroxylase
tyrosine leads to DOPA
rate limiting step in pathway
tyrosine hydroxylase is a substrate for cAMP-dependent and Ca2+ - calmodulin-sensitive protein kinase and protein kinase C
Increased hydroxylase activity is associated with the phosphorylated enzyme

SITES OF CHOLINERGIC ACTION

Cholinergic Transmission: Site Differences

Skeletal Muscle

Neurotransmitter: Acetylcholine

Receptor Type: Nicotinic

Sectioning and degeneration of motor and post-ganglionic nerve fibers results in:

an enhanced post-synaptic responsiveness, denervation hypersensitivity.

Denervation hypersensivity in skeletal muscle is due to

increased expression of nicotinic cholinergic receptors

and their spread to regions aways from the endplate.

Autonomic Effectors

Neurotransmitter: Acetylcholine

Receptor type: Muscarinic

effector coupled to receptor by a G protein

In smooth muscle and in the cardiac conduction system, intrinsic electrical activity and mechanism activity is present, modifiable by autonomic tone.

Activities include propagated slow waves of depolarization: Examples: intestinal motility and spontaneous depolarizations of cardiac SA nodal pacemakers.

Acetylcholine decreases heart rate by decreases SA nodal pacemaker phase 4 depolarization.

The cardiac action potential associated with HIS-purkinje fibers or ventricular muscle consists of five phases

Phase 0 corresponds to Na+ channel activation.

The maximum upstroke slope of phase 0 is proportional to the sodium current.

Phase 0 slope is related to the conduction velocity in that the more rapid the rate of depolarization the greater the rate of impulse propagation.

Phase 1 corresponds to an early repolarizing K+ current. This current like the Phase 0 sodium current is rapidly inactivated.

Phase 2 is the combination of an inward, depolarizing Ca2+ current balanced by an outward, repolarizing K+ current (delayed rectifier).

Phase 3 is also the combination of Ca2+ and K+ currents.

Phase 3 is repolarizing because the outward (repolarizing) K+ current increases while the inward (depolarizing) Ca2+ current is decreasing.

Phase 4 in normal His-Purkinje and ventricular muscle cells is characterized by a balance between outward Na+ current and inward K+ current. As a result, the membrane potential would normally be flat.

In disease states or for other cell types (SA nodal cells) the membrane potential drifts towards threshold. This phenomenon of spontaneous depolarization is termed automaticity and has an important role in arrthymogenesis.

Rate of phase 4 depolarization is decreased by an increase in K+ conductance--which leads to membrane hyperpolarization (takes longer to reach threshold)

Autonomic Ganglia
Neurotransmitter: Acetylcholine
Receptor type: Nicotinic
Generally similar to skeletal muscle site: initial depolarization is due to receptor activation. The receptor is a ligand-gated channel.
Blood vessels
Choline ester administration results in blood vessel dilatation as a result of effects on prejunctional inhibitory synapses of sympathetic fibers and inhibitory cholinergic (non-innervated receptors).
In isolated blood vessel preparations, acetycholine's vasodilator effects are mediated by activation of muscarinic receptors which cause release of nitric oxide, which produces relaxation.
Signal Transduction

Nicotinic Receptors

Ligand-gated ion channels

Agonist effects blocked by tubocurarine

Receptor activation results in:

rapid increases of Na+ and Ca2+ conductance

deplorization

excitation

Subtypes based on differing subunit composition: Muscle and Neuronal Classification

Muscarinic Receptors

G-protein coupled receptor system

Slower responses

Agonist effects blocked by atropine

At least five receptor subtypes have been described by molecular cloning. Variants have distinct anatomical locations and differing molecular specificities