ThePharmaFacts

Confusion Over Drug Efficacy & Potency

2021-07-20T19:48:00.001+05:30

DRUG EFFICACY & DRUG POTENCY

- Both of these are like TWO DIFFERENT beds in a single room!!

- Often these two terms ‘Drug Potency’ & ‘Drug Efficacy’ are used relatively, but these are not synonymous & refer to different characteristics of the drug

- So, this is the article from where you may clearly understand the difference between these two terms which we mentioned earlier as two different beds in a single room!

1. DRUG POTENCY:

- Amount of Drug Needed to produce maximum effect which is done by the Drug-Receptor Interaction.

- It is the ability/affinity of drug to bind receptors.

- Amount of drug is inversely proportional to potency that means lesser the amount of drug required to produce maximum effect, more will be the potency of that drug.

- It is also known as Drug Strength.

- Potency refers to the concentration OR dose of a drug required to produce 50% of that drug’s maximal effect.

2.DRUG EFFICACY [ E_MAX]:

- Efficacy is the concept of a drug after interaction with receptor.

- Hence it is an Ability of Drug to produce effect.

- This is the ability to initiate conformational changes in receptors which leads to certain effects. Efficacy is the concept of a drug after interaction with receptor.

- In other words, it is the capacity of a drug to produce a maximum response.

- Hence, it can also be termed as Maximal Efficacy [ E_MAX]. Maximal Efficacy of a drug assumes that all receptors are occupied by drug & if more drugs are added, no further additive response will be observed.

- Collectively, it can define as the ability of a drug to elicit a physiological response when it interacts with receptor.

- Efficacy is depending on:

1. Number of Drug-Receptor Complexes are formed.

2. Efficiency of the coupling of receptor activation to cellular response.

Just_Touch_me to get brief about Difference between Drug Potency & Drug Efficacy.

Both of these Terms are Mathematically Understandable from DOSE RESPONSE CURVE.

DOSE RESPONSE CURVE:

- Two aspects viz;

(I) Dose-Plasma Concentration Relationship

(II) Plasma Concentration-Response Relationship

- Intensity of Response Increases with Increase in Dose / more Precisely Increase in Concentration at Receptor).

- Drug-Receptor Interaction obeys Law of Mass Action, which is illustrated by the formula;

- Where, E is Observed Effect at a Dose [D] of drug; EMAX is Maximal Response; KD is Dissociation Constant of Drug-Receptor Complex.

- Dose-Response Curve is a Rectangular Hyperbola Logarithmic Dose-Response Curve is Sigmoid Drug Potency & Efficacy can be determined by Drug Response Curve.

- Potency & Efficacy of Drug can be determined by Dose Response Curve as shown below:

Drug B is Less Potent but Equally Efficacious as Drug A

Drug C is Less Potent and Less Efficacious than Drug A

Drug D is More Potent than Drugs A, B, & C, but Less Efficacious than Drugs A & B, & Equally Efficacious as Drug C

- Log Dose-Response Curves [DRC] IS Plotted because it has several advantages like;

(I) Wide Range of Drug Doses can be Easily Displayed on a Graph

(II) Comparison Between Agonists & Study of Antagonists becomes Easier

Dose-response curves are used to derive Dose Estimates of chemical substances.

DOSE ESTIMATES:

There are Three important Dose Estimating classical terms are there which are:

1.Lethal Doses [LDs]

2.Effective Doses [EDs]

3.Toxic Doses [TDs]

1.Lethal Doses [LDs]:

- Initially, LD50 (Lethal Dose 50%) has been a common dose estimate for acute toxicity.

- LD50 is statistically derived maximum dose at which 50% of the group of organisms (rat, mouse, or other species) would be expected to die.

- LD50 testing is no longer the recommended method for assessing toxicity because of the ethics of using large numbers of animals, the variability of responses in animals and humans & the use of mortality as the only endpoint.

- Regulatory agencies use LD50 only if it is justified by scientific necessity & ethical considerations.

- Concentrations / Lethal Dose 0% (LD0) represents the dose at which no individuals are expected to die. This is just below the threshold for lethality.

- Concentrations / Lethal Dose 10% (LD10) represents the dose at which 10% of the individuals will die.

- Lethal Concentration 50% (LC50) refers for inhalation toxicity, air concentrations are used for exposure values. The LC50 refers to the calculated concentration of a gas lethal to 50% of a group. Very occasionally LC0 and LC10 are also used.

2.Effective Doses [EDs]:

- Effective Doses (EDs) are used to indicate the effectiveness of a substance.

- Normally, effective dose refers to a beneficial effect such as relief of pain.

- It may also stand for a harmful effect such as paralysis.

- Thus, the specific endpoint must be indicated.

- The usual terms are: ED0, ED10, ED50, ED90.

3.Toxic Doses (TDs):

- Toxic Doses (TDs) are used to indicate doses that cause adverse toxic effects.

- The usual dose estimates include: TD0, TD10, TD50, TD90. [TD50 is Dose required to produce a toxic effect i 50% of population].

Determining the Pharmaceutical Relative Safety:

- Toxicologists, pharmacologists & others use effective and toxic dose levels to determine the relative safety of pharmaceuticals.

THERAPEUTIC INDEX:

- Quantitative measurement of relative safety of drug.

- Therapeutic Index (TI) is used to compare the therapeutically effective dose to the toxic dose of a pharmaceutical agent.

- TI is a statement of relative safety of a drug.

- It is the ratio of the dose that produces toxicity to the dose needed to produce the desired therapeutic response.

- The common method used to derive the TI is to use the 50% dose-response points, including TD50 & ED50.

- Que. If the TD50 is 100 & the ED50 is 20 mg, then TI would be?

- More the Safety if more is TI [TI directly Proportional to Safety]

- In Low TI i.e., Low Safety Margin, even the smaller increment in the dose would produce toxic effects.

- Like that, In High TI i.e., High Safety Margin, more reliability of the dose is possible since it would not produce toxic effects after smaller increment in dose.

- Bioavailability of a drug should be done at Low TI.

- However, the use of the ED50 & TD50 doses to derive the TI may be misleading about a drug's safety, depending on the slope of the dose-response curves for therapeutic & toxic effects.

- To overcome this demerit, toxicologists often use another term to denote the safety of a drug i.e., Margin of Safety [MOS].

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Pharmacology Syllabus [PCI]

2021-07-17T09:04:00.003+05:30

Pharmacology Syllabus [PCI]

1.General Pharmacology:

- History & Scope

- IMP Definitions

- Nature & Source of Drugs

- Essential Drugs Concept & Routes of Drug Administration

- Pharmacokinetics:

- Membrane Transport

- ADME

- Enzyme Induction & Enzyme Inhibition

- Kinetics of Elimination

- Pharmacodynamics:

- MOA

- Receptors: Theories, Classification & Regulation

- Signal Transduction Mechanisms/Transducer Mechanisms

- Dose Response Relationship

- Therapeutic Index

- Combined Effects of Drugs

- Factors Modifying Drug Action

- Adverse Drug Reactions [ADR's]

- Drug Interactions [Pharmacokinetic & Pharmacodynamic]

- Drug Discovery & Clinical Evaluation of New Drugs

2.Pharmacology of Drugs Acting on Peripheral Nervous System:

- Parasympathomimetic

- Parasympatholytic

- Sympathomimetics

- Sympatholytic

3.Pharmacology of Drugs Acting on Central Nervous System:

- General Aesthetics & Pre-Aesthetics

- Sedatives

- Hypnotics

- Centrally Acting Muscle Relaxants

- Anti-Epileptics

- Alcohols & Disulfiram

- Psychopharmacological Agents

- Drugs Acting on Parkinson's Disease & Alzheimer‘s Disease

- CNS Stimulants & Nootropics

- Opioid Analgesics & Antagonists

4.Pharmacology of Drugs Acting on Cardio Vascular System[CVS]:

- Congestive Heart Failure [CHF]

- Anti-Hypertensive Drugs

- Anti-anginal Drugs

- Anti-Arrhythmic Drugs

- Anti-Hyperlipidemic Drugs

- Therapy of Shock

- Hematinics, Coagulants & Anticoagulants

- Fibrinolytics & Anti-Platelet Drugs

- Plasma Volume Expanders

5.Pharmacology of Drugs Acting on Urinary System:

- Diuretics

- Anti-Diuretics

6.Pharmacology of Drugs Acting on Endocrine System:

- Anterior Pituitary Hormones-Analogues & their Inhibitors

- Thyroid Hormones-Analogues & their Inhibitors

- Hormones Regulating Plasma Calcium Level

- Insulin, Oral Hypoglycemic Agents & Glucagon

- ACTH & Corticosteroids

- Androgens & Anabolic Steroids

- Estrogens, Progesterone & Oral Contraceptives

- Drugs Acting on Uterus

7.Pharmacology of Drugs acting on Respiratory System:

- Anti-Asthmatic Drugs

- Drugs Used in Management of COPD

- Expectorants & Antitussives

- Nasal Decongestants

- Respiratory Stimulants

8.Pharmacology of Drugs Acting on Gastrointestinal Tract:

- Antiulcer Agents

- Drugs for Constipation & Diarrhoea

- Appetite Stimulants & Suppressants

- Digestants & Carminatives

- Emetics & Anti-Emetics

9.Autocoids & Related Drugs:

- Histamine, 5-HT & their Antagonists

- Prostaglandins

- Angiotensin, Bradykinin & Substance P

- Non-Steroidal Anti-Inflammatory Agents [NSAID]

- Anti-Gout Drugs

- Antirheumatic Drugs

10.Chemotherapy:

- Antitubercular Agents

- Antileprotic Agents

- Antifungal Agents

- Antiviral Drugs

- Anthelmintics

- Antimalarial Drugs

- Antiamoebic Agents

- Urinary Tract Infections[UTI’s] & Sexually Transmitted Diseases[STD’s]

- Chemotherapy of Malignancy

11.Immunopharmacology:

- Immunostimulants

- Immunosuppressant

12.Principles of Toxicology:

- Genotoxicity

- Carcinogenicity

- Teratogenicity

- Mutagenicity

- Treatment of Poisoning

- Symptoms & Management of Barbiturates, Morphine, Organophosphosphorus Compound

- Lead, Mercury & Arsenic Poisoning

13.Chronopharmacology:

- Definition of Rhythm & Cycles

- Biological Clock & their Significance Leading to Chronotherapy

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Mucormycosis.

2021-07-15T10:55:00.000+05:30

Mucormycosis is an angio invasive infection that occurs due to the fungi Mucorales. It is a rare disease but increasingly recognized in immunocompromised patients. It can be categorized into rhino-orbito cerebral, cutaneous, disseminated, gastrointestinal, and pulmonary types.

INTRODUCTION

American pathologist "R.D. Baker"

coined the term Mucormycosis.

ETIOPATHOGENESIS

Mucorales attack deep tissues by means of ingestion or inhalation of spores, and percutaneous injection of spores.

As soon as the spores penetrate into the lung or cutaneous tissues, the first line of defense in the healthy host is capable of destroying the spores via oxidative metabolites and cationic peptides.

Risk factors include,

uncontrolled diabetes mellitus
ketoacidosis
steroid use
extremes of age
neutropenia
hematological malignancy
AIDS
renal insufficiency
organ or stem cell transplantation
iron overload
skin trauma
broad-spectrum antibiotics

TREATMENT:

"Antifungal drugs" are required to treat mucormycosis infections but in many serious conditions we need to remove an infected organ or tissue.

These are some drugs with their possible routes:

1.INTRAVENOUS ROUTE: Amphotericin B, Posaconazole, or Isavuconazole.

2.ORAL ROUTE: Posaconazole, Isavuconazole.

G-Protein Coupled Receptors

2021-07-07T19:46:00.003+05:30

G-Protein Coupled Receptors (GPCRs)

A. Adenylyl Cyclase: cAMP Pathway

B. Phospholipase C: IP3-DAG Pathway

C. Channel Regulation

A. Adenylyl Cyclase: cAMP Pathway:

- Adrenaline binds to β-adrenergic receptor on the cell surface inducing a conformational change which permits interaction of the G-protein binding site with the stimulatory G-protein [Gs].

- The activated α subunit of Gs now binds GTP & dissociates from the βγ dimer as well as the receptor then Gs-α carrying bound GTP associates with & activates the enzyme Adenylyl Cyclase [AC] located on the cytosolic side of the membrane where ATP is hydrolyzed to cAMP which then phosphorylates & thus activates cAMP Dependent Protein Kinase [PKA].

- The PKA in turn phosphorylates many functional proteins including Troponin & Phospholamban, so that they interact with Ca2+.

- They resulting in increased force of contraction & faster relaxation respectively. Calcium is made available by entry from outside (direct activation of myocardial membrane Ca2+ channels by Gsα and through their phosphorylation by PKA) & from intracellular stores too.

- One of the other proteins phosphorylated by cAMP is Phosphorylase Kinase which then activates the enzyme Phosphorylase resulting in breakdown of glycogen to be utilized as energy source for increased contractility.

- Action of acetylcholine on Muscarinic M2 receptor [M2-R also located in the myocardial membrane] similarly activates an inhibitory G-protein (Gi).

- The GTP carrying active Giα subunit inhibits AC, and opposes its activation by Gs-α.

- The βγ dimer of Gi activates membrane K+ channels causing hyperpolarization which depresses impulse generation.

B. Phospholipase C: IP3-DAG Pathway:

- The important steps of Phospholipase cβ [PLcβ] Pathway of response effectuation (in smooth muscle) is initiated as, agonist, e.g., Histamine binds to its H1 receptor [H1-R] & activates the G-Protein Gq.

- Its α subunit binds GTP in place of GDP, dissociates from the receptor as well as from βγ dimer to activate membrane bound PLcβ that hydrolyses phosphatidyl inositol 4, 5-bisphosphate [PIP2], a membrane bound phospholipid.

- The products Inositol 1, 4, 5-trisphosphate [IP3] & Diacylglycerol [DAG] act as second messengers.

- The primary action of IP3 is facilitation of Ca2+ mobilization from intracellular organellar pools, while DAG in conjunction with Ca2+ activates Protein Kinase-C [PKc] which phosphorylates & alters the activity of a number of functional & structural proteins.

- Cytosolic Ca2+ is a veritable messenger: combines with Calmodulin [CAM] to activate Myosin Light Chain Kinase [MLCK] inducing contraction & another important regulator Calcium-Calmodulin Protein Kinase [CCPK].

- Several other effectors are regulated by Ca2+ in a CAM dependent or independent manner. Cytosolic Ca2+ is recycled by uptake into the endoplasmic reticulum as well as effluxed by membrane Ca2+ pump.

C. Channel Regulation:

- The activated G-Proteins (Gs, Gi, Go) can also open/inhibit Ionic Channels, specific for Ca2+ & K+, without the intervention of any second messenger like cAMP/IP3 & bring about hyperpolarization/ depolarization/changes in intracellular Ca2+.

- Gs opens Ca2+ channels in Myocardium & Skeletal Muscles, while Gi & Go open K+ channels in heart & smooth muscle as well as inhibit neuronal Ca2+ channels.

- Direct channel regulation is mostly the function of the βγ dimer of the dissociated G protein.

- Physiological responses like changes in inotropy, chronotropy, transmitter release, neuronal activity & smooth muscle relaxation are depicted in this mechanism.

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Physiological Barriers

2021-06-03T16:20:00.001+05:30

Physiological Barriers

Physiological Barriers to Distribution of Drugs contains a membrane (or a barrier) with special structural features which can be a permeability restriction to distribution of drugs to some tissues

Some important simple and specialized physiological barriers are:

1. Simple capillary endothelial barrier

2. Simple cell membrane barrier

3. Blood-brain barrier

4. Blood-CSF barrier

5. Blood- placental barrier

6. Blood-testis barrier

1.Simple Capillary Endothelial Barrier:

All drugs, ionized/unionized, with a molecular size less than 600 Daltons, diffuse through this barrier into the interstitial fluid
Only drugs bound to blood components are restricted because of large molecular size of the complex

2.Simple Cell Membrane Barrier:

Simple cell membrane is similar to the lipoidal barrier in the GI absorption of drugs
The physicochemical properties that influence permeation of drugs across such a barrier are summarized below:

3.Blood-Brain Barrier (BBB):

Brain capillaries consist of endothelial cells which are joined to one another by continuous tight intercellular junctions comprising of blood-brain barrier as shown below:

Drugs administered intranasally may diffuse directly into the CNS because of the continuity between submucosal areas of the nose and the subarachnoid space of the olfactory lobe
Drug may cross to brain via only one of following two pathways:

i) Passive diffusion through the lipoidal barrier having high o/w partition coefficient

ii) Active transport of essential nutrients such as sugars and amino acids. So, structurally similar foreign molecules can penetrate BBB by the same mechanism

Three different approaches have been utilized successfully to promote crossing the BBB by drugs viz;

i) Use of permeation enhancers such as Dimethyl Sulphoxide (DMSO)

ii) Osmotic disruption of the BBB by infusing internal carotid artery with mannitol

iii) Use of Dihydropyridine Redox System as drug carriers to the brain : CNS enzymes oxidize the Dihydropyridine into Polar Pyridinium Ion form that cannot diffuse back out of the brain, which result in trapping of drug in the CNS

4.Blood-Cerebrospinal Fluid (CSF) Barrier:

CSF is formed mainly by the choroid plexus of the lateral, third and fourth ventricles
Choroidal cells are joined to each other by tight junctions forming the blood-CSF barrier which has permeability characteristics similar to that of the BBB
As in the case of BBB, only highly lipid soluble drugs can cross the blood-CSF barrier with relative ease

Mechanisms for diffusion of drugs into the CNS and CSF are similar
Bulk flow of CSF continuously removes the drug & hence drug concentration in brain is always higher than that of CSF [Exception: Sulfamethoxazole and Trimethoprim]

5.Blood-Placental Barrier:

Maternal and the foetal blood vessels are separated by number of tissue layers made of foetal trophoblast basement membrane and the endothelium which together constitute the placental barrier as shown below:

Placental barrier has a mean thickness of 25 microns in early pregnancy that reduces to 2 microns at full term without alteration in its effectiveness
Drugs having molecular weight less than 1000 Daltons and moderate to high lipid solubility e.g. Ethanol, Sulfonamides, Barbiturates, Gaseous anesthetics, Steroids, Narcotic analgesics, Anticonvulsants & some Antibiotics, cross the barrier by simple diffusion
Placental barrier is not as effective a barrier as BBB or Blood-CSF Barrier
Nutrients essential for the foetal growth transported by carrier-mediated processes & Immunoglobulins by endocytosis
Teratogenicity is defined as foetal abnormalities caused by administration of drugs during pregnancy & agent causing this toxic effects is known as Teratogen
Drugs can affect the foetus at 3 stages as shown below:

It is always better to avoid all drugs during pregnancy because of uncertainty of their hazardous effects

6.Blood-Testis Barrier:

This barrier is located at sertoli-sertoli cell junction
This barrier restricts the passage of drugs to spermatocytes and spermatids
Preleptotene spermatocytes and spermatogonia are germ cells located outside the blood-testis barrier provided by the Sertoli cells
Function of this barrier is to hide germ cells present in the adluminal (Near or toward the lumen of a seminiferous tubule) compartment from the circulatory and lymphatic systems & together with local immune suppression, to provide an Immuno-privileged (toleration of antigens without eliciting an inflammatory immune response) microenvironment for the completion of meiosis

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TETRACYCLINE : ANTIBIOTICS

2021-05-23T15:52:00.001+05:30

TETRACYCLINE

All are obtained from Actinomycetes species
They are bitter solids & their hydrochlorides soluble in water
Derivatives of Octahedro Napthacene (having 4 annulated six-membered rings together)
Amphoteric compounds (having both acid & base properties)

General Information:

General Structure:

SAR of Tetracyclines:

1.Modification at C1 & C3:

- Keto-enol tautomerism of ring A in C1 & C3 is common feature to all biologically active tetracyclines, blocking this system by forming derivatives like A–C = O at C1 and C3 results in loss of antibacterial activity

- Function of C1 & C3 is essential for activity

2.Modification at C2 position:

- Antibacterial activity depends on the carboxamide (CONH2) moiety.

- Amide is best when left unsubstituted or monosubstitution is acceptable of 'alkylamino methyl amide/Mannich base' (Rolitetracycline)

- Large alkyl group on the carboxamide may alter normal keto-enol equilibrium of the C1, C2 & C3 conjugated systems and diminishes inherent antibacterial activity

- The replacement of carboxamide group or dehydration of carboxamide to the corresponding nitrile results in a loss of activity.

3.Modification at C-4 & C4a position:

- C4: Keto-enolic character of the A-ring is due to the α-C4 dimethyl amino substituent

- C4: Loss of activity is exerted when dimethyl amino group is replaced with hydrazone, oxime or hydroxyl group

- C4: Epimerization makes compound inactive (as shown below)

- C4a: α-hydrogen at C4a position of tetracyclines is necessary for useful antibacterial activity

4.Modification of the C5 & C5a position:

- C5: Alkylation of the C5 hydroxyl group results in loss of activity

- C5: Epimerization is harmful to antibacterial activity (as shown earlier at C4 position)

- C5a: α-hydrogen at C5a position of tetracyclines is necessary for useful antibacterial activity

5.Modification at the C6 position:

- C6 methyl group contributes little to antimicrobial activity thus it is tolerant to variety of substituents

- Majority of tetracyclines have α-methyl group & β-hydroxyl group at this position

- Demeclocycline is a naturally occurring C6 demethylated chlortetracycline with an excellent activity

- Removal of C6 hydroxyl group affords doxycycline, which exerts good antibacterial activity

6.Modification at C7 position:

- Nature of the aromatic D-ring makes C7 liable to electrophilic substitution. Substitution with electron withdrawing group such as nitro(-NO2) & halogen groups are introduced in some C7 tetracyclines, which produces the most potent of all the tetracyclines in vitro, but their are compounds are potentially toxic and carcinogenic

- Substituents like acetoxy, azido, and hydroxyl groups reduces antibacterial activity

7.Modification at C10 position:

- C10 phenolic moiety is necessary for antibacterial activity

- C10 substitution with para or ortho substitution with hydrogen group activates the C9 & C7 positions

8.Modification at C11 & C11a position:

- C11 carbonyl moiety is a part of one of the conjugated keto-enol system required for antibacterial activity

- C11a: No stable compounds formed by modifications at this position

9. C-12/12a position:

- Esterification of the hydroxyl group leads to enhanced lipophilicity and it should undergo hydrolysis to leave the active tetracycline with hydroxyl group at 12a position, which is necessary to produce good antibacterial action

- Transport and binding of these drugs depends on keto-enol system

D-ring needs to be aromatic and the A-ring must be appropriately substituted at each of its carbon atoms for notable activity
B-ring and the C-ring tolerate certain substituent changes as long as the keto-enol systems (at C-11, 12, 12a) remain intact and conjugated to phenolic D-ring
D, C, B-ring phenol, keto-enol system is must & A-ring must also contain a conjugated keto-enol system
Specifically, A-ring contains tricarbonyl derived keto-enol moiety at positions C-1, 2, and -3
Other structural requirements for good antibacterial activity include basic amine function at C-4 position of the A-ring

Stereochemistry:

C-4,4a,5,5a,6,12a are potentially chiral carbons depending on substituents
Oxytetracycline & Doxycycline have 6 chiral carbons since they possess 5-α-hydroxy substituent & rest have 5 chiral carbons

Classification:

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CEPHALOSPORIN : ANTIBIOTIC

2021-05-15T16:12:00.001+05:30

Cephalosporins

Derived from a fungus Acremonium which word is previously known as Cephalosporium
Discovered in 1945 by Brotzu
He observed that the culture produced substances which were effective against Salmonella typhi (an agent causing typhoid)

General Information:

General Structure:

SAR Of Cephalosporins:

1. 7-Acylamino substituents:

- Acylation of the amino group generally increases potency against gram positive bacteria, but decrease in gram-negative potency.

- High antibacterial activity is observed only when the new acyl groups are derived from carboxylic acids for gram-positive bacteria.

- Substituents on the aromatic ring that increases lipophilicity provide higher gram-positive activity and generally lower gram-negative activity.

- Phenyl ring in the side-chain can be replaced with other heterocycles with an improved spectrum of activity and pharmacokinetic properties and these include thiophene, tetrazole, furan, pyridine, and aminothiazoles

2. C-3 Substituents:

- The nature of C-3 substituents influences pharmacokinetic and pharmacological properties as well as antibacterial activity.

- Modification at C-3 position has been made to reduce the degradation (lactone of diacetyl cephalosporin) of cephalosporins.

- Pyridine and imidazole replaced -ACo (Acetoxy) group show improved activity against aeruginosa.

- Displacement of -ACo group by azide ion yields derivatives with relatively low gram-negative activity.

- Displacement with aromatic thiols of -ACo group results in an enhancement of activity against gram-negative bacteria with improved pharmacokinetic properties.

- Replacement of -ACo group at C-3 position with -CH3, -Cl has resulted in orally-active compounds.

3. 1st Position (S-Position):

- Oxidation of ring sulphur to sulfoxide or sulfone greatly diminishes or destroys the antibacterial activity.

- Replacement of sulphur(S) with oxygen(O) leads to Oxazepam (Latamoxef) with increased antibacterial activity, because of its enhanced acylating power & replacement of sulphur(S) with -CH3 group (Loracarbef) has greater chemical stability and a longer half-life.

4. C-4 Position:

- Carboxyl group of 4^th the position has been converted into ester prodrugs to increase bioavailability, and these can be given orally as well (Cefuroxime Axetil and Cefpodoxime Proxetil).

5. C-7 Position:

- Introduction of α-methoxy group (-OCH3), shows higher resistance

to hydrolysis by β- Lactamase enzyme (Cephamycin).

6. Olefinic/Alkene Linkage:

- Compounds that contain only hydrogen and carbon and at least one double or triple bond is known as Olefinic Linkage.

- This linkage between C3 & C4 is essential for antibacterial activity.

- Isomerization or transfer of olefinic bond from C3=C4 to C3=C2 leads to great loss in antibacterial activity.

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Local Anesthetics

2021-04-29T15:42:00.000+05:30

Local Anesthetics : (LA)

- These agents prevent generation and conduction of nerve impulses at the site of application or injection

- This leads to loss of sensation which is reversible

- Also causes absence of pain sensation at specific location without loss of consciousness hence also known as "Local Analgesics"

Routes of Administration :

i) Topical Anaesthesia (Surface)

ii) Intravenous (IV) - Either for regional nerve block or for large region block

iii) Spinal Anaesthesia (Within spinal theca)

Mechanism of Action of LA :

i) Generation and propagation of nerve impulses at the site of action on cell membrane are blocked

ii) Blocking of Na/K ATPase enzyme leads to Na & K ions influx & outflux restriction respectively therefore membrane stabilization

iii) Na-channel blocking prevents depolarization (i.e.more positive inside cell)

iv) This increases the threshold of excitability and thus block the nerve impulse conduction

Normal Nerve Conduction shown below :

SAR of LA :

Since, these drugs possess both hydrophilic as well as lipophilic parts, it shows Amphiphilic properties. As shown below in diagram ;

1) Lipophilic Group :-

- Lipophilicity is important to penetrate the lipid layer and reach the binding site on the the inside of the cell

- Lipophilic path contains aromatic moiety which either directly attached to carbonyl function (amino esters) or 2,6-dimethylphenyl group attach to carbonyl function through amino amide -(-NH-)- groups

- These groups are essential in binding of LA to channel receptor proteins

drug lipophilicity ∝ receptor affinity ∝ drug potency ∝ duration of action of drug

- Lipophilic groups are mostly Aryl groups since aryl group directly attached to carbonyl group enhancers and aesthetic activities

- An electron donating substituent at ortho or para or both positions in aryl group increases local anaesthetic potency

E.g. Benzocaine, Procaine, Butamben, Propoxycaine, Benoxinate

- Also, electron donating substituent give rise to Zwitterionic form and thus increases binding affinity of LA with receptors as shown below,

- Insertion of methyl in group between aromatic moiety & carbonyl function prohibits the formation of Zwitterionic form and hence greatly reduces the anesthetic potency.

- Electron donating group at ortho position of aromatic ring also provide suitable protection from Ester hydrolysis by inductive effect to give longer duration of action

E.g. Propoxycaine

- Electron withdrawing group at ortho position of aromatic ring makes the Ester group more susceptible to the Ester hydrolysis make drug with shorter duration of action

E.g. Chloroprocaine

- Aryl groups are attached to carbonyl group through -NH group in Anilide derivatives

- Aryl substitution with methyl group at both ortho positions is required to provide suitable protection from Amide hydrolysis to give longer duration of action in Anilide derivatives

E.g. Lidocaine, Etidocaine, Mepivacaine (-CH3 at both ortho positions)

2) Alkyl Chain :-

- 1 to 3 carbon chain essential to prolonged duration of action of LA by hindering the hydrolysis of esters and amides

E.g. Propoxycaine, Chloroprocaine (Esters)

Prilocaine, Etidocaine (Anilides)

3) Hydrophilic Group :-

- Secondary or tertiary amines which could be cyclic or noncyclic are attached for anesthetic activity

- This amine group forms water soluble salts with acids (as shown below) & that's why this group required to prepare parenteral preparations

Classification of LA :

1) Benzoic Acid Derivatives:

- Cocaine

- Hexylcaine (Cyclaine/Osmocaine)

- Meprylcaine (Epirocaine/Oracaine)

- Cyclomethycaine

- Piperocaine

2) Amino Benzoic Acid Derivatives:

- Benzocaine

- Butamben

- Procaine

- Butacaine

- Propoxycaine

- Tetracaine

- Benoxinate

3) Lidocaine/Anilide derivatives/Lignocaine:

- Lidocaine

- Mepivacaine

- Prilocaine

- Etidocaine

4) Miscellaneous:

- Phenacaine

- Diperodon

- Dibucaine (most potent, toxic & long acting LA)

REMDESIVIR - A BURNING TOPIC

2021-04-24T17:51:00.022+05:30

Patients all over world are facing tremendous health care hazards that are caused by the Severe Acute Respiratory Distress Syndrome Coronavirus 2 (SARS-CoV-2) pandemic. Remdesivir {First described in 2016} is the first approved treatment for severe coronavirus disease 2019 (COVID-19). It is a "Novel Nucleoside Analog" with a broad antiviral activity spectrum among RNA viruses, including Ebolavirus (EBOV) and Respiratory Pathogens like the Middle East Respiratory Syndrome Coronavirus (MERS-CoV), SARS-CoV, and SARS-CoV-2. In vivo, Remdesivir showed therapeutic as well as prophylactic effects in animal models of EBOV, MERS-CoV, SARS-CoV, and SARS-CoV-2 infection. However, the substance failed to some extent in a clinical trial on ebola virus disease (EVD), where it was inferior to investigational monoclonal antibodies in an interim analysis. As there was no placebo control in this study, no conclusions on its efficacy in EVD can be made. In contrast, data from placebo-controlled trials show beneficial effects for patients with COVID-19. Remdesivir reduces the time to recovery of hospitalized patients who require supplemental oxygen and may have a positive impact on mortality outrage, while having a favorable safety profile. Although this is an important milestone in the fight against COVID-19, approval of this drug will not be sufficient to solve the public health issues caused by the ongoing pandemic. Further scientific efforts are needed to evaluate the full potential of nucleoside analogs ( like Remdesivir ) as treatment or prophylaxis of viral respiratory infections and to develop effective antivirals that are effective & orally bioavailable.

It was December 2019,a novel coronavirus (nCoV), Severe Acute Respiratory Distress Syndrome CoronaVirus-2 (SARS-CoV-2), emerged in central China (Wuhan). Like in SARS-CoV, infections with the closely related SARS-CoV-2 cause a respiratory disease that can progress to viral Pneumonia and Acute Respiratory Distress Syndrome (ARDS) . Because of its onset in December 2019, the associated disease was called coronavirus disease 2019 (COVID-19).

Till today this pandemic causes several deaths worldwide & hitting every part of world so badly🌎. In the spectra of an uncontrolled expansion and the steadily increasing COVID-19 fatalities in summer 2021 (As per Indian Time), huge efforts were put into the identification of effective antiviral agents against COVID-19. Nucleoside/nucleotide analogs are one of the most promising antiviral drug classes in general, and significant drug discoveries emerged from this class that today form the basis for treatments against infections with several herpesviruses, Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), and Hepatitis C Virus (HCV). Remdesivir is a prodrug of a nucleoside analog with direct antiviral activity against several single-stranded RNA viruses, including SARS-CoV and MERS-CoV. The first cell-based studies of Remdesivir also showed antiviral activity against the novel SARS-CoV-2. In the absence of any effective treatment options against COVID-19, Remdesivir has been applied under "compassionate use" & not 100% efficient & complimentary drug. Recently, a randomized placebo-controlled clinical trial showed that Remdesivir reduces the time to recovery in patients with COVID-19, leading to an Emergency Use Authorization (EUA) by the U.S. Food and Drug Administration (FDA) only 2 days after the first press release from the National Institute of Allergy and Infectious Diseases (NIAID). On 3 July, the European Medicines Agency (EMA) granted a conditional marketing authorization for Remdesivir, now being the first approved antiviral treatment against COVID-19.Growth of Remdesivir is shown below.

What is Remdesivir?

Being a Pharmacist, we study all category drugs from normal sneezing coughing to highly dangerous cancer, but nowadays we all are suffering from covid-19 pandemic and this is the second wave of Corona virus and its severity and mortality rate increases more day by day. Now as the Covid-19 cases set a new benchmark daily.

This drug is a highly demanded drug across india. Cases are touching new high daily so ultimately demand is also high but its supply is down so across. We heard in many cities reports of fake injections of remdesivir and massive black marketing of the vials.

So Many Questions are arises in front of you guys as a pharmacist. What is this remdesivir & which is its class? Is it really significant over Covid-19? Who permits this drug over covid-19 treatment ? Which side effects may be shown if we take it as chronic treatment ? Which Mechanism of Action it shows ? Like that so we will discuss here pointwise.

It is Novel Antiviral drug belonging to Nucleotides analog. The Chemical structure of Remdesivir shown below, directs that structurally Remdesivir resembles Nucleotide with Phosphate derivative where one part is Nucleoside core & another is Prodrug Component.It is Antiviral Family Drug.

Mechanism of Action of Remdesivir :

Remdesivir is a Monophosphoramidate Nucleoside Prodrug that undergoes intracellular metabolic conversion to its active metabolite Nucleoside Triphosphate (NTP) as shown in the diagram below.

As described for several other direct-acting antivirals, the active metabolite of Remdesivir Triphosphate [Remdesivir-TP] subsequently targets the machinery responsible for the replication of the viral RNA genome, a highly conserved element of the viral life cycle. Nucleoside analogs are synthetic compounds that work by competition with endogenous natural nucleoside pools for incorporation into replicating viral RNA. While these compounds mimic their physiological counterparts, the incorporation of the analog molecule disrupts subsequent molecular processes. The drug target and the exact processes that lead to the inhibition of viral replication have been studied extensively in ebolavirus.

The suggested drug target, the EBOV RNA-dependent RNA polymerase (RdRp) complex, was only recently biochemically purified, which allowed for in-depth molecular analyses. Viral RdRp is the target protein for the active metabolite remdesivir-TP. Remdesivir-TP acts as the substrate for RdRp where it competes with ATP for incorporation into new strands. Inhibition of EBOV or Covid-19 RdRp most probably results from delayed chain termination, a mechanism that is known from approved antivirals against human immunodeficiency virus type 1 (HIV-1) and HBV (Hepatitis). Most importantly, the activity of human RNA polymerase is not inhibited in the presence of Remdesivir-TP.

Intracellular activation of Remdesivir and inhibition of coronavirus replication --- Way through the cell membrane by Remdesivir is facilitated by the prodrug component attached to the nucleoside core. Upon entering the target cell, the pronucleotide undergoes further phosphorylation steps to become the active Triphosphate metabolite that effectively inhibits viral RNA replication.

Delayed chain termination is caused by the following processes:

(i) Disintegration of nucleoside triphosphate (NTP) into replicating RNA by RdRp (ii) Prevention of further chain elongation after NTP along with 3 additional nucleosides and premature termination of RNA synthesis.

Side Effects :

In the Ebola trial, researchers noted side effects of remdesivir (RDV) that included:

-Increased liver enzyme levels that may indicate possible liver damage

-Nausea

-Vomiting

Dosage :

The dosing regimen understudy in the U.S. for RDV is as follows:

-An initial one-time dose of 200mg

-Followed by 100mg per day for 10 days

-Remdesivir is administered intravenously (IV) by injection.

Contraindications :

(In Pregnant women or Breastfeeding women)

In rats and monkeys, RDV affected kidney development in fetuses.

It is unknown if RDV passes into breast milk. Consult your medical practitioner before breastfeeding.

Why Remdesivir Is Not Ultimate Drug Against Covid-19?

In SARS-CoV and MERS-CoV, Remdesivir-TP interferes with the nonstructural RNA binding protein i.e. nsp12 polymerase, which is a multisubunit RNA synthesis complex of viral nonstructural proteins (nsp) produced as cleavage products of viral polyproteins. As nsp12 is highly conserved across the coronavirus family, it is most likely that the mechanism of action of Remdesivir does not differ significantly among CoVs.

Like in EBOV, Remdesivir-TP efficiently inhibits the replication of SARS-CoV and MERS-CoV by causing delayed chain termination when being incorporated into the replicating RNA. A recent biochemical analysis revealed that in SARS-CoV-2, Remdesivir-TP causes the termination of RNA synthesis at three positions after the position where it is incorporated. This mechanism was nearly identical in RdRp of SARS-CoV and MERS-CoV. The premature termination of RNA synthesis ultimately restricts further transcriptional and translational processes needed for the generation of new virions (as shown in dia-MOA).

Thus Remdesivir isn't the utmost medication to treat Covid-19 patients but can be used as the first line of defense against it. Using Remdesivir in combination with some still-found or yet undiscovered drug that could block nsp12 more efficiently & in a broad continuous manner (since it is highly conserved across Coronavirus) could turn out to be a more sure-fire strategy than Remdesivir alone.

SO TRY TO IMPROVE YOUR NATURALLY ADAPTED IMMUNITY BY CONSUMING SEVERAL CITRUS FRUITS,ALMONDS,SPINACH,GARLIC ALONG WITH HEALTHY LIFE CYCLE !

Thyroid Harmones: II

2021-04-13T00:00:00.006+05:30

Regulation of Secretion:

-Thyroid hormone secretion is controlled by Anterior Pituitary gland via thyrotropin or TSH.

-TSH is stimulated by TRH which is secreted from Hypothalamus.

-Somatostatin from Hypothalamus, T3 & T4 inhibits Anterior Pituitary gland directly from releasing TSH while only T3 & T4 inhibits Hypothalamus to release TRH.

-The action of TRH on Pituitary Gland & TSH on Thyroid gland is mediated by enhanced cAMP synthesis.

-Higher concentration of TSH acts via IP3/DAG Pathway & Mediate intracellular calcium pathway in thyroid cell.

Mechanism of Action:

-Thyroid hormones bind to ligand-binding domain of thyroid hormone receptor (TR) & and it heterodimerizes with retinoid X receptor (RXR).

-Then it undergoes conformational changes releasing 'corepressor' & binding with 'coactivator'.

-This induces gene transcription followed by Production of specific m-RNA & thus specific protein synthesis is done which is used in various metabolic and anatomic effects.

Relationship between T3 & T4:

-Secretion: T4 > T3 ( but in iodine deficiency this difference gets reduced).

-Circulation: T4 > T3 ( scenes T4 bounds to plasma proteins 15 times more tightly than T3).

-Potency: T3 > T4 (5 times).

-Action: T3 > T4 ( Peak action of T3 in 1-2 days while T4 is in 6-8 days).

-T3 is more avidly bind to Nuclear receptors, unlike T4.

-T3 causes gene transcription, unlike T4.

-About ⅓rd of T4 is converted into T3 in thyroid cells liver-kidney by D1 (iodothyronine deiodinase type 1).

-T3 is generated within the target cells ( like skeletal muscles, heart, brain, pituitary gland) with the help of D2 (iodothyronine deiodinase type 2).

-T3 is main active hormone and T4 is type of transport hormone which function as Pro-hormone to T3

-T4 may produce some non-genomic actions except gene expression

Preparations:

-L thyroxine sodium

-T3 / Liothyronine

Pharmacokinetics & Interactions: (L-thyroxine sodium)

-oral bioavailability:

~75% [food alters its absorption & hence this drug is taken before meal or in empty stomach]

Severe hypothyroidism can reduce oral absorption

Sucralfate, iron, calcium & proton pump inhibitors also reduce its oral absorption

- CYP3A4 inducers like Rifampin, Phenytoin, Carbamazepine accelerate metabolism of T4 therefore enhancement of dose of thyroid drug is mandatory

[Note- L-thyroxine is preferred over T3 because of more sustained & uniform action as well as lower risk of cardiac arrhythmias]

Uses:

-the most important role is in replacement therapy in deficiency states such as:

1)Cretinism

-due to,

i) failure of thyroid gland development

ii) defect in thyroid hormone synthesis (sporadic cretinism)

iii) extreme iodine deficiency (endemic cretinism)

-treatment: 8-12 μg/kg thyroxine daily should start as early as possible (because mental retardation which has already ensued is only partially reversible)

2)Adult Hypothyroidism (Myxoedema):

-commonest endocrine disorder due to autoimmune thyroiditis or thyroidectomy

-important drug that can cause hypothyroidism ¹³¹I, iodides, lithium, amiodarone (beta-blockers)

-treatment: L-thyroxine with low dose 50 μg/day at starting & then increase in every 2-3 weeks ab to 100-200 μg/day & further doses are adjusted at 4-6 weeks intervals (dose increment is mandatory in pregnancy)

-Doses are adjusted according to clinical response and serum TSH levels

3) Myxoedema Coma:

-characterized by mental deterioration due to hypothyroidism hence, rapid thyroid replacement is crucial

-Treatment: Liothyronine acts faster but the risk in patients with arrhythmias angina Still it is recommended with 10 μg/8 hour in younger patients OR L-thyroxine 200-500 μg IV followed by 100 μg IV OD till oral therapy can be instituted

4)Non-toxic Goitre:

-causes due to iodine deficiency

-it may be,

i) Endemic (i.e. belongs to particular people of particular region) due to iodine deficiency which is emphasize by calcium present in water, food or milk

ii) Sporadic (i.e. occasionally seen diseases within particular conditions) due to the defect in hormone synthesis

-in both cases deficiency of thyroid hormone synthesis leads to excess TSH which causes thyroid enlargement (i.e.Goitre)

-treatment: non toxic goitre and cretinism due to iodine deficiency in pregnant women can be preventable by daily injection of 150-200 μg Iodine & sometimes T4 also given despite no open hyperthyroidism

5)Thyroid Nodules (Tumour):

-treatment:

i)benign functioning rigress when TSH is suppressed by T4 therapy

ii) non functional nodule doors are non-responsive to TSH and associated with low TSH levels do not respond to levothyroxine therefore shouldn't treated with levothyroxine

[Note-Therapy should be stopped if nodule size is not decreases within 6 months or when it stops regressing after the initial response]

6)Papillary Carcinoma of Thyroid:

-type of cancer which is often responsive to TSH

-treatment:in non removable cases full dose of T4 suppress endogenous TSH production and may induce temporary regression(back to normal)

7)Empirical Uses:

-refractory anaemia

-mental depression

-menstrual disorders (infertility is not corrected by usual treatment)

-chronic, non-healing ulcer

-obstinate constipation (severe form)

Thyroid Inhibitors:

-use to lower the functional capacity of hyperactive thyroid gland

-Classification:

1) Antithyroid Drugs/Thioamides

2) Ionic Inhibitors

3) Iodides

4) Radioactive Iodine

1) Thioamides:

-inhibit thyroid hormone synthesis

-this drug binds to the thyroid peroxidase & prevent the oxidation of iodine and iodo-tyrosyl residues, thereby;

i) inhibition of iodine action of tyrosine residues in thyroid gland

ii) inhibition of coupling of iodo-tyrosine residues to T3 & T4

-first action is slower then second action in lower dose of antithyroid drugs

-thus, thyroid colloid is depleted over time and blood levels of T3 or T4 are progressively lowered

-these drugs do not interfere with trapping, peripheral conversion (EXCEPT-propylthiouracil which causes inhibit peripheral conversion of T4 to T3) and they also don't cause goitre

Pharmacokinetics:

i) quickly absorbed orally, widely distributed in body, enters in milk and may cross placenta

ii) metabolized in liver, excreted through kidney as urine

iii) effect of single dose lasts longer than would be expected from plasma t½ of these drugs

-Adverse Effects:

i) Reversible hypothyroidism occurs due to over treatment

ii) Intolerance

iii) Skin rashes

iv) Joint pain (most important and common)

v) Loss or graying of hairs

vi) Infrequent liver damage

vii)Serious Adverse effect-Agranulocytosis (very rare & reversible)

-Examples:

i) Propylthiouracil

ii) Methemazole

iii) Carbimazole

-Doses:

i) Propylthiouracil: 50-150 mg TDS followed by 25-50 mg BDS/TDS

ii) Methemazole: 5-10 mg TDS initially maintain by 5-15 mg daily in 1-2 divided doses

iii) Carbimazole:(more commonly used in India) 5-15 mg TDS initially, maintain by 2.5-10 mg daily in 1-2 divided doses

-Uses:

i)Control Thyrotoxicosis (excessive secretion of thyroid hormones) in Grave's disease & toxic nodular goitre

ii)Before thyroidectomy carbimazole use to achieve euthyroidism

iii)Propylthiouracil is used in thyroid storm as well

2) Ionic Inhibitors:

-inhibit uptake of iodide by NIS

-Examples:

i) Perchlorates (highest potency)

ii) Thiocyanates

iii) Nitrates (lowest potency)

-Perchlorates:

*10 times more potent than thiocyanate in blocking NIS

*Produce rashes, fever, aplastic anaemia, agranulocytosis

-Thiocyanates: causes liver, kidney, bone marrow & brain toxicity

-Nitrates:

*Very weak in blocking in NIS then both of the above

*They are toxic & not in clinical use

3) Iodine & Iodides:

-Though iodine is constituent of TH it is fastest acting thyroid inhibitor

-excess iodine inhibits its own transport in thyroid cells by interfering with expression of an NIS on the cell membrane

-it weakens TSH & cAMP induced thyroid stimulation

-excess iodide rapidly & briefly interferes with iodination of thyroid and thyronil residue of thyroglobulin resulting in reduced T3 & T4 synthesis known as "Wolff-Chaikoff effect"

-however, within few days the gland is capes from this effect and hormone synthesis resumes

-Pharmacokinetics: oral absorption is optimum and metabolized in intestine

-Adverse Effects:

i)Acute Reactions-swelling of lips &eyelids, angioedema of larynx, fever, joint pain, thrombocytopenia, swollen lymph nodes

ii) Chronic Reactions-(Iodism) inflammation of mucous membrane, salivation, rhinorrhea (running nose), sneezing, lacrimation, burning sensation in mouth, headache, rashes, GIT problems

-Examples:

i) Lugol's Solution- 5% Iodine in 10% potassium iodide

ii) Sodium/Potassium Iodide

-Doses:

i) Lugol's Solution: 5-10 drops/day

ii) Sodium/Potassium Iodide: 100-300 mg/day(therapeutic) or 5-10 mg/day(prophylactic) for endemic goitre

-Uses:

i)Preoperative preparation for thyroidectomy in Grave's disease & thyroid storm

ii)Prophylaxis (treatment given or action taken to avoid disease) of endemic goitre

iii) Antiseptic Uses

4) Radioactive Iodine:

-¹³¹I having medical importance

-its chemical behaviour is similar to stable isotope of Iodine

-t½ is 8 days

-it emits X-rays & β-particles

-radioactive iodine is administered as sodium salt of ¹³¹I dissolved in water and taken orally

-Diagnostic use of ¹³¹I: 25-100 μ curie ; counting & scanning is done at intervals (no damage at this dose)

- Therapeutic use of ¹³¹I: 3-6 m curie where 20-40% patients required one or more repeat doses for treatment of Graves disease at mentioned dose or treatment of multi-nodular goitre at more dose than mentioned

-Advantages:

i) Simple, convenient & inexpensive treatment

ii) No surgical risk, scar or injury to parathyroid glands

iii) Once hyperthyroid is controlled, cure is permanent

-Disadvantages:

i)Hypothyroidism- 5-10% patients of Grave's disease treated with ¹³¹I suffer from hypothyroidism [50% patients require supplementary thyroxine treatment]

ii)Long latent period of response i.e. existing but not noticeable

iii)Contraindicated in pregnancy

iv)Not suitable for any patients

[Note-¹³¹I is given as palliative therapy after thyroidectomy]

*β-Adrenergic blockers: Propranolol & other nonselective β-blockers have emerged as an important therapy to rapidly reduce manifestation of thyrotoxicosis that are due to sympathetic overactivity

*Thyroid Storm (Thyrotoxis Crisis):

- Propranolol: 1-2 mg slow IV followed by 40-80 mg oral/6 hours

- Propylthiouracil: 200-500mg oral/hours

- Diltiazem: 60-120 mg BD oral (if propranolol is contraindicated in trachycardia) for treatment of hyperthyroidism

- Dexamethasone (glucocorticoid) injection: large dose

- Paracetamol

- Hydrocortisone: 100 mg IV 8 hourly

- Iopanoic acid: 0.5-1 g oral OD or Ipodate (iodine containing radiocontrast media)

Thyroid Hormones [I]

2020-12-15T11:27:00.001+05:30

Thyroid Hormones: Analogues & Their Inhibitors

Thyroid gland:

- Location: front of Neck, below the Adam's Apple (larynx).

- butterfly-shaped gland.

- it is composed of Million clusters of follicles.

- a follicle is a structure having epithelial cells surrounding a central mass (colloid).

- Epithelial cells:

(i) follicular cells[T3 & T4]

(ii) parafollicular cells [calcitonin]

- having two lobes; either on the windpipe (trachea).

Thyroid Hormone Actions:

i.Growth & Development

ii.Intermediary metabolism (lipid,carbohydrate & protein metabolism)

iii.Caloriegenesis-production of heat via digestion of food or action of several hormones thus BMR increases

iv.Haemopoiesis

v.Modulate gene transcription

Synthesis, Storage & Release of Thyroid Hormones:

1.Iodine uptake/Trapping:

-total iodine content in body is 30-50 mg out of which ⅕th is present in thyroid

-blood iodine concentration is low i.e. 0.2-0.4 μg/dl

-thyroid cells have active transport process Na+:I2 symporter (NIS) to concentrate sodium ion which is get stimulated by TSH

-there are many locations where this type of transport happens but it is not stimulated by TSH

2.Oxidation & Iodination:

-iodide trapped by follicular cells via NIS is carried across the apical membrane of another transporter termed as Pendrin & then that iodide is oxidised by membrane-bound thyroid peroxidase enzyme to iodinium ions or hypoiodous acid (HOI) or enzyme-linked hypo iodate(E-OI) with the help of hydrogen peroxide

-these all forms of iodine combine with tyrosine residue of thyroglobulin(TG) apparently without any enzyme intervention to form mono-iodotyrosine(MIT) & di-iodotyrosine(DIT)

-these residues are still attached to TG chains

3.Coupling:

-pairs of tyrosine residues couple together to form T3 and T4 (formation of T4 >>> T3)

-but during iodine deficiency relatively more MIT is available and hence more T3 is formed thus, more active hormone(T3) is generated with a lesser amount of iodine

-coupling is an oxidative reaction and is catalyzed by the same enzyme i.e. thyroid peroxidases

-oxidation of iodide and coupling both are stimulated by TSH

- MIT + DIT = T3

- DIT + DIT = T4

4.Storage & Release:

-MIT, DIT, T3, T4 all are attached to TG & stored as colloid till it is taken back into the cells by endocytosis and broken down by lysosomal proteases(as shown in diagram)

-T3 & T4 are released to be secreted, while MIT & DIT residues are deiodinated & thus iodine release is finally reutilized.

-uptake of colloid and proteolysis are stimulated by TSH.

- normal human thyroid secrets 60-90 μg of T4 & 10-30 μg of T3.

5.Peripheral conversion of T4 to T3: (in liver and kidneys)

-about ⅓rd part of total T4 secreted goes in in this process and hence most of the plasma T3 is derived from liver

-target tissues take up T3 except brain and pituitary gland which converts T4 to T3 by their own cell components

-there is always equal amount of active(T3) & inactive(rT3) thyronine in the periphery

-this process is carried out by iodothyronine deiodinase which exist in three forms:(D1, D2, D3)

D1 = produces T3 & rT3

D2 = produces T3

D3 = produces rT3

Transport,Metabolism & Excretion:

-thyroid hormones are mostly bound to plasma proteins

-0.03-0.08% of T4 & 0.2-0.5% of T3 are present in free form

-almost all Protein-Bound Iodine(PBI) in plasma is Thyroid hormone.

-plasma protein binding affinity for T4 (decreasing order) viz:

1) Thyroxine Binding Globulin (TBG)

2) Thyroxine Binding Prealbumin (Transthyretin)

3) Albumin

-Normal concentration of PBI is 4-10 μg/dl where 0.1-0.2 μg/dl is of T3 and rest is T4.

-Only free hormone is available for metabolism, excretion as well as various actions as mentioned before.

-Metabolic inactivation of T3 & T4 occurs by deiodination & glucuronide/sulfate conjugation.

-liver is the primary site for metabolism & excretion processes along with salivary glands(Very rare) and kidneys.

-conjugates excreted as bile of which significant fraction get deconjugated in intestines & reabsorbed in enterohepatic circulation then finally excreted through urine.

-plasma t½ of T4 is 6-7 days & of T3 is 1-2 days.

-half-lives are shortened in hyperthyroidism due to faster metabolism & they get lengthened in hypothyroidism due to relatively slower metabolism.

In next post:Thyroid Hormones [II], the following topics will be covered:

1.Regulation of secretion

2.Relationship between T3 & T4

3.Pharmacokinetics & Interactions

4.Uses

5. Thyroid Inhibitors

So, be in touch folks..!

COVID PHASE-I VACCINES

2020-12-04T09:33:00.002+05:30

The Covid-19 Vaccine Race:

Phase I:

1.BEIJING MINHAI BIOTECHNOLOGY (CHINA)

INACTIVATED VACCINE

A Phase 1 trial of this vaccine started on 2 October, with 180 health people aged over 18 years. The trial is being done in Jiangsu, China.

2.IMMUNITYBIO AND NANTKWEST (USA)

VIRAL VECTOR VACCINE

The company is planning to launch a Phase 1 trial in California this month with people aged up to 55 years. It is an adenovirus (Ad5) vaccine designed to deliver both spike protein and nucleocapsid DNA to drive both cellular and antibody immunity. Earlier this year, it was chosen to be part of Operation Warp Speed to rapidly develop vaccines in the USA.

3.REITHERA (ITALY)

VIRAL VECTOR VACCINE

The Italian biotechnology company ReiThera has developed a COVID-19 vaccine, called GRAd-COV2, based on an adenovirus that infects gorillas. In collaboration with the Lazzaro Spallanzani National Institute for Infectious Diseases, they launched a Phase 1 trial at the end of July.

4.CANSINO BIOLOGICS/ACADEMY OF MILITARY MEDICAL SCIENCES (CHINA)

VIRAL VECTOR VACCINE

This Phase 1 trial will evaluate the safety and immunogenicity of a recombinant adenovirus 5 vectored COVID-19 vaccine (Ad5-nCoV) with two doses and with different administration routes in healthy adults aged 18 years and older. The trial will include 168 healthy adult aged 18 years and older.

5.VAXART (USA)

VIRAL VECTOR VACCINE

Early in 2020, Vaxart began working on an oral vaccine for COVID-19 using an adenovirus called Ad5 to deliver part of the COVID-19 virus into the body to trigger an immune response. In October, they began Phase 1 trials.

6.LUDWIG-MAXIMILIANS UNIVERSITY OF MUNICH (GERMANY)

VIRAL VECTOR VACCINE

On 30 September, Phase 1 testing for this non-replicating viral vector vaccine was approved. The trial will include 30 healthy participants aged between 18 and 55 years.

7.CLOVER BIOPHARMACEUTICALS INC., GSK & DYNAVAX (AUSTRALIA)

PROTEIN SUBUNIT VACCINE

The protein-based COVID-19 S-Trimer vaccine which uses GSK’s adjuvant system is now being tested in human clinical trials. This move comes after the promising results during the preclinical stage. The study will be conducted in 150 healthy adults in Australia. Clover has also obtained US$ 3.5 million from CEPI to prepare and launch Phase 1 clinical trials in June. It is planning a Phase 2 trial by the end of 2020.

8.VAXINE (AUSTRALIA)

PROTEIN SUBUNIT VACCINE

Vaxine launched a Phase 1 trial in July. Its vaccine combines viral proteins with an adjuvant that stimulates immune cells. Phase 2 trials are expected to start by the end of the year.

9.UNIVERSITY OF QUEENSLAND & CSL LIMITED (AUSTRALIA)

PROTEIN SUBUNIT VACCINE

Researchers at the University of Queensland, in Brisbane, are using a patented vaccine-development technique called a ‘molecular clamp'. They first create a synthetic version of the characteristic 'spike' protein that covers the virus, as this can trigger an immune response in the human body. They then attach a 'clamp' onto this synthetic protein to ensure it remains stable enough to trigger antibodies (the protein would normally denature in the human body). The researchers launched Phase 1 trials in July. In September, the vaccine makers made an agreement with the Australian government to deliver 51 million doses if the vaccine works. They expect their first supply of the vaccines to be ready by mid-2021.

10.MEDIGEN (TAIWAN)

PROTEIN SUBUNIT VACCINE

Taiwan-based vaccine maker Medigen is making a vaccine made of a combination of spike proteins and an adjuvant from Dynavax. Their Phase 1 trial started this month.

11.FINLAY VACCINE INSTITUTE (CUBA)

PROTEIN SUBUNIT VACCINE

On 18 August, Cuba announced that the Finlay Vaccine Institute in Havana would start a clinical trial on a vaccine for COVID-19. The vaccine, called Soberana 1, contains a part of the spike protein, called RBD, along with an adjuvant to boost the immune response. The vaccine will be given in two injections during the trials that will involve 676 people aged between 19 and 80 years and finish in January 2021.

12.VECTOR INSTITUTE (RUSSIA)

PROTEIN SUBUNIT VACCINE

On August 26, a Russian biological research center known as the Vector Institute registered a Phase 1/2 trial for a coronavirus vaccine called EpiVacCorona. On 14 October, Vladimir Putin announced that Russia had granted regulatory approval for this vaccine, even though Phase 3 trials have not yet begun. This is the second COVID-19 vaccine the country has approved so far.

13.WEST CHINA HOSPITAL OF SICHUAN UNIVERSITY (CHINA)

PROTEIN SUBUNIT VACCINE

On 24 August, they got approval to run a Phase 1 trial. The vaccine incorporates recombinant protein grown in insect cells. To make the vaccine, researchers encode the receptor-binding domain (RBD) in a gene, which they insert into a virus. They then infect insect cells with the virus, triggering them to make the molecule in huge amounts. The hospital’s State Key Laboratory of Biological Therapy developed the “insect vaccine”, which seems to stop infection in monkeys without showing any apparent side effects.

14.UNIVERSITY HOSPITAL TUBINGeN (GERMANY)

PROTEIN SUBUNIT VACCINE

Earlier this year, rresearchers at the University of Tubingen in Germany created a vaccine made of viral proteins, along with an immune-stimulating adjuvant. In September they launched a Phase 1 trial.

15.COVAXX (USA)

PROTEIN SUBUNIT VACCINE

COVAXX, a subsidiary of United Biomedical, registered a Phase 1 trial on 11September in Taiwan and plan to run their Phase 2/3 trial in Brazil.

16.MERCK/DOHME/IAVI (USA)

VIRAL VECTOR VACCINE

Merck has joined forces with non-profit organisation IAVI to produce a vaccine candidate that will use the recombinant vesicular stomatitis virus (rVSV) technology that is the basis for Merck’s Ebola Zaire virus vaccine, ERVEBO. The Ebola vaccine worked as well in the elderly as it did in young, healthy adults.

17.MERCK/INSTITUTE PASTEUR (USA)

VIRAL VECTOR VACCINE

Merck acquired the Austrian firm Themis Bioscience in June and is working on a vaccine originally developed at the Institut Pasteur. The vaccine uses the weakened measles virus to carry genetic material into cells. A Phase 1 trial launched in August.

18.BEIJING WANTAI BIOLOGICAL PHARMACY (CHINA)

VIRAL VECTOR VACCINE

In 2019, researchers at the University of Hong Kong and Xiamen University created a nasal-spray vaccine for the flu based on a weakened form of the influenza virus. Now they have engineered the vaccine to produce part of the coronavirus spike protein, which has started Phase 1 trials in partnership with Beijing Wantai Biological Pharmacy.

19.IMPERIAL COLLEGE (UK)

RNA VACCINE

This vaccine candidate which uses self-amplifying RNA technology (saRNA) has been developed by researchers at Imperial College, in London. The research has received £ 41 million in funding from the UK government. It has also received £ 5 million through philanthropic donations. The clinical trial in the current phase will involve administration of the two-dose vaccine to 300 healthy individuals. Volunteers have already started receiving the first dose of the vaccine. Imperial College has also created VacEquity Global Health, a social enterprise, to develop and distribute low-cost vaccines around the world, including to low- and middle-income countries. It began Phase 1/2 trials on 15 June and has partnered with Morningside Ventures to manufacture and distribute the vaccine.

20.PEOPLE'S LIBERATION ARMY (PLA) ACADEMY OF MILITARY SCIENCES/WALVAX BIOTECH (CHINA)

RNA VACCINE

The vaccine is being tested with two age groups – one with people aged 18-59 years, and another with people 60 and older.

21.MEDICAGO (CANADA)

VIRUS-LIKE-PARTICLE VACCINE

Partly funded by the cigarette manufacturer Philip Morris, Medicago uses a species of tobacco to make vaccines. Virus genes are delivered into leaves, and then plant cells create proteins that mimic those found on viruses. In July, Medicago launched Phase 1 trials on a plant-based COVID-19 vaccine in combination with adjuvants from GSK and Dynavax. If this phase is successful, it plans to start Phase 2/3 trials in October.

Vaccine Manufacturing

2020-12-01T11:34:00.001+05:30

Vaccine Manufacturing: Clinical Trials

Scientists around the world are continuously working on COVID Pandemic Vaccine Development; out of that, some vaccine markers are very close to accurate results. Around the world, more than 23 million Covid cases are found and 800,000+ deaths globally, Over the World more than 150 labs are constantly working on developing Covid-19 Vaccine. No one other than Russia has declared his vaccine is the safest vaccine over the Covid-19 pandemic. Apart from this vaccine development; the second largest problem to healthcare systems is, how to make this vaccine available to the global population at an affordable cost.

Clinical trials: Clinical trial is an investigation of a newly discovered drug on a human subject on a human subject, and reporting its safety and efficacy. It is carried out in the following ways

It is carried out in the following ways:

After successfully completing of Preclinical Phase, Vaccine go for the next Phase i.e. Clinical Phase. In Preclinical Phase we calculate our newly discovered drug effects on Preclinical Animal subjects like Rat, Mice, Monkey, etc.

In Clinical Trials, We use Human animals as subjects, wherewith the help of 4 phases, we calculate the efficacy and effectiveness of the product. Out of four, in Phase-I we ensure product safety & determine dosage on various age groups person from Pediatric patients to Gediatric patients; also ensure potential side effects of the newly discovered product but in very few people. In Phase-II we explore safety and investigate potential side effects on larger public groups. In Phase-III trials few more dosage manufactured and given them to thousand or up to ten thousands of people to access the effectiveness of the vaccine or newly discovered drug. There may be rare side effects that can only identify in large groups.

Four types of vaccines can be developed by using;

1. Whole virus

2. Protein subunit

3. Nucleic acids (RNA and DNA)

4. Viral vectors

1. Whole virus:

-most of the conventional vaccines use this mode.

-there may be two approaches viz,

i) Live Attenuated Vaccines.

ii) Inactivated Virus Vaccines.

i) Live Attenuated Vaccines

-weakened form of viruses or foreign living elements that can still able to replicate without causing any harm or illnesses are used to develop this type of vaccine.

-these types of vaccines can provide both antibodies as well as cell-mediated immune response.

-Exa: Smallpox vaccine.

-shown in the figure below:

ii) Inactivated Vaccines

-the genetic material of viruses has been destroyed so that they can't replicate but still able to develop antibodies.

-these types of vaccines can only provide an antibody-mediated immune response.

-Exa: Poliovirus vaccine

Hepatitis A vaccine

-shown in the figure below:

2. Protein Subunit:

-these types of vaccines are designed by using species of pathogens.

-pieces of pathogens often fragments of protein to trigger an immune response.

-thus, the risk of side effects is minimized but the immune response may be weak and hence it requires adjuvant to boost the immune response.

-Exa: Hepatitis B vaccine

3. Nucleic Acid:

-these types of vaccines are established by using genetic materials like RNA or DNA of pathogens to provide instructions to cells for making antigens inside the host's body

-these are easy to make and cheaper in rate

-once these types of material interact with the host's body it produces antigens by using "Cell Protein Factories" and this helps to boost immunity.

-these vaccines provide strong immunity since antigens are formed inside the host's body.

-these vaccines are not allowed for human use.

4. Viral Vector:

-these also work in the same way as the nucleic acid derivative vaccines do by giving instructions to cells for producing antigens.

-they only differ from nucleic acid derivative vaccines in one way that viral vector vaccines are designed by using "Inactive virus" to give instructions for producing antigens in the host's body.

-mostly used inactive virus/viral vector is Adenovirus.

-these vaccines may be less effective if a viral vector is already exposed before the actual vaccination in the host's body but rather it could produce strong immunity.

Androgens & Anabolic Steroids

2020-11-26T14:03:00.000+05:30

1. Androgens (Male Sex Hormone):

- development of secondary sex characters in male

- it was isolated as testicular hormone

- commercial sources: urine of male, female and testicular extracts

- it is also a product of the adrenal cortex

- androgen is able to develop secondary sex characteristics in castrated male

- e.g. testosterone

Secretion and Regulation-

- secreted by interstitial cells/Leydig cells of testes

- FSH stimulation on testes causes testosterone secretion

Pharmacological Actions-

- growth of genitalis (penis, scrotum, seminal vesicle)

- growth of hairs (pubic, axillary, beard, etc)

- thickening of the skin

- veins look prominent since subcutaneous fat is lost

- larynx grows & voice deepens

- penile erection and physical aggression

- development of the male phenotype

- spermatogenesis and maturation of spermatozoa

- rapid bone growth

- fusion of epiphysis in boys as well as girls by Estradiol formed by testosterone.(@Extradiol-visit our social media platforms for more)

- Muscle building

- Induces erythropoiesis

Mechanism of action-

- Testosterone acts via androgen receptor present in the target cell as shown in the figure below:

Pharmacokinetics-(ADME)

A - Oral: inactive due to faster first-pass metabolism in the liver

- hence, IM route is preferred

D - 98% testosterone bound to sex hormone-binding globulin ( SHBG ) & to albumin

- SHBG testosterone is inactive due to tight binding

M - major metabolic products are androsterone and etiocholanolone

E - mostly as a conjugate with glucuronic acid and sulfate

- estradiol also formed from testosterone by aromatization

* T½ 10-20 min

* Methyltestosterone and fluoxymesterone(synthetic androgens) are get metabolized slowly & longer action but less potent

* Estrogens are not produced by DHT & fluoxymesterone

Side Effects-

- acne in males and females

- excess body hairs

- irregular menstruation

- testicular atrophy (if prolonged use)

- hepatic carcinoma (if long term use of methyltestosterone)

- gynecomastia

- premature sexual behaviors

- lowering of HDL and rise in LDL especially with α-alkylated analogs of testosterone.

- cholestatic jaundice

- salt retention and edema

- oligozoospermia

Contraindications-

- carcinoma of prostate and male breast

- liver and kidney disease

- during pregnancy (masculinization of the Female fetus)

- in >65 years aged men

- CHF or coronary artery disease

Uses-

1. Testicular failure

2. Hypopituitarism

3. AIDS-related muscle wasting

4. Hereditary angioneurotic edema

5. Ageing

2. Anabolic Steroids (Synthetic Androgens):

- having higher anabolic and lower androgenic activity

- drugs e.g. Nandrolone, Oxymetholone, Stanozolol, Methandienone

Side Effects-

- jaundice

- can worsen lipid profile

Contraindications-

- same as testosterone

- migraine

Uses-

- Hypoplastic and hemolytic anemia

- To enhance physical ability in athletes

- Osteoporosis

- Acute illness, severe trauma (catabolic states)

- Malignancy-associated and anemia

- sub-optimal growth in boys

- renal insufficiency

Anti-Neoplastic Agents

2020-11-12T13:54:00.000+05:30

These are agents used for the treatment of cancer, tumor, malignancy carcinoma, sarcoma, leukemia, neoplasm.
All the above mentioned are characterized by uncontrolled and abnormal cell growth.
Primary tumors invade adjacent normal cells or tissues and form cancerous cells then, these cancerous cells separate themselves from the primary tumors and reach distant sites of the body via the lymphatic system where they divide and form secondary tumors; this is the process of Metastasis.
Oncogene is the gene that has the potential to cause cancer.
Antineoplastic agents are as follows:

1. Alkylating agents

2. Antimetabolites

3. Antibiotics

4. Plant products

5. Miscellaneous agents

1. Alkylating Agents:

- these agents having two chloroethyl-side chains.

- these agents are capable to produce highly reactive "Carbonium ion".

Mechanism of Action-

- One of two chloroethyl side chains undergoes SN1 intramolecular cyclization reaction and releases chlorine to form a highly reactive intermediate "Carbonium ion".

- this is followed by SN2 nucleophilic substitution in which alkylation of 7th nitrogen in Guanine residue of DNA happens.

- this leads to the inter-strand crosslinking of a Guanine residue.

- since DNA replication and cell division doesn't occur; leads to cell death.

Examples-

- Mechlorethamine

- Cyclophosphamide

- Melphalan

- Chlorambucil

- Busulfan

- Thiotepa

2. Antimetabolites:

- these agents show maximum effect in the S-phase of the cell cycle.

- cell cycle-specific agents.

Mechanism of Action-

- these agents interfere with the availability of normal purine and pyrimidine nucleotides precursors either by i) Inhibiting their synthesis or ii) Competing with them in DNA/RNA synthesis

Examples-

I] Purine Analogues:

- Mercaptopurine

- Thioguanine

II] Pyrimidine Analogues:

- Fluorouracil

- Floxuridine

- Cytarabine

III] Folic acid analogues:

- Methotrexate

- Azathioprine

3. Antibiotics:

- Cell Cycle Nonspecific.

- These are different agents from bacterial antibiotics except Actinomycin.

Mechanism of Action-

- They act by binding with DNA and preventing RNA synthesis.

- Hence Protein synthesis is blocked.

- Which leads to cell death.

Examples-

- Dactinomycin/ Actinomycin

- Daunorubicin

- Doxorubicin

- Bleomycin

4. Plant products:

- Cell cycle-specific.

Mechanism of Action-

- These agents bind to Microtubular tubulin.

- This causes the prevention of polymerization and assembly of microtubules which leads to mitotic spindle destruction and chromosomes fail to move apart during mitosis.

- this is Metaphase Arrest and hence cell death.

Examples:

- Vincristine

- Vinblastine

- Etoposide

5. Miscellaneous agents:

Examples:

- Cisplatin

- Mitotane

"Apoptosis (Phase II)"

2020-10-29T13:53:00.006+05:30

We deal with general ideas about Apoptosis in earlier blog (Apoptosis Phase 1). Now in this blog we are going to deal with two important points which are:

1. Apoptosis Pathways

2. Apoptosis Assays(only name)

1. Apoptosis Pathways

A] Extrinsic pathway (death receptor-mediated events)

i. Death receptors and their Ligands :

-death receptors are members of TNF (tumor necrosis factor) receptor super family.

-they have cytoplasmic domain of 80 amino acid which is called Cellular Death Domain (CDD).

-CDD plays vital role in death signal transmission from cell surface to intracellular signalling.

ii. Adaptor Proteins :

-they have critical role in pro-apoptotic signaling (i.e. apoptosis causing events)

-adaptor proteins which mediate Pro-apoptotic signaling are:

a) FADD (Fas-Associated Death Domain)

b) TADD (TNF-receptor Associated Death Domain)

iii. Caspases (Cysteinyl Aspartate Specific Proteases) :

-family of intracellular cysteine proteases

-important role in initiation and execution of Apoptosis

-14 different types of Caspases are identified till date

-all are synthesized as inactive proenzyme (Zymogen) having 32-56 kilodalton mass

-10 major Caspases are:

a. Signalling/Initiator Caspases (C2,C8,C9,C10)

b. Effector/executioner Caspases (C3,C6,C7)

c. Inflammatory Caspases (C1,C4,C5)

-Central role in cascade (signalling) of apoptosis event plays by C-3 (CPP-32)

B] Intrinsic Pathway (Mitochondria Mediated events)

i. Bcl2 Family Proteins :

-B-cell lymphoma 2

-Function: release of cytochrome-c from mitochondria by altering mitochondrial membrane permeability.

ii. Cytochrome-c (Cyt-c) :

-abundant protein of mitochondrial inner membrane

-act as an electron transport intermediate

-alteration in permeability of mitochondrial membrane by Bcl2 leads to Cyt-c release

-Cyt-c does interaction and activation of Apaf (Apoptotic Protease Activating Factor) and Procaspase-9 to form "Apoptosome" (which causes Apoptosis).

2. Apoptosis Assays :

1) Cytochromatogical alteration

2) DNA fragmentation

3) Detection of caspase, cleaved substract regulators and inhibitors

4) Membrane filtration

5) Detection of apoptosis by stain

6) Mitochondrial assays

"Apoptosis (Phase I)"

2020-10-23T12:38:00.005+05:30

So guys here we are in Apoptic Zone!

In the human body, the rate of cell synthesis and cell death is balanced to maintain the mass of the body. Hence, easily we can conclude that the life of an individual is impossible without cellular death. There are 11 types of cell death are recognized till now, from which Apoptosis shares most (even more than autophagy and necrosis).

Apoptosis

apoptosis word has Greek origin which means "falling away"
physiological cell death
useless, unwanted cells are eliminated
it is programmed cell death (PCD)
cell is active participant in its own demise or suicide
Apoptosis is important in:

1. Embryonic development -before parturition

2. Homeostasis maintenance -in adults

Morphological changes during Apoptosis:

1. Cell shrinkage

2. Organell reduction

3. Nuclear fragmentation

4. Chromatin condensation

5. Cell blebbing or changes

6. Mitochondrial leakage

Biochemical changes during Apoptosis:

1. Chromosomal DNA cleavage into fragments

2. Plasma membrane constituent change

3. Loss of electrical potential at mitochondria

4. Relocation of cytochrome-c

In our recent post on social media platforms, we provide the fact that Apoptosis retardation is one of the causes of cancer, which means it has an important role in Cancer management. Along with this, there are couple of uses of apoptosis, viz ;

1. In Embryo

a) Digit formation (lower and upper limbs)

*(Lack of apoptosis leads to webbed fingers i.e. Syndactyly)

b) Development of the nervous system.

2. In Adults

a) Normal cell number maintenance

b) Tissue homeostasis

c) Immunological tolerance

d) Elimination of abnormal cells

Topic: Apoptosis Phase-II

1.Apoptosis Pathways

2.Apoptosis Assays.

(*Wait for couple of hours for Phase-II)

"APOTOSIS"

2020-10-22T11:58:00.002+05:30

As our channel's bio says, we are prompting to biology for introducing magical articles from a huge biological world to you.

Normally in day-to-day life eventually we realize that life is a sweet lie and death is bitter truth; why this death happen so? To find the answer to this immortal question we have to go in deep into many aspects. But one thing is very clear the balance of everything must be there in respective limits.

The balance about which we were discussing that must be happening in the human body too at the macro or micro levels. You will be amazed to know that approximately 100 billion (10,000 crores) cells die every day in the human body in order to maintain balance. Out of the above 100 Billion mentioned, 50-70 billion cells (50-70%) dies by "Apoptosis" only itself.

So game on buddies! We are going to one of the most tragical fortunate zones of biology that is "Apoptosis".

Wait for 24 hours and one of our new blogs on Apoptosis will be delivered to your fingertips!

Nitric oxide a possible treatment for COVID-19.

2020-10-15T19:20:00.003+05:30

Nitric oxide a possible treatment for COVID-19.

Covid-19(Coronavirus disease) is a respiratory tract infection caused by a coronavirus closely related to SARS coronavirus. Generally, Covid-19 patients show hypoxemia associated with acute respiratory distress syndrome (ARDS). Hypoxemia means lowering of oxygen level in the blood, hence we need advanced mechanisms to transfer oxygen from alveoli to blood. Many experimental & clinical evidence explains the significant role of Inhaled Nitric Oxide(NO) as a selective vasodilator. , which has shown to restore oxygenation by helping to normalize shunts and ventilation/perfusion mismatch. NO has ability to suppress the replication of coronavirus, only NO has this unique property than other vasodilator agents. Hence it helps to clinical management of COVID-19.

Researchers in many universities continuously working on the COVID-19 vaccine, a scientist at Uppsala University have discovered the more effective way of treating the COVID-19 virus. This way closely related SARS-CoV-2 virus which found in 2003.

Nitric acid is a substance containing antiviral property, it is produced by the body itself. According to the journal Redox Biology, “Nitric acid is the only compound that shows direct relation with SARS-CoV-2 ”said Ake Lundkvist, the researcher at Uppsala University, who leads this project.

Nitric Acid is a naturally producing compound. Its main function acts as a hormone to control various organs. It regulates stress in blood vessels and regulates blood flow within the organs. In acute lung failure, to enhance the blood-oxygen saturation level Nitric oxide can be used as inhaled gas, in very less concentration.

Nitric oxide (NO) is an important signaling molecule between cells which has been shown to have an inhibitory effect on some virus infections. In 2003 SARS(Severe acute respiratory syndrome) this NO therapy was given remarkable results over a patient because inflammation in the patient’s liver decreased., S-nitroso-N-acetylpenicillamine significantly inhibited the replication cycle of SARS CoV in a concentration-dependent manner.

Role of Nitric Oxide in our body.

Nitric Oxide (NO) causes smooth muscle Relaxation by generating cGMP intracellularly.
cGMP promotes deCGMP then promotes dephosphorylation Myosin ‘M’ light Chain kinase (MLCK) so that myosin fails to interact with actin ‘A’. (M-A interact causes contraction of Muscles.)
It helps in building stamina for sportspersons, it also lowers the production of lactic acid.
It prevents you from bacterial infections.
It dilates the arteries and helps to regulate blood pressure.

Zydus Healthcare launches generic anti-diabetic Dapagliflozin tablets in India.

2020-10-09T01:00:00.003+05:30

Zydus Healthcare launched its Dapagliflozin in two variants, 10mg and 5mg with Rs17 and Rs14 respectively.

New Delhi: Leading Medicine Manufacturing company Zydus launches Dapagliflozin tablets, across the country with the brand name “Dapaglyn” at a very pocket-friendly cost.

This medicine daily prescribed as an adjuvant to diet and exercise, and the main purpose to control the glycemic level in adults suffering from type 2 diabetes mellitus, Zydus healthcare explained.

Zydus launched this anti-diabetic medicine in two strengths of 10mg and 5mg with price Rs. 17 and Rs 14 respectively, which priced at ⅓ cost than currently available medicine. Due to this reason, this therapy becomes very economical, easily accessible, and very affordable to Patients.

How does Dapagliflozin act on the human body?

Dapagliflozin is the newly invented class named by sodium-glucose co-transporter 2 (SGLT2) inhibitors, this drug blocks type 2 of sodium-glucose transporter. Which helps in 90% glucose reabsorption in the body. Due to the blocking of this transporter, results in the high amount of elimination of blood glucose through the urine.

Excretion: Urine (75%), feces (21%)

Dapagliflozin is the first in a novel class of glucose-lowering agents known as sodium-glucose co-transporter-2 (SGLT2) inhibitors and is used in the treatment of patients with type 2 diabetes. By inhibiting the transporter protein SGLT2 in the kidneys, dapagliflozin reduces renal glucose reabsorption, leading to urinary glucose excretion and a reduction in blood glucose levels.

The results of phase III clinical trials showed that dapagliflozin, at a dose of 5 or 10mg/day for 24 weeks as monotherapy in previously untreated patients, or as add-on combination therapy with metformin, glimepiride, pioglitazone or insulin-based therapy, significantly reduced both HbA1c and fasting plasma glucose levels compared with placebo. In addition, dapagliflozin was non-inferior to glipizide, in terms of glycemic control after 52 weeks, when used as add-on therapy in patients with type 2 diabetes inadequately controlled with metformin.

In most clinical trials, dapagliflozin reduced body weight. The combination of both effects (improved glycemic control and weight loss) is achieved to a greater extent in treatments that include dapagliflozin. Longer-term extension studies indicated that the efficacy of dapagliflozin on the glycemic control and weight reducción is maintained for up to 2 and 4 years. Dapagliflozin was well tolerated. Genital infections and urinary tract infections were more frequent in patients who received dapagliflozin than in placebo recipients. Hypoglycemic episodes were scarce with dapagliflozin. In conclusion, dapagliflozin is a novel option for the management of type 2 diabetes, particularly when used as add-on therapy.

Adequate levels of vitamin D reduce complications, death among COVID-19 patients.

2020-10-04T11:38:00.002+05:30

In December 2019, an epidemic of pneumonia caused by a novel virus later identified as severe acute respiratory syndrome coronavirus 2 (SARS–CoV-2) started in the city of Wuhan, Hubei province, China. Recently, the World Health Organization (WHO) has declared coronavirus disease 2019 (Covid-19), a pandemic of global health concern.

The researchers have been focused on the prevention and treatment of this disease. Nonetheless, while the development of new drugs or vaccines would take a long time before human testing and commercialization, clinical trials on available pharmaceuticals with a potential effect against Covid-19 could more easily yield useful results and, as a matter of fact, are already being performed.

Vitamin D is usually known for its role in the maintenance of bone health and calcium-phosphorus metabolism, yet many other roles of this hormone have been recently discovered, such as modulation of the immune response in both infectious and autoimmune diseases. Just recently, it is being hypothesized that vitamin D supplementation could be used as a preventive or event therapeutic option in Covid-19, but more studies are needed to validate this association.

COVID-19 tested positive patients, who were had an adequate amount of vitamin D in the blood, i.e at least present 30ng/mL of 25-HydroxyVitamin D, then they showed significantly less risk of unconsciousness, hypoxia(body starved for oxygen), and Death. apart from that they also showed a Lower Blood level of an inflammatory marker(C-reactive protein) and higher blood level of immune cells(Lymphocytes/Fighting cells).

This research gives a rough idea about the Role of VitaminD to reduce Complications, including the cytokinin storm(release of too many proteins in very short duration) and ultimately death from COVID-19. Explained by Michael F. Holick, Ph.D., MD, Professor of medicine, physiology, and Biophysics professor of medicine at Boston University School of Medicine.

Blood samples are collected from 235 COVID-19 tested positive patients, to measure vitamin D (serum level of 25-hydroxyVitamin D), The clinical trial follows up taken up by researchers, including the severity of infection, breathing difficulties, unconsciousness, resulting hypoxia, and death. Researchers also analyzed the blood samples to check and ensure the level of inflammatory marker(C-reactive proteins) and the number of lymphocytes. Then all this data was taken from vitamin D deficient COVID-19 patients compared to Vitamin D sufficient COVID-19 patients.

40 years older COVID-19 patients who had a sufficient amount of vitamin D were 51.5% less likely to die from the infection compared to patients who were Vitamin D deficient with lacking the blood level of 25-hydroxyvitamin D less than 30ng/mL.

Holick, reveled his recent study, to check the role of vitamin D on COVID-19 and the results are remarkable, being a vitamin D sufficient patients can reduce the risk of catching of COVID-19 by 54%. Being a Vitamin D sufficient not only helps you to protect from the consequences of COVID-19 but also other viruses including influenza.

According to Holick, Vitamin D supplement is a simple and cost-effective strategy to fight against coronavirus and reduce COVID-19’s adverse clinical outcomes, including requiring ventilator support, overactive immune response leading to cytokine storm & death.

Vitamin D and mechanisms to decrease viral infections.

Some recent reviews demonstrated some pathways by which vitamin D decreases the risk of microbial infections. Vitamin D follows different mechanisms in reducing the risk of viral infection and mortality. To reduce the risk of common cold, vitamin D uses three pathways: 1) Physical barrier, 2) Cellular natural immunity, and 3) Adaptive immunity.

A recent review also supported the possible role of vitamin D in decreasing the risk of COVID-19 infections and mortality. These comprise maintaining of cell junctions, and gap junctions, increasing cellular immunity by decreasing the cytokine storm with influence on interferon γ and tumor necrosis factor α and regulating adaptive immunity through inhibiting T helper cell type 1 responses and stimulating of T cells induction. Vitamin D supplementation was also found to enhance CD4+ T cell count in HIV infection.

Several in vitro studies demonstrated that vitamin D plays a significant role in local “Respiratory homeostasis” either by stimulating the exhibition of antimicrobial peptides or by directly interfering with the replication of respiratory viruses. Vitamin D insufficiency can, therefore, be involved in ARDS and heart failure and these are the manifestations of severely ill COVID-19 subjects. Therefore, vitamin D deficiency promotes the renin-angiotensin system (RAS), which may lead to chronic cardiovascular disease (CVD) and reduced lung function.

People with such comorbidities account for a higher percentage of severe ill cases in COVID-19. Although, many studies supported the immunomodulatory characteristics of vitamin D and its significant role in the maintenance of immune homeostasis; well-designed randomized controlled trials are required to elucidate the plausible role of vitamin D in protective immune responses against respiratory microbes and in preventing various types of acute respiratory tract infections.

“88% of pregnant women show asymptomatic (B types) of CORONA symptoms.”

2020-09-30T01:45:00.003+05:30

Normally COVID-19(Coronavirus) targets mainly the respiratory system of the human body, many people suffering from chronic respiratory disease those people get easily targeted by the COVID-19 virus, but if you are pregnant then your problems will be going to increases, prescribing medication for pregnant women been always tough for a gynecologist in term of mother and fetus health is a concern, but now problems are getting more worst by the entry of COVID-19.

If you are pregnant, then your mind has a lot of questions like, will your baby child live safely in this pandemic ? or if you have tested positive for Covid-19, what will you do? etc The answers have not been found yet, scientists are constantly working on it.

Indian Council of Medical Research-National Institute Research in Reproductive Health (ICMR-NIRRH), in collaboration with the Medical Education and Drugs Department (MEDD) and BYL Nair Hospital, worked on a new topic, and after seeing the results you will shock. “88% of pregnant women show asymptomatic (B types) of symptoms.”

This study running under the Indian Council of Medical Research-National Institute for Research in Reproductive Health (ICMR-NIRRH) in collaboration with Medical Education and Drugs (Department MEDD) & BYL Nair Hospital find out that most of the COVID-positive shows (TypeB) type of Symptoms.

For the investigation, information collected from 1,140 COVID-positive pregnant women. However, just 37 (11.5%) showed COVID-symptoms when they were hospitalized for delivery. The presence of the virus in women varied (0-40%) across various hospitals. “According to Our estimated result, out of every 9 asymptomatic women, there will be the presence of one symptomatic woman. ” which was displayed in the European Journal of Obstetrics & Gynecology and Reproductive Biology on September 23.

"Identification of asymptomatic pregnant ladies will secure them and their new-born child [as well as] medical staff, and it will help to break the chain of CORONA-virus spreading. The main advantage of detecting asymptomatic pregnant women is useful for ensuring safe obstetric & neonatal care.” Dr. Rahul Gajbhiye said.

Dr. Ashok Anand, head of obstetrics and gynecology said that “During pregnancy, from prescribing the medication to, so many other problems are also there, just like during pregnancy immunity level of pregnant womens has got low, which makes more probable to COVID infection.”, Over 600 COVID-positive pregnant women had treated by, Sir JJ Group of Hospitals, Mumbai.

PregCovid is open for all public and private Covid-19 hospitals in India that provide care to COVID-positive pregnant women. To be part of the registry, see https://pregcovid.com/for-covid19-hospitals/.

Some Frequently Asked Questions regarding the effect of COVID-19 on Pregnancy,

What effect will coronavirus have on my baby if I test positive for COVID-19?

As this is a very new virus, all the information and evidence is still not available to us. There is no evidence to suggest an increased risk of miscarriage if exposed to COVID-19. There is also no evidence of vertical transmission, which refers to the ability of the virus to pass to your unborn baby during pregnancy.

In a study of nine pregnant women in China who tested positive for COVID-19, all nine babies tested negative for the virus and were healthy overall. One pregnant lady in London tested positive for coronavirus and later her newborn also tested positive. However, it is unclear whether the baby contracted the viral infection in utero or shortly after birth. Expert opinion is that the baby is unlikely to be exposed during pregnancy, and it is unlikely for the baby to have any defects in development as a result. As of now, there isn’t any new evidence that says otherwise.

What are the effects of Coronavirus in the first trimester?

There is still no data available in the Lancet study on the first trimester, all pregnant women who participated in the Lancet study were all in their 2nd or 3rd trimesters. But for those who suffer from severe symptoms, then there will definitely be problems during obstetrics.

Are pregnant women a vulnerable group for Coronavirus?

It is not yet known if pregnant women are more susceptible to be infected by COVID-19 when compared to the normal population. Despite this, pregnant women are advised to reduce social contact with social distancing. It is an established fact that in some women, pregnancy alters how the body fights some viral infections. Though evidence for coronavirus is still insufficient, it is for this reason that pregnant women are advised to be extra cautious during this pandemic.

Will I be able to breastfeed my baby if I have suspected or confirmed coronavirus?

Yes. The main risk of breastfeeding is due to the close contact between you and your baby which can pose a risk of droplet infection that can spread to the baby while breathing. Discuss the risks and benefits with your treating doctor and family before you make a decision. Here are some steps to follow to minimize the risk of transmission:

Wash your hands before feeding or touching the baby, breast pump, or bottles

Try to avoid coughing or sneezing while you feed

Wear a face mask while feeding, if available.

If you are using a breast pump, follow instructions for cleaning and sterilizing properly.

Precautions for pregnant women against Coronavirus:

Here are some actions you can take to prevent getting the disease during pregnancy:

Wash your hands frequently. Hand hygiene can really protect you from exposure to COVID-19. You may hear this over and over but with good reason.
Practice social distancing. Always maintain a distance of at least 2 meters or 6 feet from others when you are in a public place. Avoid contact with others as much as possible.
Get your flu vaccination on time. Though the flu vaccine does not protect you from exposure to COVID-19, it does make you less susceptible to influenza, which can cause complications during pregnancy.
Use a tissue when you cough or sneeze, throw the tissue in the dustbin. Wash your hands right after.
Do not ignore any respiratory symptoms. If you develop a cough or any respiratory distress, do not hesitate to call your doctor. After taking a detailed history, your doctor will decide if you need to get tested for COVID-19.
Go virtual. As much as possible, consider virtual consultations instead of prenatal visits to your gynecologist. Try to minimize or altogether avoid spending time in the doctor’s waiting room or in the hospital. However, some tests will require you to be there in people such as ultrasound, blood tests, and fetal testing.
Work from home whenever possible.
Stay safe. Symptoms such as high fever with or without continuous cough may indicate a possible coronavirus infection. Avoid coming in close contact with anyone showing these symptoms.

Its time to look for support from your family and friends. Keep in touch via emails, messages, or video chats. Consider taking up a new hobby or acquiring a new skill. Do things that make you happy and put your mind at ease such as taking a long shower, meditating, or reading a book. Exercise as per your doctor’s advice and regularly do your Kegels and squats as recommended.

Do not stress too much if your due date is nearing, as hospitals have a system in place for safe deliveries and to ensure minimal risk of exposure for newborns.

Amazing facts about human body.

2020-09-12T13:50:00.002+05:30

Read some amazing & some weird facts about human body and explore out more about the brain, skeletons, muscles, eyes, bones, blood, muscles, the brain, heart and much more.

1.Human mouth daily produces about one litre of saliva through the mouth.

2.In case you smoothed out all the wrinkles on your brain, it might lay flat the scale of a pillowcase.

3.Do you know Sometimes human brain is more active while sleeping than when you’re awake.

4.Belly acid (Hydrochloric acid) can dissolve steel.

5. A human grown-up's blood veins can rotate multiple times in the Earth's equator.

6.Tongue prints are as particular as fingerprints

7."Muscle" originates from Latin term, signifying "little mouse", which is the thing that Ancient Romans thought utilized bicep muscles.

8.The jaw muscle is the strongest in the human frame.

9.Bodies emit a little measure of light that is excessively difficult for the eye to see.

10.While awaking, your brain produces enough strength to light a lightbulb.

11. The normal human being has 67 unique types of microorganisms in their tummy button.

12. While you blush, the inside of your stomach does too.

13. You lose about 4 kg of skin cells per year.

14. Data travels along the nerves at about 400 kmph!

15. Teratomas are certain kind of tumors they can grow with their own teeth and hair.

16. Astronauts can grow up to 2 inches taller in space.

17. In a normal human life heart beats approx. more than 3billion times.

18. Your left lung is around 10 percent littler than your right lung.

19. Your brain can survive for five to 10 mins without oxygen.

20. The small intestine is more or less 23 feets long.

21. Human teeth are similarly as solid as shark teeth.

22. In cases of severe hunger, the brain will begin to consume itself.

23. Human Nose can detects over a trillion distinctive scents: Study.

24. Humans get so many pairs of organs but out of them only one required to survive.

25. Your ears and your nose never stop developing.

26. Your left kidney is slightly upsidethan your right kidney.

27. You couldn't breathe and swallow at the equal time.

28. Your whole blood content is eight percent of your total body weight.

29. You know your body burns about three to 6 calories per minute during sex.

30. Cornflakes have a greater number of genes than humans do.

31. People can’t digest grass because absence of cellulase Enzyme.

32. On average, approximately 4 pounds of bacteria present around on our body.

33. In the human body The hottest recorded fever ever is one hundred fifteen fahrenheit.

34. In camera terms, the human eye is set 576 megapixels.

35. The medical call for stomach growls is “borborygmus."

36. Scientists are unable to disclose the reason behind yawning but it may be to control our human body temperature.

37. Scientists aren't exactly sure why we yawn, but it may help regulate body temperature.

38. Men’s testicles dangle underneath their bodies due to the fact sperm dies at normal body temperature.

39. After your death, your fingernails stop growing.

40. 50 percent of your hand energy comes out of your little finger.

41, Human being are the main animal presents with jawlines. As you inhale, a large portion of the air is going all through one nostril. Like clockwork, the remaining burden movements to the next nostril.

42. You have two kidneys, but you can live with one kidney also.

43. Between birth to death human loses up to 96 bones.; human birth generally with 300 bones but during time of death it has 204 bones.

44. All organs fulfill their requirement of oxygen through blood but the cornea is the only organ that gets oxygen directly from surrounding air.

45. The human body contains sufficient fats to make seven bars of soap.

46. The body’s largest organ is skin, it's 15% of total body weight.

47. Blushing is due to secretion of adrenaline".

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Only drug inspectors can probe, file FIRs for certain cognizable offences under D&C Act 1940: Supreme Court

2020-09-01T16:47:00.003+05:30

The Supreme Court recently ruled that drug inspectors can carry out an investigation and file a first information report (FIR) related to cognizable offenses which are specified as under chapter IV of the Drug and Cosmetics Act 1940. Chapter IV of the Drugs and Cosmetics Act 1940, deals with the manufacture, sale, and distribution of drugs and cosmetics activities.

Section 22(1)(d) of the Act, which deals with the powers of the ‘Inspector’, inter alia, enables the inspector to exercise such other powers as may be necessary for carrying out the purpose of Chapter IV or any Rules made thereunder. A police officer can register an FIR only if a cognizable offense, other than an offense falling under Chapter IV of the Act, is also made out. As far as FIRs that have already been filed are concerned, further investigation cannot be done by the Police officer.

The recent judgment of the Supreme Court concluded that for offenses committed under Chapter IV of the Drugs and Cosmetics Act 1940, only the ‘Drug Inspector’ has the powers to investigate any complaint, institute prosecution, and even arrest the offenders. Whereas, the police officer has absolutely no role to play in such offenses. Therefore, the police are bound to provide assistance to the drug inspector in case of need, to effectuate the arrest where there is resistance or likelihood of resistance. However, drug inspectors, who carry out any arrest, need to immediately report the arrests to their superior officers.

The move is appreciated by industry experts as well regulators, but many have also expressed the need for well-defined required infrastructure, single operating procedures for implementation.

Commenting on the judgment, Narendra Ahooja, State Drug Controller, Haryana, commented, “ The recent detailed judgment by the Supreme Court is the right step towards making the law very clear and transparent. In its order, it has defined that the actions under the provision of Drug and Cosmetics Act 1940 for cognizable offenses need to be taken by the drug inspector as notified under Section 21 of the Drugs and Cosmetic Act,1940. But to implement the order of the honorable Supreme Court in its true sense, the state FDAs need to be strengthened with required infrastructure and facilities.”

He added, “The drug inspector needs to be equipped with all the required infrastructure which have been given to a police inspector and other similar authorities. ”

SW Deshpande, Former Joint Commissioner FDA Maharashtra and Advocate Founder of PHARMALEX highlighted, “The Supreme Court’s order has wider implications. According to the order, it allows drug inspectors to carry out the investigation and as defined in the Drug and Cosmetics Act wherein the competent authority can file an FIR, it allows the drug inspectors to do so. However, in the present scenario, they are not trained to carry out these activities. Therefore this needs to be examined and statutory requirements should be jointly worked out by state and central authorities. ”

Ashish Prasad, Partner- Economic Laws Practice, said, “ The issue had to reach to the Supreme Court is quite obvious because the power granted specifically under the D&C act was being used by authorities not so empowered. The Supreme Court has now clarified that only the Drug Inspectors (and not the police) as notified by the central government are competent to initiate criminal proceedings, make arrests for offenses falling under chapter IV of the Drugs and Cosmetics Act. And the judgment brings in much-needed clarity as proceedings under the D&C Act were initiated by the police officer who (in most cases) lacked the technical qualification/ knowledge required for handling a science-based legal regime, which included handling of samples as per the procedures laid out in a special act. The procedure required to be followed under the D&C was often given a go by – presumably for lack of knowledge, by these officers which resulted in protracted litigations. Therefore, the court has clarified that the judgment will be prospective, thereby granting protection to the complaints /arrest made by an authority other than drug inspector.”

Envisaging the issues likely to come up, Mahendra Bajpai, Lawyer, Supreme Court commented, “ This judgment is bound to create problems as the drug inspectors are neither trained nor equipped to discharge duty as a policeman. The policymakers will either have to amend this pre-independence enactment or make rules and regulations to impart requisite training to drug inspectors. Until this happens, this judgment will only add chaos to an otherwise invisible and non-functional authority under the Act.”

An industry observer pointed out that it will not really work in favor of the industry. Since they will be the sole authority, there are high possibilities that they (Drug Inspectors) will arm-twist the matter according to their subject understanding. He also expressed that there is a high possibility of the system getting corrupt and being misused.

Corona Virus (COVID-19). (Detailed through WHO )

2020-08-29T20:15:00.009+05:30

Overview:

Nowadays many people infected with the COVID-19 virus. This virus mainly attacks the Respiratory system. Aged persons and those persons who suffer from other health problems like Asthma, diabetes, other chronic respiratory diseases, cancers, and various immunological diseases, can be easily affected by the COVID-19 virus.

The most ideal approach to prevent and hinder transmission is by taking various awareness programs advertisements, seminars, and explains the severity of the COVID-19 virus. Its causes and how it spread. Shield yourself as well as other people from contamination by washing your hands time by time or by using at least 60% alcohol-containing hand-sanitizers, hands rubs frequently by using these sanitizers and not touching your face.

The main reason for COVID-19 spreading is through salivary droplets or discharge from the nose when a nearby person coughs or sneezes, so it's significant that you likewise practice respiratory etiquette (for instance, by coughing into a flexed elbow).

Right now, there are no particular medicines or vaccines are available for COVID-19. However, there are many reputed universities and manufacturing industries constantly working on this, many of them are on clinical trial phages. WHO will keep on giving refreshed data when clinical discoveries become accessible.

Preventions:

Do the following things to prevent infections and slow transmission of COVID-19.

⦁ Avoid touching your face.

⦁ Stay home if you feel unwell.

⦁ Wash your hands Constantly with soap and water, or clean them with sanitizer.

⦁ Cover your mouth and nose when coughing or sneezing.

⦁ Maintain at least a 1-meter distance between you and people.

Symptoms:

Coronavirus affects many people in different ways. Most infected persons will create mild to moderate illness and cured without the need for hospitalization by using symptomatic medication.

Most common symptoms:

dry cough.
tiredness.
fever.

Less common symptoms:

Throat pain.
aches
headache.
conjunctivitis.
diarrhea.
Loss of smell and taste
a rash on the skin.
discoloration of fingers or toes.

Serious Symptoms:

chest pain or pressure.
difficulty breathing or shortness of breath.
loss of speech or movement.

If you have serious symptoms then you need hospitalization immediately. According to research mostly aged persons shows serious symptoms, due to past disease history.

Patients with having mild symptoms then those patients don’t need hospitalization they can take treatment at the home.

On normal it takes 5–6 days symptoms to show when somebody is attacked with the COVID virus, anyway it can take as long as 14 days.

Some More Frequently Used Questions Regarding Corona disease.

1) Who is working on a coronavirus vaccine?

Ans: Vaccine development is a lengthy process that often takes years, with many challenges.apart from that there are so many companies throughout the world working hard in the development of it.

Vaccines typically take about 10 to 15 years to develop and approve, through four phases that include human trials. But with Operation Warp Speed, rather than submitting all sections of the application after all four phases are done, approved vaccine projects can submit data to the FDA bit by bit.

Overall 23 pharmaceutical companies are working on it. In India the following firms are working on it listed as follows. While Zydus Cadila is working on two vaccines, Serum Institute, Biological E, Bharat Biotech, Indian Immunologicals, and Mynvax, there are 6 firms developing one vaccine each.

2) Is Russia's COVID-19 coronavirus vaccine safe?

Ans: In the Lancet study, Russian researchers reported on two small trials, each involving 38 healthy adults aged between 18 and 60, who were given a two-part immunization.

Each participant was given a dose of the first part of the vaccine and then given a booster with the second part 21 days later.

They were monitored over 42 days and all developed antibodies within the first three weeks. The report said the data showed that the vaccine was "safe, well-tolerated, and does not cause serious adverse events in healthy adult volunteers".

3) Will we get a coronavirus vaccine in 2020?

Ans: Researchers around the world have been racing to develop vaccines that can fight off the coronavirus. Now, a handful is starting the final stage of testing, or will soon. Depending on the results, some companies say their vaccines could be greenlighted for use as soon as this year.

4) Has Patanjali made a coronavirus vaccine?

Ans: Absolutely not, Patanjali made CORONIL TAB, SWASARI VATI & ANU TAILA mainly these are immune booster not confirmed official treatment of COVID-19. It will help only to increase your immunity against respiratory diseases.

Patanjali promotes these products as the First Ayurvedic COVID-19 treatment but recently the ministry of health ordered to remove all the promotional ads regarding this product and stop campaigning.

To Know More about COVID-19 visit the Following Link;

Click Here

Source: WHO's official website.