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PHARMACOLOGY

SR. NO. TOPIC PAGE NO.

01 OPIOIDS 2

02 ANTI HYPERTENSIVE 5

03 ANTI ANGINAL 11

04 ANTI ARRHYTHMIC 13

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PHARMACOLOGY

OPIOIDS SOURCE - Papaver somniferum (poppy plant)

PROTOTYPE - Morphine (agonistic activity on μ, and receptors) ACTIONS / ADVERSE EFFECTS MEDIATED BY OPIOID RECEPTORS

Sedation

(Less With Pethidine & Fentanyl)

Dysphoria

(Psychomimetic Effects)

Spinal Analgesia

Constipation

(Decreased Motility & Increased Git) (Devoid By Dextromethorphan) Modulation Of Hormone

Analgesia Analgesia Neurotransmitter Release Respiratory Depression - -

Cough Suppression - -

Truncal Rigidity (With Fentanyl, Alfentanyl &

Sufentanil)

- -

Euphoria (Dependence) - - Miosis (With Morphine) - -

Other Adverse Effects - Nausea, Vomiting, Itching, Convulsions

Withdrawal Syndrome Symptoms - Rhinorrhoea, Lacrimation, Yawning, Chills, Mydriasis, Vomiting, Diarrhoea & Anxiety

ENDOGENOUS PEPTIDE MAJOR ACTION ON

RECEPTORS ACTION

Endorphin μ

Analgesic Effects

Dynorphin k

Enkephalins δ

Nociception (New) Nociceptin / Orphanin FQ

(N/OFQ) or Orphanin like receptors (ORL1)

POTENCY






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METABOLITE

ACTIONS OF PURE OPIOIDS Analgesic Agents - Visceral, dull & constant pain is relieved more effectively than inflammatory pain. Pure Agonists - Morphine, Methadone, Pethidine, Levorphanol, Codeine, Hydrocodone, Oxycodone & Propoxyphene.

DRUG EFFECT ACTION

Morphine Central Nervous System Spinal & Supraspinal Analgesia

Pethidine & Pentazocine Peripheral Increase Heart Rate

Alvimopan Peripheral Antagonist for Paralytic Ileus

CLINICAL USE

Potency

Least

Meperidine (Pethidine)

Propoxyphene (Least Efficacious Analgesic)

Most Sufentanil

Morphine

Morphine-3-Glucuronide (M3G)

Neuroexcitatory

Seizures [Accumulation]

Morphine-6-Glucuronide (M6G) [10% of

Morphine]

Prolongs Opioid Action [Accumulation]

Pethidine

MAO - A (99%)Meperidinic Acid /

Pethidinic AcidInactive

Demethylated (1%) Norpethidine Seizure






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DRUG CLINICAL USE

Morphine Myocardial Infarction

Acute Pulmonary Edema

Pre-Anaesthetic Medication Codeine, Pholcodeine, Dextromethorphan &

Noscapine Cough Suppressants

Loperamide & Diphenoxylate Non-Infective Diarrhoea Fentanyl, Alfentanil, Sufentanil ( All Are Highly

Lipid Soluble) Adjuncts To Other Anaesthetic Agents

Pethidine Reduce Shivering After Anaesthesia

[By Its Action On A2 Receptor]

Diphenoxylate, Difenoxin (Active Metabolite) & Loperamide

Diarrhoea

Ziconotide Intrathecal Analgesia

(Blocks Voltage-Gated N Type Ca2+ Channels)

ROUTES OF ADMINISTRATION

DRUG ROUTES OF ADMINISTRATION

Morphine Oral, Rectal, I.V., I.M., Intrathecal or Epidural

Fentanyl Transdermal Patch, Buccal Transmucosal

Butorphanol Nasal Methadone Oral, I.V., S.C. or Rectal

CONTRACT INDICATION

OPIOIDS SIDE EFFECT ACTION CONTRACT

INDICATED IN

Increase Intrabiliary Pressure Constricting Biliary Smooth

Muscle Biliary Colic

Aggravate Bronchoconstriction Releasing Histamine Asthmatics

Seizures Used for Prolonged Periods Renal Failure

Increases Intracranial Tension (Morphine)

Retention of CO2

(Due to Respiratory Depression)

Head Injury

Exaggerated Response to Opioids Hypothyroidism

In-Utero Physical Dependence of Fetus & Severe Withdrawal Symptoms May Be

Precipitated After Birth Pregnancy

Tachycardia (Pethidine And Pentazocine) Anticholinergic Activity Myocardial Infarction

CAUTION - In infants, elderly and patients with pulmonary, hepatic or renal dysfunction.

MIXED AGONISTS-ANTAGONISTS

DRUG RECEPTOR ACTION

Buprenorphine

Partial Agonist

at μ Antagonist at

Analgesic& alternative to methadone for the management of opioid withdrawal.

Dissociates slowly from μ receptors & is thus resistant to






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& naloxone reversal.

Nalbuphine, Pentazocine

& Dezocine

Agonists μ Antagonists

Psychomimetic effects with hallucinations, nightmares & anxiety.

Butorphanol Agonist Analgesia but more sedation than morphine.

OPIOID ANTAGONISTS

DRUG RECEPTOR TIME ROUTE USE

Naloxone

potent

antagonists

with significant blocking action at

& receptors

Very Short

Acting

Parenterally (Ineffective

Orally)

Acute Opioid Poisoning Neonatal Resuscitation

Naltrexone Longer

Half Life Parenterally

Maintenance Drug for Opioid Poisoning

Prevent Relapse after Opioid De-

Addition Decrease Craving in Chronic

Alcoholics

Nalmefene Long

Acting Orally

Treatment of Obesity (Along with Bupropion)

Alvimopan & Methylnaltrexone

Peripheral

Opioid Antagonists

- - Opioid Induced Constipation

Naloxegol (New) - -

OPIOD DE-ADDICTION

DURATION DOSE THERAPY WITHDRAWAL

SYMPTOMS DRUG

Short Small Sudden

Stop Mild -blockers or Clonidine or Lofexidine

Long Large Sudden

Stop Severe Methadone

OPIOID POISONING Diagnosed by - Pin Point Pupil

Naltrexone - Maintenance Therapy in Opioid Poisoning, Used to Prevent Relapse, Blocking Receptors

IMPORTANT POINTS

DRUG POINT

Morphine, Hydromorphone & Oxymorphone

Strong opioid agonists

Levorphanol Similar to morphine in its actions

Heroin (Diacetylmorphine) Potent and fast acting opioid but carries high risk of abuse potential

Methadone

Long acting opioid analgesic Blocks N-methyl-D-aspartate (NMDA) receptors and reuptake of monoamines Long t½ so development of dependence and tolerance is very slow

Treatment of opioid abuse






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Opioid rotation therapy

Pethidine & Pentazocine Anticholinergic activity (can result in tachycardia)

Nalbuphine Ceiling effect to its respiratory depressant action

Tramadol Weak μ receptor agonist Inhibits reuptake of NA and 5-HT

Tapentadol receptor agonistic

NA reuptake inhibiting action

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PHYSICAL PHARMACY

RHEOLOGY

DEFINITIONS

TEAM MEANING NOTE Rheo To flow -

Logos Science -

Rheology Study of flow Suggested by Bingham &

Crawford

Rheograms /

Consistency Curves / Flow Curves

Plot of shear rate (G) as a function of shear stress (F)

Greater the slope, the greater is

the fluidity or lower is the viscosity

Viscosity (η) (Nm-2sec or dynecm-

2sec) Resistance of a fluid to flow

Higher the viscosity greater the

resistance

Poise

Shearing force required to produce a velocity of 1 cm/sec between two parallel planes of

liquid each 1 cm2 in area and separated by a distance of 1 cm.

-

Viscosity Ratio / Relative Viscosity

(ηr)

Ratio of the solution viscosity to the viscosity of the solvent (ηo)

Kinematic Viscosity (υ)

(Stokes or Centi

Stokes)

Viscosity divided by the density of the liquid at specified temperature

Fluidity (Φ) Reciprocal of viscosity Φ = 1 / η

Velocity Gradient / Rate of Shear (dv/dr)

Difference of velocity (dv) between two

planes of liquid separated by an infinitesimal distance (dr)

-

Shearing Stress The force per unit area (F/A) required to bring

about flow -

Yield Value Plastic flow rheogram does not pass through the origin but intersects with the shear stress

axis at a point -

Thixotropy An isothermal and comparatively slow recovery, on standing of a material of a

consistency lost through shearing.

Desirable property in liquid

pharmaceutical systems that ideally should have a high

consistency in the container, yet pour or spread easily.

Hooke's Law

Principle of physics that states that the force (F) needed to extend or compress

a spring by some distance (X) scales linearly

with respect to that distance.

F = kX, where k is a constant factor characteristic of the spring

its stiffness and X is small compared to the total possible

deformation of the spring.



https://en.wikipedia.org/wiki/Physics

https://en.wikipedia.org/wiki/Force

https://en.wikipedia.org/wiki/Spring_(mechanics)

https://en.wikipedia.org/wiki/Stiffness



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Young's Modulus (E) /

Elastic Modulus

Number that measures the resistance of a material to being elastically deformed.

Stiffer a material, the higher its Young's modulus. (E= σ /ϵ=Stress

/Strain)

Deformation Effect of change in the shape of a physical

object when an external force is applied to the

surface.

If a body does not change its shape, even slightly due to

external forces, the object is defined as a perfect solid object.

Perfect solid bodies are not present in nature; every object has

its own deformations.

SIGNIFICANCE OF RHEOLOGY IN PHARMACY

1. Pharmaceutical manufacturing - Mixing, filtration & packaging of liquids 2. Removal of formulation prior to use - Pouring from bottles, extrusion from tube or passage through

syringe

3. Influences selection of equipment in manufacturing 4. Affects physical stability of formulations 5. Affects rate of absorption of drugs from GIT

FLOW

SYSTEM NAME PRINCIPLE GRAPH FROM

GRAPH EXAMPLE /

NOTE

Newtonian systems

Rate of shear directly

proportional to the shear stress

applied

Slope gives the

coefficient of viscosity (η). Intercept on y axis gives

limiting viscosity

number or intrinsic

viscosity (η).

Intrinsic viscosity can be

used to determine the approximate

molecular mass

(M) of polymers using the Mark

Houwink equation[η] =

KMα Non

Newtonian Flow

Scales

(Saybolt, Redwood,

Engler)

Viscosities vary with shear rate

and are

Plastic Flow (Bingham Bodies)

Plastic material

does not flow until a particular value of shear stress has been

exceeded and at lower stresses the substance behaves as

elastic material.

Yield value

indication of force of

flocculation. (The more

flocculated the

suspension, the higher

will be the yield value.) Rheogram

does not pass

Concentrated flocculated

suspensions.





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always dependent

of the length of time that the shear

rate applied.

through the origin.

Pseudoplastic Flow

(Shear Thinning Systems)

Viscosity keeps on changing as

the rate of shear

changes and there is no single

value of viscosity. At

very high shear rates, the curve becomes linear indicating that

limiting viscosity is reached.

Viscosity decreases as the shear rate

is increased as indicated

by the curve.

Aqueous

dispersions of natural and chemically modified

hydrocolloids such as

tragacanth, methylcellulose,

carmellose,

sodium alginate, methylcellulose,

sodium carboxymethyl

cellulose.

Dilatant Flow (Shear

Thickening Systems)

Viscosity keeps on changing as

the rate of shear changes. As the

shear rate is increased the

particles become displaced from

their even distribution

which result in the creation of

larger voids. The effect is

reversible and removal of the

shear stress results in the re-establishment of the fluid nature.

Viscosity

increases as the shear rate is increased as indicated

by the curve.

Exhibited by dispersions

containing a high

concentration (= 50%) of small, deflocculated

particles.

Creates problem

in Manufacturing

Thixotropy

(Time

Dependent)

Gel-to-Sol Transformation

& Exhibits Shear Thinning

Once the shear stress has been

removed, even if the structure

which has been broken down is

reversible, it may not return to

its original structure

instantly.

Hysteresis loop

indicates that a breakdown in structure

has occurred

and the area within the

loop may be used as an

index of the

Concentrated parenteral

suspensions containing from 40% to 70% w/v

of procaine

penicillin G in water.





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degree of breakdown.

Bulges

When sheared in

a viscometer in which shear rate

(rather than shear stress) is

increased to a point, then decreased.

The shear

stress is read at

each shear rate value to

yield appropriate rheograms.

Concentrated aqueous

bentonite gel, 10% to 15% by

weight.

Spurs

A sharp point of structural

breakdown at low shear rate

- Procaine

penicillin gel

Negative Thixotropy or

Antithixotropy

Increase in thickness or

resistance to flow with

increased time of shear

-

Represents an increase in

consistency on the down

curve

Magnesia magma

VISCOSITY DETERMINATION / MEASUREMENT OF FLOW

FOR TYPE NAME DESCRIPTION NOTE

Newtonian Systems

(Single Point)

Capillary Viscometer

Ostwald U-tube viscometer

Measuring time required for the liquid to pass between two marks as it flows by

gravity through a vertical capillary tube.

-

Falling Sphere

Viscometer Hoeppler viscometer

Based on Stokes law, when a body falls through a

viscous medium it experiences a resistance or

viscous drag which opposes the downward motion.

-

Non Newtonian Systems

Multipoint

Single-point

determination is useless in

Cup & Bob Viscometer

Couette Type - Cup is rotated

Mac Michael

viscometer

Sample is sheared in the space between the outer

wall of a bob and the inner

wall of a cup into which the bob fits. Torque results

from rotation of the cup or of the bob.

Disadvantages:

Plug flow & End correction required.

Searle Type -

Rotating Bob Brookefield viscometer

-





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characterizing its flow

properties

Instrument should operate

at a variety of shear rates

Cone &

Plate Viscometer

Ferranti Shirley

Viscometer

Flat circular plate with a wide angle cone placed

centrally above it variable speed motor drives the cone and the sample is sheared in the narrow gap between the

stationary plate and the rotating cone.

Advantages: Rate of shear is constant throughout the

entire sample, sample required is less, cleaning and

filling is not tedious

DEFORMATION IN SOLIDS

Elastic Deformation

Reversible

Bonds between molecules

or atoms stay intact but only change their lengths linear relationship with

stress

If a graph of stress versus strain is plotted, the plot would be a linear one for

some lower values of strain. When the plot of stress versus strain is linear, the

system is said to be in the elastic state. This linear area is the zone in which the

object is deformed elastically.

Calculated using Hooke’s law

which states that for the elastic range of the material, applied

stress is equal to the product of the Young’s modulus and the

strain of the material.

Plastic Deformation

Irreversible

Plate sliding occurs due to the total fission of the

bonds curved relationship having a peak

When the stress is high the plot passes a

small jump on the axes. This is the limit at which it becomes plastic deformation. This limit is known as the yield strength of the material. Used in metal hardening

to pack the atoms thoroughly.

Viscoelastic

Have a viscosity factor

Dissipate energy (heat) when a load is applied

Strain rate dependent on time

Property of materials that exhibit both viscous and elastic characteristics when

undergoing deformation. Synthetic polymers, wood and human tissue, as

well as metals at high temperature. Used for isolating vibration, dampening noise,

and absorbing shock.

Brittle

Undergo extensive fragmentation generally result in tablets of relatively

high porosity because of the large number of bonding points that are created

which prevent further volume reduction.

-

Ductile Often result in tablets of low porosity

because the high degree of plastic -



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deformation enables the particles to move very close to each other.

SURFACE AND INTERFACE TENSION

DEFINITIONS

TERM DESCRIPTION FORMULA / GRAPH / NOTE

Interface Boundary between two phases

Liquid–liquid interface, emulsion

Liquid–solid interface, suspension Solid-solid, powder particles in

contact

Surface When one of the phase is gas Gas-liquid, body of water exposed to

atmosphere

Gas-Solid, Solid surface, table top

Surface Tension (γ)

Force per unit length that must be applied

parallel to the surface so as to counterbalance the net inward pull

γ = f/2L

Surface Free Energy

(increase in

surface free energy is

proportional to the increase in

surface area and surface

tension)

Each molecule at the surface possesses potential energy greater than that present in

bulk. This energy is proportional to the size of

the free surface and is called as Surface Free Energy.

dW = f x ds = γ x 2L x ds = γ x dA

W = γ ΔA

Spreading Formation of a duplex film of one immiscible

liquid over the other

Oil will spread as a film over water if the force of adhesion between the oil molecules and the water molecules is

greater than the cohesive forces between the oil molecules themselves.

Work of

Adhesion

Energy required to break the attraction

between the unlike molecules

Wa = Surface tension x Area

Wa = γL + γS – γLS

Work of Cohesion

Work required to separate the molecules of the spreading liquid so that it can flow over the

sublayer.

Wc = 2γL

Spreading Coefficient (S)

Difference between work of adhesion and work of cohesion. S is positive spreading

occurs, if S is negative the liquid does not

S = Wa – Wc = (γL + γS – γLS) – 2 γL

S = γS – (γL + γLS)





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spread and remains contracted as a lens over the sublayer.

Surface Active Agents

or

Amphiphile

Molecules and ions that are adsorbed at

interfaces. Amphiphilic nature of surface-active agents leads to adsorption at interfaces, whether these are liquid–gas or liquid– liquid

interfaces.

-

Required HLB Oil phase of an emulsion requires a specific

HLB -

Adsorbent The material used to adsorb the gas (solid) -

Adsorbate The substance being adsorbed (gas) -

Desorption Removal of adsorbate from adsorbent -

Wetting (Solid-Liquid

phenomenon)

Adsorption at solid surfaces is involved in the

phenomena of wetting and detergency Determined by Drave’s test

Contact angle Angle between a liquid droplet and the surface

over which it spreads. It has any value between 0 to 180°

Wetting agent

Surfactant that, when dissolved in water,

lowers the contact angle, aids in displacing an air phase at the surface, and replaces it with a

liquid phase.

At equilibrium, surface and interfacial

tension can be resolved as Young’s equation

γS = γSL + γL cosθ

HLB scale

(Hydrophile Lipophile

Balance)

Griffin devised an arbitrary scale of values to

serve as a measure of the hydrophilic–lipophilic balance of surface-active agents. The higher the HLB of an agent, the more

hydrophilic it is. E.g.

Spans: Low HLB; form w/o emulsions; Tweens: High HLB; form o/w emulsions

Adsorption Isotherms

The relationship between amount of gas adsorbed on a solid at equilibrium pressure or

concentration at a constant temperature is

given by adsorption isotherm.

Freundlich

isotherm -

Solid Gas Interface

However, the Langmuir assumptions are not universal. The gas can be adsorbed as

-





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multilayer on solid surface. Also, variations in isotherms arise if the solid is porous.

Solid Gas Interface

(Langmuir Isotherm - Langmuir

assumed that gas is adsorbed on active sites

of a solid.

Adsorption occurs as a monolayer)

At any given point of time there is adsorption

as well as desorption occurring. The rate of adsorption is proportional to the number of active sites available as well as the pressure

-

Type I: Ammonia on charcoal at 273 K

Type II: Multilayer formation

Nitrogen on silica gel at 77K

Type II adsorption isotherm is given by BET equation (Brunauer, Emmett, Teller equation)

Type III: Slow adsorption

Bromine on silica gel at 352 K

Type IV: Porous solid

Benzene on iron oxide gel at 320 K





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Type V: Slow adsorption; porous solid

Water vapor on charcoal at 373 K

Solid Liquid

Interface

Used in adsorption chromatography for

separation of compounds •Treatment of emergencies: Activated

charcoal •Adsorption in formulations: Loss of

antimicrobial activity due to adsorption of preservatives by solids/containers.

Many drugs, dyes, fatty acids are adsorbed from solution onto solids

such as charcoal or alumina

APPLICATION OF SPREADING COEFFICIENTS IN PHARMACY –

The surface of the skin shows presence of aqueous–oily layer having a polar–nonpolar character similar to that of a mixture of fatty acids.

Dosage forms such as lotions should spread effectively over the affected part.

For a lotion with a mineral oil base to spread freely and evenly on the skin, its polarity and hence its spreading coefficient should be positive.

MEASUREMENT OF SURFACE / INTERFACIAL TENSION

Capillary rise

Du Nouy Ring Tensiometer

Drop Drop weight Drop number

CALCULATION OF HLB

HLB of a nonionic surfactant whose only hydrophilic portion is polyoxyethylene

HLB = E/5

HLB of surfactants comprising of polyhydric alcohol fatty acid esters (glyceryl monostearate)

HLB = 20 (1-S/A)

LUNG SURFACTANT - Phosphatidylcholine

Surface active agent that covers the surface of alveoli contacted with air. It decreases the surface tension at the air–alveoli interface.





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ANATOMY PHYSIOLOOGY AND PATHOPHYSIOLOGY

BODY FLUID COMPARTMENT

Total body water (TBW) in an adult comes to around 60% of total body weight.

In infants, TBW =7 % of body weight.

Measurement of total body fluid component:

Plasma volume Evan’s blue

RBC volume Determined by TBV-PV

Extracellular effect

Also called as ‘Sucrose space’ radioactive sodium

Total body water Heavy water, by dilution principle

Interstitial fluid Cannot measured directly calculated as ECF volume-plasma volume

ICF Cannot measured directly, calculated as TBW-ECF

NERVES

POTENTIALS

Electronic potential: It occurs due to passive addition of charge.

Local potential: It occurs due to opening of the voltage gated Na ion channel.

Action potential: It occurs due to opening of many Na ion channel.

Resting membrane potential of the neuron is -70mV.

Resting Membrane Potentials

Neuron- 70mV

Skeletal muscle- 90mv

Cardiac muscle- 90mv

Thyroid- 50 mV

RBC- 10 mV

Inner hair cell- 150 mV

HYPOTHALAMUS AND ITS FUNCTION

KEY FUNCTIONS

Regulation Part of hypothalamus ADH release Supraoptic nucleus





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Circadian rhythm Suprachiasmatic nucleus

GnRH secretion Arcuate nucleus

Oxytocin release Paraventriular nucleus

Prolactin release Arcuate nucleus

Thyroid stimulating hormone

Para ventricular and neighbouring nuclei

Increased ECF (Thirst) Osmoreceptor

Response to heat Anterior hypothalamus

Response to cold Posterior hypothalamus Sexual behaviour Anterior ventral hypothalamus

Emotions Dorsal and posterior hypothalamus

Feeding centre Ventromedial nucleus

MOTOR INTEGRATION TABLE

Level of integration Principle function

Cerebral cortex Initiation of voluntary movements Placing and hoping reactions

Hypothalamus, limbic system

Emotional functions

Midbrain, thalamus Locomotor reflexes

Midbrain Righting reflexes

Medulla Antigravity reflexes, control of heart and respiratory rate

Spinal cord Control of spinal reflexes

IMPORTANT CENTRES

Lateral and posterior nucleus of hypothalamus

Sympathetic system

Medial and anterior nucleus of hypothalamus

Parasympathetic system

Micturition centre Medial frontal cortex

Relay centre of all sensory system

Thalamus

Vomiting centre Medulla

Vasomotor centre Rostral ventrolateral medulla

Vomiting centre

Respiratory centre

Reticular formation





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DRUG REGULATORY AFFAIRS

REGULATORY AGENCIES IN DIFFERENT COUNTRIES

Country Regulatory agency

USA Food and drug administration

India Central drug standard control organisation (CDSCO)

UK Medicine and healthcare product regulatory agency (MHRA)

Europe European medicines agency (EMEA)

Australia Therapeutic goods administration (TGA)

Brazil Agencia National de Vigiloncia Sanitaria (ANVISA) Japan Ministry of health labour & welfare (MHLW)

Canada Health Canada

Denmark Danish medicines agency

New Zealand Medsafe- Medicines and medical devices safety authority

Sweden Medical product agency (MPA)

Netherland Medicines evaluation board

Ireland Irish medicines board

Italy Italian pharmaceutical agency Nigeria National agency for food and drug administration and control (NAFDAC)

Ukraine Ministry of health

Singapore Centre for pharmaceutical administration health science authority

Thailand Ministry of public health

China The national medical product administration (NMPA)

Malaysia National pharmaceutical control bureau

Germany Federal institute for drugs and medical devices South Africa Medicines control council (MCC)

Sri Lanka SPC, ministry of health

Switzerland Swiss medic, Swiss agency for therapeutic products

Uganda Uganda national council for science and technology Pakistan Drugs control organization, Ministry of Health

IMPORTANT DATES CELEBRATED ALL OVER WORLD:

Date & Month Day

January 30 World Leprosy Education Day

February 4 World Cancer Day February 12 Sexual & Reproductive Health Awareness Day

March 6 Glaucoma Day

March 11 No Smoking Day

March 12 World Kidney Day December 3 World Disabled Day

March 16 Measles Immunization Day





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March 24 World TB Day

April 7 World Health Day

April 17 World Haemophilia Day April 19 World Liver Day

April 25 World Malaria Day

May 6 World Asthma Day

May 8 World Red Cross Day May 8 World Thalassaemia Day

28 July World Hepatitis Day

May 28 International Women Health Day

May 31 Anti-Tobacco Day June 5 World Environment Day

June 8 World Brain Tumour Day

June 14 World Blood Donation Day

June 21 International Yoga Day July 1 Doctors Day

July 29 ORS Day

August 1-8 World Breast Feeding Week

August 25-8 Sep Eye Donation Week September 1-7 National Nutrition Week

September 12 World Oral Health Day

September 21 World Alzheimer’s Day

September 26 World Day Of The Deaf September 28 World Heart Day

October 2 National Anti-Drug Addiction Day

October 10 World Mental Health Day

October 12 World Slight Day October 17 World Trauma Day

October 20 World Osteoporosis Day

October 21 World Iodine Deficiency Day

October 24 World Polio Day March 4 World Obesity Day

October 29 World Stroke Day

November 2 World Pneumonia Day

November 10 World Immunization Day November 14 Diabetes Day

November 20 World COPD Day

November 15-21 Newborn Care Week

December 1 World AIDS Day December 3 International Day Of Disabled Person





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COMMON ABBREVIATIONS

ANDA Abbreviated New Drug Application

BEA Breeding For Experimental Animals

BPI British Pharmaceutical Index CADD Computer- Aided Drug Design

CDC Centre For Disease Control

CIPLA The Chemical, Industrial & Pharmaceutical Laboratories.

CPCSEA Committee For Purpose Of Control &T Supervision Of Experimental Animals

CRO Contract Research Organisation

CTD Common Technical Document

DRA Drug Regulatory Affairs

EMEA European Medicine Agency FDA Food And Drug Administration

GCP Good Clinical Practices

GLP Good Laboratory Practices

GMP Good Manufacturing Practices GRAS Generally Recognised As Safe

HPLC High Performance Liquid Chromatography

HRSA Health Resources & Services Administration

IAES Institutional Animal Ethics Committee ICH International Conference On Harmonization

TB-DOT Directly Observed Therapy

UGC University Grant Commission

ICMR Indian Council For Medical Research IIG Inactive Ingredient Guide

IMP Investigational Medicinal Product

IMPD Investigational Medicinal Product Dossier

INDA Investigational New Drug Application IPC Indian Pharmaceutical Congress

ISO International Organization For Standardisation

NCE New Chemical Entity

NCPA National Community For Pharmacist Association NDA New Drug Application

NME New Molecule Entity

NSAID Non Steroidal Anti-Inflammatory Drug

OTC Over-The Counter PMS Post- Marketing Surveillances





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R&D Research & Development

SARS Severe Acute Respiratory Syndrome

SDS-PAGE Sodium Dodecyl Sulphate-Polyamide Gel Electrophoresis TGA Therapeutic Good Administrations

TMF

Trial Master File

UDV Unit Dose Vial

WIPO World Intellectual Property Right

DISCOVERIES OF CAUSATIVE AGENTS

Sr.no. Causative agent Discovered by

1 Anthrax Robert Koch

2 Tuberculosis Robert Koch 3 Cholera Robert Koch

4 HIV Luc Montaginer’s team

5 Malaria Charles Louis Alphonse Laveran

6 Leishmaniasis William Leishman 7 Dengue virus Ren kimura and Susumu Hotta

8 Influenza Wilson Smith

IMPORTANT DISCOVERIES

Sr.no. Discovery Year Scientist

1 Gravity 1687 Sir Issac Newton

2 Blood circulation 1628 William Harvey 3 Oxygen 1774 Joseph Priestley*

4 Immunization 1796 Edward Jenner*

5 Atomic elements 1803 John Dalton

6 Pasteurization 1864 Louis Pasteur 7 Radio activity 1896 Marie Curie

8 Penicillin 1928 Alexander Fleming*

9 Chemotherapy 1900 Paul Ehrlich*





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INDIAN PHARMACOPEIA EDITION LIST

First edition of IP was published in the year 1955.

Headquarter- Ghaziabad U.P.

Chairman- P.K.Pradhan ,secretary

Edition Year 1st edition 1955

2nd edition 1966

3rd edition 1985

4th edition 1996 5th edition 2007

6th edition 2010

7th edition 2014

8th edition 2018

ACTS

Sr.no. ACT Passed year

1 Opium act 1857 2 Design act 1911

3 Poison act 1919

4 Payment and wages act 1936

5 Drug and cosmetic act 1940 rules (1945) 6 Pharmacy act 1948

7 Minimum wages act 1948

8 Factories act 1948

9 Industrial act 1952 10 Drug price control order act 1995

11 Drugs and magic remedies act 1954

12 Prevention food adulteration act 1954

13 Medical and toilet preparation act 1955 14 Essential commodities act 1955

15 Trade and merchandise act 1958

16 Prevention cruelty of animal act 1960

17 Insecticide act 1968 18 Patent act 1970

19 Medical termination of pregnancy act 1971

20 Sale and promotion employee act 1976

21 Narcotic and psychotic act 1985





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22 Consumer protection act 1986

23 Establishment of AICTE 1988

24 Competition act 2003 25 National pharmaceutical pricing

policy act

2012

26 Epidemic disease act 1897

27 Industries act 1951

28 New drug policy 1994 29 Drug act 1940

AMINO ACIDS

INTRODUCTION

Amino acids are group of organic compounds two functional groups- amino and carbonyl.

Amino group is basic while the carboxyl group is acidic in nature.

Optical isomerism of amino acids: If a carbon attached to the four different atoms. It is asymmetric

therefore exhibit the optical isomerism.

BIOLOGICALLY IMPORTANT COMPOUNDS FORMED FROM AMINO ACIDS

Amino acids Amines Functions Serine Ethanolamine From choilne

Histidine Histamine

Vasodilation,

promotes gastric HCl pepsin synthesis

Phenylalanine, tyrosine

Dopamine For adrenaline, nor adrenaline

Tyrosine Tyramine Vasoconstriction

Tryptophan Tryptamine, serotonin

Elevated BP stimulated

Glutamic acid GABA Inhibitory neurotransmitter

Cysteine Taurine Constituent of bile acid

PROPERTIES OF AMINO ACIDS

Zwitter ion or dipolar ion: Is a hybrid molecule containing the positive or negative charge ionic groups.





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Isoelectric pH: Is defined as the pH at which the molecule exists as zwitter ion or dipolar ion and

carries no net charge.

Chemical properties:

o Decarboxylation: Amino acid undergoes the decarboxylation to produce the corresponding amines.

o Reaction with ammonia: The carboxyl group of the dicarboxylic amino acids reacts with the NH3

to form the amide.

AMINO ACIDS USEFUL AS DRUGS

D-penicillamine: Metabolite of Penicillin, employed for the chelation therapy of Wilson’s disease.

N- acetylcysteine: Is used in the cystic fibrosis and chronic renal insufficiency.

Gabapentin: Used as anticonvulsant.

CLASSIFICATION OF AMINO ACIDS

Structural classification:

Name sym

bol

One

Lette

r

Special group

present

Amino acids with

aliphatic side chains

Glycine gly G Alanine Ala A

Valine Val V Branched chain

Leucine Leu L Branched chain

Isoleucine Ile I Branched chain

Amino acids

containing hydroxyl

group:

Serine Ser S Hydroxyl

Trhreonine Thr T Hydroxy

Tyrosine Tyr Y Hydroxy

Sulphur containing

amino acids:

Cystine - C Sulphhydryl

Cysteine Cys Dispulphide

Methionine Met M Thioether

Acidic amino acids

Aspartic acid Asp D β- carboxyl Aspargine Asn N Amide

Glutamic acid Glu E γ –carboxyl

Glutamine Gln Q Amide

Basic amino acids

Lysine Lys K ϵ-amino





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Arginine Arg R Guanidine

Histidine His H Imidazole

Aromatic amino acid

Phenylalanine Phe F Benzene or phenyl

Tyrosine Tyr Y phenol

Tryptophan Trp W Indole

Imino acid

Proline Pro P Pyrrolidine

Nutritional classification of amino acids:

Essential amino acids Semi-essential amino

acids

Non- essential amino

acids

These amino acids cannot synthesized by the body need to be

supplied through diet.

Can be synthesized by the adults but not growing children

The amino acids which can be synthesized by the human bodies

Threonine Tryptophan Histidine Arginine

Leucine Lysine Methionine Valine

Isoleucine Phenylalanine

Histidine Arginine

Alamine Aspargine Aspartic acid Glutamic

Proline Cysteine Glutamine Glycine

Serine Tyrosine

Classification based on the basis of the fate of carbon skeleton:

Glycogenic Glycogenic and

ketogenic Ketogenic

Alanine Phenylalanine Leucine Arginine Isoleucine Lysine

Aspartate Tyrosine

Cysteine Tryptophan

Glutamine

Glutamate

Glycine

Histidine

Hydroxyproline Proline

Methionine

Serine

Threonine





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Valine

IMPORTANT NON-PROTEIN AMINO ACIDS AND THEIR FUNCTION

Sr.No. Amino acids Function

1 Ornithine, citrulline, arginosuccinic acid

Intermediate in urea cycle

2 Thyroxine Thyroid hormones

3 Homocysteine Intermediate in methionine metabolism.

4 Homoserine Intermediate in threonine, aspartate, methionine metabolism

5 Dihydroxy phenylalanine Neurotransmitter, serves as precursor of melanin pigment

6 Creatinine Derived from the muscle and excreted in urine

7 Favithiol Sulphur containing amino acid found in fertilized egg and acts as antioxidant

8 Azaserine Antibiotic

9 Alanine Component of vitamin B5 and coenzyme A

10 Aminoisobutyric acid End product of pyrimidine metabolism

11 γ- Amino butyric acid Neurotransmitter produced form glutamic acid

12 ALA Intermediate in the synthesis of porphyrin

13 Taurine Found in association with bile acids

IN BORN ERRORS OF AMINO ACIDS METABOLISM

Disorder Metabolic defects

Glycine: Glycinuria Primary hyperoxaluria

Defect in renal reabsorption Glycine transaminase

Phenylalanine

and tyrosine: Phenylketonuria Tyrosinemia type II

Alkaptonuria Tyrosinosis Albinism

Phenylalanine hydroxylase Tyrosine transaminase Homogentistate oxidase

Maleyl acetoacetate isomer tyrosinase

Sulphur

containing

amino acids:

Cystinuria

Defect inn renal absorption Impairment in cysteine reabsorption

Cystathionase





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Cystinosis Cystathionuria

Tryptophan:

Hartnup’s disease

Defective intestinal reabsorption

Aliphatic

amino acid: Maple syrup urine disease

Branched chain α – chain keto acid dehydrogenase

Histidine: Histidinemia

Histidase

Proline :

Hyperprolinemia type I

Proline oxidase

TEST FOR PROTEINS

Test Reagent Observation Amino acid

Biuret test

KOH+ hydrated copper sulphate+sodium

potassium tartrate

Purple colour Confirm presence of peptide bond

Ninhydrin’s test 2,2 dihydroxy

indane 1,3 dione Ruhemann’s purple

Alpha amino

acids

Sanger’s test 1-fluoro 2,4, dinitro benzene

By chromatography Amino acid sequence

Xanthoprotic test Conc. Nitric acid Yellow precipitated Aromatic amino acid

Millon’s test mix. of sulphuric acid and mercury sulphate

Nitro phenol mercury

sulphate Phenolic

Folin-ciocalteu test

Sodium tungstate and sodium

molybdate

For colorimetric assay Phenolic (tyrosine)

Sakaguchi test Alpha naphthol+ sodium hypochlorite

Red colour Guanidine group (arginine)

Hopkin’s test Glyoxylic acid Violet purple colour Indole ring (tryptophan)

Sulphur test Sulphur dioxide Black precipitate

Sulphhydryl group (cysteine,

cystine) not methionine

Pauly’s test Diazo benzene sulphonate

Red colour Imidazole ring (histadine)

Molisch test 10% alpha naphthol +ethanol

Red purple colour Glycoprotein





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Heller’s test HN03 White ppt Coagulation test for albumin

UREA CYCLE/ KREBS-HENSELET CYCLE/ ORNITHINE CYCLE

Definition: It is cyclic pathway in which ammonia is converted to urea.

Site: Liver

Location: Mitochondria, cytosol.

Role of fumarate: Fumarate provides a link between the urea cycle and TCA.

VITAMINS AND THEIR ALTERNATE NAME

Sr. No.

Vitamins Alternate name

1 Vitamin B1 Anti-beri beri or antineuritic factor

2 Vitamin B3 Pellagra preventive factor

3 Vitamin B5 Anti dermatitis factor or filtrate factor

4 Vitamin B7 Anti egg white injury factor, vitamin H

5 Vitamin B12

Anti pernicious anaemia vitamin

6 Vitamin D Antirachitic factor

7 Vitamin K Antihemorrhagic factor

VITAMIN THEIR CHEMICAL NAME AND THEIR ACTIVE FORM

Vitamin Chemical

name Ring Active form

A Retinol β- ionone ring Retinol, retinal, retinoic acid

B1 Thiamine Pyrimidine+thiazole Thiaminopyro-

phosphate (TPP)

B2 Riboflavin

(GPAT 2020)

Isoalloxazine (6,7-

dimethylisoalloxazine) FMN, FAD

B3 Niacin Pyridine-3-carboxylic acid NAD, NADP+

B5 Pantothenic

acid Pantoic acid+ β – alanine Coenzyme A

B6 Pyridoxine Pyridine Pyridoxal phosphate B7 Biotin Imidzole+ thiophene Biocytin

B9 Folic acid Pteridine+PABA+glutamic

acid Tetra hydro folic acid

B12 Cobolamin Corrin ring Methyl cobalamin

Vitamin

C Ascorbic acid Resemble with hexose Ascorbic acid





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Vitamin D

Cholecalciferol Steroidal ring 1,25- dihydroxy cholecalciferol

Vitamin

E Tocopherol Chromane ring α –tocopherol

Vitamin k

naphthoquinone Naphthoquinone

Phylloquinone k1

Menaquinone k2 Menadione k3

COENZYME OF B-COMPLEX VITAMIN

Sr.

No. Coenzyme

Derived from

protein Dependent enzyme

1 Thiamine pyrophosphate Thiamine Transketolase

2 Flavin monophosphate Riboflavin l-amino acid oxidase

3 Flavin dinucleotide Riboflavin d- amino acid oxidase

4 Nicotinamine adenine dinucleotide phosphate

Niacin Glucose-6- phosphatase dehydrogenase

5 Lipoic acid Lipoic acid Pyruvate

dehydrogenase

6 Pyridoxal phosphate Pyridoxine Alanine

transaminase

7 Coenzyme A Pantothenic acid Thiokinase 8 Tetrahydofolate Folic acid Formyl transferase

9 Biocytin Biotin Pyruvate

carboxylase

10 Methylcobolamin Cobalamin Methylmanoyl CoA

mutase



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