Radio pharmaceuticals

★ Radio pharmaceutical are a group of pharmaceutical drugs which have radioactivity it can be used as diagnostic & therapeutic agents.

★ Radio pharmaceutical are medicinal formulation containing radioisotope which are Used in clinical areas for diagnosis therapy.

★ The production of radioactive substance involves bombardment of atomic nuclei with sub atomic particles to produces unstable nuclei of some elements.

★ These unstable atoms have some physical & chemical properties as that of parent atom differ in rate of chemical reactions.

Terminology-;

1.Isotopes-;

Isotopes are nucleid with same atomic number but different mass number.

Example-; ₆C¹² , ₆C¹³ , ₆C¹⁴

2. Isobars-;

Isobars are the atoms with Same atomic mass & different atomic number.

Example-; ₁₉K⁴⁰ , ₂₀Ca⁴⁰

3. Atomic number-;

It is the no of protons in the nucleus.

Example-; ₆C¹² atomic no. = 6

₁₉K⁴⁰ atomic no. =19

4. Atomic mass-;

It is the total no. Of proton and neutron in the nucleus.

Ex- ₆C¹² atomic mass- 12

₂₀Ca⁴⁰ ,, ,,, - 40

5. Nucleid-;

A nucleid is an atomic species characterized by the specific constitution of its nucleus ( i.e. it's atomic no & atomic mass).

6. Isotones-;

Isotones are those elements which have same no of neutrons and different atomic no.

Example-; ₆C¹⁴ & ₇N¹⁵

7. Stable & unstable nuclei-;

The nuclei of element which having low atomic no are most stable if the no of neutron is equal to or slightly greater than ( 12more) the no of protons.

If the no of neutron is less or greater ( two or more ) than the proton , the nucleus is unstable.

Types of Radioisotopes-;

There are two types of radioisotopes—

1. Natural radioisotopes or natural radionuclide-;

★ Those radionuclide produces radiation without any stimulation are known as natural radioisotopes these isotopes are unstable due to excess of energy by emitting radiation, they achieve stability.

Example- Uranium- 238 , Radium- 226. , Cesium- 137

2. Artificial radionuclide-;

★ Artificial radionuclide are prepared by reaction like irradiation of suitable material with neutrons in a nuclear reactor.

Example- phosphorus - 32 , iodine - 131 , flourine- 18

Types of radiation-;

★ The radiation is emitted from the radioactive isotopes in the form of charged particles ( ɑ ,𝝱 and 𝛄).

★ This libration is continuous process and atoms try to give out energy and gits converted into a more stable nucleus.

1. Alpha particles-;

★ These particles are identical to Helium atoms containing 2 proton & 2 neutron .

These are heavy particles with less penetrating power & more ionisation capacity.

Alpha emitters are not used in pharmaceutical preparations.

Example- Uranium. , Radium , thorium

2. Beta ( 𝝱) particles-;

★ These are generally negatively charged some time found is positively called position.

★ These particles can penetrate into the tissues upto 1cm .

★ Ionisation power is less than ɑ - particles.

Example- carbon 14 , & sulphur-35

3. Gamma radiation-;

★ These are electromagnetic radiation similar to visible light these radiation have shorter wave length but contain high energy with greater penetrating power as compare to visible light .

★ These particles do not have mass & charge & travel with the speed of light .

Example- Iodine -131 , cobolt - 60 , cesium- 137.

Biological effects of radiation-;

★ Radiation have very dangerous effect on biological tissue.

★ These radiation causes ionisation & excitation of molecules in the body & causes abnormal chemical area.

• The abnormal chemical reactions depending upon—

★ Penetration power of radiation.

★ Energy of radiation.

★ Dose of irradiation.

★ Time exposure.

★ Particular area & tissues exposed.

★ These radiation ionisation promote a number of irreversible changes in living cells. These chemical changes alter the local pH or serve to initiate free radical chain reaction & forming peroxide & other toxic compound.

★ These radiation can create the hostile environment for tissue cell, leading to necrosis & ultimetly complete distruction of the tissues & organ occurs.

Skin change-;

A short exposure to the intense radiation produces erythema ( skin burn / redness) .

Longer exposure can causes brittleness & dryness & later causes malignant ( uncontrolled cell division & distroyed body tissues).

Somatic effect-;

★ Some effect like cancer luekamia , severe anamea & contract are visible after few months upto many years, after exposure to radiation.

Genetic effect-;

★ Long exposure radiation can alter the DIVA cells & causes cross linking between certain amino acids & protein & alter genes / chromosomes.

These mutation inherited by future generations & become harmful.

Measurement of radiation-;

★ When a radioactive atom decay , it emits a particle or electromagnetic radiation or both the intensity of radiation depends on mode of decay.

For the measurements of radiation various types of equipment are disigned.

The properties of radiation help to decide to design the method.

Radiation detector are divided into two categories depending on—

1. Collection of ions

2. Collection of photons

1. Detector used for collection of ion—

Ion - collecting detectors—

1. Gasfilled

• Electroscope

• ion chamber

• proportional counter

• Geiger- mullar counter

2. Solid state

• Barrier layer detectors

• Lithium drift detector

a. Ion chamber-;

★ ionisation chambers are the simplest of all gas filled detectors .

They depends upon the collection of all charge due to direct ionisation and electric current.

The filled gas may be Helium (He ) , Argon(Ar) air etc.

★ Gas filled detectors used in various shapes & sizes . It consists of gas filled chambers with two electrodes kept at different electric potential & with measuring devices, which indicate the flow of electric current.

It is generally used for the detection of α - particles.

Pressure-↓ atom

b. Proportional counter-;

★ It is detect low ionising charge particles.like 𝝱- Particle & 𝜸 - rays .

★ It work on the principle that when voltage between cathode & anode is sufficiently increased so that primary ions produced by the interaction of gas with charged particles.

★ These counter are similar to G.M . Counter but modify by changing the gas composition & the shape of one or both electrode.

★ The advantage of the proportional counter It's ability to distinguish between alpha & beta particles if the radioactive source emitting both alpha & beta particles is placed in the chamber & the voltage applied to the chamber slowly increased.

At a certain voltage only alpha particles are detected between at higher voltage generally beta particles are detected.

Geiger - mullar counter-;

★ It's efficient for detection of beta particles.

It consists of a stainless steel cylinder.which serves not only as the body of the tubes but as the cathodes .

A fine wire , mounted coaxially, is the anode .

The special gas mixture is also filled between anode & cathode.

Due to the potential positively charged & Negalevely charged ions are Ar+ alcohol concentration+ hydrogen carbon with ↓ pressure.

Colleted over the respective electrode each particle of radiation causes a brief pulse current flow .

Solid state detectors [ Semi conductor detector ] -;

★ A semiconductor detector in ionising radiation using to measure the effect of incident charged particles.

★ It generally used silicon or germanium.

★ In this type of detector bond gap is very small . So the large no of electron hole pairs are incident.

★ The supplied energy is proportional to the collection of electron.

★ Lithium drifted detector are most widely used in X- ray & Gamma counting & gives high purity .

★ Barium layer detectors are generally used for α- particles.

Lithium drifted- 1. Silicon

2. Germanium

Collection of photon or scintillation- detectors-;

★ Scintillation- absorb energy & get excited & lead to emission of e- . Scintillators are material that fluoresces when struck by a charged particles or high - energy Photon.

★ When the radiation incident on photo- cathodic layer .

It will pass the radiation in photomultiplier tube chamber in photomultiplier tube each electrode placed at + 100V difference primary e- when incident on 1st electrode it will further more to next electrode & movement repeated to last electrode & absorption and emission of energy occurs in the form of photon .

This photon measured by scintillation detector .

Scintillators-;

1. Organic — example- anthracene & stilbe

2. Inorganic— example— NaI = 𝜸 particles

CsI = α particles

Handling and storage of radioactive material-;

★ A care should be taken to protect people and personnel from harmful radiation during handling & storage of radioactive material.

★ These radiation may causes serious complications which as blood Cancer.

★ Lead ( pb) acts as shielding material for absorbing radiation.

The following precautions are taken while working with radioactive material—

1. These material should be handled with forceps or suitable instrument and direct contact should be avoided.

2. Any substance which is taken internally ( food , drinks , smoke etc) should not be carried in laboratory where radioactive material are used.

3. Sufficient shielding must be provided on protective clothes and other wears used by the person while handling the material.

4. It should be Stored in lead bricks shielded container with suitable level in a remote corner.

5. Radioactivity of the surrounding environment, where it is stored or handled should be monitored constantly.

6. The final disposal of radioactive material should be done with great care to animals and environment.

7. Shielding effect can be achieved by thick concrete blocks or pure distilled water layer .

Application of radioisotopes-;

★ Radioisotope are useful in medicine, agriculture, pest control, age dating, sterilization & food preservation etc.

These agent are useful in varied field of pharmacy as therapeutic applications, diagnostic agent, sterilization of parenteral products and also in various research field.

a. External sources-;

★ These are used as sealed sources implanted in a tissue and dose is without drawn by removal of source from tissue.

Teletherapy - used in post Operative treatment of lesions where surgical removal of lesions not occur

Ex- ₆₀C

Surface source- used for dermatological & opthalmic application.

Ex- P₃₂

Extracorporeal irradiation- These generate x- rays act on blood & leads to depletion of lymphocytes.

Ex- Co - 60

b. Internal source-;

★ These agents are used as solution, capsule, ampules and injection.

Ex- Au - 198 & P- 32 are used as infusion ( catheter) in treatment tumors & fluid accumulated in the abdomen or chest , also use in treatment of polycythemia .

Ex- P- 32 and I- 131 well absorbed at the site of action or gets activated at the desired place.

Diagnostic application-;

★ Radioisotope are used for finding out various diseases such as—

1. Chromated albumin (Cr- 51) — It is used for detection & quantitation of gastro- intestinal protein loss without affecting erythrocytes.

2. Iodinated albumin injection ( I - 131 & I - 125) — Used to determine blood or plasma volumes & cardiac output & detection of brain tumors.

3. Cyanocobalamin (Co- 60) —Used in the treatment of megaloblastic anaemia .

4. Iron salt — Used in lung imaging & used in determination of metabolism & absorption of iron.

5. Sterilization— Co - 60 is used for production of Gamma rays which have high penetration power . This property is used to sterilize various thermolabile substance, syringes , needle, glove & clothes etc.

6. Gallium citrate— Ga-67 used for diagnosis of lesions of the lungs, breast used in detection of lymphomas ( enlarge lymph nodes , fatigue & weight loss ) and bronchial carcinomas.

Contrast - Media [ Radiopaque ]

★ The radioactive material emits x- rays which can pass all the soft tissue of the body but are absorbed at hard tissue ( bone) .

The rays produces a black spot on photographic plate by forming a complex.

The formation of spot on soft and hard tissue depending on optical density.

These differences in their optical density help in formation of light and dark spots.

If tissue having equal optical density,spots on photographic plates are not differentiated or not clearly seen .

Types of contrast media-;

Negative—ex- Air , CO₂ , & O₂

Positive —

Iodine compound-

BaSO₄ for GIT

1. Negative contrast media- It reduces the atomic no of area to be olemo strated. Organs become more radiolucent .

X - rays penetrate more easily.

2. Positive contrast media- It increases the atomic no. Of the area to be demonstrated in ralation to surrounding tissue. Organ become radio paque by this contrast media.

BaSO₄ properties-;

★ It is also known as barium meal.

★ It is suitable for GIT contrast .

★ Ba have high atomic no.

★ No. toxic materials.

★ Inert chemical not react with other body chemical .

★ Relatively cheaper than other media.

Iodinated contrast media-;

★ It also have high atomic no.

★ Provides excellent radio opecity due to higher atomic no.

★ Radio opecity means —

Phenomenon of not permitting the passages of electromagnetic radiation.

Pharmaceutical inorganic chemistry-1 || Radio pharmaceutical