phases of drug development

7/31/2019 Phases of Drug Development

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PHASES OF DRUG DEVELOPMENT

1. PRECLINICAL TRIAL Chemicals that may have therapeutic value are tested in LABORATORY ANIMALS dueto 2 main reasons:

a. To determine presumed effects on living tissuesb. To evaluate any adverse effects

At the end of the trial, some chemicals will be discarded due to:a. Chemicals lack therapeutic activity in living animalsb. Chemicals are too toxicc. Chemicals are highly teratogenic (causes adverse effects to the fetus)

If Chemicals are approved, they will move to Phase I Studies.2. PHASE I Studies Tightly controlled than preclinical & performed by Trained Clinical Investigators Use ofHEALTHY HUMAN VOLUNTEERS to test drugs and may be paid for participation

and possible risks are informed; YOUNG MEN & WOMEN ARE NOT GOOD CANDIDATES

b/c chemicals may have an effect in womans ova.

At the end of the phase 1, some chemicals are discarded due to:a. Lack of therapeutic effect in humansb. Chemicals are too toxicc. Chemicals are highly teratogenicd. Chemicals cause unacceptable adverse effects.

3. PHASE II Studies Clinical Investigators test drugs with PATIENTS WHO HAVE THE DISEASE THAT THE

DRUG IS MEANT TO TREAT and often no charge to them.

Should sign a consent paper and possible benefits, risks, and effects are informed. Performed in Clinics, Hospitals, Doctors Offices At the end of the phase, drugs are removed from further investigation due to:

a. Too toxicb. Causes unacceptable adverse effectsc. Less Effectived. Not as effective compared to other drugs available.e. Low benefit to risk ratio (therapeutic effect of drug doesnt outweigh possible

potential risk or effect)

4. PHASE III Studies Using drug in vast clinical market All prescribers are informed of all known reactions & precautions for its safe use All prescribers evaluate reported effects to determine if they are caused by the drug or

disease.

If drug is widely used, unexpected responses occur If with unacceptable adverse effect or unforeseen reactions, drug is completely removed

from study or market.


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FDA APPROVAL

Drugs that finish Phase III Studies are evaluated by FDA APPROVAL

Relies on the committee of the experts familiar with the specialty area. Drugs with FDA Approval may be marketed. Process of drug development and approval can take 5 6 years DRUG LAG5. PHASE IV CONTINUAL EVALUATION Prescribers are obligated to report to FDA for any untoward or unexpected adverse effects

of the drug and FDA continually evaluates this condition

a. Chemical Name reflects the drugs chemical structure.b. Non Propriety / Generic Name original designation the drug is given when the

company applies for approval.

c. Propriety Name / Trade Mark / Brand Name name of approved drug given byPharmaceutical Company that developed it.

FDA PREGNANCY CATEGORY

Category A Studies indicate no risk to the fetus

Category B Animal reproductive studies indicate no risk to fetus but no adequate studies inpregnant women

Category C Has adverse effect on the fetus but adequate studies in pregnant women

Category D Positive evidence of fetal risk but potential benefits of drug for pregnant woman

may be acceptable despite potential risk

Category X Positive fetal abnormalities

Positive evidence of fetal risk

Risks outweigh benefits for pregnant women (Risk > Benefits)

Should not be used by pregnant women

THE CONTROLLED SUBSTANCES ACT OF 1970

Regulates the manufacturing, distribution, and dispensing of drugs which are known to have abuse

potential.


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SCHEDULES OF CONTROLLED SUBSTANCES

1. Schedule I (C-1) High abuse potential and no accepted medical use Ex. Heroin, Marijuana, LSD (Lysergic Acid Diethylamide)

2. Schedule II (C-II) High abuse potential with Severe dependence liability High liability for severe psychological and physical dependence Prescription is required and cant be renewed Ex. Amphetamines, Barbiturates, Narcotics

3. Schedule III (C-III) Less abuse potential than Schedule II and Moderate dependence liability High psychological dependence Prescription is required Ex. Non Barbiturates, Non Amphetamines, Limited amt of Narcotics, Sedatives, Stimulants

4. Schedule IV (C-IV) Less abuse potential than Schedule III and Limited dependence liability Can be purchased without prescription provided that:a. Distribution is made only by Pharmacistb. Pharmacist knows the purchaserc. Pharmacist, Doctor, Nurse must keep an official written record of:

Name of Patient or Purchaser

Name and Quantity of Controlled Substances Initials of Dispensing Pharmacist Ex. Anticonvulsants, Tranquilizers, Anti-Anxiety Agents, Non Narcotic analgesics,

some sedatives

5. Schedule V (C V) Limited Abuse Potential Can be purchased without prescription by at least 18y/o with suitable identification Ex. Primarily small amount of narcotics (codeine) used as anti-tussives or anti diarrheals


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DOSAGE FORM

POSOLOGY study of different dosage and dosage form

1. TABLET

Most popular dosage form and easiest to administer Dried and powdered that is compressed and moulded in small disk Formed by compressing a mixture of pure drug and inactive components to add bulk and

formed into precise size and shape.

a. Scored Tablet / Grooved Tablet For convenient division into halves or quarters Marked with indented line across the surface Can be cut using ampule file

b. Layered Tablet / Press Coated Tablet Has different layers or cores (for product identification) Separates different drugs or doses

c. Enteric Coated Tablet Coated w/ substance to prevent it to be dissolved into stomach but permits to be

dissolved into small intestines.

Not to be crushed or chewed or broken.d. Tablet Triturates Molded tablets with sugar Uses:

a. Dental Purposesb. Antiseptic Effectc. Bactericidal Agents

d. Buccal Tablet Administered into inner lining of the cheeks, gums, or teeth (between inner lining of

gums and molar teeth)

e. Sublingual Tablet Placed under the tongue (has many blood vessels for faster absorption) Allows to be dissolved and enter into blood circulation without passing the stomach


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Buccal and Sublingual Tablets

Usually Cardiovascular / Anti Hypertensive / Anginal Drugs Effect is 5 10 minutes1.

Refrain taking chewing gum (heat absorption that can BP & sugar coats into the tongue)

2. Inform patient thattheres stinging sensation (means drug is potent)3. Dont offer fluids during administration4. Offer fluids after drug is dissolved at least 30 minutes after.5. Check V/S after 15 30 minutes but observe client from time to time.6. Observe for HypotensionSigns and Symptoms of Hypotension

Pale Dizziness or Vertigo Blurring of Vision / Spots

Headache Malaise Cold and Clammy Perspiration

2. CAPSULES Enclosed in hard or soft gel or soluble shell which is usually made ofGELATIN.a. Hard Gelatin Capsule has 2 parts that slides together to enclose medicinal componentsb. Soft Gelatin Capsule to encapsulate medicinal liquids or gelc. Sustained Action Capsule or Time Release Capsule Contains small impregnated beads or small particles that require varying amounts of

time to dissolve

Reduces no. of doses administered

Effect is12 24 hours and may reach to 3 weeks

3. LOZENGES / TROCHES / PASTILLES Flat, round, or rectangular disk preparation (generally disk shaped) held in the mouth and

dissolves slowly and exerts anesthetic or antiseptic effect

Not for


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4. SUPPOSITORY Preparation for the use in the mucous membrane Medicinal substance mixed with firmed but malleable base (ex. Glycerine) Inserted into external orifices of the body (anal or vaginal) Generally should be refrigerated

Melts into body temperature to release medicinal content

GUIDE TO IDENTIFY SUPPOSITORY

1. Color white or transparent2. Mostly bullet shape3. Oily4. Covering is sealed and follows actual shape of drug (cut at the tip first not sides)Note: Have patient defecate prior administration of drug

INTRAVAGINAL SUPPOSITORY

a.

Position: DORSAL RECUMBENTb. Moisten tip of drug with KY Jelly or Plain Sterile. Dont use mineral oil or petroleum jelly forthey impedes absorption of medication

c. Instruct patient to breathe into his mouth while inserting gloved finger going downwards thenupward

d. If patient is an Adult use index fingere. If patient is a Child use 4th or 5th fingerRECTAL SUPPOSITORY

a. Position: LEFT LATERAL OR SIDELYINGb. Instruct patient to contract buttocks, breathe into mouth, and insert gloved finger upwards for

4 inches (8-10cm).

c. If child, hold the buttocks (5 20 minutes max drug will take effect)Should not be administered to the ff:

1. Rectal surgery2. Prostatic surgery (Prostate Surgery)3. Trauma of rectum (ex. Fistula , crack)4. Severe rashes or lesions

Advantages

1. Avoids irritation of upper GIT2.

If medication has foul taste or odor3. Drug released at slow steady rate

4. Direct absorption without passing to liverEx. Misoprostol (Cytotec) contains glycerine, a round suppository inserted into rectum or vaginaavout 4 inches.


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SOLUTIONS

1. SUSPENSION Liquid dosage form containing solid drug particles suspended in liquid medium Must be shaken thoroughly prior to assure uniformitya. Magmas Sometimes called MILK for they are WHITE in color. Tends to settle or separate upon standing Should be shaken before poured

b. Gels aqueous solution in hydrated formAluminum and Magnesium Hydroxide (Almg) ANTACID

Magnesium can absorb and draw out water

Ex. Maalox

Relieves patient from gas distention or pain. Sometimes contain simethione dimethicone if Maalox Plus. Adult dose: 30 ml and not >90ml Child dose: 4 5 ml not to > 20ml Can cause diarrheal or constipation if exceeded

2. EMULSION dispersion of fine droplets of oil in water; Shake it well3. SPIRITS alcoholic solutions of volatile substances (ex. ammonia)4. TINCTURES hydroalcoholic solutions usually prepared from plants5. SYRUPSsolutions of sucrose or sugar to disguise unpleasant taste of drugs; shake it well; dont

offer liquids


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TOPICAL DOSAGE FORM

1. LINIMENTS Liquid or suspension applied to skin by rubbing. Contains water, alcohol, and volatile oils Uses:

a. Relieves painb. RUBBEFACIENT EFFECT REDDENING OF THE SKIN INCREASED BLOOD

SUPPLY

c. Antiseptic Effectd. Soothing Agente. Intended for Massage (relaxing, heat activated, and repellent)

2. OINTMENTS Semi solid with oils and water and doesnt wash off easily Uses:

a. Soothing Agentb. Bacteriostatic Effect

3. TRANSDERMAL THERAPEUTIC SYSTEM Based on FICKS LAW OF DIFFUSION(Applied directly to Skin or areas with large blood

supply (should be free from irritations, rashes, lesions, etc) Heat Release of Drug

Semi-permeable membrane relieve or alleviate pain / extension of effect if oral meds are

taken)

Has NITROGLYCERINE and mixed with SOLID POLYMER or SILICON which acts ascosolvent that enhances penetration.

a. Ointment Provides relief longer than Sublingual Preparation Instructions:

a. Dont shave areab. Dont rub just leave paper in place (may irritate and reduces action of drug)c. Cover paper with plastic wrap and tape itd. Tell client that it may discolour clothing.

Ex. Nitrobid, Nitrolb. Patched Like or Topical Patch

Enhances penetration and provides controlled release of NITRATES thru semi permeable membrane for 24 hours when applied to skin

Effects can be observed within 30 minutes Ex. Nitrodisc, Nitrodur


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Patch or Sheath

Place just above the nipple in an upward manner Just tap and dont spread. Drug will be released and it stains clothing. Applied directed towards the veins or with large blood supply Not for areas with skin folds (ex. neck, antecubital) and Should be free from pressure Remove using downward manner so hair wontbe removed (ex. cream based)Instruction to Patient:

1. Clean area with water. Dont use alcohol for drug can penetrate fast and produces more heat2. If client has chest hair, may place at rotation sitesCHLONODINE applied every 7 days; anti hypertensive or angina drug

ESTROGEN good for 3 weeks then 1 week rest (ex. Ortho Evra Pulse Treatment)

NICOTINE good for 3 weeks then 1 week rest

SEOPOLOMINE anti vertigo drug (for dizziness) ; applied 4 hours before travel; effect is within

2 3 hours

PHENTANYL ex. Durajesioc (analgesic, antipyretic, effectiveness for 12 hours)


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PHARMACOKINETICS

Study of the CONCENTRATION OF THE DRUG through the process of ABSORPTION,DISTRIBUTION, BIOTRANSFORMATION, AND EXCRETION.

1. ABSORPTION movement of drugs into source of entry, into the body, and into bloodstream.Factors that affects the Absorption Rate of the Drugs

1. Route of Administration (Oral or Parenteral)2. Solubility of the Drug (Solutions are soluble than tablets and capsules)3. Condition of the site of administration4. PH of Body Fluids

Common Routes of Administration

A. For Systemic Effects Has 2 Subdivisions: Gastrointestinal and By InjectionBy Gastrointestinal Tract

1. Oral thru mouth2. Buccal into inner lining of cheek, gums, and teeth3. Sublingual under the tongue4. Rectal rectallyBy Injection

Administration by the use of needles Administration by a route other than oral

1. Intramuscular into the muscle2. Intravenous into a vein3. Subcutaneous into the tissue beneath the skin

B. For Local Effects (specific body organ)1. Topical skin or mucous membrane2. Intraarticular within the cavity of the joint3. Intraosseous into a bone4. Intracardiac into a chamber of the heart5. Intradermal or Intracutaenous into the surface of the skin6. Intraarterial into the artery7. Intrathecal / Intraspinal / Subdural / Subarachnoid / Lumbar Injection into the

spine or subarachnoid space

8. Inhalation into respiratory tract


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FLEET ENEMA

Uses:a. For total evacuation of stoolsb.

Bowel Cleanser

Standard Adult Dose: 118 ml for 12 years old and above Effect: within 2 5 minutes Position: Genupectoral / Dog Style / Knee Chest Contents:

a. Monobasic Sodium Phosphateb. Dibasic Sodium Phosphate

Contraindications:a.

Kidney Diseaseb. Sodium Restricted Diet

c. Post Anal Surgeryd. Anal lesions, rashes, and traumae. Hypertensionf. Nausea and Vomiting

PERCUTANEOUS ADMINISTRATION medication directly to mucous membrane

NORPLANT CONTRACEPTIVE THAT LAST FOR 3 YEARS


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Type of Injection Site Angle Needle

Gauge

Volume

of S

Use /

Syringe

Nursing Implications

Intradermal

(ID)

Intracutaneous

(IC)

Skin Test (ST)

a. Inner surfaceof lower arm

(antecubitalfossa)

b. Hairless,thinly

keratinized

areas of

upper chest

and shoulder

blade.

c. Inner thighNote:Avoid visible

veins, lesions,

moles,

birthmarks,

measles, redness,

erythema, scars,

Avoid bony

prominences if at

the back

10 15

degrees

26 27 0.1ml0.5ml

Tuberculin

Syringe

Allergy Testing

(check after 30 mins)

for erythema, pruritus, circumscribed area,rashes

Diagnostic Purpose

Mantoux Test to check

+ tuberculoprotein;

PPD; 48 72 hours

Vaccine Admin (BCG)

Anti-rabies vaccine

Subcutaneous

(SC / SQ)

Advantages:

Useful for

soluble &

insoluble drug

May be used for

unconscious &

uncooperative

patient

Allows slower

absorption ofdrug compared

to IM and & IV

For areas

abundant in

tissues)

a. Lower lateralaspect of

upper arm

b. Abdomen oneither side of

the umbilicus

c. Buttocks(upper outer

quadrant)

d. Anterior thighe. Outer back

45 90

45 and

60

(thin

client,

stretc

h and

bunch

1 inch

tissue)

90 (2

inches

cangive at

90

degree

s on

abdom

en

25 26 0.2ml0.5ml

Or up to2.0 ml

Penadur

Pulmin

Insulin

Syringe

(for

insulin)

Heparin

and other

Bronchodil

ator

(tuberculi

n syringe)

Insulin and Heparin

are administered at 90

degree to decreaselocal complication of

long term insulin

therapy

Other than insulin and

heparin, inject at 45

degree


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Intramuscular

(IM)

Advantages:

Rapid

absorption

Useful forsoluble &

insoluble drug

May be used for

unconscious &

uncooperative

patient

1. DeltoidMuscle

a. Adult2 3fingers below

acromion

process

b. Child 1 2fingers below

acromion

process

2. ButtocksIn sidelying

position

a. DorsoglutealGluteus

Maximus

upper /outerquadrant of

buttocks

b. Ventrogluteal

Sidelying or

Supine; Using

gluteus minimus

*has less fat

*greater thickness

of tissue and

muscles*away from sciatic

nerve or blood

vessels

*less

contaminated

*sealed by a bone

c. VastusLateralis

Child upperthird of thigh

Adult middle

outer third ofthigh

d. RectusFemorisanterior

aspect of

thigh (in line

with sciatic

nerve)

90 19 23

If drug is

viscous,

use 21

3.0 5.0ml

For medication that is

irritating to subcu

tissue

Requires rapid

absorption


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phases of drug development

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