PHASES OF DRUG DEVELOPMENT

1. PRECLINICAL TRIAL Chemicals that may have therapeutic value are tested in LABORATORY ANIMALS due to 2 main reasons: a. To determine presumed effects on living tissues b. 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 animals b. Chemicals are too toxic c. 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 of HEALTHY 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 humans b. Chemicals are too toxic c. Chemicals are highly teratogenic d. 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 toxic b. Causes unacceptable adverse effects c. Less Effective d. 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.

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 LAG
5. 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 by Pharmaceutical Company that developed it.

FDA PREGNANCY CATEGORY

Category A Category B Category C Category D Category X Studies indicate no risk to the fetus Animal reproductive studies indicate no risk to fetus but no adequate studies in pregnant women Has adverse effect on the fetus but adequate studies in pregnant women Positive evidence of fetal risk but potential benefits of drug for pregnant woman may be acceptable despite potential risk 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.

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 Pharmacist b. Pharmacist knows the purchaser c. 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

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 Purposes b. Antiseptic Effect c. 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

Buccal and Sublingual Tablets

Usually Cardiovascular / Anti Hypertensive / Anginal Drugs Effect is 5 10 minutes

1. 2. 3. 4. 5. 6. Refrain taking chewing gum (heat absorption that can BP & sugar coats into the tongue) Inform patient that theres stinging sensation (means drug is potent) Dont offer fluids during administration Offer fluids after drug is dissolved at least 30 minutes after. Check V/S after 15 30 minutes but observe client from time to time. Observe for Hypotension

Signs 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 of GELATIN.
a. Hard Gelatin Capsule has 2 parts that slides together to enclose medicinal components b. Soft Gelatin Capsule to encapsulate medicinal liquids or gel c. 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 is 12 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 <6 years old No more than 6 8 lozenges per day (=1 fruit sugar) since it can cause Nausea and Vomiting Overdosage: Take milk products or egg whites For Diabetics: should be sugar free Ex: Dequadin, Seven Seas, Valda Pastilles Orofor L (Lidocaine for local anesthetic; numbness of tongue; assess movt of tongue) Fishermans Friend Streptuss (4 6 hours) Strepsils (2 4 hours interval)

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. 2. 3. 4. Color white or transparent Mostly bullet shape Oily 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 RECUMBENT b. Moisten tip of drug with KY Jelly or Plain Sterile. Dont use mineral oil or petroleum jelly for they impedes absorption of medication c. Instruct patient to breathe into his mouth while inserting gloved finger going downwards then upward d. If patient is an Adult use index finger e. If patient is a Child use 4th or 5th finger RECTAL SUPPOSITORY a. Position: LEFT LATERAL OR SIDELYING b. 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. 2. 3. 4. Rectal surgery Prostatic surgery (Prostate Surgery) Trauma of rectum (ex. Fistula , crack) Severe rashes or lesions

Advantages 1. 2. 3. 4. Avoids irritation of upper GIT If medication has foul taste or odor Drug released at slow steady rate Direct absorption without passing to liver

Ex. Misoprostol (Cytotec) contains glycerine, a round suppository inserted into rectum or vagina avout 4 inches.

SOLUTIONS
1. SUSPENSION Liquid dosage form containing solid drug particles suspended in liquid medium Must be shaken thoroughly prior to assure uniformity a. 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 form Aluminum 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 well 3. SPIRITS alcoholic solutions of volatile substances (ex. ammonia) 4. TINCTURES hydroalcoholic solutions usually prepared from plants 5. SYRUPS solutions of sucrose or sugar to disguise unpleasant taste of drugs; shake it well; dont offer liquids

TOPICAL DOSAGE FORM

1. LINIMENTS Liquid or suspension applied to skin by rubbing. Contains water, alcohol, and volatile oils Uses:
a. Relieves pain b. RUBBEFACIENT EFFECT REDDENING OF THE SKIN INCREASED BLOOD SUPPLY c. Antiseptic Effect d. Soothing Agent e. Intended for Massage (relaxing, heat activated, and repellent)

2. OINTMENTS Semi solid with oils and water and doesnt wash off easily Uses:
a. Soothing Agent b. 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 as cosolvent that enhances penetration. a. Ointment Provides relief longer than Sublingual Preparation Instructions: a. Dont shave area b. Dont rub just leave paper in place (may irritate and reduces action of drug) c. Cover paper with plastic wrap and tape it d. Tell client that it may discolour clothing. Ex. Nitrobid, Nitrol b. 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

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 wont be removed (ex. cream based)

Instruction to Patient: 1. Clean area with water. Dont use alcohol for drug can penetrate fast and produces more heat 2. If client has chest hair, may place at rotation sites CHLONODINE 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)

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 administration 4. PH of Body Fluids Common Routes of Administration A. For Systemic Effects Has 2 Subdivisions: Gastrointestinal and By Injection By Gastrointestinal Tract 1. 2. 3. 4. Oral thru mouth Buccal into inner lining of cheek, gums, and teeth Sublingual under the tongue Rectal rectally

By Injection Administration by the use of needles Administration by a route other than oral 1. Intramuscular into the muscle 2. Intravenous into a vein 3. Subcutaneous into the tissue beneath the skin B. For Local Effects (specific body organ) 1. Topical skin or mucous membrane 2. Intraarticular within the cavity of the joint 3. Intraosseous into a bone 4. Intracardiac into a chamber of the heart 5. Intradermal or Intracutaenous into the surface of the skin 6. Intraarterial into the artery 7. Intrathecal / Intraspinal / Subdural / Subarachnoid / Lumbar Injection into the spine or subarachnoid space 8. Inhalation into respiratory tract

FLEET ENEMA
Uses: a. For total evacuation of stools b. 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 Phosphate b. Dibasic Sodium Phosphate Contraindications: a. Kidney Disease b. Sodium Restricted Diet c. Post Anal Surgery d. Anal lesions, rashes, and trauma e. Hypertension f. Nausea and Vomiting
PERCUTANEOUS ADMINISTRATION medication directly to mucous membrane NORPLANT CONTRACEPTIVE THAT LAST FOR 3 YEARS

Type of Injection

Site

Angle

Needle Gauge

Volume of S

Use / Syringe

Nursing Implications

Intradermal (ID) Intracutaneous (IC)

a.

Inner surface of lower arm (antecubital fossa) Hairless, thinly keratinized areas of upper chest and shoulder blade. Inner thigh

10 15 degree s

26 27

0.1ml 0.5ml

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

b. Skin Test (ST)

c.

Note: Avoid visible veins, lesions, moles, birthmarks, measles, redness, erythema, scars, Avoid bony prominences if at the back For areas abundant in tissues) a. Lower lateral aspect of upper arm Abdomen on either side of the umbilicus Buttocks (upper outer quadrant) Anterior thigh Outer back

Subcutaneous (SC / SQ) Advantages: Useful for soluble & insoluble drug

45 90 45 and 60 (thin client, stretc h and bunch 1 inch tissue) 90 (2 inches can give at 90 degree s on abdom en

25 26

0.2ml 0.5ml Or up to 2.0 ml

Penadur Pulmin Insulin Syringe (for insulin) Heparin and other Bronchodil ator (tuberculi n syringe)

Insulin and Heparin are administered at 90 degree to decrease local complication of long term insulin therapy Other than insulin and heparin, inject at 45 degree

b. May be used for unconscious & uncooperative patient Allows slower absorption of drug compared to IM and & IV

c.

d. e.

Intramuscular (IM) Advantages: Rapid absorption Useful for soluble & insoluble drug May be used for unconscious & uncooperative patient

1. a.

Deltoid Muscle Adult 2 3 fingers below acromion process Child 1 2 fingers below acromion process Buttocks In sidelying position Dorsogluteal Gluteus Maximus upper /outer quadrant of buttocks

90

19 23 If drug is viscous, use 21

3.0 5.0 ml

For medication that is irritating to subcu tissue Requires rapid absorption

b.

2.

a.

b.

Ventroglutea l 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. Vastus Lateralis Child upper third of thigh Adult middle outer third of thigh d. Rectus Femoris anterior aspect of thigh (in line with sciatic nerve)