ORAL ROUTE The most common and acceptable route administered as tablets,

capsules, syrup, mixtures, enteric coated tab, sustained or time release tablet.

Advantages Disadvantages- Safe

Can be self administered

Economic: NO sterilization, need for special instruments or personals

-Cannot be used in emergencies or in unconscious patient

Cannot be used for irritant drugs Or in GIT disturbances.

Cannot be used for drugs that undergo first pass metabolism

Cannot be used for unabsorbable drugs when systemic effect is needed

SUBLINGUAL ROUTE The drug is placed under the tongue and is absorbed through the buccal

mucous membrane & enters systemic circulation. For eg. Nitroglycerine for angina

Advantages Disadvantages Rapid absorption (used in

emergencies)

Bypasses the first pass metabolism

Proper control of dose by spitting or swallowing excess of drug.

Self administration is possible

Not for drugs that cause VC of sublingual mucosa.

Not suitable for irritant and lipid- insoluble drugs

RECTAL ROUTE

Suppositories or Retention enema.

Advantages Disadvantages

Rapid absorption

Useful in unconscious patient and

in children

Bypasses the first pass metabolism

Useful in vomiting

Psychological, many patients

refuse this route.

Rectal inflammation may occur

with repeated use.

Absorption can be unreliable

Parenteral ROUTE Intradermal: (e.g. vaccination)

Subcutaneous injection (S.C.) 1-Drug should be: Non irritant, Aqueous solution or fine suspension

Intramuscular (I.M.) injection: the drug is injected into skeletal muscle

Advantages •Technically easier than I.V.•No first pass metabolism and no food drug interaction•Oily solution can be given•A long term effect from a single dose can be achieved

Disadvantages•Injection can be painful•Rarely, abscesses can be formed at the site of injection

Intravenous (I.V.)Either slow bolus injection or infusion method.Advantages:•100% bioavailability.•Useful in emergencies•Useful in unconscious patient •Large volumes can be delivered intravenously.•Useful for irritant drug.

Disadvantages:•More rapid absorption can lead to increased adverse effects. •Pyrogenic reaction•Transmission of diseases e.g. viral hepatitis C & AIDS.•Aseptic technique are required. •Not suitable for insoluble substances.•Extravasation of some drugs can cause injury, necrosis and sloughing of tissues.•Depot preparations cannot be given

-Other injections

•Intra-arterial (e.g. cancer chemotherapy)

•Intraperitoneal (e.g. haemodialysis)

•Intrathecal (e.g. spinal anaesthesia)

•Intra-articular (e.g. cortisol in arthritis)

•Hypospray gun ( jet injection syringe)

•Intracardiac (e.g. adrenaline in cardiac resuscitation)

MISCELLANEOUS routes of drug administration

1) Topical administration: Drugs can be applied to various mucous

membranes and skin.

2)Inhalation: Drugs are given by inhalation are gases or solution in the

form of aerosol (by nebulizer or atomizer)-Provide a rapid access to systemic circulation.-Used to apply drugs directly to the lungs e.g. bronchodilator in asthma. Advantages:Quick onset of actionDose required is less so systemic toxicity is minimized.Amount of drug can be regulated.Disadvantage: Local irritation may cause increased respiratory secretions and bronchospasm

3) Intranasal : as nasal spray.

Intravenous drug incompatibilities Mixing of two drugs in syringe may cause physical or chemical

interactions

There is a quick check table available in drug guide that should always be referred before mixing any two drugs in the syringe

Examples: 1) Penicillin and Gentamicin. 2) Succinyl choline and thiopentone (Culminate precipitation) 3) No drug to be added to blood/plasma infusion Heparin infusion Amino acid solution, B- complex.

Intravenous drug incompatibilities (cont.)

Use of wrong vehicle for infusion Eg.: 1) Normal saline NORADRENALIN AMPHOTERICIN-B

The above drugs are always given by adding to 5%dextrose solution 2) Dextrose is wrong vehicle for the following SULFONAMIDES BARBITURATES

PHARMACOKINETICS what body does to drug?

Schematic representation of drug absorption, distribution, metabolism, and elimination

Lippincott’s pharmacology 4th edition

Absorption of drugs Movement of a drug from its site of administration into

the blood stream.Factors affecting drug absorption

Factors related to drug Factors related to patient

Degree of ionizationDegree of solubilityDegree of stabilityDoseDosage form

Absorbing surface General circulationpH Gastric Contents (food and drugs) Gut motility First pass metabolism

First pass metabolism Metabolism of some drugs in single passage

through (gut, liver, lung) before reaching systemic circulation.

Gut first pass effect: 1. Gastric acidity2. Digestive enzymes3. Mucosal enzyme Hepatic first pass effect

Plasma half life (T½) Time needed for certain concentration of drug in plasma to change by 50%.

Bioavailability Is the fraction of administered drug that gained

access to the systemic circulation in a chemically unchanged form

Bioavailability is 100% after IV and most variables after oral administration

Factors that can alter bioavailability First pass metabolism Solubility of the drug Chemical instability The dosage form Route of administration

Drug distribution process by which a drug leaves the blood

stream and enters the extra vascular tissuesFactors controlling distribution: Blood flow to the organ Binding of drugs to plasma proteins Barriers to drug distribution Physical and chemical characteristics of drug

*

Drugs in the plasma may exist in the free form or may be bound to plasma proteins or other blood components, such as red blood cells.

General features of plasma protein binding

-The extent of plasma protein binding is highly variable and ranges from virtually 0%to greater than 99%-bound, depending on the specific drug.

-Binding is generally reversible.

- extensive binding may prolong duration of action.

Plasma protein binding

Consequences of plasma protein binding

A. Plasma protein binding decreases:

Distribution of drug from the plasma to tissue sites

Renal excretion (as a result of reduced filtration)

Metabolism (as a result of diminished uptake by the liver or other metabolizing tissues).

B. Drug interactions can be produced by plasma protein binding if several drugs compete for binding sites on protein

molecules

Barriers

• Blood –brain barrier

• Placental barrier

• The blood testis barrier

Drug elimination

Definition: Removal of drug from the body.

Routes of elimination:Drug metabolism

Elimination via kidney and other routes

Redistribution of drugs form the site of action

Drug metabolism Definition: chemical alteration of drugs in the body.Sites of drug metabolism Organs: liver (main site), Lung, kidney, GIT Cellular enzymes

Phases of metabolism PhaseІ: reactions (oxidation, reduction, hydrolysis)

PhaseІІ: reactions (conjugation)

Factors affecting drug metabolism Hepatic Microsomal enzyme Genetics. Species differences Age Gender Diet Disease Route of administration Dosage  

Hepatic Microsomal enzymeHepatic Microsomal enzyme inducers:They increase Metabolism of other drugs leading to decrease their action.They increase their own metabolism leading to decrease action. examples: Phenobarbitone, Phenytoin, Testosterone, Cortisol, Tobacco Smoking, Ethyl Alcohol

Hepatic Microsomal enzyme Inhibitors: inhibit liver enzymes, decrease metabolism of other drugs and increase their actionExamples: Oestrogens, Progesterone, Cimetidine, Na Valproate, Chloramphenicol, Sulfonamides & Isoniazide.

Excretion

Renal (MAIN ORGAN) GIT Sweat Lungs Milk Nose

Process by which a drug or metabolite is eliminated from the body

Factors affecting renal excretion

1- Glomerular filtration rate.

2- Change in urinary pH:

•Alkalinization of urine (IV NaHCO3) leading to increase excretion

of acid drugs e.g. aspirin, barbiturates.

•Acidification of urine (NH4CL or vit. C) leading to increase

excretion of base drugs e.g. ephedrine, morphine.