Systemic routes of drug administration

Parenteral

Enteral

Intradermal S.C I.M I.V OTHERS?

Sublingual Oral rectal

ORAL ROUTE

The most common and acceptable route administered as tablets, capsules, syrup, mixtures, enteric coated tab, sustained or time release tablet.
Advantages Disadvantages -Cannot be used in emergencies or in unconscious patient Cannot be used for irritant drugs Or in GIT disturbances.

- Safe

Can be self administered Economic: NO sterilization, need for special instruments or personals

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) Not for drugs that cause VC of sublingual mucosa. Bypasses the first pass metabolism Not suitable for irritant and lipidinsoluble drugs Proper control of dose by spitting or swallowing excess of drug.

Self administration is possible

RECTAL ROUTE

Suppositories or Retention enema.

Advantages Disadvantages Psychological, many patients refuse this route. Rectal inflammation may occur with repeated use.

Rapid absorption Useful in unconscious patient and in children Bypasses the first pass metabolism Useful in vomiting

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)

Intravenous

Intramuscular Subcutaneous intradermal

Intrathecal in spinal anesthesia

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 action Dose 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?

Absorption Distribution Metabolism Excretion

Kinetics ADME

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

Lippincotts 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 Degree of ionization Degree of solubility Degree of stability Dose Dosage form Factors related to patient Absorbing surface General circulation pH 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 acidity 2. Digestive enzymes 3. Mucosal enzyme Hepatic first pass effect

Plasma half life (T)

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 tissues Factors controlling distribution: Blood flow to the organ Binding of drugs to plasma proteins Barriers to drug distribution Physical and chemical characteristics of drug

Plasma protein binding

*

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.

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 Phase: reactions (oxidation, reduction, hydrolysis)

Phase: reactions (conjugation)

Factors affecting drug metabolism

Hepatic Microsomal enzyme Genetics. Species differences Age Gender Diet Disease Route of administration Dosage

Hepatic Microsomal enzyme

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

Hepatic Microsomal enzyme Inhibitors:

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

Renal (MAIN ORGAN) GIT Sweat Lungs Milk Nose

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.