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Routes of Administration

Oral Route

May be used to produce local effects within GI tract e.g. antacids. Can be used to produce systemic effect via indirect action e.g.cholestyramine. For systemic effects, drug absorption by passive diffusion (non-polar lipid-soluble agents well absorbed from small intestine – absorption influenced by pK of drug & pH) & active transport (polar nutrients, sugars, amino acids & vitamins absorbed by active or facilitated transport mechanisms – drugs compete with substrates for carrier). Other factors influence absorption from GI tract – ¯absorption with gastrectomy e.g. digoxin; coeliac disease & cystic fibrosis produce surprisingly minor effects; food & drink dilute drug & can adsorb or otherwise complex it; food also alters gastric emptying; transient hepatic portal blood flow after meals result in greater availability of drugs; drug metabolism by intestinal flora may affect drug absorption & activity. Drugs with short elimination half-lives inconvenient – drug with similar actions but longer half-life may be substituted e.g. terazosin for prazosin. Sustained-release preparations aim to release steady ‘infusion’ of drug into gut lumen for absorption. ¯Dosing frequency may improve compliance & reduce adverse effects due to high peak plasma concentrations e.g. carbamazepine. Problems associated with slow-release preparations include incomplete absorption, danger of high local drug concentrations causing mucosal damage if gut lumen narrowed or intestinal transit slow, difficulty in treating overdose, reduced flexibility of dosing, & expense.

Buccal & Sublingual Route

Drugs administered to be retained in mouth for local disorders of pharynx or buccal mucosa such as aphthous ulcers (hydrocortisone lozenges) or thrush (nystatin lozenges). Sublingual administration provides direct & rapid access to systemic circulation e.g. glyceryl trinitrate.

Rectal Route

May be used for local effects e.g. sulphasalazine or for systemic effects e.g. diazepam (exposure to acidity & digestive enzymes avoided, portal circulation bypassed, route can be used in patients unable to swallow, duration of action may be prolonged).

Skin

Drugs applied topically to treat skin diseases e.g. hydrocortisone & to achieve systemic therapeutic effect e.g. glyceryl trinitrate patches. Factors affecting percutaneous drug absorption include skin condition, age, region, hydration of stratum corneum, vehicle, physical properties of drug & surface area to which drug applied. Transdermal administration bypasses presystemic metabolism.

Lungs

Drugs inhaled as aerosols or particles for local effects on bronchioles. Physical properties that limit systemic absorption minimize unwanted systemic effects.

· Nose

Steroids may be administered intranasally for local effects on nasal mucosa. Complex peptides can be absorbed intact across epithelium e.g. DDAVP for systemic effects.

· Eye, Ear & Vagina

Drugs administered topically for local effects e.g. chloramphenicol eyedrops, sodium bicarbonate eardrops, & nystatin pessaries.

· Intramuscular Injection

Lipid-soluble drugs diffuse freely through capillary walls – well absorbed intramuscularly. Polar drugs of low molecular weight also absorbed rapidly. Rate of absorption governed by total surface area available for diffusion – increased when solution distributed throughout large volume of muscle (dispersion of solution enhanced by massage of injection site). Transport away from injection site governed by muscle blood flow (varies between sites). absorption with factors causing blood flow, and vice-versa with ¯blood flow. Drugs must remain in solution til absorbed from injection site. Depot IM injections have slow absorption ® useful to compliance. Various possible disadvantages of IM injections:

1) pain (especially with large injection volumes)

2) poss. sciatic nerve palsy in buttock after injection

3) abscesses at injection site

4) serum creatine phosphokinase ® diagnostic confusion

5) anaphylaxis may be prolonged, as know way of withdrawing injection

6) haematoma formation (esp. with fibrinolytic therapy)

Subcutaneous Injection

Same factors involved as IM injection. Cutaneous blood flow less Þ absorption slower. absorption with exercise. ¯absorption with ¯blood flow eg. tourniquet. ¯absorption with addition of adrenaline (vasoconstriction). Clinically useful to obtain sustained effects from subcut injections. Done by: 1) placing drug in suspension eg. insulin zinc suspension for diabetes 2) implantation of compressed pellet under skin eg. HRT

Intravenous Injection

Advantages:

1) rapid action

2) first-pass metabolism avoided

3) used for drugs that are inappropriate for other routes

4) easily control of drugs with short ½ lives by precise titration

Disadvantages:

1) cannot be removed once injected

2) high levels if given too rapidly ® affects right heart first ® poss. Arrest

3) embolism of particles/air, sepsis + thrombosis are all risks

4) accidental extravascular leakage of toxic drugs ® local tissue necrosis

5) accidental arterial injection ® spasm + peripheral gangrene

Intrathecal Injection

Access to CNS for drugs excluded by blood-brain barrier eg. morphine (spinal anaesthesia). High risk of neurotoxicity Þ risky technique. Much care taken when preparing/administering drugs this way. Only done by trained professionals. Penicillin used to be administered this way for meningitis, but since discovered that IV is OK. Less risky, since penicillin = neurotoxin.

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