22.4 — Routes and Dosage Forms

An asthma inhaler delivers around 100 micrograms of salbutamol. A salbutamol tablet contains 2 to 4 milligrams — twenty to forty times more drug for a weaker effect on the airways and far more tremor and palpitations.

Because the inhaler puts the drug where it is needed and the tablet puts it everywhere.

Route is not a detail of convenience. It changes the dose, the speed, the side effects, and sometimes whether the drug works at all.

Oral

The default, because it is convenient, safe and cheap.

Onset is typically 30 to 60 minutes, because the tablet has to disintegrate, dissolve, be absorbed and pass the liver (Chapter 22.2).

Limitations: first-pass metabolism destroys some drugs; it cannot be used in someone vomiting or unconscious; food and other drugs interfere; and absorption varies.

The dosage forms, and the differences matter:

Immediate-release tablets and capsules — dissolve and release at once.

Modified-release — labelled MR, SR, XL, LA, CR, ER and similar. Designed to release over many hours.

And the safety rule attached to them is absolute: never crush or split a modified-release tablet unless the label says you may. Crushing delivers a whole day's dose in one go, which has caused fatal overdoses with opioids and with some heart medications. If someone cannot swallow tablets, the answer is a different formulation, not a broken one.

Enteric-coated — a coating that resists stomach acid so the drug is released in the intestine. Used to protect the stomach, as with enteric aspirin, or to protect the drug from acid. Also must not be crushed.

Dispersible and orodispersible — dissolving in water or on the tongue. Useful for swallowing difficulty and for children.

Liquids — flexible dosing, and the shaking instruction matters, because suspensions separate and an unshaken bottle gives the wrong dose from top and bottom.

And a practical safety point: oral liquid medicines must be measured with a proper syringe or measuring spoon. A kitchen teaspoon varies from around 2 to 7 millilitres, which for a child's antibiotic or paracetamol is a large error in either direction.

Sublingual and buccal

Under the tongue, or between cheek and gum.

The membranes there are thin and richly supplied with blood, and the veins drain directly into general circulation — bypassing the liver entirely.

Which is why glyceryl trinitrate works within a minute or two under the tongue and would be almost completely destroyed if swallowed (Chapter 22.2).

Also used for: buccal midazolam for prolonged seizures, given by a family member (Chapter 20.2); some anti-sickness drugs; and sublingual buprenorphine.

And the instruction is to let it dissolve rather than swallow it, which defeats the entire purpose.

Injections

Intravenous — directly into a vein.

100 percent bioavailability, immediate onset, and complete control over the dose delivered.

And no way to take it back, which is exactly why intravenous drugs are given slowly and with monitoring. Requires trained staff and carries infection and thrombosis risks.

Intramuscular — into muscle, which is well supplied with blood.

Onset in 10 to 20 minutes. Larger volumes than subcutaneous, and used for most vaccines, adrenaline in anaphylaxis, and long-acting depot injections.

Depot injections are worth noting: a drug in an oily or slow-release base, released over weeks. Used for some antipsychotics and contraceptives, and the advantage is that adherence stops being a daily question.

Subcutaneous — into the fat under the skin.

Slower and steadier absorption. Insulin, heparin, and most biologic drugs. Can be self-administered easily, which is why it is the standard route for anything patients give themselves.

And rotating the injection site matters — repeated injection into the same spot causes lipohypertrophy, lumps of thickened fat that absorb insulin erratically. This is a very common and very fixable cause of unstable glucose control (Chapter 18.7).

Intraosseous — into the bone marrow. Used in emergencies when a vein cannot be found, particularly in children and in cardiac arrest. The marrow cavity drains into the circulation, so it works almost as fast as intravenous.

Other specialist routes: intrathecal, into the spinal fluid, for drugs that cannot cross the blood–brain barrier — and a route where a wrong drug is catastrophic, which is why intrathecal medicines have specific separate handling everywhere. Also intra-articular into a joint, and intradermal for tuberculin testing and some vaccines.

Inhaled

Straight to the lungs.

Which gives high local concentration with low systemic dose, and rapid onset because the alveolar surface is enormous and the blood supply is right there (Chapter 8.2).

The devices:

Pressurised metered-dose inhalers — the familiar canister. They require coordinating the press with a slow deep breath, which a large proportion of people do not manage.

Which is why a spacer transforms them. The drug is released into a chamber and then breathed in over several breaths, no coordination needed. It increases lung delivery substantially and reduces the amount deposited in the mouth and throat. Spacers are not only for children.

Dry powder inhalers — breath-activated, so no coordination needed. They require a fast forceful inhalation, which is the opposite of the slow deep breath used with an aerosol inhaler — and confusing the two techniques is a very common reason inhalers appear not to work.

Nebulisers — turning liquid into a mist, breathed through a mask. For severe attacks or people who cannot use an inhaler. A well-used inhaler with a spacer is as effective as a nebuliser in most acute asthma, which surprises people.

Soft mist inhalers — a slow-moving cloud, easier to inhale.

And the general point: inhaler technique is checked and corrected regularly, because a large fraction of "treatment failure" is delivery failure (Chapter 21.1).

Topical and transdermal

And these are two different things, which is worth being clear about.

Topical means acting where it is applied. Steroid creams, antifungals, antibiotic eye drops.

Transdermal means crossing the skin to act on the whole body. Fentanyl, nicotine, hormone and glyceryl trinitrate patches.

Patches give steady levels for one to seven days, which is their advantage.

And they carry specific hazards worth knowing:

Heat increases absorption. A fentanyl patch under a heat pad, in a hot bath, or during a fever can release far more drug than intended, and this has caused fatal overdoses.

Old patches must be removed — applying a new one without taking off the old is a recurring and serious error.

And used patches still contain substantial drug, which makes them dangerous to children and pets, so they are folded sticky-side inward and disposed of carefully.

On topical steroids, the fingertip unit is the useful measure: the amount squeezed from the tip of the finger to the first crease, which covers roughly the area of two adult palms. It gives people a way to apply enough, since under-application from fear of steroids is a bigger practical problem than over-application (Chapter 21.7).

Rectal

Underused in some countries and standard in others, and it has genuine advantages.

It works when someone is vomiting or unconscious, which is why rectal diazepam is used for prolonged seizures and rectal paracetamol for children who cannot keep anything down.

Partial bypass of the liver, since the lower rectal veins drain into general circulation.

Absorption is somewhat variable, which is the trade-off.

Eye, ear and nose

Eye drops — and a technique point that matters: pressing gently on the inner corner of the eye for a minute after instilling reduces drainage into the nose, which both improves the drug's effect on the eye and reduces the systemic dose. This is genuinely relevant for glaucoma drops containing beta blockers, which can otherwise slow the heart and affect the airways (Chapter 21.7).

Leave five minutes between different drops, or the second washes the first away.

Nasal sprays — for local effect in allergy and congestion, and for systemic delivery of desmopressin, some migraine drugs and naloxone.

And decongestant nasal sprays should not be used beyond about five days, because of rebound congestion that becomes self-sustaining.

Ear drops — warming the bottle briefly in the hand prevents the dizziness that cold drops cause by stimulating the balance organ (Chapter 11.8).

Vaginal and urethral

Local treatment for infections and for vaginal atrophy after menopause (Chapter 15.10), and systemic delivery for some hormones.

Vaginal oestrogen is worth a specific mention: the systemic absorption is very low, so it is suitable for many women who cannot or prefer not to take systemic hormone therapy, and it treats both vaginal symptoms and recurrent urinary infections effectively (Chapter 21.3).

Choosing a route

Need	Route
Fastest possible	Intravenous
Emergency, no vein	Intramuscular or intraosseous
Vomiting	Rectal, injection, sublingual
Steady level for days	Patch, depot injection
Local effect, low dose	Inhaled, topical, eye drops
Unconscious	Injection or rectal
Everyday, long term	Oral

The general rule: use the least invasive route that gets the drug where it needs to be at the concentration it needs to be there.

Storage, and it matters more than people think

Most medicines want a cool dry place below 25 degrees, and the bathroom cabinet is the worst common storage place in the house because of heat and humidity.

Refrigerated items — insulin, most vaccines, many biologics. Between 2 and 8 degrees, and never frozen, because freezing destroys many of them irreversibly. A vaccine or insulin that has frozen is discarded even if it looks normal.

In-use insulin can usually be kept at room temperature for around four weeks, which is more practical than refrigerating a pen you use daily.

Light-sensitive drugs stay in their original container, which is one reason not to decant everything into a pill organiser without checking.

Glyceryl trinitrate spray and tablets — tablets lose potency within weeks of opening the bottle, which matters because the one time you need them is an emergency.

Keep everything in the original labelled packaging where possible, and out of reach of children — and specifically, not in a handbag on the floor, which is where a large share of childhood poisonings begin (Chapter 23.6).

Dispose of unused medicines through a pharmacy, not the toilet or the bin.

What the next page fixes

Chapter 22.5 covers painkillers — the drugs most people take most often, how each one actually works, and the specific mistakes that cause the most harm.