Introduction and Routes of Drug Administration

Drug basics

Drug = chemical producing a change in biologic function, usually via receptor agonism/antagonism. MW usually 100-1000 D (lower limit = specificity, upper limit = needs to cross membranes; exceptions: lithium 7D, large proteins >50kD → parenteral only). Most drugs weak acids/bases.

Sources: Plants (alkaloids-morphine/atropine/quinine · glycosides-digoxin · oils) · Animals (insulin, thyroxine historically) · Microbes (most antibiotics) · Minerals (Fe, Ca, Li salts) · Synthetic chemistry (largest source now) · Biotechnology (recombinant insulin, mAbs, EPO).

Nomenclature: Chemical name (structure) → Non-proprietary/generic name (rINN, internationally uniform) → Proprietary/brand name (manufacturer-specific, many per drug). Generic prescribing = cheaper, pharmacist substitutes freely; brand = when consistent quality/bioavailability matters.

Essential medicines = WHO-defined, meet priority healthcare needs, chosen on efficacy+safety+cost. India: National List of Essential Medicines.

Dosage forms

Solid: powders · tablets (plain/coated/chewable/dispersible/sublingual/enteric-coated-survives-stomach-releases-in-duodenum/sustained-release) · capsules (soft/hard, enteric-coated, spansules) · suppositories/pessaries. Liquid: solutions · suspensions/emulsions (settle on standing, shake before use) · elixirs/syrups · drops. Semisolid: ointments (oily, occlusive, dry lesions) · creams (o/w, better penetration+cosmesis than ointment) · pastes (thick, non-greasy, oozing lesions) · gels (water-washable, mucosal retention). Inhalational: pMDI (propellant, fixed dose/actuation) · nebulizer (pressurized gas) · rotahaler (patient’s own inspiratory flow). Particle size: 1-5µm → bronchioles (effective) · >5µm → oropharynx · <1µm → exhaled, no deposition.

Routes — Local

Used for accessible localized lesions, minimal systemic absorption by design. Topical (skin/mucosa: oral cavity, GI, rectal, eye/ear/nose, bronchi via inhalation, vagina, urethra, skin) · deep tissue injection (intra-articular, perineural, intrathecal, retrobulbar — slow systemic absorption) · intra-arterial (rare — angiography contrast, limb-localized anticancer infusion).

Key exception: a “local” route can be chosen deliberately for systemic effect if absorption from that site is efficient — GTN patch/ointment on skin for angina prophylaxis.

Routes — Systemic Enteral

Oral: oldest, safest, cheapest, non-invasive, self-administered. Limits: slow onset (not for emergency) · unusable if unconscious/uncooperative/vomiting · destroyed by gut juices (insulin, penicillin G) · high first-pass loss (GTN, lidocaine, testosterone) · some drugs unabsorbed (aminoglycosides).

Sublingual/buccal: lipid-soluble, non-irritant drugs only. Fast (minutes) · bypasses liver completely → drug of choice for high-first-pass drugs (GTN, buprenorphine). Can abort effect by spitting out.

Rectal: for irritant/unpalatable drugs, vomiting/unconscious patients. Slow, erratic (exceptions: diazepam solution, paracetamol suppository — reliable in children). Only ~50% bypasses liver (lower haemorrhoidal veins); other ~50% (upper haemorrhoidal → portal vein) still undergoes first-pass.

Routes — Systemic Parenteral

Shared adv: fast/sure onset (emergency), works in unconscious/uncooperative/vomiting patient, no food/enzyme interference, liver bypassed. Shared disadv: sterile+costly, invasive/painful, needs assistance, local tissue injury risk.

Inhalation (systemic): huge alveolar surface → rapid absorption AND rapid elimination on stopping → moment-to-moment titratable (general anaesthetics). Nasal: bypasses liver+gut juices; peptide drugs only (desmopressin, calcitonin, GnRH agonists).

Transdermal Therapeutic System (TTS)

Patch delivers drug at constant rate via stratum corneum, independent of application site — because the rate-controlling micropore membrane, not the skin, sets delivery speed.

Adv: self-admin, better compliance, prolonged steady action, first-pass bypassed, no peak-trough fluctuation. Disadv: expensive, local dermatitis (mild, rotate site), patch can fall off unnoticed.

Drugs: GTN (angina) · fentanyl (chronic/terminal cancer pain) · nicotine (deaddiction) · clonidine (HTN) · oestrogen (HRT) · scopolamine (motion sickness).

Novel delivery systems

Ocusert (pilocarpine, under eyelid, ~1 week) · Progestasert (IUCD, progesterone, ~1 year) · Liposomes (targeted, ↓toxicity — amphotericin B) · Monoclonal antibody conjugates (targeted anticancer delivery) · Drug-eluting stents (paclitaxel, prevents restenosis) · Implantable pumps (insulin, continuous SC) · Subdermal implants (hormonal contraceptive depot, months) · Dermojet (needleless jet injection, mass immunization).

Clinical relevance

First-pass metabolism is the deciding factor between routes: high-first-pass drugs (GTN) are ineffective orally but effective sublingually/transdermally/parenterally — same drug, route changes whether it ever reaches the systemic circulation intact. IV = route of choice whenever an immediate, titratable response is essential (status epilepticus, cardiogenic shock, anaphylaxis).

Scope of Pharmacology

Pharmacology is the study of how chemical substances interact with living systems. Two directions of that interaction are studied separately: pharmacokinetics, what the body does to a drug, and pharmacodynamics, what the drug does to the body. Clinical pharmacology narrows this to drug behaviour and effect specifically in humans, covering both healthy volunteers in early drug testing and patients in actual treatment. Pharmacotherapeutics is the applied end of the subject — choosing the right drug, dose, and duration for a given disease and patient.

A drug is, in the broadest sense, any chemical that produces a change in biological function. Most drugs act as an agonist or antagonist at a specific regulatory target, usually a receptor; a few (osmotic agents, chelators) act by a purely physicochemical mechanism rather than through a receptor.

Nature and Size of Drugs

Drugs may be solid, liquid, or gaseous at room temperature, and this physical state strongly influences which routes of administration are even possible for that drug.

Most drug molecules weigh between 100 and 1000 daltons. The lower boundary exists because a molecule needs enough structural complexity — shape, charge distribution, chirality — to bind selectively to one target and not everything else. The upper boundary exists because very large molecules cannot cross membranes to travel from the site of administration to the site of action; bulky biological drugs (proteins, antibodies, heparin) are therefore usually restricted to parenteral routes. A handful of drugs sit outside the typical range at either end — lithium ion at only 7 Da, and large therapeutic proteins running into tens of thousands of daltons.

Chemically, many drugs are weak acids or weak bases rather than strong electrolytes. This detail turns out to matter a great deal for absorption and excretion, covered under Pharmacokinetics.

Sources of Drugs

• Plants — the oldest source, and still the origin of major drug classes. Active plant constituents fall into recognizable chemical families: alkaloids (nitrogenous bases of high potency — morphine, atropine, quinine, vincristine), glycosides (a sugar linked to a non-sugar aglycone — cardiac glycosides, anthraquinone purgatives), and oils (fixed oils used as vehicles/emollients versus volatile aromatic oils used as carminatives and counterirritants).
• Animals — organ extracts and hormones purified from animal tissue (insulin, thyroxine, adrenaline historically), along with antisera.
• Microbes — the source of most antibiotics (penicillin, gentamicin, tetracycline) and some enzymes (streptokinase).
• Minerals — inorganic salts used medicinally (iron, calcium, lithium carbonate, magnesium/aluminium hydroxide, iodine).
• Synthetic chemistry — now the largest source overall, producing both close analogues of natural drugs (aiming for better selectivity) and entirely novel chemical families (benzodiazepines, fluoroquinolones, thiazides) with no natural counterpart.
• Biotechnology — recombinant DNA technology producing peptide and protein drugs that cannot practically be synthesized chemically: human insulin, growth hormone, monoclonal antibodies, erythropoietin, tissue plasminogen activator.

Drug Nomenclature

Every drug carries up to three distinct kinds of name, and confusing them is a common source of prescribing error:

The internationally standardized non-proprietary name is the WHO’s Recommended International Non-proprietary Name (rINN); older systems (British Approved Name, United States Adopted Name) have largely been harmonized with it, though some older drugs still carry more than one accepted non-proprietary name (lidocaine/lignocaine). Prescribing by generic name lets a pharmacist dispense any manufacturer’s version and is cheaper, since brand pricing partly funds marketing; prescribing by brand name is preferred only where consistent quality and bioavailability across manufacturers cannot be assumed.

Essential medicines are those the WHO considers sufficient to meet the priority healthcare needs of a population, selected on efficacy, safety, and cost-effectiveness rather than novelty. India’s own list (last titled the National List of Essential Medicines) is the applied version of this principle for the Indian health system.

Prescription vs OTC. Most drugs, including all antibiotics, are legally prescription-only. A small group considered low-risk in ordinary use (paracetamol, antacids, simple vitamins) can be sold over the counter without a prescription.

Dosage Forms

A dosage form gives the active drug a physical shape suited to administration, protects it, and demarcates a single dose.

Solid forms — powders (inconvenient orally unless bulk-dosed, e.g. oral rehydration salts), tablets (plain, sugar/film-coated, chewable, dispersible, sublingual, enteric-coated to survive gastric acid and disintegrate only in the duodenum, or sustained/controlled-release for a prolonged effect), capsules (gelatin shells, soft or hard, sometimes enteric-coated or formulated as multi-release spansules), and suppositories/pessaries for rectal or vaginal insertion.

Liquid forms — aqueous solutions, suspensions (insoluble drug dispersed with a suspending agent) and emulsions (two immiscible liquids held together by an emulsifying agent), elixirs and syrups (hydro-alcoholic or sugar-based, flavoured), and drops for oral, eye, nasal, or ear use.

Semisolid forms — ointments (oily base, occlusive, suited to dry chronic lesions but not oozing surfaces), creams (oil-in-water, better cosmetic acceptance and skin penetration than ointments), pastes (thick, non-greasy, water-absorbing — suited to oozing or inflamed skin), and gels (non-greasy, water-washable, good retention on mucosa such as oral ulcers).

Inhalational preparations — pressurized metered-dose inhalers deliver a fixed aerosolized dose per actuation using a propellant; jet nebulizers aerosolize a drug solution using pressurized gas; rotahalers deliver a powdered drug from a punctured capsule using the patient’s own inspiratory flow. Particle size determines where the aerosol deposits: particles of roughly 1–5 micrometres reach the bronchioles effectively, larger particles settle in the oropharynx, and particles under about 1 micrometre are simply exhaled without depositing at all.

Routes of Drug Administration

Factors Governing Choice of Route

The right route for a given situation depends on: the drug’s physicochemical properties (solubility, stability, irritancy), whether the site of desired action is localized and accessible or generalized, how quickly and completely the drug is absorbed by each candidate route, how much of the dose is lost to digestive breakdown or first-pass metabolism, how urgently a response is needed, how precisely the dose must be controlled, and the patient’s own condition (conscious, cooperative, vomiting).

Local Routes

Used only for accessible, localized lesions where systemic absorption from the site is minimal — the entire point being a high local concentration without exposing the rest of the body to the drug.

• Topical — applied to skin or mucosa (oropharyngeal, nasal, ocular, aural, rectal, vaginal, urethral) as lotion, ointment, cream, powder, spray, drops, or suppository.
• Deep tissue injection — a needle delivers drug to a confined space where systemic absorption is deliberately kept slow: intra-articular, perineural infiltration, intrathecal, retrobulbar.
• Intra-arterial — rarely used; mainly for angiographic contrast media or to confine anticancer drug exposure to a limb.

A drug applied locally can still act systemically if it happens to be absorbed well from that site — glyceryl trinitrate applied to skin as an ointment or transdermal patch for angina prophylaxis is the standard example of a “local route” being used deliberately for a systemic effect.

Systemic Routes — Enteral

Enteral routes rely on the gastrointestinal tract for absorption.

Oral. The oldest, commonest, safest, and cheapest route — non-invasive, painless, self-administrable, and the drug need not be sterile.

Limitations: slower and less predictable onset (unsuitable for emergencies), unusable in the unconscious, uncooperative, or vomiting patient, destruction of some drugs by digestive juices or gastric acid (insulin, penicillin G), extensive first-pass hepatic metabolism for others (glyceryl trinitrate, lidocaine, testosterone), and erratic or absent absorption of some agents altogether (aminoglycosides, streptomycin).

Sublingual/buccal. The tablet or crushed drug is held under the tongue or against the buccal mucosa; only lipid-soluble, non-irritant drugs qualify. Absorption is fast — action within minutes — and, crucially, the drug bypasses the liver entirely before reaching the systemic circulation, which is why drugs with heavy first-pass metabolism (glyceryl trinitrate, buprenorphine) are given this way rather than orally. The dose can even be “aborted” by spitting the tablet out once the desired effect is reached.

Rectal. Used for irritant/unpalatable drugs, or when the patient is vomiting or unconscious. Absorption is comparatively slow and erratic, though diazepam solution and paracetamol suppository are reliable exceptions used specifically in children. Only about half the rectally absorbed dose (from the lower haemorrhoidal veins) bypasses the liver — the rest, absorbed higher up, still undergoes first-pass metabolism — so the first-pass bypass here is partial, unlike the sublingual route.

Systemic Routes — Parenteral

“Parenteral,” from para- (beyond) + enteral (intestinal), covers all systemic routes that deliver drug directly into tissue or blood without crossing gut mucosa.

Shared advantages: faster, surer onset (valuable in emergencies), usable in the unconscious/uncooperative/vomiting patient, no interference from food or digestive enzymes, and the liver is bypassed on first pass.

Shared disadvantages: needs sterile preparation and is costlier, is invasive and often needs a second person to administer, and carries a real risk of local tissue injury.

Injections

Inhalation (systemic). Volatile liquids and gases (general anaesthetics) are absorbed rapidly across the enormous surface area of the alveoli, and — because the same surface allows the drug to diffuse back out — the effect can be titrated moment to moment simply by adjusting the inspired concentration.

Nasal. Bypasses both digestive juices and the liver; used mainly for select peptide/protein drugs (desmopressin, calcitonin, GnRH agonists) that would otherwise be destroyed orally.

Transdermal. Covered separately below, since it is examined in its own right.

Transdermal Therapeutic Systems (TTS)

A transdermal patch is an adhesive device that delivers a drug across intact skin at a constant, controlled rate into the systemic circulation, independent of where on the body it is placed. The design layers a drug reservoir behind a rate-controlling micropore membrane, so the membrane — not the skin — sets the delivery rate; this is what keeps plasma levels smooth and predictable despite site-to-site variation in skin permeability.

Advantages: self-administration, better compliance, prolonged and steady action, minimal first-pass metabolism, reduced systemic side effects, and a constant plasma concentration without the peaks and troughs of intermittent oral dosing.

Disadvantages: expensive, local irritation or dermatitis at the application site (usually mild, minimized by rotating the site), and the patch can fall off unnoticed.

Drugs available as patches: glyceryl trinitrate (angina prophylaxis), fentanyl (chronic and terminal cancer pain), nicotine (tobacco cessation), clonidine (hypertension), oestrogen (hormone replacement therapy), scopolamine/hyoscine (motion sickness, sialorrhoea).

This is a comparison across routes on one attribute (does this route pass through the liver before reaching systemic circulation, and by how much) — a table communicates it more directly than a flowchart would, since the “how much” (100%, 0%, ~50%, 0%) is the actual examinable fact, not the shape of a pathway.

Novel and Targeted Drug Delivery Systems

Developed to extend duration of action, target delivery to a specific site, or improve compliance beyond what conventional dosage forms achieve:

• Ocular inserts (e.g. ocusert) — placed under the eyelid, release a drug such as pilocarpine slowly over about a week.
• Intrauterine systems (e.g. progestasert) — release progesterone locally for up to a year.
• Liposomes — phospholipid vesicles that carry a drug to a targeted site, reducing systemic toxicity (liposomal amphotericin B in fungal infection).
• Monoclonal antibody conjugates — antibodies engineered against a specific antigen used to direct cytotoxic drugs selectively, as in some anticancer regimens.
• Drug-eluting stents — a coronary stent that locally releases an antiproliferative drug (paclitaxel) to prevent restenosis.
• Programmable infusion pumps — deliver a drug (insulin) continuously and adjustably, most often subcutaneously.
• Subdermal implants — a crystalline drug depot placed under the skin releases drug slowly over months (contraceptive hormone implants); biodegradable implants need no removal, non-biodegradable ones do.
• Dermojet — a needle-free, high-velocity jet that deposits drug in subcutaneous tissue through the skin surface; essentially painless and suited to mass immunization.

Clinical Relevance

Choosing a route is frequently the difference between a drug working in an emergency and not: a drug with high first-pass metabolism given orally may be pharmacologically inert by the time it reaches the systemic circulation, while the identical drug given sublingually, transdermally, or parenterally reaches the target intact. This is the reasoning behind giving glyceryl trinitrate sublingually or transdermally rather than as a swallowed tablet, and behind reaching for the intravenous route whenever a titratable, immediate response is required — status epilepticus, cardiogenic shock, anaphylaxis.

Diagram 1 — Injectable Routes (Cross-Section)

What to draw: A cross-section through skin, subcutaneous fat, and underlying muscle, with a needle drawn at each of the depths that corresponds to a named injectable route — intradermal (angled, shallow, into the dermis only), subcutaneous (into the fat layer beneath the dermis), intramuscular (deep, into the muscle belly), and intravenous (into a superficial vein at the skin surface).

Labelling requirements: label each needle/depth with its route name, not a number — a diagram with unlabelled needle depths tests nothing. Mark the relative angle of needle insertion for each route (intradermal is nearly horizontal to raise a bleb; subcutaneous and intramuscular are angled progressively steeper; intravenous is shallow, along the vein).

Common exam-marking mistakes:

• Drawing intramuscular and subcutaneous at the same depth — examiners specifically check that IM clearly reaches muscle, not just deeper fat.
• Omitting the bleb that intradermal injection characteristically raises — this is the single feature that separates ID from SC on sight.
• Forgetting to indicate the vein for the intravenous needle, making it indistinguishable from a subcutaneous injection.

Diagram 2 — Transdermal Therapeutic System (Layer Structure)

What to draw: A side-on layered cross-section of a transdermal patch applied to skin, showing, from outermost to innermost: the backing layer, the drug reservoir, the rate-controlling micropore membrane, the adhesive layer, and finally the skin (stratum corneum) itself. An outer protective liner (peeled off before application) sits below the adhesive layer until use.

Labelling requirements: every layer must be named individually — a patch diagram with layers drawn but not labelled earns no marks for the structure, only for the concept. Indicate the direction of drug movement (reservoir → membrane → skin → systemic capillaries) with an arrow, since the rate-controlling role of the membrane is the actual teaching point.

Common exam-marking mistakes:

• Missing the rate-controlling membrane entirely and drawing the reservoir sitting directly on the adhesive — this misses why TTS delivery is constant regardless of application site.
• Forgetting the protective outer liner, which is a scorable labelled component in most answer keys.
• Not showing systemic capillaries/circulation as the final destination, leaving the diagram looking like a static structure rather than a delivery system.

Note on First-Pass Metabolism Exposure by Route

Not rendered as a diagram — this is a comparison of routes against one attribute (does this route pass through hepatic first-pass metabolism, and by how much), which is a table’s job, not a flowchart’s. See the table in notes.md. An earlier version of this content was drawn as a diagram; on review it did not represent a genuine causal/sequential relationship worth a flowchart, and stripping it down to fit a narrow mobile canvas had already deleted the exact route-specific mechanics that made it worth looking at in the first place — the table below fixes both problems at once.

Common exam-marking mistakes:

• Treating the rectal route as a complete liver bypass, like sublingual — the ~50/50 split is the specific fact examiners check for.
• Omitting the minor pulmonary first-pass metabolism that applies to all routes, not just oral — a smaller effect, but one worth a mention in a “discuss first-pass metabolism” essay answer.

Essays (1)

Short Notes (4)

Short Answers (9)

Multiple Choice Questions (1)