Two different permissions get mixed up. Practice authority is whether you need a doctor supervising you at all. Prescriptive authority is which medicines you are allowed to write for.

Your state decides both — and each state hands the job to a different board: nursing, medicine, or pharmacy. The federal government controls the drugs themselves rather than your licence, with one important exception: prescribing controlled drugs also needs a federal DEA registration, and which schedules you may write for depends on it.

• "Independently" means nobody has to sign off on your prescriptions.
• "Without limitation" means you can prescribe anything, including controlled drugs — except schedule I, which has no medical use at all.
• Having both is called full prescriptive authority.

PAs are a special case: they always have to be attached to a physician. If that arrangement ends, they cannot prescribe until they find another one.

Handing someone a medication and deciding they should have it are two different jobs. Prescribing means you own the diagnosis, the choice of drug, and checking whether it worked.

Pick the drug in this order: work out what is wrong, choose the best drug for this person, then follow up and adjust.

• Write in pen. Never anything that can be rubbed out.
• Make sure your own name and number can actually be read.
• Do not use U for units, MSO4 for morphine, or QD for daily — these three get misread and cause real harm.

"Off-label" means using a drug in a way the FDA never approved — a different illness, dose, route or age group. It is allowed, but it is your decision to defend.

About half of people do not take their medicines the way they were told to. That is worth remembering before you assume a drug has failed.

The exact measure is worth knowing: only about half of people in developed countries take their medicines as directed 80% of the time or more.

Most of this is about being careful on purpose, and leaving a record that you were.

• Only prescribe for people who are actually your patients, with notes to prove it.
• Never for yourself, your family, or your friends.
• Write down what you examined, what you warned them about, and how you plan to check on them.
• If you asked another clinician, write that down too.

Grapefruit juice interferes with a lot of drugs, so unless you know it is harmless here, tell people to skip it.

Whether a drug goes with food or on an empty stomach is part of the prescription, not an afterthought. Empty stomach means an hour before eating or two hours after.

If someone starts a brand-new drug and then feels strange, believe them — even if no one has written that side effect down yet. Report it to MedWatch. That is how new side effects get discovered.

The same dose goes further in a smaller body. Ignoring size means too much drug for a small person and too little for a large one.

Teaching someone about their medicine does more for whether they take it than anything else you do. It also clears up the things they heard somewhere that would have stopped them.

For any new drug, cover all nine: what it is called, what it is for, how much and how often, how to take it, what side effects to expect, how to store it, what blood tests go with it, what food or drugs to avoid, and how long they will be on it.

Medication reconciliation means comparing what someone is already taking against what is about to be added — every time they move between settings, including going home.

• List every drug with its name, why they take it, how it goes in, the strength and the timing.
• Include vitamins, herbal products and anything bought over the counter.
• The going-home list adds back anything paused in hospital, and drops anything that was only for the hospital stay.

Technology has moved these numbers a long way. Replacing handwritten orders with computer entry cut medication errors by 50%, and scanning barcodes against the patient's wristband cut them by as much as 85% in some hospitals.

Absorption is how much of a dose actually gets into the blood, and how quickly. The route you choose — by mouth, into a vein, into muscle, under the skin — changes both.

Food matters in two different ways, and this is the bit exams like:

• If food slows absorption down, the drug takes longer to start working but still gets just as strong.
• If food reduces how much is absorbed, the drug never gets as strong at all.
• Food usually does the first one, and only sometimes the second.

Anything that changes how long a drug sits in the gut changes absorption too. Diarrhoea rushes it through so less gets in; constipation leaves it there longer so more does.

Babies soak up creams and ointments through the skin much more than adults do, because their skin is thin, so topical medicines can poison them. Injections into muscle work the other way in the first days of life — the muscle has little blood flow, so absorption is slow and unpredictable.

Two more things change absorption: stomach acidity, which decides how much of a drug is in its charged form, and how fast the stomach empties — a slow stomach delays anything absorbed further down in the intestine.

Distribution is the drug travelling from the blood to wherever it needs to work.

Three things decide how well that goes: how much blood reaches the tissue, how easily the drug can get out of the blood vessels, and how easily it can get inside cells. Most tissues have plenty of blood, so the first one rarely holds things up.

A lot of drug rides around stuck to a blood protein called albumin. Only the unstuck portion actually works.

• There are only a few parking spaces on each albumin molecule.
• Two drugs that both need those spaces will compete.
• If one knocks the other off, suddenly there is more free, active drug than expected — and that can tip into poisoning.

Acid and alkaline environments trap drugs on one side of a barrier. Acidic drugs pile up on the alkaline side; basic drugs pile up on the acidic side.

Doses are worked out from body surface area rather than weight, because that accounts for how much of the body is fat, and fat changes where the drug ends up.

Metabolism means the body chemically changes a drug. Almost all of it happens in the liver.

Usually that switches the drug off. But the bigger point is that it makes the drug water-soluble — the kidneys cannot get rid of greasy drugs, only watery ones.

• A substrate is a drug the liver enzymes work on.
• An inducer speeds those enzymes up, so other drugs get cleared faster and their levels drop.
• An inhibitor slows them down, so other drugs build up and levels rise.

One drug can be several of these at once.

Inducers matter twice. Starting one can wipe out another drug — adding phenobarbital to the pill can make the pill stop working. And stopping one is just as risky: the other drug is no longer being cleared quickly, so its level climbs unless you lower the dose.

Some drugs get recycled: the liver dumps them into the gut, the gut releases them again, and they get reabsorbed. That is why certain drugs hang around much longer than you would expect.

Two details that get tested. When an inducer is added, the answer is to raise the other drug's dose — with the pill and phenobarbital, the contraceptive dose has to go up. And the recycling trick only happens to drugs the liver has tagged with glucuronic acid, not to drugs in general.

The kidneys do most of the work of getting drugs out of the body — but only if the drug dissolves in water. Greasy drugs cannot be filtered out at all, which is why the liver converts them first.

If the kidneys are failing, drugs stay in the body and build up. Unless the dose comes down, they build up to a poisonous level.

In older people, do not trust a normal creatinine result. Creatinine comes from muscle, and muscle shrinks at the same time as kidney function does — so the number can look fine while the kidneys are working badly. Use creatinine clearance instead.

Newborn kidneys barely work by adult standards, so drugs cleared by the kidney need smaller doses, longer gaps between them, or both. Kidney function catches up to adult levels by about age 1.

Drugs also come out in breast milk. Greasy drugs get in easily; drugs that carry a charge or are stuck to blood proteins mostly do not.

An agonist switches a receptor on. An antagonist stops it being switched on — it is a blocker, not an off-switch.

That means a blocker only looks like it is doing something when there is something to block. Naloxone rescues someone who has overdosed on opioids. Give the same naloxone to someone who has taken no opioid and nothing visible happens at all.

• Competitive blockers let go again. They just mean you need more of the real drug to get the same effect — the full effect is still reachable. Most blockers work this way.
• Non-competitive blockers latch on permanently. They take receptors out of play, so the best possible effect is now lower, no matter how much agonist you add.

A partial agonist does a bit of both. On its own it gives a moderate effect. But given to someone already on a stronger drug, it takes the receptors and holds them at its own weaker level — so the person ends up with less effect than before, not more.

An interaction is just two drugs affecting each other. Some are deliberate — combining blood-pressure drugs on purpose. The bad ones are the accidents.

Ask one question: does this make the treatment work better or make it safer? Then it is a good interaction. Does it make the treatment weaker or more poisonous? Then it is a bad one.

• Drugs can react in the bag or syringe, especially in IV fluids. Sometimes you see it go cloudy — but not always, so looking is not enough. Check before you order.
• Drugs can also interfere with each other at any of the four stages: getting in, moving around, being broken down, being cleared out.

Two drugs can fight over the same parking spaces on blood proteins. Whichever gets knocked off is suddenly more active than expected.

Normally, blocking a drug's breakdown makes it build up and become dangerous. But there is an important exception: some drugs are inactive until the body converts them. Block that conversion and the drug simply stops working — paroxetine can do this to tamoxifen.

There are far too many combinations to memorise. Look them up.

The liver has a family of enzymes called cytochrome P450. Most drug-on-drug interactions happen there — one drug speeding those enzymes up or slowing them down for another.

Grapefruit juice is the famous example, and the details are what get tested:

• It blocks an enzyme called CYP3A4.
• It blocks it much more strongly in the gut wall than in the liver.
• So more of a swallowed drug survives the gut and gets into the blood, and the effect is stronger than intended.
• It barely matters for drugs given into a vein, because those never pass through the gut.
• More juice means more blocking.

How well the liver handles drugs changes with age, and it changes direction:

• Newborns clear drugs slowly, so doses must be lowered.
• The liver is fully grown by about age 1.
• After that, children clear drugs faster than adults until puberty — so they may need a bigger dose or doses closer together.

Half-life is how long it takes for half of whatever drug is in the body to disappear. Half — not a set number of milligrams.

Morphine's half-life is about 3 hours. If there is 50 mg in there, 25 mg goes in 3 hours. If there is only 2 mg, just 1 mg goes in those same 3 hours. The fraction is the same; the amount is not.

It tells you how far apart the doses go. A drug that disappears quickly has to be given often, or the level drops too low to work between doses. A drug that lingers can be given once a day.

After someone stops a drug, roughly 94% of it is gone after about four half-lives. That is why an overdose of a long-lasting drug is so much harder to manage — it stays at dangerous levels for a long time.

Alcohol is the odd one out: it leaves at a steady rate no matter how much you have had.

Most of preventing harm is unglamorous: prescribe fewer drugs, and know what someone is actually taking.

• Use as few medicines as you can get away with.
• Ask about everything — including things bought over the counter and things not obtained legally.
• When you add a drug that speeds up metabolism, adjust the others. Do the same when you take one away — that half gets forgotten.
• Think about timing, so one drug is not blocking another's absorption.
• If you cannot avoid combining risky drugs, watch closely for the first signs of trouble.
• Be most careful with drugs where the safe dose and the dangerous dose are close together.

With older people, add one more habit: go through the list every so often and stop what is no longer needed. Ask about herbal remedies and supplements too, and encourage them to throw out old medicines.

Over 100 drugs can disturb the heart's rhythm in a specific way (QT prolongation), and they come from all sorts of drug families — so it is worth checking rather than assuming.

Older adults get more of these reactions for four reasons: their organs handle drugs differently, they have several serious illnesses, they are on several drugs at once, and they often do not take them as prescribed.

On the QT drugs: several have been pulled off the market after deaths, and the FDA now makes every new drug get tested for the effect before approval.

A boxed warning — people also say black box warning — is the most serious warning the FDA can put on a drug that is still allowed to be sold. It is literally printed inside a heavy black box.

It does two jobs: it names the dangerous thing that can happen, and it tells you how to avoid it.

It has to show up on the package insert, on the label, and even in magazine adverts. Any drug carrying one must also come with a patient Medication Guide.

Promethazine is the example to remember. It must not be given to children under 2 because it can stop them breathing properly, and injecting it can destroy the tissue around the injection site.

The FDA has three tools, in increasing seriousness: a Medication Guide written for patients, the boxed warning aimed at prescribers, and a REMS — a Risk Evaluation and Mitigation Strategy — which puts obligations on patients, prescribers and pharmacists together.

Five things speed up or slow down how fast the liver deals with a drug.

• Age. Babies cannot break drugs down properly until about their first birthday. Older adults slow down too, so both often need smaller doses — for different reasons.
• Inducers and inhibitors. An inducer makes the liver build more enzymes, so drugs get destroyed faster and levels drop, sometimes too low to work. An inhibitor does the opposite: the drug piles up and becomes toxic.
• Nutrition. The liver's enzymes need certain nutrients to work. In someone malnourished, they may not be there.
• Competition. Two drugs that use the same liver pathway get in each other's way, and one or both hang around longer than they should.

The fifth is the first-pass effect. Anything swallowed goes to the liver before it reaches the rest of the body. If the liver is very good at destroying that particular drug, it can all be gone before it ever gets anywhere useful — so the tablet does nothing. The fix is to give it by injection instead, which skips that first trip through the liver.

Start from the assumption that anything the pregnant person takes reaches the baby. Greasy drugs cross the placenta easily, and although charged or protein-bound ones cross less well, it is safer to assume they all get through.

Pregnancy changes how the body handles drugs, and the changes pull in opposite directions:

• The kidneys work much harder — by the third trimester blood flow through them has doubled — so drugs cleared by the kidneys are washed out faster and doses often need to go up. Lithium is cleared twice as fast.
• The liver also speeds up for some drugs, including phenytoin, carbamazepine and valproic acid — again, doses up.
• But the bowel slows down, so swallowed drugs sit there longer and more is absorbed — that pushes doses down.

Teratogenesis means causing birth defects. Worth keeping in proportion: 1 to 3 in 100 babies have a major structural abnormality, about a quarter of all birth defects are genetic, and fewer than 1 in 100 are caused by drugs at all.

When the drug was taken matters more than which drug:

• Up to week 2 it is all or nothing — either the pregnancy ends, or it continues unharmed.
• Weeks 3 to 8 is when the organs are forming. This is the dangerous window for malformations.
• Week 9 onwards the organs are already built.

So if someone has taken something worrying, work out the dates first. If it was outside weeks 3 to 8, you can genuinely reassure them.

And if it was inside weeks 3 to 8: look up which malformation that particular drug causes, then arrange at least two ultrasound scans to see how much damage there is.

The old letter grades — A, B, C, D and X — are no longer used. The FDA introduced them in 1979 and finished phasing them out in 2020.

They were dropped because a single letter said too little. Category B, for example, only meant animal studies existed — which tells you very little about people, and sometimes the studies were not good enough to tell you anything at all.

You still have to know them, because almost everything written before 2020 uses them, and that is most of the literature you will read.

What replaced them is a written description in three parts: one about pregnancy, one about breastfeeding, and one about people of either sex who could become or father a pregnancy. The rule came in at the end of 2014.

Ageing changes all four stages, but not equally. Absorption barely matters; the kidneys matter most.

Getting in. Older people still absorb about the same amount of a tablet — it just arrives a bit more slowly. The one exception is drugs that need stomach acid to dissolve, and stomach acid drops with age.

Moving around. Four changes, and they push in opposite directions:

• More body fat means greasy drugs get soaked up into fat and stored, so less is active in the blood and the effect is weaker.
• Less muscle and less body water means watery drugs are squeezed into a smaller space, so they are more concentrated and the effect is stronger.
• Less albumin in the blood means fewer parking spaces, so more drug is floating free and active. This gets much worse if the person is malnourished.

Breaking down. The liver shrinks and slows, so drugs hang around longer. Oddly, tablets that the liver normally destroys on the way in now work better than expected, because less of them is destroyed. How much any of this happens varies hugely from person to person.

Clearing out. Kidney function has been declining since early adulthood. Drugs building up because the kidneys cannot clear them is the single biggest cause of drug harm in older people.

Older people react more strongly to drugs, vary more from one another, and get more side effects and interactions. Four reasons: their organs handle drugs differently, they have more illnesses, they take more medicines, and they often do not take them as directed.

Somewhere between a quarter and nearly six in ten older patients do not take their medicines as prescribed. Nine times out of ten the problem is taking too little rather than too much, and it causes up to one in ten hospital admissions.

Here is the surprising bit: roughly three quarters of that is deliberate. Not forgetting — deciding. The most common reason people give is that they did not think they needed the drug at that dose. Side effects and cost come next.

That matters, because a pill box solves forgetting. It does not solve someone quietly disagreeing with you.

• Keep the regimen as simple as you can.
• Ask about everything they take, including herbal remedies and supplements.
• Review the whole list regularly and stop what is no longer needed.
• Watch out for people living alone, seeing several prescribers, or struggling with packaging.

Four more habits worth keeping: measure drug levels where that actually guides the dose, watch for drugs interacting and for illness you have caused yourself, get old medicines thrown away, and avoid anything on the Beers list unless the benefit is worth it.

The very young and the very old are both unusually sensitive to drugs — but for opposite reasons. Babies have organs that have not finished developing. Older adults have organs that are wearing out.

In a baby, five things are still immature: how drugs get absorbed, how they stick to blood proteins, how well the brain is shielded from them, how the liver breaks them down, and how the kidneys clear them out.

The brain shield is the one that catches people out. It is not finished at birth, so drugs get into the brain far too easily. Anything meant to act on the brain — morphine, phenobarbital — needs a smaller dose, and so does anything that might affect the brain by accident.

Then it reverses. From about age 1 a child is broadly like an adult, except for one thing: children break drugs down faster than adults do. That stays true until puberty. So a child may need a bigger dose, or doses closer together — not smaller ones.

Two absorption oddities in babies: creams and ointments go through their thin skin much more easily, so topical medicines can poison them; but injections into muscle are absorbed slowly and unpredictably in the first days of life.

The Beers list names medicines that tend to cause problems in people over 65. It comes from the American Geriatrics Society and was last updated in 2023, when warfarin was added.

It is a warning list, not a banned list. You can still prescribe them if the benefit clearly outweighs the risk, and the rules relax for people in hospice or at the end of life.

Here is the part people get wrong. Someone may have been started on one of these drugs years before they turned 65. If it is working and causing no trouble, stopping it just because of their age is not good care — the book says so directly. Decide on the person, not the birthday.

There is a second list called STOPP/START that does a similar job.

Around all of this, the general habits are: keep the regimen as simple as possible, watch for drugs interacting, and go through the list every so often to stop what is no longer needed.

People inherit different versions of the enzymes that process drugs, and those versions cluster by ancestry. The result is either that the drug does not work as well, or that it becomes more dangerous.

Two gene variants are worth memorising, both more common in people of Asian ancestry:

• HLA-B\*1502 plus carbamazepine can cause severe, life-threatening skin reactions. The FDA says test first.
• HLA-B\*5701 plus abacavir can cause a fatal whole-body reaction.

Then there are drugs that arrive switched off and need the body to switch them on. If your enzymes cannot do it, the drug simply does not work — this is the opposite of what people expect:

• Tamoxifen needs CYP2D6. Those who cannot convert it get very little protection — around 8 to 10 in 100 women of European ancestry, and up to 40 in 100 of Asian descent.
• Clopidogrel needs CYP2C19. About a quarter of people have a version that barely works, leaving them under-protected against stroke and heart attack. They need a different drug.

Testing is compulsory before a couple of drugs, and recommended before warfarin and carbamazepine.

Some more detail worth having. The FDA now lists genetic markers in the package inserts of more than 250 drugs. Testing is required before maraviroc and trastuzumab, and recommended before warfarin and carbamazepine.

HLA-B\*1502 is almost entirely confined to people of Asian ancestry — it has never been found in people of European or Native American ancestry, and turns up in only 0.2% of people of African ancestry.

Two numbers to hold: women who cannot activate tamoxifen had their cancer come back 9.5 times as often in one study. And with isoniazid for tuberculosis, about 52% of Americans of European heritage break it down slowly and 48% quickly — get the dose wrong and the fast group is undertreated while the slow group is poisoned.

The KIDs List does for children what the Beers list does for older adults: it names medicines that are probably a bad idea.

The tricky part is what was taken off it. Aspirin and the fluoroquinolone antibiotics used to be on it — aspirin because of Reye syndrome, fluoroquinolones because of tendon damage. They were removed because the evidence was not strong enough, not because anyone decided they were safe.

Over-the-counter cough and cold medicines are not on the list either, even though the American Academy of Pediatrics and the FDA both say not to give them to under-4s. The reason is that the children who were harmed had been given too much, rather than being harmed by the normal dose.

All of it exists because babies, especially in the first month, are genuinely not small adults.

Two laws exist to push drug research in children — the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act — and both were made permanent by the FDA Safety and Innovation Act of 2012.

Some drugs get turned into something poisonous by the liver itself, and that product then damages the liver. Those are the hepatotoxic ones — over 50 of them.

In the US, medicines are the number one cause of sudden liver failure. But that is still rare — fewer than 1 in 50,000. Anything worse than that gets pulled off the market unless it is treating something life-threatening.

The one to remember is paracetamol, sold as Tylenol or acetaminophen. At a normal dose it is fine. Too much damages the liver. And here is the catch: a normal dose plus only two or three alcoholic drinks can cause serious liver damage.

Tell people what liver trouble feels like, and to get seen if it starts.

Choosing a drug is three steps: work out what is actually wrong, pick the best treatment for this particular person, then check whether it worked and change it if it did not.

Treat the person, not just the diagnosis. Someone with asthma and high blood pressure can be given a blood-pressure drug that tightens their airways and makes the asthma worse. It was the right drug for the blood pressure and the wrong drug for them.

• Other conditions they have, and other drugs those need.
• Their size — doses are worked out from body surface area, not weight alone.
• Their age, at both ends of life.
• Their genetics.
• How well their kidneys and liver work.

Guidelines are necessary but not enough on their own. Part of the reason is historical: drugs approved before 1997 were mostly tested on white men, so for a lot of everyday medicines nobody actually knows whether they behave differently in anyone else.

The asthma example is more specific than it looks: it is the non-selective beta blockers that tighten the airways, because they also hit receptors in the lungs. The selective ones largely do not — so this is not a warning about blood-pressure drugs in general.

On the research gap: the FDA pushed companies to include women in trials in 1997, and published wider diversity guidance in 2020.