Different categories of medicines and their actions

Iain G. Jack 4 th February 2011

Content of today’s lecture

• • • • • How can we categorise drugs?

How do drugs cause their effects?

Specific receptors: lock & key Non-specific effects Pharmacokinetics

Introduction

• • What is a drug? Any biologically active chemical that does not occur naturally in the human body that can affect living processes

A little light history

16th century Egypt • Ebers papyrus • Poppy • juniper berries • beer • lead • swine teeth • goose grease • lizard's blood • donkey hooves • crushed precious stones • excreta from various animals

Where do drugs come from now?

• Plants: • Digoxin (foxglove) • Belladonna (deadly nightshade) • Diamorphine (opium poppy) • Animal tissue: Insulin, growth hormone • Synthetic manufacture: Most modern medicines

Names of drugs

• Chemical name: describes the chemical structure: acetyl-p-amino-phenol • Generic name: a name that can be used by anyone: paracetamol • Trade name: owned by the manufacturer: Calpol

Other ways to categorise drugs • What kind of molecule is it?

• What organ system (or what disease) is it for? e.g., cardiac, psychotropic • What parts of cells are affected?

What is the drug used for?

• To cure e.g., infections, cancer • To suppress diseases or symptoms without attaining a cure e.g., hypertension, diabetes, pain control • To prevent disease (prophylactic) e.g., immunisation

How does the drug act?

• Replace a deficiency, e.g., vitamins, minerals, hormones • Interfere with cell function, e.g., block enzyme action • Kill / prevent growth of viruses, bacteria, fungi, protozoa, cancer

Categories of drug

• • • • • • • Anti-inflammatory Analgesic Antipyretic Vaccine Antihypertensive Vitamin supplement Antitussive • • • Antiviral Antifungal Antibiotic • • • Anaesthetic Surfactant Laxative

Content of today’s lecture

• • • • • How can we categorise drugs?

How do drugs cause their effects?

Specific receptors: lock & key Non-specific effects Pharmacokinetics

How do drugs work?

• Pharmacodynamics: study of how chemicals exert their effects • The practical importance of this is enabling the design of new and better drugs

Receptors

• Receptors are proteins on the cell surface or inside the cell.

• They

bind

the body’s own chemical messenger chemicals •

Convert

the binding event to a signal that the cell can recognize and respond to

signal

receptor

“Lock & Key”

• • Interaction between a receptor and its signal molecule (ligand) is like “lock & key”.

Perfect fit depends on exact 3D shape and size of both molecules.

Receptors

• Drugs also bring information to cells by fitting into the same receptor molecules.

• The drug picks the lock a response by the cell .

and triggers

drug

receptor

Cannabinoid receptor

• Where?

• Surface of brain cells and cells of digestive system and immune system • What for?

• Normal brain function and healthy appetite • So what?

• THC picks the lock.

Agonists and Antagonists

• Agonist: a drug that fits into a receptor and activates a response e.g., morphine, nicotine • Antagonist: a drug that fits into a receptor but blocks the receptor and does not activate a response.

• ??? new anti-obesity drug: antagonist to cannabinoid receptor

Content of today’s lecture

• • • • • How can we categorise drugs?

How do drugs cause their effects?

Specific receptors: lock & key Non-specific effects Pharmacokinetics

Non-specific effects

• Acidic or alkaline properties • Surfactant properties (amphotericin) • Osmotic properties (laxatives, diuretics) • Interactions with membrane lipids (anaesthetics)

Side-effects and other effects

• Not the “wanted” effect e.g. aspirin causes gastric ulcer • Diphenhydramine has a useful side effect

Side-effects and other effects

• Hypersensitivity / allergy: exaggerated adverse reaction to drug • Toxic effects e.g., Thalidomide: teratogenic • Tolerance: increasing amounts are needed to produce the same effect

Content of today’s lecture

• • • • • How can we categorise drugs?

How do drugs cause their effects?

Specific receptors: lock & key Non-specific effects Pharmacokinetics

Pharmacokinetics

How the body deals with the drug We need to consider: Dose Route of Administration Absorption and distribution Metabolism and excretion

Dose: amount of drug taken at any one time • Aim is to give the patient a dose of drug that achieves the desired effect without causing harmful side effects • Therapeutic Index (TI) is the ratio of the therapeutic dose to the toxic dose • E.g.’s of drugs with low TI include digoxin, lithium and methotrexate

Administration

Route of administration depends on: • How easy it is to use for patient • The chemical make-up of the drug • How quickly a drug needs to reach site of action • Where it has to work in the body

Routes of Administration

Intravenous Inhaled Oral Transdermal Subcutaneous or intramuscular injection Topical Rectal

Oral Route

• • Medications taken by mouth Formulated in either a solid or liquid form • Absorbed from the GI tract mainly in the small intestine which is specialised for absorption (large surface area due to villi and microvilli).

Disadvantages

• • • Onset of action is relatively slow Absorption may be irregular Some drugs destroyed by enzymes or other secretions found in GI tract • Because blood from GI tract passes through liver it is subject to hepatic metabolism before reaching systemic circulation

Buccal Route

• • Drug is formulated as a tablet or a spray and is absorbed from the buccal cavity • Sublingual absorption very fast onset of action but duration is short Buccal absorption quick onset of action that is of longer duration than sublingual route

Rectal Route

• • Drugs formulated as liquids ,solid dosages and semi solids.

The chosen preparation is inserted into the rectum where it is released to give local effect or absorbed to give a systemic effect

Rectal & Vaginal Route

Advantages • Can be used when oral route Disadvantages • Absorption irregular and unsuitable • • Useful when drug causes GI irritation Can be used for • unpredictable Less convenient than oral route local action • Low patient acceptability

Inhalation Route Advantages • Drugs inhaled through the nose or mouth to produce local or systemic effects • Drug dose required to produce desired effect is much smaller than oral route therefore reduction in side effects • • Used predominately in the treatment of asthma Drugs delivered directly to their site of action ie lungs

Topical Route

• • Skin used as site of administration Lotions ,creams ,ointments, powders • Skin has natural barrier function but specialised dosage forms have been developed that when applied they allow the drug to pass through and produce systemic effect

Parenteral Route (drugs that are given by injection) • IV route -drugs injected directly into the systemic circulation (fast onset of action) • Subcutaneous route -drugs injected into the s/c layer of the skin (easiest and least painful) • Intramuscular route –drugs injected into muscle layers

Examples in each category

Route

Inhaled Oral Transdermal Rectal I.V.

S.C / I.M

Local Action Vicks Vaporub Systemic Action Cigarette Gaviscon liquid Nurofen Tabs Zovirax sore cream Laxative Sippository Nicotene patch Paracetamol Suppository Novocaine Contraceptive Local thrombolytic therapy Adrenaline

ADME

• • A bsorption: the mechanism by which a drug enters the body D istribution: the drug is transported throughout the body • M etabolism: the drug interacts with, and is processed by, the body • E limination: the drug is removed from the body

Absorption

• • • Disintegration Dissolution Direct absorption at site of action, e.g., in the gut

Steps in distribution

• • • Drug must spread throughout blood volume Drug must get out of the bloodstream between or through endothelial cells Drug must cross the cell membrane into cells

Factors affecting distribution

Binding to plasma proteins: if a drug is bound to large plasma proteins, it will be unable to get out as the proteins are too large .

Arggh! I can’t fit through!

Factors affecting distribution

Extent of blood supply. If a tissue is well perfused with blood, drugs will get there faster. Adipose tissue has low blood perfusion so drugs reach it slowly.

Factors affecting distribution

• • pH. A drug will pass through membranes better if it is not ionised Binding of drugs to other tissue components

Metabolism: what happens to a drug Lethal Dose

Injected Dose Oral Dose

 Therapeutic Range Sub Therapeutic Time

First pass effect

• All nutrients and drugs absorbed from the gut travel in the blood directly to the liver. The liver breaks down many drugs so they are inactivated before they ever enter the systemic circulation!

• • This can decrease drug delivery to target tissues But some drugs are activated by the first pass effect

Elimination

• • Mainly in the kidney. Also bile, gut, lung, breast milk.

Elimination of a drug is usually linked to renal function.

Individual variation

• • • • • Each person is unique how they respond to a drug Age and sex (hormonal differences) Weight: some drugs are stored in fat so less effective and longer lasting in obese people Allergy Kidney & liver function: how will they affect elimination?