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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?

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content of today s lecture
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
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
A little light history
where do drugs come from now
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
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
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
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
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
Categories of drug
  • Anti-inflammatory
  • Analgesic
  • Antipyretic
  • Vaccine
  • Antihypertensive
  • Vitamin supplement
  • Antitussive

Antiviral

Antifungal

Antibiotic

Anaesthetic

Surfactant

Laxative

content of today s lecture11
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
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

receptor

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

lock key
“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.
receptors15

drug

receptor

Receptors
  • Drugs also bring information to cells by fitting into the same receptor molecules.
  • The drugpicks the lockand triggersa response by the cell.
cannabinoid 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
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 lecture18
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
Non-specific effects
  • Acidic or alkaline properties
  • Surfactant properties (amphotericin)
  • Osmotic properties (laxatives, diuretics)
  • Interactions with membrane lipids (anaesthetics)
side effects and other effects
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 effects21
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 lecture22
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
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
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
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

Routes of Administration

Inhaled

Oral

Transdermal

Subcutaneous

or intramuscular

injection

Topical

Rectal

oral route
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
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
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
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
Disadvantages

Absorption irregular and unpredictable

Less convenient than oral route

Low patient acceptability

Rectal & Vaginal Route

Advantages

  • Can be used when oral route unsuitable
  • Useful when drug causes GI irritation
  • Can be used for local action
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

Inhalation Route
  • Used predominately in the treatment of asthma
  • Drugs delivered directly to their site of action ie lungs
topical route
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
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
slide36
ADME
  • Absorption: the mechanism by which a drug enters the body
  • Distribution: the drug is transported throughout the body
  • Metabolism: the drug interacts with, and is processed by, the body
  • Elimination: the drug is removed from the body
absorption
Absorption
  • Disintegration
  • Dissolution
  • Direct absorption at site of action, e.g., in the gut
steps in distribution
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 membraneinto cells
factors a ffecting d istribution
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 a ffecting d istribution40
Factors affecting distribution

Extent of blood supply.

If a tissue is well perfused with blood,

drugswill get there faster.

Adipose tissue has low blood

perfusion sodrugs reach itslowly.

factors a ffecting d istribution41
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

Drug Concentration

Therapeutic

Range

Oral Dose

Sub-

Therapeutic

Time

Metabolism: what happens to a drug
f irst pass effect
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
Elimination
  • Mainly in the kidney. Also bile, gut, lung, breast milk.
  • Elimination of a drug is usually linked to renal function.
individual variation
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?
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