Introduction to

Pharmacology

Aims & Objectives

• Define ‘Pharmacology’

• Define and differentiate between the two branches of pharmacology

• Explain what a drug is and identify how they elicit their effect

• List how drugs are administered and their advantages/disadvantages

What is Pharmacology?

• Pharmakon = poison/drug– Drug = anything with a positive/desired effect

– Poison = anything with negative/undesired effect

• Ology = science of

• Pharmacology = science of drug action

Any one heard of Botox?Botulinum toxin = neurotoxin produced by bacterium clostridium botulinum (muscle paralysis)

THE MOST TOXIC SUSTANCE KNOWN TO MAN

1nanog/kg IV – kill you

How much would we need to wipe out world population?

4kg wipe out 7.3 billion people

We should avoid it … right?

How can we do that?

• Each agent can have desired and undesired effects

• Pharmacology exploits muscle paralysis effect of Botox medicinally for:

– muscle paralysis in spasmodic conditions

– Cosmetic

How is this regulated?

• Government has set up regulations to protect the public through the European Medicines Agency and MHRA

• These agencies make decisions on whether the benefits outweigh the risks of drug use

• Stipulate the legal status if drugs:

– POM prescription only medication

– P pharmacy medication

– GSL general sales list medication

How do I (as a prescriber) figure our what the effects and side effects of drugs are?

How do we know how much drug to use for beneficial effect or toxic effect?

What does each drug do?

When can we use these drugs? Morning/night?

How to get the drug into the body?

Pharmacology is Magic

Pharmacology is Magic

Through pharmacology we can begin to understand how a small pill can….

On top of the world

(antidepressants)

Euphoric (Morphine)

Flip you lid?

lithium

Totally chilled?

diazepam

Incredible hulk

(Anabolic steroids)

Gain weight

(steroids)

Ulcerate your

stomach?

NSAIDS

….and answer the ultimate question

Pharmacology opens doors to

• Therapeutic research, development

• Application in medical practice

• Understanding drug mechanism = explain therapeutic and adverse effects of agents

• Understand interactions– Compete, negate drug action– Synergy, work better together – have no effects

Pharmacology has two branchesrelationship between body & drug

How the body affects the drug (Pharmacokinetics)

How the drug affects the body (pharmacodynamics)

Pharmacodynamics

How the drug affects the body

What is a drug ….

• A substance used in the – diagnosis, treatment, or prevention of a disease – or as a component of a medication.

–Molecules– Smaller than proteins– Smaller than polypeptides …–Why is ‘SMALL’ advantageous?

• Quicker access into body• Reach target (chemically sensitive

site) sooner• Longer to excrete (IVUFH vs LMWH)

Drug can be ….

• AGONIST : activate receptors and elicit a response– Drug

– Hormone

– Neurotransmitter

– Signaling molecule

• ANTAGONIST– Prevent (block) effect of agonist.

• Competitive

• Non-competitive

Yellow = Naloxone

Blue = Morphine

Chemical receptor sites

• If we consider drugs to be ‘keys

• Chemical receptor sites are the ‘locks’

• Receptors = proteins located on cell membrane

– Respond to endogenous compounds (hormones etc)

• Transport systems: Ion channels

– Voltage gated (Ca++ / K+ / Na+)

– Ligand gated

• G coupled proteins

Right Drug for the right receptor

• AFFINITY: how well does the drug bind to receptor

– Depends on concentration of drug [D]

– Removal depends on how well it bound in the 1st place

– Relationship between drug concentration and receptor binding (how many receptors occupied) is calculated as

• p = [D]/[D]+Kd

• Why is affinity important?

• If we know how much drug we need to occupy our receptor site we begin to understand how much drug we need for therapeutic response = dose

Botox vs paracetamol

Drug + receptor = ?

Hopefully a chemical response … but this depends on:

EFFICACY– 2 drugs– Same concentration– Same receptor binding ability (affinity)– Different efficacy!– Different chemical effects

Example: Benzodiazepines lorazepam and temazepamhave a 10 fold difference in doseDo not assume drugs in the same class and receptor site will have similar doses!

As a result medication has its own currency

• Not everything is dosed in ‘mg’

• Or drugs in the same family need the same dose

Not always the same, but logical through pharmacology

Pharmacokinetics

How the body affects the drug

Pharmacokinetics: 4 stages

1. Absorption

2. Distribution

3. Metabolism

4. Excretion

1 2 3 4Drug in Drug out

1. Absorption• Getting the drug into the body – so that it can work!

• Everything given via mouth will go through a dissolution (break it down and dissolve it) phase

• Absorption = Pass through the gut wall into the blood stream even distribution around the body

• Absorption depends on – drug solubility

– Lipophillic (lipid = fat, phillic = love, fat loving,/soluble)

– Hydrophillic (hydro = water, phillic = love/soluble)

• Why is this important?

– Deciphering how to get the drug into the body

– lipid soluble drugs pass through the gut a lot quicker blood. Example hormones.

Routes of administrationOral (po)– most common, ease of administration!Inhaled (inh) (volatile anesthetics/local delivery in asthma)topical (top) skin/eyes/ears –local deliverySub lingual (s/l)– rapid onset action GTNRectal (pr) – bypass portal circulation Parenteral (next slide)

Parenteral administrationParenteral = bypassing the GI system

Insulin/

LMWH

Slow drug delivery.

Antibiotics 100%

bioavailableRapid access

Large volumes

Morphine/

NRT

Continual drug release

Hormones/ steroids

Targeted Continual

drug release

Adrenaline less

common = painful. Small

volume

2. Distribution• Drug is in the blood – must penetrate into tissue to act

• Half Life: Time it takes for drug concentration in the body to drop to half of the original

• Example.

• Adenosine – seconds

• Amiodarone - months

2. Distribution• Drug is in the blood – must penetrate into

tissue to act

• Half Life: Time it takes for drug concentration in the body to drop to half of the original

• Vd (Volume of distribution) how much volume the drug has to distribute its self into

• Clearance: volume of plasma/blood cleared of drug

• Why is all of this important? ….

– To figure out dose of a drug.

ExampleUnfractioned

Heparin • VD 0.07l/kg• T ½ 1.5 hours

How do we give it?• Continuous IV

infusion

LMWH• VD 4.3l/kg• T ½ 7 hours

How do we give it?• Daily SC injection

High Vd and half life = drugs remains in body a lot longer

Pharmacokinetics: 4 stages

1. Absorption

2. Distribution

3. Metabolism

4. Excretion

1 2 3 4Drug in Drug out

3. Metabolism

• Occurs throughout the body – principally in liver.

• Why is this important?– Determines therapeutic and

toxic effects of drugs

– optimise therapy, minimise harm!

• Metabolites = Prodrugs

4. Excretion

• Principally occurs in the kidneys

• Kidney = Hydrophillic agents

• Clearance via glomerular filtration– Calculate clearance via

• eGFR. Electronic calcuation

• CrCl . More specific than above, manual calculation

Why is Pharmacology important as a prescriber?

x

How should I revise?

Top 100 classes of drugs

–Blackboard, SSS theme pages ‘prescribing’

–highlights classes of drugs per organ system

–Drug of the week (PBL)

–presentations to include all of the following information

x

x

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Thank you for listening ….Any questions?