Introintro To Pharmacology

Question 1

What is pharmacology

Answer 1

Branch of medical science that deals with drugs and their uses

Question 2

First cases of pharmaceutical practice

Answer 2

-Ancient Babylonian priest giving remedies to the sick from plants and nature materials
-modern day Iraq and first apotheracy shops which were open in Baghdad

Question 3

Pharmacodynamics

Answer 3

What drugs do to us

Question 4

Pharmacokinetics

Answer 4

What we do to drugs

Question 5

Pharmacogentics

Answer 5

Unusual/individual responses

Question 6

Pharmacovigilance/toxicology

Answer 6

Safety do drugs-characterisation,detection and Nader staining of adr’s

Question 7

Molecular therapies

Answer 7

approaches being developed as a consequence of advances in molecular biology
Eg Work to inject mRNA for angiogenic proteins into mouse with myocardial ischaemia

Question 8

Nutraceuticals

Answer 8

Food or food components thought to offer health benefits
Eg micriobiota of the GI tract

Question 9

What did Paul erlich discover in1854-1915

Answer 9

Discovered Salvarasn for the treatment of syphilis

Question 10

How drugs act generally

Answer 10

-Drugs bind to cells to give an pharmacological effect
-the drug binds to a target protein
-The types of drug targets are commonly:
+Receptors
+ Enzymes
+Transport Proteins
+Ion Channels

Question 11

Agonist

Answer 11

-When an agonist drug binds, it causes an activation of a receptor
- drug+receptor <>drug receptor complex<>activated drug receptor complex for agonists causes a response

Question 12

Law of mass action

Answer 12

Rate of reaction is proportional to The concentration of reactants

Question 13

Affinity

Answer 13

How likely a drug is to bind to a receptor
High affinity would mean a low concentration is needed for an effect

Question 14

Efficacy

Answer 14

How likely the drug is to activate a receptor when bound
High efficacy means a low amount of bound drug gives a physiological effect

Question 15

Antagonist drugs

Answer 15

-Drug that binds to the receptor but may or may not cause a physiological effect
-Also reduces the effect of the agonist at the receptor

Question 16

Reversible Competitive Antagonism/ Physiological Antagonism

Answer 16

Physiological mediator/drug binds at same receptor as agonist drug
If agonist concentration increased, can overcome blockade

Eg, salbutamol and noradrenaline
 Salbutamol- β2 adrenoceptor Agonist drug- Acts in airways- Causes vasodilation and relaxation of smooth
muscle by hyperpolarization
 Noradrenaline- Non-Selective β Agonist- Acts on all β adrenoceptors- Causes vasoconstriction and contraction of smooth muscle by increased Ca flux
 If salbutamol concentration high enough, will overcome noradrenalin

Question 17

Irreversible Competitive antagonism

Answer 17

Antagonist binds at same receptor as agonist
Drugs form a covalent bond, difficult to break- Produce long lasting effects
Even if agonist concentration increases, still has no effect- Decreases the number of available receptors
Very rarely used in clinical practice- Mostly in receptor classification experiments Irreversible enzyme inhibitors are more common
Eg, MAOIs (phenelzine, tranylcypromine, iproniazid etc)

Question 18

What condition would you treat with a Maoi

Answer 18

Depression

Question 19

Pharmacokinetics

Answer 19

Administration=Delivery of drug
Absorption=Movement of drug across membranes
Distribution=Description of the movement of drugs between different body compartments
Metabolism=Chemical alteration of the drug
Elimination=Transfer of the drug from inside the body to the outside

Question 20

Administration surfaces

Answer 20

Available Surfaces:
▪Oral- Swallowed
▪Buccal- Oral Mucosa
▪Sub-lingual- “Under the tongue”
▪Skin (topical)
▪Lungs
▪Nose
▪Eye
▪Ear
▪Urethra
▪Vagina
▪Rectal

If no surface available, make one:
▪Intramuscular
▪Intravenous
▪Subcutaneous Intradermal Intrathecal (spinal) ▪Intraperitoneal (abdominal cavity)
▪Intra-arterial

Question 21

Routes of administration

Answer 21

Oral
+ Easy, cheap and convenient
+ Low infection risk
+ Painless
- Exposed to GI tract
- First Pass metabolism
- Loss through vomiting

Intravenous
+ Fast delivery to site
+ Avoids GI exposure
+ Avoids First Pass; increased bioavailability
- Reversibility?
- Infection Risk
- Pain/Fear Factor
- Administration by trained person

Lungs
+ Fast action- Why?
 Thin walls between alveoli and capillaries  High SA
+ Good point of entry
- Effects can be systemic; eg tremor from salbutamol

Transdermal
+ Long term, continuous
+ Avoids GI Tract and First Pass
+ Painless, convenient and easily administered - Skin irritation?
- Drugs need to be lipophilic to cross tissues

Question 22

Bioavailability -distribution

Answer 22

Used to define how well a drug is absorbed and reaches its site of action. Quantitatively:
Bioavailability = 𝑄𝑢𝑎𝑛𝑡𝑖𝑡𝑦 𝑜𝑓 𝑑𝑟𝑢𝑔 𝑟𝑒𝑎𝑐h𝑖𝑛𝑔 𝑡h𝑒 𝑠𝑦𝑠𝑡𝑒𝑚𝑖𝑐 𝑐𝑖𝑟𝑐𝑢𝑙𝑎𝑡𝑖𝑜𝑛 /𝑄𝑢𝑎𝑛𝑡𝑖𝑡𝑦 𝑜𝑓 𝑑𝑟𝑢𝑔 𝑎𝑑𝑚𝑖𝑛𝑖𝑠𝑡𝑒𝑟𝑒𝑑
Also:
Bioavailability = 𝑄𝑢𝑎𝑛𝑡𝑖𝑡𝑦 𝑜𝑓 𝑑𝑟𝑢𝑔 𝑟𝑒𝑎𝑐h𝑖𝑛𝑔 𝑡h𝑒 𝑠𝑦𝑠𝑡𝑒𝑚𝑖𝑐 𝑐𝑖𝑟𝑐𝑢𝑙𝑎𝑡𝑖𝑜𝑛 𝑎𝑓𝑡𝑒𝑟 𝑜𝑟𝑎𝑙 𝑎𝑑𝑚𝑖𝑛𝑖𝑠𝑡𝑟𝑎𝑡𝑖𝑜𝑛 /𝑎𝑚𝑜𝑢𝑛𝑡 𝑎𝑏𝑠𝑜𝑟𝑏𝑒𝑑 𝑤h𝑒𝑛 𝑡h𝑒 𝑠𝑎𝑚𝑒 𝑑𝑟𝑢𝑔 𝑖𝑠 𝑎𝑑𝑚𝑖𝑛𝑖𝑠𝑡𝑒𝑟𝑒𝑑 𝑖𝑛𝑡𝑟𝑎𝑣𝑒𝑛𝑜𝑢𝑠𝑙𝑦

Question 23

Measuring drugs In plasma -distribution

Answer 23

Drug concentration in plasma is key to understand ADME
Two Key Parameters:
Half Life
Time taken for a drug to reach half the original concentration in plasma
Not the same as half the time taken to metabolise/excrete! Some drugs have half lives up to 5x half-life time!
Clearance
Rate of drug elimination relative to plasma concentration
Eg, Warfarin
Half-Life ~40hrs
Therapeutic Concentration~ 5days

Question 24

Metabolism

Answer 24

Some drugs may be metabolised entirely, others may pass through a person completely unchanged
Some drugs may produce metabolites which are active in a different way
 Eg, Aspirin -> Salycylic Acid -> Glucuronide
 Aspirin= Inhibits platelet activity (clotting) + Anti
Inflammatory
 Salycylic Acid= Anti-Inflammatory only
Drugs react with one another in ways we do not expect……..
 Eg, Paracetamol and Alcohol
 Paracetamol toxicity caused by the metabolite CYP
metabolite N-acetyl-p-benzoquinone imine
 Consequently greater risk of liver damage in those with already induced CYP activity after alcohol consumption

Question 25

Metabolism -phase 1 reactions

Answer 25

Catalysing (break down) reactions
Usually in liver, but also gut Usually carried out by P450
enzymes
 Cytochrome P450 is a “Superfamily” of enzymes, primarily in liver tissue
 Carry out this initial breakdown of drugs into their initial metabolites or derivatives
 Can be different between people, hence adverse reactions, greater effect in some people etc

Question 26

Metabolism-phase 2 reactions

Answer 26

Usually make the drug “inactive”, ready for excretion
Done by conjugation or “joining”

Question 27

Metabolism-first pass

Answer 27

Some drug is extracted immediately by the liver or gut
Significantly lower concentration of drug reaches systemic circulation

This means two things:
 The dose needed to be taken is usually largest by mouth (due to passing gut and liver)
 There are different amounts needed for different people due to liver blood flow variations (can be reduced in disease, eg, HF)