Introintro To Pharmacology Flashcards
(27 cards)
What is pharmacology
Branch of medical science that deals with drugs and their uses
First cases of pharmaceutical practice
-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
Pharmacodynamics
What drugs do to us
Pharmacokinetics
What we do to drugs
Pharmacogentics
Unusual/individual responses
Pharmacovigilance/toxicology
Safety do drugs-characterisation,detection and Nader staining of adr’s
Molecular therapies
approaches being developed as a consequence of advances in molecular biology
Eg Work to inject mRNA for angiogenic proteins into mouse with myocardial ischaemia
Nutraceuticals
Food or food components thought to offer health benefits
Eg micriobiota of the GI tract
What did Paul erlich discover in1854-1915
Discovered Salvarasn for the treatment of syphilis
How drugs act generally
-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
Agonist
-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
Law of mass action
Rate of reaction is proportional to The concentration of reactants
Affinity
How likely a drug is to bind to a receptor
High affinity would mean a low concentration is needed for an effect
Efficacy
How likely the drug is to activate a receptor when bound
High efficacy means a low amount of bound drug gives a physiological effect
Antagonist drugs
-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
Reversible Competitive Antagonism/ Physiological Antagonism
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
Irreversible Competitive antagonism
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)
What condition would you treat with a Maoi
Depression
Pharmacokinetics
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
Administration surfaces
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
Routes of administration
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
Bioavailability -distribution
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
Measuring drugs In plasma -distribution
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
Metabolism
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
