Pharmacology, Drugs & Therapeutics Flashcards
What is pharmacology?
a branch of science that deals with the study of drugs and their actions on living systems
What is a drug: ‘magic bullet’?
chemical with a selective therapeutic action
Chemical Structure
-defined
Physiological response
-CNS stimulant
Physiological Targets
-Adenosine receptors, -GABA &
-Phosphodiesterienes
What are the TWO integral branches of Pharmacology??
Pharmacodynamics, PD = Drug action & Mechanisms
Pharmacokinetics, PK = Barriers (ADME - absorption, distribution, metabolism and excretion)
“drug elicits specific physiological response”
What is specificity?
when referring to a medical test, specificity refers to the percentage of people who test negative for a specific disease among a group of people who do not have the disease
Biological: “right target”
example»_space;>
Adrenaline
Adrenergic receptor- ‘beta’ (β-1)
What does it do in the heart?
Increases heart Rate
Increasing cardiac muscle’s force of contraction
Adrenergic receptor- ‘beta’ (β-2)
What does it do in the lungs?
Relaxes the airway
Dilatate smooth muscles
Chemical: “right target binding site”
Adrenaline
What does it do in the heart?
^ heart rate
^ cardiac muscle’s force of contraction
Adrenergic receptor - ‘beta’ (β-1)
Chemical: “right target binding site”
Adrenaline
What does it do in the lungs?
Relaxes the airway
Dilatate smooth muscles
Adrenergic receptor - ‘beta’ (β-2)
Chemical: “right target binding site”
Adrenaline
What does it do in the lungs?
Relaxes the airway
Dilatate smooth muscles
Adrenergic receptor - ‘beta’ (β-2)
What are receptors made out of?
Protein - amino acid sequence
ONLY allow Adrenaline to BIND
(acetyl-choline/dopamine will be present but adrenaline g-protein-coupled-receptors will only recognise adrenaline)
Binding - specific and types of receptors:
Adrenergic receptor- ‘beta’ (β-1)
Adrenergic receptor- ‘beta’ (β-2)
Target binding sites (receptors & its subtypes) provides the selectivity for the specific binding of drugs/ligands (LOCK & KEY system)
Key drug binding sites
1) Drugs targeting enzymes
(Drugs as enzyme inhibitors)
2) Drugs targeting transporters
3) Drug targeting voltage-gated ion channels
Process > Enzyme > Drug example
Intracellular > Phosphodiesterase
Neurotransmitter degration > Acetylcholine
Messenger synthesis > Cycle-oxygenase
Give a drug example;
Intracellular > Phosphodiesterase
SILDENAFIL
Give a drug example;
Neurotransmitter degration > Acetylcholine
NEOSTIGMINE
Give a drug example;
Messenger synthesis > Cycle-oxygenase
IBUPROFEN (reversible)
ASPIRIN (irreversible)
Reversible drug
The active site will not change and therefore the reaction is reversible
Irreversible drug
The enzyme will not be able to bind to the substrate as the active site will change its shape - will not be able to make a lock and key model.
Reaction will only happen once (forward reaction»_space;>)
What is Competitive binding? (can be rev/irreversible)
drug competes for the ligand active site
Neostigmine will COMPETE with _____ ________to bind yo the ACh Esterase (substrate).
Acetylcholine
What is Non-competitive binding site? (rev/irreversible)
Example of drugs??
Drugs that binds at different site
Aspirin and Arachidonic Acid will not compete together as only ASPIRIN will bind with the cyclo-oxygenase (COX) substrate
- Drug targeting transporters - allows drug to get inside from extracellular to intercellular
Noradrenaline present in the transporter & released from pre-synaptic neurone > transport to the synapse > and move into the receptor (post-synaptic neurone) and stimulate a response
2nd example; glucose
Why are transporters present?
recycle the adrenaline (neurotransmitters)
Example - cocaine
NA uptake - block by cocaine e.g. TCAs
The cocaine BLOCKS the transporters so LESS NA will be RECYCLED so there will be a GREATER response
- Drug targeting voltage-gated ion channels
Resting (outside) > Depolarised (inside)
What happens in the process of DEPOLARISATION
Na+ comes inside the synapse membrane which increases the voltage as it’s more +ive (graph inclines)
Lidocaine- blocks Sodium channel
Local anaesthetic
What are the 4 main Key types of receptors?
- Nuclear receptors
- Ligand gated ion channel
- Catalytic receptors
- G-protein coupled receptors
Drugs targeting receptors
Messengers (endogenous ligands)
E.g.
hormone, peptides, cytokines, neurotransmitters…
Catalytic receptors -
outside of receptor catalysis the inside of the receptor
G-protein coupled receptors:
G protein-coupled receptor (GPCR), also called seven-transmembrane receptor or heptahelical receptor, protein located in the cell membrane that binds extracellular substances and transmits signals from these substances to an intracellular molecule called a G protein (guanine nucleotide-binding protein).
4 Major classes Binding?
- enzymes
- voltage gated
- receptors
- transporters
What are the General characteristics of receptors?
inactive receptor { selectivity of ligands/ Molecular switch} <> active receptor {response}
Amplification of SIGNALS, what os the process?
Plenty of signalling molecules, ions flowing through a channel, second messengers (cAMP, Ca ions),
mRNA molecules for new proteins and others
Biological: “right target” + Chemical: “right target binding site”»_space;> RELATIVITY
Everything is poisonous, nothing is poisonous it is all a question of dose
List the Benefits vs risk (Market authorisation of clinical drugs):::
RISK assessment is MORE critical than the benefit
Pharmaceuticals spends huge (billions of £s) to develop a clinically safe drug
Thalomid - treatment of nausea in pregnant women
THERAPEUTIC ACTION - RISK assessment is more critical than the benefit
Pharmaceuticals spends huge (billions of £s) to develop a clinically safe drug
ADVERSE/SIDE EFFECTS - gastric upset, bleeding & ulcer
Reye’s syndrome:
Liver & Brain damage
(children, very rare)
Contraindicated under 12 year*
