Pharmacology 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?
A chemical with a selective therapeutic action.
What is Pharmacodynamics (PD)?
What the drug does to the body.
Drug action and mechanisms.
What is Pharmacokinetics (PK)?
What the body does to the drug.
Barriers (ADME).
What is biological specificity?
Right target
What is chemical specificity?
Right target binding site.
What does the B1 receptor do?
Increases heart rate; Increasing cardiac muscle’s force of contraption.
What does the B2 receptor do?
Relaxes the airway.
Dilatate smooth muscles.
What do target binding sites provide?
The selectivity for the specific binding of drugs/ligands (LOCK and KEY system).
What are the 3 key drug binding sites?
- Drugs targeting enzymes.
- Drugs targeting transporters.
- Drug targeting voltage-gated ion channels.
Drugs as enzyme inhibitors.
Intracellular breakdown - phosphodiesterase- sildenafil.
Neurotransmitter degradation - acetylcholine esterase - neostigmine.
Messenger synthesis - cyclo-oxygenase - ibuprofen (reversable) aspirin (irreversible).
Drugs as enzyme substrates
dopamine precursor L-DOPA for Parkinson’s disease.
What is meant by competitive binding?
Drug competes for the ligand active site.
What is meant by non-competitive binding?
Drug binds at different site.
Therapeutic action
Biological: right target.
Chemical: right target binding site.
Adverse/Side effects
Biological: non-specific target.
Chemical: non-specific binding site.
What is an agonist?
A drug that binds to the same active site as adrenaline and activates the B2 like adrenaline.
What is an antagonist?
Drugs that oppose the agonist function.
Block the B1 receptor.
What is Affinity?
How well a drug/ligand binds to it’s receptor.
What is Efficacy?
How well a drug/ligand activates the receptor.
Do agonists have affinity and efficacy?
Agonists have both affinity and efficacy.
Do antagonists have affinity and efficacy?
Antagonists only have affinity.
THEY PRODUCE NO RESPONSE.
What is kD?
The concentration req. to occupy 50% of receptor.
What is EC50?
The effective concentration of agonist for 50% response.
Which is usually higher, affinity(kD) or potency(EC50)?
Affinity (kD).
What is antagonism?
Drug/ligand that reduces/blocks the agonist response
Name a type of antagonism?
Receptor antagonism
Why do antagonists only have affinity?
Binds to receptors, Null response, i.e. blocks agonist response.
Competitive antagonism.
Orthosteric - same binding site of the endogenous hormone.
Block the drug by occupying the B1 binding site.
Non-competitive antagonism.
Blocks the response by by binding at a different binding site to the agonist.
No need for them to have identical structures.
Reversable and non-reversable
Reversable can dissociate from the receptor and binding sites can be re-occupied.
Non-reversable antagonists cannot dissociate from the receptor.
Reversable competitive antagonists
Max. response can still be achieved (surmountable antagonism).
Irreversible competitive antagonists.
Form covalent link with receptor.
Reduces the number of receptors available for the agonist to stimulate the response.
Non-surmountable antagonism
EC50 declines as receptor reserves decrease.
agonists maximum response drops.
Receptor Tyrosine Kinase (RTK)
Receptors for growth factors (EGF, VEGF, Insulin etc.).
Activation: Cell proliferation, differentiation, survival and metabolism.
Hyperactivation: Polyps, tumours and cancer.
Receptors for growth factors
EGF, VEGF, IGF, PDGF
Epidermal growth factor.
Vascular endothelial growth factor.
Insulin-like growth factor.
Platelet-derived growth factor
RTK
Growth factor binding RTK leads dimerization and autophosphorylation
RTK
One tyrosine kinase activates autophosphorylation of its partner and vice versa.
signalling proteins recruited to RTK.
Signalling proteins contains SH2 domain to sense and bind specific RTK.
SH2 domain
some SH2 proteins are enzymes (phospholipase C)
Some SH2 domain proteins are adaptors (Grb2).
RTK - drugs
Very limited
Insulin
Many neurotrophin analogues couldn’t pass through clinical trials.
Monoclonal antibodies.
Guanynyl cyclase receptors
Limited membrane bound
released from atria, promotes vasodilation and urinary sodium excretion.
