lecture 6 Flashcards
Occupancy Model
The drug effect depends on the number of receptor site occupied by the drug
Rate Model
The drug effect depends on the number of encounters the drug make with the receptor per unit time.
Induction Model
The drug effect is caused by conformational changes which the drug causes in the active binding site of the receptors
Perturbation Model
The drug effect is caused by macromolecules disturbances or perturbations. The disturbances caused by agonists different from antagonists.
Co-operativity Model
In this case the receptor is in between activated and inactivated states. Agonists can shift it towards activated state and antagonists can shift it towards inactivated state.
Receptor Pharmacology
The current pharmacological concept of four receptor super-families provides a useful framework for interpreting most drug-receptor interactions.
Type 1 ionotropic receptor: Ligand-gated ion channel
- nAChR has 5 subunits surrounding an ion pore
- It has a fast response
- It’s membrane bound
- Direct connection of the units to the ion channel
Type 2 metabotropic receptor: G-protein coupled receptor
- Membrane proteins that help to convert extracellular signals into intracellular response
- Fast response (secs)
- Membrane bound
- Has 7 transmembrane helices
- Indirect coupling with the G- protein and the effector inside the cell.
Type 2 metabotropic receptor: G-protein coupled receptor
- Membrane proteins that help to convert extracellular signals into intracellular response
- Fast response (secs)
- Membrane bound
- Has 7 transmembrane helices
- Indirect coupling with the G- protein and the effector inside the cell.
Type 3 receptor: Kinase-linked receptor
- Don’t use membrane proteins, an extracellular binding to these receptors causes an intracellular kinase activity.
- Slow response (hours)
- membrane bound
- Direct coupling to enzyme
- Single- Trans- Membrane helix
- Direct linkage between receptor and kinase enzyme
Type 4 receptor: Nuclear receptor
- located inside the cell, for steroid hormones other related molecules.
- They are found in cytoplasm/ nucleus
- Slow response (hour)
- Intracellular
- Effect on gene transcription
- Coupling via DNA
- Has a structure is a receptor and DNA binding domain
Types of targets (RICE) for Molecular Interactions
- Receptor
- Ion Channels
- Carriers
- Enzymes
What is the agonist for Nicotinic Acetylcholine receptor (Receptor)
Nicotine
Properties of Nicotine
- Alkaloid from tobacco plants
- Agonist of nicotinic acetylcholine receptor
- Stimulanting drug [Parasympathomimetic]
- Potential toxic side effects
What is the agonist for Beta-adrenoreceptor (Receptor)
Isoprenaline
properties of Isoprenaline
- beta-adrenergic agonist
- structural similarity to adrenaline
- treatment of slow heart rate [bradycardia]
What is the modulator for Voltage-dep. Na+-channel (Ion- Channel)
Lidocaine
properties of Lidocaine
- Local anesthetic
- Common usage as:
- Injected form for dental anesthesia
- Injected form for minor surgery
- Topical form to relieve pain from skin inflammations
What is the modulator for Voltage-dep. Ca2+-channel (Ion- channel)
Nifedipine
Properties of Nifedipine
- Dihydropyridine
- L-type calcium channel
blocker - Usage as:
- anti-anginal drug
- antihypertensive agent
What is an inhibitor of Acetylcholinesterase (Enzyme)
Neostigmine
Properties of Neostigmine
- Reversible inhibitor of acetylcholinesterase
- Interference with the breakdown of physiological ligand acetylcholine - Indirect stimulation of nicotinic and muscarinic receptors
- Usage in:
- Reversal of the effects of non-depolarizing muscle relaxants following anesthesia
- Treatment of myasthenia gravis to increase NMJ stimulation
What is an inhibitor of Cyclooxygenase (Enzyme)
Aspirin
Properties of Aspirin
- Non-steroidal anti-inflammatory drug [NSAID]
- Inhibitor of the enzyme cyclooxygenase [COX-1>COX-2] - Usage as:
- Analgesic
- Anti-platelet drug
What is an inhibitor of Choline carrier (Carrier)
Hemicholinium
Properties of Hemicholinium
- Blocks choline uptake
- Not used clinically
- Neuromuscular blocking drug
What is an inhibitor of Na+/K+-pump (Carrier)
Ouabain
Properties of Ouabain
- Cardiac glycoside
- Blocker of Na+/K+-ATPase
- Increases [Ca2+]i due to decreased NCX
- Therapeutic usage in heart failure
- Potential toxicity
Plasmalemma excitation
Key ion channels and ion pumps involved in maintenance of membrane potential and triggering of action potential
