BP 2 - Drug receptor interactions Flashcards
What are the common drug targets?
Receptors
Enzymes
Ion channels
Carrier molecules
What are the targets of drug action and medical use of benzodiazepenine?
GABA receptor
Anti-anxiety
What are the targets of drug action and medical use of penicillin?
Transpeptidase
Antibiotics
What are the targets of drug action and medical use of probenecid?
Organic ion transporter
Pronlong penicillin action
What is an agonist and antagonist receptors?
- Activate receptor
2. Block action against agonist
What is the function of enzymes at a drug target?
Inhibit/act as false substrate
What is the function of carriers at a drug target?
Block/ modulate opening/closing
What is the function of ion channels at a drug target?
Transported in place of endogenous substrate/ inhibit transport
What type of drug is benzodiazepine?
Anti-anxiety
How does benzodiazepine work on GABAA receptor?
Increase of charge when is goes through the channel, however BZ just working on the channel does nothing, but used with GABA it enhances its effect
What does NSAIDs stand for?
Non-steroidal anti-inflammatory drugs
Give 2 examples of NSAID.
Ibuprofen and aspirin
What is the effect of NSAID as a drug?
Inhibits cyclooxygenase, therefore arachidonic acid doesn’t convert into prostaglandins, in turn no inflammation, pain or fever
How does histamine act as an agonist?
Attaches to H1 receptor in smooth muscle and increasing local blood flow
How does terfenadine act as an antagonist?
Attaches to H1 receptor in smooth muscle to decrease local blood flow
What are receptor subtypes and how do they differ?
Similar structures but significant differences in their pharmacological responses
Subtypes show many diff cellular effects due to diff specificities what activates/ inhibits them and diff signal transduction mechanisms
Name 4 receptor types that respond to drugs?
Ligand gated ion channels
G-protein coupled receptors
Enzyme linked receptors
Intracellular receptors
What else are channel linked receptors called?
Ionotropic
What else are channel G-protein receptors called?
Metabotrophic
What types of ionotropic receptors are there?
Ligand gated
Voltage gated
ACh binding site
How do ligand gated receptors work?
Channel linked and need an agonist to open
E.g. nicotinic ACh receptor
ACh causes skeletal muscle to contract by opening channels
How do voltage gated receptors work?
Need change in electrical charge across the membrane to open/close
E.g. Na+ channels in N cell membranes
LA block these channels
What molecules make up the ACh binding site?
2 alpha, beta, gamma and delta
Nicotinic ACh receptor antagonists are used for what?
Muscle relaxants
What are the G-coupled receptors of epinephrine and salbutamol?
- α/β adrenoceptors
2. ß2 adrenoceptors
What are the 3 subunits of a G-coupled receptor? and which molecule produces its specificity?
- α, β, ɣ
2. α
G protein stimulatory action?
Activates adenylyl cyclase and Ca2+ channels
G protein inhibitory action?
Inhibits adenylyl cyclase and K+ channels
G protein q action?
Activates phospholipase C
List the Gs protein signal transduction mechanism
- Hormone or NT binds to receptor
- Occupied receptor changes shape and interacts with Gs protein
- G protein releases GDP and binds GTP
- Alpha subunit of protein dissociates and activates adenylyl cyclase
- Adenylyl cyclase catalyses formation of cAMP
- When no hormone/ drug the receptor reverts to its resting state
Once α1 activated by Gq what function occurs?
Activates PLC
Vasoconstriction
Once α2 activated by Gi what function occurs?
Inhibits adenylyl cyclase
Auto-inhibition of NT release
Once ß1 activated by Gs what function occurs?
Stimulates adenylyl cyclase
Accelerated heart rate
Once ß2 activated by Gs what function occurs?
Stimulates adenylyl cyclase
Bronchodilation
What stimulates all subunit receptors?
NA and adrenaline
What is a ß1 receptor antagonist?
Atenolol
What is a ß2 receptor agonist?
Salbutamol
What is a kinase linked receptor?
- Large extracellular ligand binding domain connected to intracellular domain by single memb spanning helix
What forms of kinase linked receptors are there?
o Receptor tyrosine kinase – i.e. Insulin
o Serine/threonine kinase
o Cytokine
o Guanylyl cyclase-linked
How does a kinase linked receptor work?
- Ligand binding
- Dimerization
- Autophosphorylation
Nuclear receptor examples.
o Estrogen receptor – estradiol
o Estrogen receptor – tamoxifen
Describe the classes of nuclear receptors.
Class I - in cytoplasm, form homodimers, ligands are endocrine (steroids, hormones)
Class II - present in nucleus, form heterodimers, ligands are lipids (FA)
What is a ß1 receptor antagonist?
Atenolol
What is a ß2 receptor agonist?
Salbutamol
What is a kinase linked receptor?
- Large extracellular ligand binding domain connected to intracellular domain by single memb spanning helix
What forms of kinase linked receptors are there?
o Receptor tyrosine kinase – i.e. Insulin
o Serine/threonine kinase
o Cytokine
o Guanylyl cyclase-linked
How does a kinase linked receptor work?
- Ligand binding
- Dimerization
- Autophosphorylation
Nuclear receptor examples.
o Estrogen receptor – estradiol
o Estrogen receptor – tamoxifen
Describe the classes of nuclear receptors.
Class I - in cytoplasm, form homodimers, ligands are endocrine (steroids, hormones)
Class II - present in nucleus, form heterodimers, ligands are lipids (FA)
What occurs when nuclear receptors bind to hormone response elements?
Starts gene transcription changes (+ve/-ve)
List the mechanism of Class I nuclear receptor signal transduction.
- Lipid-soluble drug diffuses across the cell memb
- Drug binds to receptor – changing shape and now activated, moving to nucleus
- Drug-receptor complex binds to chromatin, activating transcription of genes
- mRNA is translated into proteins that result in a specific biologic response
What is the function of some molecules having multiple receptors binding sites for drugs?
Binding at one site will alter binding at another site (positive or negative)
What are 3 drug-receptor interactions?
Allosteric sites
Orthosteric sites
Effector regions
What is are orthosteric and allosteric sites?
Orthosteric, which bind at the active site; and allosteric, which bind elsewhere on the protein surface, and allosterically change the conformation of the protein binding site.
