Targets & Receptor Interactions of Drugs L1 Flashcards
What are 2 sources of drugs and give examples
- natural
- asprin (willow bark), morphine (poppy), Psilocybin “magic” mushroom (psilocybin) - synthetic
what are the two types of synthetic drugs
- biologics: drugs that are made synthetically which are identical to their natural compounds
- insulin - drugs that are made synthetically and are derived from natural compounds, use natural compound structure to make a slightly different one
- opioids: use morphine to make oxycodone
what is Pharmacodynamics-
the effects drugs have on the body
what components make up Pharmacodynamics
- Molecular interactions by which drugs exert their effects
- Influence of drug concentration on the magnitude of response
what does understanding of Pharmacodynamics allow us to do
- determine approiate dose range
- compare efficiency and safety of one drug to another
what is Pharmacokinetics
effects of the body on the drug
what does ADME stand for
Absorption- from site of administration to blood
Distribution- drug leaves blood stream and is distributed between interstitial and intracellular fluids
Metabolism- body inactivates drug through enzyme modification
Excretion- drugs eliminated from the body
what does understanding Pharmacokinetics allow
design and optimise treatment for individuals
- site of administration, frequency of dose, treatment duration
what are the 6 ways drugs interact with targets
- shape
- ability for drug to bind - charge distribution
- amino acids that line active site determine charge which determines bonds that are formed between drug and target - hydrophobicity
- hydrophobic binding site attracts hydrophobic drug - ionisation of drug
- some targets will only bind un-ionised molecules, others will only bind ionised (drugs that have a charge) - conformation of target: binding site is dynamic and will change
- stereochemistry of drug
what are the 4 types of targets drugs will act on
- receptors
- endogous transmitters e.g hormones, neurotransmitters - ion channels
- selective passage of ions - carrier molecules
- transport ions and small organic molecules - enzymes
give an example of each
- receptor
- salbutamol targets B2 adrenoreceptor to treat asthma - ion channel
- lidocaine targets voltage gated sodium channels for local anesthtic - carrier molecules
- omeprazole targets proton pump for anti-ulcer - enzyme
- asprin targets cyclooxygenase for analgesic use
some drugs work just down to their physio-chemical properties therefore act non-specifically
give 3 examples
- antidotes
- acetylcysteine to treat poisoning with Paracetamol - antacids
- aluminium hydroxide - laxatives
- lactulose
what are the 4 main interactions involved in
signal transduction
interference can cause disease
describe the two types of transduction
- agonist
- a ligand that binds to receptor to boost cellular response
-mimic the action of endogenous chemical messengers
- acts as a pseudosubstrate - antagonist
- a drug that blocks the response to a ligand
- stop over activation of a cellular response
- acts as an inhibitor to ESC
what are the two types of inhibition of enzymes used by antagonists and give examples
- competitive: captopril
- binds to active site - non-competitive: penicillin
- binds to allosteric site
how do Non steroidal anti-inflammatory drugs (NSAIDs)
work
- competitive
inhibit cyclooxgenase reducing production of prostaglandin resulting in reduced inflammation
- ibuprofen, aspirin
how does Benzodiazepines work
- non competitive
binds to allosteric site on GABA receptor resulting in enhanced effects of GABA so more cl diffsues through open ion channel
what are the different types of drug action at each target
- receptor: antagonist or agonist
- ion channels: block/modulate opening or closing of them
- carrier molecules: transported to place of endogenous substrate or transport inhibited
- enzymes: inhibit or act as false substrate
how does signal transduction happen at receptors
Receptor with bound agonist is activated
The activated receptor has altered physical and biochemical properties
This leads to changes within the cell to cause a biological response
what are the 4 different types of receptors
- ligand gated ion channels
- G protein coupled
- Enzyme linked receptors
- intracellular receptors
describe ligand gated ion ionotropic receptors
receptors that are linked to channels which require agonist to open
- acetylcholine causes muscle to contract via these channels
desribe voltage-gated channels
channels not linked to receptors which require changes to membrane potential to open
Voltage-gated Na+ channels in nerve cells
describe G protein coupled receptors
receptor that is coupled to protein made from3 subunits
alpha binds GTP
active alpha activates other proteins and are often involved in second messenger pathways
Diversity of the G-protein subunits and effector proteins can illicit a diversity of responses- based on the specific G-protein alpha subunits
what are 3 alpha subunits and what are their affects
Gs: stimulates adenylyl cyclase
Gi: inhibits adenylyl cyclase
Gq: activates phospholipase C
describe Adrenoreceptors
All subunits activated by adrenaline and noradrenaline
Response in a particular cell is dependant on which receptor subtype is expressed
what are the G protein receptor subtypes and what are their effects
- A1: activates Gq causing vasoconstriction
- A2: activates Gi casuing inhibition of neurotransmitter release
- B1 and B2: activate Gs resulting in increased heart rate or brochodilation
asthma drug salbutamol works on B2 in agonistic way
Atenolol is a 1
receptor antagonist
describe enzyme (kinase) linked receptors
Large extracellular ligand-binding domain connected to intracellular domain by single membrane-spanning helix.
- Receptor tyrosine kinase – i.e. Insulin
how does insulin receptors work
dimer attached at receptor. dimers have tyrosine residues
insulin binds to receptor causing dimers to cross phosphorylate tyrosine residues
can phosphrelate other proteins such as insulin receptor substrate
promotes phophorelation of other kinases or phosphotases leading to biological action of insulin
describe nuclear receptors (intracellular receptors)
Bind to protein in nucleus- transcription factors
Wanting to control expression of receptor- use this pathway
Estrogen receptor – estradiol
Estrogen receptor - tamoxifen
what are the two main classes of nuclear receptors
- class one: in cytoplams form homodimers, ligands are endocrines, setriods and hormones
- class two: in nucleus, form heterdimers, ligands are lipids - fatty acids
binding of hormones to hormone binding site exposes DNA binding domain and can affect transicription
