Drug Targets + key info Flashcards
What is pharmacodynamics definition
Effect of drugs on the body itself
What 2 things are looked at in pharmacodynamics
The molecular interactions Drugs have effect on
Eg, effect on target,cell response
Influence of DRUG DOSAGE
Line between toxic and therapeutic
How do we use pharmacodynamics
To find suitable dosage and know effect the drug has at good concentration
What is pharmacokinetic definition
The effect the body had on the drug
What 4 things are looked at in pharmacokinetics
1- absorption or drug into blood stream
2- distribution Eg into ICF of some tissues from the blood
3- metabolism to inactivate the drug
4- excretion of the drug in urine or faeces
Why is pharmacokinetics individual optimal rather than general dosage
Peoples metabolism affects how frequently you need to take the drug
Why don’t drugs only treat area applied
They are absorbed in blood stream
Drugs can be natural or synthetic. Give example or natural drugs
Laxanes from plants for anti cancer
What are the subdivisions of synthetic drugs
Completely artificial- codeine
Derived from something in body - insulin engineered
What are drugs which are synthetic but are usually in body called
Biologics
What 5 ways do drugs interact with targets / body
1- lock and key shape dependent
2- charge / bond dependant
3- hydrophobicity
4- stereochemistry
5- ionisation changes in different ph / pka
How can weak bond / charges between drugs and target affect response
It is short term solution drug will unbind
What 4 target proteins for drugs are there
Receptors
Ion channels either ligand or voltage
Enzyme
Carrier/channel proteins
What 3 drugs have effect due to chemistry not targets
Laxatives - have lactulose which adds water to stool
Antidotes - acetylcysteine stops paracetamol overdose
Antacids - alkaline to neutralise stomach acid
What are agonists and give examples
They mimic the action of endogenous chemical messengers
Eg hormones, histamine on H1 receptors, prostaglandins
What are the effects of agonists on the 4 targets
Receptors - activated
Ion channels - modulated
Enzymes - activated
Carrier - enhanced
What are antagonists
Drugs that inhibit action of agonists and arent endogenous
What is the effects on 4 target proteins due to antagonists
Receptors - inactive
Ion channels - blocked
Enzymes - inhibited allosterically or non competitively
Carriers - inhibited
How is aspirin an example of an agonist NSAID
It binds to the enzyme cyclooxgenase irreversibly
Stops prostaglandin production (inflammatory agent)
How can benzodiazepines be an agonist
It binds to the gaba ligand channel either on the allosteric or Orthosteric site
If it binds to allosteric site as gaba, this increases effect of gaba = more Cl
Why is benzodiazepines good for anxiety
It causes sleep due to hyperpolarisation of opening Cl channels
What is the main example of a receptor drug and explain it
SALBUTAMOL
Agonist to the B2 adrenogenic receptor present in lungs
Causes Gs activation and adenylate Cyclase activity
Causes bronchi-dilation for asthma sufferers
Give example of an ion channel drug
LIDOCAINE ANAESTHETIC
it is an antagonist to the na voltage channel
Causes stop flow of na
No ap = sedation
Other than aspirin, give another enzyme target drug
Penecillin which is an antagonist to transpeptidase work
Breaks down the cell wall
Give an example of a carrier protein targeting drug
Omeprazole
which is an antagonist to H pump to stop flow of acid in the stomach to treat ulcers
Why are different receptor subtypes important eg the different histamine receptors
They have different drugs which can block them at different sites of body to stop drug having multiple effects
What do antagonists do to receptor
Stop transduction
Give an example of a ligand ion channel affected by antagonists
Nicotinic ach receptor which if blocked by antagonist stops contraction and ap
What 3 subunits does the alpha have in GCRP
Gs- stimulating: activates adenylate cyclase or ca channels
Gi- inhibiting : inhibits adenylate cyclase or opens K channels
Gq - activates phospholipase c for Ca2 release
Give an example of a GCRP subtype
Adrenergic receptors (like salbutamol B2 action)
What happens to Alpha 1 adrenergic receptor
It has its Gq subunit activated
Activates phospholipase c
Releases ca from sr
Vasoconstriction of muscle
What happens to the alpha 2 adrenergic receptor
It’s Gi subunit is activated and therefore stops adenylate cyclase activation
No pka activated
Causes no neurotransmitter release
What is the B1 adrenergic receptor function
It’s Gs is activated
Activates adenylate cyclase
Causes increased HR in the cardiac muscle
(Due to na channels opening) - adenylate cyclase causes NT release
What happens when a drug stops usual epinephrine action to increase HR on the alpha 1 adrenergic receptor
Epinephrine can’t bind
The alpha 1 receptor doesn’t activate adenylate cyclase
This causes no NT release
No NA channels open
What subunit is activated in the B2 adrenergic receptor which salbutamol is agonist to
It causes activation of Gs which causes active adenylate cyclase and therefore
Bronchidilation
Name 4 enzyme linked receptors
Insulin/ RTK
Guanylyl cyclase linked receptor
Serine/threonine kinase receptor
Cytokine receptor
WhT are the 2 classes of nuclear/intracellular receptor
Class 1- in cytosol and is a homodimer , binds to hormones
Class 2- in nucleus , is a hetereodimer , binds to fatty acids
What do receptors have in terms of binding sites
Multiple sites drugs binds to
How many binding sites do glycine receptors have on ion channel
4
How many binding sites do nicotinic ach have
Homomers have 5
Hetereomers have 2
Which sites to competitive drugs bind to eg benzodiazepines on gaba channel
Orthosteric to enhance gaba activity
