2+3: Drug Receptor+ Drug mechanics Flashcards
What does Pharmacokinetics discribe?
What the body does to/with the drug
Wht does Pharmacodynamics discribe?
What the drug does the the body (what the effect is)
What are the prinicpal target sited of drugs?
Proteins:
- Receptors
- Ion channels
- Transport systems
- Enzymes
Which signals does a receptor respond to?
- Neurotransmitters
- Hormones
Where are receptors located
Type 1-3: in cell membrane (usually)
Type 4: intracellular steroid receptors
Which Sub-Types of Receptors are there?
- Type 1: ionotropic (ion channel linked)
- Type 2: G-protein coupled
- Type 3: Kinase linked
- Type 4: intracellular steroid receptors
What are the characteristics of a Type 1 receptor?
Ionotropic receptors (ion channel coupled)
- very fast response (milli sec.)
- e.g. nAChR, GABA
Which type of receptor is an ionotrypic receptor?
Type 1
Whar are the characteristics of a Type 2 receptor?
G-protein coupled –> set off intracellular messenger system
- seconds of response
- e.g. ß1 adrenergic receptor in heart
What are the characteristics of a Type 3 receptor?
Kinase linked
- response within minutes
- e.g. insulin, Growth factor
Whar are the characteristics of Type 4 receptors?
Intracellular steroid hormones
- regulate DNA transcription
- response within hours
Which signals does an ion chanel respond to?
Which example drugs target ion channels?
- Change in voltage (voltage gated)
- Receptor binding (Receptor linked)
e.g. Local Anesthetics, Calcium channel blockers
How can transport systems be exploited as drug target?
By blocking transport systems that transport substanced against their concentration gradient ( are specific for substance + ATP dependant)
- e.g. Neurotransmitter uptake (blocking of reuptake of Noradrenaline used in antidepressants)
In which ways can drugs target Ezymes?
-
Enzyme inhibitors
- inhibit enzyme action and slows reaction down
-
False substrate
- Derivate von enzym substaten lassen “False transmitters” entstehen (e.g. Methylnoradrenaline from Methyldopa which has a less powerful effect)
-
Produgs
- umwandlung des Medikaments durch Enzym
What is a False transmitter? What is a true transmitter?
False transmitter: Transmitter that closely immitates the action of a transmitter but act a bit different
- e.g. Methyldopa (False transmitter) giving Methylnoradrenaline binding weaker to target –> causing muscle relaxation
- DOPA would be the true transmitter
What are Non-specific drug actions?
Drugs that work via theit physiochemical properties
- anitacids (bases)
- osmotic purgatives (abführmittel)
What is an agonist?
Something that enhances receptor action
What is an antagonist?
Something that blocks/ decreased receptor action
Which factors does the potency of a drug depend on?
- Affinity –> how strong/easy does the drug bind to the target
- Efficacy –> how strong is the effect of the drug on the target
What is the Affinity of a Drug?
How strongly/easy the drug binds to its target
What is teh effecacy of a drug?
How strong the effect is on the target
(e.g. conformatin change in receptor)
What are the characteristics of a full agoinst?
It binds to and activate a receptor with the maximum response that an agonist can elicit at the receptor
Whar are the charcteristics of a partial agonist?
Bind to and activate the receptor but only have a partial efficacy in comparison to full agonist
–> can have antagonist property in presence of a full agonist
What is the selectivity of a drug?
How selective the drug is to its target (will be overlap, often resulting in side-effects)
What does the structure-activity relationship descibe?
Small changes in structure can have major effects on results (because of lock-and key modell)
Descibe/draw a dose-response curve of a full agonist in comparison to a partial agonist
Describe /draw how a log- dose response curve of a full agonist with high efficacy, full agonist with low efficacy and partial agonist would look like
How efficiant are antagonist?
Not at all –> have affinity but no efficacy (don’t do anything)
What two types of Antagonists are there?
-
Competitive
- same binding site as substrate
- Shifts Dose-response curve to the right
- surmountable (überwindbar bei hohen Substratkonenztrationen)
-
Irreversible
- different binding site or binds tighly
- –> incativate enzyme/receptor
What are the characteristivs of competitive antagonist binding?
Competitive
- same binding site as substrate
- Shifts Dose-response curve to the right
- surmountable (überwindbar bei hohen Substratkonenztrationen)
What are the characteristics of irreversible antagonsit binding?
Irreversible
- different binding site or binds tighly
- –> incativate enzyme/receptor
- insurmountable (unüberwindbar bei hohen Substratkonzentration)
How would a log dose response curve look like in presence of
- agonist alone
- with competitve agonist
- with irreversible agonist
Explain the concept of receptor blockage antagonism
Competitive binding or Irreversible binding
Through which mechanisms can a drug act as an antagonist?
-
Receptor blockage
- competitive
- irreversible
-
Physiological antagonism
- opposite effect in same tissue
-
Chemical antagonism
- reduces concentration of agonist by forming chemical complexes
-
Pharmacokinietic antagonism
- reduce concentration by: decreasing absorbtio, increasing metabolism/excretion
Explain the conecegt of physiological antagonism
A drug has the opposite effect as the agonist in the same tissue
e.g. Noradrenaline is an antagonist of histamine in blood vessel (dilation vs. constriction)
Explain the conept of chemical antagonism
Antagonist reduces concentration by reducing formin chemical complex with agonist
e.g. Dimercaprol with heavy metals
Explain the concept of pharmacokinetic antagonism
decrease concentration of agonist at site of action by
- decreasing absorbtion
- increasing excretion
- increasing metabolism
What is drug tolerance?
A gradual decrease to drug afer longer time of administration
Which concepts can lead to drug tolerance?
- Pharmacokinetic factors
- adaptive increase in metabolism (e.g. enzymes)
- Receptor loss/increase
- Change in receptor (desensitisation)
- Exhaution of mediator store
- Physiological adaption (to side effects)
Explain the concept of pharmacokinetic in drug tolerance
Ther ecan be an adaptive increase in drug metabolites etc. e.g. enzmyes
Explain the concept of receptor loss/increase with drug tolerance
Receptors can be lossed by plasma endocytosis
less receptors —> less action
What happens at receptor desensitzation in drug tolerances?
Conformation change in receptor leading to desensitization
Explain the concept or exhaution of mediator site in the context of drug tolerance
E.g. Amphitamines cause release of amines
–> Amine storages get exhaused –> can’t be released
Explain the concept of physiological adaptation in the context of drug tolerance
it is a homeostatic response
often a tolerance to the drug side effects
