2+3: Drug Receptor+ Drug mechanics

Question 1

What does Pharmacokinetics discribe?

Answer 1

What the body does to/with the drug

Question 2

Wht does Pharmacodynamics discribe?

Answer 2

What the drug does the the body (what the effect is)

Question 3

What are the prinicpal target sited of drugs?

Answer 3

Proteins:

• Receptors
• Ion channels
• Transport systems
• Enzymes

Question 4

Which signals does a receptor respond to?

Answer 4

• Neurotransmitters
• Hormones

Question 5

Where are receptors located

Answer 5

Type 1-3: in cell membrane (usually)

Type 4: intracellular steroid receptors

Question 6

Which Sub-Types of Receptors are there?

Answer 6

1. Type 1: ionotropic (ion channel linked)
2. Type 2: G-protein coupled
3. Type 3: Kinase linked
4. Type 4: intracellular steroid receptors

Question 7

What are the characteristics of a Type 1 receptor?

Answer 7

Ionotropic receptors (ion channel coupled)

• very fast response (milli sec.)
• e.g. nAChR, GABA

Question 8

Which type of receptor is an ionotrypic receptor?

Answer 8

Type 1

Question 9

Whar are the characteristics of a Type 2 receptor?

Answer 9

G-protein coupled –> set off intracellular messenger system

• seconds of response
• e.g. ß1 adrenergic receptor in heart

Question 10

What are the characteristics of a Type 3 receptor?

Answer 10

Kinase linked

• response within minutes
• e.g. insulin, Growth factor

Question 11

Whar are the characteristics of Type 4 receptors?

Answer 11

Intracellular steroid hormones

• regulate DNA transcription
• response within hours

Question 12

Which signals does an ion chanel respond to?

Which example drugs target ion channels?

Answer 12

1. Change in voltage (voltage gated)
2. Receptor binding (Receptor linked)

e.g. Local Anesthetics, Calcium channel blockers

Question 13

How can transport systems be exploited as drug target?

Answer 13

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)

Question 14

In which ways can drugs target Ezymes?

Answer 14

1. Enzyme inhibitors
   
   • inhibit enzyme action and slows reaction down
2. False substrate
   
   • Derivate von enzym substaten lassen “False transmitters” entstehen (e.g. Methylnoradrenaline from Methyldopa which has a less powerful effect)
3. Produgs
   
   • umwandlung des Medikaments durch Enzym

Question 15

What is a False transmitter? What is a true transmitter?

Answer 15

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

Question 16

What are Non-specific drug actions?

Answer 16

Drugs that work via theit physiochemical properties

• anitacids (bases)
• osmotic purgatives (abführmittel)

Question 17

What is an agonist?

Answer 17

Something that enhances receptor action

Question 18

What is an antagonist?

Answer 18

Something that blocks/ decreased receptor action

Question 19

Which factors does the potency of a drug depend on?

Answer 19

1. Affinity –> how strong/easy does the drug bind to the target
2. Efficacy –> how strong is the effect of the drug on the target

Question 20

What is the Affinity of a Drug?

Answer 20

How strongly/easy the drug binds to its target

Question 21

What is teh effecacy of a drug?

Answer 21

How strong the effect is on the target

(e.g. conformatin change in receptor)

Question 22

What are the characteristics of a full agoinst?

Answer 22

It binds to and activate a receptor with the maximum response that an agonist can elicit at the receptor

Question 23

Whar are the charcteristics of a partial agonist?

Answer 23

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

Question 24

What is the selectivity of a drug?

Answer 24

How selective the drug is to its target (will be overlap, often resulting in side-effects)

Question 25

What does the structure-activity relationship descibe?

Answer 25

Small changes in structure can have major effects on results (because of lock-and key modell)

Question 26

Descibe/draw a dose-response curve of a full agonist in comparison to a partial agonist

Answer 26

Question 27

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

Answer 27

Question 28

How efficiant are antagonist?

Answer 28

Not at all --\> have affinity but no efficacy (don't do anything)

Question 29

What two types of Antagonists are there?

Answer 29

1. **Competitive** * same binding site as substrate * Shifts Dose-response curve to the right * surmountable (überwindbar bei hohen Substratkonenztrationen) 2. **Irreversible** * different binding site or binds tighly * --\> incativate enzyme/receptor

Question 30

What are the characteristivs of competitive antagonist binding?

Answer 30

Competitive * same binding site as substrate * Shifts Dose-response curve to the right * surmountable (überwindbar bei hohen Substratkonenztrationen)

Question 31

What are the characteristics of irreversible antagonsit binding?

Answer 31

Irreversible * different binding site or binds tighly * --\> incativate enzyme/receptor * insurmountable (unüberwindbar bei hohen Substratkonzentration)

Question 32

How would a log dose response curve look like in presence of * agonist alone * with competitve agonist * with irreversible agonist

Answer 32

Question 33

Explain the concept of receptor blockage antagonism

Answer 33

Competitive binding or Irreversible binding

Question 34

Through which mechanisms can a drug act as an antagonist?

Answer 34

1. **Receptor blockage** * competitive * irreversible 2. **Physiological antagonism** * opposite effect in same tissue 3. **Chemical antagonism** * reduces concentration of agonist by forming chemical complexes 4. **Pharmacokinietic antagonism** * reduce concentration by: decreasing absorbtio, increasing metabolism/excretion

Question 35

Explain the conecegt of physiological antagonism

Answer 35

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)

Question 36

Explain the conept of chemical antagonism

Answer 36

Antagonist reduces concentration by reducing formin chemical complex with agonist e.g. Dimercaprol with heavy metals

Question 37

Explain the concept of pharmacokinetic antagonism

Answer 37

decrease concentration of agonist at site of action by * decreasing absorbtion * increasing excretion * increasing metabolism

Question 38

What is drug tolerance?

Answer 38

A gradual decrease to drug afer longer time of administration

Question 39

Which concepts can lead to drug tolerance?

Answer 39

1. Pharmacokinetic factors * adaptive increase in metabolism (e.g. enzymes) 2. Receptor loss/increase 3. Change in receptor (desensitisation) 4. Exhaution of mediator store 5. Physiological adaption (to side effects)

Question 40

Explain the concept of pharmacokinetic in drug tolerance

Answer 40

Ther ecan be an adaptive increase in drug metabolites etc. e.g. enzmyes

Question 41

Explain the concept of receptor loss/increase with drug tolerance

Answer 41

Receptors can be lossed by plasma endocytosis less receptors ---\> less action

Question 42

What happens at receptor desensitzation in drug tolerances?

Answer 42

Conformation change in receptor leading to desensitization

Question 43

Explain the concept or exhaution of mediator site in the context of drug tolerance

Answer 43

E.g. Amphitamines cause release of amines --\> Amine storages get exhaused --\> can't be released

Question 44

Explain the concept of physiological adaptation in the context of drug tolerance

Answer 44

it is a homeostatic response often a tolerance to the drug side effects