Dynamics

Question 1

What are the 2 methods that a drug can take to induce an effect on the target cell

Answer 1

Receptor or non-receptor mechanisms

Question 2

What are the 4 non-receptor based mechanisms

Answer 2

Physicochemical, interaction with small ions or molecules, incorporation of drug into macromolecules, enzyme inhibition

Question 3

What are some physicochemical mechanisms

Answer 3

Osmotic diuretics
Osmotic cathartics
Neutralisation
Decreasing membrane excitability
Detergent effects

Question 4

What are some drug interactions with other molecules or ions

Answer 4

EDTA binds to Pb2+ to increase excretion
Penicillamine binds Cu2+ for excretion
PAL chelates arsenic, gold, bismuth, and mercury

Question 5

What are examples of drugs incorporated into macromolecules and their effects

Answer 5

Antimetabolites: 5-bromouracil replaces thymine in DNA synth resulting in chromosomal breakages for anti-cancerous effects
5-flourouracil replaces uracil in RNA synthesis making faulty proteins

Question 6

What are examples of enzyme inhibition

Answer 6

COX inhibitors like NSAIDs
Cholinesterase inhibitors like neostigmine
Decarboxylase inhibitors like carbidopa
Bacterial dihydrofolate reductase inhibitor like trimethoprim

Question 7

How could receptor count affect drug activity when using different concentrations

Answer 7

At high enough concentrations, all the receptors will be occupied and no increase in drug conc will affect activity

Question 8

What are some characteristics that determine receptor-drug compatibility?

Answer 8

Drug size, shape, and charge

Question 9

What are the requirements for drug and receptor binding

Answer 9

Both should be close enough
R should be complimentary to D
Binding should be reversible

Question 10

The type of interaction produced by drug and receptor depends on:

Answer 10

Chemical structure of d and r
Sites of drug loss like plasma albumin
Intermolecular binding forces

Question 11

What are the attractive forces between drug and receptor

Answer 11

Van der waals: weakest but most common
H bonds: reversible and stronger than van der waals
Ionic bond: reversible
Covalent: rarest and is irreversible (strongest)

Question 12

What are the factors that a receptor based drug response depends on

Answer 12

Affinity of drug to receptor
Efficacy of drug

Question 13

T/F: the receptor count is what determines whether a drug concentration is toxic or not

Answer 13

True (for drugs that bind to receptors)

Question 14

What are the 4 major receptor families?

Answer 14

GPCR
Ligand-gated ion channels
Enzyme linked receptor
Intracellular receptors

Question 15

How are ion channels opened or closed

Answer 15

Using ligand binding

Question 16

What happens when Acetylcholine binds to nicotinic receptors?

Answer 16

Sodium ion influx into cell (can be used to induce muscle contraction)

Question 17

What are some molecules that use GPCR?

Answer 17

Some hormones
Peptides
Neurotransmitters (adrenergic and cholinergic)

Question 18

How do enzyme-linked receptors function?

Answer 18

Ligand binds to extracellular domain, resulting in activation or inhibition of a related cytosolic enzyme usually via phosphorylation.

Question 19

How do intracellular receptors work?

Answer 19

A lipid soluble ligand diffuses into the cell and interacts with a receptor

Question 20

Give an example for intracellular receptors

Answer 20

Steroids form a complex with the intracellular receptor and migrate into the nucleus, binding to dna sequences and regulating their expression

Question 21

What are some common 2ndary messengers?

Answer 21

cAMP
cGMP
IP3
DAG
Ca2+

Question 22

What is the shape of a dose-response curve?

Answer 22

Logarithmic

Question 23

What is the shape of a graph of response vs log dose?

Answer 23

Sigmoid

Question 24

What is ED50

Answer 24

The concentration of drug that results in therapeutic effects in 50% of people

Question 25

What is LD50?

Answer 25

The dose that results in the death of 50% of users. It is usually approximated

Question 26

What is Vmax in pharmacodynamics?

Answer 26

Max response, efficacy, or intrinsic activity.

Question 27

What is the therapeutic index?

Answer 27

LD50/ED50 larger is better

Question 28

What is potency?

Answer 28

When comparing 2 drugs with the same effects, it is the ratio of dose of drug 1 vs drug 2 to produce the same effect

Question 29

The ability of a drug to form a stable complex with the receptor is called:

Answer 29

Affinity

Question 30

What is the margin of safety and what is the minimum required value?

Answer 30

LD0.1/ED99.9 the value should be greater than 1

Question 31

What is the protective index?

Answer 31

Best measure of safety ED50 producing side effects/ED50 producing desired effect

Question 32

What is a full agonist?

Answer 32

A drug that interacts with a receptor and produces a maximum response (strong agonists produce full effect while occupying less receptors)

Question 33

A drug that has reduced efficacy but maximum potency and high affinity is:

Answer 33

Partial agonist

Question 34

What is an agonist-antagonistic agonist?

Answer 34

A drug with agonistic and antagonistic activities

Question 35

A drug that produces an effect opposite to the agonist

Answer 35

Inverse agonist

Question 36

Why are inverse agonists used?

Answer 36

Some receptors produce an effect without a ligand (constitutive activity). Inv agonists block that activity. Can be used to treat hyperthyroidism and precocious puberty

Question 37

Define: Addition Synergism Potentiation

Answer 37

Addition: 2 drugs producing sane response, the net response is the sum of the response of each drug Synergism: same as addition but the response is greater than the sum of both Potentiation: one drug giving no effect coupled with a drug with an effect results in an amplified effect of the 2nd drug

Question 38

What are spare receptors?

Answer 38

Some full agonists can elicit full response without utilising all receptors, the extra receptors are called spare receptors.

Question 39

What are some effectors that give spare receptors?

Answer 39

Insulin, epinephrine, norepinephrine

Question 40

What is up-regulation and down-regulation

Answer 40

Up regulation is the increase of receptor number while the opposite happens in down regulation. The less the receptors the more drug you need for max effect

Question 41

What is tachyphylaxis?

Answer 41

Abnormal desensitization to a drug quickly

Question 42

What are the types of antagonism?

Answer 42

Physiological (ANS) Neutralisation (forming inactive complex) Pharmacological

Question 43

What is surmountable antagonism?

Answer 43

Competitive inhibition and is reversible

Question 44

What happens to ed50, affinity, and potency of an agonist when taken with a competitive antagonist?

Answer 44

ED50 inc Affinity decreases Potency is relative Vmax same Dose response curves are shifted to the right

Question 45

What are the types of unsurmountable antagonism?

Answer 45

Noncompetitve Uncompetitive Irreversible

Question 46

What is a competitive irreversible antagonist?

Answer 46

The antagonist binds irreversibly

Question 47

What is an uncompetitive inhibitor

Answer 47

One that binds to enzyme substrate complex lowering Km and Vmax

Question 48

What is a non-competitive inhibitor?

Answer 48

One that binds to enzyme-substrate complex or an allosteric site, lowering Vmax only

Question 49

What happens when irreversible antagonists bind to enzymes?

Answer 49

The dose-response curve shifts down

Question 50

What is an antidote?

Answer 50

Drug that binds another drug thereby inactivating it