L2: Pharmacodynamics 1

Question 1

What does the chemical name of a drug tell you?

Answer 1

The chemical formula and the molecular structure.

Question 2

What is the generic (non-proprietary) name of a drug?

Answer 2

• The universal name of a drug (recognized internationally) named by USAN and WHO.
• There’s one unique name per drug

Question 3

What is the trade name of a drug?

Answer 3

• Unlimited # of names

- Registered trademark (different for each manufacturer)

Question 4

What is pharmacodynamics?

Answer 4

What the drug does to the body: effect of drug on target cells (receptors, ion channels, enzymes) and organ systems and immune system.

Question 5

What is pharmacokinetics?

Answer 5

What the body does to the drug: absorption, distribution, metabolism, excretion.

Question 6

What is therapeutics?

Answer 6

Using drugs to treat or prevent a disease.

Question 7

What’s a therapeutic indication?

Answer 7

When you should use a drug and what it is used for.

Question 8

What’s a therapeutic contraindication?

Answer 8

When you should NOT use a drug.

ex: mixing drugs, medical condition, etc.

Question 9

What are the different methods of administration?

Answer 9

1. Oral (enteral)
2. Parenteral (injection)
3. Inhalation
4. Topical (skin, mucosa)
5. Sublingual
6. Rectal

Question 10

What’s the path of a drug administered orally?

Answer 10

1. Swallow
2. Goes through GIT
3. Liver: 1st pass effect
4. Systemic circulation

Question 11

What is the first pass effect?

Answer 11

The liver detoxifies the blood before it enters the systemic circulation. Therefore, any drugs that are swallowed will get partly inactivated by the liver therefore reducing the drug concentration in the systemic circulation (bioavailability).

Question 12

What is bioavailability?

Answer 12

How much of the drug is available to get into the circulation after going through the liver.

Question 13

What are the advantages of oral administration?

Answer 13

1. Easy, cheap, convenient
2. No special equipment needed (self administration)
3. Modified release tablets can adjust the time it takes to absorb the drug

Question 14

What are the advantages of parenteral (injection) administration?

Answer 14

1. Bypasses the GIT (for pH sensitive drugs)
2. Bypasses liver (no first pass - good for drugs that get easily inactivated)
3. Fast absorption
4. Accurate absorption dose
5. Certain people can inject themselves

Question 15

What are the different ways to inject a drug?

Answer 15

1. Subcutaneous (under the skin)
2. Intravenous (directly into blood stream… fastest)
3. Intramuscular
4. Cerebrospinal fluid - bypasses blood brain barrier
5. Intraperitoneal (abdominal wall)

Question 16

What are the advantages of administering a drug via inhalation?

Answer 16

1. Easy to administer
2. Rapid systemic effect (seconds to min)
3. Large surface area of lungs (alveoli have little barrier with close proximity to capillaries)

Question 17

Explain how a drug can be absorbed topically.

Answer 17

If the drug is lipid soluble, then it can reach the blood vessels in the dermis.

Question 18

What are the new methods of drug administration?

Answer 18

1. Drugs enclosed in liposome (it can pass through lipid barriers even if its not lipid soluble).
2. Implants (may last for years).
3. Transdermal (ex: microneedles)

Question 19

Why would you choose specific drug administration methods over another?

Answer 19

Administration routes affect the time course and the peak concentration of the drug in the blood.

1. Intravenous administration: high initial concentration in the blood and drops quickly as it reaches the target tissue and is distributed.
2. Oral: slower rate of rise bc it takes time for the compound to be absorbed from the gI tract. Lower peak concentration due to the 1st pass effect.
3. Rectal: Slow absorption & lower peak level

Question 20

What are the two types of drug selectivity? Give an example for each.

Answer 20

1. Selective effect: mostly targets one area (ex: intravenous iodide for selective effects on the thyroid)
2. Generalized effect: acts on all systems (ex: intravenous epinephrine for an effect on all vasculature, antacids change pH in stomach when taken)

Question 21

What’s the definition of a drug receptor?

Answer 21

a macromolecular protein target to which endogenous ligand or exogenous antagonists/agonists binds to cause a cellular response.

Question 22

How are receptors identified?

Answer 22

Through radioligand binding, isolation, and sequencing to understand their structure. This helps with the design of drugs.

Question 23

What is an antagonist and an agonist and where do they bind?

Answer 23

1. Antagonist: exogenous ligand that blocks the endogenous ligand from binding. Inhibits receptor activation by agonist.
2. Agonist: exogenous ligand that mimics the natural ligand. Initiates conformational change in the receptor and activates one or more downstream signalling pathways.

They both bind the endogenous binding site.

Question 24

What’s an allosteric binding site?

Answer 24

A different site from the endogenous binding site on the receptor. When bound, it will alter the response of the endogenous site.

Question 25

What are allosteric activator and inhibitor?

Answer 25

1. Allosteric activator: increases the response of the receptor to the ligand at a different binding site. 2. Allosteric inhibitor: decreases the response of the receptor to the ligand at a different binding site.

Question 26

What are the different transmembrane signalling mechanisms?

Answer 26

1. Intracellular receptors 2. Receptor activated enzyme 3. Receptor activated tyrosine kinase 4. Receptor activated ion channel 5. GPCR

Question 27

What is an ion channel?

Answer 27

A transmembrane protein that open to allow passage of specific ions. They exist in 3 conformations: open, closed, & inactivated.

Question 28

How can ion channels be controlled (types of ion channels)?

Answer 28

Voltage gated or receptor (ligand) gated.

Question 29

What does the affinity (how quickly the drug will bind) of a drug to its ion channel receptor depend on?

Answer 29

1. Membrane potential | 2. Channel cycling frequency (how often it opens and closes)

Question 30

What are 2 examples of receptor operated (ligand gated) ion channels? (describe it's structure and how it works)

Answer 30

1. Nicotinic cholinergic receptor. Has 5 subunits that form a pore. 2 of the subunits are alpha subunits where acetylcholine binds. the other subunits can vary which gives variability and selectivity to the receptor. To open the channel, 2 acetylcholine molecules must bind. 2. NMDA receptors: has 5 different sites of action where drugs can act for different outcomes. NMDA receptors are activated by glutamate (excitatory neurotransmitter).

Question 31

What is the effect a drug can have on a ligand gated ion channel?

Answer 31

1. Block the channel | 2. Modulate the channel (increase or decrease opening probability).

Question 32

What is a carrier protein?

Answer 32

A transmembrane protein that transports molecules across the cell membrane. Some require energy to function. Carrier molecules can be involved in passive (diffusion, facilitated transport) or active transport (ATP required).

Question 33

Describe a GPCR.

Answer 33

It's a receptor spanning the plasma membrane 7 times. It can form homo- or hetero-oligomers. It acts as an on/off switch for cell signalling. Both stimulatory and inhibitory signalling is possible as a result of GPCR stimulation. A balance between the stimulation and inhibition of GPCR's determines the resulting signal.

Question 34

How does a GPCR work?

Answer 34

1. Ligand binds to the GPCR 2. G-protein (made of alpha, beta, gamma subunits) activated. This means that the GDP bound to the alpha subunit is exchanged for GTP = ON. 3. Alpha subunit detaches and activates an effector (can be enzyme or ion channel) protein. 4. Production of secondary messenger from effector 5. Further leads to downstream signalling (cell response or ion channel opening) 6. When the alpha subunit's GTP is exchanged for GDP, it turns off.

Question 35

Give 2 examples of a GPCR and explain the sequence of events.

Answer 35

1. Muscarinic acetylcholine receptor - ACh binds GPCR, G-protein activates potassium channel, potassium exits and hyperpolarizes the cell. 2. Epinephrine receptor - Epinephrine binds to GPCR, cAMP is second messenger and leads to release of glucose.

Question 36

What is receptor turnover?

Answer 36

Receptors are dynamic. There is a constant turnover based on the body's needs. Cells respond to different physiological events by changing the number of receptors at the plasma membrane.

Question 37

How is receptor turnover accomplished?

Answer 37

The ligand bound receptor is internalized via endocytosis. Then, lysosomes can break down the receptors or some receptors can be recycled to the membrane once the ligand is removed. A small percentage of ligand bound receptors can also be recycled to the membrane, this is called retroendocytosis.

Question 38

How do tyrosine kinase receptors work?

Answer 38

The ligand bind to the receptor (extracellular) which leads to dimerization. Activated receptor leads to phosphorylation of its tyrosine residues (intracellular). this further activates a protein which leads to downstream signalling.

Question 39

What are typical agonists of tyrosine kinase receptors?

Answer 39

Insulin, growth factor

Question 40

What is a natriuretic peptide receptor?

Answer 40

A peptide receptor that activates cellular responses in the kidney and the heart.

Question 41

What is the purpose of intracellular receptors?

Answer 41

Altering gene transcription and protein synthesis (i.e. localization to the nucleus).

Question 42

Give an example of an intracellular receptor and the process that goes with it.

Answer 42

Steroid receptor. 1. Steroid hormone diffuses through the plasma membrane and binds the steroid receptor intracellularly. 2. Translocation of steroid-receptor complex to nucleus 3. Binding of complex to DNA regulatory site 4. Transcription (and translation) modified

Question 43

What are the domains of intracellular receptors?

Answer 43

1. Ligand binding domain | 2. DNA binding domain

Question 44

Compare the response times of the different types of receptors.

Answer 44

1. Ion channel: fast response (milliseconds) 2. GPCR: seconds bc the second messenger system must be activated 3. Receptor activated enzymes: minutes 4. DNA linked (ex: intracellular): hours bc it has to go through translocation, transcription, translation, and enzymatic activity.

Question 45

What can be the negative consequence of a drug targeting a cellular receptor?

Answer 45

It is not always effective and safe. Receptors can be necessary for vital functions, and if blocked or altered, it can be fatal. It is sometimes better to target the constituent of a virus or microbe directly than to target the receptor it uses to enter the cell.