Intro To Pharmacology

Question 1

What is a drug ?

Answer 1

A natural or xenobiotic substance that when taken into the body affects cellular functions

Question 2

What target proteins does drugs affects

Answer 2

Receptors, enzymes, carriers and ion channels

Question 3

What is pharmacoeconomics ?

Answer 3

Understanding cost- benefit, cost effectiveness , cost minimisation , cost utility analyses to compare pharmaceutical products and treatment strategies

Question 4

What is pharmacoepidemiology ?

Answer 4

Study of how a drug affects a whole population

Question 5

What is pharamcogenomics?

Answer 5

Study of how genetic changes in target proteins can then affect drug function

Question 6

What factors can change or affect the way a compound binds to different areas?

Answer 6

Charge , hydrophobicity or hydrophilicity of areas of the target protein

Question 7

Types of drug binding ?

Answer 7

Hydrogen , van Der waals, hydrophobic , ionic and covalent

Question 8

What does ramipril target and where is the enzyme expressed ?

Answer 8

Ramipril targets the Angiotensin converting enzyme which is important in maintaining bp. This enzyme expression is present in smooth muscles of kidneys and vasculature but NOT the smooth muscle of the gut

Question 9

What is salbutamol ?

Answer 9

It is a beta-2 adrenergic receptor agonist used to treat asthma, bronchitis and COPD. It works effectively in the lungs but not the cardiac muscle

Question 10

What is ramipril ?

Answer 10

Ramipril is a type of medicine called an angiotensin-converting enzyme (ACE) inhibitor. Like other ACE inhibitors, ramipril relaxes and widens your blood vessels. This lowers your blood pressure and makes it easier for your heart to pump blood around your body

Question 11

What is an agonism ?

Answer 11

An agonist is a chemical that binds to a receptor and activates the receptor to produce a biological response.

Question 12

What is an antagonism

Answer 12

Antagonist blocks the binding of an agonist to the target protein . This then prevents the activity of the target protein and therefore can have a downstream effect which can be measured .

Question 13

Difference between antagonist types due to binding ?

Answer 13

Non competitive -
irreversible, covalent binding and low dissociation rate, can be at same site as the agonist or allosteric site.

Competitive binding -
to agonist binding site
Non covalent

Question 14

What is a competitive and non competitive antagonist

Answer 14

.. A competitive antagonist binds to the same site as the agonist but does not activate it, thus blocks the agonist’s action.

A non-competitive antagonist binds to an allosteric (non-agonist) site on the receptor to prevent activation of the receptor.

Question 15

Agonist?

Answer 15

Agonists can either activate receptors or cause their inactivation (inverse agonists)

Question 16

Drugs

Answer 16

Some drugs can be both agonists and antagonists dependant on the tissue type

Question 17

What does occupation mean ?

Answer 17

Affinity (binding )

Question 18

Antagonist

Answer 18

It can bind at an allosteric sitter causing a change in the protein shape this can then block the agonist binding site of the target protein

Question 19

What is Codeine

Answer 19

Codeine is an opioid analgesic used to treat moderate to severe pain when the use of an opioid is indicated.

Codeine is a full agonist. This activates certain receptors in the brain. Full agonist opioids activate the opioid receptors In the brain fully resulting in the full opioid effect.

Question 20

Is codeine a prodrug ?

Answer 20

Codeine is a prodrug. A prodrug is a medication that after administration is metabolised into a pharmacologically active drug . This means codeine then changes to its effective drug whcih is morphine

Question 21

What happens when opioids bind to mu, delta and kappa receptors ?

Answer 21

A series of intracellular events occur resulting in decreased intracellular cAMP, hyper polarisation of the cell ,, decreased neurotransmitter release.

Within the activation of mu receptors in the midbrain is the dominant mechanisms of opioid induced analgesia

Question 22

Naloxone

Answer 22

Naloxone is a medicine that rapidly reverses an opioid overdose. It is an opioid antagonist. This means that it attaches to opioid receptors and reverses and blocks the effects of other opioids. Naloxone can quickly restore normal breathing to a person if their breathing has slowed or stopped because of an opioid overdose.

Nasal spray 
Quick action 
Not much side effects 
Short half life 
Antagonist

Question 23

Nalbuphine

Answer 23

Nalbuphine is an opioid agonist-antagonist used to treat pain, for pre and postoperative analgesia, and for analgesia in labor and delivery

A narcotic used as a pain medication. It appears to be an agonist at kappa opioid receptors and an antagonist or partial agonist at mu opioid receptors

Mixed agonist/ antagonist
Administered intravenously
Dry mouth, vomiting and headaches
Can damage tissue if the body depending on the dose, the can be nephrotoxic and can be irreversible

Nalbuphine is an Opioid Agonist/Antagonist. The mechanism of action of nalbuphine is as a Competitive Opioid Antagonist, and Partial Opioid Agonist.

Question 24

Tramadol

Answer 24

Tramadol is a centrally-acting opioid agonist and SNRI (serotonin/norepinephrine reuptake inhibitor) used for the management of moderate to severe pain in adults.

structurally related to codeine and morphine.

Partial agonist
Pro drug
Causes arrhythmia , constipation , headaches and depression

Question 25

Is codeine a cough suppressant ?

Answer 25

Codeine suppresses the cough reflex through a direct effect on the cough center in the medulla.

Question 26

MOA of codeine ?

Answer 26

Codeine is a selective agonist for the mu opioid receptor, but with a much weaker affinity to this receptor than morphine, a more potent opioid drug.

Codeine binds to mu-opioid receptors, which are involved in the transmission of pain throughout the body and central nervous system .

The analgesic properties of codeine are thought to arise from its conversion to Morphine,

Question 27

Metabolism of codeine ?

Answer 27

ingested dose of codeine is metabolized in the liver by conjugation with glucuronic acid to codeine-6­ glucuronide (C6G)

Cytochrome P450 2D6 is the major enzyme responsible for the transformation of codeine to morphine and P450 3A4 is the main enzyme mediating the conversion of codeine to norcodeine.

Morphine and norcodeine are then further metabolized by conjugation with glucuronic acid.

Question 28

Contraindications of codeine ?

Answer 28

Alvimopan  
( Alvimopan is in a class of medications called peripherally acting mu-opioid receptor antagonists. It works by protecting the bowel from the constipation effects of opioid (narcotic) medications that are used to treat pain after surgery)

Question 29

What is Naloxone ?

Answer 29

Naloxone is an opioid antagonist medication used to block or reverse the effects of opioid drugs,

naloxone has a high affinity for μ-opioid receptors, where it acts as an inverse agonist, causing the rapid removal of any other drugs bound to these receptors.

When taken in large quantities, opioid medications such as morphine, hydromorphone, methadone, heroin, or fentanyl are capable of causing life-threatening symptoms such as respiratory depression, reduced heart rate, slurred speech, drowsiness, and constricted pupils.

Question 30

What ways can Naloxone be administered

Answer 30

naloxone is currently available by intramuscular (IM) or subcutaneous (SubQ) injection, nasal spray, or intravenous (IV) infusion.

Question 31

Pharmacodynamics of Naloxone ?

Answer 31

Naloxone is an opioid receptor antagonist indicated in the reversal of opioid overdoses.

Naloxone has a shorter duration of action than opioids and multiple doses may be required.

The therapeutic window of naloxone is wide, as it has no effect if a patient has not taken opioids.4,7 Patients treated with naloxone may experience opioid withdrawal and a person administering naloxone should be aware that reversal of opioid overdoses may not resolve all the symptoms a patient is experiencing if other drugs are involved

Question 32

Mechanisms of action for Naloxone ?

Answer 32

Naloxone is a competitive inhibitor of the µ-opioid receptor.

Naloxone antagonizes the action of opioids, reversing their effects. If a patient has not taken opioids, naloxone does not have a significant effect on patients

Question 33

Metabolism of Naloxone ?

Answer 33

Naloxone primarily undergoes glucuronidation to form naloxone-3-glucuronide.7 Naloxone is also N-dealkylated to noroxymorphone or undergoes 6-keto reduction to naloxol.1

Question 34

MOA of Nalbuphine ?

Answer 34

The exact mechanism of action is unknown, but is believed to interact with an opiate receptor site in the CNS (probably in or associated with the limbic system).

The opiate antagonistic effect may result from competitive inhibition at the opiate receptor, but may also be a result of other mechanisms.

Nalbuphine is thought primarily to be a kappa agonist. It is also a partial mu antagonist analgesic, with some binding to the delta receptor and minimal agonist activity at the sigma receptor.

Question 35

Pharmacodynamics of Tramadol and side effects

Answer 35

Tramadol modulates the descending pain pathways within the central nervous system through the binding of parent and M1 metabolite to μ-opioid receptors and the weak inhibition of the reuptake of norepinephrine and serotonin.7,6

tramadol may produce symptoms (including dizziness, somnolence, nausea, constipation, sweating and pruritus)

Question 36

MOA of Tramadol

Answer 36

Tramadol is a centrally acting μ-opioid receptor agonist and SNRI (serotonin/norepinephrine reuptake-inhibitor) that is structurally related to codeine and morphine. Tramadol binds weakly to κ- and δ-opioid receptors and to the μ-opioid receptor with 6000-fold less affinity than morphine

Question 37

What describes the ability of acetylcholine to inhibit the epinephrine -mediated increases in heart rate?

Answer 37

Physiological antagonism.

Question 38

Exposure of airway smooth muscle cells to salbutamol triggers what?

Answer 38

1) Salbutamol binds beta2 adrenoceptors.
2) G protein Gs dissociates
3) adenylyl Cyclase is activated
4) cyclic AMP levels increase
5) myosin light chain kinase inhibited