MedChem Basics

Question 1

What is a medicine?

Answer 1

Medicines are chemicals or compounds used to cure, halt, or prevent disease; ease symptoms; or help in the diagnosis of illnesses.

Question 2

What is the difference between pharmacodynamics and pharmacokinetics?

Answer 2

Pharmacokinetics is the study of what the body does to the drug, and Pharmacodynamics is the study of what the drug does to the body.

Question 3

What formulations are available to reduce 1stpass metabolism?

Answer 3

Parenteral, IV, IM, SC, Nasal spray, MDI

Question 4

How does Ibuprofen work? Any contraindications?

Answer 4

Ibuprofen works on one of the body’s chemical pathways for pain. The drug enters the bloodstream, circulates through the body, and blocks cyclooxygenase. This reduces your body’s ability to make prostaglandins — these are the natural chemicals that trigger pain, inflammation and fever. With fewer prostaglandins in your body, pain and inflammation are reduced, and your fever goes down.

Contraindications - known hypersensitivity or idiosyncratic reaction to ibuprofen (or any of the other ingredients in the product). Known hypersensitivity to aspirin and other NSAIDs. asthma that is aspirin or NSAID sensitive. Active gastrointestinal bleeding or peptic ulceration.

Question 5

What is the “Therapeutic Window”

Answer 5

The therapeutic window describes the dosage range between a minimum effective therapeutic concentration, and the minimum toxic concentration.

Question 6

What classification and what is the mode of action of Paracetamol.

Answer 6

Paracetamol is an analgesic and acts by blocking the chemical messengers in the brain that tell your body that you have pain. It also reduces a high temperature by affecting the chemical messengers in an area of the brain that regulates body temperature.

Question 7

What do you understand by the word potency as it relates to drug action?

Answer 7

Potency (strength) refers to the amount of drug (usually expressed in milligrams) needed to produce an effect, such as relief of pain or reduction of blood pressure.

Question 8

What is drug distribution dependent on?

Answer 8

Drug distribution is impacted by several factors related to the drug and the body. The drug-related factors include blood and tissue binding proteins, pH, and perfusion. The body-related factors include body water composition, fat composition, diseases
Talk to me about absorption rates of drugs?

Question 9

What are the main therapeutic groups of medicines? Where would be a typical source of this information?

Answer 9

Cardivascular, Diabetes, analgesics, antibiotics, anti-depressant, anti-cancer, inhalation products. Pharmacopeias, websites (electronic medicines compendium, WHO, EMA), chemists, doctors

Question 10

What products do your company make?

Answer 10

Zoladex copolymer implant and Nolvadex tablets

Question 11

Where would this (pharmacological action) information be included in a marketing authorisation?

Answer 11

Module 3 Quality

Question 12

If you wanted to find out about a drug where would you go to look for the information?

Answer 12

Electronic medicines compendium or EMA website

Question 13

What are the 3 most critical factors for drug absorption from a solid dosage form?

Answer 13

Tablet hardness, tablet coating, granule size. pH at site of dissolution

Question 14

What does Warfarin do?

Answer 14

Warfarin is an anticoagulant, while the drug is described as a “blood thinner”, it does not reduce viscosity but rather inhibits coagulation

Question 15

Can you explain 1stpass metabolism and its implications?

Answer 15

The first-pass effect is a pharmacological phenomenon in which a medication undergoes metabolism at a specific location in the body. The first-pass effect occurs whenever the drug is administered orally, the drug enters the bloodtream where it is transported via the portal vein to the liver, in the liver the drug is hydrolysed to such an extent that the bioavailability is drastically reduced, decreasing the active drug’s concentration upon reaching systemic circulation or its site of action

Question 16

What is the effect of pH on product

Answer 16

GI pH is an important factor that can markedly affect oral drug absorption and bioavailability as it may have significant influence on drug dissolution & solubility, drug release, drug stability, and intestinal permeability. Different regions of the GI tract have different drug absorptive properties

Question 17

What is pH of blood?

Answer 17

Blood is normally slightly basic, with a normal pH range of about 7.35 to 7.45.

Question 18

What is process capability – how do you measure it? (Led to CpK and the differences between the two)

Answer 18

Process capability is defined as a statistical measure of the inherent process variability of a given characteristic. CpK is a measure used for short term variation and PpK for long term

Question 19

What affects the bioavailability of a drug?

Answer 19

physicochemical properties of the drug, physiological aspects, the type of dosage form, food intake

Question 20

What is a diuretic/ how do they work/ what parts of kidney do they act on?/ name some examples/ what were the problems with earlier diuretics?

Answer 20

Diuretics are medicines that help reduce fluid buildup in the body. Diuretics act on the kidneys and encourage them to release water in the form of urine. As urine contains salt as well as water, diuretics also increase the body’s salt excretion – consisting of sodium, potassium and magnesium. Older adult individuals tend to experience insufficient blood volume after taking diuretics, resulting in hypotension, dizziness, fainting, and falls.

Question 21

What affects drug metabolism?

Answer 21

Many factors affect the rate and pathway of metabolism of drugs, and the major influences can be sub-divided into internal (physiological and pathological) and external (exogenous) factors as indicated below: Internal: species, genetic (strain), sex, age, hormones, pregnancy, disease. External: diet, environment.

Question 22

What is the action of Temgesic?

Answer 22

TEMGESIC is a “pain killer”. It is used for the short term relief of severe pain. TEMGESIC belongs to a group of medicines called opioid (narcotic) analgesics. Opioid analgesics act directly on the brain and spinal cord to block the sensation of pain.

Question 23

What is a partial agonist?

Answer 23

partial agonists are drugs that bind to and activate a given receptor, but have only partial efficacy at the receptor relative to a full agonist.

Question 24

Acetylcholine triggers

Answer 24

Muscarinic Acetylcholine receptors
 Contracts SM, widens blood vessels, lowers HR

Question 25

Parasympathetic

Answer 25

Peace – rest & digest
1. Pupils – constricted
2. Salivary glands – stimulated
3. Heartbeat lowered
4. Blood pressure lowered
4. Lungs – bronchi constricted
5. Stomach – digestion increased
6. Liver – bile release increased
7. Intestine – peristalsis and secretion increased
8. Bladder - contracts

Question 26

Sympathetic

Answer 26

Stress – fight or flight
1. Pupils – dilated
2. Salivary glands – inhibited
3. Heartbeat increased
4. Blood pressure increased
4. Lungs – bronchi dilated
5. Stomach – digestion decreased
6. Liver – glucose release increased
7. Kidneys – epinephrine and norepinephrine release
7. Intestine – peristalsis and secretion decreased
9. Bladder - relaxes

Question 27

Norepinephrine triggers:

Answer 27

α1 (vascular SM), α2 (brain)
β1 (heart) & β2 (lungs) receptors
Released in stress situations

Question 28

Sympathetic agonists:

Answer 28

Phenylephrine (α1) treats:
Hypotension (constricts smooth muscles in wall of blood vessels (arteries/arterioles))  inc BP)
Nasal decongestant (constricts widened nasal mucous blood vessels)
Salbutamol (β2) treats:
Asthma (bronchi dilation – widens airways)

Question 29

Sympathetic antagonists:

Answer 29

Propanolol (β) treats:
Hypertension (blocks β1 action therefore lower HR & BP) – non selective.
Atenolol (β1) treats:
Hypertension and chest pain (blocks β1 action therefore lower HR & BP) – selective to β1 therefore not β2 in lungs.

Question 30

Bioavailability

Answer 30

Proportion of drug absorbed into systemic circulation. Drug with first pass metabolism = low bioavailability

Question 31

Bioequivalence

Answer 31

Demonstrate extent and rate of absorption in two products are equiv.
- Obtain biowaiver

Question 32

First pass metabolism:

Answer 32

“Metabolism of a drug before reaching the systemic (blood) circulation”
To overcome – routes of admin: IV, local, inhalation etc

Question 33

Drug targets:

Answer 33

1. Enzymes – Ibuprofen
2. Receptors – Buprenorphine
3. Ion channels - Na+ channel blockers (local anaesthetic)

Question 34

Receptor types

Answer 34

Agonist: Compound that binds to a receptor and triggers a response
Antagonist: Compound that binds to a receptor and doesn’t produce a response  blocks the associated response.
Neurotransmitter: Substance that sends signals between nerve cells

A competitive antagonist
competes for the same binding site with an agonist, binding is mutually exclusive.
Increasing the conc. of agonist can overcome competitive antagonist activity
A non-competitive antagonist
the antagonist, while still opposing the action of the agonist, does so without competing with it for the binding site. The agonist may bind there all it wants; it will still do no good.

Question 35

Antibiotics types

Answer 35

Bacteriostatic agent – restricts growth and reproduction – e.g. chloramphenicol
Bactericidal – causes bacteria cell death – e.g. β lactams

Question 36

Parkinson’s Drugs

Answer 36

Develops in the part of the brain that controls movement & cells begin to die. These cells produce dopamine. Loss of dopamine  issues with movement.
Levodopa: Pre-cursor to Dopamine. Can cross BBB (Dopamine can’t). Levodopa converted to dopamine by proteins. Protein MAO-B helps recycle dopamine in brain  stays longer.

Question 37

Cardiac Medication

Answer 37

Beta Blockers  Atenolol, Propanolol
Calcium Channel Blockers  Nifedipine (treat high BP)
Nitrates  Glyceryl trinitrate, spray (treat angina)
ACE Inhibitors  Enalapril, (ending in ‘pril’) (treat high BP)
Diuretics  Metolazone (remove extra fluid from body)
Antiarrhythmic Drugs  Digoxin (treat irregular heartbeat)
Blood Thinning/Anticoagulation  Aspirin, Warfarin, Heparin

Question 38

Drug Target/Treatment Areas (BNF)

Answer 38

GI system
Cardiovascular system
Respiratory system
CNS
Infections
Endocrine system
Obstetrics, gynaecology & urinary tract disorders
Malignant disease & immunosupp
Nutrition & blood
Eye
Ear, nose & throat
Skin
Anaesthesia
Immunological products & vaccines
Musculoskeletal & joint diseases

Question 39

Antidepressant Drugs:

Answer 39

Selective serotonin reuptake inhibitors (SSRI) e.g. Prozac (Fluxoetine), Citalopram, Sertraline
Selectively inhibit the re-uptake of serotonin (n/t)  increased level of serotonin.
Most widely prescribed antidepressant.

Monoamine Oxidase Inhibitors (MAOIs)
Monoamine oxidase is involved in removing the neurotransmitters norepinephrine, serotonin and dopamine from the brain. MAOIs prevent this from happening, which makes more of these chemicals available in the brain, which are useful at relieving symptoms associated with depression, such as sadness or anxiety.
Not often prescribed due to food interactions.
Wide range of side effects, so normally only prescribed now when SSRIs don’t work

Question 40

Potency

Answer 40

effective dose of drug
Potent drug = effective in low conc

Question 41

ATP

Answer 41

ATP (adenosine triphosphate) = molecule that carries energy in cell

Question 42

Analgesic/Painkillers

Answer 42

Act on peripheral and CNS
Paracetamol
NSAIDs (ibuprofen, asprin)  COX 2 inhibitors
Opioids (morphine/codeine)  Opioid receptors  addictive

Question 43

Blood thinners – Warfarin & Heparin

Answer 43

Heparin – fast acting / short duration – used in emergency settings, before surgery
Warfarin – Long onset / long duration. QP concerns: possible accumulation in the body due to the long residence time. Narrow therapeutic window, specifications need to be tight to ensure correct dosing.

Question 44

Drug Targets:
Enzymes – e.g. NSAIDs (Ibuprofen)

Answer 44

Cyclooxygenase(COX) inhibitors are non-steroidal anti-inflammatory drugs (NSAIDs), used to relieve fever and pain.
COX inhibitors can act at one or both of the isozymes,COX-1andCOX-2 (e.g. celecoxhib)
COX-1 is involved in the synthesis of prostaglandins which are responsible for maintenance and protection of the gastrointestinal tract, whilst COX-2 produces the pro-inflammatory prostaglandins responsible for causing inflammation and pain.
Inhibitors differ in their relative specificities for COX-1 and COX-2, with examples such asaspirin,ibuprofen,naproxenanddiclofenacbeing non-selective. Selective COX-2 inhibitors were developed to reduce the liability of gastrointestinal damage associated with COX-1 inhibition. Non-selective COX inhibitors are often prescribed with a proton pump inhibitor such asomeprazoleto reduce the risk of causing gastrointestinal ulceration and bleeding.

Question 45

Ion Channels:

Answer 45

Ion channelsare pore-forming protein complexes that facilitate the flow of ions across the hydrophobic core of cell membranes. They perform essential physiological functions including establishing and shaping theelectrical signals which underlie muscle contraction/relaxation and neuronal signal transmission, neurotransmitter release, cognition, hormone secretion, sensory transduction and maintaining electrolyte balance and blood pressure.They are usually classified by gating i.e. the stimulus that ‘opens’ the channel, be itchemical or mechanical stimuli.
Calcium channel blockers (e.g. amlodipine) used in the treatment of hypertension. Inhibiting the Ca2+ entry, therefore blocking the CA2+ entry and stopping it acting as an intracellular messenger. Causing smooth muscle relaxation in myocardial cells of the atria and ventricles

Question 46

ACE Inhibitors (‘prils):

Answer 46

Angiotensin converting enzyme inhibitors (ACE inhibitors) are medications that slow (inhibit) the activity of the enzyme ACE, which decreases the production of angiotensin II. As a result, blood vessels enlarge or dilate, and blood pressure is reduced. This lower blood pressure makes it easier for the heart to pump blood and can improve the function of a failing heart. In addition, the progression ofkidney diseasedue tohigh blood pressureordiabetesis slowed.

Question 47

Receptors:

Answer 47

Receptors are typically glycoproteins located in cell membranes that specifically recognize and bind to ligands

These are smaller molecules (including drugs) that are capable of ‘ligating’ themselves to the receptor protein. This binding initiates a conformational change in the receptor protein leading to a series of biochemical reactions inside the cell (‘signal transduction’) often involving the generation of ‘secondary messengers’ that is eventually translated into a biological response (e.g. muscle contraction, hormone secretion). Although the ligands of interest to prescribers are exogenous compounds (i.e. drugs), receptors in human tissues have evolved to bind endogenous ligands such as neurotransmitters, hormones and growth factors. Formation of the drug-receptor complex is usually reversible & the proportion of receptors occupied (and thus the response) is directly related to the conc. of the drug. Reversibility enables biological responses to be modulated & means that similar ligands may compete for access to the receptor. The term ‘receptor’ is usually restricted to describing proteins whose only function is to bind a ligand, but it is sometimes used more widely in pharmacology to include other kinds of drug target such as voltage-sensitive ion channels, enzymes & transporter proteins.
E.g. Acetylcholine receptors (muscarinic)

Question 48

Formulation pH and pKa

Answer 48

pH - measure of the concentration of hydrogen ions in an aqueous solution. More H ion, lower pH.
Acids have more H ions  H donors. Bases have less H ions  H acceptors.
Strong acids/bases fully dissociate in aqueous solutions but weak acids/bases only partially dissociate.
pKa - acid dissociation constant - helps you predict what a molecule will do at a specific pH / how much drug will be absorbed at a specific pH. Adjust the pH to get the drug to be dissolved and absorbed in different areas.
PKa is unique to a drug and can determine where it will dissolve / partition
Where the pKa = pH 50% of the drug ionised (dissociated) and 50% unionised. RATIO 1:1
Acid: pH of 2 units BELOW the Pka = 99 % unionised/insoluble (undissociated)
Acid: pH of 2 units ABOVE the Pka = 99% ionised/soluble (dissociated)
Only unionised drug can partition across membranes by passive diffusion (if unionised form also lipophilic)

Question 49

Product types

Answer 49

Borderline:
Products which are hard to classify.
Must decide which legislation they fall under

Orphan:
A product to treat rare, life threatening of chronically debilitating disease, where there is no current treatment or the product provides significant benefit

Radiopharmaceutical:
medicinal formulations containing radioisotopes which are used in major clinical areas for diagnosis and/or therapy

ATMP:
a medicinal product which is either: a gene therapy medicinal product. a somatic cell therapy medicinal product. a tissue engineered product.

Herbal:
a medicinal product, exclusively containing as active ingredients one or more herbal substances, one or more herbal preparations, or a combination of the two.

Special:
Unlicensed products which have been specially manufactured or imported for the treatment of an individual patient after being ordered by a:
Doctor, dentist, nurse etc

NIMP:
Not an IMP, placebo or comparator being used in the clinical trial. But may be a rescue medication.

To be replaced by AUXILARY Medicines (AXMS) – Essentially the same as an NIMP

Medicinal Gas:
as one that is manufactured, packaged, and intended for administration to a patient in anaesthesia, therapy, or diagnosis.

Medicine:
(a) substance or combo of substances presented as having properties for treating or preventing disease in human beings; or
(b) substance or combo of substances which may be used in or administered to human beings either with a view to restoring, correcting or modifying physiological functions by exerting a pharmacological, immunological or metabolic action

Medical Device:
Instrument, apparatus, appliance, software, material etc, used alone or in combo, for the purpose of:
— diagnosis, prevention, monitoring, treatment or alleviation of disease,
— investigation, replacement or modification of the anatomy or of a physiological process,
— control of conception,
Doesn’t achieve its principal intended action pharmacological, immunological or metabolic means by itself

Homeopathic:
a medicinal product prepared from substances called homeopathic stocks in accordance with a homeopathic manufacturing procedure described by the European Pharmacopoeia.
Minute amounts of substances, which are dissolved, further diluted and mixed in a manner designed to activate their healing potential, while concomitantly eliminating side effects; which would arise from using the original substances.

Question 50

Administration consideration

Answer 50

Items for consideration:
Molecular properties of the drug
Physiological nature of the route
Patient Compliance
Onset of Action
Condition being treated
Systemic or local effect
Metabolism
Acid Drugs absorbed more rapidly from stomach
Basic drugs from the small intestine

Question 51

Route of administration

Answer 51

Oral – Local (antacids) & Systemic
Vaginal – Local
Topical – Local & systemic (transdermal)
Lipophilic drugs
Buccal – Fast onset, avoids first pass, needs high Log P
IV – Rapid onset, Aq Soluble forms
IM – Rapid onset, Lipid Soluble forms
Pulmonary/Respiratory – Local (lung)

Oral (Solid/Liquid):
Stomach:
Low blood supply
Low surface area
pH 1 -3
Enzyme and acid deg
Variable volume & residence time
Food interactions
First pass metabolism
Small Intestine:
Takes time to reach target area
High blood supply
High surface area
pH 7 -8
Enzyme Deg
First pass metabolism

IV:
By-passes anatomical barriers to absorption
In solution (already diss)
Enhanced & reproducible bioavailability
Rapid clinical response (bolus)
Sustained clinical response (infusion)
But:
Needs trained personnel
Patient discomfort
Risk (Drug toxicity)
Expensive

Rectal:
Avoids first pass metabolism
Not influenced by food or gastric emptying
Avoids pH change (stomach to intestine)
Avoids destructive gastric acid
Over comes issue with tablet taste
Alternative route where oral is not possible
Alternative route for drugs which cause GI irritation
Alternative for drugs unstable to enzymes in the GI
But
Absorbing area is smaller
Patient compliance issues

Liquids:
Ease of admin
Dosage adjustment
Reduced Irritation
But:
Difficult dosing
Stability
Taste
Preservation

Respiratory (inhalers)
Fast acting and site specific
Non invasive
Dose reduction potential (because of local effect)
Avoids first pass metabolism
Minimal side effects
But
Particle size critical
Patient compliance issues if inhaler not used properly
Only 15-30% of dose reaches target area (pMDI), even lower for DPI

Extravascular (subcut, intramuscular)
Maintain Therapeutic effect to specific point
Some can be used as a depot to give sustained release
Less trained personnel required
But:
Has an absorption phase
May have greater variation in clinical response
Limited injection volume