MedChem Basics Flashcards

Question

Parasympathetic

Answer 1

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

Answer 2

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

Answer 3

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

Answer 4

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)

Answer 5

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.

Answer 6

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

Answer 7

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

Answer 8

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

Answer 9

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

Answer 10

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.

Answer 11

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

Answer 12

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.

Answer 13

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

Answer 14

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

Answer 15

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

Answer 16

effective dose of drug Potent drug = effective in low conc

Answer 17

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

Answer 18

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

Answer 19

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.

Answer 20

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-1 and COX-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 as aspirin, ibuprofen, naproxen and diclofenac being 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 as omeprazole to reduce the risk of causing gastrointestinal ulceration and bleeding.

Answer 21

Ion channels are 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 the electrical 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 it chemical 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

Answer 22

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 of kidney disease due to high blood pressure or diabetes is slowed.

Answer 23

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)

Answer 24

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)

Answer 25

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.

Answer 26

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

Answer 27

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