Pharmacology Flashcards
What is the process of drug development?
Lead compound identification Pre-clinical research in lab Filing for regulatory status Clinical trials on humans Marketing the drug Lecture 16/11/17
What is druggability?
The ability of a protein to bind small molecules with high affinity.
lecture 16/11/17
Give 4 examples of sources of drugs and an example from each.
Organic chemistry eg paracetamol
Plants eg opiates, vincristine for cancer
Elements eg platinum (cancer).
Animals, eg insulin
How do ‘magic bullets’ work?
Selective poisoning of microbes through a metabolic pathway that is absent in humans.
Give an example of a magic bullet and what it is used for.
Sulphanilamide for streptococcal infections.
Give an example of stereoisomers in pharmacology.
Levo- and dextro- amphetamine for ADHD.
What is a polyclonal antibody? Give an example.
Polyclonal antibodies are produced from a large number of B cell clones and respond to multiple epitopes. Rozrolimupab is a PAB used for ITP and Rhesus negative pregnant women.
What is a monoclonal antibody? Give an example.
Monoclonal antibodies are produced from one B cell clone and only respond to a specific epitope. Infliximab is a MAB used for inflammatory bowel disease.
Give 3 approaches to TNF-a neutralisation and an example of a drug for each.
- Chimeric antibody, eg infliximab
- fusion protein, eg etanercept
- Human antibody, eg adalimumab.
How does Infliximab work?
RA - chemical inhibition by extracellular neutralisation of TNF-a
How does Etanercept work?
Fuses to the TNF-a receptor, forming a ligand that antagonises the receptor.
How can shorter and longer acting insulin be produced?
Insulin is extracted from pig or cow pancreas. The amino acids are arranged differently in short and long acting insulin. Lecture 16/11/17
Give 3 examples of recombinant proteins as drugs.
Insulin
Erythropoietin
Growth hormone
What are glucocorticoids used for?
They are steroids used for a range of inflammatory conditions -
Ezcema, Asthma, IBD, arthritis, MS, acute vasculitis, autoimmune thrombocytopaenia.
Give 3 side-effects of glucocorticoids.
Diabetes, muscle wasting, osteoporosis.
Give 3 side effects of mineralocorticoids.
Hypertension, fluid retention, K/Ca loss.
How does methotrexate reduce cancer growth?
It interferes with DNA synthesis.
How does azothiaprine reduce cancer growth?
It interferes with DNA incorporation.
How does cyclophosphamide reduce cancer growth?
Interfered with DNA replication.
How do protein kinase inhibitors treat cancer?
Vemurafinib is an example. They inhibit formation of MAP kinase which normally increases proliferation and angiogenesis and decreases apoptosis, so it does the opposite.
How can gene therapy be used to treat pancreatitis caused by lipoprotein lipase deficiency?
Aliopgene Tiparvovec / glybera can be used to deliver an intact lipoprotein lipase gene. This is the most expensive.
If you wanted to get a drug into someone’s circulation quickly in hospital, what route of administration could you use?
IV.
Lecture 17/11/18
Where can you give medication to a fitting child who cannot take medication by mouth or IV?
Rectal - absorption of rectal veins is good
How is lithium absorbed into cells?
Facilitated diffusion through pores or ion channels. This is for small, lipid soluble molecules.
How are steroids absorbed into cells?
Passive diffusion through the cell membrane. This is for lipid soluble molecules.
How can larger proteins be absorbed into cells?
Pinocytosis - for endogenous macromolecules and recombinant therapeutic proteins.
Give 3 factors that affect absorption of drugs.
Drug structure, eg needs to be lipid soluble for gut absorption; only partially absorbed if highly polarised.
Drug formulation, eg slow-release/ enteric coating
Gastric emptying - slower if on antimuscarinics or eating, faster after some surgery eg sections of gut removed..
Explain first pass metabolism.
Drugs taken orally have to pass 4 major metabolic barriers to reach the circulation:
Intestinal lumen, intestinal wall, liver, lungs.
How are drugs metabolised in the intestinal lumen?
(First pass metabolism) - there are lots of enzymes in the intestinal lumen which metabolise drugs.
How are drugs metabolised in the intestinal wall?
There are MAO enzymes which metabolise drugs.
What type of drug is alendronate and how is it used?
It is a bisphosphonate. It inhibits osteoclast activity to treat osteoporosis. (drugs list)
What type of drug is atenolol and how is it used?
Atenolol is a selective beta blocker. It slows down the heart to reduce blood pressure and reduce the risk of CVD.
How is atracurium used?
Actracurium is a muscle relaxant which relaxes skeletal muscle during surgery.
Give the class, use and mechanism of Bendroflumethiazide.
Bendroflumethiazide is a thiazide diuretic, which treats hypertension by inhibiting sodium reabsorption at the distal convoluted tubule, causing water loss.
Give the class, use and mechanism of cefuroxime.
Cefuroxime is a cephalosporin antibiotic which is used to treat urinary and respiratory tract infections and haemophilus influenzae. It disrupts the synthesis of the peptidoglycan cell wall.
Give the class, use and mechanism of celecoxib.
Celecoxib is a COX-2 selective NSAID. It is used to treat inflammation and pain in rheumatoid arthritis and osteoporosis. It inhibits the transformation of arachidonic acid to prostaglandin precursors. Being selective for COX-2 over COX-1 reduces GI side-effects.
Give the class, use and mechanism of chloramphenicol.
Chloramphenicol is an antibiotic. It is a bacteriostatic by inhibiting peptidyl transferase activity to stop protein synthesis. It is used to treat cholera, meningitis, and conjunctivitis.
Give the class, use and mechanism of ciclosporin. Give 3 side-effects.
Ciclosporin is an immunosuppressant. It is used orally and IV for RA, Crohn’s disease and psoriasis. It lowers the T cell activity by inhibiting calcineurin, preventing transcription of IL-2.
Side effects include hypertension, headache and kidney problems.
Give the class, use, mechanism and a side-effect of ciprofloxacin.
Quinolone antibiotic
Treats upper UTIs and severe GI infections such as Shigella and campylobacter. Broad-spectrum, works on gram +ve and -ve. Inhibits DNA gyrase so cells can’t divide.
Can cause nausea, vomiting and rash.
Give the class, use and mechanism of co-amoxiclav.
Penicillin antibiotic
Amoxicillin + clavulanic acid. Amoxicillin is a b-lactam antibiotic and kills bacterial by attaching to their cell walls. Clavulanic acid is a b-lactamase inhibitor. Treats hospital acquired infections and intraabdominal sepsis such as H. pylori.
Give a main side effect of co-amoxiclav.
Diarrhoea, vomiting, allergic reactions.
Give the class, indications and mechanism of diamorphine.
= Heroin. Opioid analgesic.
Pain relief or opioid replacement therapy. When injected, it rapidly crosses the blood brain barrier and is deacetylated in the brain to form morphine, which binds to u-opioid receptors to relieve pain.
Give a side effect of diamorphine.
Respiratory depression, dry mouth, addiction.
Give the class, indications and mechanism of dalteparin.
Dalteparin is a low molecular weight heparin.
Treatment or prophylaxis of DVTs or pulmonary embolism. Often self-injected, they inhibit coagulation by binding to antithrombin, inhibiting factor X.
Give a side effect and contraindication of dalteparin apart from allergy (ALWAYS say allergy in exam for CI and SE).
Avoid if pt has active major bleeding
side effect - bleeding, increase in LFTs.
Dobutamine - class, use, mechanism?
beta-1 adrenergic agonist
heart failure, cardiogenic shock
direct stimulation of b-1 receptors of the nervous system, increasing contractility and cardiac output.
Dobutamine - CI and SE?
CI: use with caution if pt has AF.
SE: hypertension, angina, arrythmia, tachycardia
Doxazosin - Class, use, mechanism?
Alpha-1 selective alpha blocker.
Treats blood pressure and urinary retention following BPH.
Inhibits adrenaline, inhibiting vasoconstriction.
Alpha-1 blockers: CI and SE
Both: Allergy or hypersensitivity (WRITE THIS FOR EVERYTHING), including a-1 induced angioedema;
CI: orthostatic hypotension; severe hepatic impairment.
SE: hypotension and resulting weakness, dizziness; priapism due to blood trapping (not impotence as you might expect)
Ephedrine - class, use, mechanism
Adrenergic stimulant
Indirect stimulation of adrenergic receptor system by increasing noradrenaline activity at alpha- and beta-adrenergic receptors.
Used to prevent hypotension during spinal anaesthesia.
Ephedrine - CIs, SEs
CI: breastfeeding, Norephinephrine dopamine reuptake inhibitors (causes excess noradrenaline)
SEs: common - insomnia, anxiety, hypertension
serious but rarer - stroke, MI, abuse.
Erythromycin - class, use, mechanism
Macrolide antibiotic.
Used for resp and skin infections, severe pneumonia, and peptic ulcers.
Bacteriostatic - inhibits protein formation and therefore cell division.
Erythromycin - CIs, SEs
CIs - macrolide hypersensitivity. Interacts with drugs metabolised by P450.
SEs - abdominal cramps, nausea, vomiting, diarrhoea.
Ethinylestradiol - class, use, mechanism
Estrogen or estrogen receptor agonist
Used in birth control pills in combination with progestins to inhibit the surge in LH and FSH, stopping ovulation.
Ethinylestradiol - CIs and SEs
CIs - susceptibility to thrombosis, breast cancer.
SEs - breast tenderness and enlargement, headache, fluid retention. Blood clots are a rare but serious effect.
Furosemide - class, use, mechanism
Loop diuretic
Treats fluid retention and hypertension. Works by binding to the Cl transport channel, therefore inhibiting the luminal K-Na-Cl transporter in the loop of Henle and causing loss of K, Na and Cl in urine.
Taken IV or orally.
Furosemide - CIs and SEs
CIs - hypersensitivity, electrolyte imbalance.
SEs - orthostatic hypotension, tinnitus, and photosensitivity.
Ipratropium - class, use, mechanism
Muscarinic antagonist (a type of anticholinergic)
Bronchodilator in asthma and COPD.
Inhaled or nebulised.
Works by blockingmuscarinic acetylcholine receptors, which promotes degradation of cGMP, leading to smooth muscle relaxation, inhibited bronchoconstriction and mucus production.
Ipratropium = IsoPRopyl + ATROPIne.
Ipratropium - CIs and SEs
CIs: Atropine hypersensitivity. Oral admin: glaucoma, GI/urinary obstructions.
SEs: inflammation of airways, dry mouth, cough, urinary retention - think about if pt has prostatic hypertrophy.
Loperamide - class, use, mechanism
Opioid receptor agonist. AKA imodium.
Decreases frequency of diarrhoea, used in gastroenteritis, IBD, and short bowel syndrome.
Taken orally. Acts of u-opioid receptors of large intestine, decreasing muscle tone and slowing contractions of the intestines so more water can be absorbed.
Loperamide - CIs and SEs
Not recommended if blood in stool or high fever. Not used in C. diff infections as it increases risk of toxin retention. Always think about risk of toxic megacolon.
Causes abdo pain, constipation, sleepiness, and vomiting.
