PHAR2210 Drug Encyclopaedia

A little birdie (*cough*ConfessionsatUWA*cough*) told me that apparently last year's exam had a lot of very specific questions relating to drugs mentioned throughout the lectures, even if they had a minor mention on a random slide somewhere. This is my attempt to summarise all of the drugs that were covered in order to make revision a little easier. I will also include certain substances that are naturally produced by the body (hormone etc.), biologically-active substances that aren't used as drugs but were covered in the lectures due to toxicity or whatever, and general classes of drugs.

(Note: The unit coordinator raised concerns that I may have made some of you guys unnecessarily worried about the exam. So I guess you should just use this as a guide and not as something you need to stress out about? I'm actually the biggest stress-head, so maybe I shouldn't be giving advice on how to handle exam stress. Okay, I'm going to shut up now.)

Drug Name	Lecture(s)	Important Information
Acetylcholine	12, 13	Neurotransmitter mainly involved in pre-postganglionic cell junctions and in the parasympathetic nervous system. Activates nicotinic receptors (Na+ channels) Activates muscarinic receptors (G-protein-coupled) Muscarinic receptors activate Gαq, which cleaves phosphatidylinositol 4,5-bisphosphate into inositol 1,4,5-trisphosphate and diacylglycerol Inositol 1,4,5-trisphosphate stimulates release of Ca2+ and its binding to calmodulin; diacylglycerol activates protein kinase C. These pathways lead to bronchoconstriction
Acrolein	7	Found in cigarette smoke Very electrophilic and very toxic
Acyclovir	19	Purine (deoxyguanosine) analogue inhibitor of DNA synthesis Prodrug- must be activated by viral thymidine kinase and other cellular kinases Active against herpes viruses
Adrenaline	10	Naturally-occurring R-adrenaline interacts strongly with β-adrenoceptor Synthetic-only S-adrenaline interacts only weakly with β-adrenoceptor Activates β-adrenoceptors on cardiac cells to increase contractility
Aminoglycaside (class)	18	Bacterial protein synthesis inhibitor Examples: streptomycin, gentamicin Poor oral absorption due to positive charges, serious side effects including ototoxicity, hearing loss, nephrotoxicity Bind to decoding site on 30S ribosome, causing misreading of mRNA and insertion of the wrong amino acid
Amphetamine	12	CNS stimulant Uses noradrenaline transporter to enter nerve terminals Replaces noradrenaline and serotonin
Amphotericin	20	Polyene antifungal Poor oral absorption Renal toxicity with IV dosing Binds to ergosterol and creates pores through which essential ions can leak out
Artemisinin	1	340AD: Ge Hong used Sweet Annie to alleviate fever 1596: Li Shizhen used it to treat malarial fever 1970s: Artemisinin isolated 1980s/90s: Soluble derivatives synthesised 2015: Tu Youyou won a Nobel Prize for helping to isolate artemisinin Used to treat malaria
Aspirin	1, 9	Nonsteroidal anti-inflammatory drug (NSAID) ~200AD: Willow bark used as an analgesic 1763: Antipyretic effects of willow bark reported by Rev E Stone 1828: Büchner isolated pure salicin 1879: Bayer started industrial synthesis of aspirin Serious problems with gastric injury with long-term use Inhibits COX-1 and COX-2. COX-1 necessary for formation of prostaglandins via arachidonic acid
Atropine	1	1831: Mein isolated atropine from belladonna 1867: Atropine shown to block cardiac vagal stimulation Atropine blocks muscarinic acetylcholine receptors
Azathioprine	22-1	Used to treat leukaemia and inflammation Metabolises to form 6-mercaptopurine (6-MP), a guanine analogue that inhibits DNA synthesis and thus reduces production of leukocytes Can also be metabolised by xanthine oxidase to form thiouric acid (inactive) Can also be metabolised by thiopurine methyl transferase (TPMT) to form an inactive metabolite. TPMT activity may differ from individual to individual
Azidothymidine (AZT)	19	First anti-HIV drug NRTI Good oral bioavailability and well-distributed Toxic effects: granulocytopenia, anaemia etc.
Azoles (class)	20	Synthetic antifungals Imidazoles (older) and triazoles (newer) Examples: miconazole, voriconazole, itraconazole Block 14-α-sterol demethylase, which converts lanosterol to ergosterol, causing ergosterol depletion and membrane dysfunction
Benzene	6	Chronic exposure: leukaemia, bone marrow toxicity Acute exposure: CNS depression
Benzodiazepine (class)	12	Some members, such as diazepam (Valium), are anxiolytics Modulators- enhance the opening of GABA-activated Cl- channels
Carbamazepine	3	Induces its own metabolism Half-life drops from 36h to 2h after 2 weeks This is due to induction of CYP3A4
Carbapenem (class)	18	β-lactam that blocks cell wall synthesis Names all end with -penem
Celecoxib	9	COX-2 blocker Causes fewer gastric ulcers than nonselective NSAIDs
Cephalosporin (class)	18	β-lactam that blocks cell wall synthesis Names all begin with cef- 1948- Bacterial source (Cephalosporium acremonium) found in Sardinian sewer There are first-, second-, third- and fourth-gen cephalosporins, differing in activity toward Gram-positive and Gram-negative bacteria
Chloramphenicol	18	Bacterial protein synthesis inhibitor useful against typhus and other severe infections Bind to 50S ribosomal subunit and prevent peptide bond formation Toxic to mitochondria, severely toxic to bone marrow, fatal to neonates due to limited glucuronidation capacity
Cimetidine	4	Suppresses active secretion of organic cations
Clavulanic acid	18	Irreversibly inhibits β-lactamases
Clozapine	3	Half-life decreased in smokers due to CYP450 induction
Cobicistat	3	"Pharmacokinetic enhancer"- inhibits CYP450, slows down metabolism of other drugs Found in Stribild
Codeine	3, (4)	Used to treat mild to moderate pain Codeine is non-analgesic, but it is metabolised to the analgesics morphine and morphine-6-glucuronide Metabolised by CYP2D6 (blocked by fluoxetine) (Morphine may undergo enterohepatic recirculation)
Colistin	17, 18	Polymixin "drug of last resort" used to treat antibiotic-resistant bacteria Poor oral absorption, toxicity issues Acts as a cationic detergent to disrupt cell membranes Best antibiotic against carbapenem-resistant NDM-1 Resistance to colistin by Mcr-1 reported in China in 2015 Mcr-1 encodes a phosphoethanolamine transferase which may alter the lipopolysaccharides in bacterial cell membranes, decreasing affinity for polymixins
Cortisone	12	Powerful anti-inflammatory glucacorticoid
Debrisoquine	3	A heart drug that is a CYP2D6 substrate
Deutetrabenazine	3	Used to treat Huntington's Chorea Replaced H-atoms on tetrabenzine's methyl groups with deuterium (D) Deuterium slows down hepatic metabolism (as opposed to tetrabenzine)
Dexamethasone	12	Powerful anti-inflammatory glucacorticoid
Didanosine	19	Purine analogue inhibitor of DNA synthesis
Diethylstilbesterol (DES)	6	Used to prevent miscarriages Caused vaginal and uterine tumours in female offspring
Diphenhydramine	11	Decongestant Binds to histamine receptors on vascular smooth muscle cells, causing decongestion Also binds to muscarinic acetylcholine receptors on salivary glands, causing dry mouth
Echinocandins (class)	20	Antifungal agents. Safer than amphotericin, but narrower spectrum Example: capsofungin Inhibit 1,3-β-D-glucan synthase, blocking synthesis of 1,3-β-D-glucan and thus altering membrane permeability
Enalapril	2	Lowers blood pressure Ethyl group cleaved off by hepatic esterases Becomes its active form: enalaprilat
Enflurane	10	Volatile inhalational anaesthetic agent used in surgery Racemic R-enantiomer undergoes oxidation by CYP2E1, eventually converted to an achiral metabolite
Esomeprazole	10	Pure S-enantiomer of omeprazole
Ethanol	7, 8	Inhibits CYP2E1 Inhibits bioactivation of paracetamol into NAPQI Can cause fetal alcohol syndrome if used in pregancy. FAS Triad: growth retardation, low IQ, craniofacial abnormalities Meconium markers of foetal alcohol exposure include ethyl-glucuronide, ethyl-sulfate and fatty acid ethyl esters Can also cause ARND (Alcohol-Related Neurodevelopmental Disorders)- CNS impairment in offspring not displaying structural FAS symptoms
Fluorouracil	12	Anti-cancer drug that blocks DNA synthesis Acts as a false substrate, replacing uracil in purine biosynthesis Cannot be converted to thymidylate, blocking DNA synthesis
Fluoxetine	1, 3, 12	Antidepressant (SSRI) Inhibits serotonin reuptake Inhibits CYP2D6 Blocks formation of morphine and morphine-6-G from codeine
GABA (γ-aminobutyric acid)	13	Formed from glutamate in the brain Inhibitory in many CNS pathways Receptors: GABAA and GABAC are ion-channels; GABAB is G-protein-coupled
Glucocorticoid (family)	16	Binds to glucocorticoid receptor, causing dimerisation, dissociation from heat-shock proteins and translocation into the nucleus Once in nucleus: increases gene expression by binding to GRE (glucocorticoid response element), decreases gene expression by binding to nGRE (negative glucocorticoid response element) or has other effects through binding to NFκB
Glutamate	13	Fast-acting. Excitatory in CNS
Glycine	13	Inhibitory in spinal cord Antagonised by strychnine
HIV Protease Inhibitors (class)	19	Inhibit HIV Protease Examples: saquinavir, ritonavir, atazanavir Very effective at reducing viral loads Side effects: gastrointestinal problems, drug interactions, increased risk of heart disease
Ibuprofen	10	NSAID S-ibuprofen is the active stereoisomer: marketed as dexibuprofen in Europe
Imipramine	5	High volume of distribution
Insulin	12, 15, 21	Reduces blood glucose levels Causes glucose channels (GLUT4) to become embedded in the cell membrane, allowing the cells to take up more glucose 3 main pathways, all via IRS (insulin receptor substrate). APS/c-CBL/CAP-mediated pathway creates a targeting site for GLUT4 in cell membrane. IRS/PI3K/Akt-mediated pathway exocytoses GLUT4 storage vesicles (GSVs) and thus embeds GLUT4 into the cell membrane. There is also a long-term pathway: Ras/Raf/Mek/MAP Kinase -> Transcription Factors Excessive insulin can cause hypoglycaemia (Type A ADR)
Isoniazid	17	Narrow-spectrum antibiotic used to treat tuberculosis
Ketamine	10	S-enantiomer has strongest anaesthesia activity and fewer side-effects R-enantiomer associated with psychosis, agitation and amnesia
Lumiracoxib	7, 9	COX-2 selective NSAID Banned in Australia due to 8 serious cases of hepatotoxicity It is simply Diclofenac (a drug that nonselectively inhibits COX-1 and COX-2) with an extra methyl group
Lenalidomide	8	Thalidomide analogue used to treat multiple myeloma
Macrolide (class)	18	Broad-spectrum bacteriostatic drug Examples: erythromycin Binds to 50S ribosomal subunit, plugging the "ribosomal tunnel" and preventing transfer of tRNA from A site to P site Gastrointestinal side effects common, risk of cardiotoxicity
Meperidine (MPPP)	7	Street drug Can cause Parkinson's-like symptoms if contaminated by MPTP MPTP crosses blood-brain barrier and is activated by MAO-B in astrocytes to form MPP+ MPP+ accumulates in dopaminergic neurons, promotes redistribution of dopamine, forms reactive oxygen species, inhibits electron transport chain
Methoxychlor	10	Organic pesticide Originally achiral, but undergoes CYP-catalysed oxidative O-demethylation (i.e. oxygen loses -CH3 group). Results mainly in S-hydroxy metabolite
Mianserin	10	Antidepressant Racemic- each stereoisomer undergoes a different metabolic pathway Chiral centre not altered by metabolism
NNRTI (class)	19	Non-Nucleotide Reverse Transcription Inhibitors Examples: efavirenz, delavirdine etc.
Nystatin	20	First antifungal Discovered by Hazen and Brown Polyene- similar mechanism to amphotericin B (amphotericin is better)
Omeprazole	10	Proton pump inhibitor Reduces gastric acidity and heartburn Racemic mixture
Pancuronium	12, 13	Produces paralysis during anaesthesia Antagonises nicotinic acetylcholine receptors (Na+ channels) Competitive antagonist
Paracetamol/ acetaminophen	7, 12	Over-the-counter analagesic Inhibits cyclooxygenase Intrinsic hepatotoxicant Undergoes sulfation, glucuronidation and bioactivation Bioactivated via CYP2E1, CYP3A4 and CYP1A2 to form NAPQI (toxic metabolite) NAPQI can be trapped by glutathione Glutathione can be replenished by N-acetylcysteine
Penicillin	17, 18	Antibiotic Fleming fround that Penicillum mould inhibited bacterial growth Florey pioneered clinical testing of penicillin β-lactam that blocks cell wall synthesis Can isomerise to form penicilloic acid, creating a novel antigen that triggers an antibody response in susceptible individuals
Phenylephrine	11	Binds to α-adrenoceptors in vascular smooth muscle cells Causes vasoconstriction, relieving nasocongestion Binds only weakly to other receptors, so unlikely to produce adverse effects
Phenytoin	8	Treats epilepsy Risk of "foetal hydantoin syndrome" if used in pregnancy- involves craniofacial and heart malformations, low birth weight, mental deficits Bioactivated by CYP450 to form a reactive epoxide- detoxified by epoxide hydrolase to form nontoxic diol metabolite Bioactivated by fetal peroxidases to form phenytoin hydroperoxide- blocked by antioxidants
Prednisolone	12	Powerful anti-inflammatory glucacorticoid
Probenecid	4	Suppresses active secretion of organic anions
Prontosil	17	Sulfonamide Found to be bacteriostatic by Domagk
Salbutamol	11, 14	Used to treat asthma Interacts with β2-adrenoceptors, releases Gαs and thus activates adenylate cyclase. This converts ATP into cAMP cAMP activates cAMP-dependent protein kinase A Causes bronchodilation
Salvarsan	17	Introduced by Ehrlich Used to treat syphilis
Serotonin (5-hydroxytryptamine)	13	Many actions- increase gastrointestinal mobility, vasodilation, platelet aggregation
Sparteine	3	A heart drug that is a CYP2D6 substrate
Stribild	3	A cocktail of anti-HIV drugs Contains "pharmacokinetic enhaner" cobicistat (CYP inhibitor that slows down the metabolism of other HIV drugs) Only needs to be taken once daily
Strychnine	13	Antagonises glycine Causes convulsions and muscle contraction
Suxamethonium	13	Short-acting muscle relaxant used in short surgical procedures Binds to a ligand-gated ion channel, keeping it open Prevents repetitive depolarisations and thus sustained muscle contraction from occurring
Tetracycline (class)	17, 18	Broad-spectrum antibiotics Prevent aminoacyl-tRNA from binding to A site Poor oral absorption, toxicity includes irritation of the GI tract, hyperpigmentation, staining of teeth etc.
Thalidomide	8, 10	1956: Used to treat nausea and insomnia in pregnancy Well-tolerated in mothers, but led to a large increase in rare limb malformations (amelia: no limbs, phocomelia: shortened long bones) Many theories surrounding mechanism for teratogenicity One such theory is chiral toxicity- however, not much experimental data to support this
Theophylline	3	Half-life decreased in smokers due to CYP450 induction
Thiopental	2	Very lipophilic
Tri-o-cresylphosphate (TOCP)	6	Plasticiser used in varnishes, lubricants etc. Has anticholinesterase activity 1 week following exposure: delayed neuropathy syndrome
Valproate	9	Anticonvulsant Hepatotoxic and teratogenic Teratogenicity possibly through inhibition of histone deacetylase enzymes (HDACs) which regulate chromatin remodelling Antiepileptic properties maintained over a range of structural changes, hence valproate analogues are being investigated to reduce teratogenicity
Warfarin	2, 5	99% protein-bound Low volume of distribution