Selec%vity of Binding: Chemical structure, molecular size, electrical charge: is all reciprocal Originator VS generic: generic is a copy the

generic: generic is a copy the same as the originator, most have bioequivalence (small molecule:
Drug Receptor Interac%ons Possibili%es: affinity (ability of drug to bind to receptor), antagonist (drug may fit receptor but changed manufacturing process with same product, chemical synthesis, biologicals: manufactured in living
not open it; affinity but no efficacy, low affinity), agonist (drug fits receptor and has an effect, triggers intracellular process, system), original goes through full R&D process, determining factors: dosage form, intended use,
receives a response, affinity and efficacy). pharmacokineDcs
How well a drug works depends on: how well it binds to a receptor, Beta blockers: propranolol (reducing exercise induced angina aQacks, non-selecDve antagonist, crosses BBB, B1
how well it activates the receptor to produce a stimulus, and then a response and B2 blocker – induce asthma), atenolol (modified prop, B1 selecDve adrenoceptor antagonist, low lipid
Antagonists: compe%%ve (reversed if bonds are weak, occupies orthosteric site), solubility, anDhypertensive / anDanginal agent), inhibit the acDon of the stress hormone on beta receptors
non-compe%%ve (binds to allosteric site), reversible (more potent if lower Plant-based Venoms + Marine based Animal Mineral-based Microorgani
concentraCon needed to produce EC, efficacy the same if there is no change in toxins based sm based
maximum, blue more potent than purple, right shiFs of the agonist CR curve, alkaloids proteins, Cone snails Hormones Antacids Fungi
cannot say without a change in max response, used for overdose reversal, (nitrogen polypepDdes, (venoms contain (insulin from (aluminium (anDbioDcs:
symptomaCc relief, allergies), irreversible (decrease in efficacy containing enzymes + free conotoxins, ion pigs + cows, hydroxide, penicillin,
and maximum, cancer, chemo, HIV) compound, acids, channel toxins oestrogen calcium staDns, ergot
Antagonism: physiological (have opposing effects but not working at the same morphine, neurotoxic cause paralysis), from urine of carbonate), iron derivates),
receptor e.g. contraction VS relaxation of a blood vessel), chemical (e.g. antacid atropine, (paralysis, NMJ, ziconoDde pregnant deficiency bacteria
inactivates another chemical), pharmacokinetic (affects concentrations at the quinine), resp failure), (novel non- cows), anaemia (anDbioDcs:
target site), allosteric (binds to different site on receptor to affect ligand binding or stimulation of second messengers) glycosides hemotoxic opioid, 10,000 heparin (ferrous tetracycline,
state if a parallel shift is observed, the direction, max response (only if adding higher dose doesn’t produce a larger (sugar and (coagulaDon, more potent (anDcoagula sulphate), chloramphen
response) and potency non-sugar bleeding), than morphine) nt from thyroid icol)
moity), captopril bovine lungs disorders
opioids (envenomaDon + pig (iodine)
(>40 decreases BP, intesDne)
morphine + treats
codeine hypertension).
alkaloids),
aspirin (WT,
salcilin),
poppy
plant)
paclitaxel
(anD-
cancer)
Pharmacokinetics: what the body does to the drug, pharmacodynamics: what the drug does to the body Synthesis scale up: screening <1mg, preclin g, clin trials kg
CRCs: increase drug concentration = increased response, more response at lower concentration = increased potency, MarkeDng: approved by TGA, scheduling, entered onto ARTG
increased max response = higher efficacy Access: markeDng approval, data base entry on TGA, scheduling
Bioavailability: proportion of drug that reaches the systemic circulation as intact after administration Undesirable effects: 1961 thalidomide disaster (fetal abnormaliDes, now treats leprosy but not in women with
Vd = dose / [drug in plasma] Roaccutane or on contracepDon), clioquinol (for Alzheimer’s, issues with synthesis), ACVI-conotoxin (for
Vd = volume / kg OR volume / 70kg neuropathic pain, didn’t block N)
PBAC submission
SecDon 1 SecDon 2 SecDon 3 SecDon 4
Disease area + main clinical evaluaDon, trial Economic model, Pricing + uDlisaDon
comparator, context, data translaDon, cost
advantages of new effecDveness
medicine
ARTG: low level risk = listed (comp meds, unscheduled meds, AUST L number), high level risk = registered
(prescripDon, most OTCs, AUST R number)
Phases of clin trials: if successful proceed to clinical trials with human parDcipants.
Phase I: 50-100 Phase II: 200-400 Phase III: >3000 Phase IV
First administraDon of first trials in small Extended + extensive Post markeDng studies,
drug to small pop. Side select group with clinical trials with long further examinaDon of
effects, establish disorder, determine paDent numbers, sites effects on specific
zero order elimina%on kine%cs: same amount of drug removed per hour (excreCon of drug < entry of drug; reaches dosing schedule, safety + efficacy, + invesDgators, paramaters and
toxicity), linear pharmacokineDc therapeuDc range, max extensive safety + comparator studies.
1st order elimina%on kine%cs: constant proporCon removed from body with Cme e.g. 50% every 3 hours, exponenCal profiles established. tolerated dose, efficacy data, long- Once drug has high
First pass metabolism: drug metabolised establish 10 end points term tolerance / drug safety, efficacy and
by liver before reaches circulaCon, interacDons info gained quality TGA
effect of drug on body reduces, registraDon occurs for
Pro drugs: require metabolism 1-2 years
by liver to work AUST L: evaluated for quality and safety, cannot make therapeuDc claims
Factors influencing drug AUST R: evaluated for quality, safety and efficacy, can only make therapeuDc claims to pracDDoners
distribu%on: size, lipophilicity
(more soluble = easily move),
degree of ionisaCon
Binding of drugs to plasma proteins:
drugs can’t interact with target but aren’t
filtered by the kidneys, increased duraCon
but decreased effecCveness
How the SNS transmits signals:
The preganglionic neuron releases ACh onto
N receptors of the postganglionic
neuron, which then releases NA onto
adrenergic receptors of the target organ.
Myasthenia Gravis: Destroys ACh receptors at
skeletal muscle, treatment: increase binding of
ACh to receptor, rely on the bodies producDon
of ACh before introducing drugs
PD: Neurological disorder with impaired voluntary
movements; decrease in the levels of dopamine in BG and SN, treatment: L-DOPA - crosses BBB, converted to D in
periphery, forms NOAD and AD
Schizophrenia: excessive dopamine acDvity in ML and MF cortex, treatment: decrease dopamine acDvity, levels and
synthesis or antagonize the dopamine receptor
Determining if a drug is working pre or post juncDonally: drug works at mulDple sites of acDon within the NT, can either:
Inhibit the producDon / release of neurotransmiQer at the pre-synapDc terminal = pre-synapDcally acDng, inhibit the post-
synapDc terminal: add antagonists which will bind and inhibit receptors on the post-juncDon, Destroy whatever organ
downstream of it is, difference in response to various sDmuli based on the drug you use, Can add drugs that inhibit the
release of neurotransmiQer, inhibit the receptor or destroy the organ: Helps determine if the drug is working pre- Direct harm (adverse paDent / client outcomes), Drugs are regulated by dose +
juncDonally or post-juncDonally indirect harm (results from delay of treatment ingredient
PBS: Gives access to prescripCon medicine in a Cmely, affordable and reliable way. Reduced price, affordable access, market implementaDon), economic harm S4 and S8 can only be adverDsed to
access (consistent demand, subsidizaCon), incenCve for innovaCon, compeCCve advantage (aUracCveness, reduced cost), (encouragement towards spending money pracDDoners via self-regulaDon
compeCCve edge, revenue generaCon, investors. Ipilimumab for melanoma would cost $30,000 per infusion. on unnecessary meds without awareness: S3 can be adverDsed within appendix H
Pharmacoeconomic analysis performed prior to addiCon of drugs to use cost-minimisaCon approach to determine if the open seen in comp meds) Can only be adverDsed for approval
drug is cost-effecCve. Safety (harm/adverse risk), efficacy indicaDons but not therapeuDc claims
Pre-clinical drug development (does the drug do what it’s supposed to?), Can prompt consumer to visit GP for a
Quality quality (is the manufacturing done according product
ComposiDon, excipients (masks taste), enteric coaDng (prevents degradaDon), synthesis scale. Chemical
characterizaDon. AcDve form developed into final dosage. Biological characterisaDon via modelling a to GMP?)
disease stated in vivo highlights potenDal cellular effects, off target effects and toxicity. Serendipity Chemical Mod RaDonal Design Screening
Efficacy Proof of concept (in vitro, in vivo). Cellular effects, off target effects, model disease state in animals (1 Accidental / coincidental Modifying exisDng drug Knowledge of the Analysis via mass
rodent, 1 non-rodent). Warfarin (rat poison, structures; isomers of target and ligand to assays, acDve hite
Safety Must meet toxicology requirements. Does the drug do what it is meant to? How does it affect the body? suicide, thrombosis) chemicals funcDon create compound Paclitaxel, bark from
Natural compounds: Widely contribute to therapeuDcs, 50% of drugs, capacity of plants, microorganisms, insects and Cis-plaDn, e. coli, mice differently BB pronethalol to Pacific Yew, anD-
higher animals to manipulate simple building blocks into enormous structural array of small ‘drug like’ molecules (secondary tumours, 20% remission Synthesis of treat high HR and cancer
metabolites). More efficient + cheaper than pharmaceuDcals. Enhance producers chances of survival defensively (plants) and Penicillin when sulphonamide from angina; synthesised
offensively (snakes and spiders). E.g. poppy plant, tyrosine into morphine. staphylococcus was lep prontosil, which then with NA and A to
Sildenafil: orally acCve, enhance erecCle response, metabolized by CYP enzymes, contraindicated if taking nitrates. in petri dish; mould lead to the creaDon of create a mimeDc that
Side effects: related to vasodilaCon elsewhere, hypotension, flushing, nasal congesCon, visual disturbances (targets PDE-5 grew around bacteria; other diureDc drugs and antagonised beta
in the eye), ventricular tachycardia anDbacterial effects carbutamide to treat adrenoreceptors to
Surrogate endpoints: lab measurement or physical sign used as a subsCtute for a clinically meaningful endpoint. Used to which prevented the heart failure. prevent SNS acDvity.
reduce cost + duraCon of clinical trials, useful in phase II but not phase III. E.g. lower BP in CV trials, tumor shrinkage, division of gram posiDve Propranolol, oxy link
increased CD4 cells in HIV/AIDS. bacteria. to produce more
Blood pressure (BP) = Cardiac Output (CO) x Total peripheral Resistance (TPR) potent ant, less lipid
Drug discovery: idenDfy potenDal target site, synthesise drug, determine MoA. Chemists using different methods to soluble; B1 atenolol,
synthesize the drug (RDD). Quality considered. anDhype, anDanginal
Biosimilars: relate to similar biological products
Pharmacodynamic tolerance: habituaCon or adaptaCon, taking same dosage of drug overCme decreases response,
Pharmacokine%c tolerance: body has more efficient metabolism / removal of drug COC
(oestrogen, progestogen
(progesterone +
testosterone))
Advantages No ovulaCon (lighter
periods, regular cycles,
reduced dysmenorrhea,
reduced blood loss,
reduced premenstrual
tension), suppression of
ovarian cysts + endo,
protect against endo +
ovarian cancer
Disadvantages AUributable to
progesterone (weight
gain, nausea, dizziness,
depression), aUributable
to oestrogen and maybe
progestogen (CV
complicaCons: deep vein
thrombosis, pulmonary
embolism), aUributable
to oestrogen (growth of
cancer cells, migraines,
decreased lactaCon)
Mechanism Increased progesterone
and O reduce FSH and
LH from AP, decreased
ovulaCon and
endometrial lining,
increase cervical mucus
Use 28 days, 7 inacCve
tablets, higher efficacy
POP Injectables and implants
2nd generaCon High progesterone
levonorgestrel concentraCon
Avoid adverse effects of Same mechanism of
oestrogen if lactaCng acCon as COCs, reliable
No adverse effect on inhibiCon of ovulaCon,
blood coagulaCon (no very effecCve
risk of DVT)
Headache, bloaCng, Can’t withdraw,
weight gain, unreliable menstrual chaos,
inhibiCon of ovulaCon delayed return of
ferClity, weight gain,
increased osteoporosis
Increased progesterone Increased progesterone
triggers variaCon in FSH levels reduce FSH and LH
and LH levels (decrease from anterior pituitary,
endometrial lining, decreased ovulaCon and
increase cervical mucus endometrial lining,
thickness) increase cervical mucus
Lower efficacy, must be More reliable than POP,
compensated with 3 increase progesterone
hours of missing dose

Fourier-transform Mass spectroscopy (MS) Paper spray MS Direct analysis in real

infrared spectroscopy time (DART) MS
(FTIR)
Compares samples to Gold standard, most Detects substances low Ionising radiation to
existing chemical accurate, not used in concentrations that separate it into
spectra, automatically portably, large FTIR can’t e.g. fentanyl, fragments which is
matched to closest equipment etizolam interpreted via MS
documented spectra, Portable, used for
low matches = festivals
meaningless, pure Efficient and accurate
samples >750/1000

5-HT (serotonin)
Storage High concentraDons in
intesDnal wall (increase
moDlity), blood platelets
(increase aggregaDon) and
brain (appeDte, mood,
vomiDng)
Response (SoA) Lungs: bronchoconstricDon
Blood vessels:
vasoconstricDon and
vasodilaDon
Platelets: increase
aggregaDon
GIT: increase moDlity
Sensory nerve: excitaDon
CNS: nausea, increase
mood, appeDte
Clinical Use SSRIs: Prozac blocks
sertraline and increases
5HT in clep, treats
depression
Nitric Oxide Histamine
Biologically acDve gas, High concentraDon in
important mediator in lungs, skin, GIT
vasculature and In mast cells
macrophages, NeurotransmiQer in CNS
neurotransmiQer (PNS + (histaminergic neuron);
CNS, nitrergic neurons), hisDdine converted
synthesized on demand
Blood vessels Lungs
(vasodilaDon), platelets (bronchoconstricDon),
(decrease aggregaDon), blood vessels (increased
macrophages (host vascular permeability),
defence, inducible form, stomach (increased
produced in response to gastric acid secreDon),
sDmuli) GIT (increased moDlity),
sensory nerve
(excitaDon), CNS
(nausea,
arousal/wakefulness)
Angina, pulmonary PepDc ulcers (receptor
hypertension antagonists inhibit
VasodilaDon decrease gastric acid secreDon),
HR ansd BP allergic reacDons (anD-
histamine decreases
vasodilaDon and
vascular permeability,
crosses BBB,
drowsiness)
Opioids Act on cells adjacent to dopamine (stops cells from braking dopamine release, by acCvaCng
receptor the cell releases dopamine). Strongly rewarding (posiCve enforcing behaviour,
psychological dependence, indirect effect on reward + dopamine). Pre-synapCc agonists at mu
opioid receptor; inhibit release of ACh, prevent interacCon with M, induce muscle contracCon.
Naloxone antagonises the MOR, promotes release of ACh from parasympatheCc nerves, binds
to M ron GI smooth muscle to promote peristalsis.
Codeine: weaker potency, minor pain, less likely to cause physical addicCon
Benzos and Benzos: physical dependence associated with changes in GABA receptor acCvaCon in the CNS
alcohol leading to pharmacodynamic tolerance. Target the y-amino butyric acid GABA receptor via
acCvaCon of GABA receptor.
Alcohol: increases GABA receptor funcCon, induced conformaConal change to the receptor
(indirectly inhibits GABA and glutamate and creates influx of chloride ions). Contributes to
hyperpolarisaCon of the neuron, enhances inhibitory effect of GABA, making neuron less
responsive. Sense of well-being, anC-aniety, sedaCves and anC-epilepCc
Cocaine Blocks dopamine uptake, acCvates receptors for long and increases dopamine, compeCCve
inhibitor of DAT (interacts with transporters of NA and 5HT), increases biophase levels of
dopamine, acCvates 5H3 receptors
Amphetamine Increase dopamine in synapse (enters nerve terminal, displaces dopamine from vesicles,
moves out into the nerves), indirectly acCng sympathomimeCc, enters never terminal DAT,
reversal of normal transported, release other monoamines. Releases noradrenaline and 5HT,
increases HT
LSD SelecCvely acCvates brain 5HT receptors, antagonists treat schizophrenia.
MDMA Transient release of dopamine and 5HT reuptake, direct acCvaCon of 5HT receptors, induces
state of emoConal and sensory awareness
Ketamine Blocks glutamate receptors, acCng within channel of glutamate ion pore. Site within the
receptor to prevent Ca2+ from releasing. Strong psychological dependence.
Cannabis THC9: strong affinity for CB1 over CB2, cannabinol binds to C2: acts at periphery; lil’ addicCve
Cannabidiol doesn’t have the same psychoacCve effects
SyntheCc cannabinoids: full agonists of CB1 (much stronger)

Lab 1 Lab 2 Lab 3

Guinea pig ileum; longitudinal GastrointesCnal smooth muscle Biventer cervicis nerve-muscle;
smooth muscle. Rightward shiF of Naloxone is an antagonist for the tubo used to ensure that the
HA in presence of antagonist. No mu-opioid receptor (inhibits nerve is being sCmulated. Tissue
decrease in potency: antagonist agonist acCon on smooth muscle responded to exogenous CCh in
does not inhibit acCvity at the twitch). It has reduced potency presence of venom. Venom
muscarinic receptors and efficacy. caused direct skeletal muscle
Codeine added = decrease in TR to paralysis, no ACh released.
electrical sCmulaCon ConcentraCon at cervices caused
ContracCle response to addiCon of by CCh antagonised by tubo
histamine mediated by H TransmiUer causing twitches is
receptors ACh, acCng via acCvaCon of N
Muscarinic and histamine receptors
receptors = longitudinal smooth Inhibit response to ES, no effect
muscle on log CRC to CCh = inhibiCon of
ResCng tension 1g transmiUer release
PharmacokineDc tolerance: body’s reduced response to a drug
TransmiUer released by Tubo acts post-synapCcally as an
aper prolonged use e.g. reduced effecDveness of benzos in sCmulaCon = ACh, subtype of antagonist on N ACh receptors to
reducing anxiety
receptor mediaCng response is M induce muscle relaxaCon, inhibit
TherapeuDc index: raDo of a drug’s efficacy to its toxicity,
Tolerance to an opiate agonist = opening of Na+ channels
narrow = precise dosing
TR inhibited by high dose of
Mediators of biphasic aQack: histamine, leukotrienes,
morphine, increase gradually
prstaglandin
Big pharma: development of biologicals, biotech: development of small molecule drugs Noradrenergic nerves: innervates gut (a+b), heart (b), blood vessels (a+b), transmiUers: noradrenaline, adrenaline
Myotoxins: some induce irreversible damage to skeletal muscle fibres (adrenal medulla), dopamine (peripheral NS: CNS), formed from tyrosine, release: adrenaline hijacks uptake system,
Cispla%n: chemotherapy drug used to treat tesCcular + ovarian cancers indirectly acts sympathomimeCc, displaces noradrenaline, removal: inacCvaCon mainly by reuptake into nerve,
Adrenergic receptor: binds to adrenaline and elicits its physiological funcCon blocked by cocaine (increased concentraCon of noradrenaline in synapse, build up in synapCc cleF)
Drugs that bind at the same receptor site as the endogenous ligand but do not ac%vate it: anChypertensive for high Cholinergic nerves: release: snake + spider venom associated with acCvaCon and inacCvaCon (act at NMJ, paralysis of
BP and HR; antagonist of M ACh = promotes vasodilaCon, reduces blood flow resp muscles), response: cholinergic NS innervates skeletal muscle (N), heart (M), GI tract (M), blood vessels (M-not
Back of house pill tes%ng: less visible, test samples of drugs being used, focuses on quality of substances and innervated), removal: inacCvaCon by enzymaCc breakdown in synapse (occurs in <1ms), highly concentrated at NMJ.
increasing public awareness of drug characterisCcs, dangers and consequences, mobile services, MS Prostaglandins / leukotrienes: local mediators and neurotransmiUer (CNS), synthesised on demand (not stored),
Front of house: patron focussed, provides drug, not always individually focussed derived from phospholipids, important mediators of inflammatory reacCon (generated by local Cssues, blood vessels,
Heroin = more intense withdrawal syndrome than methadone platelets, lungs, mast cells).
Biochemical tes%ng: enzyme/substrate reacCons, protein-protein interacCons, binding affinity Covalent bonds = hard to break, hydrogen, electrosta%c and van der Waal’s = easy to break