Topic 2

Front 1

What is pharmacology?

Back 1

Study of drugs and the study of the effects of drugs

Front 2

A ‘drug’ can be defined as?

Back 2

A ‘drug’ can be defined as a chemical substance that has actions on living tissues.

Front 3

Pharmacotherapeutics is defined as what?

Back 3

"Pharmacotherapeutics - defined as curing, treating or preventing disease and thealleviation of pain and suffering; Drug abuse: (non-medical use) and Toxicology:(poisons)."

Front 4

Pharmacodynamics is?

Back 4

Pharmacodynamics: what the drug does to the body?

Front 5

what do all drugs have in common?

Back 5

ALL DRUGS HAVE SIDE-EFFECTS

Front 6

Natural or plant-derived substances include?

Back 6

Natural or plant-derived substances: Atropine, Curare, Morphine, cocaine and marijuana

Front 7

what is Atropine?

Back 7

"Atropine is a naturally occurring tropane alkaloid extracted from deadly nightshade (Atropa belladonna), Jimson weed (Datura stramonium), mandrake (Mandragora officinarum) and other plants of the family Solanaceae. It is a secondary metabolite of these plants and serves as a drug with a wide variety of effects. It is a competitive antagonist for the muscarinic acetylcholine receptor types M1, M2, M3, M4 and M5"

Front 8

what is Curare?

Back 8

"Curare is a common name for various arrow poisonsoriginating from South America.Curare is an example of a non-depolarizing musclerelaxant that blocks the nicotinic acetylcholine receptor(nAChR), one of the two types of acetylcholine (ACh)receptors. The main toxin of curare, d-tubocurarine,occupies the same position on the receptor as ACh with anequal or greater affinity, and elicits no response, making ita competitive antagonist.Muscle relaxants are used in modern anesthesia"

Front 9

describe what morphine, cocain and marijuiana are, emphasise on morphine?

Back 9

"Morphine, cocaine and marijuana.

Morphine is a potent opiate analgesic drug that is used torelieve severe pain.Morphine is a potentially highly addictive substance. It cancause psychological dependence and physicaldependence as well as tolerance,with an addictionpotential identical to that of heroin."

Front 10

describe the process for all new drugs?

Back 10

"All new drugs are tested on cells grown in tissue culture, animal tissuesand intact animals, before they can be tried in humans. Then there arephases of clinical testing before drugs can be approved for generaldistribution"

Front 11

• discuss the various ways drugs are classified

Back 11

"Drug classification• By source(e.g. cannabinoids and digitalis (a plant glycoside))• By chemical formula(e.g. xanthine derivatives by mode of action e.g. muscle relaxants)• By therapeutic use(e.g. antidepressants, antihypertensives and antiinflammatories)• By system acted upon(e.g. CNS depressants, respiratory stimulants)By drug schedule, e.g. S4, S7The Standard for the Uniform Scheduling of Medicines and Poisons (SUSMP), is a document used in the regulation of drugs and poisonsin Australia. Schedule 8 Controlled Drug (Possession without authority illegal)By popularity, e.g. Australia’s “top 10” prescribed drugs by cost."

Front 12

• describe how drugs are administered

Back 12

"Routes of AdministrationDrugs can be given by a variety of routes, for example:• By mouth (orally)• Under the tongue(sublingually where they diffuse into blood vessels)• Dermal(applied to skin, sometimes as patches)• By injection which is subcutaneous (under skin), intravenous,intramuscular, into a joint or into soft tissue.Rectally (into the rectum); Vaginally; Nasally, into the eye or ear; Implanted under the skin."

Front 13

describe what is pharmacokinetcs the study of?

Back 13

Pharmacokinetics: the study of the metabolism and action of drugs with particular emphasis on the time required for absorption, duration of action, distrubution in the body and method excretion

Front 14

describe what ADME is...

Back 14

"ADMEPharmacokinetics - Absorption, Distribution, Metabolism and Excretion (ADME).• duration of action• size of dose• frequency of dosage• drug/drug interactions• drug/food interactions"

Front 15

where does GI absorption occur?

Back 15

Gastrointestinal absorption occurs in : Mouth and esophagus, stomach and intestine

Front 16

what has limited exposure length?

Back 16

mouth and esophagus has limited exposure length

Front 17

what organ only absorbs well?

Back 17

the stomach only absorbs well: lipophilic compounds and weak acids

Front 18

what absorbes both weak acids and bases? how?

Back 18

the intestine absorb both weak acids and weak bases which are non-ionised and thus absorbed

Front 19

Greatest amount of absorption occurs in the? why?

Back 19

"Greatest amount of absorption occurs in theintestines because: large surface area of small intestine, slow transit time, thin epithial lining ( which allows passive diffusion, facilitated diffusion and active transport)"

Front 20

how do drugs enter the blood?

Back 20

"Many drugs bind toplasma proteins whenthey enter the blood.The drug may bind tothe major plasmaproteins such asalbumin (acidic drugs)and ß-globulin (basicdrugs)."

Front 21

describe how warfarin is absorbed?

Back 21

"The anticoagulant warfarin (deep vein thrombosis) is extensively bound to plasma proteins. When certainother drugs are given simultaneously, they compete with warfarin and dislodge it from binding sites soincreasing its free, active concentration in the blood. This can then lead to prolonged, potentially fatal bleedingif even a slight injury"

Front 22

what is Volume of Distribution?

Back 22

VD (Volume of Distribution) given an indirect measure of the degree of distribution of a drug within the tissues.

Front 23

what kind of process entails Biotransformation?

Back 23

"Biotransformation (drug metabolism) is a biological process that changes the chemical structure and properties ofchemical compounds"

Front 24

where does biotransformation occur?

Back 24

"Biotransformation Occurs in the liver, also kidney and can increase or decrease a drug’s activity.Before entering the systemic circulation, blood leaving the gastrointestinal tractpasses through to the liver via the hepatic portal circulation."

Front 25

what is the effect of a drug as a result of biotransformation?

Back 25

"Thus, any drugtaken orally may undergo extensive metabolism before reaching its site ofaction. This is known as ‘first pass effect’. (also known as first-pass metabolismor presystemic metabolism)."

Front 26

describe what first pass effect (FPE) involves?

Back 26

‘first pass effect involves two processes, phase I and Phase II

Front 27

FPE: Phase I processes include

Back 27

"Phase I processes include oxidation, reduction and hydrolysis• Introduction of a polar group• Increased water solubility• Abolition of pharmacological activity"

Front 28

FPE: Phase 2 processes include

Back 28

"Phase II involves conjugation(drugs made bigger by adding new chemical groups but final moleculesare more water-soluble). Eg morphine is combined with glucuronic acidto produce a water-soluble glucuronide that can be excreted in bile"

Front 29

desribe where enterohepatic recycling occurs in detail

Back 29

"Enterohepatic recycling occurs Through the liver only part enters thebloodstream, the rest is made more watersolubleby liver enzymes, by a processcalled conjugation, and then the metabolite(conjugate) is excreted in bile. When bilereaches the intestine, bacteria break downthe conjugate releasing the original drugwhich is then reabsorbed, passes in thehepatic portal vein to the liver and aproportion passes into the blood streamwhilst the remainder is reconjugated andexcreted in bile. Overall this prolongs theabsorption of a drug (little by little it entersthe bloodstream."

Front 30

what is half life concenpt and what does it take into account? what is the equation for HL?

Back 30

"Half-life is an important concept that takes intoaccount metabolism and excretion of drugs.Half-life = t½ = time for plasma concentration todecrease by 50%. If the half life of a drug is 2hours and its initial concentration is 10microgram per ml of blood, this means that after2 hours its concentration will be 5 microgram perml."

Front 31

Oral doses are usually given at?

Back 31

"Oral doses are usually given at intervals of onehalf-life. This means that plasma levels arealways kept ""topped up""."

Front 32

Half life is the major determinant of?

Back 32

Half life is the major determinant of dose frequency

Front 33

Two drugs (X and Y) are given atthe same time intervals. The halflife of drug X is double that ofdrug Y.Thus which drug will accumulateto a greater degree?

Back 33

drug X

Front 34

Pharmacodynamics is the study of?

Back 34

"Pharmacodynamics is the study of what the drug does to the body, or more specifically the study of thebiochemical and physiological effects of drugs on living systems and includes therapeuticactions and adverse effects."

Front 35

how do most drugs produce their actions ?

Back 35

"Most drugs produce their actions by interacting with specific drugtargets such as receptors or enzymes"

Front 36

what does pharmacodynamics involve?

Back 36

Pharmacodynamics involves an agonist and an antagonist

Front 37

what is an agonist?

Back 37

"Agonist – Chemicals or drugs that bind to and activate a receptor thus eliciting a response.They have intrinsic activity or efficacy. A partial agonist is said to have less intrinsic activity orefficacy i.e. they do not fully activate the second-messenger system"

Front 38

what is a curare?

Back 38

"CurareCurare is a common name for various arrow poisonsoriginating from South America.Curare is an example of a non-depolarizing musclerelaxant that blocks the nicotinic acetylcholine receptor(nAChR), one of the two types of acetylcholine (ACh)recep"

Front 39

what is an Antagonist?

Back 39

"Antagonist – Chemicals or drugs that bind to butDO NOT activate a receptor. They have no biologicaleffect or intrinsic activity at the level of the receptor.They do however block or reverse the effect of an agonist"

Front 40

what does a ligand refer to?

Back 40

Ligand refers to a key/chemical that fits a particular lock/receptor

Front 41

what is the following diagram an illustration of?

Back 41

"(1) – Competitive antagonistThe curve shown in A is the agonist effectof a drug in the absence of an antagonist.Curve B shows the effect in the presenceof a fixed concentration of an antagonist."

Front 42

what is the following diagram an illustration of?

Back 42

reersible-competitive antagonist: "Reversible – Competitive• Inhibitor competes with substrate for bindingat active site• Structural analogs of substrate or transitionstate• Increases Km (or decreases affinity)• Can be overcome be increasing substrate"

Front 43

what is the following diagram an illustration of?

Back 43

(2) Non-competitive antagonistThe curve shown in A is the agonist effect of a drug in the absence of anantagonist.Curve B is the effect in the presence of a fixed concentration of the antagonist.Note: the effect of the antagonist cannot be completed over come at higherconcentrations. Why?

Front 44

what is the following diagram an illustration of?

Back 44

"Reversible – Noncompetitive• Does not compete with substrate for activesite• Binds to enzyme and ES• Decreases Vmax• Km usually unchanged as substrate bindingunaffected"

Front 45

describe in detail a dose response curve

Back 45

"A dose response curve: Log dose-responsecurves have a sigmoidshape with anapproximately linearregion over 20-80% ofmaximal response.They are widely used tostudy drug action andto work out theconcentration of thedrug used to produce50% of maximalresponse."

Front 46

what is the molar concentration of agonist required to produce half the maximum response?

Back 46

"The molar concentration of agonist required to produce half the maximum responseis the EC50. This is an estimate of potency"

Front 47

what is efficacy?

Back 47

Efficacy is the ability of a drug to produce an effect at a receptor

Front 48

what is the defenition of Potency

Back 48

"Potency – an estimate ofthe concentration of adrug that will elicit aresponse."

Front 49

"Which has the greaterpotency Drug A or DrugB?Which drug has thegreater potency Drug Aor Drug C?"

Back 49

"Drugs “A” and “B” have a similar potency i.e. a similar concentration of the drug produces 50%of the maximum effect.Drug “C” is more potent than either drug “A” or “B”. This means a lower concentration of the drugis needed to produce a similar effect"

Front 50

"Drugs A and D havesimilar values for Emaxand EC50.Which drug would besafest one to use? Why?"

Back 50

"The shape of the curves is also important. Drugs “A” and “D” have similar values for Emax andEC50 BUT drug “D” has a much steeper curve. This can have important clinical implicationsbecause it means a slight change in the concentration of the drug can produce large changes ineffect. This can be undesirable effects with drug treatment."

Front 51

what is the therapeutic window

Back 51

"Therapeutic window = range of plasma drug concentrations between the toxicrange and the ineffective range. If the range is narrow then the drug is said tohave a low therapeutic index."

Front 52

what does a broad therapeutic window mean?

Back 52

"A broad therapeutic window means there is awide gap between the desired effect of thedrug and the toxic effects of the same drug"

Front 53

what doesa narrow therapeutic index mean?

Back 53

"A narrow therapeutic index means there isa narrow gap between the desired andtoxic effect of a drug"

Front 54

Drugs with a broad therapeutic window are?

Back 54

"Drugs with a broad therapeutic window are generally safe and easy to use. eg. PenicillinDrugs with a low therapeutic window are difficult to use and levels are commonly monitored by frequentlymeasuring plasma concentrations"

Drugs with a broad therapeutic window are

Front 55

"What is the nature of the interaction between drug A or drug B and Y?A) Y is a non-competitive antagonist of both drug A and drug BB) Y is a non-competitive agonist of both drug A and drug BC) Y is a competitive agonist of both drug A and drug BD) Y is a competitive antagonist of both drug A and drug BE) Y is a irreversible competitive antagonist of both drug A and drug B"

Back 55

D - Y is a competitive antagonist of both drug A and drug B