Pharmacology

Question 1

Pharmacokinetics

Answer 1

What the body does to the drug
I.e. metabolism, absorption

Question 2

Pharmacodynamics

Answer 2

What the drug does to the body
I.e. Binding, drug-receptor interaction

Question 3

Drug

Answer 3

A chemical substance of known structure
When administered to a living organism produces a biological effect

Question 4

Medicine

Answer 4

Usually, but not necessarily, contains one or more drugs which is administered with the intention of producing a therapeutic effect

Question 5

Therapeutics

Answer 5

Use of drugs to diagnose, prevent or treat illness or pregnancy
I.e. medical use of drugs

Question 6

Formulations

Answer 6

How the drug is ‘packed’
E.g. different chemical substances (excipients)
Combined to produce a medicine
Allows the drugs to survive in the gut
Make it suitable

Question 7

Excipients

Answer 7

Substances ‘formulated’ along side the drug

Question 8

Nomenclature of drugs and medicines

Answer 8

Drugs have at least three different names
Chemical name
Generic name
Proprietary name

Question 9

Nomenclature of drugs and medicines: chemical name

Answer 9

Describes the chemical structure
Specifically describes exactly what the drug is

Question 10

Nomenclature of drugs and medicines: generic name

Answer 10

Class of drugs to which molecule belongs

Question 11

Nomenclature of drugs and medicines: proprietary name

Answer 11

Manufacturer’s name for the drug
The “trade name”

Question 12

Ligand

Answer 12

A molecule that binds to a receptor
E.g. ACh

Question 13

Receptor

Answer 13

The molecular ‘target’ for a drug
Complex protein
E.g. ACh receptor

Question 14

Agonist

Answer 14

A molecule that ‘activates’ a receptor
Depolarisation

Question 15

Antagonist

Answer 15

Blocks or reduces agonist mediated responses

Question 16

Affinity

Answer 16

How well the ligand (e.g. agonist) binds to receptor
I.e. the strength of agonist-receptor interaction
High affinity may activate the receptor in a more significant way

Question 17

Ligands: exogenous

Answer 17

From and made outside the body
E.g. morphine

Question 18

Ligands: endogenous

Answer 18

From and made within the body
E.g. acetylcholine

Question 19

Ligands might be a

Answer 19

Drug - e.g. morphine
Neurotransmitter - e.g. 5HT, ACh
Hormone - e.g. corticosteroid

Question 20

Ligands: receptor

Answer 20

Acts on different receptors
Different effects from the same ligand
E.g. ACh acts on beta receptors in the heart and nicotinic AChRs in skeletal muscle

Question 21

What do we want from a drug/medicine

Answer 21

Desirable pharmacological action
Acceptable side effects (or none)
Reach it target in the right concentration at the right time
Remain at the site of action for sufficient time
Rapidly and completely removed from the body when not longer needed

Question 22

How do drugs produce effect

Answer 22

Interact in a ‘structurally specific’ way its target
Steric interaction - based on spatial 3D relationship
Lock and key mechanism
Local electrostatic charges

Question 23

Properties that affect drug-receptors binding

Answer 23

Physico-chemical properties
Steric properties

Question 24

Properties that affect drug-receptors binding: physico-chemical properties

Answer 24

Charges are compatible allowing the ligand to bind to the receptor
Large complex molecule have positive and negative charges
E.g. electrostatic charges

Question 25

Properties that affect drug-receptors binding: steric properties

Answer 25

Physical shape of the ligand and the receptor Molecular structure of a drug and the binding site

Question 26

Pharmacogenomics

Answer 26

Drug targets are proteins Proteins encoded in genome Genetic variation in drug receptor Genetic variation in proteins involved in cellular processes Genetic variation in enzymes that process/inactivated drugs Lead to differences in the way people respond to any given drug

Question 27

Oxytocin

Answer 27

Endogenous ligand mainly released in childbirth Syntocinon - synthetic version, delivered to speed up aspects of childbirth Multiple receptors - mammary gland myoepithelial cells (milk release), uterus myometrium (contraction), mesolimbic pathway (emotional attachment and bonding to baby)

Question 28

Targets for drug action

Answer 28

Binding to a protein Proteins sub-serve important roles - physiological regulation Receptors Ion channels Carrier molecules Enzymes

Question 29

Receptors: agonist ligand

Answer 29

Endogenous - ACh activates Exogenous - nicotine activates Change the shape of the receptor so positive ions can enter the cell Causing excitation and depolarisation.

Question 30

Receptors: antagonist ligands

Answer 30

E.g. curare inactivates receptors, it blocks ACh receptors so ACh can’t bind Mecamylamine; allosteric - doesn’t block the binding site but changes it so ACh can’t bind

Question 31

Receptors: G-protein

Answer 31

Linked trans-membrane receptors Ligand binds e.g. opiate drug Alters receptor conformation Activation of intracellular second messenger cascade Diverse intracellular effect - cellular excitability Modulation of other ion channels - e.g. Ca2+, cell excitability Down-regulation of G-protein linked receptors

Question 32

Ion channels

Answer 32

Selective pore in the membrane Allows movement of ion across membrane Complex membrane proteins Molecular selectivity filter Blockers Modulators

Question 33

Ion channels: blockers

Answer 33

Ligand is blocking the channels so no charged ions through the channel

Question 34

Ion channels: modulators

Answer 34

Changes how the channel behaves Different regulations E.g. increases or decreases amount of ions through the channel

Question 35

Carrier proteins/ molecules

Answer 35

Facilitators for transport - e.g. ligands or cellular products across the membrane Active transport Facilitated diffusion E.g. digitalis blocks sodium potassium ATPase

Question 36

Enzymes: enzyme inhibitor

Answer 36

Blocking the binding site on the enzyme The ligand can’t bind Reaction to be inhibited Substrate analogues E.g. aspirin blocks cyclooxygenase which is involved in production of thromboxane and prostaglandins

Question 37

Enzymes: false substrate

Answer 37

Take the place of the endogenous ligan Enzyme produces an abnormal metabolite or inappropriate product

Question 38

Enzymes: pro-drug

Answer 38

Ligand is processed by the enzyme and converted into an active drug E.g. codeine converted to morphine in the liver

Question 39

Drug specificity

Answer 39

Non-specific interactions Drug may bind to the something other than the target More likely with larger doses

Question 40

Pharmacokinetics: ADME

Answer 40

Absorption Distribution Metabolism Excretion

Question 41

Absorption

Answer 41

Process by which the drug reaches the systemic (blood) circulation Drug must be in a solution that can be absorbed Soluble Affected by - route of administration, permeation

Question 42

Routes of administration: enteral administration

Answer 42

Via the gut Oral ingestion and gut absorption E.g. oral, buccal, rectal Positives - low infection risk, very simple (self administration) Negatives - harsh environment (drug meets to be protected), first pass metabolism

Question 43

First pass metabolism

Answer 43

Through the gut then the liver then circulatory system Can be lost through excretion and metabolism Reduces bioavailability

Question 44

Routes of administration: parenteral administration

Answer 44

Not via the gut E.g. injection or topical

Question 45

Routes of administration: parenteral administration - topical

Answer 45

Positives - local effects, low systemic effects, limited first pass metabolism, suited to slow continuous long periods of administration, systemic absorption, low infection risk Negatives - process of lipid permeation (lipid soluble), small molecular size, carrier molecules, irritant to increase absorption

Question 46

Routes of administration: parenteral administration - injections

Answer 46

Intravascular (IV, IA) - drug enters directly into the blood stream Intramuscular (IM) - drug injected into skeletal muscle Subcutaneous (SC) - drug absorbed from subcutaneous tissue Dermal (ID) - dermal vascular layer Depot injection - slow release formulations Positives - rapid bioavailability for IV, avoids first pass metabolism Negatives - infection risk, targeting risk

Question 47

Bioavailability

Answer 47

Proportion of active drug that reaches the systemic circulation and is free to bind to its target Affected by - route of administration, formulation Not a measure of how effective a drug is

Question 48

Factors affecting distribution

Answer 48

Protein binding Blood flow Membrane permeation/tissue solubility

Question 49

Protein binding

Answer 49

Partly bound to plasma protein and in plasma water Reversible Bound to not the target so become inactive Protein binding can reduce availability of drug Only unbound drug can bind to target

Question 50

Blood flow

Answer 50

Primarily through circulatory system Tissue perfusion rate per tissue The VRG (e.g. lungs and gut) absorb the drug readily as it has good blood supply

Question 51

Membrane permeability

Answer 51

Lipophilicity Charged molecules diffuse less efficiently Uncharged molecular have better access to membrane bound compartments Balance - need to cross membrane but also soluble to be absorbed Fick’s law - thickness, surface area and characteristics of layer

Question 52

Metabolism

Answer 52

Inactivated drugs Liver, kidney, intestine, lungs, plasma, skin and placenta Metabolic rate determine duration of drug action Make drug soluble Excretory form - inactive and hydrophilic

Question 53

Phase I of metabolism

Answer 53

Produces toxic metabolites Processing the drug Doesn’t inactivate the drug Oxidation, reduction, hydrolysis reactions Change polarisation, increase water solubility, reduce pharmacological activity May activate prodrugs

Question 54

Phase II of metabolism

Answer 54

Converts toxins to soluble metabolites for excretion Inactive drug for excretion Conjugation - adding endogenous substance Water soluble and biologically inactive Converting the drug by covalently joining to other molecules - methylation; CH3, acetylation; COCH3, glutathione conjugation

Question 55

Excretion

Answer 55

Kidney/renal main route Filtration Unbound metabolites can be processed via glomerular filtration Proximal convoluted tubule cells actively secrete into nephron Reabsorption of Lipophilicity drugs, unionised at urine pH Other routes - biliary, saliva, breast milk, sweat and tears

Question 56

Excretion: biliary excretion

Answer 56

Large metabolites and fatty substances are absorbed by hepatocytes and converted into bile Excreted into the duodenum that is excreted in the faeces

Question 57

Excretion: enterohepatic circulation

Answer 57

Reactivated the drug Sent round the circulatory system again Gut bacteria convert drug to original form Resorbed across intestinal wall Be metabolised in the liver again and re-secreted into bile

Question 58

Drug elimination half-life

Answer 58

T1/2 Time taken to decrease plasma concentration to 50% Estimates the time taken to void/excrete drug Bioavailability of drug in the blood decreases with each half-life Elimination is normally around 4 or 5 half-lives