Pharmacokinetics and Pharmacodynamics

Question 1

Define ligand

Answer 1

A molecule that binds to the receptor ( e.g ACH)

Question 2

Define receptor

Answer 2

the molecular target for a drug (e.g ACH receptor)

Question 3

Define agonist

Answer 3

a molecule that activates a receptor

Question 4

Define antagonist

Answer 4

blocks or reduces agonist mediated responses

Question 5

Name some facts about ligands

Answer 5

-exogenous vs endogenous
-might be a drug, neurotransmitter, hormone
-can act on different receptors
-synthetic vs natural

Question 6

Define targeting within context to pharmacology

Answer 6

a molecule, usually a protein, that is accessed by a drug to produce a therapeutic effect

Question 7

What is a “ideal” drug?

Answer 7

-Desirable pharmacological action
-acceptable side effects
-reach its target in the right conc at the right time
-remain at the site of action for sufficient time
-be rapidly and completely removed from the body when no longer needed

Question 8

What properties effect drug-receptor binding?

Answer 8

-physio chemical properties (electrostatic charges)
-steric properties (physical structure)

Question 9

Define affinity

Answer 9

how well the ligand e.g agonist binds to receptor

Question 10

What are the links between genetic variation and pharmacology?

Answer 10

-drug targets are often proteins
-protein is encoded in the genome
-genetic variation in drug reception is possible
-genetic variation in proteins involved in cellular processes is possible
-genetic variation in enzymes that process/ inactivate drugs
-genetic variation could lead to differences in the way people respond to any given drug

Question 11

Define pharmacogenomics

Answer 11

the way an individual’s genetics attributes affect response to therapeutic drugs

Question 12

Where are oxytocin receptors found?

Answer 12

-mammary glands myoepithelial cells
-uterus myometrium
-mesolimbic pathway

Question 13

What are the targets for drug action?

Answer 13

-most drugs initially work by binding to a protein
-proteins sub serve important roles-physiological regulation

common protein targets include: receptors, ion channels, carrier molecules, enzymes

Question 14

Give an example of receptors as a target for drug acton

Answer 14

-endogenous ligand (ACh) activates
-exogenous agonist drug (nicotine activates)
-antagonist- e.g curare inactivates receptor

Question 15

Describe G protein linked trans-membrane receptor

Answer 15

-ligand binds
-alters receptor conformation
-activation of intracellular second messenger cascade

-diverse intracellular effects-cellular excitability
-modulation of other ion channels
-down regulation of G protein linked receptors

Question 16

Describe the structure of ion channels as a target for drug action

Answer 16

-complex membrane proteins- actual physical pore
-molecular sensitivity filter-specific substrates
-e.g cl-, Na+, K+, Ca++

Question 17

Describe the structure/ function of carrier proteins as a target for drug action

Answer 17

-facilitators for transport
-active transport
-facilitated diffusion
-inhibitors or false substrates are common drug types

Question 18

Name some enzymes that are a target for drug action

Answer 18

-cyclooxygenase
-thromboxane and prostaglandins
-pain, inflammation, clotting
-aspirin

Question 19

Describe false substrate and pro drug production

Answer 19

false substrate- abnormal metabolite produced
pro drug- active drug produced

Question 20

What are the broad families of drugs that interact with enzymes?

Answer 20

-enzyme inhibitors
-false substrates
-prodrugs

Question 21

Why is drug specificity important?

Answer 21

-no drugs act with complete specificity
-non-specific interactions are very possible
-a drug may be preferentially bind to a relevant target

-more likelihood of non-specific interaction becoming significant with larger doses

Question 22

What 4 proccesses determine the time of onset and duration of drug action in the body?

Answer 22

Absorption
distribution
metabolism
excretion

describes the disposition of the drug

Question 23

Define absorption

Answer 23

process by which drug reaches the systemic circulation

Question 24

What is absorption affected by?

Answer 24

-route of administration
-permeation-the absorption process

-regardless of route of administration, drugs must be in solution to be absorbed

Question 25

what's the difference between enteral administration and parenteral adminosttraion?

Answer 25

enteral: -Via gut -oral/buccal/rectal parenteral: -Not via gut -e.g injections/topical

Question 26

pros and cons of enteral routes

Answer 26

-oral ingestion-gut absorption -low infection risk -very simple (self administered) -harsh environment-stomach/duodenum -first pass metabolism

Question 27

Describe first pass metabolism

Answer 27

can be lost via: -excretion -interstitial wall, interstitial lumen -metabolism through the gut -metabolism through the lungs or liver -leads to reduced bioavailability -FPM avoided by drug into a region of gut that does not drain into hepatic portal vein

Question 28

Pros and cons of topical

Answer 28

-local effects -low systemic effects -limited first pass metabolism -suited to slow continuous, long period administration -risk of systemic absorption (direct absorption to blood) -low infection risk -proccess of lipid permeation so drug must be: lipid soluble, small molecular size,use a carrier molecule- usually irritant to increase absorptions

Question 29

Name different types of injection

Answer 29

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 - for slow-release formulations

Question 30

Pros and cons of injections

Answer 30

-infection risk -rapid bioavailability for IV/IA -targeting risks -avoid first pass metabolism

Question 31

define bioavailability

Answer 31

the proportion of active drug that reaches the systemic circulation and is free to bind to its target -its affected by administration route and formulation e.g enteric coating -not a measure of how effective the drug is

Question 32

What factors affect distribution?

Answer 32

-protein binding -blood flow -membrane permeation/tissue solubility

Question 33

Describe distribution in regards to protein binding

Answer 33

-partly bound to plasma proteins and partly in plasma water -binding is usually reversible -dynamic equilibrium for most drugs -only the unbound fraction can cross membranes or bind to receptors

Question 33

Describe what the unbound drug in the plasma may do

Answer 33

-diffuse through capillary walls -produce a pharmacological effect -be metabolised/excreted -subtle changes in binding can have profound effects -may be a particular problem in the elderly, malnourished patients

Question 34

Describe distribution of drug through blood flow

Answer 34

-primarily through circulation system -tissue perfusion rate per tissue-important

Question 35

List the main tissue perfusion rates that effect the distribution of a drug

Answer 35

lung- 1000 brain-56 gut-300 bone/cartilage/fat - 3 all ml min-1 per 100g

Question 36

describe lipophilicity

Answer 36

-charged molecules, ions, ionised molecules diffuse less efficiently -uncharged, non ionised drugs have better access to membrane bound compartments

Question 37

Describe why metabolism is important for drugs

Answer 37

-metabolism typically inactivates drugs -liver is key organ involved -kidneys, intestines, lungs, plasma, skin and placenta also involved -metabolic rate can determine the duration of drug action -pro-drug activation -little or no activity until they undergo metabolic activation (codeine, L-dopa, gabapentin enacarbil)

Question 38

What are the two phases of metabolism?

Answer 38

Phase I - produces toxic metabolites (oxidation,hydroxylation, dealkylation, deamination) Phase II -converts toxins to soluble metabolites for excretion (conjugation) -Phase II can precede phase I, Phase II can occur in the absence of phase I

Question 39

What can phase I of metabolism chemical reactions change?

Answer 39

-polarisation of the substance -increase water solubility -reduce pharmacological activity -may activate pro-drugs cytochrome p450 cyp3A- can metabolise 50-60% of all known drugs

Question 40

What can phase II of metabolism chemical reactions change?

Answer 40

-making it water soluble -biologically inactive -converting the drug/toxin by covalently joining them to other molecules

Question 41

Define conjugation

Answer 41

adding of an endogenous substance

Question 42

Describe excretion via the kidney/renal route (main route)

Answer 42

-filtration -only unbound drugs/metabolites can be processed via glomerular filtration -PCT cells actively secrete into nephron -reabsorption of lipophilic drugs, unionised at urine PH -other routes: biliary, salivary ,breast milk, sweat and tears

Question 43

describe biliary excretion/ principal excretory route

Answer 43

-hepatocyte uptake -bile -duodenum -excretion in faeces but gut bacteria can convert drug to original form, drug can be reabsorbed across intestinal wall, re circulate in the blood, be metabolised in liver again and resecreted into bile. (enterohepatic circulation)

Question 44

What is half life in regards to drugs?

Answer 44

time taken to decrease plasma concentration to 50%