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Principles of Pharmacology Flashcards

1
Q

what is pharmacology?

A

the study of drug action and how this influences physiological function

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2
Q

what is therapeutics?

A

patient focused drug prescribing and treatment of disease

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3
Q

why is selectivity important?

A

for drugs to be effective therapeutic agents, they must show high degree of selectivity for a particular drug target
to avoid side effects/adverse effects

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4
Q

what are the 4 types of drug target?

A

receptors
enzymes
ion channels
transport proteins

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5
Q

what are the 4 types of drug-receptor interactions?

A

electrostatic
hydrophobic
covalent
stereospecific

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6
Q

what classification of drugs bind to and block receptors, produce no response

A

antagonists

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7
Q

what classification of drugs has an affinity for receptors but sub maximal efficiacy

A

partial agonists

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8
Q

what classification of drugs has an affinity for a receptor, maximal efficacy

A

full agonists

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9
Q

what is affinity?

A

determines strength binding of drug to receptor

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10
Q

what is efficacy?

A

ability of individual drug molecules to produce effect once bound to a receptor

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11
Q

what is potency?

A

refers to concentration or dose of drug needed to produce defined effect

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12
Q

what is a high potency drug?

A

a drug which produces large response at low concentrations

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13
Q

what are electrostatic drug-receptor interactions?

A

most common mechanism, includes H bonds and Van der Waals forces

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14
Q

what are hydrophobic drug-receptor interactions?

A

important for lipid soluble drugs

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15
Q

what are covalent drug-receptor interactions?

A

tend to be irreversible

less common

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16
Q

what are stereospecific drug-receptor interactions?

A

drugs exist as stereoisomers and interact stereospecifically with receptors

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17
Q

what are the major pharmacokinetic factors? ADME

A

absorption
distribution
metabolism
excretion

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18
Q

what is the concept of absorption?

A

passage of a drug from the site of administration into the plasma

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19
Q

what is the concept of bioavaliability?

A

fraction of initial dose that gains access to systemic circulation

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20
Q

what is the major determinant of absorption and bioavaliability?

A

the site of administration

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21
Q

what are examples of drug administration?

A

oral
inhalation
dermal/percutaneous
intra-nasal
intravenous

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22
Q

do drugs tend to be water soluble or lipid soluble?

A

water soluble

23
Q

what are the ways drugs move around the body?

A

bulk flow transfer

diffusional transfer

24
Q

how does the IV route of administration differ from all other routes?

A

IV - bulk flow transfer delivers drug directly to intended site of action
all other routes - must diffuse over at least 1 lipid membrane

25
what are the mechanisms by which chemicals diffuse over plasma membranes? diffusional transfer
simple diffusion diffusion across aqueous pores (not very common) carrier mediated transport electrochemical gradient
26
what are the main factors affecting distribution?
regional blood flow plasma protein binding capillary permeability tissue localisation
27
how does regional blood flow affect distribution?
different tissues receive different amounts of cardiac output more drug is distributed to tissues with most blood flow this blood flow is also affected by exercise, meals etc
28
how does plasma protein binding affect distribution?
only free drugs (not bound to plasma protein) can diffuse out of the blood and access tissues e.g albumin, testosterone binding globulin etc
29
how does capillary permeability affect distribution?
very lipid soluble drugs can diffuse across endothelial cells less lipid soluble drugs need transport via carrier proteins
30
what organ is the hardest to access
Brain - BBB
31
what organ is easiest to target
liver due to discontinuous capillaries
32
what is drug metabolism?
conversion of drugs to metabolites that are water soluble and easier to excrete and eliminate
33
what are the two phases of drug metabolism?
1. main aim to introduce reactive group to drug 2. main aim to add conjugate to reactive group
34
where and how are drugs metabolised?
Liver, cytochrome P450 enzymes
35
what is an issue for orally administered drugs?
absorption through the small intestine into the hepatic portal blood supply may lead to 'first pass hepatic metabolism'
36
what is first pass hepatic metabolism
orally administered drugs pass into the hepatic portal system, passing through the liver before systemic circulation the drug may be heavily metabolised before reaching systemic circulation
37
how is first pass hepatic metabolism overcome?
larger doses are administered to ensure enough drug reaches systemic circulation however, the extent of FPHM differs between people so drug effects and side effects are difficult to predict
38
how are drugs excreted?
mainly via kidney and liver (urine/bile) but also through lungs and breast milk
39
what are the major routes for drug excretion in the kidney?
glomerular filtration active tubular secretion passive diffusion across tubular epithelium (this is reabsorption so needs to be avoided for excretion)
40
what is active tubular secretion?
removal of water soluble drugs from tubule to urine 80% of renal plasma passes onto blood supply to proximal tubule proximal tubule has two active transport carrier systems - one acidic and one basic
41
what is passive diffusion across the tubular epithelium?
reabsorption from kidney tubule into blood lipid soluble extent of reabsorption dependent on urine pH and drug metabolism
42
what is biliary excretion of drugs?
liver transports drugs from plasma to bile via transporters bile is then excreted into intestines and eliminated in the faeces enterohepatic recycling can occur and significantly prolong drug effect (not excreted)
43
what is bulk flow transfer
intravenous route
44
what is diffusional transfer
molecule by molecule cross a short diffusion distance inhaled, intradermal, intramuscular, subcutaneous etc (as they all cross at least one lipid membrane)
45
what can unionised drugs do?
cross membranes as they are lipid soluble
46
what do ionised drugs require
carrier proteins as they are not lipid soluble but are water soluble so easy transfer in blood less reaches tissue
47
what does the ionisation of a drug depend on
the pH of the site where it is absorbed relative to the pKa if pKa = pH then drug equally dissociated - for acids(low pKa): if pH less than pKa drug is unionised (more acidic pH than the acid = less ionisation) if pH greater than pKa drug is ionised (if pH is more alkalotic than the acid = highly ionised) - for bases(high pKa): if pH greater than pKa drug is unionised (more alkalotic pH than the base = less ionisation) if pH less than pKa drug is ionised (pH more acidic than the base = highly ionised)
48
how does tissue localisation affect drug distribution
lipid soluble drugs will be better distributed to areas with high fat content e.g brain water soluble drugs will be better distributed to areas with high water content e.g lean muscle
49
types of capillary permeabilities
continuous - BBB discontinuous - liver (big gaps) fenestrated - kidney (medium sized regular gaps)
50
what is glomerular filtration dependent on
size of drug - smaller is faster
51
what is active tubular secretion dependent on
available transporters better for acidic or basic drugs (water soluble)
52
what is passive reabsorption dependent on
urine pH extent of drug metabolism better for lipid soluble drugs
53
what type of drugs are more likely to be excreted and why
water soluble drugs reduced passive reabsorption in kidney DCT therefore excretion of drug is increased
54
what is enterohepatic circulation
bile created from drugs excreted by liver to hepatic duct goes to gallbladder is excreted to intestines is then reabsorbed by intestines to the liver again and cycle continues

Pharmacology (9 decks)

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