pharmacology Flashcards

1
Q

What does intracellular binding describe?

Hint - which set of stairs is involved in every single secondary messenger system?

A

ligand + receptor binding → enzyme cascade activation → cellular response/s

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2
Q

What do receptors allow?

Hint - signals + intracellular or extracellular change

A
  • extracellular signals across PM to respond to stimuli

- so extracellular substances (can’t pass through) → intracellular change

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3
Q

Which molecular responses can receptors allow?

Hint - 2 are very cellular, one to do with channels and one to do with +VE feedback

A
  • opening of ion channels
  • secretion of other signalling molecules
  • cell motility (movement)
  • modification of cell cycle
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4
Q

What type of signalling is utilised by type 2 and type 3 receptors?

A
  • type 2 receptors → G-protein pathway

- type 3 receptors → enzyme-linked cell surface pathway

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5
Q

Describe type 1 receptors.

Hint - type of transmission, what its coupled to how many times its repeated

A
  • associated w/ fast neurotransmission (GABA, 5-HT, ACh)
  • receptors are coupled to ion channels and sit on the cell membrane like subunit
  • subunits repeated 4/5x within membrane
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6
Q

What is a ‘binding domain?’

A

where small molecule (substrates) will bind

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7
Q

Describe the example of type 1 nicotinic ACh receptors (stimulatory) and how they work.

A
- consists of 5 membrane spanning subunits:
• 2 x α (binding domain for ACh)
• β 
• γ
• δ
1. 2x ACh molecules bind to 2 alpha units 
2. opens ligand-gated Na+ ion 
3. depolarises cell as influx of Na+
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8
Q

Describe type 2 receptors and how they work.

Hint - 4/5 → ligand binds domain, signal transmitted, domain + signalling molecule and GP activation

A
  • single polypeptide chain (400-500 AA residues)
  • ligand attaches to binding domain → signal travels through chain → signalling molecule (receptor) binds to domain → G-protein activated
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9
Q

Draw, label and describe the structure of a type 2 receptor.

Hint - looks like the piping of plumbing in the house

A
  • receptor protein forms seven transmembrane α-helices embedded in membrane
  • long intracellular (3rd) loop between α-domains 5 and 6 where G protein couples to receptor

(see notes for diagram)

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10
Q

Describe G-proteins and their subunits.

(Hint - activity, all 3 types of radiation in physics, describe the most active and then how the other two connect to the membrane when inactive what all 3 subunits form)

A
  • highly-mobile intracellular membrane proteins with 3 subunits (α, β and γ)
  • α subunit:
    • more mobile than β and γ subunits
    • functions as a GTPase enzyme (converts GTP → GDP)
  • β and γ subunits – form complex which is v. hydrophobic therefore they stay closely associated w/ the membrane
  • when inactivated, all 3 subunits form complex with GDP bound to α-subunit

(see notes for diagram of resting state)

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11
Q

Describe the 3 stages of (G-protein-coupled) activation of type 2 receptors.

(Hint - use the diagrams on your notes)

A

1)
- ligand + receptor (bind) → conformational change in α, β and γ complex
- α-subunit dissociates from other 2, converts: GDP → GTP
2) α-subunit coupled to GTP, associated with specific allosteric target enzyme (e.g. adenylate cyclase)
3)
- α subunit hydrolyses GTP → GDP
- inactivates enzymatic ability of α-subunit + allows activation of target enzyme
- inactive α-subunit re-associates with β and γ complex
- G-protein changes: substrate → product.

(see notes for diagrams)

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12
Q

What can a G-protein mechanism act as and how?

A
  • signal amplifier

- single activated receptor can activate several G-proteins

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13
Q

Which 4 membrane proteins do targets for G proteins activate?

(Hint - Na+)

A

1) adenylate cyclase – producing intracellular cAMP
2) guanylate cyclase – producing intracellular cGMP
3) phospholipase C/inositol phosphate system
4) regulators of ion channels

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14
Q

What is cAMP produced from a type 2 (G-protein) receptor, how is it inactivated, what does it specifically target and what are these molecules subsequently used for?

(Hint - 2, PK and DEs)

A

• cAMP (cyclic 3’,5’-adenosine monophosphate) acts as a secondary messenger → inactivated by hydrolysis into 5’-AMP
• cAMP:
- specifically targets inactive protein kinases → activate (ATP as phosphate source)
- activate PKs to phosphorylate (activate) downstream enzymes

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15
Q

Give an example of a role that cAMP has in cells.

A

the breakdown of glycogen in β-adrenoceptors

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16
Q

Which involvements does cAMP have in cells other than β-adrenoceptors, how it can be broken down and how can it be inhibited?

(Hint - cardiac, muscle, p, drugs)

A
  • increased activity of voltage-gated Ca2+ channels in the heart
  • inactivation of myosin light chain kinase in SM
  • cAMP broken down by phosphodiesterase
  • inhibited by drugs (i.e. caffeine)
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17
Q

Describe the 5 stages by which receptor guanylate cyclases act as an example of type 2 receptor. Which secondary messenger is involved?

(Hint - EC + ligand, IC domain + GP, gc → cG, cG binds cG-PK, GK + pi → Thr/Ser residues)

A

1) ligand binds on extracellular domain
2) G-protein activates intracellular domain (guanylyl cyclase)
3) guanylyl cyclase produces: → cGMP
4) cGMP binds to cGMP-dependent protein kinase (G-kinase)
5) G-kinase phosphorylates downstream proteins on threonine/serine residues
- cGMP = secondary messenger

(see notes for diagram)

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18
Q

How does the receptor phospholipase C (or inositol phosphate system) act as an example of a type 2 receptors and which actions are steps associated with?

(Hint - PIP →

  1. GP and p-lipase
  2. PIP splits → Dog + Inspo
  3. both these products act as 2s
  4. Dog → PKC → targets
  5. Inspo leading to Ca release)
A
  • based on phospholipid phosphoinositide-4,5-diphosphate (PIP2)
    1. G-protein activates target enzyme (phospholipase)
    2. phospholipase splits: PIP2 → diacylglycerol (DAG) + inositol-1,4,5-triphosphate (InsP3)
    3. InsP3 + DAG act as 2° messengers
    4. DAG activates PKC which is serine/threonine kinase, → phosphorylates certain target enzymes
    5. InsP3 binds to endoplasmic receptors → open endoplasmic Ca2+ channels → influx of Ca2+ into cytosol needed for certain actions
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19
Q

How do regulators of ion channels act as an example of type 2 receptors? Give a specific example of this in the body.

(Hint - all about GPs and muscu receptors, main NT, K)

A
  • G-proteins directly activate ion channels.

- e.g. interaction of ACh and muscarinic receptors opens K+ channels via G-protein pathway

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20
Q

What is a kinase?

A

enzyme that catalyses the transfer of phosphate groups

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21
Q

What are the 4 forms of type 3 receptor?

Hint - TYR, LINKED TYR, TYR P, SER/THR

A

a. Receptor tyrosine kinases - TYR
b. Receptor linked tyrosine kinases – LINKED TYR
c. Receptor tyrosine phosphatases – TYR P
d. Receptor serine/threonine kinases – SER/THREIONINE

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22
Q

State the six stages by which tyrosine kinases work as an example of type 3 receptors and give 2 examples of molecules.

(Hint - ligand EC, change + 2 poly → dimer, tyr K + Pi, auto Pi by tails, SH2 + SH3, genes affected and cells respond
- 2 hormone examples)

A

1) ligand binds to extracellular binding site
2) conformational change in shape → 2 polypeptides form dimer
3) cytoplasmic tyrosine kinase activated by phosphorylation
4) autophosphorylation → cytoplasmic tail groups can phosphorylate each other (+Pi)
5) activated tyrosine kinases (phosphotyrosines) now binding sites for proteins with SH2 + SH3 domains → act as ligands.
6) proteins/enzymes + transcription factors are activated → gene transcription altered → cellular response
- i.e. receptors for growth factors + insulin
(adapter protein – an important class of protein)

(see notes for image of process)

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23
Q

State the molecule that each abbreviation stands for and state the other names where applicable:

a) GAP (Hint - GTPase…)
b) GEFs (Hint - a type of DNA base exchanger + how to ask for help in WW1)
c) Raf (Hint - ser/thr and k.)
d) ERK (Hint - an EC type of SR kinase)
e) TF
f) FAK (Hint - like adjusting + then sticking on your glasses)

A

a) GTPase activating protein
b) Guanosine exchange factors i.e. Sos
c) serine/threonine kinase i.e. MAPKKK
d) extracellular signal regulating kinase
e) Transcription factor
f) Focal adhesion kinase

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24
Q

Explain integrins and the integrin protein family as an example of receptor-linked tyrosine kinases type 3 receptors.

(Hint - all about cell parts attaching, 2 types of radiation and di elements)

A
  • integrins → typical example
  • proteins which function by attaching cell cytoskeleton + ECM → biochemically sensing whether adhesion occurs
  • α + β subtypes which form transmembrane heterodimers (2 different proteins joined)
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25
Q

State the 4 stages of the messenger process of receptor-linked tyrosine kinases an example of type 3 receptors.

(Hint - The 2 GeRBert brothers (Vinculin and Paxilin) ran into trouble when trying to steal a TALoN from Actin and so SeCuRity came after them and they were F’d so they called out for help (SOS). So that is how they got into trouble/the bad situation in the first place)
draw the image to help you

A
  1. binding of a ligand (e.g. collagen) to integrins
  2. allows chain to interact with structural proteins (e.g. talin + vinculin)
  3. adapter proteins and membrane-bound tyrosine kinases (e.g. Src)
  4. then phosphorylate another downstream tyrosine kinase FAK

(see notes for image)

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26
Q

What are receptor tyrosine phosphatases and receptor serine/threonine kinases as examples of type 3 receptors and how do they differ from receptor tyrosine kinases?

(Hint - tyr p add water and see/thr add Pis)

A
  • both activated in same way as receptor tyrosine kinases, but:
  • receptor tyrosine phosphatases - function to deactivate target proteins by hydrolysis
  • receptor serine/threonine kinases - specifically phosphorylate proteins
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27
Q

Which components are required in the signalling process?

Hint - DACT

A

1) discriminator (receptors)
2) transducers (allosteric enzymes activated/inactivated by substrate binding) i.e. G-proteins, membrane linked tyrosine kinase
3) amplifiers (second messengers - allosteric enzymes activated to different degrees with multiple binding sites)
4) couplers (adapter proteins - allow allosteric enzymes to form close associations, enabled by adapter proteins)

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28
Q

What is Ras, what family does it belong to and what are the other members of this family?

(Hint – all of the Raf brothers Rab, Ras, Rho + Rac are part of the same family)

A
  • a small GTPase
  • other members of this GTPase family:
    1. Rho and Rac - GTPases → associated w/ integrin to cytoskeletal signaling
    2. Rab - family of GTPases → associated w/ intracellular transport
    3. Ras
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29
Q

Describe Ras.

(Hint - in the family, Ras is the main man and the others are all sidemen. Ras has a motor like a trimetric G-protein motor but it’s a dead motor as it is 100x slower than one)

A
  • can exist in active (GTP-bound) OR inactive (GDP-bound) states
  • functions like trimeric G-proteins but hydrolyses GTP 100x slower
  • could mean it stays active for long periods of time
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30
Q

Which 2 regulatory proteins control the GTPase (Ras, Rhab, Rho and Rac) family and how?

(Hint - a jumper brand and the name of a toy giraffe)

A

1) GAP - acts to enhance Ras hydrolysis rate

2) GEFs (i.e. Sos) - promotes exchange of GDP for GTP

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31
Q

Describe Ras activation of MAP (mitogen-activating protein) kinase using the following keys:

→ = phosphorylation 
--- = activation 
‘’’’’ = promotion of transcription 

(Hint – The 2 GeRbert brothers got into a bit of trouble and so one of their mates from the RAb brothers ‘Ras’ came to help them out and he came along really actively (hence the GTP) with his brother [start here] Raf who came in his MEK motor but there was too much trouble and one of them ended up in the EmeRgency room. So the rest of them went looking for this room but the MAPKK was too complex so they simplified it down to MAPK but then the police came and they realised they needed to get TF out so GENE TRANSCRIPTION could occur)

A

Raf → MEK — serine/threonine kinase ERK → MAPKK → MAPK → TF (transcription of a specific gene)

(see document for diagram)

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32
Q

Usually, what type of receptors are type 4 receptors?

A

DNA receptors

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33
Q

Describe the structure of type 4 receptors.

Hint - 4-10 in nuclear area, two domains which bind different things

A
  • large proteins of 400-1000 AAs found in nucleus
  • have binding domain (steriod hormone substrate binds)
  • also have DNA-binding domain (DNA binds)
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34
Q

How does a type 4 receptor attach to DNA and what does this promote?

A
  • wraps around at specific DNA sequences (hormone-responsive elements)
  • promotes increased RNA polymerase activity → gene transcription
35
Q

What property of type 4 receptors allows molecules to easily enter cells and how specific is this?

(Hint - think about the structure of these molecules)

A
  • steroids lipid-soluble so enter cell nucleus easily via nuclear membrane
  • DNA receptors very specific to hormone
36
Q

What are xenobiotic drugs and what does the body do with these? Give examples of them.

A
  • foreign compounds with no nutritional value

- body wants to eliminate these, e.g. pesticide, pollutants

37
Q

State and explain the 2 types of effects that xenobiotics elicit from from patients and why.

(Hint – biologically kinetics are all about the body)

A
  1. pharmacodynamic effects → what drug does to body

2. pharmacokinetic effects → what body does to drug

38
Q

Explain how penicillin dosage in patients was first determined and what were the problems with this.

A
  • scientists had to measure drug levels in patient’s urine as majority excreted there
  • this amount re-administrated to patient to provide correct dosage to kill bacteria
  • pharmacodynamic effects of drug were positive and proven that penicillin fought against infection → pharmacokinetic effects affected plasma levels of drug in body
39
Q

What happens to an aspirin tablet when it taken orally?

Hint - conc. needed, drug levels for effect, factors for plasma levels, factors for therap. effect

A
  • specific concentration needed to allow pharmacodynamic effect
  • drug taken + reaches level for therapeutic effect
  • different factors contribute to increase/decrease of plasma levels of drug
  • balance of factors determines whether therapeutic effect will be achieved
40
Q

Describe the route of administration of a drug.

A
  • distributed in systemic circulation (by blood)
  • tissue depots: drug storage (fat, bone) → lowers plasma conc. of drug to site of action
  • binding of drug to plasma proteins → lowers drug plasma conc.

(see notes for a diagram)

41
Q

How are some drugs distributed in the body due to poor bioavailability? Use penciclovir as an example of this.

(Hint - administration, how its activated etc…)

A
  • some drugs administered in form of a pro-drug (famciclovir), absorbed + metabolised → converted into active drug (penciclovir) which reaches site of action
  • famciclovir better absorbed by body when given orally
  • metabolism activates drug
42
Q

What does a higher the dosage mean for the drug?

A

remains in the body for longer

43
Q

What do the ADME (absorption, distribution, metabolism and excretion) characteristics of a drug depend on?

(Hint - 2. has MILD examples)

A
  1. route of administration of drug
  2. physio-chemical properties of drug (crossing plasma membrane)
    - drug structure
    - molecular weight
    - lipophilicity/polarity
    - ionisation
44
Q

What are the 4 main chemical properties that affect drug absorption?

(Hint - MILD)

A
  • drug structure
  • molecular weight
  • lipophilicity
  • ionisation
45
Q

What are the 6 main physiological properties that affect drug absorption?

(Hint - the PMS-PEG, think drug monograph, think gastric and membranes)

A
  • pH of site
  • SA of membrane
  • mesenteric blood flow
  • gastric emptying
  • presence of food
  • efflux transporters/ionisation
46
Q

For the mentioned properties state how they affect drug absorption:

a) ionisation
b) pH
c) mesenteric blood flow
d) gastric emptying
e) presence of food
f) efflux transporters

A

a) highly ionised – harder to get through membrane
b) can alter ionisation (e.g. GI tract)
c) blood flowing through gut → drug entering systemic circulation to be distributed
d) how long drug is retained in stomach
e) affects where the drug is being absorbed
f) transporters in PM which remove drug if it moves into cell interior

47
Q

What is bioavailability (F)?

A

percentage of administered dose reaching systemic circulation as unchanged drug (not metabolites)

48
Q

Which 2 things is bioavailability governed by?

Hint - simple AF

A
  • ‘absorption’
  • ‘first-pass metabolism’ (the blood from the gut moves past the liver first, so it depends how much of the drug is metabolised by the liver before getting into the systemic circulation)
49
Q

For each type of drug administration, state the location in the body, the methods used and how it enters the site of action:

a) enterally (part of GI tract)/orally
b) parenterally
c) directly into the bloodstream (infusion of large amounts)
d) topically

A

a)
- location: oral, rectal mucosa
- methods: oral spray,. tablet, suppository (rectum)
- enters site of action: epithelium of GI tract
b)
- location: except from intestine (not mouth or rectum)
- methods: cream, patch, injection
- enters site of action:
• may cross the epithelium (skin/lungs)
• may avoid the epithelium (subcutaneous- fat underlying skin, intramuscular, intrathecal-spinal cord, intraperitoneal junction)
c)
- location: N/A
- methods: intravenous, intra-arterial
- enters site of action: directly into the bloodstream – doesn’t go through GI tract
d)
- location: skin, eyes, vagina, nasal mucosa, airways
- methods: cream, inhaler, eye drops
- enters site of action: directly to where the site of action is

(see notes for a table)

50
Q

Describe the stages of getting a drug from a dose to its effect.

(Hint: dose → A → F → M → D → E)

A

drug dose → absorption → free drug in plasma → metabolic activation/tissue reservoirs or metabolic inactivation/excretion → drug available at the site of action → effect

51
Q

What is pharmacokinetics?

A

a study of drug processes to understand size + duration of response

52
Q

What does the distribution of a drug usually involve and how is it considered?

A
  • compartments
  • drugs diluted as you go through each layer in body
  • volume of dilution through each barrier is important
53
Q

For each drug (s), state the type of drug, factor affecting its distribution and its basic pharmacokinetics as a table:

a) heparin
b) warfarin
c) tubocurarine
d) ethanol, diazepam, morphine, paracetamol

A

a)
- type of drug: anticoagulant
- main factor affecting its distribution: very high MW >15,000
- its basic pharmacokinetics: retained in the bloodstream and cannot leave – therefore good as we want it to stay in blood
b)
- type of drug: anticoagulant
- main factor affecting its distribution: 99% bound to plasma protein
- its basic pharmacokinetics: dose is free in the plasma
c)
- type of drug: neuromuscular blocker
- main factor affecting its distribution: highly-ionised
- its basic pharmacokinetics: restricted to extracellular fluid – hard to pass through plasma membrane
d)
- type of drug: painkiller
- main factor affecting its distribution: highly lipid-soluble; distributed in total body water
- its basic pharmacokinetics: can move around body easily

(see notes for table)

54
Q

What is plasma protein binding and how is it relevant to pharmacology?

(Hint - describe binding, acidic/basic drugs, equilibrium set-up, % bound and why)

A
  • loose electrostatic bonding to lots of albumin + acid glycoproteins in blood
  • acidic drugs → bind albumin
  • basic drugs → bind glycoproteins
  • equilibrium of drug binding to protein + free set up
  • drugs 90-99% bound (e.g. non-steroidal, anti-inflammatories, warfarin, diazoxide) to reduce free drug concentration of plasma to reach site of action
55
Q

In which 3 ways is a drug eliminated from the body?

Hint - the two main renal organs and then the lab/synthetic way

A
  1. renal excretion
  2. liver metabolism (depends on physiochemical properties)
  3. chemical transformation of the drug (chemically degradation of a drug)
56
Q

What is glomerular filtration?

A
  • filtration by size

- large molecules remain in body, small molecules passed through kidney tubule + excreted

57
Q

Which 2 types of compounds are not metabolised (cleared by glomerular filtration)?

(Hint - SC two food/liquid groups)

A
  • small water-soluble molecules

- complex carbohydrates (polysaccharides)

58
Q

Where is tubular reabsorption?

A

carries molecule back into bloodstream from kidney

59
Q

Which types of drugs are always metabolised and how?

A
  • lipophilic drugs

- if metabolism didn’t occur, drug would be recycled endlessly through glomerular or enterohepatic re-absorption.

60
Q

What is tubular secretion?

A

secretion into the tubule from the blood

61
Q

For each stage of drug metabolism, state the type of reaction that occurs and what it entails:

a) phase I
b) phase II (c)
c) phase III (mac)

A

a) functionalization reaction → introduction/removal of functional group
b) conjugation reactions → product of phase I is conjugated to a small molecule to increase water solubility
c) phase III → product/s of phase II made up into macromolecules

62
Q

The addition/unmasking of which group usually occurs during phase I metabolism and which chemical reactions allow a drug to become more soluble?

(Hint - the North Pole, HORHIM reactions with one IdW reaction)

A
  • polar group
  • reactions:
    • oxidation
    • reduction
    • hydrolysis
    • hydration
    • isomerisation
    • miscellaneous
63
Q

State the 3 main parts of a phase II/conjugation reaction from a drug to a conjugate.

(Hint - CAC but alphabetically about the groups: added, catalysed and donated)

A
  • addition of polar group
  • catalysed by transferases
  • cofactor donor
64
Q

In a phase II reaction, how specific are enzymes and what do they convert?

(Hint - add water-solubility to lots of molecules at a time)

A
  • enzymes have low substrate specificity – can catalyse many reactions
  • converting lipid-soluble into water-soluble
65
Q

What are the 5 main properties of drug-metabolising enzymes?

Hint - the 4 Ls and then an I

A
  • low substrate-specificity (not specific to one compound)
  • low reaction-specificity (catalyse different reactions)
  • lower catalytic rates but present in high concentrations
  • substrates usually lipophilic (can access enzymes + be acted upon → converted to more polar products)
  • inducible enzymes (cells can be induced to produce lots of enzyme so some drugs lose effect after period of time as body has produced lots of enzyme to metabolise it)
66
Q

In which 2 sub-cellular compartments does drug metabolism occur in the liver and how?

(Hint - 2 types of membrane SC)

A

1) SER - a continuous network of filamentous, membrane-bound channels → accessible to small, lipid-soluble drugs → microsomes hold metabolising enzymes
2) cytosol → using enzymes

67
Q

WHich enzymes in each category are used in drug metabolism in the cytosol of liver if they are:

a) microsomal enzymes (Hint - CFGE)
b) cytosolic enzymes (Hint - A SAGA)
c) mitochondrial enzymes (Hint - AM)

A

a) CYT P450, flavin monooxygenase (FMO), glucanosyl transferase, epoxide hydrolase
b) aldehyde oxidase, aldehyde dehydrogenase, alcohol dehydrogenase, glutathione transferase, sulphotransferase
c) aldehyde dehydrogenase, monoamine oxidase

68
Q

Give an example of an oxidation that is a phase II drug metabolism reaction.

A
  • oxidations catalysed by CYT P450 – to become more water soluble
  • e.g. C and N-hydroxylation
  • N-, S-, O- dealkylation
69
Q

Give an example of a toxic phase II drug metabolism reaction.

(Hint - T and F → 2 forms of the same drug)

A
  • terfenadine (T) → non-drowsy antihistamine + prodrug
  • (oxidation) rapidly oxidation in liver by CYT P450 3A4 → producing active drug fexofenadine (F)
  • T = cardiotoxic, F = is not
  • normal use → no evidence of cardiotoxity
  • if patients took substances to inhibit CYT enzyme then plasma T levels = high + cardiotoxic
70
Q

Which 4 commonly-used substances inhibit CYT P450?

Hint - GEAU

A
  • grapefruit juice
  • erythromycin, clarithromycin – related antibiotics
  • antifungal drugs (ketoconazole, itraconazole)
  • ulcer drug cimetidine

(see notes for diagram)

71
Q

In which 5 ways can microsomal drug metabolism be modified?

Hint - CIAGI

A
  • competition between substrates e.g. warfarin/tolbutamide
  • inhibition of enzymes by drugs e.g. cimetidine, erythromycin
  • induction of enzyme systems (repressor gene function inhibited which normally stops enzyme-production → operator gene more active → more enzyme produced → rate of barbiturates + other drug metabolism increases → drugs become less effective)
  • age, nutritional status, liver disease
  • genetic polymorphism (some individuals have less/more of enzyme so metabolism rates vary)
72
Q

What is the significance of liver in drug handling and metabolism?

(Hint - major site of, first pass, bile production, liver function decreased)

A
  • major site of drug metabolism + drug metabolising enzymes
  • ‘first pass metabolism’ – drug delivery directly to liver after oral administration before reaching gut
  • bile formation - excretory route for less polar substances
  • liver diseases, failure, reduction of plasma proteins synthesis compromises drug metabolism/excretion
73
Q

What does the drug effect in individual patient depend on?

Hint - DARM-POPRG-DT

A
  • dose, potency, efficacy
  • mechanism of action
  • route of administration, extent of absorption
  • patient compliance
  • age, body weight, sex
  • rate of inactivation/excretion (liver, kidney function)
  • genetic factors
  • other drugs
  • placebo effect
  • disease
  • tolerance to drug
74
Q

What is clearance?

A

volume of blood cleared of drug per unit time (ml/min or L/hour) e.g. by elimination

75
Q

What is half-life?

A

time required for drug concentration to fall to half of initial value (linked to clearance)

76
Q

What is volume of distribution?

Hint - a pretend value needed for salt to dissolve in body

A

hypothetical volume of body fluid needed to dissolve the total amount of drug

77
Q

Which 2 variables relate the concentration of drug in plasma to total amount of drug in body?

A
  • plasma concentration/time profile for drug can be studied

- plasma concentration for different dosage regimes can be predicted

78
Q

What does a typical concentration/time curve for a single oral dose look like and which part is used in drug calculations?

A
  • (see notes for curve)

- we use AUC, area under the curve

79
Q

What is the formula for total body clearance of a drug?

Hint - CLDA

A

Cl (L/hr) = Dose(mg)/AUC0(mg*hr/L)

80
Q

Which other factor is used to calculate drug dosage?

A
  • half-life (t½)
81
Q

How can we calculate how many tablets do we need to reach steady plasma concentration?

A
  • a typical conc./time curves for repeat administrations
82
Q

When DAG activates PKC it phosphorylates target enzymes. Which actions are these enzymes associated with?

(Hint - MII chai with one neuro thing)

A
  • muscle contraction
  • inflammatory response
  • increased NT release
83
Q

When InsP3 binds to endoplasmic receptors causing an influx of Ca2+ into cytosol which actions is this important for?

(Hint - HCM)

A
  • muscle contraction
  • control of exocrine gland secretion
  • hormone release