Class Test (all lectures😎) Flashcards

1
Q

What other conditions can be caused from hypertension?

A

ischemic heart disease
stroke
heart failure
chronic renal failure

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2
Q

what other conditions can be caused from atrial fibrillation

A

heart attack

stroke

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3
Q

what is atrial fibrillation

A

irregular and abnormally fast heart beat

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4
Q

what other conditions can be caused from ischemic heart disease or coronary artery disease

A

heart failure

stroke

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5
Q

what other conditions can occur from diabetees

A

ischemic heart disease

stroke

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6
Q

what other conditions can occur from heart failure

A

hyperthyroidism

COPD

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7
Q

what diseases are involved in Ischemic heart disease/ coronary artery disease

A

angina
myocardial infarction (heart attack)
sudden cardiac death

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8
Q

How does mortality occur from stroke?

A
  • immediate death from thromboembolic event
    or
  • later death due to complications associated with loss of swallowing reflex (aspiration pneumonia)
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9
Q

what is the most common type of stroke

A

ischaemic

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10
Q

what is an ischemic stroke

A

occur as a result of an obstruction within a blood vessel supplying blood to the brain
OBSTRUCTION
weither thrombotic or embolic

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11
Q

what is a haemorrhagic stroke?

A

rupture in blood vessels

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12
Q

In an embolic ischemic stroke where does the blood clot come from ?

A

somewhere else in the brain

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13
Q

what are the key signs of a stroke?

A

Face paralysis
Arms (lack of movement, no power to grasp)
Speech
Time (phone 999 is is an emergency!)

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14
Q

what is a TIA

A

think of a TIA as a mini stroke a temporary ischemic attack

not associated with a permanent occlusion but a spasm or temporary clot that has formed and gone away

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15
Q

what is the biggest risk factor for a stroke?

A

TIA

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16
Q

what should you do if a stroke is suspected?

A

administer 300mg aspirin

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17
Q

what do CT scans show?

A

if the stroke is caused by a bleed (haemorrhagic) or a clot (ischemic, this is much more common)

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18
Q

are antiplatlets given if the patient has had an haemorrhagic stroke?

A

no

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19
Q

what should be done on admission for a patient having a stroke

A

Image within 24 hours of admission
assess swallowing reflex
stop all medicines

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20
Q

What medicines should especially be stopped when someone is admitted to hospital following a stroke, pending results of the CT scan and swallowing assessment results?

A
Anticoagulants
Thrombolytics
Antiplatlets
NSAIDS
Statins
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21
Q

What can be given as thrombolysis

A

Aletplase (tissue plasminogen activator)

Aspirin (300mg)

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22
Q

How long does it take to recover from a stroke?

A

18 months

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23
Q

At what time is the risk the highest for having another stroke?

A

Risk is highest early after just having had the stroke

but risk still increases as time goes on

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24
Q

What is the secondary prevention checklist for after a stroke?

A
Antiplatlets/anticoagulants
Blood Pressure
Cholesterol
Diabetes
Exercise
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25
Q

should antiplatlets be given after a haemorragic stroke?

A

NO

they shouldn’t be given on the day of admission or the following day!

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26
Q

What is used to predict risk of stroke in AF patients?

A

CHA2DSVAS score

if score greater than 2 then antiplatlet is required

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27
Q

IS INR monitoring required for DOACS

A

no

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28
Q

What does an INR score of <2 mean?

A

Blood clots too quickly

increase the patients warfarin

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29
Q

What does an INR score of >3 mean

A

Blood clots too slowly

Decrease the patients warfarin

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30
Q

What is a good INR

A

between 2-3

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31
Q

is there an antidote for DOACS

A

no (unlike warfarin which there is a Vit. K antidote for if too much warfarin is taken)

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32
Q

Should antihypertensives be administered immediately after a stroke?

A

No as the patient is usually HYPO-tensive after a stroke

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33
Q

What antihypertensive should be given to a <55 y/o patient

A

ACE inhibitor

ARB

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34
Q

What antihypertensive should be given to a >55y/o patient or an african caribbean patient of any age

A

CCB or thiazide like diuretic

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35
Q

What lipid lowering agent should be given

A

Simvastatin 40mg

LFT’s and lipids should be checked 1 month after initiation

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36
Q

What should max. simvastatin dose be while on amlodipine?

A

20mg

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37
Q

Should simvastatin be used in patients who have experienced a haemorrhagic stroke?

A

Probs not

Statins shouldn’t be used in haemorrhagic stroke patients unless the risk of a CV event outweighs the risk

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38
Q

Is diabetes a risk factor for stroke?

A

Yes

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39
Q

What lifestyle advice should be offered post-stroke

A

Exercise
Loose weight
Stop smoking (smoking increases patents risk of stroke by ~50%)
Alcohol?

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40
Q

What is a problem to consider when deciding to crush tablets or open capsules for putting in a feeding tube?

A

this means that they become unliscenced

consider legal liability issues?

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41
Q

What considerations should be taken into account when using soluble dispersible tablets

A

they can be used in a feeding tube
consider that they may have faster absorption, shorter duration and faster onset of action compared to when they are used in the non-dispersible form

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42
Q

What medicines should be started with someone that haas had a stroke?

A
initially stop all the patients medicines
start:
- aspirin 300mg initially
statin
anticoagulant
antihypertensive
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43
Q

when might the enteral feeding route be used

A

patient with swallowing difficulties
partial intestinal failure
phsycologial problems

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44
Q

what is TPN

A

total peripheral nutrition

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45
Q

what is PPN

A

peripheral parental nutrition

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46
Q

what delivers more nutrition TPN or PPN

A

TPN

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47
Q

how is TPN usually administered?

A

through a larger vein in the neck

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48
Q

when is parental nutrition used?

A

when there is inadequate absorption because of short bowel syndrome
when there is a GI fistula
when there is a bowel obstruction
when there is prolonged bowel rest for one reason or another
when there is severe malnutrition/ significant weight loss

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49
Q

what is enteral feeding

A

feeding through a tube

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50
Q

what form does the drug need to be in to cross the lipid/GIT membrane?

A

unionised form

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51
Q

what problems can occur with enteral feeding?

A
  • binding of the drugs to the tube
  • direct interaction of the drug and the feed (reduced drug absorption)
  • direct interaction of the drug and the feed causing tube blockage
  • drug- drug interactions
  • need for drug administration on an empty stomach
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52
Q

In E.F what drugs are associated with binding of drugs to the tube?

A

carbemazepine
diazepam
phenytoin

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53
Q

In E.F what drugs are associated with direct interaction of the drug and the feed, causing reduced drug absorption?

A
  • carbemazepam
  • ciprofloxacin
    phenytoin
    (generally drugs that are highly protein bound)
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54
Q

In E.F what kind of drugs are associated with direct interactions of the drug + feed causing tube blockage?

A

acidic solutions (e.g. chlorphenamine or promethazine)

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55
Q

In E.F what drugs cause an additional consideration needing them to be administered on an empty stomach

A

Penicillin

Ketoconazole

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56
Q

What do drug tests test for?

A

Only specific drugs or drug classes
Can only detect substances when they are present above cut-off levels

After drug screening

Quantative

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57
Q

What does drug screening test for?

A

immuno-assay
test positive or negative

QUALATATIVE

screening then testing

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58
Q

what is an example of a common screening test

A

Pregnancy test as it is qualitative not quantative

It doesnt tell you how much baby you have but it tells you that you have a baby

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59
Q

What are the positive aspects of a drug screenig test

A

inexpensive
easily automated
quickly produce results

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60
Q

What lab drug testing methods are used?

A
  • gas chromatography
  • high performance liquid chromatography
  • gas chromatography
  • GC + MS + MS
  • LC + MS
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61
Q

What factors are considered in test reliability

A

test sensitivity and test specificity

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62
Q

what is test “sensitivity”

A

proportion of + results a testing method correctly identifies
True Positive Rate

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63
Q

what is test “specificity”

A

proportion of - results a testing method correctl identifies
True Negative Rate

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64
Q

What is the limit of detection

A

lowest amount of the analyse that can be dented but not quantified
Lower than LoQ

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65
Q

What is the limit of quantification

A

Lowest amount of analyse in the asme that can be quantataimvley determined with suitable precision and accuracy
Higher than LoD

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66
Q

What is window of detection

A

Length of time substance or metabolites can be detected in a biological matrix

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67
Q

What should % accuracy be for HPLC assay of drug in a dosage form?

A

> 99.5%

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68
Q

What should % accuracy be for HPLC assay of drug metabolite in plasma be?

A

> 90%

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69
Q

When does cross reactivity occur?

A

When a test cannot specify between substances tested for and substances that are chemically similar

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70
Q

What is the range of specificity

A
A specific method is one that measures only ONE particular analyte and which does NOT suffer interference if another substances are present in the sample
MOST specific - IR Spectroscopy
then HPLC and GC 
then titration
then UV (not very specific)
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71
Q

What is the test matrix?

A

Biological specimen used for testing for the presence of the drug

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72
Q

What window of detection does breath have

A

Short (mins-hours)

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73
Q

What window of detection does blood have

A

short (mins-hours

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74
Q

What window of detection does oral fluid have

A

short (mins to hours)

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75
Q

What window of detection does urine have have

A

medium (hours to weeks)

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76
Q

What window of detection does sweat have

A

medium (hours to days)

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77
Q

What window of detection does meconium have

A

long (weeks to months)

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78
Q

What window of detection does hair have

A

very long (days - years)

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79
Q

what is a point of care test (POCT)

A

conducted when a specimen is collected

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80
Q

What do specimen validity tests determine

A

whether a speccing has been diluted, adulterated, substituted

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81
Q

What do specimen validity tests for urine determine

A

Compare urine specimen characteristics with acceptable density and composition ranges for human urine
- detect any adulterants
creatine and pH analysis

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82
Q

What levels indicate that a urine specimen has been diluted?

A

creatinine concentration > 2mg/DL or <20 mg DL

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83
Q

Why is infection especially bad in patients that are suffering from cancer/malignancy?

A

They cannot mount a white cell count to an infection and fight it off!

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84
Q

What causative organism is likely to be casing infected COPD

A

moraxhalla
strep. pneumonia
haemophillus influenzae

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85
Q

What antibiotic is usually 1st line for respiratory infections?

A

amoxicilin

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86
Q

What organism is likely to cause cellulitis

A

Staph. aureas

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87
Q

What antibiotic is good for cellulitis

A

Fluloxacillin

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88
Q

How are aminoglycosides excreted?

A

renally

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89
Q

How are glycopeptides excreted?

A

renally

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90
Q

How are cephalosporins excreted?

A

renally

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91
Q

How are penicillins excreted?

A

renally

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92
Q

How are anti-vitals excreted?

A

renally

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93
Q

How are macrolides excreted?

A

hepatically

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94
Q

How are tetracyclines excreted?

A

hepatically

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95
Q

How are isoniazid excreted?

A

hepatically

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96
Q

How are rifampicin excreted?

A

hepatically

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97
Q

How is ceftriaxone excreted?

A

both hepatically and really

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98
Q

what are the three types of ACUTE renal failure

A

pre-renal
intra-renal
post-renal

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99
Q

What happens in pre-renal failure

A

reduction in renal perfusion
(compromised blood supply to the kidney caused by maybe traumatic blood loss, cardiac failure or drugs that cause reduced renal perfusion)

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100
Q

What are the different types of intra-renal failure

A

renal tubular necrosis
interstitial nephritis
glomerulonephritis

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101
Q

What happens in ‘renal tubular necrosis’

A

intra-renal failure
- renal hypo=perfusion
caused by nephrotoxicity (caused by nephrotoxoty may be caused by antibiotis)

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102
Q

what happens in interstitial nephritis

A

Intra-renal failure
nephrotoxicity caused by penicillins, cephalosporins
nephritis is inflammation of the kidney

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103
Q

what happens in Glomerulonephritis

A
immune complexes form 
glmoerulonephritis is inflammation of the kidney caused by an immune response
e.g.
- endocarditis
- phenytoin
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104
Q

what happens in “post-renal” failure

A

urinary tract obstruction

  • kidney stones
  • thrombosis
  • tumours
  • benign prostatic hypertrophy
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105
Q

what kind of renal replacement is used in acute renal failure

A

hemofiltration (if <10ml/min)

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106
Q

what is chronic renal failure

A

progressive deterioration over months or years

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107
Q

when do symptoms of chronic renal failure start to be seen?

A

when renal function is <30 ml/min

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108
Q

what is required at end stage renal failure

A

renal replacement

  • hemodialysis
  • chronic ambulatory peritoneal dialysis
  • kidney transplantation
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109
Q

what may cause chronic renal failure

A
  • chronic glomerulonephritis
  • chronic pylenephritis
  • interstitial nephritis
  • hypertension
  • urinary obstruction
  • polycystic kidney disease
  • diabetes mellitus
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110
Q

How is distribution affected in renal impairment?

A
  • distribution of water soluble drugs (fluid retention/dehydration)
  • changes in pH
  • decreased binding of drugs to albumin (consider acidic drugs like warfarin and phenytoin)
  • increased binding to alpha-1-acid glycoprotein (AAG) (consider basic drugs such as propranolol, verapamil, prazosin etc, they become highly bound to AAG during renal failure .)
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111
Q

What changes are seen to albumin in renal failure

A

Albumin levels are lower in kidney/renal failure especially if it is nephrotic kidney failure

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112
Q

How is the volume of distribution of Digoxin altered in renal failure?

A

It is decreased

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113
Q

How are drugs eliminated renally?

A

Glomerular Filtration (passive)
Active secretion
Reabsorption

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114
Q

what drugs are renally excreted via glomerular filtration

A
small MW drugs 
unbound drugs (fu)
Drug Cl(renal)= fuXGFR
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115
Q

What happens in active renal secretion?

A

Organic ion/cation transport proteins do the secretion
- efflux transporters (PgP)
not inhibited by protein binding at all
Drug Cl (renal)>fu X GFR

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116
Q

How are drugs renally absorbed?

A
Passive (small/unionised/lipophillic drugs)
Active (glucose and vitamins)
pH dependent (weak acids/bases with pH close to urine)
Drug CL (renal) < fuX GFR
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117
Q

What is the general eon for renal clearance (remember for any drug all these processes can occur)

A

Renal Clearance = filtration + secretion - reabsorption

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118
Q

What drugs are metabolised in the kidney

A

cortisol
insulin
vit D
therefore there clearance/activation is reduced in renal failure

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119
Q

How is hepatic metabolism altered in patients with renal failure?

A
Hepatic metabolism is altered
- effects on CYP
- inhibitory metabolites may accumulate
- regeneration of the parent drug
Varies according to CYP enzyme 
- accumulation of waste products or toxic metabolites/ accumulation of renally cleared metabolites
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120
Q

IS it alright to give someone with renal failure morphine?

A

You should be concerned about giving someone with renal failure morphine because of its associated toxic metabolite accumulation in renal impairment

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121
Q

What exogenous marker of renal failure us used?

A

Cr EDTA

consider it as actual GFR

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122
Q

What endogenous marker of renal failure is used?

A

urea
creatinine
cystatin C

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123
Q

What are some limitations associated with using the Cock-croft gault equation

A

Cock-croft Gault eqn. assumes that the patients…

  • creatinine concentration is at steady state (this isn’t true if renal function is rapidly changing)
  • creatinine production is normal
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124
Q

How is creatinine produced?

A

Creatine (liver) –> creatine phosphate (muscle) –> creatinine

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125
Q

When/ in what patient groups is creatinine production not always normal?1

A
  • creatinine production is lower in the elderly/ malnourished people/ people with muscular dystrophy
  • lower in children
  • lower if severely under or overweight

Cock-croft gault equation for estimating renal function often OVER-ESTIMATES renal function in elderly patients

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126
Q

What is a normal BMI

A

18.5-24.9

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127
Q

What is an underweight BMI

A

<18.5

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128
Q

What is an overweight BMI

A

25-29.9

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129
Q

What is a severely obese BMI

A

35-39.9

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130
Q

What is a morbidly obese BMI

A

> 40

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131
Q

What PK factors does obesity impact upon?

A

Drug VD

Drug Clearance etc…

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132
Q

What drug characteristics does VD depend upon?

A

MOleculular size
ionisation state
water/lipid solubility

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133
Q

What kind of tissue is increased in obesity?

A
Adipose tissues
Muscle and connective tissues
Blood volume
alpha-1 acid glycoprotein
cholesterol
triglycerides
free fatty acids

All these factors alter drug distribution and protein binding

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134
Q

How much water does adipose tissue contain?

A

30% water

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135
Q

How is hepatic function altered in obesity?

A

Phase 1 metabolism-CYP enzymes are affected (CYP3A4 function decreases while the others increase)

Phase 2 metabolism increases

Liver blood flow increaes
Consider does the patient have a bigger liver?

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136
Q

how is renal function altered in obesity?

A
increased renal plasma flow (increased C.O., increased blood volume, increased hydrostatic pressure)
increased GFR
(no change in renal hypertrophy)
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137
Q

what age is a preterm neonate

A

born at <37 weeks gestation

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138
Q

what age is a term neonate

A

born at 37-42 weeks gestation

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139
Q

what age is a post-tern neonate

A

born at >42 weeks gestation

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140
Q

what age is a neonate?

A

0-28 days old

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141
Q

what age is an infant

A

28 days –> 24 months

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142
Q

what age is a child

A

2-12 yrs

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143
Q

what age is an adolescent

A

12-18 urs

144
Q

how is stomach pH altered in children

A

stomach pH is neutral at birth
then falls to pH3
then back to neutral
finials settles to adult pH at age of 2 years

145
Q

how is gastric emptying and motility altered in children

A

gastric emptying and motility reduced in neonates (0-28 days) but, increased in older infants

146
Q

how is gut wall and lumen altered in children

A

gut wall permeability is high at birth
decreases over the first few weeks of life

Initially in babies…
bile secretion is reduced
first pass metabolism is reduced
but there is increased beta-glucoronidase activity
active and passive transport systems begin to mature

147
Q

What is protein binding like in neonates?

A

LOW albumin (low protein binding of acidic and neutral drugs, greater free fraction)

Low alpha-acid glycoprotein (low binding of basic drugs, greater free fraction)

endogenous binding inhibitors (bilirubin, free fatty acids)

Reduced protein binding

148
Q

What does reduced protein binding cause

A

higher free fraction of the drug

  • free fraction is active and free to interact with receptors
  • bound fraction is inactive and not free to interact with the receptors
149
Q

what kind of dose adjustment is required if a patient has a high volume of distribution?

A

Higher VD than normal –> larger dose required to ensure same therapeutic concentrations are reached

150
Q

when does baby GFR change?

A

increases rapidly in first 2 weeks

reaches adult value relative to size within 1-2 years

151
Q

when does renal tubule secretion mature?

A

within first 12-15 months

152
Q

when does reabsorption processes mature

A

up until adolescence

153
Q

what CYP enzymes are absent at birth?

A

CYP 1A2 (needed for theophylline metabolism)

154
Q

what CYP enzymes are working at birth?

A

2C9 and 2C19 (warfarin phenytoin) only 30% of full expression

2D6 (BB, antiarrythimics) only 4% of adult expression at birth

155
Q

what is the definition of substance misuse?

A

illegal, non medical use of a limited number of substance, most of them drugs which have properties of altering the mental state in ways that are considered by social norma and defined by the statute to be inappropriate, undesirable, harmful, threatening or at a minimum culture-alien

156
Q

What factors need to be present to diagnose dependence?

A

Must be at least 3 of the following presnt simultaneously in the last 12 months

  • cognitive behaviour aspects
  • consequences
  • psychological
157
Q

What cognitive behaviour aspects are associated with drug dependence

A

strong desire or compulsion to use the substnace

difficulties in controlling the use of the substance

158
Q

what consequences are associated with drug dependence

A

neglect of alternative interests due to substance misue

persistence of substance use despite evidence of harmful consequences

159
Q

what psychological consequences are associated with drug dependence?

A

tolerance

withdrawl symptoms

160
Q

How many factors need to be present to diagnose dependence

A

at least 3 of the following present simultaneously in the last 12 months

161
Q

What factors need to be present to diagnose drug mususe

A

1 or 2 factors present

162
Q

What is tolerance

A

Identicle doses of a drug induce decreasing levels of effect

higher doses are required to achieve the same effect

163
Q

what is addiction

A

compulsive and repetitive use of a drug often at portantially harmful doses
tolerance and physical dependence may develop

164
Q

what is dependence

A

result from chronic use of a drug

  • has produced tolerance
  • adverse physical symptoms (withdrawal symptoms) occur from sudden discontinuation and rapid dose reduction
165
Q

what is methodone

A

a MU opioid agonist

166
Q

what is morphine

A

a mu-opioid agonist

167
Q

what is buprenorphine

A

a partial agonist at Mu and Kappa opioid receptors
an antagonist at delta receptors
(because only a partial agonist then naloxone will only partially reverse the effects of buprenorphine)

168
Q

why does buprenorphine have a longer duration of a action compared to morphine

A

it slowly dissociates from its receptor

169
Q

what happens when buprenorphine binds to Mu and Kappa receptors?

A

hyperpolarisation

reduced neuronal excitability

170
Q

what is NALOXONE

A

an opioid antagonist

block the effects of opioids

171
Q

What can result from severe alcohol use

A

Malnutrition
Malabsorption of Vit B
May progress to Korsakovs psychosis, wernickes encephalopathy, aggression

172
Q

what can result from use of cannabinioids

A

psychosis/paranoia

THC is the mind altering substance- tetra hydro cannabinol

173
Q

what can use of opioids lead to

A

anxiety and depression

174
Q

what can use of BZ lead to

A

anxiety
depression
memmory loss
aggression

175
Q

what can use of stimulants/hallucinogens lead to

A
mania
depression
nightmares
psychosis
flash-backs
176
Q

What can used of image enhancing drugs/steroids/tanning drugs lead to?

A

aggression
depression
diabetic complications
liver disorders

177
Q

what are some general health risks associated with taking durgs

A
infections (anthrax, botulism)
BBV
liver damage
cardiomyopathy/cardiac enlargement 
impaired cognitive function
consider implications of drugs that prolong QT interval
178
Q

does methadone prolong the QT interval

A

AYE it does!
prolong QT interval –> torsade de points –> sudden death
ECG screen

179
Q

what does disulfuram do

A

used as an alcohol deterrent
- non toxic when administered alone
but, when administered with alcohol it makes the person sick as it changes the metabolism of alcohol
this causes:
flushing, systemic vasodialtion, respiratory difficulties, nausea and hypotension and makes them feel really unwell!

180
Q

how does disulfuram work/

A

it inhibits acetylhydrogenase which normally metabolises alcohol

181
Q

what are the dangers of relapse

A

tolerance has decreased
OD risk has increased
encourage naloxone supply

182
Q

what can be supplied in I.E.P

A
syringe
spoon
filter
alchol wipe
citric acid sachet
cin bin
information about health promotion
water for injection
foil for smoking the drug
183
Q

what cannot be supplied in I.E.P.

A

tourniquet

184
Q

what changes can a pharmacist make in a methadone Rx

A

minor typographic errors (spelling)
words and figs of total Q (but not both)
pharmacist making change must write name, date of change, sign and GPhC number

185
Q

what is the WHO definition of an ADR

A

any response to a drug which is noxious, unintended and occurs at doses used for prophylaxis, diagnosis or therapy

186
Q

what scenarios are excluded in the definition of ADR

A
accidental/intentional poisoning
therapeutic failures
drug abuse
errors in drug administration
(remember all ADRs are adverse events but not all adverse events are ADRs)
187
Q

what is toxic epidermal necrolysis

A

potentially life threatening skin disorder
widespread redness
big bits of detatchemtn of skin and mucous membranes
resulting in exfoliation and possible sepsis and or death
affects >30% of the skin and mucous membranes

188
Q

what is SJS

A

stevens-johnson syndrome
affects skin, mucous membranes, genitals and eyesc
caused my unpredictable adverse reaction to certain medications or sometimes caused by infection
starts with flu like symptoms ,
then a red/ purple rash forms, spreads and forms blisters
affected skin eventually dies and falls off!
medical emergency
affects <20% skin and mucous membranes

189
Q

what are the symptoms of SJS/TEN

A
fever 
sore throat
skin rash 
rash forms blisters 
skin falls off when pressure is applied
(skin, mucous membranes (crusty haemorrhages), genitals, eyes (conjunctivitis)
190
Q

does SJS/TEN occur immediately?

A

it can occur immediately or may occur several weeks after drug exposure

191
Q

what are some of the ADR associated with tetracyclines

A

black hairy tongue

teeth staining

192
Q

what are some of the ADR associated with admidarone

A

slate grey pigmentation

193
Q

what is the ADR associated with thalidomide

A

phocomelia (rare congenital deformity in which the hands or feet are small and attatched close to the body/trunk, they are very underdeveloped or may be completely mssing

194
Q

what are the limitations on clinical trials of medicinew

A

only small number of patients
restricted population (not representative of many different patient groups re. age/sex/ethnicity)
narrow indication
only short duration of drug exposure

195
Q

how many patients are involved in Phase 1 clinical trials?

A

20-50 healthy volunteers

gather preliminary data

196
Q

how many patients are involved in phase 2 clinical trisls

A

150-300 patients with disease

determine safety and dosage regimen data

197
Q

how many patient are involved in phase 3 clinical trials

A

200-400 more varied patient groups

determine short term safety and efficacy

198
Q

what is phase 4 clinical trials

A

post approval studues

determine any specific safety issues

199
Q

what cardiotoxicity is often experienced from anti-cancer therapy

A
cardiac dysfunction
heart failure
arterial hypertension
vasospastic ischemia 
thromboembolic ischemia
arrythmia
QT prolongation
200
Q

is cardiotoxicity from chemo. reversible?

A

some of it is irreversible while some is reversible

201
Q

what is type 1 cardiotoxicity

A

non-reversible damage

PERMANANT DAMAGE

202
Q

What is the pathophysiology of type 1 cardiotoxicity

A

cell loss

necrosis/apoptosis

203
Q

What is the manifestation of type 1 cardiotoxicity

A

cardiomyopathy
heart failure
MI
thrombosis

204
Q

How is type 1 cardiotoxicity diagnosed?

A
injury marker release
progressive contractile dysfunction
cardiac remodelling 
progressive CV disease 
CV therapy required
205
Q

What is type 2 cardiotoxicity

A

REVERSIBLE/ NON-PERMANANT damage

206
Q

What is the pathophysiology of type 2 cardiotoxicity

A
Cellular dysfunction
( mitochondrial dysfunction/protein dysfunction)
207
Q

what is the manifestation of type 2 cardiotoxicity

A

temporary contractile dysfunciton
vasospastic angina
arterial hypertension

208
Q

How is type 2 cardiotoxicity diagnosed?

A

no injury marker released
- reversible contractile dysfunction
reversible arterial hyper perfusion
eventually this leads to normalised CV function

209
Q

Please give an example of a chemotherapeutic drug that is well documented to produce cardiotoxicity problems

A

doxorubicin

fortunately, problems/reduction in contractile function may recover if compensatory hypertrophy occurs

210
Q

what are the risk factors for doxorubicin and CV toxicity

A

high cumulative dose over time (>200mg/m)
pre-existing heart disease
age (young children and adults >65y/o)
mediastinal (chest radiation)
combination therapy (this may have a synergistic effect)

211
Q

when does doxorubicin associated cardiotoxicity occur?

A

typically months to years after exposure

212
Q

what may be the result of doxorubicin associated cardiotoxicity

A
myocyte death (irreversible)
systolic and diastolic heart failure
remember there is a genetic element to this and patient variation does occur
213
Q

explain the processes of heart failure

A

1) normal heart
2) cardiomyocute injury or impairment
3) maladaptive changes
4) cardio-myopathy
5) heart failure

214
Q

what the cardiac myocyte is killed can it be replaced?

A

NO
(heart muscle becomes thinner, looses its contractility, all 4 chambers become dilated)
heart pumping and refilling is reduced

215
Q

what happens as the heart is put under more and more stress?

A

time goes on, heart suffers from reduced cardiac function and greater cardiac stresses
compensatory mechanisms become diminished (cardiac hypertrophy, activation of survival factors)
put under more and more stresss
leads to heart failure

216
Q

what exact effect does doxorubicin have on cardiac myocytes

A

loss of myofibrils
vacuolar degeneration
interstitial fibrosis

217
Q

what is the mechanism of dioxin cardiotoxicity

A

1) Lipid oxidation at the cell and mitochondrial membranes
2) Mitochondrial DNA damage
3) Produce Reactive oxygen species –> energy depletion
4) impaired calcium handling in sarcoplasmic reticulum
5) transcription of muscle proteins inhibited
6) Impaired singling –> down regulation of adrenoceptors
7) induction of apoptosis (cardiac cell death)

218
Q

what genetic variation can increase the risk of SJS or TEN

A

genetic variation in HLA (human leucocyte antigen complex)
this HLA-B*15:2 complex helps the immune system to distinguish the body’s own proteins from proteins that are made by foreign invaders

219
Q

what ethnic groups most commonly have genetic variation in HLA complex?

A

chineese
south-east asian
FDA recommends screening for this genotype before commencing treatment with carbemazapine

220
Q

what kind of illnesses do children suffer from?

A

ones that are only acute and not long term

221
Q

is drug absorption the same in children as it is in adults?

A

NAW!
absorption is reduced in neonates and infants, it gradually increases during childhood

consider gastric emptying, bowel salts, length of intestine for absorption, differences in plasma proteins

222
Q

what is gastric pH at birth

A

pH6-8 (in both term and pre-tern neonates)

this is due to residual amniotic fluid in the wee baby’s tummy

223
Q

when is adult pH 2-3 reached?

A

by the age of 2-3 years

224
Q

How does the higher pH of baby’s tummy affect drugs?

A

Affects GI absorption of drugs

  • acid labile drugs (e.g. penicillins) aren’t broken down as much and so have increased bioavailability (F)
  • drugs that are weekly acidic have lower bioavailability in neonates, they exist in the ionised form so aren’t absorbed (e.g. phenobarbital or phenytoin)
225
Q

do neonates have increased gastric emptying?

A

yes

  • caused my milk
  • longer GI transit times
  • different peristaltic action (decreased peristalsis)
  • reduced S.a for absorption
  • drug absorption is affected
226
Q

IS BILIARY function reduced in neonates?

A

YEP
( rate of bile acid synthesis, pod size, intestinal transit o bile acids are all reduced)

This causes reduced oral bioavailability for drugs that require solubilisation, ones that are hydrophobic/fat soluble

227
Q

what about colonisation of the baby’s stomach by bacteria

A

varies with age and route of delivery/birth/type of feeding/ any medicines?

228
Q

what is the difference in TBW:fat in babies compared to adults

A

higher TBW: fat ratio
they have a higher water content (think babies are squishy and full of water)
this will increase VD for hydrophilic drugs and decrease VD for hydrophobic drugs

229
Q

what is the difference in blood albumin in babies compared to adults

A
babies have a lower albumin
drugs that are normally highly bound to albumin are less bound
increased free drug concentration
increased plasma concnetration
toxicity?
increased drug excretion as it is free
230
Q

what is the difference in alpha-1 acid glycoprotein in babies compared to adults

A

babies have a lower alpha-1 acid glycoprotein
- drugs that are normally highly bound to alpha-1 acid glycoprotein are less bound
higher VD of these drugs
increased plasma concentration?
toxicity?
greater bioavailability

231
Q

what is TBW? and EXW?

A
TBW= total body water 
ECW= extracellular water
232
Q

how does TBW change as the baby grows?

A

TBW % doesn’t change that much after 1 year of age

233
Q

how does EXW change as the baby grows/

A

continuous decrease in ECW from infancy–> young adulthood

234
Q

how is Phase 1 enzyme metabolism different in babies compared to adults?

A

it is reduced

235
Q

how is phase 2 enzyme metabolism different in babies compared to adults?

A

it is reduced

236
Q

how is hepatic blood flow different in neonates compared to adults

A

hepatic blood flow is reduced in neonates

initially babies 1st pass metabolism is lower than adults, this gradually increases as does cardiac output over time

237
Q

what does drug elimination via the kidneys depend on?

A

glomerular filtration
tubular excretion
tubular reabsorption

238
Q

How quickly does GFR increase in neonates

A

very rapidly

reaches adult level about 12 months

239
Q

when does tubular secretory capacity in neonates mature

A

matures much more slowly than neonates

matures at 15 months of age

240
Q

what does tubular reabsorption mature in neonates?

A

reaches adult levels at 2 years of age

241
Q

if parental administration is required what route should be used

A

IV, (s.c is less common)

- it might be hard to find the vein

242
Q

should IM administration be used in wee babies?

A

NO, this is very distressing and painful for the wee baby

243
Q

what considerations should be taken into account when administering drugs IV to a baby

A

they only have a small blood volume so a large volume of liquid cannot be administered or else this may cause heart failure 💔

244
Q

are orodispersible tablets a good shout to give to babies/ children

A

good as it doesn’t require swallowing but may be problematic as children only have a small

245
Q

what must always be remembered when calculating doses for children/

A

calculated doses MUST NEVER EXCEED EXCISTING ADULT DOSE!

246
Q

How should chronic conditions in children be treated?

A

Regular clinical review should be undertaken considering the childs age/weight/physiological development to ensure that the dose remains appropriate

247
Q

what patient characteristics is usually used to calculate child doses

A

body weight (body surface area is more accurate and a better correlate in terms of body processes but is considered impractical for a majority of drugs that have a wide therapeutic window)

248
Q

what is different between the tastebuds of children and that of acults

A

childen have more taste buds
they are more sensitive to bitter/sweet tastes
regenerate every 2 weeks

249
Q

what important consideration needs to be made in terms of child median and excipients

A

unknown effect of GRAS (generally regarded as safe) excipients in children

250
Q

what adverse effect can the excipient Aspartame have in children?

A

PKU (phenylketonuria)

251
Q

what adverse effect can the excipients ethyl/polyparabens have in children?

A

endocrine disruption –> infertility

252
Q

what adverse effect can the excipient (proplyethylene glycol) have in children?

A

lactic acidosis/seizures

253
Q

what adverse effect can the excipient sodium metabisulphite have in children?

A

airway distress

254
Q

what adverse effect can the excipient EDTA have in children?

A

haemolysis (RBC rupture)

255
Q

what adverse effect can the excipient ethanol have in children?

A

alcohol intoxication

256
Q

what adverse effect can the excipient Benzylalcohol have in children?

A

gasping baby syndrome

257
Q

what adverse effect can the excipient Tween80 have in children?

A

hypotension

258
Q

what is the aims of a medicaiton review

A
  • improve therapy
  • reduce risk of potential or actual problems
  • improve cost effectiveness (reduce waste or use medications that are better value for money)
259
Q

what is a medicines review

A

structured clinical examination of a patients medicines
objective of reaching an agreement with the patient about treatment,
optimise the impact of medicines
minimise the number of medicines related problems
reduce waste

260
Q

what is a grade 0 med review

A

review of medicine without patient and without medical records

261
Q

what is a grade 1 med rev.

A

interact with patient

enquire re. compliance

262
Q

what is a grade 2 med. rev.

A

primary/secondary care have drug history and medical notes

263
Q

what is a grade 3 med rev

A

drug history
medical records
lab data

264
Q

what pt groups will get the most benefit from a med. rev.

A
elderly
frail
polypharmacy
high risk meds 
residents in care homes
patients recently discharged from hospital
265
Q

what shouild be considered in a medicines review>

A

med appropriatness
clinical need
does the pt have any concerns/problems
monitoring

266
Q

what are some examples of anticholinergic medicine

A

parkinsons medications
diphenhydraomine
antipsychotics
chlorpromazine

267
Q

what are the side effects of anticholinergic meicines

A
dry mouth
blurred vision
constipation
drowsiness
sedation
hallucination
impaired memmory
increase fall risk :-(
268
Q

what is the calgary cambridge model

A
Provide structure and build rapport throughout
-initiate the session
gather information
physical examination if appropriate
explanation and planning
closing the session
269
Q

what medicines should be stopped in sick days (unwell with vomiting or diarrhoea, fevers, sweating or shaking)

A
Stop when unwell, start 24-48 hours after eating and drinking normally
ACE inhibitors
ARBs
NSAIDS
Diuretics
Metformin
270
Q

what should you do if you are taking insulin and you are unwell

A

golden rule NEVER STOP TAKING INSULIN
- when you aren’t well the body natural response is to make more sugar so, if unwell you will need to take more insulin, have more fluid to drink and do more testing
to reduce the risk of DKA (diabetic kept acidosis) this is dangerous and occurs when the body blood sugar is too high and the body cannot produce more insulin
Always test for ketones in urine too when unwell and a diabetic

271
Q

what is a drug interaction

A

pharmacological or clinical response to the administration of a drug differs from the known effects of the two agents when given alone

272
Q

what is the object drug

A

the one that is affected by the itneraction

273
Q

what is the precipant drug

A

the drug that actually causes the interaction

274
Q

what happens in a pharmacokinetic drug interactions/

A

altered level of the object drug

275
Q

what happens in a pharmacodynamic interaction

A

change in activity of the object drug, but no change in concentration level!

276
Q

where can drug drug interactions occur?

A
site of absorption
plasma peoteins
liver (site of metabolism)
site of action
site of excretion/reabsorption
277
Q

How does chelation result in altered absorption?

A

antibiotics (e.g. tetracycline) will chelate with metal ions in antacids (iron, aluminium, calcium) and will form insoluble complexes this is bad as there is a loss of therapeutic effect of tetracycline (pharmacokinetic interaction)

278
Q

Why is it bad if there is an interaction between drugs causing a change in gastric pH

A

many drug absorption is dependent on stomach pH, if the stomach pH is changed then a particular drug may not be absorbed as dissolution may not occur, if dissolution doesnt occur then the drug wont go into solution and therefore wont be absorbed

279
Q

What are some examples of drugs that increase the rate of gastric empting

A

metoclopramide

domperidone

280
Q

what are some examples of drugs that decrease the rate of gastric emtying

A

opioids

anticholinergics

281
Q

what are the dangers associated with drugs that decrease the rate of gastric emptying?

A

decreased time for dissolution of drugs, therefore there is decreased time for absorption
This can be very dangerous if an important drug isn’t adequately absorbed (e.g. Digoxin)

282
Q

what are the dangers associated with drugs that interact via plasma protein binding?

A

e.g Digoxin and Quinadine
Digoxin is extensively bound to plasma proteins , as is quinadine
Quinadine will displace the digoxin from the plasma proteins
Therefore the plasma concentration of digoxin will be higher, this is dangerous
However, the main issue in this scenario is because the quinine also alters the excretion of digoxin resulting in digoxin toxicity
- arrhythmia, visual disturbances, GI disturbances

283
Q

what is the role of Phase 1 drug metabolism

A

OXIDATION
increase water solubility (for excretion)
reduction
hydrolysis

284
Q

what single CYP enzyme is omeprazole metabolised by?

A

CYP219

285
Q

what single CYP enzyme is diclofenac metabolised by?

A

CYPC19

286
Q

what single CYP enzyme is des metabolised by?

A

CYPC19

287
Q

What happens if metabolism of an anti diabetic medicine is inhibited

A

This is bad…
Metabolism inhibited
Concentration will be increased
It will have more effect on reducing blood sugar levels
Blood sugar levels will fall to very low concentrations
Hypoglycaemia
Pt may have a seizure

288
Q

Is Rifampicin an CYP enzyme inducer or inhibitor?

A

Inducer

289
Q

Is Carbamazepine an CYP enzyme inducer or inhibitor?

A

Inducer

290
Q

Is Phenobarbital an CYP enzyme inducer or inhibitor?

A

Inducer

291
Q

Is Nevirapine an CYP enzyme inducer or inhibitor?

A

Inducer

292
Q

Is Pioglitazone an CYP enzyme inducer or inhibitor?

A

Inducer

293
Q

Is St Johns Wort an CYP enzyme inducer or inhibitor?

A

Inducer

294
Q

fo CYP inducers have a gradual onset or offset/

A

gradual as time is needed to produce the new CYP proteins!

295
Q

what does CYP induction cause?

A

reduction of plasma concentration of substrate drugs

risk of therapeutic failure

296
Q

what concerns are associated with removal of a CYP inducer

A

toxic levels of substrate
or also
greater formation of toxic metabolites (if pro-drug)

297
Q

is carbidopa a CYP inhibitor or inducer

A

inhibitor

298
Q

is levodopa a CYP inducer or inihibitor

A

inhibitor

299
Q

What are P-Glycoproteins

A

use ATP to pump foreign things out of the cell

300
Q

where are P-Gp’s expressed

A

in the intestine
kidney
bile cannuli
blood brain barrier

301
Q

What happens if P-Glycoproteins are inhibited?

A

More drug will be in the blood stream

potential toxic effects

302
Q

What happens if P-Glycoproteins are induced?

A

there will be less drug in the blood stream

diminished therapeutic effects

303
Q

What does digoxin do to PGP’s

A

PgP substrate

304
Q

What does diltiazem do to PGP’s

A

Pgp substrate

305
Q

What does ciclosporin do to PGP’s

A

Pgp substrate

306
Q

What does dabigatran do to PGP’s

A

Pgp substrate

307
Q

What does etiolate do to PGP’s

A

Pgp substrate

308
Q

What does macrocodes do to PGP’s

A

Pgp inhibitor

309
Q

What does amiodarone do to PGP’s

A

Pgp inhibitor

310
Q

What does quinadine do to PGPs

A

Pgp Inhibitor

311
Q

what does verapamil do to Pgps

A

Pgp inhibitor

312
Q

What does rifampicin do to PGP’s

A

Pgp inducer

313
Q

What does dexamethasone do to PGP’s

A

Pgp inducer

314
Q

What does ST Johns Wort do to PGP’s

A

Pgp inducer

315
Q

clarithromycin

A

Pgp inhibitor

this results in increased bioavailability and decreased renal clearance

316
Q

what happens in a pharmacodynamic interaction

A

Classic competitive antagonism where one drug attenuates the affect of another (beta agonist salbutamol/beta antagonist propranolol)
OR
one drug may augment the action of another drug
ramiptil (ACE i) + amlodipine (CCB)

317
Q

how are DDI’s assessed for in drug development?

A

mechanism based approach (this is because it is physically impractical to assess for all possible DDIs)
also DDI usually occur by a number of mechanisms and not just the one

318
Q

what processes fo pharmacokinetic interactions affect drugs

A
absorption
distrubution
metabolism
excretion
(changes drug serum concentration)
319
Q

what happens in a pharmacodynamic interaction

A

drug A is altered by the presence of drug B without affecting its pharmackinetics/serum concentration
drug synergism or drug antagonism

320
Q

what drug absorption interactions can occur

A

changes in gastrointestinal pH
chelation and other complexing mechanisms
changes in GI motility
induction of inhibition of drug transporter proteins
malabsorption caused by drugs

321
Q

what drug distrubution interactions can occur

A

protein binding interactions

induction or inhibition of drug transporter proteins

322
Q

what drug metabolising interactions can occur

A
changes in first pass metabolism
inhibition or induction of 1st pass metabolism
enzyme induction
enzyme inhibition
genetic factors
323
Q

what drug excretion interactions can occur

A
changes in urine pH
changes in acute renal tubule excretion
changes in renal blood flw
changes in biliary excretion
entero-hepatic shunt
324
Q

why is GI pH a big deal

A

any time the pH of the environment is changed then the drug ionisation will also be change

325
Q

js info about potential DDIs required>

A

yep well defined profile of potential interactions is required by the FDA and other regulatory bodies for all drugs and drug candidates

326
Q

what family are CYP enzymes from ?

A

hemoprotein

327
Q

what aspects of CYP enzymes is important for their activity

A

Porphyrin iron in the middle

Important for transferring the oxygen molecule onto the drug molecule for the oxidation reaction

328
Q

drug A CYP substrate
+
Dryg B CYP inhibitor

A

increase substrate

risk of toxicity

329
Q

drug A CYP substrate
+
Dryg C CYP inducer

A

decrease of substrate
reduce substrate efficacy
therapeutic failure?

330
Q

drug A CYP substrate
+
Dryg B CYP substrate

A

???

331
Q

what does st johns wort do to CYP enzymes?

A

inducer

332
Q

what does sulfamexazole do to CYP enzymes?

A

inhibitor

333
Q

what does amiodarone do to CYP enzymes?

A

inhibitor

334
Q

what does cimetidine do to CYP enzymes?

A

inhibitor

335
Q

what does fluoxetine do to CYP enzymes?

A

inhibitor

336
Q

what does fluconazole do to CYP enzymes?

A

inhibitor

337
Q

what does ritonavir do to CYP enzymes?

A

inhibitor

338
Q

do CYP inhibitors have a long lasting action

A

Yes
rapid onset
long lasting action

339
Q

what mechanisms do CYP inhibitors work

A

oxidative metabolism
or
N-oxidation if inhibitor contains an amine functional group

340
Q

What is “oxidative metabolism” in inhibition of CYP enzymes

A

production of reactive intermediate that alkalises the protein on the heme group of the CYP enzyme
the enzyme doesnt work anymore

341
Q

What happens if the CYP inhibitor contains an amine functional group

A

N-Oxidation
formation of an irreversible metabolic intermediate between nitro-group and the heme iron bit of the CYP enzyme
CYP enzyme no longer works :-(

342
Q

Is amiodarone a CYP inducer or inhibitor

A

AMiodaroe itself isn’t actually a CYP inhibitor but its metabolites are

343
Q

how is ritonavir used

A

It is used as a sacrificial drug, it is given alongside other antiretrovirals (HAART) and used in combination as a booster for other protease inhibitors
Blocks the metabolism of other protease inhibitors by the CYP enzyme so that they can have more effect!

344
Q

what family of proteins do Pgp belong to

A

ABC- transporter subfamily

345
Q

What shape is the Pgp

A

transmembrane molecular pump

it is cone shaped

346
Q

what kind of drugs does Pgp recognise?

A

a wide range of drugs!

347
Q

what are the steps of Pgp action?

A

1) Pgp sits int eh cell membrane and searches for foreign hydrophobic molecles
2) Pgp finds one of the foreign molecules, it grabs it
3) this initiates 2x ATP molecules to bind
4) conformational change in the Pgp molecule
3) the new conformation has an opening towards the outside of the cell and by this mechanism the foreign thing you don’t want is ejected out of the cell

348
Q

what are some of the interactions that can occur between Pgp and a drug (e.g amiodarone)

A

hydrophobic (week interactions, packing interactions, van der waals, electrostatic forces)

hydrogen bonding interactions (sulfur-hydrogen or iodine-hydrogen)

aromatic cage formation

349
Q

what kind of chemistry do antacids normally have?

A

they are chemically weak bases
hydroxides/triscilates/carbonates
formulated as metal salts (calcium, aluminium,magnesium)

350
Q

what do antacids do

A

they increase gastric pH therefore they can cause drug issues by altering the pH dependent dissolution, most drugs contain an ionisable group and therefore changes in pH will have a knock on effect on drug dissolution profiels

351
Q

what is the rate limiting step in drug dissolution profilews

A

dissolution

352
Q

what are the main concerns considering pharmacoDNYAMIC interactions

A

drugs that have similar modes of action but opposite pharmacodynamic effects

353
Q

what happens if you give salbutamol + bisopralol

A

negative interaction at the receptor level

354
Q

what happens if you give ramipril + amlodipine

A

positive interaction at the receptor level

355
Q

what happens if youbgive bisoprolol+ verapamil

A
negative interaction at the receptor level, additive cardiac depressant effects of verapamil and CCB, resulting sharper depression in cardiac response
serious cardiac depression can occur
bradycardia
asystole
sinus arrest
not good!