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Flashcards in Pharmo Deck (442):
0

What are the different sorts of active failure in prescribing?

Violation - Directly contravening known guidelines
Slips - e.g. Copying one dose for multiple drugs
Lapses - e.g. Missing a contraindication
Mistakes - e.g. Not knowing to reduce a drug in renal failure

1

What is reasons model of accident causation?

A number of factors that come together, all required but non sufficient to cause the error alone. Includes latent conditions, active failure and failure of defences.

2

Why do errors happen?

High expectations from day 1
Exhaustion on nights
Lack of senior support
Routine task boredom
Lack of familiarity with patients
New drugs
Increased uses of drugs
Older patients with co morbidities and poly pharmacy

3

What is the individual vs systems base for medical drug errors?

Individuals fault - fear, retrain, litigation, naming and shaming
System fault - safeguards, barriers, acceptance and improvement

4

What is pharmacovigilance?
What are the aims?

The process of id and responding to safety issues about marketed drugs.
- id previously unrecognised safety hazards
- what causes the toxicity
- obtain evidence of safety to allow widening of drugs use
- identify false positive adrs

5

What are type a and type b drug reactions?

A - predictable, exaggerated pharmocological response, dose dependant, common, high morbidity low mortality
B - unpredictable, not expected, in dependant of dose, rare, high mortality

6

What are the dissadvantages of a clinical trial vs clinical prescription?

Small number of patients vs millions
Restricted age, pmh and dhx vs anyone indicated
Limited duration vs lifelong
Specialists prescribers vs generalists
High level of clinical monitoring vs low

7

How are adrs identified?

Spontanious reporting
Cohort studies
Case control studies

8

What is the yellow card scheme?
What drugs should be especially reported?

A report of potential adrs to mhra
Mhra then consider the cohort or case control studies

Black triangle drugs (1st year out of trials)
Unusual or serious reactions from established drugs

9

Problems with yellow card scheme?

Significant undereporting
Delays in reporting
Poor data - filled in too fast
Misleading reports
No control group (how many recieve with no issues)
Difficulty recognising previously unknown adrs

10

Why is reporting of adrs low?

Failure of pt to report
Adr is trivial
Not knowing report
Lack of time
Uncertainty of causal relationship
Experience with process

11

What is bioavailability? How is it calculated?

Fraction of administered drug that reaches systemic circulation
F = AUC (oral) / AUC (iv)

12

What factors effect bioavailability?

Active - gi membrane pumps, enzymatic destruction, first pass metabolism
Passive - lipid solubility, molecular size of drug, pKa of drug

13

What factors determine drug distribution?

Lipophilicity
Plasma protein binding
Tissue protein binding
Variation in compartment size etc. (E.g. Obese with more fat)

14

How do we work out volume of distribution of a drug?

Calculate concentration (C0) in plasma at time zero by extrapolating backwards from successive concentration measurements.
Vd = initial dose / C0
Assumes immediate distribution of the drug

Alternatively plot Vd using initial dose over current concentration against time then extrapolate back to get Vd at time 0

15

What does Vd show?
What would a reading of 5L, 10L, 200L suggest?

Equivalent volume of plasma a drug is distributed within - indicitive of compartments
5 - in plasma
10 - in ECF
200 - in muscle or fat too

16

How can Vd be expressed?

Total (e.g. 8L) or as a propotion of weight (e.g. 0.2 L/kg)

17

What reactions occur in phase 1 metabolism?

Redox reactions, hydroxylation

18

What enzymes are most commonly involved in phase 1 metabolism? Which subset?

CYP450
CYP459 3A4

19

How does phase 1 metabolism contribute to differing half lives of drugs?

CYP enzymes very generalist and therefore have variable rates with different drugs

20

What non modifiable factors can influence drug metabolism?

Ethnicity
Sex
Age
Genetics

21

What does pharmacogentetics allow?

An understanding how different genotypes will relate to different drugs to determine which drugs are effective and which are safe

22

Give an example of pharmacogenetics applied to antihypertensive drugs
Why? What is given instead?

Ace inhibitors is less effective in black people
Afro caribbeans patients have lower RAS activity so medication would not be so effective.
Thiazide or calcium channel blocker.

23

What adr are afrocaribbean pts more likely to suffer from lisinopril?

Angioedema

24

What is the formula for half life?

T1/2 = 0.7 Vd/CL

25

What is the definition of half life?

The constant fraction of a drug eliminated over a certain time period

26

What are routes for drug elimination?

Urinary
Bile
Exhaled air
Breast milk
Sweat
Tears

27

How is steady state concentration calculated in an infusion?

CpSS = dose rate / clearence

28

How long does it take for a drug given at a constant rate to reach steady state?

Five. Half lives

29

Roughly how is a loading dose calculated?

Loading dose = Vd x desired CpSS

30

Should a loading dose be adjusted for renal failure? What about maintainance doses?

Loading no, maintenance yes.

31

What is the most common drug target?

Enzymes

32

What are some examples of unconventional drug action?

Being an enzyme (streptokinase)
Reacting with small molecules (antiacids)
Binding free molecules (chelating agents)

33

What could cause non linear pharmacodynamics?

Limitations in second messengers

34

Define antagonist

Has no intrinsic efficacy blocking the receptor

35

Define partial agonist

An agonist that is unable to reach a full response even when all receptors are activated as such also acts as a partial antagonist

36

Define affinity, how is it recorded from a graph of binding vs concentration?

The tendency for a drug to bind to bind to its receptor
Defined by Kd, the concentration at which half the receptors are bound.

37

What is efficacy, how is it recorded from a graph of concentration against effect?

The maximal response of a drug when bound to. Its receptor
Measured by Emax (response where further increase in drug concentration provides any additional effect)

38

What is potency? How is it recorded from a concentration response graph?

The drug concentration at which 50% of emax is obtained
Recorded as EC50

39

What do competitive antagonists change?

Decrease potency, no change to efficacy

40

What effect on a dose response curve would a non competitive agonist have?

No effect on potency, reduced efficacy

41

In what situation would a noncompetive antagonist not effect efficacy of a drug"

Low enough dose with spare receptors

42

What do selectivity and specificity refer to in pharmocology?

Selectivity - the affinity of a drug for a particular receptor (highly selective may still effect others as dose increases)
Sensitivity - the drug effects a specific subtype of receptor (e.g. Beta 1 only)

43

How is. Therapeutic index calculated?

Td50/Ed50

44

WHat is therapeutic window?

The range of drugs concentrations that elicit a desired effect without unacceptable adverse effects.

45

List some pharmacokinetic dd interactions

Absorption - eg. Changes to gut motility (metoclopramide).
Distribution - protein binding interactions (e.g. Aspirin displacing warfarin)
Metabolism - cyp induction or inhibition
Elimination - altered urine pH (e.g. alkanisation of urine to excrete aspirin)

46

Name some cyp enzyme inducers and inhibitors

Inducers - Rifampicin, chronic alcohol, carbamezapine, st johns wort, sulphonureas
Inhibitors - Cimetidine, acute alcohol, isonazid, valporate, sulphonamides

47

How do cyp induction and inhibition differ (other than the obvious)!

Induction - onset over several weeks (increasing expression of the enzyme)
Inhibition - onset over several days (competitive and non competitive inhibition)

48

How can pharmacodynamic ddis be used beneficially?

Enhance therapeutic effect (combination therapy)
Antagonise unwanted effect

49

Give some examples of direct and indirect unwanted pharmacodynamic ddis

Direct - adrenaline and maoi both causing increased sympathetic stimulation
Indirect - furosemide causing hypokalaemia enhancing digoxin

50

Which drug classes most commonly cause pharmacodynamic ddis?

Anticonvulsants
Antibiotics
Anticoagulants
Antidepressants
Antiarrhythmics

51

What diseases most prevalently cause drug disease interactions?

Hepatic
Renal
Heart

52

Enzyme inducers are

PCBRAS
Phenotoin
Carbamezapine
Barbituates
Rifampicin
Alcohol (chronic)
st Johns Wort

53

Enzyme inhibitors are

GODEVICES
Grapefruit juice
Omeprazole
Disulfarim
Erythromycin
Valproate
Isoniazid
Ciprofloxacin
Ethanol (acute)
Sulphonamides

54

Side effects of COCP

Venous thromboembolism
Htn
Mi/stroke
Ca breast and cervix
Mood swings
Decreased glucose tolerance
Choleostasis
Breast tenderness

55

When should COCP not be given?

Contraindicated
Smoker >35
Breast cancer

With advice
Cured breast cancer
Obese

Caution
Migraine
Young smoker
Htn
Previous vte


56

Benefits of COCP beyond pregnancy?

Menstrual relief
Acne reduction
Decrease risk of endometrial, colorectal and ovarian cancer

57

Which cocp has extra anti acne effect?
Why?
What is the associated problem?
Other use?

Dianette
Contains cyproterone acetate which acts both as a progesterone and an anti testosterone.
Higher risk of thromboembolism vs other COCPs
Hirtuism

58

What are the constituents of microgynon?

Ethinyloestrodiol
Levonorgestrel

59

Which generations of progesterone are associated with increased risk of thromboembolism?

3+4

60

Side effects of POP?

Weight gain
Acne
Irritability
Depression
Fluid retention

61

What are the advantages of POP?

No associated risk of venous thromboembolism, stroke or MI and Ca breast

62

Why does cocp increase risk of cancer of the cervix?

Causes inversion of cervix exposing columnar epithelium to acid causing metaplasia then dysplasia.

63

What drugs are used for emergency contraception? What are the timeframes?

Levenorgestrel (up to 72 hrs)
Ullipristal (up to 120 hrs)
Copper iud (up to 120 hrs)

64

What is a big risk of emergency contraception?

All increase risk of ectopic pregnancy.

65

What are the benefits of HRT?

Relieves menopause symptoms
May reduce osteoporosis incidence

66

What does hrt not change?

Cvd risk

67

What are risks of hrt?

Ca breast
Ihd/stroke
Venous thromboembolism
Uterine bleeding

68

What patients can recieve hrt in pure oestrogen form?

Hysterectomy patients

69

When might antioestrogens be used?

Tamoxifen - ca breast
Clomipnene - infertility due to decreased ovulation

70

Why may antiprogesterones be used? Example?

Mifepristone
Abortion or labour induction

71

What do the different lipoproteins carry?

Chylomicrons - tag gi to tissues
Vldl - tag liver to tissues
Ldl - cholesterol liver to tissues
Hdl - cholesterol tissues to liver

72

What is the association between cholesterol, smoking, htn and chd?

Risk of chd is higher than the sum of the parts when combined

73

What study showed the relationship between chd and raised cholesterol? In which ethnicities?

Framingham - northern europe and usa

74

What is the relationship between bmi and cholesterol?

Increases with increasing bmi (even within normal range)

75

How do statins work?

Inhibit hmg coA reductase
Decreases hepatic cholesterol synthesis
Increases expression of ldl receptors
Hepatic cholesterol returns to normal
But increased ldl receptors mean higher clearence

76

What are the benefits of statins to someone with a high cholesterol? Someone with a normal cholesterol?

Decrease in cholesterol by 10% reduces cvd risk by 15%
Also
- antiinflammatory
- reduced thrombotic risk
- plaque reduction
- improved endothelial cell function

77

Side effects of statins

Myopathy (up to rhabdomyolitis)
Muscle pain (myalgia)
Elevated transaminase
Gi complaints
Arthralgia
Nightmares

78

What are fibric acid derivatives more commonly known as? Give two examples

Fibrates
Benzofibrate
Gemfibrozil

79

How do fibrates work?

Stimulate PPAR increasing trasncription of lipoprotein lipase
Causes reduced ldl, increased hdl (both moderate) and marked reduction in tag (30%)

80

What is a contraindication for fibrates?

Choleocystitis

81

What is the interaction between statins and gemfibrozil?

Both additive effect increasing risk of rhabdomyolisis and gemfibrozil inhibits statin glucuronidation increasing its side effect profile greater than the sum of the parts.

82

What is nicotinic acid also know as? What is its mechanism of action?

Niacin
Inhibits lipoprotein synthesis in liver reducing vldl, tag and tc.

83

What are adverse effects of niacin?

Flushing
Hepatotoxicity
Glucose intolerance
Peptic ulcers
Itching

84

What must niacin be given with? Why?

Aspirin, to reduce itching

85

What is an example of a cholesterol lipase inhibitor? How do they work?

Ezetimibe
In brush border of gi tract, limiting absorption of cholesterol

86

Side effects of ezetimibe

Abdo pain, diarrheoa, flatulance

87

What dietary control can be applied to hyperlipidemia?

Low fats, cholesterol and alcohol
High fish oil, fibre, vit c and e

88

What are the current nice statin guidelines?

Primary prevention 20mg atorvastatin if qrisk above 10% in next 10 years
Secondary prevention 80mg atorvastatin (reduce if risk of adrs or ddis)

89

What are the abnormal values of
Fasting bm
Random bm
Hba1c
Gtt
In diagnosing diabetes?

Fasting >7
Random >11.1
Hba1c >6.5
Gtt >11.1

90

Classes of non insulin antidiabetics

Biguanides
Sulphonylureas
Glitazones
Alpha glucosidase inhibitors
Gliptins
GLP1 agonist
SLGT2 ingibitors

91

Example, pd and adrs/benefits of biguanides

Metformin
Increases insulin sensitivity increasing peripheral glucose uptake and decreasing gluconeogenesis
Adrs - gi upset, lactic acidosis (therefor not in cardiac or resp failure)
Benefits - limited weight gain, low hypo risk, low cost

92

Example, pd and adrs of sulphonylureas

Gliclazide
Increases insulin release by blocking k channels
Adrs - hypos, weight gain, gi upset, rashes
Benefits - can use in renal failure

93

Example, pd and adrs of glitazones

Pioglitazone
Increases insulin sensitivity via PPARs
Adrs - weight gain, bladder cancer, chf, fluid retention
Benefits - low risk of hypo

94

When would you not use a glitazone?

Cvd

95

When would you not use a sulphonurea?

When hypos would be an issue (eg driving)

96

Example, pd and adrs of GLP1 agonist

Exenatide
Mimics glucogon like peptide 1 released from GI tract - causes increased insulin release and decreased gastric emptying, increased satiety, and decreased glucagon release
Adrs - expensive! Injection site problems, gi upset
Benefits - weight loss, good efficacy

97

Example, pd and adrs of gliptins

Saxogliptin
Stop dpp4 breaking down glp1, increases glp1 therefore increased insulin, decreased glucagon, satiety and slowed gi emptying
Adrs - gi upset, gord
Benefits - weight loss

98

Example, pd and adrs of SGLT2 inhibitors

Dapagliflocin
Increases renal glucose excretion
Adrs - thrush, uti, hypos, polyurea
Benefits - weight loss

99

Rapid acting insulin
Long acting insulin

Lispro (rapid)
Glargine (long)

100

Side effects of insulin therapy?

Hypos
Lipodystrophy at injection site
Allergies to suspension

101

Insulin regime for someone unable to administer their own insulin example:

Twice daily mix of short and intermediate acting insulin (e.g. Humalog 25 - 75% intermediate lispro protamine and 25% rapid acting lispro)

102

Insulin regime for someone who can monitor their own bm and administer own insulin

Long acting (e.g. Glargine) overnight then short acting (eg. aspart) at meals

103

In what ways can antibacterials be classifed? Which is the most useful clinically? Why?

Bacteriocidal vs bacteriostatic
Broad vs narrow spectrum
Chemical structure
Target site - most useful as we can predict action on certain bacteria

104

What must an antibiotic be able to do in order to be effective?

Selectively damage pathogen over body cells
Reach the site of action

105

What are the three main ways a bacteria can become resistant to an antibiotic?

Production of inactivating enzymes
Altering the target site
Altering concentration (decreased influx or increased efflux)

106

What are the three mechanisms of horizontal bacterial resistance?

Conjugation
Transduction
Transformation

107

How can an appropriate antibiotic be chosen for an infection?

Disk sensitivity testing

108

What are issues with disc sensitivity testing?

Abx may not be able to reach site of action
Wrong bacteria cultured
Bacteria may develop resistance during treatment
Wrong dose or route may be used for abx

109

How are doses calculated for sensitive antibiotics like vancomycin?

Calculate minimum inhibitory concentration using an E-test

110

What are the two GENERAL pharmacodynamic principles of antibiotics? Examples of each

Time dependant killing - cell wall ABX - achieved with regular dosing or infusion
Dose dependant killing - aminoglyosides and quinolones (e.g. 1 does of ciprofloxacin for gonorrhoea

111

What are the different classes of anti cell wall antibiotics? (Main and subsidiary). Examples from each

Beta lactams
Penicillins (penicillin!)
Cephalosporins (ceftriaxone)
Carbapenems (meropenem)

Glycopeptides (vancomycin)

112

What antibiotic would be appropriate in a case of MRSA?

Vancomycin

113

What is the spectrum action of meropenem? What does it not work on?

G pos and neg
Anaerobes
No action against mrsa

114

What is the spectrum of cephalosporin?
What does it not work on?

G pos and neg
Does not work on anaerobes or mrsa

115

What side effects are associated with cephalosporin?

Allergic reaction
Clostridium difficile infection

116

Which penicillin abx is naturally active against beta lactamase producing bacteria?
Which penicillin is active against gram neg?

Flucloxacillin
Amoxicillin

117

How do beta lactam abx work?
How do glycopeptides work differently?

Competitively inhibit penicillin binding protein stopping cell wall synthesis
Bind to the petidoglycan cell wall stopping penicillin binding protein from binding

118

What is the basic structure of the cell wall of a bacteria?

Peptidoglycan - carbohydrate chains joined by amino acid bridges

119

What common bacteria would penicillin V not be useful against? What penicillin could be used instead

Staphylococci - many produce beta lactamase
Flucloxacillin

120

What is responsible for enabling the gram neg actions of amoxicillin?

Able to penetrate cell membranes

121

What is a good use of cephalosporins?

Penetrate csf thus meningitis

122

On what bacteria would vancomycin not work?

Gram neg

123

What are the side effects of vancomycin? Which other group of abx share these effects?

Ototoxicity
Nephrotoxicity

124

What are the three main classes of abx that inhibit protein synthesis? Why are they specific to bacteria?

Tetracyclines
Aminoglycosides
Macrolides
As they target prokaryotic ribosomes (30s+50s - 70s)

125

Which of the 3 classes of abx that effect protein synthesis target the 50s subunit? How do they work?

Macrolides
Inhibit peptidyl transferase responsible form moving the growing aa chain from the p site to the a site.

126

What are the tetracyclins? Moa, adrs, spectrum.

Tetracyclin, doxycyclin
Bind to 30s subunit inhibing trna binding causing misreading of mrna.
Stained teeth in children, gastric prokinetics thus diarrheoa
Broad spectrum

127

Example of an aminoglycoside and spectrum.

Gentamicin
Gram -ve with slight gram +ve

128

What are the side effects of the macrolides?

Cyp450 inhibitor
Gastric prokinetic

129

What classes of drugs effect nucleic acid synthesis?

Quinolones (ciprofloxacin)
Sulphonamides + trimethoprim (trimethoprim, sulfadazine)
Metronidazol

130

How do the quinilones work? Example

Ciprofloxacin. Inhibits dna gyrase stopping supercoiling of dna

131

Effect of sulphonamides and trimethoprim?

Inhibit folate synthesis (by inhibiting enzymes including dihydrofolate reductase)

132

What are the anti tb antibiotics?

Rifampicin
Isoniazide
Pyrazinamide
Ethanbutol

133

What drugs would you give to a fungal infection? How do they work?

Azoles - inhibit cell membrane synthesis
Nystatin - inhibits cell membrane function

134

Differentiate antigenic shift and antigenic drift in flu

Shift - 2 different flu viruses in one host swap material producing a novel virus - high risk
Drift - slow mutation of the virus seen in the year to year changes in seasonal flu

135

Which flu subtypes can have an animal resevoir?

A only

136

What are the surface proteins of influenza virus? What do they do?

Haemogglutanin - binds to salysiliate receptor on host cell
Neuroaminidase - releases the virus from the cell surface after budding out

137

How does the virus loose its envelope once in the cell?

Ion influx through m2 ion channel for protons (and activated by protons - low pH)

138

What drugs block M2 ion channels in flu?
ADRs?

Amantadine, rimantadine

Antiparkinsons drugs thus serious cns side effects (nervousness, anxiety, agitation, insomnia, exacerbation of seizures in epileptics, exaggerations of psychotic symptoms in scizophrenics

139

Why are m2 ion channel blockers poor antivirals?

Severe cns side effects
Rapidly develop resistance

140

Give an example of a neuramonidase inhibitor. Side effects?

Oseltamivir
Vomiting, abdo pain, epistaxis

141

What are the effects of neuraminidase inhibitors?

Shorten illness duration
Decrease risk of death
Prophylaxis

142

What is the recommended treatment window for oseltamivir? Too whom should it be given?

48 hours
At risk patients with flu like symptoms during a suspected current outbreak of flu

143

How does acyclovir work?

Inhibits viral dna polymerase

144

What are the aims of asthma therapy?

Minimal symptoms
No exacerbations
Minimal use of reliever
No limit to physical activity
Normal lung function
Aim for early control then step up and down as needed

145

What are the steps of asthma therapy?

1 - SAB2 agonist
2 - add inhaled steroid 400mcg
3 - add LAB2 agonist, consider increasing steroid to 800mcg
4 - increase steroids up to 2000mcg, add novel drug
5 - oral steroid

146

Why do we try to limit use of SAB2 in asthma?

Indication of poor control
Overuse causes mast cell degranulation

147

What are the actions of a intermittently used SAB2 agonist?

Relax airway smooth muscle
Inhibit mast cell degranulation

148

How does beta 2 stimulation relax smooth muscle?

Alpha s
AC
Increase cAMP
Activate PKA
Increase K+ conductance
Hyperpolarisation

149

Give an example of LAB2 agonist that also acts as a SAB2 agonist
What happens if this is used as a reliever too?

Formoterol
Decreases exacerbation number

150

Example of a long acting beta 2 agonist that does not have short acting effect?

Salmeterol

151

What is the advantage of giving a LAB2 with a steroid combined? 2 examples please.

Ease of use - increase compliance
Ensures steroid is being given, not just beta agonists

Symbicort - formoterol and budesinide
Seretide - salmeterol and fluticosone

152

How are inhaled steroids modified to reduce systemic side effects? Why does this work?

Lipophilic side chain
Increases receptor affinity, high local uptake, increased hepatic metabolism

153

How can steroid inhalers get into systemic systems? How can side effects be reduced? Which steroid is good and bad for this?

Swallowed rather than inhaled
Use a steroid that is highly metabolised on first pass eg. budesonide
Beclamethasone undergoes little first pass

154

What novel drugs can be given in asthma - brief moa and side effects please

Methylxanthines such as aminophyllin antagonise adenosine and is a phosphodiesterase inhibitor (increases cAMP). Can cause arrhythmia and fits
Leukotrine receptor antagonists such as montelukast block action of leukotrines - not very efficacious - can cause angioedema, anaphylaxis and fever

155

Where does COX act to convert arachidonic acid into prostaglandins?

Arachidonic acid
COX
Endoperoxides
COX
PGg
COX
PGh
UNKNOWN MECHANISM
PGe

156

What do prostaglandins cause generally?

Vasodilation
Hyperalgesia
Immunomodulation
Fever

157

Where do prostaglands act to cause pain? In what ways?

Peripherally - EP1 receptor - GalphaQ
decreases K channels and increases Na channels causing depolarisation of neurones
Increased sensitivity to bradykinin

Centrally - EP2 receptor - GaplhaS
Increased PKA decreases glycline affinity reducing inhibition of second order neurones

158

How do prostaglandins cause fever?

IL1 stimulates hypothalamus to produce COX2 stimulating Ep3 receptors GalphaI increasing cellular calcium increasing temperature

159

Where is COX 1 expressed? What about COX2

1 - wide spread - gastric mucosa, renal parenchyma
2 - in inflammed areas, hypothalamus

160

Which of cox one and two has the larger active site?

Cox 2

161

How do nsaids inhibit cox?

Competitive antagonsim

162

What is the Pk of Nsaids?

Heavily protein bound
Two groups - t1/2 under 6 hrs or over 10 hrs

163

Why do nsaids cause gastric symptoms?

Decreased cox1 - decreased mucus secretion and decreased mucosal blood flow

164

When is nsaids action on the kidneys particually important?

Heart patients
Renal patients
Hepatic patients

165

Side effects of nsaids

Gastric
Bleeding
Wheezing
Reyes syndroms
Stevens johnson syndrome

166

Give some positive and negative ddis of nsaids

Positive - with opiate - good relief
Negative - protein displacement - e.g. Warfarin, methotrexate
- nsaid + aspirin - competes for cox 1 site of aspirin decreasing efficacy

167

What are unique facts about aspirin?

Irreversible inhibition of COX1
T1/2 less than 30 minutes but metabolised to salicylate with t1/2 over 4 hours (though this binds reversibly!)
Zero order at higher dose

168

What is the classification of paracetamol?

Non-Opiate Analgesic Drug
nOAD

169

How is. Paracetamol thought to work?

Weak cox 1-3 inhibitor

170

What are the layers of the adrenal cortex? What do they excrete?

Glomerulosa - minralocorticoids
Fasciculata - glucocorticoids
Reticularis - sex steriods

171

What does cortisol feed back on?

Negativly on hypothalams (reducing CRH) and pituitary (ACTH)

172

Metabolic actions of glucocorticoids?

Raises blood glucose - stimulates glygogenolysis and gluconeogeneis
Proteinolysis
Lipolysis at low concentrations
Lipid deposition at high concentrations


173

Why might corticosteroids cause hypertension?

Increased sensitivity of blood vessels to vasoconstrictors
Mineralocorticoid effect on kidney increases salt and water reabsorption

174

Side effects of glutocorticosteroids

Weight gain
Increased appatite
Fat redistribution (moon face, buffalo hump, central obesity)
Proteinolysis (striae/thin skin)
Glucose intolerance
Hypertension
Infection

175

Signs of aldosterone deficiency?

Hyponatraemia
Dehydration
Hypotension
Hyperkalaemia

176

Signs of aldosterone excess?

Hypernatraenia
Hypertension
Hypokalaemia

177

Describe the process of crossover with respect to steroids

Most steroid drugs have both glucocorticoid and mineralocorticoid effects

178

Which drugs have equal glucocorticoid and mineralocorticoid effects?

Hydrocortisone1:1

179

Which drugs have very stronger glucocorticoid effects than mineralocorticoid effects? Which ones? much more so

Prednisolone 4:1
Dexamethasone 25:1
Betamethasine 25:1

180

Which steroid is mainly mineralocorticoid

Fludrocortisone

181

What do you need to consider about a steroid dose before administrating?

Crossover
Duration of action
Equivalent dose

182

Describe the absorption of steroids orally

Highly lipophyllic so well absorbed with high bioavailability

183

Where are steroids metabolised?

Liver and kidney

184

Examples of steroid routes of administration

Iv - hydrocortisone
Oral - prendisolone
Inhaled - budesinide
Topical - beclamethasone

185

How do steroids reduce inflammation?

Inhibition of t and b cell responses
Inhibit nf kappa b - signalling molecule for inflammation
Reduced cytokine transcription
Reduced expression of cell adhesion molecules
Reduced phagocytic function
Immunosupression

186

What is the molecular moa of steroids?
What is a variation on this?

Diffuses in to cell as lipid soluble
Bind to receptor in cytoplasm (often causing it to dissociate from a heat shock protein)
Enters nucleus and binds to point on dna - hormone response element
Activates or inhibits protein transcription

Can bind to receptors within the nucleus as opposed to cytoplasm

187

What is activation of transcription called by steroids?
What about inactivation?

Trans-activation
Cis-repression

188

What do steroids transactivate?

Annexin one - decreases arachodronic acid synthesis

189

What do steroids cis-repress?

POMC (reducing ACTH production)
Keratin (hence thin skin)
Osteocalcin (osteoporosis)

190

As well as transactivation and cisrepression what do steroids do?

Transrepression
Binding to proteins causing decreased cytokines, chemokines, adhesion molecules and inflammatory enzymes, receptors etc.

Some surface receptor action - this would create a rapid respone

191

Examples of when to use steroid use

Decrease Inflammation
To Suppress Immunity To An Extent
Replace Insufficiency
Diagnosis - Dexamethasone Suppression Test
Preterm Labour

192

Why do steroids cause osteoporosis?

Inhibit osteoblasts
Increase osteoclasts
Reduce calcium absorption
Reduce sex steroid production

193

How long will it take to suppress the hpa axis with steroids?

3 weeks

194

What can occur in hypoadrenal crisis?

Hypotension
Hypoglycaemia
Hyponatraemia
Hyperkalaemia
Severe dehydration

195

Other than steroids name two other immunosuppressants (classes and drugs)

Azathioprine
Calcineurin inhibitors (ciclosporin, tacrolimus)

196

How does azathioprine work?

Metabolised to 6mecaptopurine
Decreases dna and rna synthesis

197

What makes azathioprine unpredictable?
What are the side effects?

Broken down at different rates in different people

Bone marrow supression
Malignancy
Infection
Hepititis

198

Which class of immunosuppressants is dependant on cyp for metabolism?

Calcineurin inhibitors

199

How do calcinurin inhibitors work?

Bind to eponimous bonding proteins (e.g. Ciclosporin binding proteins)
Inhbits calcineurin
Inhibiting production of IL2 in t cells needed for costimulation

200

What are side effects of calcineurin inhibitors?

Nephrotoxic
Htn
D and v
Mouth ulcers

201

What is the odd sounding immunosuppressant? How does it work?

Mycophenolate mofeti

Inhibits guanosine synthesis in b cells only

202

How does methotrexate work as a dmard

Inhibits purine metabolism increasing adenosine that has a regulatory effect on immune cells.

203

Side effects of methotrexate

Liver failure
Mouth ulcers
Pnemonitis / intersitial lung disease
Teratogenic

204

What dmard would be used in pregnancy?

Sulphasalazine

205

Why is methotrexate used only weekly?

Metabolised to polygluyamates with long half life

206

What does sulphasalazine consist of? What does each component do?

Sulfapyridine - enters body for RA
Salacilate - remains GI for IBD

Overall inhibits t cell proliferation and neutrophil degranulation and chemotaxis

207

What do you need to be careful of with anti tnf agents?

Reactivation of latent tb
Increased risk of malignancy if there has been prior malignancy

208

How do anti tnf agents modify disease?

Decrease inflammation
Decreased angiogenesis
Decreased joint destruction

209

What are the endogenous opioids?

Enkephalins
Endorphins
Dynorphins

210

What are the three sorts of opiod receptors? What are they? Where are they found?

M - supraspinal
K - spinal cord
D - widely distributed
GPCRs

211

What happens when an opioid receptor is triggered?

M - k efflux therefore hyperpolarisation therefore decreased Ca
K - decreased Ca influx
D - decreased Ca release
All decrease Ca so there is less synaptotagmin activation so less neurotransmitter release

212

What opiate adrs are associated with the different receptors? What are general ones?

M - nausea, vomiting, resp depression, constipation, drowsiness, hypotension
K - dysphoria
General - allergy, dependance, tolerance

213

Example of a partial opiate agonist?

Buprenorphine

214

T1/2 of morphine?

1-7 hours

215

Why is heroin so active in the brain?

Twin acyl groups so very lipid soluble so crosses bbb prior to metabolism to morphine

216

What drugs do opiates interact with

Alcohol
Barbituates
Anaesthetics
Naloxone

217

Why does morphine cause resp depression?

M receptor mediated decreased co2 sensitivity

218

How does warfarin work?

Inhibits vit K reductase necessary for the convesion of glu to gla domains on clotting factors 2, 7, 9 and 10

219

What drugs interact with warfarin indifferent ways?

Cephalosporins kill gut bacteria so low vit K potentiating effects
Cyp inducers and inhibitors influence metabolism
Protein percipitant drugs e.g. Aspirin displace warfarin

220

Comment on the onset and offset of warfarin. What can be done to mitigate both.

Onset is slow as it takes time to replace fully functional clotting factors with altered ones - give heparin cover until inr acceptable

Offset also takes several days for the reverse reason. Can reverse with - vit K or fresh frozen plasma (if life threatening bleed)

221

What is INR?

A standardised prothrombin time for the kit used

222

What is prothrombin time?

Measures extrinsic pathway of coagulation
Blood + citrate
Overwhelm citrate with calcium and add tf
Measure time until clot forms

223

What are risks of warfarin in pregnancy?

First trimester teratogenic
Risks child cerebral haemorrhage on delivery and bleeding from mother

224

What inr would you aim for if you had a pe, dvt or af?

2-3

225

What inr would you aim for if you have a prosthetic valve or dvt/pe/af were still problematic at 2-3?

2.5-4.5

226

How does unfractionated heparin work?
What is different about LMWH?

Binds to antithrombin III increasing its affinity for factors II and X
LMWH is small so cant span II so only binds X

227

What are some novel anticoagulants? How do they work?

Fondaparinux - selective factor ten a inhibitor
Dabigitran - direct thrombin inhibitor

228

Adverse effects of heparin?

Bruising
Bleeding
Osteoporosis
Thrombocytopenia

229

What causes thrombocytopenia in heparin use?

Autoimmune response within a couple of weeks directed against platelets

230

What monitoring is needed in LMWH and UFH?

LMWH - none!
UFH - APTT (activated partial thromboplastin time)

231

What is APTT

Activated partial thromboplastin time
Overwhelm citrate with calcium, add activator (not TF

232

How does aspirin work as an anti-platelet

Inhibits cox 1 irreversibly
Decreasing txa2
Decreasing g alpha q stimulation and thus decreasing calcium release via. iP3

233

How does clopidogrel act as an antiplatelet?

Blocks adp receptor stopping g alpha i stimulation inhibiting cAMP mediated suppression of calcium release (reducing the reduction of a reducer!)

234

What is an example of a GP IIb/IIIa inhibitor?

Tirofiban

235

What are the different sorts of medications required in anaesthesia?

Premedication - anxiolytic - mirtazapine
Induction agent - IV anaesthetic - ketamine
Maintenance agent - volatile gas - sevoflurine
Paralytic - neuromuscular blocker - rocuronium
Pain relief - opiate - morphine
Antiemetic - dopamine antagonist - metaclopramide
Regional anaesthesia - sodium channel blocker - lidocain

236

What is the term for general anaesthesia without the use of inhaled anaesthetics?

Total intravenous anaesthetic (TIVA)

237

When might you use a volatile gas anaesthetic over a intravenous anaesthetic?

Needle phobics

238

What is the most common action of anaesthetic agents?

Bind to GABAa receptors potentiating GABA increasing its potency and its efficacy
Have the same effects at glycine channels in the spinal cord

239

What are the unusual anaesthetics?
What do they do differently?

Ketamine, Xe, N2O
Bind allosterically to NMDA receptors antagonising glutamate. As allosteric reduces efficacy but not potency

240

Where do anaesthetics act?
To what ends?

Reticular formation - decreases arousal
Hippocampus - decreased memory
Dorsal horn - decreased pain and decreased reflexes
Brainstem - depressed respiration and cvs function

241

What does a low blood:gas partition mean for an inhaled anaesthetic?

Faster induction and recovery

242

What does a high oil:gas partition mean for an inhaled anaesthetic?

High potency but also retention so slow recovery

243

What is MAC

Minimal alveolar concentration - the minimum concentration of anaesthetic in the alveoli that induces a state in which 50% fail to move to surgical stimuli

244

What increases MAC (making it harder to anaesthetise

Young age
Hyperthermia
Pregnancy
Alcoholism
Stimulants

245

What decreases MAC increasing response to ananesthetic

Old age
Hypothermia
Other depressants - anaesthetics, opiates, N2O

246

What is a disadvantage of TIVA?

Less easily reversed due to high protein binding

247

How do iv anaesthetics distribute?

Initially to target tissue then into fat

248

When does high blood gas coefficient lead to slower induction?

Indicates higher protein bound state

249

How is the effect of anaesthesia graded?

Guedels signs
Stage 1 - slight decreased eye movement
Stage 2 - increased excitability and tone, erratic breathing
Stage 3 - increasing levels of relaxation, breathing decreases
Stage 4 - flaccid, apnoic, paralysed

250

What are the 5 aims of anaesthesia?

Hypnosis
Analgesia
Amnesia
Relaxation
Reflex depression

251

What is the depolarising neuromuscular blocker? How does it work? What may need to be given alongside it?

Suxamethonium
Activates prolonged depolarisation that desensitises receptors
Atropine

252

Differentiate local and regional anaesthesia

Regional is larger area e.g. Epidural, spinal, femoral

253

What is directly proportional to potency, speed and duration of local anaesthetics

Potency - lipid solubility
Speed - lower pKa
Duration - degree of protein binding

254

What is the order of effect of local anaesthetics?

Small mylinated
Unmylinated
Large mylinated

255

Name 5 classes of diuretics with examples of each

Carbonic anhydrase inhibitors - acetazolamide
Osmotic diuretic - mannitol
Loop diuretic - frusemide
Thiazide diuretic - bendroflumethiazide
Potassium sparing diuretic - spironolactone

256

MOA of carbonic anhydrase inhibitors

Inhibit luminal CA decreasing CO2 available for reabsorption and increasing luminal HCO3
Due to lower CO2 in cells decreased H+ thus decreased activity of Na/H antiporter thus decreased Na+ reabsorption
Higher HCO3 and H in lumen so increased water.

257

Problems with carbonic anhydrase inhibitors

Hypokalaemia - increased Na to DCT therefore increased Na/K antiporters and increased DCT flow washes away K+ increasing gradient

258

What is the characteristic of an osmotic diuretic? When are they used?

Filtered but not reabsorbed
Maintain urine out put during surgery, cerebral oedema

259

How do loop diuretics work?

Inhibit NKCC2 channels in ascending loop of henle.

260

Side effects of loop diuretics - why?

Hypokalaemia - high Na in DCT = increased Na/K antiporter, increased flow past DCT carries away K increasing gradient
Hypocalcemia/magnesia = loss of luminal positive potential from re-secretion of absorbed K through ROMK thus less drive for other cation absorption
Ototoxicity = high dose alters endolymph composition

261

Mechanism of thiazides

Inhibits Na/Cl synporter in DCT

262

Side effects of thiazides

Hypokalaemia
Hypoglycemia
Gout (thiazide excreted by same channel as uric acid thus competes)

263

Mechanism spirolactone

Blocks aldosterone from binding to receptor thus:
Decreased basal Na/K ATPase
Decreased apical ROMK
Decreased apical ENaC
Thus decreased Na absorption and K secretion

264

Side effects of spironolactone

Hyperkalaemia
Gynecomastia

265

Uses of carbonic anhydrase inhibitors

Glaucoma
Mountain sickness

266

Diuretics to use in CHF

1 Loop
2 Thiazide

267

Diuretic to use in liver disease

1 spironolactone
2 loop

268

Why would you not use acetazolamide in liver failure?

Excretion of NH3 requires proteination in the kidney tubule

269

Why is spironolactone beneficial in liver failure?

Avoids hypokalaemia which stimulates ammonia production

270

Which diuretics are used as antihypertensives?

Thiazides
Spironolactone off label

271

What is conns syndrome?

An aldosterone producing adenoma
Causes sodium and water retention with concurrent htn.
Treat with spironolactome

272

Other than spironolactone name another. K sparing diuretic

Amiloride

273

What should be considered when prescribing in renal failure?

Potassium levels
Renal function levels
Reduce renal excreted drugs in line with gfr
Stop nephrotoxic drugs

274

Give some examples of nephrotoxic drugs

Ace inhibitors
Aminoglycosides
Penicillin
Cyclosporins
Metformin
Nsaids
Calcineurin inhibitors

275

When and why are ace inhibitors 'nephrotoxic'

Bilateral renal artery stenosis
Needs efferent arteriole vasoconstriction to maintaing gfr
Ace inhibitors stop vasoconstriction

276

What is the prevalence of htn?
What is the benefit of lowering bp by 10mmHg?

40%
Reduces stroke risk by 60% and CHD by 40

277

What percentage of Htn is secondary? What are causes? What is the commonest?

10%
Renal disease (80%)
Conns syndrome
Phaeochromocytoma
Coarctation of aorta
Eclampsia
Cushings sydrome
Steroids
Ocp

278

Lifestyle tx of htn?

Decrease weight to normal
Decrease salt intake
Limit EtOh
Exercise
Fruit and veg
Smoking cessation to reduce cvd risk factors

279

What are the cut off values for htn?

Norm - 180/110

280

What is the initial therapy for HTN?
Second line? Third? Fourth?

White under 55 - ACEi
Black or over 55 - CC blocker/thiazide

Second line is ACEi and one other
Third line is all three
Fourth line is all three and beta blocker and referral to specialist

281

Side effects of an acei?

Hyperkalaemia
Dry cough
Angioedema
Renal failure with bilat renal artery stenosis

282

What might you use if a pt on ace i complains of dry cough?

Angiotensin receptor blocker eg. Losartan

283

Example of an alpha 1 blocker
Moa
Side effects

Doxazosin
Blocks alpha 1 thus vasodilates
Postural hypotension, dizzyneas, headache

284

What are the two groups of calcium channel blockers?

Dihydropryidines (amelodipine)
Non dihydropyridines (verampamil, diltazem)

285

Side effects of the dihydropyradines and why

Flushing (vasodilation)
Oedema (no venodilation)
Sweating (increased sympathetics)
Tachycardia (reflex from lower bp)

286

Side effects of verapamil/diltazem

Bradycardia
Constipation
Negative ionotrophy

287

What study shows the efficacy of the main groups of antihypertensives - what did it conclude about them?

Allhat
All three classes showed a 8% reduction in event rate at 5 years with the same bp reduction

288

What medications alter the prognosis of heart failure?

Ace inhibitors/ARBs
Beta blockers
Spironolactone

289

Which trials show the efficacy of spironolactone in chf?

RALES

290

What medications only show symptom relief in heart failure without effecting prognosis?

Loop diuretics
Thiazide diuretics

291

What is the disadvantage of beta blockade in CHF?
How is this mitigated?
How is it thought beta blockers change long term outcomes?

Decreased rate and contractility worsting CO
Start at low dose
Over time CO returns to normal but PVR is lowered due to reduced renin secretion by sypathetic stimulation

292

What are mechanisms of SVT generation?

Accelerated automaticity of SA node
Reentry circuit (AVNRT)
Accessory pathway (AVRT)
Ectopic activity (AF/flutter)

293

Why do people get AF?

Usually secondary to something
Htn
Chf
Hyperthyrodism
Alcohol

294

What is the term for a AVRT that passes through the AV node, through the ventricles then up the accessory pathway

Orthidromic

295

What is the term for a AVRT that passes through the accessory pathway, through the ventricles then through the AV node in reverse?

Antidromic (will have broad QRS)

296

Short term measures to control SVT

Cardiovert if unstable
Vasalva / carotid sinus massage
Adenosine
Beta blocker, verapamil or diltiazem

297

Long term measures to control SVT

Catheter ablation
Verapamil/diltaziem/beta blocker
Amiodarone
Flecainide

298

How is AF managed if onset has been within 48 hrs?

Dc cardioversion
Flecainide/amiodarone

299

What is done to control AF rhythm if onset more than 48 hrs ago?

Warfarinise for 6 weeks

300

What can be used for rate control in AF?

Beta blockers
Calcium channel blockers
Digoxin

301

What drug shouldn't be given alone for atrial flutter? Why?

Flecainide
Will slow atrial rate allowing one to one conduction to the ventricles paradoxically increasing ventricular rate

302

How should VT be treated graded on severity?

Arrest - ALS
Unstable - DC cardioversion
Stable - amiodarone/lidocain then DC cardiovert if necessary

303

How should non sustained VT episodes be treated chronically?

Beta blockers, or, if very symptomatic amiodarone/flecainide

304

What are causes of VT?

Brugada
Idiopathic
LQTS (congenital, acquired)

305

Examples of each subclass of Na channel blockers and brief MOA

1a. = Disopyamide - binds to open NaC, dissociates slowly so lengthens AP
1b. = lidocain - binds to inactive NaC, dissociates rapidly shortening AP. Use dependant block reducing afterdepolerisations
1c. = flecainide - dissociates very slowly, no effect on AP length

306

General action of na channel blockers

Blocking voltage gaited na channels decreasing slope of phase 0 of AP. Decreases rate of AP conduction through the heart.

307

When should Na channel blcokers never be used? Which trial showed this?

Structural heart disease
CAST

308

Side effects of class 1abc na channel blockers

1a - long qt , hypotension
1b - dizzyness, drowsyness
1c - increased ventricular response to atrial flutter

309

Side effects of beta blockers

Bronchoconstriction
Hypotension
Lethargy

310

How do beta blockers influence cardiac function?

At sa node reduce GalphaS thus decrease cAMP thus decrease HCN and rate
On myocytes decreases PKA reducing calcium channel phosphorylation and activation

311

What are the class three antiarrhythmics?

Eg amiodarone and solatol
K channel blockers but useful drugs also other functions as though theoretically k channel blocking is beneficial by prolonging AP it actually is proarrhythmic

312

Amiodarone side effects

LQTS
Pulmonary fibrosis
Fucks with thyroid
Hepatic injury

313

How do the non-dihydrophyramidine ccbs effect heart rate?

Blocks inward calcium flow in the sa and av node slowing initiation and conduction,
Negative chronotrophy and ionotrophy

314

When would you not give verapamil or diltaziem?

Heart failure - they are negative ionotrophs

315

Half life of amiodarone

10-100 days

316

How does adenosine work?

Binds to A1 receptors in av and sa nodes activating K conductance hyperpolarising the cell causing massive slowing in conductance

However, t1/2 very short so wears off quickly

317

Side effects of adenosine

Bronchospasm
Sense of doom
Chest pains
Flushing

318

What are the two main mechanisms of arrhythmia generation? What are the sub sets of each?

Impulse generation (afterpotentials, ectopic focus, enhanced automaticity)
Conduction (re-entry)

319

What are the four classes of chemotherapy?
Examples

Antimetabolites - methotrexate
Intercalating agents - doxyrubacin, bleomycin (kind of)
Alkylating agents - cisplatin
Spindle poisons - taxanes, vinca alkaloids

320

Anticancer actions of methotrexate

Inhibits dhfr stopping production of tetrahydrofolate which is oxidised back to dihydrolate by thymidylate synthase. This oxidation drives DUMP to DTMP the precursor of thymine.

321

How does cisplatin work in cancer?

Bound to cl- in plasma due to high plasma cl-
Enters cell loosing cl- as low concentration
Now positive it can bind to negative groups on DNA. It has two binding sites so binds two regions interstrand or intrastrand interfering with dna synthesis and rna transcription

322

How does doxyrubacin work in chemo?

Intercalates between base pairs interfering with replication and trascription
Creates a complex with dna and topoisomerase inhibiting dna breaking and religation triggering apoptosis
Produces free radicals damaging DNA

323

How does bleomycin act in chemo?

Creates superoxides damaging dna activiating a dna cleaving enzyme

324

How do the taxanes work in chemo?

Inhibit microtubule degridation by stabilising beta tubulin
Thus cant dissasemble to pull microtubules apart
Cell sticks in metaphase

325

How do vinca alkaloids work in chemo?

Inhibits microtubule formation by binding to beta tubulin subunit so cells cant divide

326

In what phases do the different chemo drugs act?

Antimetabolites - S
Alkylating - G1 and S
Intercalating - All
Spindle poisons - M

327

What are the different compartments of a tumour defined by cell replication? Which is most amenable to chemo?

A - labile
B - stable
C - permanent

A as chemo doesnt tend to work on G0

328

What is the hypothesis for repeated dosing of chemo?

Fractional kill hypothesis
Repeatedly killing a set fraction of cancer cells until negligible left

329

What cancers are sensitive to chemo? What arent?

Lymphoma - germ cell are
Prostate and brain arnt

330

Indications for chemo?

Curative
Palliative
Neoadjuvant

331

What predicts a bad outcome for chemo?

Advanced stage
Weak patient
No molecular target markers
Bad scores

332

What is the disadvantage of oral chemo?

Taken at home and people think because it is oral it is milder.
People less likely to report serious side effects of chemo as they don't want it to be stopped

333

General chemo side effects

Bone marrow suppression
Alopecia
Mucositis
Nausea and vomiting
Diarrheoa
Myopathy
Renal failure

334

Specific side effect of bleomycin

Pulmonary fibrosis

335

What can cause variability in chemo pharmokinetics?

A - d/v, compliance
D - ascities, hypoalbuminia
M - liver dysfunction
E - renal dysfunction

336

DDIs of chemo?

Warfarin
NSAIDs with methotrexate
Enzyme inducers / inhibitors

337

What are the problems with most antiepileptics and pregnancy?

4 times the risk of OCP failure and teratogenicity (2-8%)

338

What teratogenic consequences are there to antiepileptics? How can they be mediated?

Neural tube defects
Digit hypoplasia
Learning difficulties

Give folate and vit K supplement

339

Which antiepileptics act on VGNaC?

Carbamezapine
Phenytoin
Lamotrigine

340

How do VGNaC blockers produce a use dependant block?

Bind to inactivation gate and must be depolarised to bind thus voltage dependant

341

When can carbamezapine be used? When cant it be used?

Complex partial seizures ++
Generalised tonic clonic seizures +
NOT absence seizures

342

General antiepileptic ADRs

Ataxia, dizzyness, drowsiness, nausea, vomiting

343

Which antiepileptic can cause stevens johnson syndrome in 2-5%?

Phenytoin

344

Which antiepileptic can disturb BP?

Carvamezapine

345

Specific side effect of valpourate?

Hepatic failure
Weight gain

346

Specific side effects of phenytoin?

Gingival hyperplasia
Stevens johnson
Neutropenia

347

What is special about carbamezapine pharmacokinetics?

Induces own cyp metabolism reducing own t1/2

348

Are antiepileptics heavily or lightly protein bound? Consequence of this?

Heavily
Long t1/2

349

What is special about phenytoin pharmacokinetics

Non linear

350

Which antiepileptic needs liver monitoring?

Valporate

351

Which antiepileptic needs plasma level monitoring? How else can conc. be measured?

Phenytoin
By saliva conc

352

Which antiepileptic can be used in pregnancy? What is the risk of teratogenesis?

Lamotragine
2%

353

Which antiepileptic does not effect cyp? Does it still interact with ocP

Lamotrigine
Yep - ocp decreases lamotrigine concentration

354

How does valpourate work?

Inhibits gaba degridation and increases gaba synthesis
Also some action as a VGNaC blocker

355

What antiepileptics have ddis with aspirin and antidepressants?

Carbamezapin
Valproate

356

What is the antidote to benzo od?

Flumazenil

357

Adrs of benzos?

Sedation
Tolerance
Confusion
Resp and cvs depression
Withdrawal and dependance

358

Clinical features of parkinsons disease?

Pill rolling RESTING tremor
Lead pipe rigidity
Bradykinesia
Instability
Mood changes / cognitive changes
Expressionless facies

359

Differentials of parkinsons? What distinguishes them?

Multiple system atrophy - autonomic features
Drug induced parkinsonism (on antipsychotics or metoclopramide)
Progressive supranuclear palsy (opthalmoparesis)
Essential tremor (isolated tremor)

360

How is parkinsons diagnosed?

Clinical
Positive response to treatment
DAT scan (tracer absorbed by dopaminergic neurones thus rduced in Parkinson's - can be used to differentiate from essential tremor)

361

How is adrenaline made?

Tyrosine
- tyrosine hydroxilase
LDOPA
- dopa decarboxilase
Dopamine
- dopamine hydroxilase
Noradrenaline
Adrenaline

362

What breaks down dopamine?

MAO
COMT

363

Treatment options for parkinsons?

Levodopa (with carbidopa)
Dopamine receptor agonists
MOAI
COMT inhibitors
Anticholinergics
Surgery

364

When is ldopa most effective? Why? What class of drug can be used when it isnt useful?

Early disease when there are still dopaminergic neurones
Use a dopamine receptor agonist

365

Side effects of Ldopa?

On off movements
Freezing
Dystonia
Nausea vomiting
Flushing
Psychosis
Hallucinations
Tachycardia

366

Pk of LDOPA
How do we alter it

Oral
90% inactivated in intestine
9% converted peripherally
1% in the CNS
Alter with carbidopa to stop peripheral conversion allowing smaller dose with less ADRs

367

What drugs interact with LDOPA

MOIs - HTN crisis
Antipsychotics

368

What should you bare in mind when prescribing a COMT inhibitor in parkinsons?

Should not be given alone - needs something to work on!

369

Example of a COMT inhibitor

Entacapone

370

MOA for entacapone

Stops peripheral breakdown of LDOPA increasing amount and also reducing competition for transport into cns against its metabolite
Thus prolongs motor response to LDOPA

371

Example of a MOAI
What does it do?
How should it be used?

Selegiline
Prolongs ldopa
Denovo or in combo

372

Example of a dopamine receptor agonist? When are they used?

Apomorphine
End stage when there are very few dopaminergic neurones for LDOPA to act on

373

Side effect of Apomorphine

Compulsive behaviour (gambling, shopping, hypersexuality)

374

Advantage of apomorphine over levodopa

Less motor side effects

375

Why give anticholinergics to parkinsons?
Example
Use

Ach antagonises dopamine thus reduce ACh
Amantidine
Drug induced disease

376

What do anticholinergics not help with in parkinsons?

Bradykinesia

377

Adrs of anticholinergics

Confusion
Blurred vision
Drowsiness
Dry mouth

378

What is the pathology of myasthenia gravis?

Autoimmune igg binding to ACh receptor binding site competitivly antagonising acetylcholine
Ach remains in cleft so is broken down by acetylcholinesterase

379

Symptoms of myasthenia gravis

Fatiguable weakness esp of extraoccular and bulbar muscles
Symetric limb weakness

380

What exacerbates myasthenia gravis?

Neuromuscular blockers
Beta blockers, ccbs, aceis

381

What complications can occur with myasthenia gravis? What participates each?

Overtreatment - cholinergic crisis
Undertreatment - myasthenic crisis

382

Symptoms of a cholinergic crisis

Salivation
Lacrimation
Urination
Deification
Gi upset
Emesis

383

Treatment of myasthenia gravis

Acetylcholinesterase inhbitors (neostigmine)
Corticosteroids
Azathioprine
Iv immunoglobulin
Plasmapheresis

384

Signs of depression?

2 of the following that are persistant (>2 week)
Low mood
Anhedoina
Low energy

Also poor sleep, hoplessness, self harm, low libido, low appetite

385

Theories of depression causation

Decreased monoamine transmitters (NA and 5HT)
Abnormality of monoamine receptor
Deficiency in molecular functioning distal to receptor

386

ADRs of SSRIs

Anorexia
Mania
Suicidal intention
Extrapyramidal side effects
Serotonin sydrome in od

387

MOA of tricyclics

Inhibit NA reuptake
Inhibit 5HT reuptake
Muscarinic blocker
Alpha 1 blocker

388

ADRs of tricyclics

Sedation
Seizure
Arrhythmia
Poor eye accomodation
Postural hypotension
Constipation

389

Other than ssri and tca, what other class of antidepressant are used? Example?

Serotonin Noradrenaline Reuptake Inhibitor
Venlafaxine

390

MOA of SNRI

Low dose increases serotonin
High dose increases NA

391

Additional side effects of SNRI over SSRI

Sleep disturbance
HTN
Dry mouth

392

What drugs work well in bipolar?

Antiepileptics
Lithium

393

Why no antidepressants in bipolar?

Increase mania
Dont effect the depression

394

Symptoms of mania

Overactivity
Poor sleep
Rapid speech
Poor judgement
Promiscuous
Delusions of grandure

395

How does lithium work?

? Competes with ca/mg channels
? Increases 5HT
? Attenuates second messengers of neurotransmitter

396

ADRs of lithium

Memory issues
Thirst
Polyuria
Tremor
Nephrotoxic
Thyrotoxic
Hair loss

397

What monitoring does lithium require?

3 monthly levels and thyroid every 6 months

398

Examples of positive schizophrenia symptoms

Disturbance in thinking
Hallucinations
Delusions
Unusual speech
Behavioural change
Lack of insight

399

Causes of schizophrenia?

Biological Genetic Upbringing
Thought to be due to excess dopamine with possible 5HT involvement

400

What is the target pathway for dopamine antagonists in schizophrenia? What effects does this have? What other pathways are effected? Side effects?

Mesolimbic - therapeutic reduction in positive symptoms
Mesocortical - increases negative symptoms
Nigrostriatal - extrapyramidal side effects
Tuberoinfundibular - hyperprolactiemia

401

What are extrapyramidal effects?

Tarditive dyskinesia
Pseudoparkinsonism
Acute dystonic reactions (muscle spasms of the neck, jaw, back, eyes, tongue)

402

Examples of typical antipsychotics

Haloperidol
Chlorpromazine

403

MOA of typical antipsychotics

Dopamine blockers
Anticolinergics
Alpha adrenoceptor blockers
Antihistamines

404

Advantages and disadvantages of typical antipsychotics?

Ad - known course and side effects
Di - more sedating

405

Side effects of antipsychotics

Postural hypotension
Weight gain
Neuroleptic malignant syndrome
Extrapyramidal side effects

406

Name 2 atypical antipsychotics

Olanzapine
Rispiridone
Quetiapine
Clozapine

407

Which antipsychotic is most efficacious? Why isnt it used more?

Clozapine
Bad side effects

408

What factors stimulate vomiting?

Irritation of stomach
Chemoreptor trigger zone
Vestibular apparatus

409

What is released by the stomach on irritation and thus is a drug target for vomiting? What does it stimulate? Where else is this found?

5HT stimulating CNX
Chemoreceptor trigger zone

410

What does the vestibular apparatus release in response to noxious stimuli?

ACh
Histamine

411

Where do all stimulants for vomiting come together?

The medullary vomiting centre

412

What are the different classes of antiemetic?

D2 antagonist
5HT antagonist
Antihistamine
ACh antagonist

413

MOA of domperidone?

Decreases CTZ activation (dopamine antagonist)
Activates gastric emptying (ACh agonist)

414

MOA metoclopramide

Decreases CTZ triggering (D2 antagonist)
Increases gastric emptying (increases ACh)
Decrease stimulation from irritation (5HT atagonist)

415

Which of domperidone and metoclopramide produces worse extrapyramidal effects? Why?

Metoclopramide, crosses BBB

416

What other side effects are assocaited with dopamine receptor antagonists used in nausea other than extrapyramidal?

Galactorrheoa

417

Example of a 5HT antagonist used in nausea and vomiting
How does it work?

Ondansterone
Lowers stimulation of CTZ and stimulation of vagus by irritated stomach

418

Adrs of ondansterone

Flushing
Headaches
Constipation

419

Example of ach antagonist in nausea and vomiting
How does it work

Hyoscine
Blocks ach from vestibular apparatus

420

What is hyoscine particually useful in?

Motion sickness

421

Adrs of hyoscine

Dry mouth
Blurred vision
Paroxismal bradycardia
Low sweating
Itching

422

What h1 antagonist is useful in nausea and vomiting? How does it work?

Cyclizine
Crosses bbb and decreases histamine from vestibular apparatus

423

Side effect of cyclizine

Qt prolongation
Seditive

424

Types of laxatives and examples?

Bulk forming - isphaghula husk
Faecal softners - arachis oil
Osmotically active - macrogel and lactulose
Irritant - senna

425

Wich laxatives are best for soft faeces constipation

Stimulants like senna

426

Which laxatives are best for impacted faeces?

Osmotic and bulk forming
Lactulose, macrogels and ispaghula husk

427

Major complication of laxatives - how does it happen?

Hypokalaemia

Hypokalaemia causes decreased bowel inertia and constipation
Laxative decreases amount of absorbed from bowel (+ feedback) also decreases Na absorption so kidneys raise Na reabsorption increasing renal K loss
Worse hypokalaemia and thus back to the top

428

What is an important consideration when giving a laxative regarding dehydration? Which laxative avoids this problem?

Must be given with fluid
Macrogels - powder so must be dissolved mandating fluid intake

429

What laxatives have an immidiate (or rapid) onset?

Magnesium enema (osmotic) - within an hour
Senna (Irritant) - 8 to 10 hours

430

What laxatives are useful in patients with perianal disease?

Faecal softners like arachis oil

431

What laxative is used in liver failure? Why?

Lactulose
Metabolised by bacteria to acetic and lactic acid acidifying the colon increasing NH4 excretion

432

How do ispaghula husks work?

Resistant to digestion
Pull h2o into bowel
Distends bowel triggering contraction and movement

433

Contraindications to bulk forming laxatives

Obstruction
Adhesions and ulceration - cause obstruction!

434

What happens if you keep using senna?

Colonic atony resulting in constipation

435

What is a good laxitive to use with IBS

Ispaghula husks
Absorbs water so is a good laxative if constipated and absorbs water from diarrhoea improving faeces composition

436

Types of anti diarrheoal

Antimotility
Bulk forming
Specific treatments

437

What are antimotility antidiarrhoeal?

Opiates / loperamide
Decreases bowel motility so increases fluid reabsorption

438

What is a risk of antimotility antidiarrhoeals in IBD

Toxic megacolon

439

What specific diseases treatments can aid in diarrhoea

Pancreatic supplements
Bile acid suppressants in chrones

440

What would antidiarrhoeals worsten?

Overflow constipation
Infection

441

No pharmocological laxatives?

Treat underlying cause (dehydration, obstruction, parkinsons)
High fibre diet
Increase fluids
Exercise
Stop causative drugs (codein, calcium, anticholinergics, tca/ssri