Pharmo Flashcards
(442 cards)
0
Q
What is reasons model of accident causation?
A
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.
1
Q
What are the different sorts of active failure in prescribing?
A
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
2
Q
Why do errors happen?
A
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
Q
What is the individual vs systems base for medical drug errors?
A
Individuals fault - fear, retrain, litigation, naming and shaming
System fault - safeguards, barriers, acceptance and improvement
4
Q
What is pharmacovigilance?
What are the aims?
A
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
Q
What are type a and type b drug reactions?
A
A - predictable, exaggerated pharmocological response, dose dependant, common, high morbidity low mortality
B - unpredictable, not expected, in dependant of dose, rare, high mortality
6
Q
What are the dissadvantages of a clinical trial vs clinical prescription?
A
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
Q
How are adrs identified?
A
Spontanious reporting
Cohort studies
Case control studies
8
Q
What is the yellow card scheme?
What drugs should be especially reported?
A
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
Q
Problems with yellow card scheme?
A
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
Q
Why is reporting of adrs low?
A
Failure of pt to report Adr is trivial Not knowing report Lack of time Uncertainty of causal relationship Experience with process
11
Q
What is bioavailability? How is it calculated?
A
Fraction of administered drug that reaches systemic circulation
F = AUC (oral) / AUC (iv)
12
Q
What factors effect bioavailability?
A
Active - gi membrane pumps, enzymatic destruction, first pass metabolism
Passive - lipid solubility, molecular size of drug, pKa of drug
13
Q
What factors determine drug distribution?
A
Lipophilicity
Plasma protein binding
Tissue protein binding
Variation in compartment size etc. (E.g. Obese with more fat)
14
Q
How do we work out volume of distribution of a drug?
A
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
Q
What does Vd show?
What would a reading of 5L, 10L, 200L suggest?
A
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
Q
How can Vd be expressed?
A
Total (e.g. 8L) or as a propotion of weight (e.g. 0.2 L/kg)
17
Q
What reactions occur in phase 1 metabolism?
A
Redox reactions, hydroxylation
18
Q
What enzymes are most commonly involved in phase 1 metabolism? Which subset?
A
CYP450
CYP459 3A4
19
Q
How does phase 1 metabolism contribute to differing half lives of drugs?
A
CYP enzymes very generalist and therefore have variable rates with different drugs
20
Q
What non modifiable factors can influence drug metabolism?
A
Ethnicity
Sex
Age
Genetics
21
Q
What does pharmacogentetics allow?
A
An understanding how different genotypes will relate to different drugs to determine which drugs are effective and which are safe
22
Q
Give an example of pharmacogenetics applied to antihypertensive drugs
Why? What is given instead?
A
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
Q
What adr are afrocaribbean pts more likely to suffer from lisinopril?
A
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
