CP1 Therapeutics Flashcards
1
Q
Leading Cause of heart failure
A
Ischemic heart disease
2
Q
Gold standard for CHF diagnosis
A
Echocardiogram showing <45% ejection fraction
3
Q
Goals of treatment for CHF (6)
A
Identify/Treat Causes Reduce Cardiac Workload Increase Cardiac Output Counteract neurohormonal maladaptation Relieve symptoms Increase quality of life
4
Q
Thromboembolism prophylaxis for Atrial Fibrillation
A
High-Med risk = Warfarin
Low risk = Aspirin
5
Q
Pharmacological action of ACE-inhibitors
A
Inhibit RAAS by preventing conversion of angiotensin 1 to angiotensin 2
6
Q
Examples of ACE inhibitors
A
enlapril, lisinopril, ramipril
7
Q
Therapeutic effects of RAAS inhibition
A
Reduce arterial/venous vasoconstriction (reduce preload/afterload)
Reduce salt/water retention (reduce circulating volume)
Inhibit neurohormonal adaptation/cardiac remodelling
8
Q
How should you implement an ACE-inhibitor regime
A
low dose then titrate upwards (may go past licensed max dose)
9
Q
What should be monitored during ACE-i therapy
A
Urea/creatinine (renal function)
K+ (before and during treatment - hyperkalaemia)
Blood pressure
10
Q
ACE-i Contraindications
A
NSAIDS
Severe renal imparment
Hypotension (<100mmHg)
11
Q
Complications of ACE-i therapy
A
Hyperkalemia
Severe first dose hypotension (especially during concurrent diuretic therapy - should withhold in first few days of ACE-i introduction)
deterioration in renal health
Dry cough
12
Q
Examples of AT1 receptor antagonists
A
Losartan, Candesartan, Valsartan
13
Q
Pharmacology of AT1 receptor antagonists
A
Oppose actions of angiotensin at the AT1 receptor
14
Q
Advantage of AT1 receptor antagonists
A
No cough whilst being equally as effective as ACE-is
15
Q
Benefits of diuretics in heart failure
A
reduce circulating volume (reduce preload and afterload), cause venodialtion (reduce preload)
16
Q
Complication of Diuretics
A
Hypokalaemia
17
Q
Examples of Beta-blockers
A
Metoprolol, Bisoprolol, Carvedilol, Nebivolol
18
Q
Benefits of using beta-blockers in CHF
A
reduce sympathetic stimulation of heart, oppose neurohormonal adaptation, anti-arrhythmic
19
Q
What kind of failure are Beta blockers most effective at treating
A
ischemic heart failure
20
Q
How should you implement a Beta-blocker regime for CHF
A
start low dose and titrate up
21
Q
What should you counsel a patient for when starting beta-blockers
A
Symptoms may get worse initially
22
Q
Contraindications of Beta-blockers
A
Asthma, symptomatic bradycardia, severe heart failure
23
Q
What is the mechanism of Spironolactone
A
Aldosterone receptor antagonist
24
Q
What is the role of Spironolactone in CHF
A
Reverses left ventricular hypertrophy at sub-diuretic doses - reducing mortality by 35%
25
How does Digoxin work
Na+/K+ ATPase blockage, causing Na+ accumulation in cells leading to increased exchange for Ca2+ , increasing cardiac contractility, impairing atrioventricular conduction (useful in AF) and inducing some bradycardia
26
What should digoxin therapy be reserved for
CHF with AF
27
Digoxin contraindications
concurrent heart block, bradycardia
28
How should you implement a digoxin therapy
Titrate dose to ensure ventricular rate does not drop below 60bpm (this indicates toxicity)
29
What should always be monitored in a patient with heart failure
Renal function, potassium,
30
What causes thiazides to become ineffective
Renal failure (no secretion in distal convoluted tubule)
31
Signs of Digoxin toxicity
Anorexia, nausea, Visual disturbances, Diarrhoea
32
NICE guidelines for the management of heart failure (full flowchart)
1 )Evidence of LV dysfunction = ACE-i + Betablocker (if mild stable failure)
Cough = switch Ace-i to an AT1RA
2) If symptoms still there, add Aldosterone antagonist (spironolactone)/ATRA/Hyrdalazine + Nitrate
3) if symptoms still present consider Digoxin
4) If Odematous use a diuretic (Thiazide/Loop)
33
What biochemical signalling factors increase acid secretion
Histamine acting on H2-receptors
Gastrin acting on CCK receptors
Vagal Ach via M3 receptors
34
What factors decrease acid secretion
Prostaglandins (E2 + I2) which inhibit the proton pump and stimulate bicarbonate release (gastroprotective)
35
Goals of treatment for Dyspepsia
Symptomatic relief/cure
suppress acid release
promote mucosal protection
eradication of underlying cause (e.g. H-pylori)
36
Common causative foods for dyspepsia
chocolates, spicy foods, fatty foods
37
Examples of antacids
Sodium Bicarbonate
Magnesium Hydroxide
Aluminium Hydroxide
38
How effective are Antacids
offer symptomatic relief but no cure
39
Why are calcium salts bad for long term control of dyspepsia
Promote gastrin release
40
Method of action for antacids
raise stomach pH
41
Method of action for alginates
when combined with saliva a viscous foam forms on top of the stomach, protecting the oesophagus during reflux
42
Examples of H2-antagonists
Ranitidine, Famotidine
43
How effective are H2-antagonists
Short term relief
44
Best time to use H2-antagonists
Night time
45
Why is imetidine no longer used as a H2 -antagonist
Cyp450 inhibitor, causing alteration of the metabolism of antigoaculants, phenytoin (anti-epileptic), carbamazepine (anti-epileptic) and TCAs
46
How to proton pump inhibitors work
inihibit H+/K+ proton pump, reducing H+ secretion
47
Why are PPis selective
become active at acid pHs
48
Complication of PPIs
increased risk of campylobacter infection
49
What do prokinetic drugs do
increase movmement of gastric contents from stomach to duodenum
50
Examples of prokinetic drugs
Domperidone, metocloperamide
51
What condition do prokinetic drugs help the most
GORD
52
What is the regime for Helicobacter Pylori eradication
TRIPLE THERAPY
PPi/H2 antagonist + 2 ABx
2 of: Metronidazole, Amoxicillin, Clarithromycin
1 week of triple therapy + 4-6 weeks PPI
53
What is the stepped approach to non H-pylori dyspepsia
Step 1: Antacid/alginate +antacid
Step 2: H2-antagonist
Step 3: PPI
54
What drugs are associated with peptic ulceration
```
NSAIDS
Oral steroids (particularly with NSAIDS)
```
55
Why do NSAIDS cause peptic ulceration
COX inhibition, causing reduced COX-1 production (which is gastroprotective)
56
Why do Steroids cause peptic ulceration
Lipocortin inhibitor causing decreased cytoprotective PLA2 production
57
What is the best regime for minimisation of gastric damage due to increased risk factors
PPI prophylaxis with misoprostol (prostaglandin analogue)
58
Contraindictions to misoprostol
pregnancy (can cause uterine contraction causing increased abortion risk)
59
What are the red flag signs for a patient with dyspepsia
ALARMS 55, anorexia, loss of weight, anaemia, recent onset/progressive symptoms, malaena/haematemesis, swallowing dificulty), >55 y/o
60
Flow chart for dyspepsia management
mild = antacid/H2 antagonist
recurrent = PPI
ALARMS 55 present = GP referral for endoscopy/H-pylori test
if H-pylori +ve = Triple therapy with PPI + 2 of metronidazole, amoxicillin and clarithromycin for 1 week ,then 4-6 weeks of a PPI
If negative just a PPI
61
Goals of treatment for Hypertension
Reduction in BP to specific targets with as few side effects as possible
SBP <140mmHg
DBP <90mmHg (<80mmHg in diabetes and CKD)
62
When are ACI-is nephroprotective
In diabetics
63
Apart from hyperkalaemia, what is another important side effect of ACE-is
Angioedema
64
Examples of Calcium channel inhibitors
Verapamil (rate limiting) , Amlodipine, felodipine, nifedipine
65
examples of alpha blockers
Doxazosin, prazosin
66
Why are alpha blockers last choice for Hypertension
Widespread side effects making them poorly tolerated
67
What line are diuretics for Hypertensive control
3rd
68
How do Thiazide Diuretics work
inhibit Na+/Cl- in DCT reducing circulating volume
69
Important side effects of Thiazides
```
Hypokalaemia
Hypercalcaemia
Postural hypotension
Impaired glucose control
altered lipid profile
Impotence
```
70
Contraindications for thiazides
Gout
71
Examples of Thiazide Diuretics
Chortalidone, Indapamide
72
Adverse effects of Calcium channel blockers
Peripheral odema
Postural hypotension
Constipation
73
Side effects of beta blockers
Bronchospasm
| Reduced Hypoglycaemic awareness `
74
What lifestyle changes can be done to treat hypertension
decreased consumption of alcohol, caffeine, fat, salt, smoking
Increased: weight loss, fruit, oily fish, exercise
75
How do you confirm hypertension, knowing the patient has implemented lifestyle changes already
```
ambulatory measurement (around 14 measurements)
on both arms
```
76
Classify Hypertension
Stage 1 >140/90
Stage 2 >160/100
Severe >180/110
77
Who should be treated with antihypertensives
Stage 1 +end organ disease/diabetes/CV disease/high CV risk (>20% over 10 years)
All Stage 2 + above
78
When treating hypertension, what factors promote the use of ACE-is/AT1RAs
Heart Failure, Left ventricular hypertrophy, diabetes
79
When treating hypertension, what factors promote the use of Calcium channel blockers
afro-caribbean ethnicity
80
When treating hypertension, what factors promote the use of Thiazides
old age
81
When treating hypertension, what factors promote the use of beta blockers
myocardial infarction, IHD, CHF
82
When treating hypertension, what factors promote the use of alpha blockers
resistance to other drugs, prostatic hypertrophy
83
When treating hypertension, what factors contraindicate the use of ACE-is/AT1RAs
renovascular disease
84
When treating hypertension, what factors contraindicate the use of Thiazides
Gout
85
When treating hypertension, what factors contraindicate the use of beta blockers
Asthma/COPD
| Heart Block
86
Flochart for hypertension treatment
Step 1: <55/non black/ high renin = Ace inhibitor
>55/black/low renin = calcium channel inhibitor
Step 2: ACE-i + Ca2+ blocker
Step 3: add diuretic (1st line thiazide-like, e.g endapamide/clortalidone)
Step 4: add alpha blocker/spironlactone/other diuretic/beta blocker
87
aside from hyperlipidaemia patients, Who should be prescribed statins
patients with high risk of cardiovascular events (renal failure, diabetes, hypertension)
88
How do nitrate assist in pharmacological management of ischemic heart disease
Release NO, causing venodilation (decreased preload/cardiac work), as well as coronary artery vasodilation, improving coronary blood flow
89
First line for IHD intervention + why
Beta blockers, as coronary flow is only in diastole, so decreasing heart rate prolongs diastole period, increasing coronary blood flow
90
Names of rate limiting calcium channel blockers
verapamil, diltiazem
91
What did the HOPE trial indicate
ACE-is reduce mortality in IHD
92
Names of potassium channel activator
Nicorandil
93
Method of action of potassium channel activators
Donates nitric oxide, promote vasodilation via ATP sensitive K+ channel activation
94
How does aspirin act as an antiplatelet
irreversible inhibition of COX leading to prostacyclin > thromboxane production, endothelial cells regenerate COX via nucleus but platelets cannot as they aren't nucleated
95
How does Clopidogrel work
ADP receptor antagonist leading to glycoprotein IIb/IIIa inhibition (prevents platelet aggregation)
96
Aspirin Contraindications
Asthma
97
What is the management of IHD (for someone with the cardiovascular risk needed for intervention)
antiplatelet (low dose aspirin or clopidogrel)
BP controlled <140
<5mmol/l cholesterol (<3mmol/L LDL), statin if >
Symptomatic relief of angina use a GTN spray/sublingual tablets
98
What are the drug choices for the prevention of IHD
1st choice - Beta blockers/ if CI use rate limiting calcium channel blocker or a Dihydropyridine calcium blocker (both +/- oral nitrate)
2nd choice - if beta blocker add a Dihydropyridine, if using a dihydropyradine add a beta blocker
3rd choice if still refractory add nicorandil
99
Whats an important interaction to consider when prescribing prevention for ischemic heart disease
Rate limiting calcium channel blockers and beta blockers are contraindicated for concurrent therapy as they may induce life threatening bradycardia
100
how do you structure IHD intervention (stable angina intervention)
Offer GTN for relief, assess CV risk (clotting, lipids and BP lifestyle) and control where necessary, then if there is still symptoms attempt to prevent with beta blockers/ca2+ inhibitors/nicorandil
101
what is added to management when comparing stable angina and unstable angina
LMWH
102
How does Warfarin work
inhibits Vitamin K dependent coagulation
103
Indications for warfarin therapy
artificial heart valves, AF, PE, DVT
104
How long is Warfarin's action delayed + why
around 3 days, as it inhibits new factor formation, and the stores may last for up to 3 days
105
How do you monitor warfarin
INR (target 2-3)
106
what drugs does warfarin interact with
Cyp450 inducers/inhibitors (potentiated by inhibitors)
107
Name some cytochrome p450 inhibitors
Amiodarone, Fibrates, erythromycin, cimetidine (H2 antagonist)
108
Name some cytochrome p450 inducers
Barbiturates, Carbamazepine, phenytoin
109
Signs of warfarin potentiation
increased bleeding risk
- gastric ulcer bleeding
- haemorrhagic stroke
- haemoptysis
- haematuria
- easy bruising
110
How does warfarin interact in pregnancy
Teratogenic, particularly in 1st trimester
| can cause fetal vit k deficiency in the 3rd trimester
111
alternative to warfarin in pregnancy
LMWH
112
Heparin method of action
antithrombin 3 activator, inhibiting serine protease, inhibiting factor 9,10,11 formation
113
What is long term heparin use (>5 days) associated with
Thrombocytopenia
114
What type of heparin requires monitoring
Unfractionated
115
What test monitors heparin's action
Activated partial thromboplastin time (intrinsic pathway)
116
How does Dabigatran work
Oral thrombin inhibitor
117
What is used to prevent MI in patients who have previously had an MI
Low dose aspirin
118
How does Dipyridamole work
Inhibits phosphodiesterase, prevents cGMP/cAMP breakdown causing decreased platelet aggregation
119
How does abciximab work + when is it given
Monoclonal antibody against glycoprotein IIb/IIIa, to patients undergoing angioplasty
120
What time of day should statins be taken
At night (cholesterol synthesis is highest)
121
What are the actions of paracetamol
Analgesia
| Antipyrexia
122
Minimum for liver damage with paracetamol
14 tablets
123
NSAID actions
Analgesia
Antipyrexia
Anti-inflammatory
124
NSAID adverse effects
GIT ulceration/erosion
Reduction in renal perfusion
Bronchospasm
Reduced platelet aggregation (reversible)
125
How should you prescribe NSAIDS
Lowest effective dose for the shortest period of time necessary to control symptoms,
Regular review required
Consider co-prescription of a PPI, particularly in high GI risk/long term
126
Name some weak opioids
Codeine
Dihydrocodeine
Dextropropoxyphene
Tramadol (po)
127
Name some Strong opioids
```
Morphine
Diamorphine
Oxycodone
Buprenorphine
Fentanyl
```
128
What are weak opioids most effective with
Paracetamol
129
why may Chinese people not respond to codeine
90% don't have a CYP450 2D6 gene
130
Routes of administration of strong opiods
```
Oral
Rectal
Transdermal
Sublingual
Topical
Intramuscular
Subcutaneous
Intravenous
Epidural
Intrathecal
```
131
ADR for opioids?
```
N + V (usually requires an antiemetic)
Constipation
Sedation
Respiratory depression (in toxcicity)
Hypotension
Urinary retention
```
132
What is breakthrough pain
transient exacerbation/recurrence of pain in patients who have stable pain relief usually
133
What may precipitate breakthrough pain
End of dose failure
Incident pain
Spontaneous pain
134
How do you convert to an alternative opioid?
Determine 24 hour requirement and use conversion factor for alternative opiate
135
What are some common opioid equivalences for 60mg morphine p.o
Hydromorphone p.o - 9.8mg
Oxycodone p.o - 30mg
Fentanyl (transdermal patch) 25 micrograms/hr
136
What opioid should be used in morphine allergy
Tramadol, oxycodone or fentanyl
137
Advantages of patient-controlled analgesia
```
Rapid analgesia
Readily prepared
Patient satisfaction
No dose delay
Patient acceptabilityNo peaks/troughs
```
138
Disadvantages of patient-controlled analgesia
Expensive
Requires IV access
Training
Monitoring
139
Why would you use diamorphine (heroin) instead of morphine
It has better aqueous solubility
140
What should be monitored during opioid therapy
```
Pulse
BP
O2 Sats
Respiration rate
Pain intensity
Sedation score
Side effects
Amount of opioid used
```
141
How does Tramadol work
mu-agonist , inhibits NA uptake/5-HT release
142
What is Naloxone
Opioid receptor antagonist
143
When would you use Naloxone
Opioid overdose
144
Signs/Symptoms of neuropathic pain
Burning, Pins and needles, Scalding, shooting, Stabbing
| Hyperalgesia, Allodynia
145
Best treatments for neuropathic pain
```
TCAs
Anticonvulsants (carbamazepine, gabapentin, pregabalin)
Opioids
Local anesthetics
Capsaicin
```
146
How do TCAs work
Inhibit neuronal NA/5-HT reuptake
147
How do Gabapentin and Pregabalin work
Prevent ca2+ mediated activation of dorsal horn neurones
148
How does Salbutamol work
B2-adrenoreceptor agonist, causing AC activation, increasing intracellular cAMP, promoting muscle relaxation
149
What does prolonged B2-agonist use do
Receptor downregulation
150
What may reduce the chance of receptor downregulation in salbutamol use
Inhaled corticosteroid
151
What is the requirement when prescribing a Long-acting beta 2 agonist
The patient is also on a steroid
152
How does a Xanthine work
Adenosine receptor antagonist OR phosphodiesterase inhibitor
153
Examples of Xanthines
Theophylline, Aminophylline
154
The best example for Xanthine use
Aminophylline intravenously for an acute asthmatic attack
155
How do muscarinic antagonists work
Block parasympathetic bronchoconstriction
156
Examples of Muscarinic antagonists
ipratropium/tiotropium
157
What role do corticosteroids have in asthma treatment
Prevention (do not reverse an attack)
158
Example of steroids used in asthma
Beclometasone (becotide inhaled or prednisolone orally)
159
How do steroids work
Act on intracellular DNA receptors to influence protein production (anti-inflammatory)
160
Side effects of steroids
```
Throat infections, hoarseness (inhaled) - advise to wash mouth out after use
Adrenal suppression (oral)
```
161
Name bronchodilators used in asthma treatment
SABAs
LABAs
Xanthines
Muscarinic antagonists
162
Name Anti-inflammatory agents used in asthma treatment
Corticosteroids
| Leukotrienes receptor antagonists
163
Example of Leukotriene receptor antagonist
Montelukast
164
What is a leukotriene
Pro-inflammatory product of arachidonic acids
165
What is Omalizumab
MAB against free IgE (not bound IgE)
166
What line is Omalizumab used at for asthma treatment
Last resort
167
What is the treatment cascade for Asthma
1. SABA (+ inhaled ICS if >2 times a week)
this will change to everyone gets a SABA+ICS
2. +LABA trial
3. if LABA fails, try LTRA/Xanthine
4. Increase dose of inhaled steroid
5. Add oral steroid
168
What may require you to step up asthma treatment
use of salbutamol inhaler >2 times a week
169
What may assist with poor inhaler technique (in young and old)
Spacer devices
170
What order should asthma drugs be taken in
Bronchodilator before steroid
171
Treatment cascade for COPD
1. SABA/SAMA
2. if FEV1 >50% replace SABA/SAMA with LABA/LAMA
if FEV1<50% add LABA+ICS or replace SAMA with LAMA
3. LAMA+LABA+ICS
172
How do NSAIDS provoke asthma
Increase Leukotriene production (as there is reduced prostaglandin production meaning there is more free AA for LT production)
173
How do statins work
HMG-CoA Reductase inhibitors
174
Examples of Statins
Simvastatin, Pravastatin, Atorvastatin, Fluvastatin
175
What are the effects of statins
Reduction in plasma cholesterol, upregulation of hepatic LDL receptors leading to increased LDL uptake
176
When aren't statins effective + what is the best to try
Homozygous familial disease, atorvostatin
177
When should you consider statin use
High cholesterol OR if they have risk factors for CVD
178
Standard prescription following an MI
Statin
Aspirin
Beta-Blocker
ACE-i
179
What risk of CVD in the next 10 years requires statin treatment
>10%
180
Cautions for statins
Use carefully in liver disease
181
Most important side effect of statins
Rhabdomyolysis/myopathy
182
Least likely statin to cause Rhabdomyolysis
Pravastatin
183
What should be monitored when starting statins
Liver function
184
Drug contraindications for simvastatin
Erythromycin
Amlodipine
Verapamil
Diltiiazem
185
Patients with med-high risk of developing CVD
```
Males >55
Males 45-55/Females >55 with@
1. Family history of IHD
2. Smokers
3. Overweight
4. S Asians
```
186
How do fibrates work
PPAR-alpha activators, promoting VLDL breakdown
187
What are fibrates useful for
reducing triglycerides
188
ADR Fibrates
Rhabdomyolysis
189
What does Ezetimibe do
Cholesterol absorption inhibitors
190
How do fish oils affect cardiovascular health
High omega 3 replaces COX and produces a different balance of TXA/PGI (PGI more potent, TXA less potent)
191
Treatment cascade for Dyslipidaemia
IF INCREASED CHOLESTEROL (or high CVD risk)
1. statin + reduced risks
2. Add a fibrate
3. add Ezetimibe
IF INCREASED TRIGLYCERIDES
1. Lifestyle chances
2. Fibrate/Fish oil?
192
What action do antipsychotics have
Dopamine D2- receptor antagonist
193
What are Extrapyramidal side effects of dopamine receptor blockers
drug-induced parkinsonism
Restlessness
abnormal movements
Tardive Dyskinesia
194
Examples of atypical antipsychotics
clozapine, olanzapine, risperidose, sertindolequetiapine
195
Metabolic side effects of antipsychotics
Weight gain
Hyperglycaemia
Dyslipidaemia
196
Cardiovascular sided effects of antipsychotics
```
Cardiac arrhythmias (QT-prolongation)
Severe postural hypotension (Chlorpomazine)
Increase stroke risk (Olanzapine/respirodone)
```
197
How does Clozapine work
D2, D4, 5-HT antagonist
198
Side effect of Clozapine
Agranulocytosis (neutropenia)
199
What needs monitoring during clozapine treatment
FBC (checking WBC) every week for 18 weeks, every 2 weeks for a year then every 4 weeks after
200
Who is Clozapine restricted to
patients who have failed to respond to 2 antipsychotics (including 1 atypical)
201
What is Neuroleptic malignant syndrome
life-threatening ADR to antipsychotics causing fever, muscular rigidity, altered mental status, autonomic dysfunction and elevated CK
202
Side effects Chlorpromazine
Skin photosensitivity
203
What is needed for an antipsychotic to be considered ineffective
4-6 weeks of failure to response
204
What antipsychotic should be used for violent/aggressive patients
Haloperidol
Lorazepam
205
What antipsychotics are used for EOL care and what do they do
Haloperidol and Lavpromazine due to sedative/anti-emetic effects
206
What is a depot preparation + why would you use it
Bolus in oil, given every 1-4 weeks, providing long term control for patients with compliance issues
207
How should Clozapine be counseled
Required regular blood tests
Should report signs of infection
Should report any increase/irregularity in pulse
208
How should patients be counselled with respect to antipsychotics
May affect driving/enhance alcohol effect
may cause anxiety/headache/insomnia
Should report movement disorders
209
what counts as responding well to antipsychotics
only 1 acute episode in 1-2 years = responds well
210
What correlated with clinical efficacy for dopamine antagonists
D2 affinity
211
How may Euthyroidism be achieved in hyperthyroidism
Antithyroid drugs
Thyroidectomy
Radioactive Iodine
212
How do Thionamides work
Decrease thyroid hormone production by inhibiting iodination of thyroglobulin via thyroperoxidase inhibition
213
How long does it take for thionamides to work
Several weeks
214
important ADR for thionamides
Agranulocytosis
215
Examples of Thionamides
Carbimazole, propylthiouracil
216
What role do beta blockers have in hyperthyroidism
reduce the action of catecholamines causing symptomatic relief from anxiety, tremors (only in non-selective BBs) and palpitations
217
What are the 2 medical treatment options for hyperthyroidism
1. High dose Carbimazole 1-2 months until remission then 18 month maintenance dose (+BB for symptomatic relief)
2. 'Block and replace' - High dose carbimazole until 0 thyroid activity, then adding thyroxine with the carbimazole + titrate to mimic appropriate thyroid activity (+BB for symptomatic relief)
218
Treatment for hypothyroidism
Levothyroxine
50-100 micrograms a day in young, increased after 6 weeks by 25-50 micrograms until appropriate levels are achieved
25 micrograms in elderly + those with IHD, which is then increased by 25micrograms every 3-4 weeks until TSH normalisation 1
219
Important ADR for thyroxine
may worsen/uncover angina
220
Length of time for thyroxine treatment
lifelong
221
Aim of epilepsy treatment
Control seizures with fewest possible side effects
| Monotherapy preferred
222
How do antidepressants affect seizure threshold
They can lower it
223
1st + 2nd choice for generalized seizures
1st Valproate/Carbamazepine (Lamotrigine if childbearing age)
2nd Levetiracetam
224
1st + 2nd choice for absence seizures
1st Ethosuximde
| 2nd Valproate/Lamotrigine
225
How does Valproate work
GABA potentiation, inducing Na-channel block
226
Valproate side effects
Weight gain, Tremor, sedation
227
Contraindication for Valproate
Pregnancy, impaired liver function (essential to have regular LFTs)
228
Carbamazepine side effects
Rash, Dizziness, Double Vision, CYP450 induction, teratogenesis
229
Phenytoin side effects
increased gum growth, nystagmus if toxic
230
Lamotrigine mechanism
Use-dependent blockage of sodium channels, reduction in glutamate release
231
What indicates lamotrigine should be withdrawn
Rash + flu like illness (risk of bone marrow toxicity)
232
Why may epilepsy be less controlled during pregnancy
enzyme induction and increased volume of distribution
233
What may prevent neural tube defects
Folic acid 5mg daily in 1st trimester
234
What is Status epilepticus
Continuous seizure for 30+ minutes OR 2 fits without recovery between
235
How do you treat status epilepticus
IV benzo
```
i.v. orazepam
or
Diazepam i.v/rectal
or
Clonazepam
or
Phenytoin slow i.v
```
last resort = general anesthetic such as propofol
236
When may treatment withdrawal be considered for epilepsy
Seizure free for 2-4 years
237
How do you withdraw a patient from epilepsy treatment
Gradual withdrawal, reduce dose every 4 weeks, stop driving during withdrawal
238
How do sulphonylureas work
inhibit ATP-sensitive potassium channels in beta cells causing increased insulin release
239
Side effects Sulphonylureas
Weight Gain
| Hypoglycemia
240
How do Meglitinide analogues work
rapid onset beta cell potassium channel closure causing increased insulin release (different receptor to sulphonylureas) `
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Contraindication for metformin
renal impairment
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Mechanism for Glitazones
PPAR-gamma activator, acts as an insulin sensitizer
reduces hepatic glucose output
increased peripheral glucose utlization
increased fatty acid uptake into adipose cells
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What should be monitored during glitazone therapy
Liver function
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Treatment Cascade for T2DM
1. 3 month trial lifestyle modification
2. Metformin (SU if renally impaired)
3. Dual Therapy (Metformin + SU/Glitazone/D4PPi/SGTL2i/GLP1RA)
4. triple therapy with metformin + 2 other drugs OR Insulin if metformin not tolerated
5. Insulin
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Aside from anti-hyperglycaemic drugs, what other drugs that should be considered when treating diabetes
Need to control BP and CVD risk factors
Ace-inhibitors nephroprotective in diabetes so 1st line for antihypertensives (however other drugs are just as effective as lowering blood pressure)
Simvastatin should also be prescribed
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What is the aim for diabetes treatment in terms of glycemic control and Blood pressure
<6.5-7.5% HBA1c, <135/75mmHG BP
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Examples of SSRIs
Citalopram, Sertraline, Fluoxetine, paroxetine
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How do SSRIs work
selectively inhibit reuptake of serotonin from neurones, enhancing synaptic concentrations of 5HT + downregulating presynaptic 5HT-Rs
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Why are SSRIs 1st line treatment for depression
better tolerated than TCAs and are safer in overdose
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Examples of TCAs
Amitryptaline, dothiepin, Lofepramine, Nortryptaline
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Side effects of TCAs
Sedation, Dry mouth, blurred vision, constipation, urinary retention (due to antimuscarinic effects), QT interval prolongation, predisposition to heart block/arrhythmias
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Why may sedation be a benefit for TCA controlled depression
sleep is impaired in depression often
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Who aren't TCAs suitable for
IHD patients, >70 y/o, patients at high risk of suicide
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Aside from TCAs and SSRIs, what are some other antidepressants in use + give an advantage of each if possible
1. Noradrenaline reuptake inhibitors (Reboxetine, useful for when TCAs are contraindicated but patient is resistant to SSRIs)
2. Seratonin-noradrenaline reuptake inhibitors (Venlafaxine, less side effects)
3. Noradrenergic and Specific Serotonergic antidepressents (mirtazapine, limited antimuscarinic effects)
4. Seratonin receptor modulators (Nefazodone)
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Complications with Venlafaxine
GI issues, Hypertension
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How do Monoamine oxidase inhibitors work
Inhibit monoamine oxidase increasing NT concentration
| Also cause indirect increased sympathic stimulation via tyramine metabolism
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What is the Cheese reaction with MOAIs + how may it be prevented
ingestion of high tyramine foods (such as cheese/yeast extract/avocado/banana/pickeled herring) may precipitate a catecholamine storm when taken during MAOI therapy, selective reversible inibitors of MAO-A prevent this reaction, since tyramine is metabolised by MAO-B
258
Treatment cascade for mild depression
1. 'watchful waiting' for 2 weeks
2. SSRIs (TCAs if sleep is an issue) + adjunct psychological treatment should be considered
3. Consider gradual withdrawl after 6 months if clinical improvement
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How should non-responsive depression be managed
Swap to another SSRI for 6 months, 2+ depressive episodes indicated treatment for 2 years
260
What mechanism does St Johns Wort have
similar to SSRIs
261
How does St Johns Wort interact with the metabolism
CYP450 inducer
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Can St Johns Wort be used in conjunction with SSRIs
No as it increased toxicity
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First line treatment for bipolar disorder
Lithium
264
When should Lithium be avoided
Renal impairment
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2nd line treatment for bipolar disorder
Anticonvulsants (valproate/carbamezepine)
266
Mechanism of action for Benzos
GABA potentiation
267
Problematic aspects of Benzos
Tolerance + Dependence
| Should be limited to 2-4 weeks
268
Drugs to consider in treating anxiety
Beta blockers
Benzos
Antidepressants
Buspirone
269
How does Buspirone work
Activates 5-HT1a receptors, binds to dopamine receptors
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Buspirone side effects
Dizziness
Nausea
Headaches
271
What drugs may cause secondary diarrhoea
```
Antibiotics
Orlistat (lipase inhibitor)
Misoprostol
PPIs
Digoxin
Metformin
Iron Salts
acarbose
```
272
First line treatment for diarrhoea
Oral rehydration therapy
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What is the role of antimotility agents in diarrhoea
used for symptomatic relief via presynaptic inhibition of Ach release (via mu-opioid receptor)
274
Side effects of using antimotility agents in diarrhoea
May prolong infection via reduced clearance of pathogen from GI tract
275
Examples of antimotility agents
Codeine, Loperamide, TCA, antimuscarinics
276
First line therapy for constipation
balanced diet with good amount of fibre
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What treatment is available for constipation not responsive to dietary modification
Osmotic Laxitives (e.g. lactulose)
278
How do osmotic laxatives work
increase fluid volume in colon osmotically
279
Aside from osmotics, what are some types of laxatives
Magnesium, Bulking agents, Stimulant Laxatives
280
How do Stimulant laxatives work
metabolites stimulate GI activity
281
What are some options for IBS treatment
```
Lactulose/Loperamide for constipation/diarrhoea
Antispasmodic agents (antimuscarinics, mebeverine)
TCAs (low dose)
```
282
Treatment for Ulcerative colitis + Crohns
5-Aminosalicylates (more so for UC)
e.g. Sulphasalazine , Mesalazine or 5-ASA
+ corticosteroids 1st line
Prenisolone
Immune suppressants may be required in severe disease (methotrexate, azathioprine, cyclosporine, infliximab)
Surgery is curative in UC, may be a benefit in Crohn's too
283
How should you counsel Mesalazine (5-aminosalicylate)
Patient should report blood dyscrasia (sore throat, fever, easy bruising), side effects may include: rash, headache, diarrhoea
284
What nay exacerbate IBD
NSAIDS, Smoking (Crohn's), alcohol
285
What should be counseled with Aziothioprine (immunosuppressant used in IBD)
Pancreatitis, myelosuppresion (bruising/bleeding, infections)
286
What type of IBD is methotrexate effective in
Crohn's
287
How do NSAIDS and Methotrexate interact
increase methotrexate toxicity
288
How should methotrexate be monitored
FBC, U+E, LFT, report fevers/coughs (indicate neutropenia), report cough/dyspnoea (pulmonary toxcicity)
289
What can happen if ciclosporin is given in addition to steroids
increased risk of pneumocystitis carinii
290
what can infliximab lead to the increased risk of
TB development
291
In a liver function test, what results most indicate hepatocellular damage
Raised ALT/AST
292
In a liver function test, what results most indicate Cholestasis
Raised ALP/GGT/Bilirubin
293
In a liver function test, what results most indicate Enzyme induction
Raised GGT
294
In a liver function test, what results most indicate Chronic liver disease
Raised Bilirubin/INR + Decreased Albumin
