Therapeutics online course Flashcards
(368 cards)
1
Q
What is the difference between ADRs and Side effects?
A
side effect maybe beneficial or a disadvantage
2
Q
what is a type A ADR?
A
- the normal pharmacological response is undesirable
- dose-relate
- predictable
- usually managed by dose adjustment
3
Q
How can you minimise GI damage due to NSAIDs?
A
- identify patients at risk e.g. 65 years, history of ulcers, infection with H.pylori
- prophylaxis with PPI
- give in combination with misoprostol- a stable PGE1 analogue, acts on prostanoid receptors to inhibit gastric H+ secretion
4
Q
What is agranulocytosis?
A
absence of neutrophils
5
Q
What are the symptoms of agranulocytosis?
A
mouth ulcers, severe sore thread, infections
6
Q
What medications can cause agranulocytosis?
A
clozapine, carbimazole, carbmazepine
7
Q
How do NSAIDs damage the kidneys?
A
inhibit renal PGs
8
Q
What drugs can cause Stevens-Johnson syndrome?
A
carbamazepine and phenytoin
9
Q
What allele is associated with Stevens-johnson syndrome?
A
HLA-B*1502
10
Q
What drugs are known to increase activity of metabolising enzymes?
A
- rifampicin
- phenytoin
- ethanol
- carbamazepine
- St John’s Wort
11
Q
What does enzyme induction do to plasma concentration of drugs?
A
decreases
12
Q
What drugs inhibit Cy P450?
A
- erythromycin/ clarithromycin
- ciclosporin
- psoralen (from grape fruit juice)
13
Q
What has a quicker effect: enzyme induction or inhibition?
A
inhibition
14
Q
What drugs does simvastatin react with?
A
- macrolides
- amlodipine
- verapamil
- ditiazem
15
Q
How can you prescribe a statin with amlodipine?
A
pravastatin does not interact or use 20mg simvastatin as maximum dose
16
Q
What can NSAIDS prevent being eliminated from the kidney?
A
methotrexate
17
Q
which diuretic cause hypokalaemia?
A
loops and thiazide
18
Q
What do you prescribe with caution with non potassium sparing diuretics?
A
ACEi- increase risk hypotension
digoxin-increase toxicity
19
Q
What is prescribed with caution with potassium sparing diuretics?
A
ACEi-risk hyperkalaemia
20
Q
What are the potassium sparing diuretics?
A
sprinolactone
21
Q
which calcium channel blockers should not be prescribed with beta blockers?
A
verapamil and diltiazem
22
Q
Which calcium channel blocker can be prescribe with beta blockers?
A
dihydropyridines
23
Q
Give an example of a direct oral anticoagulant
A
rivaroxaban
24
Q
How do DOACs work?
A
factor x inhibitor
25
What are the benefits of DOACs?
fewer interactions
| no requirement to monitor
26
What should be avoided with St. Johns wart?
```
oral contraceptives
antiepileptics
some HIV drugs
ciclosporin
warfarin
simvastatin
MAOIs and SSRIs
```
27
What are two food interactions?
cranberry juice and warfarin
| grape juice and simvastin and some Ca-antagonists
28
what are the key warfarin interactions?
NSAIDs-increased risk of bleeding
| antibiotics (esp erythromycin and ciprofloxacin) enhanced Gi bleeding
29
What are the key NSAID interactions?
warfarin
| methotrexate- methotrexate toxicity
30
What should not be prescribe with ACE inhibitors?
potassium sparing diuretics
31
What should not be perescribed with verapamil?
beta-blockers-asystole
| digoxin- digoxin toxicity
32
What can cause digoxin toxicity?
amiodarone and varapamil
33
what can cause myopathy?
statins and macrolides
34
What are the steps of WHO good prescribing?
Step 1: Define the patient's problem
Step 2: Specify the therapeutic objective
What do you want to achieve with the treatment?
Step 3: Verify the suitability of your P-treatment
Check effectiveness and safety
Step 4: Start the treatment
Step 5: Give information, instructions and warnings
Step 6: Monitor (and stop?) treatment
35
What alternative approaches should be taken in renal impairment?
-Choose short acting agents (e.g. tolbutamide as a choice sulphonylurea)
-Gentamicin – increase the dosage interval in renal impairment
-Choose non-renally excreted alternatives
E.g. amlodipine in hypertension
Gliclazide in 2DM
36
What drugs should not be given in renal impairment and why?
-Some drugs must be avoided in renal impairment
e.g. metformin
-Some drugs require renal excretion to act may become ineffective in renal impairment
Thiazide diuretics
37
What drug does not cross the placenta?
heparin
38
what key drug types are issues in pregnancy?
```
Anti-epileptics
Anticoagulants
Antibiotics –Antihypertensives - labetalol, nifedipine, methyldopa
Antidiabetics – insulin
Metformin, glibenclamide
Antidepressants
```
39
what are the anti-epileptic drugs?
phenytoin
valporate
carbamazepine
40
What risks does phenytoin carry in pregnancy?
- craniofacial abnormalities
- hypoplasia of distal phalanges
- growth deficiency
- mental deficiency
41
What risk does valproate pose in pregnancy?
associated with neural tube defects
42
What risk does carbamazepine pose in pregnancy?
similar to phenytoin but decreased risk
43
What is the advice for prescribing for epilepsy in pregnancy?
- Continuation of treatment is preferable - counselling
- Or planned discontinuation
- Carbamazepine was preferred (5mg folic acid given to reduce chances of neural tube defect)
- Lamotrigine used first line in generalised tonic-clonic seizures to avoid teratogenic / interacting drugs
44
What drugs prevent oral contraceptives working?
- AEDs: phenytoin, carbamazepine and phenobarbital
| - rifampicin
45
What are the risks of warfarin in pregnancy?
- chondroplasia punctata (altered bone growth)
- optic atrophy
- mental retardation
46
In which trimesters should warfarin be avoided?
1 and 3
47
What should be prescribe instead of warfarin in pregnancy?
LMWH
48
Aminophylline is used at 500 micrograms per kg per hour (and then adjusted accorded to monitoring)
how much would a 65kg man need?
500 micrograms x 65 x 1 = 32.5 mg per hour infusion
49
What does a 1% solution mean?
1g per 100ml
50
If a solution is 1% how much of the drug is in 2m?
20mg
51
If a solution is 2% how much of the drug is in 5ml?
100mg
52
what ration is equal to a 1% solution?
1:100
53
How much drug is there is a 1:200,000 ratio?
5 micrograms/ml
54
The standard adult dose for anaphylaxis is 500 micrograms i.m.
If the solution is given as 1:1000 how many pls should be administered?
So, with 1ml vial of 1:1,000 adrenaline the volume given would be 0.5 ml.
Reason: 1:1000 = 1 mg/ml and need to give 500 micrograms
55
What abbreviation is used for as required?
p.r.n
56
What are the different abbreviations for drug route?
po: oral
im: intramuscular
iv : intravenous
sc: subcutaneous
neb: nebuliser
57
Define hypertension
It may be defined as “A blood pressure which is associated with significant cardiovascular risk”
58
What can cause secondary hypertension?
- renal disease
- renovascular disease
- Conn’s syndrome
- Cushing’s syndrome
- hyperthyroidism
- phaeochromocytoma
- pregnancy
- Drugs ( e.g. NSAIDs, corticosteroids, sympathomimetics)
59
How does renal disease cause an increase blood pressure?
not excreting as much fluid
60
How does renovascular disease increase blood pressure?
narrowing renal artery causes an increase in RAAS
61
How does Conn's syndrome increase blood pressure?
increase in aldosterone which is a fluid retaining hormone
62
How does Cushing's syndrome increase blood pressure?
- sodium retention
| - increase sympathetic activation
63
How does hyperthyroidism increase blood pressure?
-increase sympathetic activity
64
What is pheochromocytoma?
adrenaline secreting tumor
65
What contributes to essential hypertension?
- obesity
- insulin resistance
- excessive alcohol consumption
- genetics
- environment
- fetal programming -->low birth weight
- salt sensitivity
- age
- ethnicity
66
How does obesity increase blood pressure?
production of angiotensinogen from adipocytes
67
what are the NICE targets for hypertension treatment?
- SBP < 140mmHg (<140 mmHg in diabetes; <130 mmHg with complications)
- DBP < 90mmHg (<80mmHg in diabetes)
68
What is blood pressure the product of?
cardiac output x total peripheral resistance
69
Describe the RAAS pathway?
- Renin is released due to low BP, low Na+ or activation of beta-adrenoreceptors
- renin converts angiotensinogen into Angiotensin I
- ACE converts AI into angiotensin II
- Angiotenin II stimulates the release of aldosterone and causes vasoconstriction
70
Does vasoconstriction increase cardiac output or total peripheral resistance?
total peripheral resistance
71
When should ACEi not be prescribed and why?
renal disease --> blood pressure is very dependent on RAAS so if use ACEi then BP will drop substantially
72
What may ACEi do to electrolyte levels?
increase potassium --> decrease aldosterone causes sodium lose and potassium retention
73
When should ACEi be considered particularly protective?
in DM against nephropathy
74
What is an alternative to ACEi which do not cause a cough?
AT1 receptor antagonists
75
What do AT1 receptor antagonists block?
AII
76
What are the two types of Calcium channel blocker?
- rate-limiting --> effects on heart and vascular smooth muscule
- dihydropyridines --> more on vascular smooth muscle
77
Give an example of a rate limiting calcium channel blocker?
verapamil
78
Give an example a DHP
amlodipine
79
What is a contraindication of rate limiting CCB?
heart failure
80
When are right limiting CCB used?
ischaemic heart disease
81
Which diuretic are second line antihypertensives?
thiazide-like
82
How do diuretics lower blood pressure?
Inhibit Na+/Cl- in distal convoluted tubule so secrete more sodium and water
83
What are the side effects of diuretics?
- Hypokalaemia (monitor potassium)
- Postural hypotension
- Impaired glucose control
84
How do alpha blockers work?
competitive receptor antagonists of a1-adrenoreceptors on cardiac muscle
85
How do beta blockers work?
- Reduction in sympathetic drive to the heart, reducing cardiac output
- A reduction in sympathetically evoked renin release
86
What are the side effects of beta blockers and why?
Blockade of peripheral b2-adrenoceptors opposes vasodilatation to skeletal muscle ~ cold extremities and fatigue
87
what is an example of a beta blocker?
atenolol
88
What are the adverse effects of ACEI?
- Cough
- Severe first dose hypotension
- Renal damage (monitor eGFR)
89
What are the adverse effects of calcium channel blockers?
- Peripheral oedema (vasodilation of peripheral small vessels)
- Postural hypotension
- Constipation (some due to calcium channels in GI tract)
90
What are the adverse effects of thiazides?
- Diabetogenic
- Alter lipid profile
- Hypokalaemia
- Postural hypotension
91
what are the adverse effects of beta-blockers?
bronchospasm
92
What are the adverse effects of alpha-blockers?
- wide spread so poorly tolerated
| - postural hypotension
93
Which antihypertensive do you use for diabetes?
ACEi
94
Which antihypertensive do you use for CHF?
ACEi
95
What antihypertensive do you use for IHD?
beta blocker
96
What are the ACD guidelines?
- hypertension and type 2 diabetes and under 55 and not black = ACEi/ATRA. Then ACEi/ATRA + CCI or diuretic. Then ACEi/ATRA + CCI + diuretic
- over 55 or black give CCI, then CCI +ACEi/ATRA or diuretic. Then ACEi/ATRA +CCI+ diuretic.
- FINALSTEP- referral + spironolactone or alpha blocker or beta blocker
97
What are the risk factors for IHD?
- Male gender
- Family history
- Smoking*
- Diabetes mellitus*
- Hypercholesterolaemia*
- Hypertension*
- Sedentary lifestyle*
- Obesity *
98
What causes stable angina?
atherosclerotic disease, which limits the heart’s ability to respond to increased demand
symptoms on exertion but are relieved by rest
99
What causes unstable angina?
generally due to plaque rupture and the formation of a non-occlusive thromboembolism, or less commonly vasospasm (Prinzmetal angina)
100
What is the management for IHD?
Lifestyle advice directed at
- Smoking cessation
- Increased exercise
- Healthy diet
- Weight reduction of appropriate
Coronary artery bypass grafting (CABG) is the most effective approach
Angioplasty with stenting is also used
Using a balloon catheter to dilate / destroy the stenosis and insert a cage intraluminally to prevent restenosis
101
How do nitrates work?
- nitrates release nitric oxide which activate GC increasing cGMP release
- Venodilatation, leading to a decrease in preload and a reduction in cardiac work
- Coronary vasodilatation, improves coronary blood flow
102
How do beta blockers affect coronary flow?
Coronary flow only occurs during diastole, then by slowing the heart the diastolic period will be increased, as will the time for coronary blood flow.
103
Why do CCB work in IHD?
- Vasodilatation and improve coronary blood flow, so preventing symptoms.
- Verapamil (and to a lesser extent diltiazem) also have myocardial depressant and bradycardic actions, so reducing cardiac work.
- Verapamil also exerts Class IV anti-arrhythmic activity.
104
How does nicorandil work?
Nicorandil: combined NO donor and activator of ATP-sensitive K-channels.
The target is the ATP-sensitive K+-channel (KATP):
Potassium leaves the smooth muscle as a result causing hypo-polarisation
105
How does aspirin work?
Favours prostacyclin production over thromboxane as inhibits both endothelial and platelet cyclo-oxygenase (COX). Endothelial cell as nucleated and can regenerate COX, platelets lack nuclei and can not
106
How does clopidogrel work?
ADP receptor antagonist (prevents platelet aggregation)
107
When is clopidogrel prescribed?
Used in pts who can not receive aspirin (e.g. in asthma)
108
What is the pharmacological treatment of IHD?
- Low dose aspirin and/or clopidogrel
- BP controlled to < 140/85 mmHg
- Hypercholesterolaemia (to < 5mmol/l, LDL below 3mmol/l, or a 30% reduction)
- For symptomatic relief or occasional treatment, a GTN spray or sublingual tablets would be appropriate
109
What drug treatment is given for long term control of angina?
-1st choice: b-blockers for more pronounced stable and unstable angina
But not Prinzmetal angina
Oral long-acting nitrates might be added.
-2nd choice: if a b-blocker is ineffective or contra-indicated, then verapamil (or diltiazem) would be used or failing that a long-acting dihydropyridine (DHP).
Calcium channel blockers are particularity effective at reversing vasospasm
First choice drugs for Prinzmetal angina.
-In refractory disease: a b-blocker plus DHP but not with verapamil. Nicorandil might also be added to therapy.
110
How is unstable angina treated differently to stable angina?
addition of Low molecular weight heparin to therapy
111
What are the guidelines for pharmacological management of CHF?
- All patients with Left ventricular systolic dysfunction should receive an Angiotensin-converting enzyme inhibitor (ACE inhibitor) and a Beta-blocker
- All patients with oedema should receive a diuretic
112
How do ACE inhibitors work in CHF?
- Reduce arterial and venous vasoconstriction (reduce after- and pre-load)
- Reduce salt/water retention, hence reduce circulating volume
- Inhibits RAAS, prevents cardiac remodelling?
- Also used in hypertension
113
How do you prescribe ACEis?
- Low dose then titrate up
| - Monitor creatinine / eGFR and K+ before and during treatment
114
Which beta blocker is used in CHF?
bisoprolol
115
What type of diuretic is used in CHF?
loop
116
How do diuretics work in CHF?
- Reduce circulating volume
- Reduces preload on the heart
- Relieve pulmonary and peripheral oedema
117
How does spironolactone work?
- Spironolactone – mineralocorticoid (aldosterone) receptor antagonist (MRA)
- Now being used as an effective agent which reverses the LVH
118
How does digoxin work?
+ve inotrope by inhibiting Na+/K+ ATPase, Na+ accumulates in myocytes, exchanged with Ca2+ leading to increased contractility.
119
which condition is digoxin good for?
AF
120
What does digoxin do in AF?
-Impairs AV conduction and increases vagal activity (via CNS).
-The heart block and bradycardia is beneficial in heart failure with atrial fibrillation
Slowing the heart rate improves cardiac filling
121
How do you monitor digoxin?
measure pulse and make sure >60bpm
122
What is the management for LV dysfunction?
- ACEi/ATRA and a beta blocker
- then add aldosterone antagonist or ATRA + ACEi or hydralazine plus nitrate
- then add digoxin
123
How does warfarin work?.
- Vitamin K essential for production of prothrombin and coagulation Factors (Vitamin K important for post-ribosomal carboxylation of glutamic acid residues of these proteins).
- Warfarin blocks Vitamin K reductase, needed for Vit K to act as a cofactor (Vitamin K Epoxide Reductase Complex, VKORC):
124
When is warfarin used?
- in patients with replaced heart valves
- atrial fibrillation
- PE
- DVT
125
How is warfarin monitored?
INR
126
What can increased action of warfarin cause?
BLEEDING:
- gastric
- cerebral
- haemoptysis
- blood in faeces
- blood in urine
- easy bruising
127
How do heparins work?
- Activate Antithrombin III (natural protein)
| - Antithrombin – inactivates some clotting factors and thrombin by complexing with serine protease of the factors
128
What is the most important difference between warfarin and heparins?
warfarin can take several days to work whilst heparins work immediately
129
How do you monitor heparins?
APTT coagulation screen
130
How do you monitor DOACs?
you don't have to
131
How do DACs work?
inhibit activated factor X
132
In which way is warfarin better than DOACs?
warfarin is easier to reverse with vitamin K
133
Describe the arachidonic acid pathway
- Arachidonic acid in the membrane is split by PLA2 to create free AA
- cyclo-oxygenase converts AA into endoperoxides
- endoperoxides make prostaglandins. PGI2 in endothelial cells causes vasodilatation and prevents platelet aggregation but thromboxane in platelets causes platelet aggregation.
134
How is NO produced?
L-arginine + O2= NO + citrulline
| by nitric oxide synthase
135
How does aspirin work?
inhibit COX (irreversible). Endothelial cells have a nucleus so can produce new COX hence PGI2 is still produced by endothelial cells but platelets do not have a nucleus and hence thromboxane is not produced
136
How does dipyridamole work?
Phosphodiesterase inhibitor. Phosphodiesterase breaks down of cAMP and cGMP which inhibit aggregation
137
What causes glycoprotein IIb-IIIa expression?
ADP binding to platelets
138
What does glycoprotein IIb-IIIa do?
binds bibringen to von Willebrand factor to cross-link platelets
139
How does clopidogrel work?
Blocks ADP receptor
140
How does Abciximab work?
monoclonal antibody against Gp IIb/IIIa
141
How does alteplase work?
breaks down fibrin by converting plasminogen into plasmin
142
What are the signs and symptoms of peptic ulceration?
- Epigastric pain which may be precisely located by the patient by pointing.
- Relationship of pain to food is variable
- Hunger pain, which is relieved by eating.
- Night pain which is relieved by food, milk or antacids.
- Waterbrash – appearance of water in the mouth
- Nausea and less frequently vomiting.
- Vomiting blood.
143
What are the causes of peptic ulceration?
- H.pylori
| - NSAIDs
144
How do you test for H.pylori?
- Urea breath test - 13C urea: pt given 13C urea and bacterial ureases convert it to 13CO2 which is absorbed and exhaled from the lungs
- H.pylori antigens / antibodies in blood, saliva, stools.
145
What are the warning signs of serious disease with dyspepsia?
-Aged over 45 (or 55?) years
-Weight loss
-Anaemia
-Dysphagia (difficulty in swallowing)
-Haematemesis (vomiting blood)
-Melaena (tarry stools)
-Upper abdominal masses
-Persistent symptoms with repeat requests for OTC remedies
Onset of new symptoms
146
What stimulates gastric acid secretion?
- Histamine via H2 receptors
- Gastrin
- Acetylcholine via M-receptors – M3 on parietal cells
147
What decreases gastric acid secretion?
- Prostaglandins (E2 and I2)
| - Also cytoprotective via bicarbonate and mucus release
148
what are examples of antacids?
- sodium bicarbonate
- magnesium hydroxide
- aluminum hydroxide
149
How does sodium bicarbonate work?
HCO3- + H+ =CO2 + H20
150
How does magnesium hydroxide work?
Mg(OH)2 + 2HCl = MgCl2 + 2H2O
151
How does aluminium hydroxide work?
Al(OH)3 + 3HCl = AlCl3 + 3H2O
152
How do alginates work?
The alginic acid, when combined with saliva, forms a viscous foam which floats on the gastric contents forming a raft which protects the oesophagus during reflux.
153
How do H2 receptors work?
Histamine H2 receptors: coupled via adenylyl cyclase to increase cAMP which activates the proton pump:
154
Which H2 receptor antagonist is no longer used and why?
cimetidine --> drug interactions
155
How do proton pump inhibitors work?
Widely used, act via irreversible inhibition of the proton pump (H+/K+-ATPase):
156
What is a complication of PPIs?
Increased risk of Campylobacter infection (food poisoning) due to increased pH.
157
What do pro kinetic drugs do?
Cause Gastric emptying
| Movement of gastric contents from stomach to duodenum - drugs which do this will be of benefit in GORD.
158
How does domperidone work?
increased closure of oesophageal sphincter (good for reflux disease) and opens lower sphincter.
159
How does metocloperamide work?
acts locally to increase gastric motility and emptying (combined with analgesics to accelerate absorption
160
What is the treatment for H.pylori?
```
2 from:
Metronidazole
Amoxicillin
Clarithromycin
plus
PPI and/or H2 antagonist.
for 1 week and then PPI alone for a month
```
161
How do you treat non-h.pylori dyspepsia?
Step 1: antacid or alginate and antacid
Step 2: H2 antagonist
Step3: proton pump inhibitor
162
Why do NSAIDs cause peptic ulcers?
-block cox enzyme and so stop production of prostaglandins which are protective
163
How does misoptostol work?
- a stable PGE1 analogue, acts on prostanoid receptors to inhibit gastric H+ secretion.
164
When is misoprostol prescribed?
with NSAIDs in at risk patients
165
What is a contraindication of misoprostol?
females of child bearing age as it causes contractions
166
What are the signs and symptoms of liver disease?
- Jaundice and pruritus (hyperbilirubinemia)
- Nausea and vomiting (hyperbilirubinemia)
- Hepatomegaly
- Ascites (build up of fluid in abdomen --> aldosterone is normally metabolised in the liver)
- Dark urine and pale stools in cholestasis
- Spider naevi in alcoholic liver disease
167
What are the causes of liver disease?
```
Infection
-Viral hepatitis
Adverse drug reaction
-Halothane
-Paracetamol overdose
-Clavulanic acid in ‘Augmentin’ - co-amoxiclav
-Valproate
-Amiodarone
-Herbals
Alcohol abuse
Obesity ~ cirrhosis
Cancer
-Primary or secondary (metastasis)
```
168
What liver function tests measure hepatocyte health?
amionotransferases (alanine=ALT and aspartate =AST)
169
What LFT measures obstruction?
```
Alkaline phosphatatse (ALP)
Gamma-glutamyl transpeptidase (gamma GT)
```
170
What LFT measures function?
- albumin
| - coagulation (INR)
171
How does RBC breakdown occur?
- iron and globing are reused, biliverdin is formed from harm and reduced o bilirubin
- bilirubin is uncogaugated and water insoluble
- the liver conjugates bilirubin to make it water soluble and excreted as bile
- bile salts are used to emulsify fats via enterohepatic cycling
- remaining bile is secreted as sterecobilinogen in stools
172
Why do aminotransferases rise out to acute liver damage?
they are in high concentration in hepatocytes so if the liver is damaged they leak out
173
Where is alkaline phosphatase usually present?
membranes of the liver
174
When is alkaline phosphatase raised?
- choleostasis
| - metastasis of liver
175
When is Gamma GTs raised?
- induced by alcohol and some other drugs
- cholestasis
- cellular damaged
176
What are the LFT results of acute hepatitis?
- ALT & AST: increased
- ALP: increased or normal
- Bilirubin: increased or normal
- GGT: increased or normal
- Albumin: normal (long half life)
- INR: increased or normal
177
What are the LFT results for choleostasis?
- ALP: increased
- GGT: increased
- Bilirubin: increased
- ALT & AST: normal or increased
- Albumin: normal
- INR: normal or increased (reduced vit K absorption)
178
What are the LFT results for chronic liver disease?
- GGT: increased
- Bilirubin: increased
- Albumin: decreased
- INR: increased
- ALP, ALT & AST: normal or increased
179
What is prehepatic jaundice?
Water insoluble unconjugated bilirubin produced faster than liver can conjugate it for excretion
180
What can cause prehepatic jaundice?
- Often due to haemolysis – haemolytic anaemias such as spherocytosis
- Gilbert’s syndrome – 5% of pts have reduced levels of UDP-glucuronosyl transferase which conjugates bilirubin
181
What is heptocellular jaundice?
- Transaminases leak out
- Liver can not convert insoluble bilirubin from the blood to water soluble bilibubin
- Reduced bilirubin excretion
182
Define cholestasis?
Bile cannot flow from the liver to the duodenum
183
What are the types of cholestasis?
intraheptic or extra hepatic
184
What can cause intrahepatic cholestasis?
- Primary biliary cirrhosis: autoimmune damage to bile ducts
- Hepatocellular damage
- In pregnancy with unknown cause (~3rd trimester
185
What can cause extra hepatic cholestasis?
- Gallstones
| - Carcinoma head of pancreas
186
Why are stools pale and urine dark in obstructive jaundice?
- can not excrete bilirubin in the bile=Pale stools
| - Water soluble bilirubin excreted in the urine =Dark urine, Bilirubin in the urine confirms obstructive jaundice
187
What is prescribed for jaundice and how does it work?
colestyramine --> bile binding agent and prevents it being recycled
188
What complications can arise due to ascites?
- oedema secondary to hypoproteinaemia
- sodium retention due to secondary hyperaldosteronism
- portal hypertension
189
What is prescribed for ascites?
spironolactone (+ furosemide? + NaCl restriction due to aldosterone keeping sodium)
190
What are the symptoms of encephalopathy?
- Changes in personality
- Disorientation
- Confusion and drowsiness
- Sensitivity to centrally acting drugs
191
Why does encephalopathy occur due to liver disease?
The gut flora produce many nitrogenous products, including ammonia, which are normally cleared by the liver.
192
What is prescribed for encephalopathy?
neomycin/metronidazole (anti-bacterial) and lactulose (flush bowel out or bacteria)
193
What is prescribed for gastric bleeding and how does it work?
ranitidine (H2 receptor antagonists --> reduces acidity)
194
What is prescribed for osophageal varicies?
beta blockers, octreotide
195
What causes osophageal varicis?
increased portal vein pressure
196
What are the common causes of diarrhoea?
- Rotavirus: damages small bowel villi
- Invasive bacteria: damage epithelium.
- Adhesive enterotoxigenic bacteria: adhere to brush border, increase cAMP leading to Cl- and Na+ secretion followed by water:
- antibiotics
- orlistat
- PPIs
197
What is oral rehydration therapy?
Solution of electrolytes to replace the electrolytes lost in diarrhoea e.g. Dioralyte.
Must be isotonic
Glucose allows transport of Na via a symporter
198
why may anti motility agents not be prescribed in diarrhoea?
In infection they may reduce clearance of infective organisms from the GI tract, possibly prolonging infection.
199
How do opioids work as anti motility agents?
Reduce tone and peristaltic movements of GI muscle by inhibiting presynaptically (via µ-opioid receptors) the release of acetylcholine which allows more time for water reabsorption
200
How do osmotic laxatives work?
Enters the colon unchanged and converted by bacteria to lactic and acetic acid - raise fluid volume osmotically.
201
How does magnesium work as a laxative?
- Osmotic effect.
| - Mg2+ also release cholecystokinin which increases GI motility.
202
How does Senna work?
Senna extracts, enter colon metabolised to anthracene derivatives which stimulates GI activity.
203
What is IBS?
- This is a common, long-standing disorder
- Present for at least 12 weeks within 1 year
- Pain, bloating - relieved by defecation
- Episodes of diarrhoea and/or constipation.
204
How is IBS treated?
-Lactulose or loperamide for respective symptoms?
-Antispasmodic agents:
Antimuscarinics e.g. inhibit parasympathetic activity
-Mebeverine: direct relaxant of GI smooth muscle - probably acting as a phosphodiesterase inhibitor:
-Amitriptyline (TCA)
Low doses widely used + effective
Provide some pain relief
Antimuscarinic effects
Alters the sensitivity of sensory nerves in low GIT?
205
What is inflammatory bowel disease?
Encompasses both ulcerative colitis and Crohn’s disease
206
What are the clinical features of inflammatory bowel disease?
- Diarrhoea
- Faecal incontinence
- Rectal bleeding, bloody diarrhoea
- Passing of mucus
- Cramping pains
- Weight loss
- In Crohn’s disease there may also be mouth ulcers and anal skin tags
207
What are the complications of crohn's disease?
there may be malabsorption, leading to deficiencies of folate, and iron associated with iron-deficiency anaemia respectively.
208
What are the complications of ulcertative colitis?
Blood loss in ulcerative colitis may also lead to iron-deficiency anaemia.
209
What conditions are associated with inflammatory bowel disease?
arthritis, uveitis and an increased risk of thromboembolism
210
What is ulcerative colitis?
- Inflammation which involves the rectum and spreads to the colon.
- Inflammation tends to be superficial, affecting the mucosa.
211
What is Crohn's disease?
- May affect any part of the GI tract but mostly the ileum and / or colon are involved.
- T-lymphocytes are activated and lead to transmural inflammation and the extensive involvement may lead to the formation of fistulae.
212
How do 5-aminosalicylates work?
inhibits leukotriene and prostanoid formation, scavenge free radicals, decrease neutrophil chemotaxis.
213
What else can be used to treat IBD?
corticosteroids and immunosuppressants
214
What is mesalazine?
5-aminosalicylate
215
How do you cancel a patient for Mesalazine?
Risk of blood dyscrasia, pts should report:
- Sore throats
- Fevers
- Easy bruising or bleeding
Aminosalicylates are associated with side effects which include rashes, headaches, and diarrhoea.
216
What is aziothioprine?
immunosuppressant
217
What are the risks and how do you cancel for azithioprine?
```
-Risk of pancreatitis
Requires FBC monitoring (6-8 weeks)
-Counsel risk of myelosuppression
Bruising & bleeding
Infections
```
218
How do you monitor methotrexate use?
- Full blood count, renal function and LFT
- Report fever/cough – may indicate infection due to neutropenia
- Report cough/dyspnoea – may indicate pulmonary toxicity
219
What is asthma?
It is defined as reversible increases in airway resistance, involving bronchoconstriction and inflammation
220
How is asthma characterised?
Characterised by reversible decreases in the FEV1:FVC (less than 70-80% suggests increased airway resistance)
Variations in PEF which improve with a b2 agonist (+ morning dipping)
221
How is bronchial calibre controlled?
Parasympathetic
- Acetylcholine (A.Ch.) acts on muscarinic M3–receptors:
- Bronchoconstriction
- Increase mucus
Sympathetic
- Circulating adrenaline acting on beta2-adrenoceptors on bronchial smooth muscle to cause relaxation
- Plus sympathetic fibres releasing noradrenaline (NA), acting at b2-adrenoceptors on parasympathetic ganglia to inhibit transmission
- Beta2-adrenoceptors also on mucus glands to inhibit secretion
222
What is COPD?
- It is a combination of Chronic bronchitis + Emphysema in varying proportions
- Chronic bronchitis – increased mucus, airway obstruction, intercurrent infections
- Emphysema – involves destruction of alveoli
223
What are the characteristics of COPD?
- FEV1 is reduced
| - There is little variation in PEF
224
What are the clinical features of asthma?
- Wheezing
- Breathlessness
- Tight chest
- Cough (worse at night /exercise)
- Decreases in FEV1, reversed by a b2-agonist
225
Describe the pathophysiology of an asthma attack
- mast cells and mononuclear cells are activated
- release of spasmogens causes bronchospasm which results in the early phase
- at the same time chemotaxis are released resulting in the inflammatory response recruiting white cell and so causing the late phase response hours later
226
What are the spasmogens?
- histamine
- prostaglandin
- leukotrines
227
Which enzyme produces prostaglandins?
COX
228
Which enzyme produces leukocytes?
LOX
229
What are the chemotaxis?
leukotriene
230
How does salbutamol work?
B2 adrenoreceptor agonist --> increase cAMP
231
What are xanthine?
bronchodilators- given iv in an emergency
232
What is an example of a xanthine?
aminophylline
233
What is reflumilast?
selective PDE IV inhibitor (stops breakdown of CAMP)
234
When is reflumilast used?
COPD
235
How do Muscurinic M-receptor antagonists work?
-block parasympathetic bronchoconstriction.
236
how do corticosteroids work in asthma?
preventativ- anti-inflammatory by activation of intracellular receptors, leading to altered gene transcription (decrease cytokine production) and production of lipoortin which interfere with the arachidonic acid pathway by inhabitation of PLA2 which converts membrane arachidonic acid into free AA
237
Why are steroids given with Beta2-agonists?
reduces receptor down-regulation
238
what are the side effects of steroids?
-throat infections, hoarseness
239
How do leukotriene receptor antagonists (LTRA) work?
work as a relieved a receptor and prevent leukotrienes causing bronchospasm
240
What is the stepwise treatment of asthma?
Step 1: short acting B2 agonist plus regular inhaled steroid
Step 2: + trial of long actin beta 2 against or LTRA or xanthine
Step 3: increase steroid dose
Step 4: add oral steroid
241
What is the treatment for COPD?
- bronchodilators (shot and long acting)
- inhaled steroids? (biology of disease makes less effective but effective in 15%)
- antibiotics for intercurrent infections
- stop smoking
- oxygen therapy
242
What are the stepwise guidelines for COPD?
Step 1: short acting beta agonist or short-acting antimuscurinic as required
Step 2: if FE1> 50% add long-acting beta2 agonist or long-actin antimuscurinic instead of short acting. If FEV1<50% then add long acting beta agonist and inhaled steroid or replace short acting antimuscurinic with long acting antimuscurinic
Step 3: long acting antimuscurinic plus long acting beta 2 agonist plus inhaled steroid
243
How can NSAIDs cause asthma attacks?
they can increase leukotriene production as they inhibit cox enzyme so arachidonic acid is converted into leukotrienes
244
What is the time course of human insulin analogues?
have a rapid onset but short duration of action
245
When are human insulin analogues used?
- May be injected just before a meal or when necessary just after a meal.
- Increase flexibility and are useful for pts prone to pre-lunch hypoglycaemia and those who tend to eat late in the evening and may be at risk of nocturnal hypoglycaemia.
246
What is the time course of short acting insulins?
Soluble insulins have relatively short-lived effects of 6-8 hours, with peak effects at 2-5 hours.
247
How can you create intermediate and long-acting insulins?
- Combination of insulin with protamine gives rise to intermediate acting insulin (isophane insulin)
- binding to zinc gives intermediate to long acting insulin
- combination with protamine plus zinc gives long-acting insulin.
- Crystalline insulin zinc suspensions are also long-acting.
- Biphasic preparations contain both an intermediate-acting agent (e.g. isophane insulin) with a shorter acting form (e.g. soluble insulin).
248
Describe a twice daily regime of insulin
2 daily injections, one 30 minutes before breakfast and one before the evening meal of short- and longer-acting insulins in combination, with two thirds of the insulin given as the morning dose. This is the most common regimen.
249
Describe the basal bolus regimen
a single dose of medium-acting insulin is given at bedtime and doses of short acting insulin are given 30 minutes before each meal. This allows more flexibility with the timing of meals
250
What is the lifestyle advice for type 2 diabetes?
- to reduce the amount of simple carbohydrates in the diet
- limit the intake of mono and disaccharides, increase non-starch polysaccharides
- reduce the intake of fat to reduce the risk of atherosclerosis, such that fat is 30-35% calorific intake and carbohydrate is 50-55% .
- weight loss in obese
- increased exercise
251
How long do you wait for lifestyle changes to take effect before moving onto medication for type II DM?
3 months
252
How do sulphonylureas work?
- Inhibit ATP-sensitive potassium (KATP) channels.
- Glucose leads to ATP production which inactivate these channels, leading to cellular depolarisation, which results in calcium influx and insulin secretion.
- When glucose is low, ATP levels fall and ADP rises, channels open, with membrane hyperpolparization and this decreases insulin release.
- Sulphonylureas bind to a receptor associated with these channels, resulting in channel closure, which leads to insulin release.
253
What are the side effects of sulphponylureas?
-Cause weight gain (+increase insulin resistance), often avoided in obesity
-Awareness may be lost when using beta-blockers
-Associated with causing hypoglycaemia, especially
in the elderly,with long acting agents such as glibenclamide and missing meals
254
How dod meglitinide analogues work?
These also act on beta-cells but at a site distinct from the sulphonylurea receptor to cause closure of the KATP-channels, leading to depolarisation and insulin release.
255
What is the time course of meglitinide analogues?
Rapid rate of onset and are given at meal times to stimulate post-prandial insulin secretion, which is relatively short-lived.
256
What is another name for meglitinide analogues?
prandial glucose regulators (PGRs).
257
What kind of drug is metformin?
biguanide
258
When is metformin recommended?
in obese patients as does not cause weight gain
259
When is metformin contraindicated?
renal impairment
260
How do thiazolindiediones work?
Activate nuclear peroxisome proliferator-activated receptors gamma (PPAR-g), which alters gene expression and results in insulin-like effects.
‘Insulin sensitisers’ which work by enhancing glucose utilization in tissues, and so reduce insulin resistance
261
What are the effects of thiazolindieiones?
- reduced hepatic glucose output
- increased glucose transporters (GLUT) in skeletal muscle with increased peripheral glucose utilization
- Increased fatty acid uptake into adipose cells
262
What is the stepwise management of DM II?
step 1:diet
step2: metformin if normal renal function or sulphonylurea if renal function poor
step 3: 2 from metformin, sulphonylureas or glitazonne
263
How do thionamides work?
Decrease the production of thyroid hormones by inhibiting the iodination of thyroglobulin and this occurs via inhibition of thyroperoxidase.
264
What is a complication of thionamides?
May cause agranulocytosis leading to leucopenia.
If patients report with sore throats, mouth ulcers, bruising or non-specific illness, a full blood count should be carried out and the drug withdrawn if there is leucopenia.
265
Why are beta-blockers used in hyperthyroidism?
They will reduce the actions of catecholamines at beta-adrenoceptors, which are augmented in this condition. Non-selective beta-blockers (e.g. propranolol) are required to relieve the tremor.
266
What is the block and replace regime for hyperthyroidism?
-high foes carbimazole to suppress all thyroid activity then add thyroxine to treatment
267
How do glucocorticoids act?
- Inhibit synthesis of COX-2 and inducible nitric oxide synthase
- Inhibit synthesis of cytokines (interleukins, tumour necrosis factor) and chemokines
- Stimulate production of lipocortin (which inhibits PLA2 and the synthesis of prostaglandins leukotrienes)
268
What are the uses of glucocorticoids?
Anti-inflammatory / immunosuppressive therapy
- Allergic/ septic emergency i.v.
- Asthma, COPD – inhaled, oral (see Asthma tutorial)
- Ulcerative colitis, Crohn’s disease – oral, rectal (see lower GI tutorial)
- Rheumatoid arthritis - oral
- Skin conditions, e.g eczema, psoriasis – topical, oral
- Organ transplantation
- Others, inc. rhinitis, conjunctivitis
Replacement therapy
-Addison’s disease – need for steriod replacement, life-long.
Others
- Neoplastic disease
- Pre-term labour (enhance fetal lung maturation)
269
What are the side effects of oral glucocorticoids?
- Diabetes
- Osteoporosis
- Mental disturbances
- Peptic ulceration (esp. with NSAIDs)
- Visual: cataract and glaucoma
- Cushing’s syndrome (at high doses)
- Suppression of growth (children)
- Adrenal suppression – sudden withdrawal can cause acute adrenal insufficiency, hypotension and death
- Infections- increased susceptibility/ severity, particularly chickenpox (and measles)
270
What are the side effects of mineralocorticoids and why?
- Sodium and water retention
- With potassium loss
- And may cause hypertension/ worsen CHF
271
What is hypercholestolemia?
elevated plasma cholesterol
272
What is atherosclerosis?
focal lessons (plaques) on the inner surface of an artery.
273
What diseases does atherosclerosis lead to?
- Ischaemic heart disease (IHD)
- Peripheral vascular disease (PVD)
- Cerebrovascular disease
274
What are the risk factors for atherosclerosis?
- Genetic
- Hypercholesterolaemia (raised LDL or lowered HDL)*
- Hypertension*
- Smoking*
- Obesity*
- Hyperglycaemia*
- Reduced physical activity*
- Infection??
275
What drugs can cause dyslipidaemia?
- Beta-blockers
- Thiazides
- Corticosteroids
- Retinoids - monitor
- Oral contraceptives
- Anti HIV
276
What are lipoproteins?
transport lipids
277
What are the types of lipoproteins?
HDL, LDL, VLDL
278
What does HDL do?
good cholesterol- mops up cholesterol from around the body and takes it to the liver
279
What is xanthomata?
lipid deposits on eyelids
280
How does atherosclerosis form?
- risk factors cause damage to endothelium
- LDL binds to receptor on endothelium in normal way
- damage to endothelium causes monocyte and macrophages to migrate to the sub endothelial level and release ROS.
- This oxidises LDL which damages the LDL receptor
- there is poor delivery of cholesterol so it starts to accumulate below the endothelium
- cholesterol rich plaque with connective tissue forms
281
What are the non-pharmacological managements for high cholesterol?
Modify risk factors:
- Stop smoking
- Treat HT/DM
- Exercise
- Drug-induced?
Low cholesterol diet
- but only 25-30% of cholesterol comes from diet (rest synthesised by liver)
282
How do statins work?
- HMG-CoA Reductase Inhibitors
- HMG-CoA reductase is the 1st committed step in cholesterol synthesis
- Reduce plasma cholesterol
- The reduction in hepatic cholesterol synthesis leads to an upregulation of hepatic LDL receptors, promoting LDL uptake
283
What is a genetic cause of hypercholesterolaemia?
homozygous familial hypercholesterolaemia,
284
How is treatment for homozygous familial hypercholesterolaemia different?
Less effective in homozygous familial hypercholesterolaemia, can not make LDL receptor.
Atorvastatin may be effective.
Statins effective in heterozygous disease
285
How do statins not prevent the production of necessary cholesterol at other sites?
Statins are hepatoselective
- the liver is the main site of cholesterol synthesis, extrahepatic sites synthesise essential cholesterol
- 1st pass metabolism: 5% reaches systemic circulation
286
what is the common prescription for high risk cardiovascular patient?
stain, aspirin, Beta-bloker and ACEi
287
What is the NICE guideline for prescribing statins?
>10% risk CVD in next disease
288
When should statins be taken and why?
Taken at night
| offsets a nocturnal increase in cholesterol synthesis
289
Which statin does not need to be taken at night?
atorvastatin
290
when do you give high intensity statin vs low intensity?
high intensity after a cardiac arrest
291
what is a caution for statin?
liver dysfunction --> monitor all patients for liver dysfunction
292
what is another risk for statins?
-rhabdomyolysis (break down of muscle which can cause renal failure due to toxin release)
293
What increases risk of rhabdomyolysis with statins?
fibres
294
What does simvastatin interact with?
- Contraindicated with macorlides
- Interaction with amlodipine, verapamil, diltiazem
For amlodipine plus statin:
Pravastatin does not interact
Use 20mg simvastatin as maximum dose
295
How do fibrates work?
- Activate: PPAR-a, alters lipoprotein metabolism
- promote breakdown in VLDL (with small reductions in LDL and increase in HDL).
- Also reduce trigycerides – used with statins when TGs (+ cholesterol) raised
- Decrease glucose, use in DM
296
What are the adverse effects of fibres?
rhabdomyolysis.
297
When can cholesterol absorption inhibitors be used?
in conjunction with a statin
298
Why are fibres not commonly used?
reduce IHD but not mortality
299
How does sitostanol work?
- A functional food
- Present in Benecol margarine
- Prevents absorption of cholesterol
- Reduces LDL cholesterol by 10-15%
- Helpful add on to dietary restrictions and statin therapy
300
what is the stepwise management of dyslipidaemia?
- if hypercholesterolaemia give statin and lifestyle changes
- if hypertriglyceridaemia alone lifestyle alone and then if that doesn't work then add a statin
- if this doesn't work add ezetimibe (cholesterol absorption inhibitor)
301
How do SSRIs work?
Selectively inhibit the neuronal reuptake of 5-HT, thus enhancing synaptic concentrations of 5-HT and downregulating presynaptic 5-HT receptors.
302
How do tricyclic antidepressants work?
Inhibit the neuronal uptake of noradrenaline and 5-HT, leading to augmented concentrations in the synaptic cleft.
303
What are the side effects of TCAs?
- dry mouth
- blurred vision
- constipation
- urinary retention
- sedation
304
In what patients are TCAs contraindicated and why?
-TCAs may cause cardiac effects such as QT interval prolongation and the potentiation of catecholamines also predisposes to heart block and arrhythmias.
dangerous in overdose.
-They are not suitable for patients with ischaemic heart disease, aged over 70 years or those patients who are thought to be at high risk of attempting suicide.
305
When are noradrenaline reuptake inhibitors used?
Useful for patients who cannot take TCAs but are resistant to the effects of SSRIs.
306
How do serotonin-noradrenaline reuptake inhibitors work and how are they better than TCAs?
Inhibits serotonin and noradrenaline reuptake but fails to bind to additional receptors - fewer side-effects ( lack of sedative and antimuscarinic side-effects but does cause gastrointestinal side-effects).
307
What Asan adverse effect of SNRIs?
hypertension
308
How do noradrenergic and specific serotonergic antidepressants work?
Exhibits alpha2-adrenocepter antagonist activity, inhibiting negative feedback by these presynaptic receptors and thus producing an increase in noradrenaline and 5-HT transmission.
309
How do serotonin receptor modulators work?
Inhibition of serotonin reuptake and the selective inhibition of postsynaptic serotonin receptors.
310
How do mono-amine oxidase inhibitors work?
MAOIs inhibit the monoamine oxidases, which increases the concentration of these neurotransmitters.MAOIs also prevent the breakdown of the indirectly acting sympathomimetic amine, tyramine (from diet) - causes the release of catecholamines and leads to a hypertension.
311
What are the step managements for Depression?
Step 1: if mild give CBT otherwise SSRI
| Step 2: alternative SSRI or reboxetine (NRI) or mitazapine (NaSSA) or TCA
312
What is firstling bipolar treatment?
lithium
313
When is lithium contraindicated?
renal impairment
314
What other drugs are used for bipolar?
- anticonvulsants
| - neuroleptics (antipsychotics)
315
What can be used for sympathetic relief of annuity ?
- propanolol (beta blocker)
| - benzodiazepines
316
How does buspirone work?
Buspirone activates 5-HT1A receptors, binds to dopamine receptors.
317
what does buspirone treat?
Anxiety
318
what are the side effects of buspirone?
- dizziness
- nausea
- headache
319
What is the treatment for generalised seizures?
- 1st choice valproate or carbamazepine or lamotrigine (in females of childbearing age)
- 2nd levetiracetam
320
What is the treatment for absence seizures ?
1st choice: ethosuximde
| 2nd choice: valproate/lamotrigine
321
How does valproate work?
- Potentiates GABA
| - Causes Na-channel blockade
322
What are the side effects of valproate?
- sedation
- weight gain
- tremor
- liver damage (monitor)
323
How does carbamazepine work?
use-dependent blockade of NA-channels
324
What are the side effects of carbamazepine?
- rashes
- dizziness
- double vision
325
What is the issue with phenytoin?
Many side effects
- increased gum growth
- nystagmus a toxic effect
Associate with causing birth defects
Zero order kinetics
-metabolism saturates and so get disproportionate increases in plasma concentration on increasing dose
-Rates of metabolism varies between patients
– requires plasma conc monitoring
326
How does lamotrigine work?
-use-dependent blockade of Na-channels, reduces release of glutamate
327
What is the risk of lamotrigine?
bone marrow toxicity
328
How can you detect bone marrow toxicity?
rash/flu like illness
329
What monitoring is required for anti-epileptic drugs?
Haemtological effects
- Many may cause leucopenia (fever, sore throat, rash, mouth ulcers )
- FBC should be monitored
- If severe leucopenia, withdraw under cover of another drug
- Lamotrigine – associated with aplastic anaemia
- Valproate – may cause thrombocytopenia
Liver
- Carbamazepine & valproate may affect hepatic function ~ altered liver function tests (LFTs)
- LFT (essential with valproate) & INR monitoring
Skin
- May cause rashes
- More serious may cause Stevens-Johnson syndrome; toxic epidermal necrolysis (carbamazepine, lamotrigine, phenytoin, valproate)
330
What is pain?
An unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage
331
What are the causes of acute pain?
- injury
| - post-operative flare
332
What are the types of chronic pain?
- nociceptive
- neuropathic
- visceral
- mixed
333
What are the examples of nociceptive pain?
- osteoarthritis
| - rheumatoid arthritis
334
What are the different types of neuropathic pain?
central and peripheral
335
What causes central neuropathic pain?
- post-stroke
- multiple sclerosis
- spinal cord injury
- migraine
- HIV
336
what causes peripheral neuropathic pain?
- post-herpetic neuralgia
| - diabetic neuropathy
337
what causes visceral pain?
- internal organ
- pancreatitis
- inflammatory bowel syndrome
338
What causes mixed pain?
- lower back
- cancer
- fibromyalgia
339
Describe the WHO pain ladder
Step 1: simple analgesics e.g. Aspirin and paracetamol
Step 2: opioids suitable for use in mild to moderate pain +simple analgesics
step 3: opioids suitable for sever pain +simple analgesics
340
What are the actions of paracetamol?
Analgesic and antipyretic actions
341
What is the treatment for paracetamol overdose?
acetylcysteine
342
How do NSAIDs work?
Inhibit cyclo-oxygenase (COX) responsible for arachidonate metabolism to cyclic endoperoxides, preventing formation of prostaglandins and thromboxanes
343
What are the actions of NSAIDs?
Analgesic, antipyretic and anti-inflammatory properties
344
What are the adverse effects of NSAIDs?
GI tract:
- GIT erosion and ulceration
- Ibuprofen (< 1200 mg daily) has best GI profile
Renal
- Reduce renal blood flow
- Acute renal failure
- Sodium, potassium and water retention
‘A’ (airway) Respiratory-Bronchospasm
‘B’ (blood) Haematological
-Reduce platelet aggregation
Aspirin - Irreversible
NSAIDs - Reversible
345
Why is dicofenac not suggested to be prescribed?
increases cardiac risk
346
What are the weak opioids?
- Codeine
- Dihydrocodeine
- Tramadol (po)
347
What are the strong
| opioids?
- Morphine
- Diamorphine
- Oxycodone
- Buprenorphine
- Fentanyl
348
Why do some people not respond to codeine?
Codeine metabolised to morphine via Cyp P450 2D6
- 10 % Caucasian population unable to convert
- 90 % Chinese population unable to convert
349
What are the opioid adverse effects?
- Nausea & vomiting
- Constipation
- Sedation
- Respiratory depression (overdose)
- Hypotension
- Urinary retention
Need to anticipate adverse effects and provide treatment
350
What are the steps for prescribing morphine?
Pain assessment, including current analgesia
Determine opioid requirement
- Use short acting preparation, regularly plus prn doses
- E.g. 5 mg 4 – 6 hr, 5 mg prn
- onvert total daily dose to Modified release formulation
- Taken every 12 or 24 hours
351
What is breakthrough pain?
Transient exacerbation or recurrence of pain in patient who has mainly stable or adequately relieved background pain
- End of dose failure
- Incident pain
- Spontaneous, unpredictable pain
352
How do you treat breakthrough pain?
- 10% total daily regular dose prescribed prn
| - Marked variability between patients (5 – 20%)
353
How do you convert to an alternative opioid?
- palliative care section of BNF
- Determine 24 hour requirement
- Use conversion factor for alternative opiate to determine new 24 hour requirement
- Convert to appropriate dosage regimen
354
What drugs are used for patient controlled analgesia?
- morphine
| - Tramadol, oxycodone or fentanyl if morphine allergy
355
What are the advantages of patient controlled analgesia?
- Rapid analgesia once pain at steady state
- Ready prepared
- Patient satisfaction
- No dose delay
- Patient acceptability
- No peaks or troughs
356
What are the disadvantages of patient controlled analgesia?
- Expensive
- Requires IV access
- Training
- Monitoring
357
What is given in an epidural usually?
Commonly fentanyl with (levo)bupivicaine (local anaesthetic + opioid)
358
What are the adverse effects?
- hypotension
- wrong route
- infection
359
How do syringe drivers work?
continuous subcutaneous infusion
360
what are the indications for syringe drivers?
- Unable to take medicines by mouth (e.g. N&V, dysphagia)
- Bowel obstruction
- Patient does not wish to take regular medication by mouth
361
What is used for syringe drivers?
Diamorphine is opioid of choice due to excellent aqueous solubility
Possible to mix with other drugs:
- Haloperidol, cyclizine (N&V)
- Levomepromazine, midazolam (restlessness & confusion)
- Midazolam (seizures)
- Hyoscine N-butylbromide (excessive respiratory secretions)
362
How do you monitor opioid therapy?
- Pulse
- BP
- Respiration rate
- Oxygen saturation
- Pain intensity
- Sedation score
- Opioid usage
- Opioid side effects
363
How does tramadol work?
```
mum agonist (30 % of analgesic effect)
Inhibits noradrenaline uptake and 5-HT release
```
364
How do you manage an opioid overdose?
naloxone --> Opioid antagonist
| Higher affinity for opioid receptor than agonist
365
What are the symptoms of neuropathic pain
- Burning
- Electric shock
- Pins and needles
- Scalding
- Shooting
- Stabbing
366
What are the signs of neuropathic pain?
- hyperalgesia (more sensitive to pain)
| - allodynia (non-pain stimuli cause pain)
367
What are the pharmacological treatments for neuropathic pain?
- Tricyclic antidepressants
- Anticonvulsants (Carbamazepine, Gabapentin, Pregabalin)
- Opioids
- Local anaesthetics
- Capsaicin
368
How do anticonvulsants work against pain?
- Prevent voltage dependent Ca2+ channel activation in dorsal horn neurones
- Do not affect voltage gated Na+ channels
