Conditions Flashcards
(227 cards)
1
Q
NSAIDS are type of drug that can have a side effect of ototoxism. Name 4 other drugs that have a side effect of ototoxism, thus leading to sensorineural hearing loss, hyperacusis and tinnitus
A
Furosemide
Cisplatin
Carboplatin
Gentamicin
2
Q
Describe the effect of the baroreceptor reflex in heart failure and what ‘loads’ will eventually increase, via which path?
Briefly describe each path
A
Baroreceptor reflex -> stimulation of a adrenoreceptors in the heart -> vasoconstriction of VSM -> increase in afterload (high ventricular force of contraction to eject the same amount of volume out of the heart)
Baroreceptor reflex -> stimulation of b adrenoreceptors in the heart + kidney -> increased ATII (via RAAS) -> increased aldosterone -> high Na+ and H20 reabsorption -> increased preload
3
Q
How does activation of B1 adrenoceptors in the heart increase blood pressure?
A
Increase in cardiac output (via the increase in ATII -> increasing preload via the increase in aldosterone leading to Na+ and H20 retention)
4
Q
How does activation of a1 adrenoceptors in the heart lead to an increase in blood pressure?
A
Via the increase in venous return and the increase in TPR: both as a result of the increase in vascular smooth muscle tone
5
Q
What clinical blood pressure value is classed as a stage 1 hypertensive for someone 80+?
A
150/90 mmHg
6
Q
For hypertension treatment, if potassium levels are < or =4.5mmol/l, what drug do you add to their current drug list?
A
Low dose spironolactone
7
Q
For step 1 treatment of hypertension, who do you give an ACEi/ARB to and who do you give a CCB to and why?
A
ACEi/ARB: Type II diabetic or <55 and isn’t Black African or Afro-Caribbean family origin (as their renin levels are normal/higher so want to target their RAAS)
CCB: >55 or Black African or Afro-Caribbean family origin (as their renin levels are lower so RAAS system does not need to be targeted)
8
Q
When a patient has been started on Ramipril (1. name another drug in its family) what test needs to be checked in a few weeks?
If the levels have not been returned to normal, what does this indicate.
A
Kidney function tests. GFR originally low when started on Lisinopril as low ATII levels leads to vasodilation of the EA but as weeks pass, GFR should return to normal… if this doesn’t occur then patient has RENAL ARTERY STENOSIS
9
Q
Can NSAIDS be given to someone on Lisinopril?
Why?
A
No. As NSAIDS will inhibit prostaglandins leading to vasoconstriction and prostaglandins are needed for the AA to vasodilate
10
Q
How does Ramipril cause angioedema, a dry cough and vasodilation?
A
High bradykinin levels and due to bradykinin being a substrate to ACE (on the apical surface of lung epithelial membrane)
11
Q
Do ARBs/ACEi’s effect potassium levels?
A
Yes, they lead to hyperkalaemia
12
Q
A part from ACE, what other way can ATII be made?
A
Via chymases
13
Q
Name 2 ARBs
A
Losartan
Candesartan
14
Q
Do Angiotensin receptor blockers cause an increase in bradykinin levels?
And why?
A
Do not cause an increase to bradykinin levels as ATII is still produced so, like in the typical RAAS system, vasodilators are inhibited
15
Q
What receptors do ARBs target?
Where are these receptors predominantly found?
A
Angiotensin 1 receptors found in the heart
16
Q
What class of calcium channel blockers are used for hypertension?
Name 3 drugs in this class
A
Dihydropyridine
- Amlodipine
- Nifedipine
- Nimodipine
17
Q
What are Dihyrdropyridines selective to and describe their mechanism of action
A
Dihydropyridines are selective to L type calcium channels found at peripheral VSM and brain (vascular smooth muscle), inhibiting the influx of Ca2+, via LTCC, into cells thus SR isn’t stimulated to release its Ca2+ store and cause contraction so VSM dilate
18
Q
One side effects of Nimodipine is headaches.
Why is this and what is Nimodpine specifically used for?
A
Nimodipine is used for SAH.
Due to Dihydropyridines being selective to LTCC found in the brain, you get vasodilation leading to a headache
19
Q
Name 2 other side effects of Dihydropyridines, as a result of vasodilation
A
Ankle/Peripheral oedema Flushing Tachycardia Nausea Dizziness
20
Q
You should not give Dihydropyridines if you have issues with which organ?
Why?
A
Heart because you get negative inotropy and this triggers a compensatory tachycardia thus leading to PALPITATIONS
21
Q
Name 2 non-dihydropyridine drugs that are calcium channel blockers
What are they used to treat?
A
Supraventricular tachycardias
Verapamil
Diltiazem
22
Q
Name 2 thiazide drugs used in hypertension
What is their mechanism of action?
What effect does it have on glucose and potassium and what does it thus lead to?
A
Bendroflumethiazide and Indapamide
Inhibit Na/Cl cotransporter on DCT so ↑Na+ and H20 excretion
Get HYPOkalaemia
Become HYPERglycaemic thus leading to hyperuricaemia
23
Q
Name 3 B adrenoceptor BLOCKERS, used in hypertension and discuss why an asthmatic patient should not be prescribed this drug?
A
Labetalol (used in ER + PRE-ECLAMPSIA)
Bisoprolol
Metoprolol
Drugs act on B1 (heart and kidney) and B2 (lungs) (as the drug is non-selective) thus get bronchospams (drug inhibits the normal vasodilatory effect of the stimulation of B2 receptors)
24
Q
What condition is Tamsulosin used to treat?
What class of drugs does Tamsulosin belong to?
A
Benign prostatic hyperplasia BPH
a adrenoceptor BLOCKER
25
Explain the INITIAL treatment for chronic heart failure (preserved and reduced ejection fraction)
Give Furosemide to reduce FLUID RETENTION and CONGESTIVE SYMPTOMS
26
Name 3 congestive symptoms present in heart failure
SOB
Ankle oedema
Fatigue
27
Discuss the steps needed to treat reduced ejection fraction heart failure (after you have treated them with a loop diuretic)
1. ACEi (Ramipril, Lisinopril) or Beta blocker (Bisoprolol). If INTOLERANT to ACEi - give ARBs (Losartan, Candesartan)
2. MRA (mineralcorticoid receptor antagonists) (Spironolactone) if symptoms persist
28
What diuretics act at the PCT?
SGLT2 inhibitors
Osmotic diuretics
Carbonic anhydrase inhibitors
29
What diuretics act on the TAL?
Loop diuretics
30
What diuretics act on the DCT?
Thiazides and thiazide-like diuretics
31
What diuretics act on the CD?
Aldosterone receptor antagonists
K+ sparing diuretics
ADH antagonists
32
What diuretic is used to treat Nephrotic Syndrome?
Is a high or low dose given?
Name 2 other diuretics that could also be given in conjunction with the diuretic above.
High dose Furosemide
with or without:
- Thiazides
- Amiloride (K+ sparing diuretic)
33
What diuretic should you give to treat Chronic Kidney Disease?
What diuretic should you absolutely AVOID? Why?
Give Loop diuretic
Avoid Amiloride as it is potassium sparing and due to the low GFR in CKD, the person already has high fluid and electrolyte retention (too ↑K+ leads to arrhythmias)
34
What drug group does Acetazolamide belong to and what is it used to treat?
Carbonic anhydrase inhibitors
Glucoma
35
Describe the MOA of carbonic anhydrase inhibitor
(Acetazolamide binds to carbonic anhydrase on the PCT apical membrane) inhibits CA so less H20 + CO2 is converted to HCO3- + H+.
Thus the NHX (on the apical membrane cannot work) as there is less H+ to be pumped out of the epithelial cell so Na+ conc. in the lumen increases (it can’t be pumped in).
CAi also inhibits the rejoining of H+ + HCO3- in the lumen so NaHCO3 is now excreted.
36
2 side effects of Acetazolamide
Hypokalaemia
Metabolic acidosis (due to HC03- being excreted via NaHCO3)
37
Why do you get hypokalaemia as a side effect for some diuretics?
ENaC is UP-REGULATED in the DCT and CD due to the high [Na+] in the DCT and CD. Although Na+ is excreted, some Na+ (typically in the DCT and CD) use ENaC to re-enter the epithelia and then 3Na-2K-ATPase on b.membrane so Na+ pumped into blood and K+ pumped into ep. cell. Then K+ via ROMK pumped into lumen and excreted
38
Name 2 SGLT2 inhibitors
CanaGLIFLOZIN
| DapaGLIFLOZIN
39
Assign each effect to each drug:
Loop diuretic/Thiazide
Ca2+ loss/Ca2+ reabsorption
Loop diuretic -> Ca2+ loss
Thiazide -> Ca2+ reabsorbed
40
Name 2 drugs that lead to hyperkalaemia and both act on the principal cells at the CD
Discuss each of their functions and how they lead to hyperkalaemia
Amiloride inhibits ENaC on the apical surface of the Principal cells...
Spironolactone is a mineralcorticoid receptor antagonist thus Aldosterone cannot bind so ENaC and 3Na-2K-ATPase expression in the Principal cell is inhibited...
...thus 3Na-2K-ATPase stops working on the basolateral surface (as there are low principal Na+ levels) so less K+ is pumped into principal cell and out of principal cell via ROMK
41
What diuretic is used to treat Adult Polycystic Kidney Disease
Describe its MOA
Tolvaptan - an ADH antagonist and aquaretic
Tolvaptan binds to ADH receptor on CD, thus inhibiting the up-regulation of Aquaporins on the apical surface so more water is excreted and sodium levels increase (this is needed as you are hyponatraemic in APCKD)
42
What is refractory oedema and how is it treated?
Peripheral oedema persisting even with diuretic and sodium restriction treatment (probably due to an underlying pulmonary or cardiac condition)
1. Check salt intake (24 hour sodium excretion if needed)
2. i.v. Furosemide (by pass 1st pass metabolism)
43
What is Bartter’s Syndrome?
decreased function
(Think of it like am extreme Furosemide)
Autosomal recessive defect in TAL so get:
- Hypokalaemia
- Hyponatraemia
- Low Cl
- Low Mg
- Normal/low BP
- Hypocalcaemia
44
What is Gitelman’s Syndrome?
decreased function
(Think of it like an extreme thiazide)
Defect with ?DCT leading to:
- hypercalcaemia -> hypertension
- hyponatraemia
- low Cl
- hypokalaemia
45
What is Liddle’s Syndrome?
increased function
(Think of it like an extreme Amiloride)
Autosomal dominant disease leading to defect in CD:
- Hyponatraemia
- Hyperkalaemia -> hypertension
46
Give an indication of Mannitol
RICP
47
What diuretic is used to treat ascites?
Spironolactone
48
Which diuretic has a side effect of impotence (erectile dysfunction)?
Spironolactone
49
List the ADRs categories and compare the first two categories, giving examples within the first two categories
Type 1: Augmented: common, dose related, reduce warfarin dose to reduce bleeding, predictable due to knowledge of its PK and PD, not life threatening
Type 2: Bizarre: uncommon, not dose related, stop penicillin treatment or get life threatening anaphylaxis, unpredictable
Chronic
Delayed
End of use
50
Discuss how pharmacogenomics played a part in adverse drug reactions in the treatment of HIV and Epilepsy
HIV: People with a SPLIT ANTIGEN lead to a hypersensitive reaction occurring with Abacavir (an ARV)
Epilepsy: predominantly Asian patients have a SPLIT ANTIGEN leading to Stevens-Johnson syndrome or more extreme toxic epidermal necrolysis when using Carbamazepine
51
What condition are you mostly trying to reduce when giving menopausal women HRT
Why?
Osteoporosis
Oestrogen favours osteoclasts>osteoblasts and oestrogen levels are higher in menopause
52
For HRT, sex steroid hormones containing oestrogen should not be given on its own due to the increased risk of endometrial and ovarian cancers so give 2 drug combinations that should be given to patients (opposed oestrogen technique)
Oestradiol + Medroxyprogesterone acetate
Oestradiol + Levonorgestrel
53
What is UNopposed oestrogen?
What is a risk factor of opposed oestrogen?
Oestrogen replacement therapy (ERT) (e.g. Oestradiol on its own)
BREAST cancer
54
Name 3 anti-oestrogen drugs used in HRT and STATE each of their functions
Clomifene- anovulation
Tamoxifen- treat breast cancer and anovulation
Raloxifene - postmenopausal women that have/increased risk of osteoporosis
55
What is the MOA of Clomifene
Clomifene binds to oestrogen receptor at endometrium, preventing oestrogen from binding so HPG axis increases 2^ follicle’s release of oestrogen so LH surge can then occur so ovulation can occur
56
What are the 2 MOA’s of the active metabolite of Tamoxifen?
1. AGONIST at ENDOMETRIUM
Same as Clomifene - quiz yourself
2. ANTAGONIST at BREAST
Oestrogen receptor antagonist at breast tissue so oestrogen cannot bind so cell cycle is inhibited so breast cells die
57
Ulipristal acetate is a selective progesterone receptor modulator.
State and describe its two functions
Emergency contraception:
Ulipristal acetate binds to progesterone receptors in the OVARY preventing progesterone from binding so progesterones local levels are high and bind onto oestrogen receptors thus inhibiting LH surge so no ovulation (and thus fertilisation)
Uterine fibroids:
Ulipristal acetate binds to progesterone receptors at the ENDOMETRIUM so local progesterone levels are high and bind to oestrogen receptors so oestrogen cannot bind and produce its proliferative effect on the functional layer of the endometrium
58
COCP and POP (low dose progestogen) are both metabolised by CYP 450 enzymes in the liver. (To later be excreted in urine as glucuronic acid - progestogen and sulphates and glucuronides - oestrogen)
Categorise and name specific drugs that induce the production of CYP 450 enzymes and thus reduce the efficacy of COCP and POP
Mild anti-depressant: St John’s Wort
Anti-epileptic: Carbamazepine and Phenytoin
Antibiotics: Rifampicin and Rifabutin
(these drugs thus contraindicate the contraception)
59
Before prescribing a statin for prevention of cardiovascular disease, what important test should be done?
At the 3 month point of treatment what test should be done here and what results should be expected?
Prior do a FULL LIPID PROFILE including:
- HDL levels
- Non-HDL levels
- TGs
At 3 months:
-non-HDL levels should have >40% reduction
60
Give two points of advice that should be given to patients using statins in order to prevent a cardiovascular event
Explain why
Don’t take grapefruit (CYP3A4 inhibition - statin will then have a GREATER effect as not metabolised)
q.h.s - take at night. So drug is acting with the circadian rhythm of LDL-R production/activity
61
What is the treatment of primary prevention of cardiovascular disease?
20mg Atorvastatin once daily
62
What is the treatment for the secondary prevention of cardiovascular disease?
If you ALSO have CKD, what amendment would be made?
80mg Atorvastatin once daily
If have CKD - 20mg Atorvastatin once daily
63
What combination statin therapy can be used in the secondary prevention of cardiovascular disease?
Include doses
40mg Atorvastatin + 10mg Ezetimibe
64
What drugs induce CYP3A4?
4
Macrolides
CCB - Diltiazem, Amlodipine
Amiodarone
65
Atorvastatin is a statin.
Name another statin.
Discuss their MOA.
Simvastatin inhibits the HMG-CoA reductase enzyme in the liver (rate limiting step of the Melvanoate pathway) so cholesterol is not produced.
Low intracellular LDL levels signals the production of LDL-R in the same cell, which are then put onto the surface of the cell.
So LDL’s from the circulation are brought into the cell (so a. plaque) reduces.
VLDL is prevented from being secreted out of the cell due to low intracellular cholesterol levels.
66
What antihyperlipidemic drug should not be prescribed with warfarin, and why?
Fenofibrate - exacerbates 🩸
67
What antihyperlipidemic drug reduces triacylglycerides?
Describe two major side effects
Fenofibrate
Myositis - muscle atrophy
Acute Cholecystitis - increased saturation of cholesterol in bile (RUQ pain + fever)
68
What antihyperlipidemic drugs should not be given/should be adjusted when given to a patient with
A) liver disease
B) kidney disease
A) Ezetimibe (CAI - Cholesterol absorption inhibitor) (metabolised in liver)
B) Simvastatin/Atorvastatin
69
What is the MOA of a cholesterol absorption inhibitor?
Ezetimibe is involved in the Enterohepatic circulation and is a NPC1L1 transporter inhibitor, so this transporter found on the brush border of SI cannot aid the reabsorption of cholesterol (50% reduction)
Also increases LDL-R expression so more LDL is stored in cells than is in blood.
70
Describe the MOA of Alirocumab (a monoclonal antibody)
Typically PCSK9 (an enzyme) binds to LDL-R on hepatocytes membranes and aid the internalisation and thus metabolism of these receptors (once they have an LDL bound to them).
PCSK9 inhibitors prevent this from happening so the LDL-R stay on the surface for longer
71
Name rapid acting insulin
Insulin aspart
72
Name long acting insulin
Insulin degludec
Insulin glargine
73
Name short acting insulin
Soluble insulin:
1. Humulin S
2. Actrapid
74
Name intermediate acting insluin
Isophane insulin:
| NPH
75
What signs are present in diabetic ketoacidosis DKA crisis?
the main triad + possible accompanying conditions(4)
Triad:
1. Blood glucose >11mmol/l
2. pH <7.3
3. Ketosis
Plus:
- Trauma
- Poor insulin adherence (absolute insulin deficiency leads to ketone production)
- Infection
- ADR
76
DKA Crisis Treatment
ECG throughout as [K+] fluctuates
1st. IV fluids
2nd. IV 100u/mL insulin
3rd. Glucose - if become hypoglycaemic
77
All of the hypoglycaemic agents are administered p.o. (orally), except from 1 - name the drug category and its route of administration
GLP-1 RA Glucagon-like peptide 1 receptor agonist
(More insulin released)
s.c. Subcutaneous
78
Name the 2 hypoglycaemic drugs types that CAUSE hypoglycaemia and weight gain
Sulfonylureas
Thiazolidinediones
79
What is the MOA of Biguanides?
(Metformin) inhibits gluconeogenesis and glycogenolysis in liver cells, thus promoting the use of glucose present in skeletal muscle
80
Describe the elimination of Metformin
It is not metabolised (in the liver)
It is excreted via urine (by the kidney)
81
If GFR is <30 why should Metformin treatment be suspended?
As Metformin will now not be excreted so it’ll be at high concentrations in the blood leading to LACTIC ACIDOSIS
82
Name a specific Sulfonylurea and describe its MOA
Gliclazide inhibits the ATP sensitive K+ channel of pancreatic B islet cells so K+ cannot leave the cell leading to depolarisation of cell membrane, thus stimulating an influx of Ca2+. Ca2+ then stimulates the fusion of Insulin vesicles with the cell membrane and insulin leaves the cell.
83
Name 2 Thiazolidinediones
What are their MOA?
RosiGLITAZONE + PioGLITAZONE increase the expression of PPAR-y gene. More PPAR-y means there is increased sensitisation of insulin so more glucose is converted to TRIGLYCERIDE.
84
What drug is given when you have a DKA Risk?
SGLT2 inhibtor (Dapagliflozin or Napagliflozin)
85
Name 2 Dipeptidyl peptidase-4 inhibitors DPP-4I
What are their MOA?
SitaGLIPTIN + SaxaGLIPTIN
Inhibition of Dipeptidyl peptidase-4 leads to higher incretin levels (GLP-1 and GIP) so more insulin is produced in pancreatic B islet cells.
86
Name 2 glucagon-like peptide 1 receptor agonists
ExenaTIDE
LiragluTIDE
87
Which hypoglycaemic drug can be given if there is renal failure?
Gliclazide as it is metabolised hepatically
88
What effects do Non-Dihydropyridines have on the heart?
4
Explain.
Increase:
- PR interval (atrial and ventricular depolarisation prolonged)
- ERP (effective refractory period)
- Prolonged AP
- Prolonged AVN repolarisation
89
What are the 3 effects that Metoprolol have on the heart
A)PR interval
B)AVN repolarisation
C)Phase 4 depolarisation
- PR interval increased
- Prolonged repolarisation of AVN
- Decreased slope of Phase 4 depolarisation
90
What is Class I of the Vaughan Williams classification and name 2 drugs in this class and what heart issues they are used for.
What effect do they have on the heart?
Explain.
Sodium channel blockers:
IB - Lidocaine used for ventricular tachycardia:
↓AP due to open Na+ channels on postsynaptic membrane being blocked thus Na+ influx into the postsynaptic neurone is inhibited
↑QRS - ventricular depolarisation/contraction
IC - Flecainide used for SV Arrhythmias (so brady or tachycardia) and Wolff-Parkinson-White Syndrome:
↑AP duration + ↑PR: acting in Phase 0 of ventricular AP so atrial depolarisation/contraction lasts longer
↑QRS
91
Name 2 drugs present in Class V of Vaughan Williams classification, that begin with ‘A’
Functions?
Use?
Adenosine binds to Gi protein-coupled Adenosine A1 receptors at SAN. So less adenyl cyclase made -> less ATP converted to cAMP -> less cAMP means less K+ pumped out via ligand gate and less Ca2+ pumped in via VGCC. HIGH K+ leads to hyperpolarisation so you do not get membrane depolarisation so AP is delayed in SAN. Used in SVT.
Atropine - used to treat vagal bradycardia. Atropine is a selective muscarinic antagonist blocking vagal activity so sympathetic activity in heart is greater so AVN CONDUCTION is FASTER and HR increases
92
When is Digoxin used (2) ?
MOA?
Also in Class V
Heart failure w/ sinus rhythm
AF
Digoxin - 3Na-2K-ATPase inhibitor so Phase 4 prolonged. Greater [Na+]i so ↑AP duration. + inotrope (a cardiac glycoside). Increased contractility and CO.
93
When is Ivabradine used?
Also in class V
Function?
Angina w/ sinus rhythm, severe heart failure
Ivabradine - inhibits If current in SAN so ↑AP duration due to reduced Na+ influx - takes longer for depolarisation to occur: slow HR
94
Name 2 anti-arrhytmic drugs that can be used SVT?
Adenosine
Amiodarone
95
Name 8 causes of atrial fibrillation
ATRIAL BP
```
Alcoholic liver disease
Thyroid disease
Rheumatic heart disease (damage to the valves after rheumatic fever)
Ischaemic heart disease
Atrial myxoma (cancer in LA)
Lung disease
```
BP
Pheochromocytoma (cancer of chromaffin cells in adrenal gland)
96
What drug classes are used to treat arterial thrombi (low RBC)?
What drug class is used to treat venous thrombi (high RBC)?
AT:
Antiplatelets
Fibrinolytics (dissolve existing clots)
VT:
Anticoagulants
97
Low dose Aspirin MOA + use
a cyclo-oxygenase inhibitor
Dose + route
Aspirin IRREVERSIBLY inhibits COX-1 enzyme so Arachnoid acid cannot be converted to Prostaglandin H2 so PH2 cannot be converted to Thromboxane A2 - so less platelet aggregation
Secondary prevention of cardiovascular disease - 75mg swallow daily
98
High dose aspirin use
Doses
Used for its pain relief
(Ends up promoting platelet aggregation due to the inhibition of endothelial prostacyclin)
Used in:
300mg chewable daily - NSTEMI, STEMI and unstable angina
300mg orally daily - suspected TIA until know diagnosis
99
What drug can be give if Aspirin is contraindicated?
What class does this drug belong to?
Name 2 other drugs in this class
Clopidogrel can be given when Aspirin is contraindicated.
Prasugrel and Ticagrelor also belong to the ADP Receptor Antagonist class
100
In the ADP Receptor Antagonist class, which 2 drugs are irreversible and what are their MOA?
Clopidegrel and Prasudegrel both prevent ADP (Adenosine diphosphate) from binding to PY12-R so GbIIb/IIIa cannot be activated so get no platelet aggregation
101
Due to Clopidogrel and Ticagrelor both causing prolonged bleeding, how many days before surgery should each drug be stopped?
Clopidogrel - 7 days
| Ticagrelor - 5 days
102
Can ADP Receptor Antagonists be give to a patient with hepatic failure?
Only Ticagrelor can be given as the other 2 drugs are pro drugs
103
Name 2 drugs that contraindicate Clopidogrel
Erythromycin
PPIs
-Both inhibit CYP 450s so Clopidogrel pro drug will not be released.
104
Name an anti-platelet drug that targets the common final pathway?
Describe its MOA
Abciximab (a glycoprotein IIb/IIIa receptor inhibitor) prevents fibrinogen and von-Willebrand factor from binding to GPIIb/IIIa-R so get reduced platelet aggregation
105
Dipyridamole belongs to which class of drugs?
What us its MOA?
Dipyridamole is a phophodiesterase inhibitor so PDE in platelet cells can no longer convert cAMP to AMP so higher cAMP levels leads to lower Ca2+ levels and thus inhibition of GPIIb/IIIa-R so you get less platelet aggregation.
106
Name a anti-fibrinolytic drug, its use and its MOA
Tranexamic acid binds to plasminogen, inhibiting it from breaking down (so plasmin not formed so fibrin clot can’t be broken down)
Used in post-partum haemorrhage and menorrhagia.
107
If you’ve had an acute ischaemic stroke (<4.5 hours), which thrombolytic drug should be given?
Alteplase
108
Name 2 fibrolytic drugs
Alteplase
Streptokinase
109
What are the 3 main functions of NSAIDS?
Anti-inflammatory
Analgesic
Anti-pyretic
110
Describe the anti-pyretic mechanism of NSAIDS
Inhibits hypothalamic COX-2 where cytokine stimulated
PGE2 (Prostaglandin E2) is produced. Lower levels of hypothalamic PGE2 means the thermoregulatory system in the hypothalamus is not stimulated so temperature drops.
111
List NSAIDS from COX-1 selectivity to COX-2 selectivity
6
AIN-DCE
```
Aspirin
Ibuprofen
Naproxen
Diclofenac
Celecoxib
Etoricoxib
```
112
What effect do NSAIDS have on the
A) Glomerulus
B) CD
A) low prostaglandin levels means AA vasoconstricts so less renin is stimulated to leave the JGA lining the AA so less ATII is produced so EA vasodilates - so GFR drops
B) reduced Na+ reabsorption in CD so get natriuresis so and BP drops
113
Aspirin and Etoricoxib.
Which one has more GI side effects?
Why?
List some GI side effects.
Dyspepsia, peptic ulcers, bleeding, perforation.
Aspirin has more GI side effects because it is COX-1 selective (whereas Etoricoxib is COX-2 selective) and this means that less PGE2 (Prostaglandin E2) will be produced, as a result of the COX-1 inhibition.
So there will be reduced gastric mucosal perfusion, so acid cannot be removed, less mucus will be produced from the fovea cells so there will be less of a protective layer.
114
To treat RA, LT NSAIDS are prescribed.
Which selectivity is best to prescribe and why?
COX-2. Less GI side effects, less Renal side effects, less analgesic side effects. COX-2 enzyme is heavily found in bones, where there is endothelial damage so swelling will reduce in joints.
115
NSAIDS and Methotrexate are both used to treat RA.
They are both highly protein bound.
What does this mean?
NSAIDS will displace Methotrexate so Methotrexate plasma levels will be higher - leading to HEPATOTOXICITY and LEUKOPENIA RA as Methotrexate is an immunosuppressant.
Will need to give a lower Methotrexate dose
116
A part from activated charcoal, what drug can be given to treat a paracetamol overdose?
N-acetylcysteine
117
Morphine is an opioid and a strong agonist.
What GPRC type are they most bound to?
Where are these receptors found?
What effects would this cause?
Name 3
Binds to Mu receptors, predominantly found in the GI and in the brain.
Leads to:
- reduced GI motility so get constipation
- euphoria
- itching due to the release of histamines
- respiratory depression due to medulla unresponsiveness to CO2
- analgesia due to the release of enkephalins
118
If a strong opioid agonist is needed but patient has renal failure, what drug should be given?
Fentanyl (less renally excreted than Morphine)
119
Give 3 reasons why you would prescribe Fentanyl over Morphine?
1. Less sedation
2. Less constipation
3. Less itching (less histamine release)
120
What medicine for constipation should be given to patients on opioids?
What is its functions?
Docusate sodium:
Stimulant laxative - Increase peristaltic GI motility
Stool softener - more fluid can enter the stool
121
Codeine is a moderate agonist, a weak opioid and a pro-drug.
What Phase I enzyme is it metabolised by and what metabolite is made?
CYP 2D6 -> Morphine
122
Codeine is a good analgesic but it has another main function.
What is it?
Cough depressant.
123
What is the half life of Buprenorphine?
37 hours
124
Give 3 routes of absorption for Buprenorphine
Transdermal
Buccal
Sublingual
TBS
125
What is the elimination of Buprenorphine?
Metabolised by CYP3A4 then glucoronidation by Phase II enzymes
Excreted biliary>kidney
126
Describe Naloxone’s affinity to Mu receptors compared to Morphine and Buprenorphine.
Naloxone is an antagonist.
Naloxone displaces Morphine but not Buprenorphine so affinity scale:
Buprenorphine > Naloxone > Morphine
127
Describe the excitement phase seen in Stage 2 of Guedel’s sign
4
Guedel’s signs are seen as a result of the effect of general anaesthesia on the CNS
Erratic breathing
Delirium
Increased muscle tone
Moderate eye movement
(but unconscious)
128
Volatile drugs are a general anaesthetic.
What describes their potency?
What is potency?
MAC Minimum Alveolar Concentration
Minimum concentration of a drug for it to produce its biological effect
129
What is often added to volatile gases?
Why?
Nitrous oxide.
Reduce dosing.
130
What 3 volatiles do not potentiate (increase the power of) the inhibitory GABAa mediated Cl- conductance channels?
Where do they bind instead? - What is their MOA here?
Xe, N2O (nitrous oxide), ketamine
Excitatory NMDA glutamate receptors - they inhibit the influx of Ca2+ (and Na+)
131
Name 3 local anaesthetics
LidoCIANE
RopivaCAINE
BupivaCAINE
132
After failure of low dose inhaled corticosteroid use, before going up a ladder in treatment, what are 3 things you should revise before prescribing a new treatment?
What is the next level of treatment advised in
A) BTS
B)NICE
1. Adherence
2. Inhaler technique
3. Removal of triggering factors
A) BTS - add on a LABA (££)
B) NICE - add on a LTRA (leukotriene receptor antagonist) (£]
133
Name 3 inhaled corticosteroids ICS
Describe their MOA
FluticASONE
BeclometASONE
Budesonide
Lipophilic so pass through plasma membrane. Glucocorticoids GC bind onto GC Receptor Complex in cytoplasm. This whole complex binds onto the NF-kB molecule in the cytoplasm. Inhibiting NF-kB from entering the nucleus and triggering the formation of mRNA. mRNA inhibited for the transcription of inflammatory cytokines.
134
Name 2 short acting B2 agonists
| Name 2 LABA
(Decrease bronchoconstriction + increase cilia movement)
SABA:
- Salbutamol
- Terbutaline
LABA:
- Formoterol
- Salmeterol
135
Name a LTRA Leukotriene receptor antagonist.
MOA?
Montelukast binds to CysLT-1 Receptor (a GPCR) - preventing LTC4 (Leukotriene C4) from binding to it and causing OEDEMA
136
Theophylline belongs to which drug group?
MOA?
Methylxanthine
Adenosine receptor antagonist
137
Treatment for acute severe asthma
5
O2
Nebulised SABA (Terabutaline or Salbutamol)
Nebulised Ipratropium bromide w/ SABA if no success alone
Oral prednisolone (7-14 days post acute attack)
i.v. Amniophylline
138
List the 5 tasks of management of COPD
Task 1: diagnosis (peak flow)
Task 2: stop smoking
Task 3: Multidisciplinary team (exercise and nutrition)
Task 4: flu and pneumococcal yearly vaccinations
Task 5: medications
139
Name 3 biological effects of using steroids in asthma
1. Remove mucus
2. Reduction in inflammatory mediators
3. Widen airways
140
Why should withdrawal therapy be monitored when coming off immunosuppressants?
Risk of adrenal insufficiency which can lead to Adrenal/Addison’s Crisis
141
Azathioprine is a anti-proliferative immunosuppressant and a disease-modifying anti rheumatic drug (DMARD).
Name 3 conditions it can be prescribed for.
Describe its MOA.
Systemic lupus erythematosus, Vasculitis and Myasthenia gravis
Azathioprine is broken down into its active metabolite 6-mercaptopurine which is then produces 6 TIMP and is metabolised by TPMT. To have these actions:
1. Purine synthesis inhibition
2. Myelosuppression - low WBC replication/activation
3. Low T-Lymphocyte
142
Name 3 factors that need to be clinically monitored whilst taking Azathioprine
1. TPMT levels prior to treatment
2. LFTs due to hepatitis risk
3. FBCs due to bone marrow suppression
143
Mycophenolate mofetil is a anti-proliferative immunosuppressant and a DMARD.
What is its MOA?
Name 3 side effects
Side effect:
1. Nausea/vomiting
2. Myelosuppression
3. Mucositis
MOA:
Inhibits Inosine Monophosphate Dehydrogenase thus B and T cells proliferation inhibition
144
What is Wegener’s granulomatosis?
What drugs are given to treat it?
Describe the MOA of these drugs.
Wegener’s granulomatosis is ANCA vasculitis of arterioles in the lungs and kidneys. Granulomas and necrosis present in arterioles.
Cyclophasphamide + Mensa
Cyclophosphamide: cross links DNA to prevent replication + suppresses T and B cells
Mensa: prevents Haemorrhagic cystitis by Mensa binding to Acrolein (a product of Cyclophosphamide) and excreting with it
145
Name 5 symptoms/signs of Wegener’s granulomatosis
```
Gangrene
Sore eyes
Pulmonary haemorrhage
Kidney failure
Sore JOINTS
```
146
What clinical monitoring needs to take place when prescribing Cyclophosphamide (2)?
- FBC due to myelosuppresion
| - GFR so you can adjust Cyclophosphamide dose if kidney function is worsening
147
What drug group does Tacrolimus belong to?
Name another drug in this class.
What is the MOA of Tacrolimus?
Calcineurin inhibitors
Ciclosporin
Inhibits IL-2 (cytokine) production by inhibiting calcineurin so T cells can no longer be activated
148
One of the major side effects of Calcineurin inhibitors is nephrotoxicity.
So, what clinical monitoring needs to occur whilst on this drug?
GFR and BP
149
Which immunosuppressant causes gingival hyperplasia?
Calcineurin inhibitors - Tacrolimus and Ciclosporin
150
Name 4 CYP 450 inducers that lead to a lower concentration of Calcineurin inhibitors in the body?
Carbamazepine
Phenytoin
Rifampicin
Omeprazole
151
Name 3 CYP 450 inhibitors that lead to a greater dose of Calcineurin inhibitors
Many antifungals
HIV Antivirals
Ciprofloxacin
152
Which DMARD is highly teratogenic and is used to treat RA?
It is also an anti-cancer drug. Describe its MOA here.
Methotrexate
Inhibits Dihydyrofolate reductase in the S phase (in fast dividing cells) of DNA and RNA replication so less pyrimidines and purines are made so less DNA, RNA and proteins made
153
Methotrexate should only be administered p.o or im/sc once a week due to its long half life.
What are some side effects of Methotrexate?
-Myelosuppression
-Mucositis
(both can be treated by putting them on FOLATE ACID)
- Hepatitis
- Pancreatitis
154
Name a DMARD that is safe in pregnancy and needs limited blood monitoring.
What is its MOA?
Name 2 conditions that it can be used in
Sulfasalazine can be used in RA and IBD.
In RA:
The 5-aminosalicylic acid, an anti-inflammatory, component helps alleviate joint PAIN + STIFFNESS
The Sulfapyridine component helps to fight INFECTION
155
Rheumatoid arthritis.
What monoclonal antibody is a:
A) TNF-a inhibitor (2)
A) Adalimumab + Infliximab
156
In Lymphoma and RA, the B cells release what marker?
What drug binds to this marker?
CD20 antigen
Rituximab
157
Drugs that reduce the amount of TNF-a released from cells have what biological effect, to ameliorate Rheumatoid Arthritis pathologies?
1. Less bone destruction due to less bone reabsorption and less cartilage damage
2. Less angiogenesis
3. Less inflammation so less WBC recruited to joint space
158
Drugs that lead to B cell apoptosis (e.g. Rituximab) lead to what pathological gain in order to ameliorate the destruction caused by Rheumatoid Arthritis?
1. B cell can no longer be a APC so less T cells recruited and activated
2. Less cytokines released (TNF-a’s and IL’s)
3. Less Ig’s produced
159
Name a muscarinic receptor antagonist involved in the vomiting reflex. What is its MOA?
Hyoscine hydrobromide competitively binds to mAChR found in Chemoreceptor Trigger Zone (1) and Vestibular nuclei (2)
So:
1 - So signal can’t be sent to vomiting centre in medulla
2 - So signal can’t be sent to CTZ
160
Name 2 H1 receptor antagonists and their uses
Cyclizine - motion sickness
Promethazine - morning sickness
161
Name 2 5HT3 receptor antagonists
Ondansetron
| Metoclopramide
162
Name 2 D2 receptor antagonists (that are not antipsychotics), what are their uses and side effects?
Both can also be used as a prokinetic
Metoclopramide:
Uses - GORD, Acute migraine with vomiting, chemotherapy cytotoxicity
SE - Extra-pyramidal side effect: parkinsonism and dystonia. Galactorrhoea
Domperidone:
Use: to increase lactation in breastfeeding mothers
Side effects: prolonged QT interval and ventricular tachycardia -> combined effect can lead to sudden death. Galactorrhoea
163
Describe the MOA of D2 receptor antagonists
Increase [ACh] to act on mAChR in gut:
So gastric emptying + peristalsis
164
Name 3 anti-psychotics and their uses as an anti-emetic
Chlorpromazine - vertigo, motion sickness
Prochlorperazine - morning sickness
Haloperidol - cytotoxic drugs
165
Name 2 corticosteroids that act on the CTZ.
What is their uses (2)?
Discuss 3 side effects
Dexamethasone
Methylprednisolone
Functions: peri-operative, cytotoxic drugs
Side effects:
1. increased appetite due to high Na+ retention
2. insomnia due to high stress/cortisol levels
3. high BLOOD SUGAR due to high Na+ and glucose reabsorption via SGLT2
166
Name a cannabinoid drug
What receptor does it act on and where is this receptor found?
Nabilone acts on CB1-R (cannabinoid 1 receptor) in the CTZ
167
What anti-emetic has a side effect of Stevens-Johnsons syndrome?
What drug group does it belong to?
Use?
Discuss its MOA?
Aprepitant prevents to action of SUBSTANCE P in the CTZ and PERIPHERAL NERVES. It also enhances the effects of 5HT3 antagonists. It is used for DELAYED vomiting due to chemotherapy.
It belongs to Neurokinin 1 receptor antagonists (NK1RA).
168
Loperamide is an opioid receptor agonist that can be used as an anti-diarrhoeal.
What is its MOA? (Slows down 2 aspects and increases 1)
Binds to Mu opioid receptors in the Myenteric/Auerbach’s plexus thus reducing SM tone and peristalsis but increasing SEQUENTIAL contractions of the gut
169
Name 2 osmotic laxatives and their MOAs
Macrogol - retain the water that they came with
| Lactulose - draw water in
170
Bisacodyl is a stimulant laxative.
Name 3 other stimulant laxatives and their MOA.
Glycerol suppositories, Senna and Docusate sodium all increase intestinal motility and increase the transfer of water and electrolytes to the lower gut
171
Name 2 bulk forming laxatives and their MOA
Isphaghula husk and Methylcellulose both increase faecal bulking and they are hydrophilic so increase water retention
172
Name 2 antacids
Alganic acid
Aluminium Hydroxide
173
Name a H2 receptor antagonist
Ranitidine
174
If an elderly patient needs to be kept on NSAIDS but also need to be treated for peptic ulcers, instead of stopping NSAIDS treatment (as a treatment method for PUD), what drug should be prescribed alongside the current NSAID prescription?
What drug group does this drug belong to?
What is its MOA?
Misoprostol is a prostaglandin analogue that agonises PGE2- R (Prostaglandin E2 receptors) so gastric mucus secretions can be made
175
What drug can be given for PUD, and if contraindicated what drug can be prescribed in place of it?
Omeprazole. Can give Ranitidine instead
176
If your gastritis is caused by an Autoimmune condition, what is the treatment?
Why give this treatment?
LT Cyanocobalamin
It is Vit B12 preventing pernicious anaemia due to the iron loss caused by the bleeding in the mucosa
177
What is the 3 part treatment for an Helicobacter pylori infection?
Amoxicillin + PPI + Clarithromycin (or Metronidazole)
178
If H. pylori infection persists, what drug should be added to treatment?
Bismuth subsalicylate (an antacid)
179
What are the main cytotoxic chemotherapeutic groups and where do they act on?
Give named examples of each
Anti-metabolites *Methotrexate, 5-fluorouracil*: DNA Synthesis
Alkylating agents *Cyclophosphamide*: DNA Replication
Intercalating agents: DNA transcription and DNA duplication
Mitotic inhibitors - spindle poisons *Paclitaxel, Vincristine*: Mitosis
180
What is the MOA of 5-Fluorouracil?
Inhibits Thymidylate synthase so less DNA can be made (via Pyrimidine synthesis pathway) and less purines can be made as less Dihydrofolate can be made
181
Name 2 mitosis inhibitor and its MOA
Vincristine inhibits the polymerisation of the spindle fibres, before they meet at the metaphase plate.
Paclitaxel stimulate polymerisation and inhibits the depolymerisation of the spindle fibres at the metaphase plate so the SISTER CHROMATIDS are unable to move to opposite polls.
182
Using CHEMO-TOX MAN, what are the major side effects of chemotherapy agents
Vincristine - peripheral neuropathy
Cisplatin/Carboplatin - sensorineural hearing loss and nephrotoxic
Myelosuppression:
5-Fluorouracil
6-mercaptopurine
Methotrexate
Cyclophosphamide - haemorrhagic cystitis
183
Describe the MOA of Heparin and what to do if a patient has an overdose and the MOA of this.
Heparin binds to Antithrombin III and potentiates its effects on inhibiting Xa and Thrombin IIa thus fibrin cannot be made.
i.v. Protamine sulfate irreversibly binds to Heparin so Heparin cannot bind to Antithrombin III.
184
What side effect occurs 2-14 days after starting Heparin and discuss its pathology
Heparin induced thrombocytopenia as an AI response occurs producing antibodies for HEPARIN PLATELET FACTOR 4 COMPLEX thus killing platelets
185
What affect can heparin have on the adrenal gland?
And what can this lead to?
Heparin can reduce the aldosterone secretion from the adrenal gland (so have adrenal insufficiency) thus leading to hyperkalaemia.
186
Name 2 low molecular weight heparins and discuss why they do not need to be monitored with aPTT, whereas Heparin does.
Dalteparin and Enoxaparin do not need to be monitored as they only bind to Antithrombin III, whereas Heparin binds to Antithrombin III, macrophages, plasma proteins and endothelial cells
187
Between Heparin and Dalteparin, what are their routes of administration?
They both have poor GI absorption
Dalteparin is given s.c.
Heparin is given i.v. (or s.c.)
188
Name a vitamin K antagonist and its indications (5)
Warfarin:
- DVT
- PE
- VTE
- AF patient with high risk of stroke
- INR 2.5 with bio-prosthetic heart valve replacement
189
Describe the MOA of Warfarin sodium
It competitively inhibits Vitamin K epoxide reductase so the active form of Vitamin K cannot be produced. So this active form is not able to be involved in the hepatic synthesis of its clotting factors - II, VII, IX and X.
190
What is the Warfarin reversal treatment?
Give:
1. Vitamin K1
2. Prothrombin complex concentrate
191
What does the CHA2DS2VASC SCORE help you diagnose?
The likelihood of a patient with AF having a stroke caused by a thromboemboli.
192
Name 4 DOACs direct acting anti-coagulants and what are their MOA?
Edoxaban, Abixaban, Rivaroxaban inhibit Xa
Dabigatran inhibits Thrombin IIa
193
What antidotes are available for DOACs?
Andexanet - replaces Xa (Edoxaban, Abixaban, Rivaroxaban)
Idarucizumab - monoclonal antibody for the reversal of Dabigatran
194
Name 3 Benzodiazepines
Lorazepam
Diazepam
Midazolam
195
Name 4 anti-epileptic drugs that act by blocking Na+ channels
Sodium valproate
Lamotrigine
Carbamazepine
Phenytoin
196
Name 4 side effects of Sodium valproate
Teratogenic - causes neural tube defects
Weight gain
Inhibits CYP2C9 (metabolises phenytoin, warfarin, omeprazole)
Pancreatitis
197
What are 3 MOAs of Sodium valproate?
Briefly discuss each one
1. Sodium channel blockers (open sodium channels are blocked thus preventing the influx of Na+ so takes longer for depolarisation to occur)
2. Calcium channel blockers (post synaptic inhibitory complex)
3. GABAa agonism/potentiation (increase Cl- inflow so membrane is hyperpolarised so an action potential cannot be generated)
198
What anti-epileptic drug is safe to use in pregnancy?
Discuss its MOA
Levetiracetam
Binds to (inhibits) SV2a (Synaptic Vesicle Glycoprotein 2A) vesicles, preventing them from being released into the synaptic cleft
199
Name the seizure types under their major categories
A) Focal onset seizures
B) Generalised onset seizure
A) Aware, Impaired awareness
B) Tonic-clonic, Myoclonic, Atonic (loss of muscle tone), Absence (abrupt loss of awareness)
200
What are reflex seizures?
Give some examples
Seizures caused by a particular stimulus
Hot water immersion, orgasm, musicogenic, photogenic
201
What is the definition of epilepsy?
2 or more reflex seizures occurring more than 24 hours apart.
202
Describe dopamine degredation
Monoamine oxidase pathway: dopamine -> (via MAO) acetic acid -> (via COMT) Homovanillic acid
Catechol-o-methyl transferase pathway: dopamine -> (via COMT) 3-Methyldopa -> (via MAO) Homovanillic acid
203
Name 2 acetylcholinesterase inhibitors.
PyridoSTIGMINE
| NeoSTIGMINE
204
What is the absorption of Levodopa?
How can diet effect its absorption?
Levodopa is absorbed by ACTIVE TRANSPORT, and so is protein. So high protein diet means that protein competitively competes with L-DOPA for the BBB so more LDOPA will be metabolised in the periphery - by aromatic amino acid decarboxylase
205
Carbidopa can be given alongside Levodopa to reduce GI side effects (nausea and vomiting).
What combination therapy can be given in replacement of these 2 drugs (2)?
What properties make up these drugs?
What are other benefits of this combination therapy (2)?
Co-beneldopa
Co-careldopa
They contain Levodopa and peripheral DOPA decarboxylase inhibitors
- lower doses
- more L-DOPA reaches the brain
206
Name 4 dopamine receptor agonists and one of its psychological side effects
Amantadine
Apomorphine
Rotigotine
Ropinirole
Impulse control disorders (pathological gambling)
207
Name 2 monoamine oxidase inhibitors and discuss how they can fatally lead to a hypertensive crisis
Rasagiline and Selegiline inhibit monoamine oxidases from metabolising TYRAMINE (in your diet) so high tyramine levels lead to blood pressure rising.
208
Name a catechol-o-methyl transferase inhibitor and discuss its MOA
Entacapone inhibits peripheral COMT, limiting the metabolism of LDOPA to 3-methyldopa so less 3-MT is competing with LDOPA for the active transport at the BBB. This means that more LDOPA reaches the brain
209
Name 2 anticholinergic drugs and discuss their MOA
Anticholinergics inhibitors, Orphenardine and Procyclidine, inhibit ACh release from striatum, so ACh cannot stimulate the release of GABA NTs from the GABA neurones in the striatum so the GABA NTs can no longer inhibit the release of dopamine from the substantia nigra. Now the dopamine can inhibit the release of ACh from the striatum. THIS TREATS THE TREMOR.
210
What surgeries can be done to treat Parkinson’s disease?
Group into:
A) Increases movement (2)
B) Decreases movement (1)
Increases movement:
- Substantia nigra stimulation
- Lesion of the internal globus pallidus
Decreases movement:
-Lesion fo the thalamus
211
What is the MOA of MAOI?
Inhibit MAO so less dopamine is broken down so enhances the effects of L-DOPA (thus reducing the dose of L-DOPA)
212
What is the MOA of Thiazolinediones?
Pioglitazone activates PPAR-y receptors in muscle cells, thus increasing the sensitisation of insulin in that cell and decreasing the hepatic glucose output
213
NSAIDS are highly protein bound.
Name 3 other drugs that are highly protein bound, and if taken in conjunction with NSAIDS will quickly enter the toxic range.
Sulfonylurea, Methotrexate and Warfarin
214
SIRS + infection = child sepsis
What does SIRS stand for?
What 4 factors make up SIRS (having at least 2 of these factors, signifcantly increases a childs risk to having sepsis and dying from it)
Systemic inflammatory response syndrome
1. High BP
2. High RR
3. Temperature hot or cold
4. WCC high or low
215
How can phenytoin cause Osteomalacia/Rickets?
It decreases vitamin D absorption os bone has lower mineralisation and more osteoids (so bone is more fragile)
216
What stomach protection can you give when prescribing long term NSAIDS?
PPIs (Lansoprazole, Omeprazole)
217
What is the full name of the antibodies found in the blood in ANCA Associated Vasculitis?
What sized vessels does ANCA Associated Vasculitis typically affect?
Antineutrophilic cytoplasmic antibodies.
Typically affects small>medium sized.
218
Briefly describe the pathophysiology of ANCA Associated Vasculitis
Cytokines TNF-a and IL1 cause the translocation of proteinase and myeloperoxidase from inside the neutrophils and granulomas to their surfaces.
Cytokine IL2 activates the naive T cell, which produces the T helper 2 cell. T helper 2 cell stimulates the humoral response so B cells are produced -> which then produce plasma cells -> which then produce cANCA (cytoplasmic anti-neutrophilic cytoplasmic antibodies) and pANCA (perinuclear anti-neutrophilic cytoplasmic antibodies).
cANCA bind to proteinases.
pANCA bind to myeloperoxidases.
219
What protein stimulates granuloma formation?
CD4 (on T helper cells)
220
Give 3 reasons as to why Glucocorticoids are given to treat ANCA Associated Vasculitis?
It inhibits transcription factors involved in the synthesis of TNF-a, IL1 and IL2.
Less TNFa - less translocation of the 2 antigens.
Less IL1 - less granuloma formations and less translocation of the 2 antigens.
Less IL2 - less naive T cell activation
221
Name a DMARD that can be given to treat ANCA Associated Vasculitis
Cyclophosphamide
222
Name a monoclonal antibody that can be given to treat ANCA Associated Vasculitis
Why?
Rituximab. It causes the lysis of B lymphocytes by binding to the CD20 antigens on B cells.
223
ANCA Associated Vasculitis treatment:
For an induction (where active disease is put into remission) Glucocorticoids, Cyclophosphamide and Rituximab can be given.
Name 3 drugs that can be given in order to remain in remission?
Rituximab, Methotrexate and Azathioprine
224
Name a drug/mouthwash that is used for painful, inflammatory conditions in the oropharynx (e.g. swollen throat, mouth)
Also, give its trade name.
Give 3 functions of this drug.
Difflam (trade name)
Benzydamine hydrochloride
locally acting NSAID (reduced inflammation) with local anaesthetic (reduced sensation) and analgesic (reduced pain).
225
Name 2 local side effects of inhaled corticosteroids
1. Dysphonia (hoarse voice)
| 2. Oral thrush
226
Name 2 systemic side effects of medium to high dose ICS in children?
1. Growth failure
| 2. Adrenal insufficiency
227
If a child comes in with adrenal insufficiency, how will they present?
Name 2 investigations.
What is the treatment?
1. Shock
2. Decreased level of consciousness
Investigation: blood glucose level, ?child on ICS, serum biochemistry
Treatment: IM Hydrocortisone
