All Content Flashcards
(457 cards)
1
Q
Define Pharmacokinetics.
A
The movement of a drug within the body.
2
Q
What does ADME stand for?
A
Absorption
Distribution
Metabolism
Excretion
3
Q
What is PK affected by?
A
Renal function
Liver function
Pyrexia
4
Q
What is Bioavailability?
A
The percentage of drug that makes it into the desired body compartment from where it can have efficacy
5
Q
What factors govern the distribution of a drug from the interstitium?
A
- Blood flow - how vascularised a tissue is
- Drug lipophilicity and hydrophilicity - lipophilic drugs can travel straight through a membrane, hydrophobic cannot
- Protein binding eg. Warfarin to Albumin
6
Q
How does protein binding affect distribution and efficacy?
A
Only free drug can cause a response.
Drug can be displaced from protein binding by another drug.
Relevant in Renal failure (hypoalbuminaemia), Pregnancy (fluid balance), Heart failure etc.
7
Q
What does a high Vd (volume of distribution) mean?
A
Spread across the entire body and tissues - less in plasma
8
Q
What does a low Vd mean?
A
Confined to the plasma
9
Q
What is the equation for Vd?
A
Vd = dose/conc of drug in plasma
10
Q
What drug has a particularly high Vd?
A
Digoxin
11
Q
What is the relationship between half life and Vd?
A
T1/2 and Vd are proportional
12
Q
Would a fat patient have a higher or lower Vd than a skinny patient? Would they need a higher or lower dose of drug?
A
Higher Vd, would need a higher dose of drug.
13
Q
What is the Phase 1 of metabolism? Give examples
A
(CYP) P450 mediated drug modifications eg. oxidations
Most drugs are inactivated by this, but some can be activated (eg. Levodopa) and others can just be modified (eg. Codeine to Morphine)
14
Q
Name one example of a CYP enzyme inhibitor, what CYP it inhibits and what this leads to.
A
Grapefruit juice.
Inhibits CYP3A4
Inhibits Statin metabolism
15
Q
Name one example of how genetics can affect CYP metabolism.
A
CYP2D6
Affected by Race - 7% of whites don’t have, 30% of blacks have it over-active.
Metabolises antiarrhythmics, antidepressants and opioids
16
Q
Define the “half life” of a drug.
A
The time in which the concentration of a drug in the plasma decreases by half.
17
Q
Define the relationship between T1/2 and clearance
A
Inversely proportional - T1/2 goes up with reduced clearance (GFR).
18
Q
Name 4 things that will affect the T1/2 of a drug.
A
Renal stenosis, Hepatic stenosis, Age (muscle mass), fat, Haemorrhage, DDIs
19
Q
Describe First Order drug elimination kinetics.
A
Concentration dependent - a constant PROPORTION of drug is eliminated per unit time
20
Q
Describe Zero Order drug elimination kinetics.
A
Independent of Concentration - a constant AMOUNT of drug is eliminated per unit time
21
Q
What order elimination kinetics do most drugs exhibit?
A
First Order
22
Q
What does alcohol do to elimination kinetics of aspirin and phenytoin?
A
Makes them zero order
23
Q
What does CpSS stand for?
A
Steady state plasma concentration (of drug)
24
Q
How many half lives does it take to reach CpSS?
A
5
25
What is the clinical significance of CpSS?
Therapeutic benefit is optimal at stead state plasma concentration
26
How many half lives does it take to fully eliminate a drug from CpSS?
5
27
What must be given if a drug has a long half life?
A loading dose to reach minimum effective concentration
28
Why might Digoxin lead to Digitoxicity?
Has a very long (40 hour) half life - takes a long time to be eliminated - renal failure can make this even worse
29
What is the equation for calculating loading dose?
Loading dose = Vd x CpSS / Bioavailability
30
What are the units of Vd?
L/Kg
31
What is the equation for calculating T1/2?
```
T1/2 = Log(2)/K
T1/2 = 0.693/K
K = clearance/Vd
```
32
What is the equation for calculating K in the T1/2 equation?
K = clearance/Vd
33
What are the units of clearance?
ml/min
34
What is the "Selectivity" of a drug?
The chance of it interacting with only the intended receptors - chance of it producing adverse effects
35
What is the "Affinity" of a drug?
The likelihood it will bind to a receptor
36
What is the Kd?
Dissociation constant - the concentration of drug at which 50% of a drug will interact with receptors.
37
What is the "Efficacy" if a drug?
The ability of a drug to produce a response on receptor binding.
38
What is the "Potency" of a drug?
Dose required to produce the required response
39
Define Ec50.
The effective concentration - the concentration of drug needed to produce 50% of the maximum response. A measure of potency.
40
What is the "Therapeutic Index" of a drug?
The relationship between a concentration of a drug that causes a desired effect and an adverse (toxic) effect.
41
What is the equation for the Therapeutic Index of a drug?
TI = Toxic conc/Ec50
42
What is the "Therapeutic Window" of a drug?
The range of dosages that produce a safe, effective treatment.
43
Name one example of a CYP enzyme inhibitor, what CYP it inhibits and what drug it inhibits.
Cranberry juice
| Inhibits CYP2C9, involved in Warfarin metabolism -> increased hemorrhagic effect
44
Define "Adverse Drug Reaction".
An unwanted or harmful reaction that occurs after administration of a drug.
45
Name all 5 types of Adverse Drug reaction, with an explanation of what each is.
A - Augmented - dose related eg. overdose of insulin causing hypoglycaemia
B - Bizarre - unpredictable eg. allergy
C - Chronic - due to prolonged use eg. Cushing's due prednisolone
D - Delayed - effects years after treatment - eg. cancer due to alkylating agents used in chemo
E - End of treatment - eg. Unstable angina when B blockers are stopped
46
Name 4 causes of drug response variability.
1. Body weight
2. Age and sex
3. Genetics eg. race
4. Health eg. kiney/liver failure
47
Name 4 things that increase the risk of an ADR.
1. Polypharmacy
2. DDIs
3. Co-morbidities and age
4. Narrow therapeutic index drugs
48
What is the "Constitutive actvity" of a receptor?
Activity caused by endogenous ligands within the body.
49
What is an "Inverse Agonist"?
Causes a response, but the opposite of what is expected.
50
Give an example of a partial agonist and its therapeutic use.
Buprenorphine.
Opioid addiction.
Higher affinity than opioid, but lower response (lower efficacy) - reduces withdrawal while causing fewer side effects.
51
Describe the pharmacokinetics of a competitive antagonist.
```
Can be out-competed at high concentrations - higher affinity though. Potency is reduced, so shift of curve to the right.
Max response unchanged.
Lowers Km (conc required to reach half of max speed)
```
52
Describe the pharmacokinetics of a non-competitive antagonist.
Binds to allosteric site of a receptor - reduces max response
Does not affect potency
Lowers Vmax (max rate of reaction)
53
What is Km?
Concentration of substrate needed to reach half of Vmax
54
Give an example of an example of a contraindication in asthma that could cause an ADR.
B blockers in asthma.
55
What is the equation for MAP?
MAP = CO x TPR
56
What is the difference between Primary Secondary hypertension?
```
Primary = idiopathic
Secondary = caused by something
```
57
What are the stages of hypertension and what are the BP values?
Stage 1 = 140/90
Stage 2 = 160/100
Stage 3 = 180/110
58
What is the target BP in diabetics?
130/80
59
Name 4 lifestyle changes that can reduce hypertension?
Exercise
Stress
Diet
Caffeine reduction
60
Name the 3 types of drugs used for hypertension treatments.
ACD
- ACE/ARBs - Ramipril/Losartan
- Calcium channel blockers - Amlodipine
- Diuretics - Thiazide
61
Give an example of an ACE inhibitor
Ramipril
62
Give 3 side effects of a Ramipril
Dry cough - bradykinin not broken down
Low BP - renal failure
Hyperkalaemia
63
Give a contraindication of Ramipril
Not when breastfeeding - causes infant hypotension
64
Give an example of an ARB
Losartan
65
Why might you use an ARB over and ACE inhibitor?
Does not affect Bradykinin - no cough
66
How do L-type Calcium channel blockers work?
Stop calcium entering cells, preventing smooth muscle contraction
67
What are the 3 classes of Calcium channel blockers?
1. Dihydropyridine eg. amlodipine
2. Phenylalkamine eg. verapamil
3. Benzothiazipine eg. diltiazem
68
Give one DDI of amlodipine
Statins
69
Why are dihydropyridines better than phenylalkamines for hypertension?
They are selective for smooth muscle. Phenylalkamines act on the heart too.
70
Name 3 side effects of amlodipine
- Sympathetic activation eg. tachy
- Palpitations
- Flushing/sweating
71
Name the best diuretic for hypertension
Thiazide
72
Name 4 side effects of Thiazide
- Hypokalaemia
- Increased urea
- Impaired glucose tolerance
73
Describe the guidelines for treating hypertension.
If patient less than 55 years old or has heart failure or diabetes: Give A
If patient is more than 55 years old or black: C
Then A+C
Then D
74
Why are black people treated differently for hypertension?
Naturally have reduced Renin levels
75
Name 2 other hypertension treatments and their MOAs.
A-blockers - block peripheral a channels which usually cause vasoconstriction
B-blockers - reduce cardiac output/contraction (reduced sympathetic stimulation)
76
What is a contraindication of B-blockers?
Do not give to asthmatics
77
Name 3 side-effects of B-blockers
Bronchoconstriction
Bradycardia
Lethargy
78
Define Heart failure.
The inability of the heart to produce enough cardiac output to adequately perfuse the organs
79
What is decompensation in Heart Failure?
Decrease in arterial BP, increased heart rate, heart works harder, condition worsens, heart has to work harder against vasoconstricted arteries
80
Name 4 treatments of Heart failure and how they help.
1. Diuretics - furosemide - oedema
2. ACE - reduces afterload due to due to less vasoconstriction and fluid
3. Spironolactone - given with ramipril and furosemide, reduces "Aldosterone escape"
4. B-blockers - reduces heart rate, improves filling
81
What is "Aldosterone escape"?
Hyperaldosteronism after heart failure
82
Name every type of diuretic and where it acts.
```
Osmotic - mannitol
Loop - furosemide - NKCC2
Thiazides - NCC in DCT 1 - Thiazide
Aldosterone antagonists - Spironolactone + Amiloride - DCT 2 + CD
ADH anatagonists - Lithium
```
83
Name a Loop diuretic and the channel it acts on
Furosemide
| NKCC2
84
Name 4 side effects of Loop diuretics
- Hypokalaemia - metabolic alkalosis
- Hypotension - acute kidney injury
- Loss of Ca2+
- Gout
85
Name a Thiazide diuretic and the channels it acts on
```
Thiazide
NCC (NaCl channels)
```
86
Name 4 side effects of Thiazides
- Hypokalaemia - metabolic alkalosis
- Hypotension - acute kidney injury
- Hypercalcaemia - do not give to hypercalcaemics
- Gout
87
Name 2 aldosterone antagonists
Spironolactone
| Amiloride
88
Describe how Aldosterone works on the kidney to increase reabsorption
Increases ENaC expression and Na/KATPase - increased Na and water loss
89
Describe the MOA of spironolactone
Blocks Aldosterone binding
90
Describe the MOA of amiloride
Blocks ENaC channels
91
What are the Potassium-sparing diuretics?
Spironolactone
| Amiloride
92
Name a ADH antagonist
Lithium
93
Name 2 side effects of Spironolactone
Hyperkalaemia
| Impotence
94
Name a DDI of Potassium-sparing diuretics
ACE - hyperkaemia
95
Name 2 DDIs of Thiazide and Loop diuretics
1 . Digoxin - hypokalaemia
| 2. Lithium - increased toxicity
96
Name 4 uses for Diuretics
1. Hypertension
2. Heart failure
3. Nephrotic syndrome
4. CKD
97
Describe Diuretic resistance
Insufficient diuretic reaches the lumen of the kidney tubules, due to:
- Reduced GFR in pump failure
- Fewer nephrons in CKD
- Reduced albumin (furosemide needs to be bound to albumin to be secreted) in nephrotic syndrome
98
List 4 nephrotoxic drugs
Vancomycin, Gentamicin, Aciclovir, NSAIDs
99
What do ACE inhibitors affect in the kidney?
Angiotensin 2 - vasoconstricts the efferent
100
What is the management of Hyperkalaemia?
Calcium gluconate, Insulin, Glucose, Sodium resonium
101
Give a good case study for Pharmacovigilance
Thalidomide in the 50s - caused limb deformities
102
Give a good case study for Pharmacovigilance
Thalidomide in the 50s - caused limb deformities in pregnant women
103
Give a risk management example
The Pill - can cause thromboembolism - however, dose was lowered without compromising effectiveness and risk reduced
104
What is Pharmacogenetics?
How genetics affect response to a certain drug
105
What is Pharmacogenetics and give an example
How genetics affect response to a certain drug
| Eg. How ACE is less effective in Black people due to lower Renin levels
106
What is the precursor for Steroid drugs?
Cholesterol
107
How should progesterone be given? (IV/Oral)
IV - bound by albumin in blood
108
What can reduce the effectiveness of contraceptives?
CYPs can be induced (increased) by:
- Anti-epileptics
- St John's wort
- Rifampicin
- Soya food - reduces oestrogen storage, faster use
109
What can HRT be used for?
Menopause - reduces symptoms
Reduces osteoporosis
Does not affect heart disease increased risk
110
What is HRT?
Opposed oestrogen - ERT = unopposed, increases endometrial cancer risk
111
What are the risk factors of HRT?
- Breast cancer
- Venous thromboembolism - oestrogen is thrombogenic
- CVS disease increase (lipid profile fucked)
- Increased stroke risk
112
Name a Progesterone receptor antagonist
Mifepristone
113
What is Mifepristone?
Progesterone receptor antagonist
| Pregnancy termination
114
What does SERM stand for?
Selective Oestrogen Receptor Modulator
115
What are SERMs used for?
Used for infertility, ovarian dysfunction and breast cancer eg. Tomoxifen, Clomiphene
116
Give an example of a SERM
Tamoxifen, Clomiphene
117
What is Clomiphene used for?
Induces ovulation, tricks hypothalamus into releasing LH and FSH
118
What is Tamoxifen used for?
Acts as ER (HER 2) receptor antagonist - causes cells to arrest cell cycle in breast.
119
Why is Tamoxifen only used if endometrium has been taken out?
It is an ER agonist in the endometrium
120
What is synthetic oestrogen called?
Oestradiol
121
What is synthetic progesterone called?
Medroxyprogesterone acetate
122
What is the morning after pill called?
Ulipristal acetate
123
What is Ulipristal acetate?
Progesterone receptor modulator (like a SERM) - inhibits ovulation
124
What is the main target for cardiovascular disease prevention?
Cholesterol (LDL)
125
What is the target cholesterol level?
4mmol/L
126
What is the MOA of statins?
HMG-CoA reductase inhibitor - reduces cholesterol synthesis
| Upregulates LDL receptors to clear out LDLs via liver
127
What do statins do to the lipid profile? (LDL, HDL, TAGs)
LDL down
HDL up
TAGs down
128
Name a Statin
Atorvastatin, simvastatin (shorter half life)
129
Name 3 benefits of Statin therapy
Reduced CVD risk:
- Reduced endothelial damage
- Anti-inflammatory
- Antioxidant
130
What CYP metabolises Statins? What must not be taken with them?
CYP3A4 - Grapefruit juice
131
What are the side-effects (ADRs) of Statins?
- Myalgia - test for Creatine Phosphokinase elevation
- LFT increases
- Rarely rhabdomyelosis
132
What should be tested for in myalgia when using statins?
Creatine Phosphokinase
133
Why is atorvastatin better than simvastatin?
Simvastatin needed to be taken at night when receptors highest due to low half life.
134
Name all the drugs used to treat Hypercholesterolaemia (4)
Statins
Fibrates
Nicotinic acid
Cholesterol absorption inhibitors
135
Name a Fibrate
Fenofibrate
136
How do Fibrates work?
Increase lipoprotein lipase production, clearing TAGs faster, lowering LDL and raising HDL
137
How is Fenofibrate given?
With statins usually.
138
What are the side effects of Fenofibrate?
- GI upset
- Increased Myalgia/Rhabdo risk with Statins
- Gall stones
- LFT increases
139
Name a Nicotinic acid
Niacin
140
What is the MOA for Niacin?
Antilipolytic, reduces TAG and LDL, greatly increases HDL
141
What are the ADRs for Niacin?
Flushing, headache, GI disturbance
142
Name a Cholesterol absorption inhibitor
Ezetimibe
143
What is the MOA for Ezetimibe?
Brush border absorption inhibitor - often given with statins
144
Name a PCSK9 inhibitor
Alirocumab
145
What is Alirocumab?
PCSK9 monoconal antibody inhibitor
146
What other things can lower cholesterol?
Exercise
Fish oils
Fibre
147
What programme measures CVS risk?
QRISK
148
What is always given after an MI?
Any lipid lowering agent
149
Name the types of insulin for Type 1 Diabetes, an example of each and how long each one lasts
```
Ultrafast acting - Apart - mins
Rapid acting - Novorapid - hour
Short acting - Humulin S - hours
Intermediate acting - Humulin I - one a day
Long acting - DEGLUDEC - two days
```
150
What is the most efficient way of administering insulin
Insulin pump, detects insulin levels
151
What are the ADRs of insulin?
- Hypoglycaemia
- Hyperglycaemia
- Lipodystrophy - scarring from injections
- Pain on injection
152
What is Type 1 diabetes?
Autoimmune destruction of Beta cells
153
What is Type 2 diabetes?
Insulin resistance around the body and gradual beta cell failure
154
What drugs are used to treat Type 2 Diabetes?
- Metformin (Biguanides)
- Sulphonylureas
- Pioglitazone (Glitazones)
- Exenatide (GLP-1 agonists)
- Sitagliptin (DPP-4 inhibitors)
- Glifozins (SGLT2 inhibitors)
155
How does Metformin work?
Reduces Insulin resistance, reduces hepatic glucose production
156
What are the ADRs of Metformin?
- GI upset
| - Vitamin B12 deficiency
157
When should Metformin not be given?
If patient has bad CKD or co-morbidities
158
How do Sulphonylureas work?
Stimulate B cells to release Insulin
159
What are the ADRs of Sulphonylureas?
- Weight gain
| - Hypoglycaemia
160
How does Pioglitazone work?
Increased insulin sensitivity within muscle and adipose tissue and reduced glucose production in liver
161
What are the ADRs of Pioglitazone?
- Weight gain
- Sodium and fluid retention
- Heart failure
162
Name a GLP-1 agonist
Exenatide
163
How does Exenatide work?
Increases insulin secretion and reduces glucagon production
164
Why is Exenatide good?
Promotes weight loss
165
What are the ADRs of Exenatide?
- Hypoglycaemia
| - GI upset
166
Name a DPP-4 inhibitor
Sitagliptin
167
What is the MOA of sitagliptin?
Reduces GLP-1 breakdown, then GLP-1 agonist effect - increased insulin, reduced glucagon
168
Name an SGLT-2 inhibitor
Glifozins - add on therapy
169
Name the 4 classes of antiarrhythmic drugs
- Class 1 - Na channel blockers
- Class 2 - B-blockers
- Class 3 - Potassium channel blockers
- Class 4 - Calcium channel blockers
170
What are the 5 phases of the non-pacemaker action potential?
0 - Depolarisation - Na in
1 - Peak Na opening and K+ starts to open
2 - Calcium channels open - plateau phase
3 - K+ causes repolarisation
4 - NaKATPase maintains baseline
171
Describe how Class 1 antiarrhythmics work
Na channel blockers
| Affect Phase 0 - slower depolarisation, but same peak
172
Describe how Class 2 antiarrhythmics work
B-blockers
| Affect Phase 2, prolonging plateau and affecting Phase 4 (slower to reach)
173
Describe how Class 3 antiarrhythmics work
K-channel blockers
| Increase AP duration (Phase 2 and 3), increase refractory period - can be pro-arrhythmic
174
Describe how Class 4 antiarrhythmics work
Calcium channel blockers
Phase 2 reduced
Decreases Phase 4 spontaneous depolarisation
175
Describe the Phases of a Pacemaker action potential
Phase 4 - Funny channels, gradual depolarisation - Na channels
Phase 0 - Reaches threshold, Ca2+ channels open
Phase 2 - Ca channel peak opening
Phase 3 - K+ repolarisation
No 1
176
How do Calcium channel blockers affect the pacemaker potential?
They reduce conduction velocity, increasing the refractory period
177
Name 2 core mechanisms of inducing arrhythmias
- Abnormal impulse generation
| - Abnormal conduction
178
Name 3 causes of abnormal impulse generation in the heart
- Ectopic foci
- Early afterdepolarisation - eg. Hypokalaemia
- Delayed afterdepolarisation - eg. Digoxin toxicity, leads to increased Ca2+
179
Name 2 causes of abnormal conduction in the heart
- Heart block
| - Re-entrant loops
180
Name a re-entrant loop disease
Wolff-Parkinson-White syndrome - accessory pathway into ventricles
181
Name all the antiarrhythmic drug classes and give an example of each
```
Class 1 -
b - Lidocaine
c- Flecainide
Class 2 - Bisoprolol/Labetalol
Class 3 - Amiodorone, Sotalol
Class 4 - Verapamil, Diltiazem (NOT AMLODIPINE)
```
182
Name the MOA of Lidocaine and its main use
```
Given IV - relevant
Ventricular tachycardia re-entrant loops
Na channel blocker, only active channels/ischaemic
Phase 0 slow down
Raises QRS time
```
183
Name 3 ADRs of Lidocaine
- Dizziness
- Drowsiness
- Abdominal upset
184
Name the MOA of Flecainide and its main use
Used in AF/WPW
| Reduces automaticity in all cells, increases refractory period - can be pro-arrhythmic
185
What must Flecainide be given with?
AV node blockers to prevent ventricular arrhythmia
186
Name the MOA of B-blockers
Increases refractory period in AV node, increases PR interval, reduces heart rate
187
Name 2 side effects of B blockers
- Bronchoconstriction - asthmatics
| - Hypotension - do not use in heart failure or heart block
188
Name the MOA of Amiodorone and its uses
Used in most arrhythmias and WPW
Increases action potential duration and refractory period, decreases Phase 0 (Na) too
Also reduces AV node conduction
189
Name 3 ADRs for amiodorone
- Pulmonary fibrosis
- Hepatic injury
- LDL increase
190
What 2 drugs must not be given with Amiodorone?
- Warfarin
| - Digoxin
191
Name the MOA of Sotalol and its use
Used in tachycardia
Increases action potential duration and refractory period and slows AV node conduction
ORAL ONLY
192
Name 3 ADRs of Sotalol
- Pro-arrhythmic
- Fatigue
- Insomnia
193
Name the MOAs of Diltiazem and Verapamil and their uses
Slow AV node conduction and increase refractory period
- Controls supraventricular tachycardia ventricles
- Stops AV node re-entry
194
Name the side-effects of Diltiazem and Verapamil
- Decreased cardiac output
| - GI problems
195
What should Verapamil and Diltiazem not be given with and why?
B-blockers - can cause AV node block
196
Name 5 other Heart drugs
- Adenosine
- Vernakalant
- Ivabridine
- Digoxin
- Atropine
197
Describe the MOA of Adenosine
Rapid IV bolus, very temporarily (secs) blocks AV node
Hyperpolarises by binding A1 receptors
Stops re-entrant supraventricular arrhythmias
198
Describe the MOA of Vernakalant
Slows atrial conduction via K+ blocking
199
Describe the MOA of Ivabridine
Blocks funny channel of SA node, slows SA node but does not affect BP - used in sinus tachycardia
200
When must Ivabridine not be given?
Pregnancy - teratogenic
| Heart failure - reduces heart rate
201
Describe the MOA of Digoxin in AF
Used with Ca2+ channel blockers to slow down heart rate in AF
Enhances vagal activity and slows AV node conduction by inhibiting NaKATPase
202
When would Digoxin be used?
AF with Bisoprolol
203
Name 2 ADRs of Digoxin
Kidney failure due to Digoxin toxicity
| Bradycardia
204
Describe the MOA of Digoxin in Heart Failure
NaKATPase inhibitor - causes NA build up in the cell
NCX fails, so no Ca2+ pumped out
Ca2+ increases force of contraction
205
Describe the MOA of Atropine
Antimuscarinic - speeds up AV conduction and heart rate
206
What is Atropine used for?
Bradycardia
207
Describe the course of action for drugs for a patient with AF
1. Bisoprolol - reduce rate
2. Digoxin
3. Flecainide (with bisoprolol, reduces VF risk)
208
Describe the course of action for drugs for a patient with VF
Amiodorone through central line
| Lidocaine/Bisoprolol
209
Name the drug for treating WPW
Amiodorone
210
Describe the course of action for drugs for a patient with a re-entrant SVT
```
Acute -
1. Adenosine
2. Verapamil
Chronic -
1. Bisoprolol
2. Flecainide
```
211
Describe the course of action for drugs for a patient with a sinus tachycardia
Ivabradine
| Bisoprolol
212
Name the two types of AF and their treatments
Stable - no syncope - Bisoprolol, digoxin, flecainide
| Unstable - syncope - Amiodorone, anticoagulant
213
What determines what anticogaulant should be used?
Where the clot occurred
Arterial: platelet rich, antiplatelets and fibrinolytics
Venous: low platelet:, use parenteral anticogulants (heparins) and oral anticoagulants (warfarin)
214
Name 4 anti-platelet agents
- Aspirin
- Clopidogrel/Ticagrelor
- Abciximab
- Dipyrimadole
215
Name the MOA of Aspirin
COX-1 inhibitor
| Prevents Thromboxane A2 formation from arachidonic acid
216
Describe the MOA of Aspirin as an anti-platelet drug
COX-1 inhibitor
| Prevents Thromboxane A2 formation from arachidonic acid
217
When should Aspirin be given?
Secondary prevention of Stroke/TIA, post-op, secondary prevention of MI in stable angina
218
Name the MOA of Clopidogrel/Ticagralor
P2Y-12 inhibitor (ADP receptor antagonist)
219
Describe the MOA of Clopidogrel/Ticagralor
P2Y-12 inhibitor (ADP receptor antagonist)
| Prevents binding of ADP to P2Y-12, inhibits the activation of GP2b/3a receptors, meaning no platelet cascade
220
When should Clopidogrel be given?
Post-stroke, post-MI (with aspirin), in people intolerant to aspirin
Given for 12 months post-MI
221
Describe the MOA of Abciximab
GP2b/3a inhibitor -> usually lead to binding of fibrinogen to vWF
IV bolus
Also an irreversible binder
222
Name one risk of Abciximab
Thrombocytopenia
223
Describe the MOA of Dipyrimadole
PDE5 inhibitor - inhibits cellular re-uptake of adenosine, leading to increased plasma adenosine, which inhibits platelet aggregation
Also prevents expression of GP2b/3a via cAMP inhibition
224
When should Dipyrimadole be used?
In combination with oral coagulants after valve replacement surgery
225
Name one Fibrinolytic and one group of fibrinolytics
- Streptokinase
| - "teplase" group
226
Why can Streptokinase only be given once?
Antigenic (from a bacteria), so can cause immune reaction
227
Name 3 anticogulants
- Warfarin
- Heparin (LMWH)
- Bempiparin
228
Describe the MOA for Warfarin
Inhibits Vitamin K conversion, leading to loss of factors 2, 7, 9 and 10 (need Vitamin K as a co-factor)
229
Why does Warfarin need to be given a few days before effect needed?
It only inhibits the production of new clotting factors
| Will need heparin cover initially
230
Name 5 therapeutic uses of Warfarin
- DVT prophylaxis
- PE prophylaxis
- AF prophylaxis
- Following orthopaedic surgery
231
What needs to be taken into account when determining Warfarin PK?
- Highly protein bound
- Needs CYP2C9 - inhibited by Cranberry juice
- Teratogenic - DO NOT GIVE IN PREGNANCY, GIVE HEPARINS
232
Explain why Warfarin leads to dangerous bleeding and what antidotes exist
Can be difficult to manage for long time, causes bleeding
| Can use Vitamin K analogue
233
Name 4 Warfarin DDIs
- CYP 2C9 can be affected by Amiodorone, clopidogrel, alcohol, metronidazole
- Aspirin - increases bleeding
- Cephalosporin antibiotics reduce Vitamin K
- NSAIDs displace warfarin from plasma warfarin
- St John's wort, Phenytoin increase breakdown speed
234
Name 2 parenteral anticoagulants
- Heparin
| - Bempiparin
235
Describe the general MOA of heparins
Inhibit the action of coagulation factors
| Bind to anti-thrombin and increase action
236
What does anti-thrombin do?
Inactivates Thrombin and multiple factors
237
Name an unfractionated heparin
Heparin
238
Name a low molecular weight heparin
Bempiparin
239
Compare using a low molecular and unfractionated heparin
LMWH require less monitoring (more predictable) as they only target factor 10 and so are less likely to cause thrombocytopenia
UFH needs to be IV bolus
LMWH is slower onset
240
Describe the pharmacokinetics of UF Heparins
Poorly GI absorbed, must be given via IV bolus or subcutaneously (they are negatively charged large molecules)
241
What does PPCI stand for?
Primary Percutaneous Coronary Intervention
242
Give 5 uses of Heparins
- AF
- DVT
- PE
Prior to Warfarin (faster)
Used in pregnancy as does not cross placenta
243
What is Factor 2?
Thrombin
244
Name 3 ADRs of Heparins
- Bleeding/bruising
- Hepatic and renal damage
- Thrombocytopenia
245
What is used to determine whether Warfarin should be given?
The patient's INR
246
How is Heparin reversal carried out?
Via Protamine Sulphate
247
How does Protamine Sulphate work?
Causes Anti-thrombin to dissociate from heparin
248
What is Fondaparinux and how does it work?
Inhibits Factor 10 and Thrombin
249
Describe the process of vomiting
```
CTZ in medulla receives signal to vomit
Nausea occurs
Retrograde peristalsis
Deep inspiration
Epiglottis closes
Abdominal muscles contract
LOS contracts
```
250
How can the CTZ be activated?
- Vestibular nuclei
- Gut stretching
- Drugs/toxins
251
Name 2 anti-emetic drugs that act on the Vestibular nuclei
- Hyoscine hydrobromide
| - Cyclizine/Promethazine (pregnancy)
252
Name 3 anti-emetic drugs that act on visceral afferents of the gut
- Ondansetron
- Metaclopromide
- Domperidone
253
Name 4 anti-emetic drugs that act on the CTZ
- Haloperidol
- Dexamethosone
- Aprepitant
254
Describe the MOA of Hyoscine hydrobromide
Antimuscarinic
| Blocks AcH in Vestibular nuclei of CTZ
255
Name a reason you would want to use Hysocine hydrobromide
Can be used as a patch
256
Describe the MOA of Cyclizine/Promethazine
Anti-histamines (H1)
| Blocks H1 in Vestibular nuclei of CTZ
257
Give a use of Promethazine
Morning sickness in pregnancy
258
Give 2 side-effects of anti-emetics of Vestibular nuclei
- Sedation
- Dry mouth
- Consitpation
259
Describe the MOA of Ondansetron
5HT antagonist
| Reduces GI motility, inhibits CTZ
260
Describe the MOA of Metaclopramide
D2 receptor antagonist
| Increases gastric emptying by increasing LOS tone and increases peristalsis
261
Describe the MOA of Domperidone
D2 receptor antagonist
| Can cause significant cardiac side effects
262
Describe the MOA of Haloperidol
D2 receptor antagonist
| Acts on CTZ
263
Describe the D2 receptor antagonist side-effects
- Sedation
| - Parkinsonism
264
Describe the MOA of Aprepitant
Neurokinin 1 antagonist
Inhibits CTZ
Side effects: Headache, diarrhoea
265
What drug would you choose for motion sickness?
Hyoscine hydrobromide
266
What drug would you give for GORD/paralytic ileus?
Domperidone/metaclopramide
267
What drug should be given to women in hyperemesis gravidarum - worse morning sickness due to b-HCG?
Promethazine + metaclopramide + ondansetron
268
How is diarrhoea treated?
Opioid receptor agonists
269
Name 2 opioid receptor agonists
- Loperamide
| - Codeine and morphine
270
Describe the MOA of Loperamide/Codeine
```
Acts on Micro receptors
Reduces peristalsis (reduced muscle tone)
```
271
Name 4 side-effects of opioid receptor agonists
Paralytic ileus, nausea and vomiting, sedation, addiction
272
Name 2 Osmotic laxatives
- Lactulose
| - Movicol
273
What is the MOA of Sodium Docusate
Increases intestinal mobility and softens stools
274
What should be given for constipation at different ages?
Child: Movicol/Sodium docusate
Adult: Movicol
275
Name 4 gastric acid drugs
- Ranitidine - H2 receptor antagonist
- Omeprazole - PPI
- Antacids
- Alginates
276
Describe the MOA of Omeprazole
Destroys active proton pumps - takes hours to have effect, so mainly for long term use
Will take 2-3 days after drug is stopped to recover
277
Name 2 ADRs of Omeprazole
- Diarrhoea
- Nausea and vomiting
- Osteoporosis risk
278
Where is arachidonic acid from in the diet?
Vegetable oils - Linoleic acid
279
Name the 2 COX isoforms and where they are found
COX-1 - constitutively active in most tissues
| COX-2 - inducible in inflamed tissues
280
What is COX-1 involved with in the body?
GI protection, platelet aggregation, renal blood flow, chronic pain and inflammation
281
What is COX-2 involved with in the body?
Tissue repair and healing, inhibition of platelet aggregation, fever, tumour cell growth
282
How do NSAIDs work?
Inhibit COX, preventing conversion of arachidonic acid to prostacyclins, such as prostaglandins and thromboxane
283
Describe how the effect of Aspirin changes with dose
At low dose - NSAID
| At high dose - anti-platelet - irreversible COX inhibitor
284
How do NSAIDs produce an analgesic effect?
- Local action at site of pain to reduce inflammation
| - Reduce PGE2 synthesis in dorsal horn, reducing neurotransmitter release in pain relay
285
How do NSAIDs produce an anti-inflammatory effect?
Reduce PGE2 synthesis during injury which usually lead to vasodilation and swelling
286
How do NSAIDs produce their anti-pyretic effects?
Inhibition of hypothalamic COX-2 where cytokine produced PG synthesis is elevated
287
What is the ending of drugs with lower side-effects profiles that inhibit COX-2 inhibitors?
coxib
288
Why are NSAIDs almost completely absorbed in the GI system?
They are slightly acidic
289
What happens at high doses of Aspirin?
Salicyclic acid, which is produced from aspirin, can conjugate with glycine to form a toxic compound
290
Name 5 NSAID GI ADRs
```
Dyspepsia
Nausea
Peptic ulceration
Bleeding
Perforation
```
291
Why do NSAIDs lead to GI ADRs?
- Reduce mucous and bicarbonate release
- Increase acid secretion
- Reduce mucosal blood floow
292
Name 3 Renal ADRs of NSAIDs
- Reduce GFR
- Reduced Renin secretion
Only problem in CKD/heart failure patients
293
Name a COX-2 inhibitor
Celecoxib
294
What is a potential effect of COX-2 inhibitors relative to anti-platelets?
Can cause platelet aggregation and oppose COX-1 inhibitors
295
Name 3 CVS ADRs of NSAIDs
- Increased salt and water retention, exacerbates HF and hypertension
- Vasoconstriction as ADH no longer inhibited by prostaglandins
- Increased risk of MI
296
Name 6 NSAID DDIs
DDIs with highly protein bound drugs - NSAIDs displace the drugs
- Sulphonylurea - hypoglycaemia
- Methotrexate - hepatotoxicity
- Warfarin - increased bleeding
297
Name 6 NSAID DDIs
DDIs with highly protein bound drugs - NSAIDs displace the drugs
- Sulphonylurea - hypoglycaemia
- Methotrexate - hepatotoxicity
- Warfarin - increased bleeding
298
Why should Aspirin not be given to under 12s?
Reyes syndrome
299
Which is more suitable for pregnant women? Paracetamol or NSAIDs?
Paracetamol
300
What is the product of paracetamol in the liver? What does it do? How is it treated?
NAPQI
Treated by acetylcystiene
Uses up glutathione
301
What does NAPQI lead to?
Nausea, vomiting, abdominal pain, liver damage, death
302
How does Acetylcysteine work?
Thiol donor, increases the level of glutathione
303
What do Nociceptors release in response to pain?
Substance P and Glutamate
304
How is pain modulated peripherally and centrally?
Peripherally: Substantia gelatinosa - reduces pain
Centrally: Peri-aqueductal grey - reduces pain in
305
How do Opioids work?
MOP/DOP/KOP receptors activated, cAMP decreased, less Substance P, less nociceptor activation
306
Name 2 strong opioid agonists
- Morphine
| - Fentanyl
307
Describe Morphine as a drug
Can be taken both orally and IV
Can affect baby
Affects MOP mainly
Does not cross BBB
308
Name 4 side-effects of Morphine
- Respiratory depression
- Emesis - triggers CTZ
- Constipation
- Asthma attack - causes release of histamine
309
Describe Fentanyl as a drug
```
IV
Highly protein bound, crosses CNS
6 minute half life
100x morphine potency
Safer than morphine as releases less histamine, shorter half life, sedates less
```
310
Name 3 side-effects of Fentanyl
- Respiratory depression
- Constipation
- Vomiting
311
What CYP is Fentanyl metabolised by?
CYP3A4
312
Describe Codeine as a drug
Oral
| Expression dependent on CYP2D6
313
What CYP is Codeine metabolised by?
CYP2D6
314
What does Buprenorphine do to opioid receptors?
Agonise and antagonise
315
Describe Buprenorphine as a drug
Metabolised by CYP3A4
| Excreted by biliary system, so safe in renal impairment
316
Compare Buprenorphine and its MOA to morphine
Higher affinity for MOP receptor, not easily displaced
Lower efficacy
Antagonises KOP
317
What is Naloxone?
Opioid antagonist
318
How must Naloxone be given?
IV, slow infusion, not bolus, as needs to antagonise morphine until it is removed from body
319
What is the treatment for the withdrawal of opioid addiction?
Methodone - opioid antagonist (full)
320
Define chemotherapy
The treatment of cancer with cytotoxic drugs
321
Describe the "Fractional Cell Kill Hypothesis"
Chemotherapy will kill all multiplying cells
Bone marrow cells will recover faster than cancer cells
Chemo must then be restarted again quickly
322
Name 3 sites of action of cytotoxic chemo agents
- Antimetabolites
- Alkylating agents
- Spindle poisons
323
Describe the MOA of alkylating agents and name one
Cisplatin
| Forms platinum bonds (adducts), breaks DNA, stops replication
324
Describe 3 mechanisms of resistance to alkylating agents
- Enhanced DNA repair mechanisms
- Efflux pumps
- Glutathione increase
325
Describe the MOA of Methotrexate
Antimetabolite
| Dihydrofolate reductase inhibitor
326
Describe the MOA of 5-fluorouracil
Antimetabolite
| Thymidylate synthase inhibitor
327
Describe the MOA of Taxanes/Vinca alkaloids
Spindle poisons
Prevent spindle formation in mitosis
Vincristine
328
Describe how chemotherapy is administered
Via an IV pump into a central line:
- Hickman line into SVC
- PICC line into arm - can be an outpatient
329
Why do the Central Lines travel under the skin first?
Macrophages in the skin can prevent infection
330
Name 6 side-effects of chemotherapy
- Acute renal failure - from lysis of cells
- GI perforation at site of tumour
- DIC
- Vomiting - drugs act on CTZ
- Alopecia
- Thrombophlebitis of veins
- Bose lines on nails
- Mucositis
- Lung fibrosis
331
What is a neoadjuvant?
Shrinks cancer before surgery
332
What is an adjuvant?
Given after surgery to reduce relapse risk
333
Name 3 Rheumatological conditions
- SLE
- RA
- Vasculitis
334
Name 8 Immunosuppressants
- Prednisolone
- Azathioprine
- Cyclosporin
- Mycophenolate mofetil
- Cyclophosphamide
- Methotrexate
- Sulfasalazine
- Rituximab
335
What is Prednisolone used for?
SLE, vasculitis, crohn's
336
What class of drug is Prednisolone?
Corticosteroid
337
What is the MOA of Prednisolone?
IL-1 and IL-6 inhibition from macrophages, inhibiting T-cell activation
338
Why do patients need to be taken off Prednisolone gradually?
Need to give adrenal glands time to resume their normal function
339
Name 2 side-effects of corticosteroids
Increase the progression of age-related diseases:
- Cataracts
- Osteoporosis
340
What does DMARD stand for?
Disease Modifying Anti Rheumatic Drug
341
What is the main use of Azothiaprine?
Steroid-sparing - cuts short the amount of time steroids need to be used
342
What needs to be assessed in patients before giving them Azothiaprine?
TPMT levels - individuals vary in levels (polymorphic)
TPMT metabolises Azothioprine
Low levels of TPMT lead to myelosuppression
Must check bone marrow during treatment
343
Describe the MOA of Azothioprine
Decreases DNA and RNA synthesis, reducing inflammation -> reduced amount of new inflammatory cells can be produced
344
Name the side-effects of all immunosuppressants
- Nausea and vomiting
- Bone marrow suppression
- Increased cancer risk
- Increased infection risk
- Hepatitis
345
Name a Calcineurin inhibitor
Cyclosporin
346
When is Cyclosporin used?
Transplantation, demratitis etc.
Not used in rheymatology due to renal toxicity
Inhibits cytochrome P450s
347
Describe the MOA of Calcineurin inhibitors
Prevent IL-2 production by Calcineurin inhibition, so not T-cells activated
348
Describe the effect of all 5 interleukins
```
Hot T-Bone Steak
1 - Hot - Fever
2 - T-cell activation
3 - Bone - bone marrow activation
4 - StE - IgE
5 - Ak - IgA
```
349
Describe the MOA of Mycophenolate Mofetil and when it is used
Primarily in transplantation
| Inhibits guanosine synthesis, impairing B and T cell proliferation
350
What is inductive and maintenance therapy?
```
Inductive = induce remission
Maintenance = maintain levels
```
351
Name 4 side-effects of Mycophenolate Mofetil
- Vomiting
- Nausea
- Diarrhoea
- Myelosuppression
352
Describe the MOA of Cyclophosphamide
Strong boi
| Alkylating agent - suppresses B and T cell activity
353
What is Cyclophosphamide used for?
Lymphoma
SLE
ANCA-vasculitis
354
What must Cyclophosphamide be given with and why?
Must be given with Mesna
| If not, can lead to hemorrhagic cystitis due to toxic metabolite
355
Name 3 ADRs of Cyclophosphamide
Toxicity
Bladder cancer risk
Infertility
- Mycophenolate mofetil is much safer for SLE, don't use this
356
What is Methotrexate used for?
```
Gold standard in RA
Also:
- Malignancy
- Psoriasis
- Crohn's
```
357
Describe the MOA of Methotrexate in malignancies
Dihydrofolate reductase inhibition
Used in thymidine synthesis from tetrahydrofolate - inhibits DNA and RNA synthesis
Greater effect in rapidly dividing cells
358
Describe the MOA of Methotrexate in RA
Inhibits Adenosine production
359
Name 3 side-effects of Methotrexate
- Mucositis
- Marrow suppression
- Teratogenic and abortion causing
360
What should Methotrexate never be given with?
NSAIDs - NSAIDs reducing bloodflow to Kidneys + methotrexate's toxicity to kidneys = RIP
361
Who should Methotrexate not be given to ideally?
Women of child-bearing age
| High infertility risk and teratogenic
362
Describe the MOA of Sulfasalazine
2 parts
Anti-inflammatory and anti-infection
Inhibits T-cells via IL-2 inhibition
Reduces Neutrophil function
363
Name 5 ADRs of Sulfasalazine
- Myelosuppression
- Hepatitis
- Nausea
- Vomiting
- Rash
But very safe in practice and SAFE IN PREGNANCY
364
What is the MOA of Rituximab?
Binds CD20 on B cells
365
What is the MOA of Infliximab?
Blocks TNF-alpha, reduces inflammation, reduces erosion of joints
366
Name a danger of giving someone a TNF-alpha inhibitor
Could cause TB reactivation, as TNF is essential for granuloma formation
367
Name two antibiotic types and give examples of each of antibiotics that target: Cell wall synthesis
Beta-Lactams - Penicillin
| Glycopeptides - Vancomycin
368
Name two antibiotic types and give examples of each of antibiotics that target: DNA synthesis
Quinolones - Ciprofloxin - interact with DNA gyrase
| Folic acid antagonists - Trimethoprim
369
Name two antibiotic types and give examples of each of antibiotics that target: Protein synthesis
Tetracyclines - Doxycycline
| Aminoglycosides - Gentamicin
370
What is an antibiotic breakpoint?
The MIC + pharmacokinetic properties of antibiotic are used to predict likely response of infection
371
What is the difference between a bacteriostatic and bactericidal agent?
```
Bacteriostatic = slows down growth
Bactericidal = will kill
```
372
Describe the two pharmacokinetic types of antibiotic killing
- Time-dependent
| - Concentration-dependent
373
Name 2 nephrotoxic antibiotics
- Vancomycin
| - Gentamicin
374
What is Co-amoxiclav?
Amoxicillin
| Clavulanic acid - B-lactamase inhibitor
375
Name a DDI of Metronidazole
Alcohol
376
Describe the pathogenicity of Influenza virus
Binds to Sialic acid receptor via Haemagluttinin
| Leaves via vesicle - Neuraminidase cleaves off and allows removal
377
Name 3 antiviral targets on influenza virus
- Haemagluttinin
- M2 ion channel
- Neuraminidase
378
Name an M2 channel blocker and what this does
Amantidine
| Inhibits viral uncoating
379
Name a Neuraminidase inhibitor
Ostelmavir
380
What class of virus is Varicella Zoster?
Herpes virus
381
Where does VZV lie dormant?
Dorsal root ganglion
382
Describe the difference between HSV 1 and HSV 2
HSV 1 - genital and oral ulceration
| HSV 2 - genital ulceration
383
What is the MOA of Acyclovir
Guanosine analogue, stops viral DNA synthesis
| Needs to be phosphorylated by a viral protein to activate first though, so this could be a method of resistance
384
Name another 2 antivirals
Valaciclovir
| Tamiflu (ostelmavir)
385
Name all 4 stages of Guedel's signs
1 - Analgesia and conscious, normal
2 - Unconscious, erratic, excitable, erratic breathing
3 - Surgical anaesthesia, patient relaxes
4 - Respiratory paralysis, death
386
What is the MAC of an anaesthetic?
Minimum alveolar concentration
| Potency (alveolar concentration) at which 50% of subjects fail to move to surgical stimulus
387
What determines MAC?
Age, pregnancy, alcoholism, weight, NO (increases MAC)
388
What receptor target do most anaesthetics target?
GABA
389
Name 2 regional anaesthetics
Lidocaine, bupivacaine
390
What is the MOA of Lidocaine?
Use-dependent Na channel blocker - blocks pain fibres
391
What is Asthma hypersensitivity driven by?
TH2
392
What are the pathophysiological effects of asthma?
```
Mucosal oedema
Bronchoconstriction
Mucus plugging
Airway remodelling
Bronchial hyperresponsiveness
```
393
What is the first step treatment for Asthma?
Short acting B2 agonist
Salbutamol, salmetreol, formoterol
Inhibits mast cell degranulation
394
What can happen if Salbutamol is used too much?
Can reverse airway control - increase mast cell degranulation
395
Name a selective COX-2 inhibitor
Celecoxib
396
What is the second step in the treatment of Asthma?
Inhaled corticosteroids
Prednisolone/Beclamethosone
Works better on people with eosinophilic asthma
397
What is the MOA of corticosteroids?
Inhibits transcription factors for pro-inflammatory proteins
398
How can steroid effectiveness be increased, biochemically?
Addition of a lipophillic side chain
399
What is the risk with using beclamethosone in COPD patients?
Immunosuppressive
400
What is the third step in the treatment of Asthma?
Long-acting B2 agonist
Formoteral, Salmeterol
Can add in a LABA if not steroid controlled too
401
Why should NSAIDs not be given during labour?
- Delays labour
- Increases bleeding
- Prematurely closes Ductus arteriosus - foetal blood supply compromised
402
Name 4 alternative step-three Asthma treatments
```
Leukotriene receptor antaognist - Montelukast
Methylxanthine - Theophylline
LAMAs
- Tiotropium bromide
- Ipratropium bromide
```
403
Why is acetylcysteiene used in paracetamol toxicity rather than just glutathione?
Acetylcysteiene can enter the liver hepatocytes, while glutathione cannot
404
Describe the MOA of Montelukast
Leukotriene receptor antagonist
| Prevents mast cells from releasing leukotrienes, which cause bronchoconstriction
405
Name 3 side-effects of Montelukast
- Angioedema
- Dry mouth
- Fever
406
What is the MOA of Theophylline and what is it used in?
Adenosine antagonist - increased cAMP and PDE inhibitor
| Used in severe COPD/Asthma
407
Describe the MOA of LAMAs?
M3 inhibitor - stops constriction
Long-acting
In COPD and Asthma
408
Name 3 side-effects of LAMAs
Dry mouth, urinary retention, glaucoma
409
Name the treatment steps for acute severe asthma
1. Oxygen
2. Nebulised salbutamol
3. Oral prednisolone
4. Can then give nebulised ipratroprium bromide
410
What should Ipratroprium bromide be given with in life threatening Asthma?
Oxygen, as want to oxygenise the blood as much as possible
411
What should Ipratroprium bromide be given with in life threatening COPD?
Air - want to prevent shutting off of breathing due to hypoxic drive
412
Why are LAMAs not useful first line therapy in asthma but useful in COPD?
Bronchoconstriction in asthma due to B2 receptors
| In COPD is due to muscarinic receptors
413
Define a seizure
Sudden irregular electrical activity in the brain causing physical mnaifestations
414
Define convulsions
Uncontrolled shaking movements due to repeated muscle contraction
415
Define status epilepticus
Epileptic seizures occurring without recovery of consciousness in between - emergency
416
Name the two overall classifications of seizures
Partial
| Generalised
417
Define a partial simple seizure
Seizure of a part of the brain
| No loss of consciousness
418
Define a complex partial seizure
Seizure of a part of the brain
| No loss of consciousness
419
What is the first line treatment for partial seizures
Carbamazepine
420
Name 5 types of generalised seizures and give a short description of each
```
Tonic: Increased tone
Atonic: Without tone - drop attack
Tonic-clonic: muscles tense, then conulsions happen
Absence: stop-mid sentence
Myoclonic: shock-like muscle jerking
```
421
What could give a false-positive EEG result for a seizure?
Syncope
422
What other investigations should be carried out on someone who is suspected of having a seizure?
ECG - arryhthmias
| MRI
423
Name 4 classes of drugs for epilepsy
Na channel blockers
GABA potentiators
Ca channel blockers
Levitiracetam
424
Name 3 Na channel blockers used in epilsepsy and describe their MOA
- Lamotrigene
- Sodium valproate
- Carbamazepine
425
Name 4 side-effects of Na channel blockers
Affects cerebellum and brainstem:
- Bradycardia
- Dysdiadokokinisea
- Ataxic gait
- Nystagmus
426
Name a Ca channel blocker used in epilepsy and what it is used for
Ethosuximide
(sodium valproate)
Absence seizures
427
Name 3 GABA potentiators and their type
GABA-transaminase inhibitor - Vigabatrin
Gabapentin - increases GABA production
Diazepam - Benzodiazepines - only used to stop seizures
428
Describe the MOA for Levetiracetam
Inhibits pre-synaptic ca channel activity
429
How are anti-epileptics prescribed?
Monotherapy only
430
What is the first line for generalised/tonic-clonic seizures?
Sodium valproate or Lamotrigene
| Second line: Levetiracetam
431
What is Phenytoin?
A sodium channel blocker - anti-convulsant
Used for status epilepticus
Has a small therapeutic window
432
Name a liver enzyme inhibitor
Sodium valproate
433
Name a liver enzyme inducer
Carbamazepine
434
Name 4 side-effects of all anti-epileptic drugs
Dizziness
Fatigue
Ataxia
Diplopia
435
Why is Sodium Valproate a teratogenic drug?
Reduces folate, leading to neural tube defects
436
What is the initial management of a general seizure?
Lorazepam
| Midazolam if they are a child or don't have IV access
437
What is the treatment for status epilepticus
Lorazepam
| If more than 20 mins, give Phenytoin
438
Name 4 clinical features of Parkinson's
- Tremor - "pill-rolling"
- Rigidity - lead pipe, cog-wheeling
- Bradykinesia
- Bradyphonia
- Micrographia
439
What is Dopamine degraded by?
COMT
| Monoamine oxidase
440
Why is L-dopa given rather than dopamine?
Can cross BBB
441
Describe the process of L-dopa being given to a patient and what happens to it in the body
Given orally
Absorbed by active transport - competes with amino acids
90% inactivated in abdominal wall by MAO and COMT
9% converted to dopamine in peripheral tissues by DOPA decarboxylase
442
What must L-dopa not be taken with? (2)
Protein foods
| Pyridoxine - increases peripheral breakdown
443
What must L-dopa be given with?
With a DOPA decarboxylase inhibitor and a COMT inhibitor
444
Give an example of a L-dopa mix
Co-careldopa
| Co-beneldopa
445
Name 4 side-effects of L-dopa
Nausea
Hypotension
Psychosis
Tachycardia
446
Name 3 dopamine receptor agonists
Ropinirole
Rotigotine
Apomorphine
447
What is a major side-effect of dopamine receptor agonists?
Dopamine dysregulation syndrome
- Gambling
- Hypersexuality
448
Name 4 side-effects of dopamine receptor agonists
- Sedation
- Hallucinations
- Confusion
- Nausea
- Hypotension
449
Name 2 Monoamine Oxidase B inhibitors
Selegiline
| Rasagaline
450
Name 1 COMT inhibitor
Entacapone
451
What is important to note about COMT inhibitors?
Do not work without L-dopa, just reduce peripheral breakdown of L-dopa - reduces symptoms of "wearing off"
452
What drugs affecting neuromuscular transmission exacerbate Myasthenia Gravis?
B-blockers
ACE inhibitors
Aminiglycosides (gentamicin)
Chloroquine
453
Name the complications of not treating and over-treating myasthenia gravis
Not treating: Acute exacerbation (myasthenic crisis)
| Overtreatment: cholinergic crisis
454
Name the treatment for Myasthenia Gravis
Pyridostigmine - AcHesterase inhibitor
455
What are the side-effects of Pyridostigmine?
SLUDGE
456
What can Pyridostigmine not be given with?
Hypertension medications, as can lead to bradycardia
457
What can be given to a patient before giving them cyclophosphamide to prevent haemorrhagic cystitis?
MESNA
