Pharmacology Flashcards
(273 cards)
1
Q
B1-adrenoceptor couples to the g-protein….
A
Gs
2
Q
The sympathetic nervous system releases noradrenaline as a __________ _____________ and adrenaline as a ___________ ___________
A
Post-ganglionic transmitter
Adrenomedullary hormone
3
Q
B1-adrenoceptors are activated in which locations? (2)
A
Nodal cells
Myocardial cells
4
Q
Activations of b1-adrecopteors NASA positive/negative chronotropic force
A
Positive
5
Q
Chronotropic is an increase in
A
Rate
6
Q
Ionotropic is…
A
Force
7
Q
Increase in heart rate in presence of noradrenaline is due to what?
A
Increase in slope of phase 4 of action potential
Reduction in threshold for AP initiation due to enhanced Ica
8
Q
Increase in contractility in the presence of noradrenaline is due to?
A
Increased in phase 2 of AP
Sensitisation of contractile proteins to calcium
9
Q
The duration of systole is ______in the presence of noradrenaline
A
Decreased - this is a positive lusitropic reaction
10
Q
Noradrenaline causes a ______ in the efficiency of the heart muscle
A
Decrease - heart starts to use oxygen less efficiently
11
Q
Effect of noradrenaline on the Na-K-ATPase
A
Increases activity which is important for the normal balance of ions across the membrane
12
Q
Parasympathetic system releases ___ to the cardiac muscle
A
ACh
13
Q
In the heart, ACh acts on ____ muscarinic cholinoceptors largely in the ______ cells
A
M2
Nodal
14
Q
The M2 receptor couples to the ____ g-protein
A
Gi
15
Q
Coupling through Gi decreases the activity of ______ _______ thus reducing _______. The ________ potassium channel is opened causing a hyperpolarisation mediated by _________
A
Adenylate cyclase, cAMP.
GIRK, G-by subunits
16
Q
Parasympathetic action of the cardiac muscle is…. (3)
A
Decreased chronotropic effect
Slight decrease in contractility
Decreased conduction in AV node
17
Q
Why does the parasympathetic stimulation of the heart have little/no effect on ventricular contractility?
A
There is no parasympathetic stimulation on the ventricles
18
Q
Parasympathetic stimulation of the heart may cause ….
A
Arrhythmias to occur in the atria
19
Q
Vagal manoeuvres can can be used to…
A
Suppress atrial tachycardia
20
Q
The funny current is mediated by channels that are activated by….(2)
A
hyperpolarisation and cAMP
21
Q
other name for funny current channels
A
HCN
22
Q
Blocking HCN channels causes what?
A
decrease of slope of pacemaker potential and reduces HR
23
Q
Drug used to block HCN channels
A
Ivabradine
24
Q
Ivabradine
A
Selectively blocks HCN Channels - slows HR in angina and reduces cardiac O2 consumption
25
cAMP is converted to 5'AMP by ...
PDE - phosphodiesterase
26
Inhibition of PDE has a positive/negative inotropic
positive
27
Drug which inhibit PDE in acute heart failure
milrinone
28
Catecholamines that act as b-adrenoceptor agonists (3)
dobutamine, adrenaline, noradrenaline
29
Actions of b-adrenoceptor agonists
increase rate, force and CO and O2 consumption
30
Medical situations for use of adrenaline
Cardiac arrest; anaphylactic shock
31
Dobutamine is used in what medical situation?
acute but potentially reversible Heart Failure
32
Adrenaline is administered...
IC, IM, SC or IV infusion
33
Dobutamine is administered...
as an IV infusion
34
Advantage of dobutamine
causes less tachycardia than other b1 agonists
35
Examples of b-adrenoceptor antagonists
Propanolol, atenolol, bisoprolol, metoprolol
36
non-selective and partial agonist b-adrenoceptor drug
alprenolol
37
Effects of b-blockers at rest
little effect
38
Effect of b-blockers during exercise
cardiac stress, rate, force, CO are significantly reduced
39
Disadvantage of b-blockers during exercise
can reduce maximal exercise tolerance
40
Use of b-blockers in medical situations (4)
Disturbance of cardiac rhythm; treatment of angina; treatment of HF; treatment of HBP
41
How do b-blockers act in A-fib and SVT
delay conduction through the AV node
42
Use of b-blockers in angina
Alternative to calcium entry blockers
43
Treatment of HF with b-blockers
must be low-dose to prevent cardiac death
44
Another suggested drug in HF
carvedilol
45
Carvedilol is...
a1 - antagonist, b-blocker
46
Adverse effects of b-blockers (6)
Bronchospasm; Aggravation of HF; Bradycardia/Heart Block; Hypoglycaemia; Fatigue; Cold extremities
47
What is atropine?
Non-selective muscarinic ACh receptor antagonist
48
When is atropine used first line?
In severe or symptomatic bradycardia, particularly following MI. Also used in anticholinesterase poisoning
49
What type of drug is digoxin?
cardiac glycoside
50
What does digoxin bind?
a-subunit of Na-K ATPase
51
What is the end effect of digoxin binding the Na-K ATPase?
Increases the Calcium in the cell and thus the calcium uptake into the sarcoplasmic reticulum and increase CICR
52
Where should digoxin be used with caution?
In those with hypokalaemia or on diuretics
53
Half life of digoxin
40 hours
54
Digoxin is a chronotropic agent - True or False?
False - it is an inotropic agent - it increases contractility by increasing calcium available for CICR
55
Direct effects of digoxin on the heart (2)
shortens the AP and refractory period.
56
Indirect effects of digoxin on the heart
- increased vagal activity
- slows SAN discharge
- increased refractory period
57
Adverse effects of digoxin on the heart? (2)
excessive depression of AV node conduction - heart block
| Propensity to cause arrhythmias
58
Non-cardiac adverse effects of digoxin (4)
nausea
vomiting
diarrhoea
disturbance of colour vision
59
Calcium sensitiser
Levosimendan
60
Mechanism of action of levosimendan
binds to troponin C and increases sensitivity to calcium
61
where is levosimendan used?
in acute decompensated heart failure
62
Amrinone and Milrinone act to...
inhibit PDE in cardiac and smooth muscle cells and hence increase cAMP
63
Why is it suspected that amrinone and milrinone decrease survival?
Increase arrhythmias
64
Where are amrinone and milrinone used?
limited to acute heart failure
65
Which molecule is important in the activation of PKG to cause VSM relaxation?
cGMP
66
___ stimulates the production of cGMP
Nitric Oxide - NO
67
Substances that activate the production of NO (3)
bradykinin, ADP, 5-HT
68
3 effects of organic nitrates
Venorelaxation; arteriolar dilation; increased coronary blood flow
69
When are organic nitrates used?
in stable angina and ACS
70
Benefits in angina from using GTNs (3)
decreased preload, decreased afterload and improved perfusion
71
common organic nitrates used
GTN
| isosorbide mononitrate
72
longer acting organic nitrate
isosorbide mononitrate
73
GTN sprays do not undergo first pass metabolism - true or false?
false - they undergo first pass metabolism, ISMN does not undergo first pass metabolism
74
Drug used orally for prophylaxis of angina
ISMN
75
Adverse effects of organic nitrates
postural hypotension;
| headaches; formation of methaemoglobin; tolerance
76
Molecules that stimulate endothelin production
Adrenaline
AngII
ADH
77
situations where renin is released (3)
decreased renal perfusion pressure; increased renal sympathetic activity; decreased glomerular filtration
78
where is angiotensinogen produced?
liver
79
The AT1 receptor causes smooth muscle relaxation - true or false
false - it causes smooth muscle contraction
80
the RAAS overall contributes to a(n) _______ in MABP and blood volume
increase
81
Where does aldosterone originate?
the zona glomerulosa of the adrenal cortex
82
Aldosterone causes the tubular _______ of Na
reabsorption
83
Aldosterona production leads to a(n) _______ in blood volume and MABP
increase
84
Example of an ACE inhibitor
lisonopril
85
ACE converts AngI to AngII - true or false
true
86
example of an AT1 receptor blocker
losartan
87
ACE acts to ... (2)
inactivate bradykinin
| convert AngI to AngII
88
ACE inhibitors have an effect on cardiac contractility - true or false?
false - the mechanism of action means that ACEIs will cause venodilation and vasodilation - this reduces the strain on the heart but does not affect the heart contractility
89
Where is the greatest effects of ACEIs?
Brain, kidneys, heart
90
Main adverse effects of ACEIs
hypotension
| dry cough
91
ARBs are useful in patients who...
find the ACEIs dry cough intolerable
92
ACEIs and ARBS are contraindicated in which two groups?
Pregnancy
| Bilateral renal artery stenosis
93
3 clinical uses of ACEIs and ARBs
Hypertension
Cardiac Failure
Following MI
94
a1-adrenoceptors act to...
constrict vascular smooth muscle
95
b1-adrenoceptors act to...
increased cardiac rate, force and AV node conduction velocity
96
b2-adrenoceptors act to...
relaxes bronchial and vascular smooth muscle
97
b1- adrenoceptor antagonists can be used in the treatment of (3)
Angina pectors; hypertension; heart failure
98
action of b-blockers in angina pectoris?
decreases O2 requirements; counter-elevated sympathetic activity; increase the amount of time spent in diastole
99
Action of b-blockers in hypertension?
reduce CO; reduce renin release from kidney; a CNS action that reduces sympathetic outflow
100
Arrhythmias can be formed from defects in which two ways?
defects in impulse conduction or impulse formation
101
Types of defects in impulse formation (2)
Altered Automaticity
| Triggered Activity
102
Pathological reasons for altered automaticity
SAN firing frequency is pathologically low (escape beats); latent pacemaker fires faster than the SAN (ectopic beats)
103
Causes of ectopic rhythms
ischaemia, hypokalaemia, increased sympathetic activity
104
Triggered Activity can be either of...?
EAD
| DAD
105
Where do EADs come from?
```
Phase 2 (Ca) and Phase 3 (Na);
associated with prolonged AP and drugs prolonging the QT interval
```
106
Where do DADs appear?
after complete repolarisation
107
Where do EADs appear?
during the inciting AP
108
What is DAD associated with?
Ca overload provoked by catecholamines, digoxin, heart failure
109
What are the 3 defects in impulse conduction?
Re-entry; conduction block; Accessory tract pathways
110
What are re-entry arrhythmias?
self-sustaining electrical circuit where action potentials can create a self-sustaining loop
111
Types of partial block?
Mobitz type I
| Mobitz type II
112
Mobitz type I conduction block
PR interval gradually increases from cycle to cycle until a beat is missed
113
Mobitz type II conduction block
PR interval is constant but every n-th beat is mossed
114
Complete block is...
when the atria and ventricles beat independently
115
Example accessory tract
Bundle of Kent
116
What do accessory tracts predispose patients to?
tachyarrhythmias
117
Class I agents are what?
Sodium channel blockers
118
Class II agents are what?
b-adrenoceptor antagonists
119
Class III act on?
Voltage gated K+ channels
120
Class IV agents act on?
Calcium channel
121
How do Class I agents work?
they act on the SAN in a use dependent manner; there are varying degrees of block from short acting to long acting
122
Action of adenosine?
activates A1-adenosine receptors coupled to Gi/o - opens ACh sensitive K channels
123
When is Adenosine used?
to terminate paroxysmal SVT - atrial firing of 140-250bpm
124
Action of Digoxin?
stimulates vagal activity; slows conduction and prolongs refractory period in AV node
125
What is digoxin used to treat?
used to treat AF
126
What is the action of Verapamil?
type IV agents - blocks LTCC; slows conduction and prolongs refractory period in AV node and bundle of His
127
When is verapamil used to treat?
Atrial flutter, AF
128
Two types of diuretics
Loop and thiazide
129
Action of thiazide diuretics
block the reabsorption of sodium and chlorine in the distal convoluted tubule
130
Action of loop diuretics
block the Na-K-Cl symporter in the ascending loop of henle
131
Potential side effect with Loop diuretics?
hypokaleamia
132
Because of the side effects of loop diuretics, which drug should they be used with caution with?
Digoxin
133
Diuretics are used in which conditions?
hypertension and heart failure
134
Example of a thiazide diuretic
Bendrofluazide
135
Example of a loop diuretic
Furosemide
136
General side effects of diuretics
hypokalaemia, tiredness, arrhythmias, hyperglycaemia in diabetics, gout, impotence
137
Where are cardioselective beta-blockers used?
angina, hypertension, heart failure
138
Effect of b-blockers on the heart?
increased rate, contractility and decreased O2 efficiency
139
Example of cardioselective b-blockers
atenolol, metoprolol, bisoprolol
140
Side effects of b-blockers in general
tired, bronchospasm, heart failure, cold peripheries,
141
Two main groups of calcium antagonists
dihydropyridines; rate limiting calcium antagonists
142
Action of dihydropyridine CCBs?
L-type CC blockers which are more vascular in their action
143
Where are dihydropyridines preferentially used?
in hypertension and angina
144
Side effect of dihydropyridines?
innocent ankle oedema
145
Example of dihydropyridine CCB
amlodipine
146
Where are rate limiting CCBs used?
angina, hypertension and supraventricular arrhythmias
147
Where are rate limiting CCBs more selective for?
myocardium
148
Why should rate limiting CCBs be avoided with b-blockers?
they cause a degree of heart block which would cause bradycardia when combined
149
Examples of rate limiting CCBs?
verapamil, diltiazem
150
a-adrenoceptor antagonists cause what?
vasodilation
151
Example of an a-adrenoceptor antagonist
doxazosin
152
Action of ACE inhibitors
blocks conversion of Ang I to Ang II thus preventing vasoconstriction
153
Indications for the use of ACEIs
hypertension, heart failure, diabetic nephropathy (hypertension)
154
Contraindications for ACEIs
renal artery stenosis
155
Examples of ACEIs
lisinopril, Ramipril
156
Side effects of ACEIs
cough, renal dysfunction, angioedema
157
Why should ACEIs never be used in pregnancy?
causes foetal kidney abnormalities
158
Alternative to ACEIs if they are not tolerated?
Angiotensin receptor blockers
159
Example of ARB
Losartan
160
Action of nitrates?
venodilators and nitric oxide donors
161
When are nitrates used?
in angina, acute HF and MI
162
Main side effects of nitrates?
headache and hypotension, tolerance is also an issue
163
Examples of nitrates?
Isosorbide mononitrate, glyceryl trinitrate
164
Action of anti-platelets?
prevent new thrombosis
165
Indications for use of anti-platelets?
angina, MI, cerebrovascular attacks, TIA
166
Examples of anti-platelets
aspirin, clopidegrel, ticagrlor, prasugrel
167
Main side-effects of anti-platelets
haemorrhage, peptic ulcer haemorrhage, aspirin sensitivity in asthma
168
Actions of anti-coagulants
prevent new thrombosis
169
Examples of anticoagulants
heparin (IV only); Warfarin (oral only); Rivaroxaban; Dabigatran
170
Warfarin blocks which clotting factors?
2,5,7,9,10
171
When is warfarin used?
DVT, PE, NSTEMI, AF
172
Risks of using warfarin?
haemorrhage - needs careful INR monitoring
173
How can warfarin be reversed?
Vitamin K
174
Action of rivaroxaban?
inhibits factor X
175
Action of dabigatran?
thrombin factor IIa inhibitor
176
Action of fibrinolytics
dissolve formed clots but not liked due to risk of haemorrhage
177
Where are fibrinolytics used?
STEMI, PE and CVA in selected cases
178
Examples of fibrinolytics
Streptokinase, tissue plasminogen activator
179
Anti-cholesterol agents?
Statins
| Fibrates
180
Action of statins
block HMG CoA reductase
181
Where are statins used?
hypercholesterolaemia, diabetes, angina, MI, CVA, TIA, high risk of MI or CVA
182
Example of statin
simvastatin
183
Side effects of statins?
muscle pain, myopathy, rhabdomyolysis
184
Indications for fibrates?
hypertriglyceridaemia, low HDL
185
Example of a fibrate
benzofibrate
186
Drug used in supraventricular arrhythmias
adenosine
187
Drugs used in SV arrhythmias and ventricular arrhythmias
amiodarone, beta-blockers, flecainide
188
side effects of amiodarone
phototoxicity, pulmonary fibrosis, thyroid abnormalities
189
Two actions of digoxin
blocks AV node conduction, increases ventricular irritability
190
What is digoxin useful for treating?
atrial fibrillation
191
Side effects of digoxin?
nausea, vomiting, yellow vision, bradycardia, heart block, ventricular arrhythmias
192
vascular wall damage exposes (2)
collagen and tissue factor
193
primary haemostasis causes what 3 things?
local vasoconstriction, platelet adhesion and acitvation, stabilised soft plug
194
Fibrinogen is converted to fibrin by?
thrombin
195
activated platelets secrete thromboxane A2 mediated by which enzyme?
COX 1
196
Exposed collagen binds the platelet __ ______ _____ to which glycoprotein __ receptors also bind
von willibrand factor, Ib
197
Fibrinogen is converted to fibrin by?
thrombin
198
vascular wall damage exposes (2)
collagen and tissue factor
199
activated platelets secrete ___ which is mediated by the COX 1 enzyme
thromboxane A2
200
Exposed collagen binds the platelet __ ______ _____ to which glycoprotein __ receptors also bind
von willibrand factor, Ib
201
thrombin is also known as factor__
II
202
cells bearing tissue factor are exposed to factor ___ from the plasma to form a complex ____
VIIa, VIIa:TF
203
The TF:VIIa complex activates factor __
X
204
Factor X works with factor _ to activate prothrombin to thrombin (factor II)
factor V, implicated in factor V leiden thrombophilia
205
Factor II activates further platelets and causes the release of ______ _ from platelet granules
factor V
206
Factor II liberates factor ___ from von willebrand factor
factor VIII - normally bound to vWF
207
Factor XI or TF:VII activate factor
IX
208
factor IX forms a complex with factor ___ which powerfully activates factor II
VIII
209
Factor VIII activated by thrombin cross-links the fibrin polymer to...
form a fibrin fibre network and a solid clot
210
What is a thrombosis?
a haematological plug in the absence of bleeding
211
Chances of thrombosis are increased in...
virchows triad
212
Virchows triad consists of?
injury to vessel wall (atheromatous plaque rupture), abnormal blood flow, increased coagulability of the blood
213
An arterial thrombus is also known as a (white/red) thrombus
white
214
Why is an arterial thrombus white?
many platelets in a fibrin mesh
215
Where is an arterial embolus likely to travel?
artery of brain or other organs depending on site of origin
216
A venous thrombus is also known as a (white/red) thrombus
red
217
Where is a venous embolus likely to travel?
the lung (PE)
218
How are arterial thrombi usually treated?
anti-platelets
219
How are venous thrombi usually treated?
anti-coagulants
220
anti-platelets are used to treat which type of thrombus?
arterial
221
anti-coagulants are used to treat which type of thrombus?
venous
222
A venous thrombus is also known as a (white/red) thrombus
Red
223
An arterial thrombus is also known as a (white/red) thrombus
white
224
A venous thrombus is rich in...
fibrin
225
Warfarin blocks the modification of which 2 factors?
X and II
226
Rivaroxaban inhibits which factor within prothrombinase
Xa
227
prothrombinase is made up of which two factors
Xa/Va
228
Heparin, LMWH and fondaparinux inactivate factor Xa via...
antithrombin III
229
antithrombin III inactivates...
factor Xa
230
Heparin inactivates factor __a via....
IIa via antithrombin III
231
Dabigatran directly inhibits
IIa
232
Heparin inactivates factor __a via....
IIa via antithrombin III
233
Heparin, LMWH and fondaparinux inactivate factor Xa via...
antithrombin III
234
prothrombinase is made up of which two factors
Xa/Va
235
antithrombin III inactivates...
factor Xa
236
Rivaroxaban inhibits which factor within prothrombinase
Factor Xa
237
factors dependent on vitamin K
II, VII, IX and X
238
warfarin blocks what enzyme essential in recycling vitamin K
vitamin K reductase
239
II, VII, IX and X are all factors dependent on...
vitamin K
240
vitamin K reductase is inhibited by
warfarin
241
anticoagulants can be used to prevent and treat:
DVT, post-operative thrombosis, in artificial heart valves, atrial fibrillation
242
Warfarin is an...
anti-coagulant
243
The effects of warfarin should be monitored using...
the international normalised ration - prothrombin time
244
plasma half-life of warfarin
40 hours
245
Factors potentiating the effects of warfarin
Liver disease, high metabolic rate, drug interactions (inhibition of platelets)
246
Factors lessing warfarin action
pregnancy, hypothyroidism, vitamin K consumption, drug interactions
247
To inhibit factor IIa, heparin needs to bind?
Antithrombin III and IIa
248
to inhibit factor Xa, heparin needs to bind?
just antithrombin III
249
Examples of LMWHs
Exoaparin, Dalteparin
250
LMWHs are administered...
subcutaneously
251
fondaparinux is...
chemically related to the LMWHs
252
Advantage of elimination of LMWHs
first order rather than zero order
253
Heparin is preferred over LMWHs in which situation?
renal failure
254
Adverse effects of Heparin and LMWHs
Haemorrhage, osteoporosis, hypoaldosteronism, hypersensitivity reactions
255
dabigatran, and rivaroxaban are administered
orally
256
Advantages to dabigatran and rivaroxaban are?
they have a predictable level of anti-coagulation and a convenient administration route
257
Clopidogrel blocks ADP P2Y receptor irreversibly
Clopidogrel blocks ADP P2Y receptor irreversibly
258
Clopidogrel blocks _____receptor irreversibly
Clopidogrel blocks ADP P2Y receptor irreversibly
259
Aspirin blocks _____ irreversibly
COX -1
260
Tirofiban blocks GPIIb/IIa receptor whose expression is increased by ADP and TXA2
Tirofiban blocks GPIIb/IIa receptor whose expression is increased by ADP and TXA2
261
Tirofiban is given IV in short term treatment to prevent MI in high risk patients with unstable angina
Tirofiban is given IV in short term treatment to prevent MI in high risk patients with unstable angina
262
Anti-platelet drugs are used in what type of thrombus
arterial
263
Examples of the main anti-platelets
aspirin, clopidogrel, tirogiban
264
Clopidogrel is given when...
patients are intolerant to aspirin
265
Fibrinolytics are used...
to reopen occluded arteries in MI or stroke
266
Examples of fibrinolytics
Streptokinase, alteplase, duteplase
267
Fibrinolytics act to activate...
plasminogen
268
Streptokinase is not...
an enzyme
269
Streptokinase shouldnt be given in patients with a recent
streptococcal infection
270
Ateplase and Duteplase are...
recombinant tissue plasminogen tissue activator
271
Alteplase and duteplase advantages...
less allergic reactions, more selective for clots
272
haemorrhage due to fibrinolytics can be controlled by...
oral tranexamic acid
273
tranexamic acid inhibits
plasminogen activation
