Pharmacology Flashcards
1
Q
what are the regulatory influences on the action potential of the nodal tissue of the heart
A
autonomic input (para and symp), stretch, temp, hypoxia, blood pH, thyroid hormones
2
Q
what phase is the upstroke of the action potential in nodal tissue and describe it
A
phase 0, increased ICal (long calcium current)
3
Q
what phases are missing from the action potential of nodal tissue that are present in cardiac myocytes
A
phases 1 and 2
4
Q
describe phase 3 of the action potential in nodal tissue
A
downstroke of AP, repolarisation, increased Ik (delayed rectifier potassium current) (outward)
5
Q
describe phase 4 of the action potential in nodal tissue
A
pacemaker potential; Ib (background sodium channel (inward)), increase If (funny channel), ICaL (long calcium current (inward)) and decreased IK (delayed rectifier potassium current outward)
Ib, ^IF, ICal, -Ik
6
Q
what is funny current (If)
A
mediated by hyperpolarisation-activated and cyclic neucleotide gated (HCN) channels that conduct Na+ and K+ (inward)
7
Q
what determines the upstroke of the action potential
A
opening of voltage gated calcium channels (L-type channels)
8
Q
why are they called calcium long channels
A
as produce a long calcium current by staying open for a long period of time
9
Q
during phase 0 what is the inward movement is calcium being opposed by
A
outward movement of positive charge (hyperpolarisation) via back currents and V activated potassium channels (slow to open) why mem potential only reaches +10mV
10
Q
what causes the down stroke of a membrane potential in nodal tissue
A
opening of V activated potassium channels (delayed rectifier)
11
Q
how do potassium channels cause repolarisation
A
as move positive charged potassium ions out of cell making inside membrane potential negative
12
Q
what state are the calcium channel in during repolarisation of AP in nodal tissue
A
inactivated
13
Q
what give rise to the pacemaker potential
A
net movement of pos charge into the cell by different types of ion channel (e.g. sodium selective channels background)
14
Q
what is the role of the transient calcium channel ICaT
A
opens very briefly during pacemaker potential to give final kick to reach threshold and initiate opening of L type channels
15
Q
when do Ik channels open
A
during downstroke of AP
16
Q
when are Ik channels closed
A
during pacemaker potential to speed up depolarisation
17
Q
what activates funny channels
A
neg mem potentials (v neg= hyperpolarisation)
18
Q
what current is active during phase 1 of myocyte AP
A
Ito- transient outward potassium current
19
Q
what current is active during phase 0 of myocyte AP
A
sodium current (inward)
20
Q
what is phase 4 of myocyte AP
A
diastolic potential, resting potential, steady
21
Q
what is phase 4 in normal tissue similar to
A
pacemaker potential
22
Q
what maintains the steadiness diastolic potential
A
potassium’s ability to move out of the cell and maintain potential
23
Q
what opens V activated sodium channels in cardiac myocyte AP
A
AP form SA node at ventricular muscle
24
Q
what is the upstroke of the AP in cardiac myocytes regulated by
A
sodium channels
25
what upstroke AP's do calcium channels mediate
normal and PM
26
is the upstroke of a cardiac myocyte or PM quicker
cardiac myocyte
27
what stops the depolarised membrane potential from reaching +100mV
competing conductance
28
describe phase 1 of a cardiac myocyte AP
brief stage of repolarisation caused by transient outward current due to potassium channel that opens very briefly
29
what is Ik1 current
inward rectifier potassium current
30
what happens to calcium channels during the upstroke of a cardiac myocyte AP
opened- slightly delayed, opened for long period of time
31
what currents are present during the plateau phase
ICal (increased) and INal
32
why does the membrane potential not change greatly during the plateau phase
a calcium ions are moving out of the cell
33
what enters muscle cells to dribe contraction
calcium
34
can another action potential be fired during the plateau phase, why
no, because of v activated sodium channels being activated (only conduct or a millisecond but long plateau period permits calcium entry over a long period of time)
35
what provides small current to the plateau but could also disrupt rhythm of the heart
late sodium current INaL
36
in phase three what are the two currents that activate and reduce membrane potential to the resting pot of -90mV
Ik and Ik1
37
what direction is sodium channelled
inward
38
what direction is potassium channelled... except in?
outward, funny channel
39
what direction is calcium channelled
inward
40
what is noradrenaline
post-ganglionic transmitter
41
what is adrenaline
adrenomedullary hormone
42
what do adrenaline and noradrenaline activate
B1 adrenoceptors in nodal and myocardial cells
43
what does the activation of B1 adrenoceptors by the sympathetic system activate and via what mechanism
activates adenylyl cyclase in increase cAMP concentration. By coupling through Gs protein
44
what mechanisms cause the positive chronotropic effect of sympathetic stimulation in terms of the pacemaker potential
increase in slope of pacemaker potential caused by enhanced If and ICa
45
changes in what current cause a decrease in the AP threshold
increased ICa
46
generally which beta receptors are present where in the body
beta 1 heart, beta 2 airways
47
what are increases in heart rate mediated by
action on SA node
48
what is a positive inotropic effect
increased contractility
49
changes in what part of the cardiac action potential in atrial and ventricular myocytes cause increased contractility
increase in phase 2
50
changes in which current cause increase contractility
enhanced Ca2+ influx
51
sensitisation of what to what causes increased contractility
sensitisation of contractile proteins to Ca2+
52
what is a positive dromotropic response
increase in conduction in AV node
53
what changes in current increase conduction in the AV and SA node
increased If and ICa
54
what is automaticity
tendency for non nodal regions to acquire spontaneous activity
55
what is a positive Lusitropic action
decreasing the duration of systole
56
what cause a decrease in the duration of systole
increased uptake of Ca2+ into the sarcoplasmic reticulum
57
what effect does sympathetic stimulation have on the activity of the Na+/K+ ATPase
increases it
58
what effect does sympathetic stimulation have on mass of cardiac muscle
increases it (cardiac hypertrophy)
59
how is the frank staling curve affected by sympathetic stimulation
curve elevated
60
what happens at any end diastolic pressure during symp stimulation
stroke volume increased
61
why is contractility increased during sympathetic stimulation
as more calcium enters cell during plateau phase
proteins in the contractile apparatus become more sensitive to calcium
62
what affect does symp stim have on systole and why
reduces it so heart has more time to refill (if not would reduce stroke volume)
63
what is acetylcholine
post-ganglionic transmitter for the parasympathetic system
64
what does acetylcholine activate
M2 muscarinic cholinoceptors, largely in nodal cells
65
what effect does coupling of activated M2 muscarinic cholinoceptors with Gi protein do
1- decreases activity of adenylate cyclase and reduces [cAMP]I
2- opens potassium channels (GIRK) to cause hyperpolarization of SA node
66
what effect does the parasympathetic system have on heart rate
reduces it
67
what effect does the parasympathetic system have on slope of pacemaker potential and how
reduces it by reducing If and ICa
68
what effect does the parasympathetic system have on the threshold for AP and how
increases it via reducing ICa channels
69
what happens when GIRK channels are opened
potassium leaves cell, hyper polarising it and making it less excitable
70
what inotropic effect does para stim have and why
(negative) decreases contractility (in atria only) as decrease in phase 2 of cardiac action potential and decreased Ca2+ entry
71
what dromotropic effect does para symp have and how
(negative) decreases conduction in AV node- decreases activity of voltage dependent Ca+ channels and hyper polarisation via opening of K channels
72
what may para stim cause in the atria and why
arrhythmias as AP duration is reduced and so too the refractory period
73
what do vagal manoeuvres do
increase parasympathetic output
74
when may vagal manoeuvres be employed
in atrial tachycardia, atrial flutter, or atrial fibrillation to suppress impulse conduction through the AV node
75
what is the valsalva manoeuvre used to do
activates aortic baroreceptors (popping your ears)
76
what does massage of the bifurcation of the carotid artery do and why is it not recommended
stimulates baroreceptors in the carotid sinus- could dislodge deposit causing thrombis= stroke
77
what current mediates pacemaker potential
funny current (If)
78
what are the channels that mediated funny current activated by
(gated HCN channels)
hyperpolarisation
cyclic AMP
79
what does hyperpolarisation follow action potential do to HCN channels
activates HCN channels in the SA node
80
what does activation of CHN channels in the SA node cause
a slow phase 4 (pacemaker potential) depolarisation
81
what does block of HCN channels do to the slope of pacemaker potential and therefore heart rate
decreases slope and heart rate
82
what increases the activation of HCN channels
cAMP
83
what drug can be used as a selective blocker of HCN channels
ivabradine
84
what is ivabradine used to treat, how
angina as slow HR and reduces O2 consumption
| angina is a coronary artery disease which reduces the blood supply to the cardiac muscle
85
what is RyR2
the major mediator for sarcoplasmic release of stored calcium ions
86
what activate RyR2
Ca2+ influx during muscle contraction
87
what plasma membrane ATPase allows calcium efflux during muscle relaxation
Na+/Ca2+ exchanger 1 (NCX1)
88
only when what happens can muscle relaxation occur
when calcium has been removed from the cytoplasm
89
what ion rato does NCX1 move in/out of cardiac muscle cells
1 calcium out 3 sodium in
90
how is Ca put back into the SR
via Ca2+ATPase (SERCA), (sequesters calcium back into SR)
91
summarise how B1 adrenoceptor activation modulates cardiac contractility
(sympathetic stimulation)
B1 adreno activated= make cAMP
cAMP activate protein kinase A= phosphorylation reactions
L type Ca channels phosphorylated= opens= calcium influx= increased force of contraction
PKA also phosphorylates proteins in contractile machinery= more sensitive to calcium= pro-contractility
phospholamban phosphorylated by PKA= increase activity of CaATPase= increased pumping of Ca2+ into SR= increased rate of relaxation
92
how is cardiac force affected when you prevent the breakdown of cAMP
increase cardiac force
93
what are three agonists that act on B adrenoceptor
dobutamine, adrenaline and noradrenaline
94
what class of drugs do dobutamine, adrenaline and noradrenaline belong to
catecholamines
95
what are the pharmacodynamic effects of of B-adrenoceptor ligands
increase force, rate, CO and O2 consumption
decrease cardiac efficiency (O2 consumption less than cardiac work)
can cause disturbances in cardiac rhythm
96
what is adrenaline used to treat
cardiac arrest (IV), anaphylatic shock (IM)
97
what is dobutamine used to treat
acute (but potentially reversible heart failure)
98
how is adrenaline a mixed antagonist
as acts on both alpha and beta adrenoceptors
99
why does adrenaline have a short half life
as rapidly metabolised and removed from plasma by uptake systems of many tissues and nerves
100
what effect does adrenaline have on blood supply to organs
causes constriction of vessels around organs not essential at the time which reduces blood flow and redirects it to the heart
101
what type of beta receptor is present in cardiac muscle
B1
102
what type of beta receptor is present in respiratory smooth muscle
B2
103
how does adrenaline affect the coronary artery
dilates it to improve blood supply to the heart
104
what is a beta blocker
beta adrenoceptor antagonist
105
what do the physiological effects of B-adrenoceptor blockade depend upon
the degree to which the sympathetic nervous system is activated
106
name a non-selective beta blocker
propanolol
107
name 3 selective beta blockers
atenolol, bisoprolol, metoprolol
108
name a non selective and partial agonist
alprenolol
109
what are the pharmacodynamic effects of non-selective blockers
little effect at rest, during exercise; HR, force and CO significant depressed, O2 requirement and coronary vessel diameter reduced too
110
what is meant when a beta blocker has mixed activity
mildly stimulates heart and acts as antagonist to block agonist behaviour)
111
what are the clincal uses of a B-adrenoceptor antagonist
arrhythmias (tachycardia,atrial fibrillation or supraventricular tachycardia), angina, heart failure (compensated), hypertension
112
how do beta blockers treat excessive sympathetic activity (arrhythmias)
-blockers decrease excessive sympathetic drive and help restore normal sinus rhythm
113
how do beta blocker treat Atrial fibrillation (AF) and supraventricular tachycardia (SVT)
delay conduction through the AV node and help restore sinus rhythm
114
how do beta blockers treat angina
calcium entry blockers, help reduce O2 consumption and pain
115
what are stress induced arrhythmias
Increased delivery of noradrenaline and adrenaline causes emergence of latent pacemakers-stress induced arrhythmias
116
what is heart failure
when heart is giving insufficient cardiac output to provide adequate tissue perfusion
117
what is compensated heart failure
patient is stable and managed by drugs
118
what list the adverse effects of beta blockers
bronchospasm, aggravation of cardiac failure, bradycardia, hypoglycaemia, fatigue, cold extremities
119
why do beta blockers cause bronchospasma
block of airway smooth muscle B2-adrenoceptors (can be severe in asthmatics)
120
why do beta blockers cause aggravation of cardiac failure
patients with heart disease may rely on sympathetic drive to maintain an adequate CO
121
why do beta blockers cause bradycardia
heart block – in patients with coronary disease; B-adrenoceptors facilitate nodal conduction
122
why do beta blockers cause hypoglycaemia
in patients with poorly controlled diabetes – the release of glucose from the liver is controlled by B2-adrenoceptors
123
why do beta blockers cause fatigue
CO (β1) and skeletal muscle perfusion (β2) in exercise are regulated by adrenoceptors
124
why do beta blockers cause cold extremities
loss of B2-adrenoceptor mediated vasodilatation in cutaneous vessels
125
what adverse effects are at less of a risk with B1-selective agents
bronchospasm and hypoglycaemia
126
why do beta blockers pose an extra risk in hypoglycaemia
as hypo warning mechanisms (anxious, tremor, HR and force increases) could be suppressed by beta blocker
127
what is atropine
a non selective competitive antagonist of Muscarinic ACh Receptor
128
what are the pharmacodynamic effects of atropine
increase HR (more pronounced in athletes), no effect on arterial BP (as resistance vessels lack para innervation), no effect on response to exercise
129
how does atropine act
blocks effect of parasympathetic stimulation on the heart
130
why does atropine increase HR in athletes more
as have increased vagal tone and HR is much lower
131
what are the clinical uses for atropine
first line for severe bradycardia, particularly following MI (IV) and in anticholinesterase poisoning
132
why must you give a dose of a least 300-600 micrograms of atropine to treat bradycardia after an MI
as low doses will decrease HR
133
what is digoxin
A aardiac glycoside that increases contractility of the heart
134
how does Digoxin Increases Contractility
by Blocking the Sarcolemma ATPase
135
what does the Na+/Ca2+ exchanger move in and out
3 na out 2 k in
136
what are the by Sarcolemma ATPase
sodium potassium pump, Na+/Ca2+ exchangerm L-type Ca2+ channel
137
what part of Na+/K+ ATPase
alpha subunit
138
what can dangerously enhance the effect of digoxin and how
low plasma K+ as in competition with this to bind
139
what are the indirect electrical effects of digoxin
increased vagal activity, slows SA node discharge, slows AV node conduction (increases refractory period)
140
what are the direct electrical effects of digoxin
shortens action potential and refractory period in atrial and ventricular myocytes
141
does digoxin increase or decrease parasympathetic drive
increases it
142
what is oscillatory afterpotentials and what causes it
because of Ca2+ overload, 'delayed after depolarisation', id reaches threshold for AP then could cause self propagating AP= ventricular arrhythmia= tachy cardia= ventricle fibrillation
143
what are the clinical uses of digoxin
Iv in acute heart failure, orally in chronic heart failure
144
how does digoxin help in heart failure with atrial fibrillation
increase in AV node refractory period is beneficial, helps to prevent spreading of the arrhythmia to the ventricles
145
what causes the most severe adverse affects of digoxin
suppression of both nodes
146
what are the severe adverse effects of digoxin (2)
excessive depression of AV node conduction (heart block)
propensity to cause arrhythmias
147
what are the extracardiac effects of digoxin
```
(all involving Na/K ATPase)
nausea
vomiting
diarrhoea
disturbances of colour vision
```
148
what is Levosimendan
inotropic drug and calcium sensitiser
149
what does Levosimendan do
Binds to troponin C in cardiac muscle sensitizing it to the action of Ca2+
opens KATP channels in vascular smooth muscle causing vasodilation (reduces afterload and cardiac work)
150
name two inodilator drugs
amrinone and milrinone
151
how do inodilators act
Inhibit phosphodiesterase (PDE) in cardiac and smooth muscle cells and hence increase [cAMP]i
152
what effect to inodilators cause
Increase myocardial contractility, decrease peripheral resistance (haemodynamic indices are improved), but worsen survival – perhaps due to increased incidence of arrhythmias
153
what is the use of inodilators limited to
IV administration in acute heart failure
154
what are three common types of anti hypertensive drugs
Thiazide Diuretics
Beta Blockers
Vasodilators
155
what are 4 types of vasodilator drugs commonly used to treat hypertension
Calcium Antagonists
Alpha Blockers
```
ACE Inhibitors (ACEI)
Angiotensin Receptor Blockers (ARB)
```
156
what are 6 types of anti anginal drugs
```
Beta Blockers
Calcium Antagonists
Nitrates
Nicorandil
Ivabradine
Ranolazine
```
157
what are the three types of anti thrombotic drugs
antiplatelet, anticoagulants, fibrinolytics
158
what do antiplatelet drugs do and name 4
prevent platelets from forming; Aspirin, Clopidogrel, Prasugrel, Ticagrelor
159
what do anticoagulant drugs do and name 3
attack clotting factors; Warfarin, Rivaroxaban, Dabigatran
160
what do fibrinolytic drugs do and name 2
streptokinase, tPA
161
what are two types of anti cholesterol drugs
statins, fibrates
162
what do diuretics do
block Na reabsorbtion in the kidneys (makes you pee out more sodium)
163
describe thiazide diuretics (strength, use and an example)
mild, used in hypertension, Bendrofluazide
164
describe loop diuretics (strength, use and an example)
stronger than thiazidem used in heart failure, furosemide
165
what are the side effects of diuretics
hypokalaemia (low potassium) = tired, arrhythmias
hyperglycaemia= diabetes
increased uric acid= gout
impotence
166
what beta adrenoceptor do cardioselective B blockers act on
B1 receptors
167
what are cardioselective beta blockers use in and give an example of one
used in angina, hypertension and heart failure; atenolol
168
what beta adrenoceptor do non selective B blockers act on
B1 and B2
169
give and example of a non selective beta blocker and what it is used in
propanolol, used less in cardiology, more in thyrotoxicosis (hyperactive thyroid as B2 involved with these symptoms)
170
what are the side effects of a beta blocker
never use in asthma= bronchospasm
tiredness
heart failure (can worsen is short term, good in long/medium term)
cold peripheries
171
what are the two types of calcium agonist
Dihydropyridines, Rate limiting calcium antagonists
172
describe rate limiting calcium antagonists (use, what to avoid and 2 examples)
used in hypertension, angina and supraventricular arrhythmias (AF, SVF), avoid use with beta blockers, Verapamil, Diltiazem
173
describe Dihydropyridines (use, side effects and an example of one)
used in hypertension and angina, can cause ankle oedema, amlodipine
174
why do you avoid the use of rate limiting calcium antagonists with a beta blocker
as they block AV node in heart and use with beta blocker would suppress conduction in the heart why too much- heart block
175
what do alpha blockers do
Block aplha adrenoceptors to cause vasodilatation
176
what are alpha blockers used in
hypertension and prostatic hypertrophy
177
give an example of an alpha blocker
doxazosin
178
what are the side effects of alpha blockers
postural hypotension
179
what do Angiotensin Converting Enzyme Inhibitors do
Block angiotensin I becoming angiotensin II
180
what are ACE inhibitors used in
hypertensio, heart failure
181
give an example of an ACE inhibitor
lisinopril
182
how do ACE inhibitors affect the kidneys
most neutral but...
Good for kidneys in diabetic nephropathy
Bad for kidneys in renal artery stenosis
183
what are the side effects of ACE inhibitors
cough (irritating and dry), renal dysfunction, Angioneurotic oedema
184
what is Angioneurotic oedema
life threatening response, if causes larynx to swell which could obstruct breathing. If patient had this reaction in the past never give ace inhibitor
185
what should you never use ACE inhibitors in and why
pregnancy induced hypertension and damages fetus
186
what do angiotensin receptor blockers do
block angiotensin II receptors
187
give an example of an angiotensin receptor blocker and their side effects
losartan, renal dysfunction
188
how do Angiotensin receptor blockers affect the kidneys
Good for kidneys in diabetic nephropathy
Bad for kidneys in renal a stenosis
189
what do all angiotensin blocker drugs name end in
artan
190
why would you swap an ACE inhibitor for an Angiotensin Receptor Blocker
if patient has dry irritating cough or ankle oedema
191
can you use an Angiotensin Receptor Blockers in pregnancy induced hypertension
no
192
what do nitrates do and give an example of one
Venodilators
| e.g. Isosorbide monoritrate
193
what are nitrates used in
angina and acute heart failure
194
what are the side effects of nitrates
headache and hypotension/collapse
195
tolerance in nitrates is common how is it avoided
have 8 hours a day nitrate free
196
what are antiplatelet agents used in
angina acute MI, CVA(cerebralcasvualr accident (stroke))/TIA (transient ischaemic attack), patients at high risk of MI and CVA
197
what are the side effects of antiplatelet agents
haemorrhages, peptic ulcer= haemorrhage
| aspirin sensitivity= asthma
198
what is a haemorrhage
escape of blood from a damaged vessel
199
what do anticoagulants do
prevent new thrombosis via blocking factors 2, 7, 9, 10
200
name two examples of anticoagulants and how they are administered
heparin IV, warfarin oral
201
when should anticoagulants be used
DVT, pulmonary embolism, NSTEMI, atrial fibrillation
202
what is NSTEMI
Non-ST-elevation myocardial infarction
203
what are the side effects of anticoagulants
haemorrhage anyway
204
what can the effects of warfarin be overcome with
Vitamin K
205
what is rivaroxaban
factor X a inhibitor
206
what is dabigatran
thrombin factor IIa inhibitor (Xa converts Prothrombin (II) to Thrombin (IIa)
207
what is the dose of anticoagulants controlled by
INR- international normalised ratio
208
what do fibrinolytic drugs do
dissolve formed clot
209
give two examples of fibrinolytic drugs
streptokinase, tissue plasminogen activator (tPA)
210
when should fibrinolytic drugs be used
STEMI (selected cases only of pulmonary embolism and CVA)
211
what are the side effects of fibrinolytic drugs
haemorrhage
212
when should fibrinolytic drugs be avoided
recent haemorrhages (some CVAs), trauma, bleeding tendencies, severe diabetic retinopathy, peptic ulcer
213
what are the two types of anticholesterol drugs
statins and fibrates
214
give an example of statins
simvastatin
215
what does simvastatin do
blocks HMG CoA reductase
216
what are statins used in
```
hypercholesterolaemia
diabetes
Angina/MI
CVA/TIA
High risk of MI and CVA
```
217
what are the side effects of statins
myopathy and Rhabdomyolysis renal failure
218
give an example of fibrates
bezafibrate
219
what are fibrates used in
hypertriglyceridaemia,
| low HDL cholesterol
220
what do the names of all statins end in
statin
221
what anti arrhythmic drugs should be used to treat supra ventricular arrhythmias (SVT)
use adenosine in acute phase
222
what does adenosine do
creates transient blockage in AV node
223
what anti arrhythmic drugs should be used to treat Ventricular/ Supraventricular Arrhythmias
Amiodarone
Beta Blockers
Flecainide
224
what is Amiodarone
long acting anti arrhythmic drug
225
what are the side effects of anti arrhythmic drugs
Phototoxicity
Pulmonary fibrosis
Thyroid abnormalities
(Hypo or Hyper)
226
what are the two effects of digoxin
blocks AV conduction, increases ventricular irritability which produces ventricular arrhythmias
227
what should digoxin be used to treat
atrial fibrillation
228
why must the administration of digoxin be carefully monitored
as has narrow therapeutic window and can result in digoxin toxicity
229
what are the symptoms of digoxin toxicity
Nausea, vomiting
Yellow vision
Bradycardia, Heart Block
Ventricular Arrhythmias
230
when do you not use diuretics
gout
231
what does CCF stand for
conjested cardiac failure
