pharmacology Flashcards
1
Q
describe phase 4 of the ventricular AP
A
- Resting potential
- the outward flux of K+ is dominant
2
Q
describe phase 0 of the ventricular AP
A
- Upstroke
- the inward fluff Na+ is dominant
3
Q
describe phase 1 of the ventricular AP
A
- early repolarisation
- outward flux of K+ is dominant
4
Q
describe phase 2 of the ventricular AP
A
- plateau
- inward flux of Ca2+ is roughly balanced by outward flux of K+
5
Q
describe phase 3 of the ventricular AP
A
- final repolarisation
- the outward flux of K+ I dominant
6
Q
What is the difference between the ventricular AP and the atrial AP?
A
- an additional ultra rapid delayed rectifier means that is absent in ventricular cells means that the plateu phase is less evident in atrial cells
7
Q
how is the pacemaker potential generated in pacemaker cells?
A
the outward flux of K+ is reduced and the inward flux of Ca 2+ and Na+ is increased which generates the pacemaker potential
8
Q
adrenaline activates …… receptors coupled to …… to …… HR in sympathetic stimulation
A
- B1
- Gs
- increase
9
Q
sympathetic stimulation causes decreased contractility T/F?
A
False
increased contractility
10
Q
sympathetic stimulation …….. conduction velocity to the AV node
A
increases
11
Q
sympathetic stimulation increases automaticity, what does this mean?
A
- the tendency for non nodal regions to acquire spontaneous activity
12
Q
sympathetic stimulation decreases the duration of systole T/F?
A
True
due to increased uptake of Ca2+ into the SR
13
Q
sympathetic stimulation decreases activity of the Na+/K+ ATPase T/F
A
false
increases
14
Q
sympathetic stimulation causes an increased mass of cardiac muscle T/F
A
true
15
Q
in parasympathetic stimulation acetylcholine actives …… receptor coupling through …… causes …… HR
A
- M2
- Gi
- Decreased
16
Q
What does parasympathetic stimulation cause?
A
- decreased contractility
- decreased conduction in AV node
- may cause arrhythmias to occur in atria
17
Q
what effect does blocking HCN channels have?
A
- decreases the slope of the pacemaker potential
- reduces HR
18
Q
Name a drug that selectively blocks HCN channels and what it is used for?
A
- ivabradine
- used to slow HR in angina
19
Q
Name some beta adrenoreceptor agonists that act on the heart?
A
- dobutamine, adrenaline and noradrenaline
20
Q
Describe the effect of beta adrenoceptor agonists on the heart?
A
- increase force, rate and cardiac output
- decrease cardiac efficiency (O2 consumption increased more than cardiac work) can cause disturbances in cardiac rhythm
21
Q
Name a B1 adrenoceptor agonist that is given as an IV infusion for the treatment of acute Heart failure?
A
Dobutamine
22
Q
propanolol is a selective blocker of beta adrenoceptors T/F
A
False
It is non selective
23
Q
name some selective blockers of beta 1 adrenoceptors?
A
atenolol
bisoprolol
metoprolol
24
Q
Name an antagonist that is non selective and a partial agonist?
A
alprenolol
25
describe the pharmacodynamic effects of non selective blockers?
- at rest, little effect on rate, force, CO or MABP
- during exercise or stress, rate, force and CO are slightly depressed - reduction in max exercise tolerance
- coronary vessel diameter marginally reduced but myocardial O2 requirement falls, thus better for oxygenation of the myocardium
26
how can beta adrenoceptor antagonists be used clinically?
For the treatment of:
- arrhythmias
- atrial fibrillation
- supra ventricular tachycardia
- angina
- heart failure (low dose in compensated cardiac failure)
- hypertension
27
describe some adverse effects of beta blockers?
- bronchospasm (in asthmatics)
- aggravation of cardiac failure
- bradycardia (in patients with coronary disease)
- hypoglycaemia (in patients with poorly controlled diabetes)
- fatigue
- cold extremities
28
What is atropine?
non selective muscarinic ACh competitive antagonist
29
describe the pharmacodynamic effects of atropine?
- increase HR
- no effect on arterial BP
- no effect on response to exercise
30
describe the clinical uses of atropine in relation to the heart?
- first line management of severe or symptomatic bradycardia - following MI
- also used in anti cholinesterase poisoning
31
Describe the effect of digoxin?
- Na+/K+ ATPase inhibited
- increased [Na} and reduced Vm
- decreased Na+/Ca2+ exchanged and increased [Ca2+]
- increased storage of Ca2+ in SR
- increased CICR: increased contractility
32
What do inotropic drugs do?
enhance contractility
33
describe the pharmacodynamics of digoxin?
- Binds to the alpha subunit Na+/K+ ATPase in competition with K+ - effects can be dangerously enhanced by low plasma [K+]
34
describe the indirect action of digoxin on electrical activity?
- increased vagal activity
- slows SA node discharge
- slows AV node conduction - increases refractory period
35
describe the direct action of digoxin on electrical activity?
- shortens the AP and refractory period in atrial and ventricular myocytes
- toxic concentration cause membrane depolarisation and oscillatory afxterpotentials likely due to Ca2+ overload
36
what are the clinical uses of digoxin?
- IV in acute HF
- oral in chronic HF (in patients remaining symptomatic despite other treatment)
- HF with atrial fibrillation
37
describe the side effects of digoxin?
- excessive depression of AV ode conduction
- propensity to cause arrhythmias
- nausea
- vomiting
- diarrhoea
- disturbances of colour vision
38
name an inotropic drug that is a calcium sensitiser?
Levosimendan
39
describe the mechanism of levosimendan?
- makes troponin C more sensitive to calcium
| - opens KATP channels in vascular smooth muscle causing vasodilation
40
What is levosimendan used for?
- treatment of acute decompensated HF
41
name some inodilators?
amrinone and milrinone
42
What do inodilators do?
- inhibit phosphodiesterase in cardiac and smooth muscle cell and hence increase [CAMP] I - increase myocardial contractility, decrease peripheral resistance
- use limited to IV administration in acute HF
43
describe the clinical use of adrenaline?
given in cardiac arrest and the immediate management of anaphylactic shock
44
adrenaline has a ..... plasma t1/2 due to uptake/metabolism
short
45
Describe the mechanism of adrenaline in cardiac arrest?
- positive inotropic and chronotropic effects via B1
- redistribution of blood flow to the heart from 'non-essential tissues'
- dilates coronary arteries via activation of B2
46
Name 3 types of common anti cholesterol drugs
- statins
- fibrates
- PCSK 9 inhibitors
47
Name 3 common types of hypertensive drugs
- thiazide diuretics
- beta blockers
- vasodilators (calcium antagonists, alpha blockers, ACE inhibitors, ARBs)
48
describe the mechanism of simvastatin and when it is used?
- statin that blocks HMG coA reductase
- used in: hypercholesterolaemia
diabetes
angina/MI
CVA/TIA
49
Describe the side effects of simvastatin?
- myopathy
| - rhabdomyolysis (renal failure)
50
what is bezafibrate and what is it used for?
- it is a fibrate used in hypertriglyceridaemia and low HDL cholesterol
51
Name 2 PCSK 9 inhibitors and describe their use?
- alirocumab, evolocumab
| - used in the treatment of familial hypercholesterolaemia
52
How do PCSK 9 inhibitors work?
- they inhibit the binding of PCSK 9 to LDLR, PCSK9 inhibitor increase the number of LDLRs available to clear LDL thereby lowering LDLC levels
53
What do diuretics do?
block Na reabsorption in kidneys
54
Give an example of a thiazide diuretic and its use?
- bendrofluazide
| - used in Hypertension
55
Give an example of loop diuretics and its use?
- furosemide
| - used in HF
56
Give the side effects of diuretics?
- hypokalaemia - tired
- arrhythmias
- hyperglycaemia - diabetes
- increased uric acid - gout
- impotence
57
give examples of cardioselective beta blockers and their use?
- atenolol, bisoprolol
- only block beta 1 receptors
- used in angina, acute coronary syndrome, MI, hypertension, HF
58
give examples of non selective beta blockers and their use?
- propanolol, carvedilol
- block beta 1 and beta 2 receptors
- used in thyrotoxicosis, migraine
59
what are the side effects of beta blockers?
- asthma - contraindicated in brittle/severe asthma
- tired
- HF
- cold peripheries
- can worsen HF
60
Give examples of dihydropyridine calcium antagonists and their use and SE?
- amlodipine
- used in hypertension and angina
- SE: ankle oedema
61
give examples of rate limiting calcium antagonists and their use and SE?
- verapamil, diltiazem
- used in hypertension, angina and supra ventricular arrhythmias
- SE: avoid use with beta blocker
62
What do ACE inhibitors do?
block angiotensin I becoming angiotensin II
63
give an example of an ACE inhibitor and its uses and SE?
- lisinopril
- used in hypertension and HF
- SE: cough, renal disturbance, angioneurmtic oedema
- cannot be used in pregnancy: hypertension
64
What do ARBs do?
- block angiotensin II receptors
65
Give examples of ARBs and their use and SE?
- losartan
- used in hypertension and HF
- SE: renal dysfunctional and no cough
- never use in pregnancy - hypertension
66
what do alpha blockers do?
block alpha adrenoceptors to cause vasodilation
67
Give examples of alpha adrenoceptors and their use and SE?
- doxazosin
- used in hypertension and prostatic hypertrophy
- SE: postural hypotension
68
What do mineralocorticoid antagonists do?
block aldosterone receptors
69
give examples of mineralocorticoid antagonists and their use and SE?
- spironolactone, eplenerone
- used in HF and resistant hypertension
- SE: gynaecomastia, hyperkalaemia, renal impairment
70
Name some common anti anginal drugs?
- vasodilators: nitrates, nicorandil, calcium antagonists
- slow HR: beta blockers, calcium antagonists, ivabradine
- metabolic modulator: ranolazine
71
Give an example of a nitrate, its use and SE?
- isosorbide mononitrate
- ventilators used in angina and acute HF
- SE: headache, hypotension/collase
- tolerance common
72
What is Nicorandil?
- vasodilator
- K ATP channel inhibitor
- SE: Headache, mouth/GI ulcers
73
What is ivabradine?
- If channel modulator in the sinus node
- slows HR only in sinus rhythm
- does not work in atrial fibrillation
- altered visual disturbance
74
What is ranolazine?
- late sodium channel modulator
- decrease calcium load on the heart
- effective in refractory angina
75
what do anti platelet and anti coagulant agents do?
- prevent new thrombosis
76
Give examples of anti platelet agents, their use and SE?
- aspirin, clopidogrel, ticagrelor, prasugrel
- used in: angina, acute MI, CVA/TIA
- SE: haemorrhage anywhere, peptic ulcer = haemorrhage, aspirin sensitivity = asthma
77
Give examples of anticoagulants?
- heparin
- warfarin
- rivaroxaban
- dabigatran
78
How is Warfarin used and what are the SE?
- blocks clotting factors (2,7,9,10)
- used in DVT, PE, NSTEMI, atrial fibrillation
- SE: haemorrhage anywhere
79
how is streptokinase used and what are the SE?
- tissue plasminogen activator
- use in STEMI, PE, CVA
- SE: haemorrhage
80
What do fibrinolytic drugs do?
dissolve formed clot
81
Name some common types of drugs used in HF?
- ACE inhibitor
- ARBS
- beta blockers
- mineralocorticoid antagonists
- neprilysin inhibitors
- diuretics
- digoxin
82
What does digoxin do?
- produces delay in AV node conduction (good in AF)
| - increases ventricular irritability which produces ventricular arrhythmias (bad)
83
Name some of the side effects of digoxin?
- narrow therapeutic window
- nausea
- yellow vision
- bradycardia, heart block
- ventricular arrhythmias
84
What is Salcubitril valsartan and what are its SE?
- neprilysin inhibitor
| - SE: hypotension, renal impairment, hyperkalaemia, angioneurotic oedema
85
cardiovascular disease is strongly associated with elevated ....... and decreased .............
LDL, HDL
86
What are lipoproteins?
microscopic spherical particles of 7-1000 nm diameter consisting of:
- a hydrophobic core
- a hydrophilic coat
- apoproteins
87
What are apoproteins?
- recognised receptors in liver and other tissues allowing lipoproteins to bind to cells
88
What apoproteins do HDL particles contain?
- apo-A-I and apoA-II
89
What apoproteins do LDL particles contain?
- apoB-100
90
What apoproteins do VLDL particles contain?
-apoB-100
91
What apoproteins do chylomicrons particles contain?
- apoB-48
92
What do ApoB containing lipoproteins do?
Deliver TAGs i) to muscle for ATP biogenesis
| ii) to adipocytes for storage
93
where are chylomicrons formed?
In intestinal cells and transport dietary triglycerides - the exogenous pathway
94
Where are VLDL particles formed?
In liver cells and transport TAGs synthesised by that organ - the endogenous pathway
95
Summaries the life cycle of ApoB containing liposomes?
- assembly: with apoB-100 in the liver and ApoB-48 in the intestine
- intravascular metabolism: involves hydrolysis of the TAG core
- receptor mediated clearance
96
How are chylomicrons and VLDL particles activated?
by the transfer of ApoC-II from HDL particles
97
What is the role of MTP?
lipidates apoB-100 forming nascent VLDL that coalesces with TAG droplets
98
ApoC-II facilitates the binding of ......... and ...... to .....
chylomicrons/VLDL/LPL
99
What does LPL do?
hydrolyses core TAGs to free fatty acids and glycerol which enter tissues
100
What are chylomicron and VLDL remnants?
particles depleted of triglycerides (but still containing cholesteryl esters)
101
What is the clearance of LDL particles dependent on?
- LDL receptor expressed by the liver and other tissues
102
How does cellular uptake of LDL particles occur?
- through receptor mediated endocytosis
103
What does released cholesterol do?
- inhibits HMG coA reductase (rate limiting enzyme in cholesterol synthesis)
- may be stored as cholesterol ester or used as a precursor for bile salt synthesis
104
Why is LDL the 'bad' cholesterol?
- triggers the release of inflammatory substances which causes division of smooth muscle cells and deposition of collagen in the TI resulting in an atheromatous plaque
105
Describe the structure of an atheromatous plaque?
- lipid core which is the produce of dead foam cells
| - fibrous cap which is made up of smooth muscle cells and connective tissue
106
Why is HDL the 'good' cholesterol
- plays a key role in removing excess cholesterol by transporting it in plasma to the liver
107
How do statins work?
- act competitively to inhibit HMG coA reductase which is the rate limiting step in cholesterol synthesis in hepatocytes
108
What does decreased hepatocyte cholesterol cause?
- compensatory increase in LDL receptor expression and enhanced clearance of LDL
109
What do fibres do?
act as agonists of a nuclear receptor (PPARalpha) to enhance the transcription of several genes including that encoding LPL
110
Name some drugs that inhibit cholesterol absorption and how do they work?
- bile acid binding resins (colestyramine, colestipol, colsevlam) cause the excretion of bile salts resulting in more cholesterol to be converted to bile salts by interrupting enterohepatic recycling
111
How does ezetimibe work?
inhibits NPC1L1 transport protein in enterocytes of the duodenum, reducing the absorption of cholesterol causing a decrease in LDL
112
Describe the use of anticoagulants?
- mainly used in the prevention and treatment of venous thrombosis and embolism
- carries a risk of haemorrhage
113
How does warfarin work?
- competes for binding to hepatic vitamin K reductase preventing the production of active hydroquinolone
- renders factors II, VII, IX and X inactive
114
Warfarin has a high therapeutic index T/F?
False
| It has a low therapeutic index
115
How does heparin work?
- binds to antithrombin III, increasing its affinity for serine protease clotting factors to increase their rate of inactivation
116
Give examples of LMWH and how they work?
- enoxaparin and dalteparin
| - inhibit factor Xa
117
The elimination of heparin is first order T/F?
- false
| - elimination of LMWH is first order, heparin is 0 order
118
Name an orally active inhibitor that acts as a direct inhibitor of thrombin?
- dabigatran
119
When are anti platelet drugs used?
- in the treatment of arterial thrombosis
120
How does aspirin work?
- irreversibly blocks cycloxygenase in platelets preventing TXA2 synthesis but also COX in endothelial cells inhibiting the production of prostaglandin I2
121
What is the main side effect of aspirin
GI bleeding and ulceration
122
How does clopidogrel work?
Links to P2Y12 receptor by a disulphide bond producing irreversible inhibition
123
When in Tirofiban used?
- given IV in short term treatment to prevent MI in high risk patients with unstable angina
124
How are fibrinolytic used?
- principally to reopen occluded arteries in acute MI or stroke
- IV administration ASAP
125
What does streptokinase do?
- reduces mortality in acute MI
126
what do alteplase and duteplase do?
- recombinant tissue plasminogen activators
- more effective in fibrin bound plasminogen
- show affinity for clots
