Pharmacology Flashcards
1
Q
Adrenaline activates B2 adrenoceptors in the heart to cause increased heart rate. True/False?
A
False
Acts on B1 adrenoceptors
2
Q
Which muscarinic receptor does ACh act on in the heart to cause decreased heart rate?
A
M2 receptors
3
Q
What does adenylyl cyclase do?
A
Increases production of cAMP
4
Q
Which channels, when blocked, decrease the slope of the SA node action potential?
A
HCN channels
5
Q
Name a drug that is a selective blocker of HCN channels and for what heart condition it is mainly used
A
Ivabradine
Used for angina
6
Q
Sympathetic stimulation decreases AV nodal delay. True/False?
A
True
7
Q
Sympathetic stimulation causes increased automaticity. What is this?
A
Increased tendency for non-nodal regions to acquire spontaneous conduction activity
8
Q
Sympathetic stimulation causes a decrease in the duration of systole. True/False?
A
True
9
Q
What factors increase venous return?
A
Increased skeletal muscle activity
Adrenergic effects on blood vessels
Increased depth + frequency of respiration
10
Q
What is the function of ryanodine receptors with regards to calcium action + action potentials?
A
Enable release of Ca++ from sarcoplasmic reticulum through the process of calcium-induced calcium release
11
Q
What is the function of SERCA with regards to calcium action + action potentials?
A
Removes Ca++ from the cytoplasm to bring about relaxation
12
Q
What happens when phosphalamban is phosphorylated with regards to calcium action + action potentials?
A
This increases Ca++ storage in the SR and also activates SERCA to promote relaxation
13
Q
What happens when troponin I is phosphorylated with regards to calcium action + action potentials?
A
Decreases affinity of troponin C for calcium, thus accelerating relaxation
14
Q
Name a B1 agonist drug used sometimes in heart failure
A
Dobutamine
15
Q
Propranolol is a selective B2 receptor antagonist. True/False?
A
False
It is non-selective
16
Q
Name a selective B1 antagonist drug
A
Atenolol
Metoprolol
17
Q
Give some clinical uses of B-blockers
A
Arrhythmias
Hypertension
Angina
Heart failure (low-dose)
18
Q
Give some adverse effects of B-blockers
A
Aggravate asthma Aggravate heart failure Cold extremities Bradycardia Fatigue
19
Q
Which class of drug is atropine?
A
Non-selective muscarinic antagonist
20
Q
Name the main clinical use of atropine
A
Reverse bradycardia modestly
21
Q
What are the dangers of digoxin?
A
It has a low therapeutic ratio and is thus toxic, especially in hypokalaemia
Can cause heart block
22
Q
What is an indirect effect of digoxin?
A
Slows AV node conduction to increase refractory period
23
Q
What does Levosimendan do?
A
Binds to troponin C to increase its affinity for Ca++
24
Q
In the smooth muscle cell, calcium binds with _____, which undergoes a conformation change. The __-__ complex then interacts with _____ to activate it. The active ____ then phosphorylates ___-__ which, when phosphorylated, ultimately causes contraction.
A
In the smooth muscle cell, calcium binds with calmodulin, which undergoes a conformation change. The Ca-CaM complex then interacts with MLCK to activate it. The active MLCK then phosphorylates myosin-LC which, when phosphorylated, ultimately causes contraction.
25
In the endothelial cell, Ca-CaM complex activates ___ which binds _-____ and __ to form NO, which rapidly diffuses into the smooth muscle cell (to ultimately cause relaxation).
In the endothelial cell, Ca-CaM complex activates eNOS which binds l-arginine and O2 to form NO, which rapidly diffuses into the smooth muscle cell (to ultimately cause relaxation).
26
In the smooth muscle cell, NO does 2 things:
1] activates ___ ____ which synthesises cGMP from ___. cGMP activates protein kinase _ which ultimately causes relaxation.
2] keeps Ca-dependent _ channel open, allowing _ to efflux, leaving _ve charge in the cell which causes membrane potential to ______ so we get relaxation.
In the smooth muscle cell, NO does 2 things:
1] activates guanylate cyclase which synthesises cGMP from GTP. cGMP activates protein kinase A which ultimately causes relaxation.
2] keeps Ca-dependent K channel open, allowing K to efflux, leaving -ve charge in the cell which causes membrane potential to hyperpolarise so we get relaxation.
27
How do organic nitrates (GTN) work in the smooth muscle cell?
Combines with SH groups to liberate NO, which then acts like endogenous NO in signalling pathways
28
Nitrates cause arteriolar dilation at low doses. True/False?
False
| Mainly cause venorelaxation, but can cause arteriolar dilation at high doses
29
How do nitrates help in angina?
Decrease preload + afterload
| Improve perfusion to ischaemic zone (dilates collateral vessels)
30
Name 2 examples of organic nitrates used clinically
GTN tablet/spray
| Isosorbide mononitrate
31
Why is it important to have nitrate-low periods?
Repeated use can develop tolerance and reduce efficacy
32
Endothelin-1 causes vasodilation. True/False?
False
| Causes vasoconstriction
33
Which substances cause upregulation of endothelin production?
Adrenaline
Angiotensin II
ADH
34
Which substances cause downregulation of endothelin production?
Nitric oxide
| ANP
35
Name antagonists of the endothelin-1 receptor used in treating pulmonary hypertension
Bosentan
| Ambrisentan
36
Name a renin inhibitor
Aliskiren
37
Renin inhibitors (aliskiren) can be used in conjunction with an ARB or ACEi. True/False?
False
38
What are the effects of ACE?
Converts AT I to AT II
| Inactivates bradykinin
39
Name an ACEi used in Tayside
Lisinopril
40
Name an ARB used in Tayside
Losartan
41
What are the main differences between ACEi and ARBs?
ARBs do not inhibit bradykinin and do not produce dry cough
42
How do calcium antagonists work?
Prevent opening of Ca channels to limit intracellular Ca++ to reduce heart rate and force of contraction
43
Verapamil is selective for cardiac L-type channels. True/False?
True
44
Amlodipine is selective for which L-type channels?
Smooth muscle L-type channels
45
Amlodipine is preferred to verapamil - why?
Minimises unwanted effects on cardiac muscle, e.g. heart block
46
Why is verapamil useful in arrhythmias?
Slows conduction of AV node, can help reduce AF
47
K+ channel openers act primarily on arterial smooth muscle. True/False?
True
48
Name two K+ channel opener drugs
Minoxidil
| Nicorandil
49
Name two alpha blockers
Prazosin
| Doxazosin
50
What is the main/overall action of diuretics?
Increase Na, Cl and water excretion
| Indirectly relax vasculature
51
What is the undesirable effect of diuretics?
Loss of K+
52
Name a thiazide diuretic and conditions it is used in
Bendroflumethazide
| Mild heart failure, hypertension
53
Name a loop diuretic and conditions it is used in
Furosemide
| Chronic heart failure, acute pulmonary oedema
54
What are some side effects of diuretics?
Hypokalaemia
Arrhythmias
Gout
Impotence
55
What is the main side effect of dihydropyridine Ca antagonists?
Ankle oedema
56
Name conditions in which amlodipine can be used
Hypertension
| Angina
57
In addition to hypertension and angina, verapamil can be used for what?
SVT arrhythmias (AF, VT) but NOT alongside B blockers
58
ACEi and ARBs are safe in pregnancy. True/False?
False
| NEVER use in pregnancy
59
Name conditions in which nitrates can be used
Angina
| Acute heart failure
60
Name some antiplatelet agents
Aspirin
| Clopidogrel
61
Name some anticoagulants
Heparin (IV)
| Warfarin (oral)
62
What do fibrinolytics simply do?
Dissolve formed clots
63
Name a commonly used fibrinolytic
Streptokinase
64
CV disease is associated with low LDL and HDL. True/False?
False
| High LDL and/or low HDL causes CV disease
65
The bigger the HDL:LDL ratio, the better (in terms of health). True/False?
True
66
What are the components of a lipoprotein?
Hydrophobic core + hydrophilic coat
67
What makes up the hydrophobic core of a lipoprotein?
Esterified cholesterol
| Triglycerides
68
What makes up the hydrophilic coat of a lipoprotein?
Amphipathic cholesterol
Phospholipids
Apoproteins
69
Name the major lipoproteins
HDL
LDL
VLDL
Chylomicrons
70
What does HDL contain?
apoA1 and apoA2
71
What does LDL contain?
apoB100
72
What does VLDL contain?
apoB100
73
What do chylomicrons contain?
apoB48
74
What is the function of apoB lipoproteins (LDL, VLDL, chylomicrons)?
Deliver triglycerides to muscle for ATP genesis + to adipocytes for storage
75
Chylomicrons are formed in liver cells and transport triglycerides formed in the liver. True/False?
False
| VLDL is formed in the liver and takes part in the endogenous pathway
76
What is the exogenous pathway of triglyceride transport?
Chylomicrons formed in intestinal cells to transport dietary triglycerides
77
What are the three stages of the life cycle of apoB lipoproteins?
Assembly
Metabolism [hydrolysis]
Clearance
78
Which enzyme breaks down triglyceride into 2 fatty acids and monoglycerol?
Pancreatic lipase
79
Why does the triglyceride molecule need to be broken down?
It is insoluble and cannot be absorbed into the enterocyte
80
What happens when monoglyceride and 2 fatty acids are in the enterocyte?
Combine to reform triglyceride
81
Which receptor enables amphipathic cholesterol to enter the enterocyte?
NPC1L1 protein
82
What needs to be added to the chylomicron to allow its export from the enterocyte?
apoA1
83
Exported chylomicron enters the blood and is deposited into the venous system. True/False?
False
| Deposited into lymphatics and then the venous system
84
Where and how is VLDL assembled?
Liver cells, from free fatty acids derived de novo + from adipose tissue
85
Before chylomicron and VLDL can offload their contents, they need to be activated. How does this happen?
HDL transfers apoCII to VLDL and chylomicrons which facilitates their binding
86
Which enzyme hydrolyses apoB lipoprotein (chylomicron, VLDL, LDL)?
Lipoprotein lipase (LPL)
87
What facilitates binding of chylomicrons and VLDL to LPL?
apoCII (that was transferred from HDL)
88
What does LPL do to apoB lipoproteins?
Attacks and hydrolyses core triglycerides to fatty acids and glycerol which can be absorbed
89
What are chylomicron and VLDL remnants?
Particles depleted of triglyceride but still containing cholesterol ester
90
apoCII is returned to HDL in exchange for which apoprotein? How does this facilitate clearance of apoB lipoprotein?
apoCII is returned to HDL in exchange for apoE, a high affinity ligand for receptor-mediated clearance
91
All apoB100 and apoB48 remnants are cleared via receptor-mediated clearance. True/False?
False
| Only 50% of apoB100 remnants are cleared this way
92
What happens to the remaining apoB100 remnants?
Eventually become LDL
93
Which receptor is vital for LDL clearance? Where is it importantly located?
LDL receptor in liver
94
How does cholesterol release from LDL influence cholesterol release by hepatocytes?
The more cholesterol returning to the liver (in LDL), the less liver is synthesised by hepatocytes
95
How does cholesterol release inhibit cholesterol synthesis by hepatocytes?
Inhibits HMG CoA reductase
| Downregulates LDL receptor expression
96
Why is LDL "bad" cholesterol?
Uptake during endothelial injury causes LDL oxidation to atherogenic OXLDL
Macrophages uptake OXLDL, converting cholesterol into foam cells, forming a fatty streak and ultimately a plaque
97
Why is HDL "good" cholesterol?
Accepts excess cholesterol and delivers it to the liver (reverse cholesterol transport)
It then interacts with scavenger receptors that enable uptake of cholesterol into hepatocytes
98
What are the drugs of choice for reducing LDL (and moderately increasing HDL)? Give examples
Statins - simvastatin, atorvastatin
99
How do statins work?
Inhibit HMG CoA reducatase, causing decrease in de novo cholesterol synthesis + increase in LDL receptor expression to enhance cholesterol clearance
100
When and how are statins administered?
Orally at night
101
What other drugs can be used for decreasing triglycerides?
Fibrates - bezafibrate, gemfibrozil
102
How do fibrates work?
Inhibit PPAR-alpha to enhance LPL production
103
What do bile acid binding resins do?
Cause excretion of bile salts, causing more cholesterol to be converted into bile salts
104
Name some bile acid binding resin drugs and a notable side effect
Colestyramine
Colestipol
Can cause GI irritation
105
What does Ezetimibe do?
Inhibits NPC1L1 protein to reduce cholesterol absorption by enterocytes, ultimately causing decrease in LDL
106
What are the 3 components of Virchow's triad? What do they predispose to?
Abnormal blood flow
Vessel wall injury
Increased coagulability of blood
These predispose to thrombosis
107
An arterial thrombus is a white thrombus. True/False?
True
108
What colour is a venous thrombus?
Red
109
Where do white thrombi commonly lodge?
Brain (detached embolus from left heart)
110
Where do red thrombi commonly lodge?
Lung (detached embolus from right heart)
111
What do VIIa, XIa and XIIa do downstream in the blood coagulation pathway?
Activate X to Xa
112
What does Xa do downstream in the blood coagulation pathway?
Activates II to IIa
| [prothrombin to thrombin]
113
What does IIa (thrombin) do downstream in the blood coagulation pathway?
Activates fibrinogen to fibrin, the component of fibrin clots
114
What happens in response to endothelial damage in terms of platelets?
Adhere to site of injury and become activated, attracting other platelets, causing aggregation
115
What mediators do activated platelets secrete/synthesize? What do they do?
ADP, 5-HT, TXA2
| Enhance platelet aggregation
116
Name the inactive precursors of the main clotting factors involved in coagulation
II, VII, IX, X
117
What do the inactive precursors of clotting factors require initially in order to be able to become activated?
Gamma-carboxylation
118
What does the enzyme which carries out gamma-carboxylation of clotting factor precursors require?
Vitamin K
| [in its reduced, hydroquinone form]
119
What are the two forms of Vitamin K that exist?
K1 from diet
| K2 from bacteria in intestine
120
How does warfarin work?
Competitively binds to vitamin K reductase, causing inhibition and thus reducing hydroquinone VK [ultimately inactivating clotting factor precursors]
121
How is warfarin administered? How fast is its onset of action?
Oral
| 2-3 days
122
What is the main risk with anticoagulant drugs?
Risk of haemmorhage
123
How does liver disease potentiate activity of warfarin?
Decreased clotting factors
124
How does a high metabolic rate potentiate the activity of warfarin?
Increased clearance of clotting factors
125
How does pregnancy decrease the effect of warfarin?
Increased synthesis of clotting factors
126
How might a warfarin overdose be treated?
Vitamin K/clotting factor infusion
127
What does Antithrombin III (ATIII) do?
Inhibits IIa and Xa to inhibit coagulation
128
How does heparin cause anticoagulation?
Accelerates inhibition of IIa and Xa through ATIII - increases affinity of the latter for the former
129
Heparin must bind to ATIII and IIa in order to inhibit IIa. True/False?
True
130
Heparin must bind to ATIII and Xa in order to inhibit Xa. True/False?
False
| Only needs to bind to ATIII
131
LMWH inhibits IIa but not Xa. True/False?
False
| Inhibits Xa but not IIa
132
Give examples of LMWHs
Enoxaparin
| Dalteparin
133
How is heparin administered?
Intravenously or subcutaenously
134
How is LMWH administered?
Subcutaneously
135
Name an oral active inhibitor of thrombin
Dabigatran etexilate
136
Name an oral active inhibitor of Xa
Rivaroxaban
137
What is the role of vWF in platelet pathway?
Acts as a bridge to help platelets adhere to damaged endothelium
138
Which enzyme aids platelet synthesis of TXA2?
COX
139
Which receptor does ADP bind with to enhance platelet aggregation?
Which drug blocks this receptor?
P2Y12 receptor
| Clopidogrel blocks this
140
Which platelet receptors does fibrinogen bind with to enhance platelet aggregation?
Which drug blocks this?
GPIIb/IIIa receptors
| Tirofiban
141
Which drug blocks the synthesis of TXA2 through inhibiting COX enzyme?
Aspirin
142
How is aspirin administered?
Oral
143
How is clopidogrel administered?
Oral
144
What is the role of plasmin in the coagulation cascade?
Enforces fibrin degradation to form fibrin fragments (clot lysis)
145
How do fibrinolytic drugs work?
Activate plasminogen to form plasmin to cause clot lysis
146
Give examples of fibrinolytic drugs
Streptokinase
Aleplase
Duteplase
147
How are fibrinolytic drugs administered?
Intravenously
