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Flashcards in Pharmacology Deck (147):
1

Adrenaline activates B2 adrenoceptors in the heart to cause increased heart rate. True/False?

False
Acts on B1 adrenoceptors

2

Which muscarinic receptor does ACh act on in the heart to cause decreased heart rate?

M2 receptors

3

What does adenylyl cyclase do?

Increases production of cAMP

4

Which channels, when blocked, decrease the slope of the SA node action potential?

HCN channels

5

Name a drug that is a selective blocker of HCN channels and for what heart condition it is mainly used

Ivabradine
Used for angina

6

Sympathetic stimulation decreases AV nodal delay. True/False?

True

7

Sympathetic stimulation causes increased automaticity. What is this?

Increased tendency for non-nodal regions to acquire spontaneous conduction activity

8

Sympathetic stimulation causes a decrease in the duration of systole. True/False?

True

9

What factors increase venous return?

Increased skeletal muscle activity
Adrenergic effects on blood vessels
Increased depth + frequency of respiration

10

What is the function of ryanodine receptors with regards to calcium action + action potentials?

Enable release of Ca++ from sarcoplasmic reticulum through the process of calcium-induced calcium release

11

What is the function of SERCA with regards to calcium action + action potentials?

Removes Ca++ from the cytoplasm to bring about relaxation

12

What happens when phosphalamban is phosphorylated with regards to calcium action + action potentials?

This increases Ca++ storage in the SR and also activates SERCA to promote relaxation

13

What happens when troponin I is phosphorylated with regards to calcium action + action potentials?

Decreases affinity of troponin C for calcium, thus accelerating relaxation

14

Name a B1 agonist drug used sometimes in heart failure

Dobutamine

15

Propranolol is a selective B2 receptor antagonist. True/False?

False
It is non-selective

16

Name a selective B1 antagonist drug

Atenolol
Metoprolol

17

Give some clinical uses of B-blockers

Arrhythmias
Hypertension
Angina
Heart failure (low-dose)

18

Give some adverse effects of B-blockers

Aggravate asthma
Aggravate heart failure
Cold extremities
Bradycardia
Fatigue

19

Which class of drug is atropine?

Non-selective muscarinic antagonist

20

Name the main clinical use of atropine

Reverse bradycardia modestly

21

What are the dangers of digoxin?

It has a low therapeutic ratio and is thus toxic, especially in hypokalaemia
Can cause heart block

22

What is an indirect effect of digoxin?

Slows AV node conduction to increase refractory period

23

What does Levosimendan do?

Binds to troponin C to increase its affinity for Ca++

24

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.

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