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? Give one special use of this drug
A
False
It is non-selective
Thyrotoxicosis
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
Bronchospasm (aggravate asthma) Hypoglycaemia (especially in diabetes) Cold extremities Bradycardia Fatigue Acute heart failure
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, arrhythmias, nausea, vomiting, diarrhoea and disturb colour vision
22
Q
What is an indirect effect of digoxin?
A
Slows AV node conduction to increase refractory period (good in heart failure and AF - increase cardiac output)
23
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.
24
Q
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).
A
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).
25
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.
26
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
27
Nitrates cause arteriolar dilation at low doses. True/False?
False
| Mainly cause venorelaxation, but can cause arteriolar dilation at high doses
28
How do nitrates help in angina?
Decrease preload + afterload
| Improve perfusion to ischaemic zone (dilates collateral vessels) - INCREASE CORONARY BLOOD FLOW
29
Name 2 examples of organic nitrates used clinically
```
GTN tablet/spray (short acting)
Isosorbide mononitrate (long acting)
```
30
Why is it important to have nitrate-low periods? List some other side effects of nitrates
Repeated use can develop tolerance and reduce efficacy
| Postural hypotension, headaches
31
Endothelin-1 causes vasodilation. True/False?
False
| Causes vasoconstriction
32
Which substances cause upregulation of endothelin production?
Adrenaline
Angiotensin II
ADH
33
Which substances cause downregulation of endothelin production?
Nitric oxide
| ANP
34
Name a renin inhibitor
Aliskiren
35
Renin inhibitors (aliskiren) can be used in conjunction with an ARB or ACEi. True/False?
False
36
What are the effects of ACE?
Converts AT I to AT II
| Inactivates bradykinin
37
Name an ACEi used in Tayside
Lisinopril
38
Name an ARB used in Tayside
Losartan
39
What are the main differences between ACEi and ARBs?
ARBs do not inhibit bradykinin and do not produce dry cough - block AT II from working on receptor
40
How do calcium antagonists work?
Prevent opening of Ca channels to limit intracellular Ca++ to reduce heart rate and force of contraction
41
Verapamil is selective for cardiac L-type channels. True/False?
True
42
Amlodipine is selective for which L-type channels?
Smooth muscle L-type channels
43
Amlodipine is preferred to verapamil - why?
Minimises unwanted effects on cardiac muscle, e.g. heart block
44
Why is verapamil useful in arrhythmias?
Slows conduction of AV node, can help reduce AF
45
K+ channel openers act primarily on arterial smooth muscle. True/False?
True
46
Name two K+ channel opener drugs. What are they used in?
Minoxidil
Nicorandil
Severe hypertension
47
Name two alpha blockers. What is their action? What are they used in? List one side effect.
```
Prazosin
Doxazosin
Block alpha adrenoceptors causing vasodilatation
Hypertension (and BPH)
Postural hypotension
```
48
What is the main/overall action of diuretics?
Increase Na, Cl and water excretion from the kidneys
| Indirectly relax vasculature
49
What is the undesirable effect of diuretics?
Loss of K+
50
Name a thiazide diuretic, give its action and conditions it is used in
Bendroflumethazide
Inhibit NaCl reabsorption in distal tubule
Mild heart failure, hypertension
51
Name a loop diuretic, give its action and conditions it is used in
Furosemide
Inhibit NaCl reabsorption in the Loop of Henle
Chronic heart failure, acute pulmonary oedema
52
What are some side effects of diuretics?
```
Hypokalaemia
Arrhythmias
Hyperglycaemia
Gout
Impotence
```
53
What is the main side effect of dihydropyridine Ca antagonists? Give an example
Ankle oedema
| Amlodipine
54
Name conditions in which amlodipine can be used
Hypertension
| Angina
55
In addition to hypertension and angina, verapamil can be used for what? Give one side effect
```
SVT arrhythmias (AF, VT) but NOT alongside B blockers
Heart block
```
56
ACEi and ARBs are safe in pregnancy. True/False?
False
| NEVER use in pregnancy
57
Name conditions in which nitrates can be used
Angina
| Acute heart failure
58
Name some antiplatelet agents. What is their mode of action? List a major side effect.
Aspirin
Clopidogrel
Prevent new thrombus getting bigger
Haemorrhage
59
Name some anticoagulants. What is their mode of action? List a major side effect.
Heparin (IV)
Warfarin (oral)
Prevent new thrombus getting bigger
Haemorrhage
60
What do fibrinolytics simply do?
Dissolve formed clots
61
Name two commonly used fibrinolytics. List a major side effect
Streptokinase
Tissue plasminogen activator (tPa)
Haemorrhage
62
CV disease is associated with low LDL and HDL. True/False?
False
| High LDL and/or low HDL causes CV disease
63
The bigger the HDL:LDL ratio, the better (in terms of health). True/False?
True
64
What are the components of a lipoprotein?
Hydrophobic core + hydrophilic coat
65
What makes up the hydrophobic core of a lipoprotein?
Esterified cholesterol
| Triglycerides
66
What makes up the hydrophilic coat of a lipoprotein?
Amphipathic cholesterol
Phospholipids
Apoproteins
67
Name the major lipoproteins
HDL
LDL
VLDL
Chylomicrons
68
What does HDL contain?
apoA1 and apoA2
69
What does LDL contain?
apoB100
70
What does VLDL contain?
apoB100
71
What do chylomicrons contain?
apoB48
72
What is the function of apoB lipoproteins (LDL, VLDL, chylomicrons)?
Deliver triglycerides to muscle for ATP genesis + to adipocytes for storage
73
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
74
What is the exogenous pathway of triglyceride transport?
Chylomicrons formed in intestinal cells to transport dietary triglycerides
75
What are the three stages of the life cycle of apoB lipoproteins?
Assembly
Metabolism [hydrolysis]
Clearance
76
Which enzyme breaks down triglyceride into 2 fatty acids and monoglycerol?
Pancreatic lipase
77
Why does the triglyceride molecule need to be broken down?
It is insoluble and cannot be absorbed into the enterocyte
78
What happens when monoglyceride and 2 fatty acids are in the enterocyte?
Combine to reform triglyceride
79
Which receptor enables amphipathic cholesterol to enter the enterocyte?
NPC1L1 protein
80
What needs to be added to the chylomicron to allow its export from the enterocyte?
apoA1
81
Exported chylomicron enters the blood and is deposited into the venous system. True/False?
False
| Deposited into lymphatics and then the venous system
82
Where and how is VLDL assembled?
Liver cells, from free fatty acids derived de novo + from adipose tissue
83
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
84
Which enzyme hydrolyses apoB lipoprotein (chylomicron, VLDL, LDL)?
Lipoprotein lipase (LPL)
85
What facilitates binding of chylomicrons and VLDL to LPL?
apoCII (that was transferred from HDL)
86
What does LPL do to apoB lipoproteins?
Attacks and hydrolyses core triglycerides to fatty acids and glycerol which can be absorbed
87
What are chylomicron and VLDL remnants?
Particles depleted of triglyceride but still containing cholesterol ester
88
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
89
All apoB100 and apoB48 remnants are cleared via receptor-mediated clearance. True/False?
False
| Only 50% of apoB100 remnants are cleared this way
90
What happens to the remaining apoB100 remnants?
Eventually become LDL
91
Which receptor is vital for LDL clearance? Where is it importantly located?
LDL receptor in liver
92
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
93
How does cholesterol release inhibit cholesterol synthesis by hepatocytes?
Inhibits HMG CoA reductase
| Downregulates LDL receptor expression
94
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
95
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
96
What are the drugs of choice for reducing LDL (and moderately increasing HDL)? Give examples
Statins - simvastatin, atorvastatin
97
How do statins work?
Inhibit HMG CoA reducatase, causing decrease in de novo cholesterol synthesis + increase in LDL receptor expression to enhance cholesterol clearance
98
When and how are statins administered?
Orally at night
99
What other drugs can be used for decreasing triglycerides?
Fibrates - bezafibrate, gemfibrozil
100
How do fibrates work?
Inhibit PPAR-alpha to enhance LPL production
101
What do bile acid binding resins do?
Cause excretion of bile salts, causing more cholesterol to be converted into bile salts
102
Name some bile acid binding resin drugs and a notable side effect
Colestyramine
Colestipol
Can cause GI irritation
103
What does Ezetimibe do?
Inhibits NPC1L1 protein to reduce cholesterol absorption by enterocytes, ultimately causing decrease in LDL
104
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
105
An arterial thrombus is a white thrombus. True/False?
True
106
What colour is a venous thrombus?
Red
107
Where do white thrombi commonly lodge?
Brain (detached embolus from left heart)
108
Where do red thrombi commonly lodge?
Lung (detached embolus from right heart)
109
What do VIIa, XIa and XIIa do downstream in the blood coagulation pathway?
Activate X to Xa
110
What does Xa do downstream in the blood coagulation pathway?
Activates II to IIa[prothrombin to thrombin]
111
What does IIa (thrombin) do downstream in the blood coagulation pathway?
Activates fibrinogen to fibrin, the component of fibrin clots
112
What happens in response to endothelial damage in terms of platelets?
Adhere to site of injury and become activated, attracting other platelets, causing aggregation
113
What mediators do activated platelets secrete/synthesize? What do they do?
ADP, 5-HT, TXA2
| Enhance platelet aggregation
114
Name the inactive precursors of the main clotting factors involved in coagulation
II, VII, IX, X
115
What do the inactive precursors of clotting factors require initially in order to be able to become activated?
Gamma-carboxylation
116
What does the enzyme which carries out gamma-carboxylation of clotting factor precursors require?
Vitamin K
| [in its reduced, hydroquinone form]
117
What are the two forms of Vitamin K that exist?
K1 from diet
| K2 from bacteria in intestine
118
How does warfarin work?
Competitively binds to vitamin K reductase, causing inhibition and thus reducing hydroquinone VK [ultimately inactivating clotting factor precursors]
119
How is warfarin administered? How fast is its onset of action?
Oral
| 2-3 days
120
What is the main risk with anticoagulant drugs?
Risk of haemmorhage
121
How does liver disease potentiate activity of warfarin?
Decreased clotting factors
122
How does a high metabolic rate potentiate the activity of warfarin?
Increased clearance of clotting factors
123
How does pregnancy decrease the effect of warfarin?
Increased synthesis of clotting factors
124
How might a warfarin overdose be treated?
Vitamin K/clotting factor infusion
125
What does Antithrombin III (ATIII) do?
Inhibits IIa and Xa to inhibit coagulation
126
How does heparin cause anticoagulation?
Accelerates inhibition of IIa and Xa through ATIII - increases affinity of the latter for the former
127
Heparin must bind to ATIII and IIa in order to inhibit IIa. True/False?
True
128
Heparin must bind to ATIII and Xa in order to inhibit Xa. True/False?
False
| Only needs to bind to ATIII
129
LMWH inhibits IIa but not Xa. True/False?
False
| Inhibits Xa but not IIa
130
Give examples of LMWHs
Enoxaparin
| Dalteparin
131
How is heparin administered?
Intravenously or subcutaenously
132
How is LMWH administered?
Subcutaneously
133
Name an oral active inhibitor of thrombin
Dabigatran etexilate
134
Name an oral active inhibitor of Xa
Rivaroxaban
135
What is the role of vWF in platelet pathway?
Acts as a bridge to help platelets adhere to damaged endothelium
136
Which enzyme aids platelet synthesis of TXA2?
COX
137
Which receptor does ADP bind with to enhance platelet aggregation? Which drug blocks this receptor?
P2Y12 receptor
| Clopidogrel blocks this
138
Which platelet receptors does fibrinogen bind with to enhance platelet aggregation?Which drug blocks this?
GPIIb/IIIa receptorsTirofiban
139
Which drug blocks the synthesis of TXA2 through inhibiting COX enzyme? What is it's adverse effect?
Aspirin
| GI bleeding and ulceration (give with PPI)
140
How is aspirin administered?
Oral
141
How is clopidogrel administered? What is it's action?
Oral
| Binds to P2Y12 receptor via a disulphide bond causing irreversible inhibition
142
What is the role of plasmin in the coagulation cascade?
Enforces fibrin degradation to form fibrin fragments (clot lysis)
143
How do fibrinolytic drugs work?
Activate plasminogen to form plasmin to cause clot lysis
144
Give examples of fibrinolytic drugs
Streptokinase
Aleplase
Duteplase
145
How are fibrinolytic drugs administered?
Intravenously
146
What is the 'funny current'?
Influx of sodium and potassium inwards during sinus rhythm
147
What are some uses of ACEi and ARBs?
Hypertension
| Heart failure
148
List the side effects of ACEi
Dry cough
Hypotension
Renal dysfunction
Angioneurotic oedema
149
In what situation, must you avoid ACEi and ARB? In what situation are they useful in.
Pregnancy
Bilateral renal artery stenosis
Diabetic nephropathy
150
What is used to control warfarin dosing?
International normalised ratio (INR)
151
Give some side effects of statins and fibrates
Mysositis
| Rhabdomyolosis
152
What are some considerations when prescribing streptokinase?
Action blocked after 4 days by Ig generation
| Be careful of allergic reactions in recent streptococcal infections
153
Give one side effect of tPa
Haemorrhage
