NS, CV and renal pharmacology Flashcards
1
Q
What is the treatment for second and third degree heart block?
A
Emergency treatment required - Atropine (IV) or Isoprenaline (IV)
2
Q
Class I Anti-arrhythmic drugs
A
Sodium channel blockers
3
Q
Class II anti-arrhythmic drugs
A
Beta blockers
4
Q
Class III anti-arrhythmic drugs
A
K+ channel blockers/Prolong A.P duration
5
Q
Class IV anti-arrhrhymic drugs
A
Calcium channel blockers
6
Q
What are the differences between Class Ia,b and C anti-arrhythmic drugs?
A
Differences due to recovery/unbinding of drugs
7
Q
What is the main affect of Class I anti-arrhrhymic drugs?
A
Block Na+ channels to decrease phase 0 - depolarisaiob
8
Q
Dysopyramide
A
Sodium channel blocker (Class 1A anti-arrhythmic drug) used to treat ventricular arrhythmias
9
Q
Lidocaine (IV)
A
Sodium channel blocker (Class 1b anti-arrhrhymic drug) used in treatment prevention of ventricular tachycardia and fibrillation during and immediately after myocardial infarction
10
Q
Flecainide
A
Sodium channel blocker (Class 1c anti-arrhrhymic drug) used to prevent paroxysmal atrial fibrillation and recurrent tachyarrythmias associated with abnormal conduction pathways
11
Q
Amiodarone, sotalol, Bretylium
A
K+ channel blockers, prolong A.P depolarisation
12
Q
What is Amidarone used to treat?
A
Tachycardia associated with WPW syndrome
13
Q
What is Sotalol used to treat?
A
used in paraxysmal supraventricular dsyrthmias and suppresses ventricular ectopic beats, and short runs of ventricular tachycardia
14
Q
outline the mechanism of CCB’s
A
act on L-type channels, shorten the plateau of the AP and reduce the force of contraction. Reduced Ca2+ entry reduces after depolarisation and thus suppresses premature ectopic beats
15
Q
Veramapil
A
CCB
16
Q
Diltiazem
A
CCB
17
Q
outline the side effects of CCBs?
A
bradycardia, negative inotropic effect, constipation (verapamil), hypotension (diltiazem)
18
Q
Loop diuretics, site of action
A
Act on thick ascending limb (TAL) of loop of Henle to inhibt Na+/K+/Cl-
19
Q
Furosemide, Butetamide
A
Loop diuretics
20
Q
Thiazides site of action
A
Distal tubule
21
Q
Why might thiazides be preferred over loop diuretics?
A
Thiazides are less powerful than loop diuretics so preferred in treating uncomplicated hypertension. In contrast to loop diuretics thiazides reduce Ca2+ excretion and so is favourable in elderly patients
22
Q
Thiazides mechanism of action
A
Bind to the Cl- site of distal tubular Na+/Cl- cotransport system inhibiting its action causing natriuresis with loss of Na+ and Cl-, results in reduced blood volume.
23
Q
Clinical uses of thiazide diuretics
A
Hypertension, mild heart failure (loop diuretics preferred), severe resistant oedema, nephrogenic diabetes insipidus
24
Q
Adverse effects of loop diuretics and thiazides
A
hypotension, gout, hypokalemia (caues dysrhythmias, increased digoxin toxicity and hyperglycaemia)
25
Potassium sparing diuretics- site of action
Act exclusively on distal parts of nephron: collecting tubule and collecting duct
26
Aldosterone antagonist - mechanism of action
Competitive inhibtion of intracellular aldosterone receptors, decreases the numbre of luminal Na+ channles and decreases number of basolateral Na+-K+-ATPases. This inhibits Na+ retention and K+ secretion
27
Spironolactone
Potassium sparing diuretic - aldosterone antagonist
28
Na+ channel blockers - mechanism of action
Inhibit Na+ re-absorption by blocking lumenal sodium channels and decreasing K+ excretion
29
Triameterene, Amiloride
Potassium sparing diuretic - Na+ channel blockers
30
Clinical uses of potassium sparing drugs
used with K+ losing diuretics, heart failure, primary aldosteronism (conns syndrome), resistant essential hypertension, secondary hyperaldosteronism caused by hepatic cirrhosis complicated by ascites
31
Osmoitic diuretics - site of action
Main effect is exerted on parts of the nephron that are FREELY permeable to water: proximal tubule, descending limb of the loop and collecting tubules
32
Osmotic diuretics - mechanism of action
Increase filtrate osmolairty, passive water reabsoprtion is reduced by the presence of non reabsorbable solute within the tubule
33
Clinical use of Osmotic diuretics
Used in emergency treatment of acutely raised intraocular or intracranial pressure
34
Clinical uses of carbonic anhydrase inhibitors
Glaucoma, altitude sickness, little use as a diuretic drug due to rapid tolerance
35
What is nephrotic syndrome?
Increased permeability of the glomerular basement membrane to proteins leading to proteinuria. Increases volume of interstitial fluid leading to tissue swelling and activation of RAAS.
36
Treatment of glomerular nephritis
Antihypertensive, loop diuretic, immunosuppresive
37
Consquences of glomerular nephritis
Acute renal failure, chronic renal failure, dialysis or transplantation
38
Acute Kidney Injury
Abrupt reduction in kidney function resulting in failure to maintain fluidm electrolye, and acid-base homeostasis. Decreased urine production and fluid-electrolyte imbalance.
39
Pre-renal causes of AKI
Causes that decrease effective blood flow to the kidney e.g. reduced cardiac output - heart failure, MI, bradycardia. Drugs - ACE inhibitors, NSAIDS
40
Renal causes of AKI
Blockage of renal vasculature = uric acid crystals, cholesterol emboli, vasculitis, endothelial damage (blood clots). Glomerulonenephritis Interstitial nephritis
41
Post renal causes of AKI
Urinary tract obstruction, benign prostatic hypertrophy, cancers/tumours, stones, non-emptying bladder, crystal deposition
42
Disopyramide, procainamine, quinidine
Class 1a antiarrythmic drugs - sodium channel blockers. Intermediate dissociation rate, leading to moderate decrease in phase 0 and increased QRS and QT interval Used to treat AF (triggered by vagal overreactivity) and VT
43
lidocaine, mexiletine
Class 1b anti-arrhythmic drugs -sodium channel blockers. Fast dissociation rate, decreased AP duration and QT interval. Used to treat and prevent VT and VF immediatley after Myocardial infarction
44
Flecainide, Moncizine, propafenone
Class 1c anti-arrhythmic drugs, blocks with slow dissociation rate causing large decrease in phase 0, leading to increased QRS and QT interval. Used to treat AF and recurrentt tachycardias associated with adnormal conduction pathways and WPW syndrome
45
Class 1a anti-arrhythmic drugs side effects
Atropine like (urinary retention, dry mouth, blurred vision, constipation) and Quinide causes syncope (due to triggering torsades de pointes)
46
Class 1b anti-arrhythmic drugs side effects
CNS, drowsiness, disorientation and convulsions
47
Beta blockers mechanism
Block cardiac B1 adrenoreceptors to reduce sympathetic drive to the heart, decreasing heart rate
48
Propranolol
Non selective B antagonist, long acting, oral
49
Timolol
Non selective B antagonist, used to treat glaucoma (decreases AH formation)
50
Atenolol, bisoprolo, metoprolol
B1 Selective antagonist
51
Pindolol
B1 Selective partial agonist
52
Nevbivolol
B1 selective antagonist and also increases NO (leading to less fatigue, bradycardia,and impotence)
53
Labetalol
Mixed alpha/beta adrenergic antagonist
54
Carvedilol
Mixed Alpha1/beta antagonist
55
Clinical uses of beta blockers
Rate control in SVT, rate and rhythm control in AF and flutter, VT
56
Adverse effects of B blockers
Bronchospasm (caution in asthma), negative inotropic effect, bradycardia, fatigue, increased risk of hypoglycaemia (diabetics)
57
Sotalol, amiodarone, bretylium
Class 3 anti-arrhythmic drugs-prolong AP duration by prolong phase 3 by blocking K+ channels
58
Amidarone
K+ channel blocker. Also a modest Na+ and Ca2+ blocker and alpha adrenergic receptor antagonist and decreases cardiac B1 adrenergic receptor expression. When given orally has slow onset (up to 3 weeks) and a very long plasma half life
59
Amidarone side effects
thyroid abnormalities, corneal deposits, pulmonary disorders, skin pigmentation
60
Class 3 anti-arrhythmic drugs clinical uses
SVTs, WPW syndrome, ventricular tachycardias
61
Sotalol
Class 3 anti-arrhythmic also a non selective B blocker. Lacks the adverse ADRs seen in amidarone
62
Verapamil, Diltiazen
Class IV anti-arrhythmic drugs. Calcium channel blockers to slow down AVN conduction
63
Therapeutic uses of Class IV anti-arrhythmic drug
paroxsmal SVT, AF (but NOT if due to WPW)
64
Class IV anti-arrhythmic drug side effects
bradycardias, negative inotropic effect, constipation (verapamil), hypotension (more with diltazem)
65
Ist line treatment for hypertension \<55 years
ACE inhibitor or angiotensin receptor AT1 blockers
66
Captopril, Enalapril
ACE inhibitors
67
ACE inhibitors effects
reduce TPR with little effect on HR or cardiac output
68
ACE inhibitors adverse effects
Dry cough (due to accumulation of bradykinin)
69
Losortan, Candesartan
Angiotensin receptor (AT1) blockers
70
?Why mgiht AT1 blockers be preffered over ACE inhibitors
NO dry cough - no bradykinin accumulation
71
Aliskiren
Renin inhibitor
72
Renin inhibitors
e.g. Aliskiren. reduces plasma renin activity by binding and inhibiting activity
73
Contraindication of RAAS inhibitors
In pregnancy (due to fetotoxicity)
74
Common ADRs of RAAS inhibitors
hypotension (with thiazides), hypersemsitvity (head & neck angioedema), hyperkalaemia
75
1st line hypertension treatment in African/Carribbean and elderly (\>55 years)
Calcium channel blockers
76
Nifedipine, Amlodipine
CCB, dihydropines, act preferentially on vascular smooth muscle, use in hypertension and angina
77
Phenylalkylamines
Verapamil - CCB act on cardiac preferentially
78
Benzothiazepines
Diltiazem, CCB with an intermediate effect on cardiac and smooth muscle
79
ADRs of Calcium channel blockers
Postural hypotension, flushes/tremors (nifedipine), AV block and negative ionotropic effects (verapamil, diltiazem)
80
Treatment for hypertension when ACEi/CCBs do not work?
Also give patient diuretics
81
Treatment in resistant hypertension
B Blockers and alpha antagonists
82
Statins, fibrates, bile-acid binding resins
Lipid lowering drugs
83
Statins mechanism
inhibits HMG-CoA reductase (key enzyme in cholestrol production)
84
Simvastatin, Atorvastatin, Pravastatin
Statins
85
Clinical uses of Statins
Primary and secondary prevention of CHD, (in patients with chronic kidney disease, diabetes type 1 and 2) familial hypercholesterolaemias, in children (\>10years)
86
Contraindications in statins
In pregnancy
87
Statins ADRs
Muscle. (more serious: myopathies, hepatotoxicity)
88
Fibrates mechanism and effects
activator of peroxisomal proliferator activator receptor (PPARalpha) leads to increasedity, lipoprotein lipase activity and increase HDL synthesis
89
Clinical uses of Fibrates
In combination with statins/ in various dyslipidaemias
90
Fenofibrate, gemfribrozil
Fibrates (lipid lowering drugs)
91
Colestyramine, cholestipol
Bile acid binding resins (lipid lowering drugs)
92
Bile acid binding resins mechanism and effects
Enhance plasma cholesterol clearance via enterohepatic circulation. Get decrease in LDL (but no increase in HDL and triglyceride :( )
93
Clinical uses of bile acid binding resins
In patients with liver disease/pregnancy (with caution) when statins are not recommended
94
Ezetimibe
Lipid lowering drug, decreases cholesterol absoroption
95
Nicotinic acid/Niacin
Lipid lowering drug
96
Aspirin
COX-1 Inhibitors (antiplatlet agent)
97
Clopidogel mechanism
Antagonists of ADP Receptors (antiplatlet drug). Reduced expression of GPIIb/IIIa leads to platlet aggregation
98
Dipyridamole
Phosphodisterase inhibitors
99
ABCIXIMAB, Eptifibatide, tirofiban
Glycoprotein IIb/IIIa receptor inhibitors
100
Aspirin therapeutic uses
Primary prevention of ACS (in stable angina):Low dose Aspirin 75-150mg/day
In unstable angina: higher loading doses 150-300mg
Secondary prevention of MI = in combination with ACEI, statins and B blockers
101
Aspirin Side Effects
GI bleeding, Cerebral Haemorrhage
102
Clopidogrel clincial uses
Secondary prevention of MI (with aspirin or alone)
103
Anticoagulant mechanism of Heparin
Binds reversibly to to antithrombin III (ATIII) and greatly accerlates the rate at which it inactivates coagulation enzymes thrombin and factor Xa
104
Side effects of Heparin
Bleeding, immune thrombocytopenia, osteoporosis, hypersensitivity
105
Protamine Sulfate
Herpain antagonist (IV admin) used to to stop bleeding caused by heparin
106
Fondapariunux
Synthetic pentasaccheride inhibitor of activated factor Xa
107
Fondaparinux clinical uses
Acute coronary syndromes (unstable angina, NSTEMI, STEMI), stroke, deep-vein thrombosis, pulmonary embolism, prophylaxis of venous, thromboembolism follwoing orthapedic surgery
108
Enoxaparin
Low molecular weight Heparin
109
Hirudin, Bivalirudin
Direct thrombin inhibitors
110
Direct thrombin inhibitors therapeutic uses
Prevention of stroke and systemic embolism. Prophylaxis of venous thromboembolism (After hip or knee replacement surgery)
111
Rivaroxaban
Selective factor Xa inhibitor
112
Warfain
Oral anticoagulant. Inhibits Vitamin K reductase
113
Warfain -drug interactions
Antibiotics (decreased vitamin K avalibilty) excess alcohol (increases warfain), drugs inhibiting hepatic drug metabolism, NSAIDS (increase internal bleeding) Hypothyroidism (decreases warfain) and Hyperthyroidism (ncrease warfain)
114
Warfain: side effects and contraindication
Bleeding.
Teratogenic (avoid in 1st trimester in pregnancy)
115
Clinical uses of anticoagulants
treatment of unstable angina (NSTEMI), Prophylaxis of venous thromboembolism,
116
Alteplsae
fibrinolytic agent - recombinant tPA. Prevents conversion of plasminogen to plasmin
117
Reteplase
Fibrinolytic agents- recombinant tPA prevents conversion of plasminogen to plasmin
118
Streptokinase
fibronlytic agent
119
Urokinase
fibrinolytic agents
120
Tranexamic acid
anti-thrombolytic
121
First line treatment of heart failure
ACE inhibitor +B-blocker + Diuretic
122
Digoxin, Oubain
Cardiac glycosides
123
Milrinone, Enoximone
Phoshodiesterase type 3-inhibitors cardiac selective
124
Minoxidil, Diazoxide, Nicorandil
Potassium (ATP-sensitive) channel activators (openers)
125
Uses and effects of phoshodiesterase inhibitors in CHF
Use: short term treatment in acute decompensation of CHF
Effects: increased CO, reduced right atrial pressure, reduced TPR, overall has little affect of HR and BP
126
Phosphodiesterase inhibitors side effects
Nausea, vomiting, liver abnormalities, thrombocytopenia, lethal arrthymias (with prolonged use)
127
Glyceral trinitrate, isosorbide dinitrate, isosorbide mononitrate, sodium nitroprusside
Nitrates, and nitric oxide releasing drugs
128
Ivabradine
I (funny) current inhibitors (SA node)
129
Ranolazine
blocker of persistent cardiac sodium channels
130
Moxonidine
Imidazoline I1 receptor agonists
131
Levosimendan
Calcium sensitising positive inotropes
132
Loop diuretics. Site of action
Thick ascending limb of the loop of henle
133
Loop diuretics. Mechanism
Inhbition of the luminal Na+ /K+/2Cl- cotransporter
134
Furosemide, Bumetanide
Loop diuretics
135
loop diuretics - therapeutic uses
For treatment of salt and water overload in: acute pulmonary oedema, CHF, renal failure, nephrotic syndrome.
Liver cirrhosis with ascites
Hypertension complicated by renal impairment
136
Thiazides site of action
early distal tubule
137
Thiazides mechanism
Inhibition of Na+/Cl- transporter
138
Bendroflumethiazide, Chlorothiazide
Thiazides
139
Chlortalidone, Indapamide, Metolazone
Thiazide-like drugs
140
Thiazides therapeutic uses
hypertension, in mild heart failure, severe resistant odema, prevention of kidney stone formation in idiopathic hypercalcicuria, nephrogenic diabetes insipidus
141
Adverse effects of loop diuretics and thiazides
Hypotension, Gout, Hypokalaemia (Dysrhythmias, increased digoxin toxicity, hyperglycaemia)
142
Spironalactone, Epleronone
Aldoesterone antagonists (Potassium sparing diuretic)
143
Amiloride, Triamterene
Na+ channel epithelial blockers
144
Potassium sparing diuretics therapeutic uses
To prevent hypokalalemia, heart failure, resistant essential hypertension, aldosteronisms
145
Adverse effects of potassium sparing diuretics
Main= hyperkalaemia (more common in patients with renal diseases)
146
Mannitol
Osmotic diuretic
147
Mechanism of osmotic diuretics
Increase filtrate osmolarity. decreasing passive water reabsorption. Act of parts of the nephron freely permeable to water: Proximal tubule, descending limb of loop of henle, collecting tubule (in the presence of ADH)
148
Osmotic diuretics therapeutic uses
In acute renal failure.
Non renal uses: in emergency treatment of raised intracranial and intraocular pressure (glaucoma)
149
Acetazolamide
Carbonic anhydrase inhibitors
150
Carbonic anhydrase inhibitors clinical uses
Glaucoma, alitude thickness - little use as a diuretic drug due to rapid tolerance
151
152
Phenylephrine - site of action
alpha 1 selective agonist
153
Phenylephrine and Methoxamine uses
Selective Alpha 1 agonists cause smooth muscle constriction, used as nasal decongestants
154
Methoxamine
Selective alpha 1 agonist
155
Clonidine - site of action and effects
Selective alpha 2 agonist prevents NA release and hence reduces BP used as an antihypertensive
156
Dobutamine - site of action
B1 agonist
157
Dobutamine effects and uses
Dobutamine is an B1 agonist which increases cardiac contractility and so is used to treat cardiogenic shock
158
Adrenaline - therapeutic uses
Cardiac arrest and anaphylatic shock
159
Terbutaline -site of action
B2 agonist
160
Carbidopa
Inhibits NA synthesis by inhibiting DOPA decarboxylase. Used to treat parkisons disease alongside Levodpa
161
alpha-methyl-p-tyrosine
Inhibits tyrosine hyroxylase, inhibiting synthesis of NA - prossible us in phaechromocytoma
162
Isoprenaline
NON SELECTIVE Beta agonists
163
Oxymetazoline
NON SELECTIVE alpha agonist
164
Doxazocin, Prazosin - site of action
Selective alpha 1 agonists
165
Effects of Prazosin
Alpha 1 antagonist causing vasodilation and fall in aterial pressure (smooth muscle relaxation of bladder)
166
Yohimbine - site of action
Selective alpha 2 antagonist
167
Amphetamine, Tyramine
Indirectly acting sympathimimetic. Substrate for NET - rapidly displaces NA and increases NA in the synapse.
168
Cocaine, impramine
Inhibits NET -and therefore NA uptake, increasing NA in synapse
169
Guanethidine
Substrate for NET and VMAT. Displaces NA slowly (high doses will destory neurones)
170
Reserpine
Inhibits VMAT and therefore vesicular NA uptake. Free NA is metabolised by MAO
171
Side effects of Reserpine
Depression and parkinsonism
172
NA is metabolised by what two enzymes
Monoamine Oxidase (MAO) and Catechol-O-methyl transferase
173
Alpha-methyldopa
False NA precursor. Metabolised to methyl-NA acts as a alpha 2 agonist (this inhibits release of NA), used to treat pregnancy induced hypertension.
174
175
Carbachol
Muscarinic receptor agonists
176
Bethanecol
Muscarinic agonist - use to assist bladder empyting or to stimulate GI
177
Pilocarpine
Muscarinic receptor agonist - selectivity for constrictor pupillae, sweat, salivary, lacrimal. (minimal activity on smooth muscle and heart) Used to treat glaucoma. Stable compound actions last for one day.
178
Oxotremorine
Muscarinic agonist
179
Methacholine
Muscarinic receptor agonist
180
Atropine
NON Selective muscarinic antagonist
181
Clinical uses of Atropine
Adjunct anaesthia, treat anticholinsterase poisoning, bradycardia, GI hypermotility
182
Atropine side effects
Urinary retention, dry mouth, blurred vision, constipation
183
Scopolamine
Non selective muscarinic receptor antagonist.
184
Pirenzipine
M1 selective antagonist - treatment for peptic ulcers
185
Ipratropium
Non selective muscarinic antagonist
186
What is Ipratripiom used to treat?
Irritant induced bronchospasm by inhilation/nebulisers, asthma, bronchitis, COPD
187
Tioptropium
Simular to Iproatropium but with improved PK. Binds to all muscarinc receptors - but with so M3 selectivity
188
Oxybutynin
M3 selective antagonist
189
Nicotinine
Stimulates autonomic ganglia, leads to tachycardia, increased BP and increased secretions
190
Trimetaphan
Blocks nicotinic receptors and therefore action of ACH. used for emergency lowering of blood pressure
191
Hexamethonium
Blocks channels on autonomic ganglia - doesnt not compete with ACh
192
Hemicholinium
Blocks the uptake of choline
193
Botulinum toxin
Prevents vesicles fusing and releasing ACh (Botox)
194
Vesamicol
Vesamicol acts presynaptically by inhibiting ACh uptake into synaptic vesciles leads to empty vesicles fusing with neuron membranes and reducing ACh release.
195
Tubocurarine
non depolarising competitve nACh receptor antagonist
196
Gallamine
Non depolarising competitive nACh antagonist - synthetic analogue of tubocuraine
197
Pancuronium
non depolarisng competitive nACh antagonist - synthetic analogue of tubocuraine
198
Suxamethonium
Nicotinic acetylcholine receptor agonist, depolarizing neuromuscular blocker, resulting in persistent depolarization of the motor end plate. Used to induce short term muscle relaxation and short term paralysis
199
α-Bungarotoxin
Bind irreversibly and competitively to the nACh receptors causing paralysis and respiratory failure
200
Triethylcholine
Acts presynaptically. It is a drug that mimics choline (false transmitter) and causes failure of cholinergic transmission by interfering with synthesis of acetylcholine in nerve endings.
201
Streptomycin
Inhibits Ca2+ entry presynaptically
202
Neomycin
Inhibits Ca2+ entry presynaptically
203
ß-Bungarotoxin
Acts pre-synaptically to block ACh release
204
Neostigmine
Parasympathomimetic that binds and inhibits acetylcholinesterase. Used in people with myasthenia gravis.
205
Edrophonium
Anticholinesterase reversible inhibitor
206
Physostigmine (Eserine)
Physostigmine is a parasympathomimetic, specifically, a reversible cholinesterase inhibitor which effectively increases the concentration of acetylcholine at the sites of cholinergic transmission. Physostigmine is used to treat glaucoma. Because it crosses the blood-brain barrier, it is also used to treat the central nervous system effects of atropine overdose and other anticholinergic drug overdoses
207
Disopropyl fluorophosphate (DFP)
Diisopropyl fluorophosphate is a parasympathomimetic drug irreversible anti-cholinesterase and has been used in ophthalmology as a miotic agent in treatment of chronic glaucoma
208
Sarin
Inhibitor of anticholinisterase
209
Pralidoxime
Dyflos/Sarin antidote
210
