Pharm block 2 Flashcards
(262 cards)
1
Q
classes of diuretics
A
carbonic anhydrase inhibitors (acetazolamide); osmotic diuretics (mannitol); loop diuretics (furosemide - K+-wasting); thiazides (hydrochlorothiazide - K+-wasting); K+-sparing diuretics (triamterene/amiloride; spironolactone); natriuretic peptides (nesiritide)
2
Q
carbonic anhydrase inhibitor drugs
A
acetazolamide; related: dorzolamide (topical, eye)
3
Q
carbonic anhydrase inhibitors pk
A
oral, iv; excreted via proximal tubule
4
Q
carbonic anhydrase inhibitors renal pd
A
indirectly blocks bicarb reabsorption; alkalinisation of urine; metabolic acidosis; inc K+ secretion downstream; inc NaCl reabsorption (-> tachyphylaxis)
5
Q
carbonic anhydrase inhibitors intra-ocular pd
A
block NaHCO3 secretion; dec aqueous humor formation
6
Q
carbonic anhydrase inhibitors choroid plexus pd
A
dec rate of cerebrospinal fluid formation
7
Q
carbonic anhydrase inhibitors uses
A
glaucoma - topical dorzolamide, systemic acetazolamide in emergencies; urinary alkalinisation - inc excretion of weak acids (uric acid, cysteine, aspirin) (theoretical); mountain sickness - choroid (cerebral edema, respiratory alkalosis)
8
Q
carbonic anhydrase inhibitors adverse effects
A
metabolic acidosis; kidney stones; renal K+-loss; CNS toxicity (drowsiness, paresthesias)
9
Q
carbonic anhydrase inhibitors contraindications
A
hepatic cirrhosis (reversal of NH4+ -> trapping acidic urine by alkalinisation) - NH4+ -> hepatic encephalopathy
10
Q
mannitol characteristics
A
non-absorbable, non-metabolizable sugar
11
Q
mannitol pk
A
MUST be IV; excreted via glomerular filtration
12
Q
mannitol pd
A
retains h2o in tubule; some inc in natriuresis
13
Q
mannitol uses
A
water diuresis (when preferred to Na excretion); maintain tubular flow (non-responders -> test dose); reduce intra-cranial/-ocular pressure
14
Q
mannitol adverse effects
A
EC volume expansion (-> CHF, pulmonary edema); dehydration, hypernatremia
15
Q
loop diuretics
A
FUROSEMIDE; bumetanide; torsemide; ethacrynic acid
16
Q
loop diuretics pk
A
oral, iv, instant onset
17
Q
loop diuretics pd
A
inhibit Na/K/Cl symporter in thick ascending limb -> directly affects blood flow
18
Q
furosemide uses
A
EMERGENCIES; edematous conditions (acute pulmonary edema, acute CHF); acute hypercalcemia/hyperkalemia; acute renal failure - adjust oliguria, inc K secretion (flushing tubules -> non-oliguric renal failure); anion overdose (combine w/saline - bromide, fluoride, iodide); forced diuresis; (hypertension, CHF - second line for refractory cases; short-term)
19
Q
furosemide adverse effects
A
HYPOKALEMIA; hypokalemic metabolic alkalosis; ototoxicity; hyperuricemia (->gouty attack); hypomagnesaemia; allergic rxns (sulfonamide moiety)
20
Q
furosemide contraindications
A
other ototoxic drugs (aminoglycoside antibiotics)
21
Q
thiazide diuretics - hydrochlorothiazide pd
A
inhibition of NaCl symporter in distal convoluted tubule; UNLIKE LOOP diuretics -> inc Ca reabsorption
22
Q
hydrochlorothiazide pk
A
usually oral
23
Q
hydrochlorothiazide adverse effects
A
similar to loop diuretics (less pronounced); hypokalemia, hypokalemic metabolic acidosis; hyperuricemia; hypernatriuria; impaired carb tolerance, hyperlipidemia; allergic rxns
24
Q
hydrochlorothiazide uses
A
hypertension - inexpensive, proven, effective, safe, one daily dose, no dose titration needed; congestive heart failure; nephrolithiasis from IDIOPATHIC HYPERCALCIURIA (normal serum Ca!) - intestinal Ca-hyperabsorbers, renal ca/PO4 leakers; nephrogenic diabetes insipidus
25
metolazone pk
oral (65% bioavail)
26
metolazone pd
similar to thiazide diuretics; also effective when GFR\<30ml/min;
27
metolazone uses
hypertension; edema; use instead of other thiazides in combo treatment of FUROSEMIDE RESISTANCE
28
K+-sparing diuretics - triamterene, amiloride pk
triamterene - hepatic metabolism, renal excretion; amiloride - renal excretion
29
triamterene, amiloride pd
mild inc in NaCl excretion via effects in late distal tubule/collecting duct
30
triamterene, amiloride adverse effects
HYPERKALEMIA (muscle weakness, fatigue, arrhythmia) esp in combo w/ACE inhibitors; metabolic acidosis; triamterene - acute renal failure (w/indomethacin), kidney stones
31
K+-sparing diuretics - spironolactone pk
prodrug of canreonate - IV
32
spironolactone pd
aldosterone antagonist -\> delayed effect; mild inc in NaCl excretion in the late distal tubule, collecting duct
33
spironolactone adverse effects
HYPERKALEMIA esp. in combo w/ACE inhibitors; metabolic acidosis; gynecomastia
34
natriuretic peptide - nesiritide characteristics
B-type; in cardiac ventricles, released in response to myocardial distenstion; drug from E. coli; counterregulation of RAAS
35
nesiritide pk
IV peptide drug
36
nesiritide pd
activate guanylyl cyclase -\> vascular smooth muscle relaxation; interlinked antagonisms for renin, ATII, aldosterone, ADH - inc GFR, dec Na reabsorption
37
nesiritide uses
acute severe heart failure
38
five classes of antihypertensive drugs
diuretics, beta-andrenoceptor antagonists (beta-blockers), Ca-channel blockers, angiotensin inhibitors (ACE inhibitors, AT1 blockers), alpha-adrenergic blockers
39
centrally-acting antihypertensive drugs
clonidine, methyldopa, reserpine
40
vasodilators
nitrates, nitroprusside, dihydralazine
41
classification of blood pressure for adults
normal =160/\>=100
42
(reserpine) characteristics
rauwolfia alkaloid; obsolete but good model drug
43
(reserpine) pk
oral; effects persist for up to 6 weeks (intolerable)
44
(reserpine) pd
depletes biogenic amines from neuronal vesicles by inhibition of reuptake, CNS/periphery
45
(reserpine) uses
none
46
(reserpine) adverse effects
denervation of sympathetic system -\> parasympathetic system prevails; nasal congestion, hypersecretion (bad for asthmatics); bronchoconstriction; mental depression (suicidal thoughts); parkinsonism; ulcerogenic
47
clonidine characteristics
alpha2 sympathomimetic drug; 2nd choice for treating hypertension; interesting off-label uses
48
clonidine pk
oral, iv, transdermal patch
49
clonidine pd
centrally mediated hypotensive effects - alpha2 agonist -\> dec CO, relax capacitance of vessels, dec peripheral resistance -\> renal blood flow maintained; may have initial hypertensive episode; pronounced rebound after prolonged use
50
clonidine uses
2nd line treatment of hypertension
51
clonidine adverse effects
high doses -\> bradycardia, AV-block, fxn'l cardiac failure, dry mouth, drowsiness, sedation, constipation
52
clonidine other clinical uses
symptomatic treatment of w/drawal syndromes (heroin, alcohol, benzodiazepines); prevent/treat alcoholic delirium; postmenopausal syndrome; refractory diarrhea (short bowel syndrome); adjunct in analgo-sedation (-\>dexmedetomidine)
53
methyldopa characteristics
centrally acting antihypertensive safe in PREGNANCY
54
methyldopa pk
oral
55
methyldopa pd
centrally mediated hypotensive effects comparable, not identical, to clonidine
56
methyldopa adverse effects
mostly like clonidine; Coombs test may turn positive
57
alpha1-blockers
prazosin, terazosin, doxazosin
58
prazosin, terazosin, doxazosin pk
oral, iv
59
prazosin, terazosin, doxazosin pd
blockade of alpha1-receptors in arterioles/venules; no effect on inhibitory feedback for NE release (selective for alpha1)
60
prazosin, terazosin, doxazosin adverse effects
first dose phenomenon (hypotension, syncope) -\> give initial dose at bedtime; orthostatic hypotension; tests for antinuclear factor (ANF) may turn positive (reflex tachy)
61
choice of diuretic drug in hypertension
CHOICE: thiazides (hydrochlorothiazide); 2nd line: K+-sparing - amiloride, triamterene, spironolactone; for GFR \<30ml/min or refractory hypertension - loop diuretic (furosemide) or thiazide (METOLAZONE)
62
rules for routine use of thiazides
low dose, take in morn; combo w/k-sparing diuretic if hypokalemia a problem (watch for hyperkalemia); keep pt on dry weight but may cause dehydration -\> mental confusion, aggravate COPD, peripheral arterial occlusive disease; important adverse effects - hypokalemia, hyperuricemia, impaired glucose tolerance, hyperlipidemia
63
beta-adrenoceptor antagonists (beta-blockers)
propranolol (non-selective); atenolol, metoprolol (beta1\>beta2); pindolol (partial agonist); labetalol (alpha, beta-blocker, beta2 agonist); carvedilol (alpha/beta blocker); esmolol (beta1\>beta2, short-acting, emergencies)
64
beta-blockers characteristics
beta1 selectivity is relative -\> NEVER use for asthma, COPD; use in CHF is tricky - use tiny doses
65
unselective beta-blockers contraindications
pregnancy; diabetes; beta1-blockers can be considered; asthma, COPD, PAD, SA/AV abnormalities
66
alpha1-blockers vs. beta-blockers
alpha1-blockers don't affect insulin-sensitivity -\> minimal changes in CO -\> don't cause cold extremity syndrome; beta-blockers don't cause orthostatic hypotension
67
calcium channel blockers
VERAPAMIL, diltiazem, nifedipine (and dihydropyridines); huge advantage over beta-blockers bc can give to diabetics, asthmatics, in pregnancy, COPD
68
verapamil, diltiazem, nifedipine pk
oral, iv, bound by serum proteins
69
verapamil, diltiazem, nifedipine pd
block L-type ca channels -\> "cardiodepressant" (antiarrhythmic), arteriolar vasodilation
70
nifedipine (dihydropyridine) adverse effects
due to excessive vasodilation -\> dizziness, headache, REFLEX TACHY, peripheral edema, constipation
71
verapamil, diltiazem adverse effects
bradycardia, slow SA/AV conduction
72
MI risk with antihypertensive drug therapy
short-acting, fast acting Ca channel blockers nifedipine, diltiazem and verapamil was associated w/inc risk of MI
73
second generation Ca channel blockers - long-acting
AMLODIPINE (standard - no inc risk of MI), felodipine, nisoldipine
74
second generation Ca channel blockers - slow onset
AMLODIPINE, felodipine
75
second generation Ca channel blockers - increased vascular selectivity
nisoldipine
76
second generation Ca channel blockers - increased potency
isradipine
77
interaction Ca channel-blockers and beta-blockers
beta blockers can potentiate the vasodilating effects of ca-channel blockers; 1+1=3
78
angiotensin inhibitors
ACE - inhibitors; ATII (AT1 subtype)-blockers
79
ACE-inhibitors
CAPTOPRIL, enalapril, enalaprilat, lisinopril, benzaepril, fosinopril, moexipril, quinapril, ramipril; all used for hypertension, some also for CHF
80
ATII (AT1)-blockers
losartan (hypertension, CHF); valsartan (hypertension)
81
ACE inhibitors - captopril pk
oral
82
captopril pd
ATII antagonism (ACE inhibition) -\> dec vasoconstriction/NE release/ aldosterone secretion
83
bradykinin-related ACE inhibition pd
keeps bradykinin active -\> vasodilation -\> no reflex tachy, no significant change in CO, no h2o/na retention, some dec of sympathetic tone
84
captopril adverse effects
hypotension, dry cough, bronchospasm, skin rashes, angioneurotic edema, neutropenia, leukopenia, taste perversion, hyperkalemia, proteinuria
85
captopril contraindications
renal artery stenosis, renal failure; history of angioedema (asthma, COPD); pregnancy (oligohydramnion)
86
captopril toxicity
hypotension w/o marked tachy
87
captopril unwanted interactions
NSAIDs inhibit bradykinin pathway - dec antihypertensive response; K-sparing diuretics aggravate hyperkalemia; hypersensitivity to other drugs can be aggravated; inc plasma levels of digoxin, lithium
88
captopril therapeutically exploited interactions
K-wasting diuretics yield over-additive antihypertensive effect
89
ACE inhibitors - enalapril/enalaprilat characteristics
enalapril is prodrug of enalaprilat
90
enalapril pk
oral
91
enalaprilat pk
iv - hypertensive emergencies
92
enalapril, enalaprilat pd compared to captopril
longer duration of action
93
enalapril, enalaprilat adverse effects compared to captopril
no sulfhydryl-group -\> no taste perversion
94
ACE inhibitors - others
most are prodrugs; fosinopril, moexipril - hepatic elminiation,, others renal;
95
ACE-inhibitors uses
hypertension; chf; MI; progressive renal disease in diabetic nephropathy (hyper-and normo-tensive pt's)
96
losartan characteristics
angiotensin II subtype 1 blocker (AT1 blocker)
97
losartan pk
oral
98
losartan pd
LIKE ACE-inhibitors -\> dec vasocontriction, dec NE release, dec aldosterone secretion; UNLIKE ACE inhibitors -\> NO effect on bradykinin
99
losartan adverse effects
like ACE inhibitors (except bradykinin-related ae's) - no/less cough, no angioedema
100
losartan contraindications
renal artery stenosis, renal failure, pregnancy
101
single drug therapy of hypertension
THIAZIDE or BETA BLOCKER or ca channel blocker or ACE inhibitor (or alpha1 blocker)
102
combination therapy of hypertension
thiazide w/beta-blocker, ca channel blocker, or ACE inhibitor; ca channel blocker w/beta-blocker or ACE inhibitor
103
triple therapy of hypertension
combo therapy with furosemide or clonidine
104
positive criteria for selection of antihypertensive drugs - diuretics
old age, black race, chf, chronic renal failure (loop diuretics)
105
positive criteria for selection of antihypertensive drugs - beta-blockers
youth, white, post-MI, migraine, senile tremor, atrial fibrillation (to control ventricular rate), paroxysmal supraventricular tachy
106
positive criteria for selection of antihypertensive drugs - long-acting ca channel blockers
old age, black race, migraine
107
positive criteria for selection of antihypertensive drugs - ACE inhibitors
youth, white race, type I diabetes w/nephropathy, impotence from other drugs; NOT IN PREGNANCY
108
positive criteria for selection of antihypertensive drugs - AT1-blockers
same as ACE inhibitors but can't be used due to hypersensitivity/cough; NOT IN PREGNANCY
109
positive criteria for selection of antihypertensive drugs - alpha-blockers
prostatism, diabetes mellitis, dyslipidemia
110
Traditional treatment of CHF
inotropic - muscle changes
111
vasodilators used for chf
hydralazine - arterioles; minoxidil - arterioles; nitrates - veins/venules; ACE inhibitors - arterioles, veins
112
treating a symptom - fatigue
rest, positive inotropes
113
treating a symptom - edema
salt restriction, diuretics, digitalis
114
treating a symptom - dyspnea
diuretics (loop)
115
treating a symptom - congestion
nitrovasodilators, diuretics
116
treating a symptom - poor cardiac contractility
positive inotropes, digitalis
117
treating a symptom - increased pre/afterload
ACE inhibitors, ang-blockers, veno/vasodilators
118
treating a symptom - cardiac tissue remodeling
ACE inhibitors, ang-blockers, beta-blockers, spironolactone
119
treating a symptom - irreversible heart failure
heart transplantation
120
cardiac glycosides
digoxin, digitoxin
121
problems with cardiac glycosides
narrow therapeutic margin; complicated/unfavorable pk; sensitivity varies b/n pt's, could change during therapy; severe, lethal ae's
122
digoxin cardiac effects
inc myocardial contractility; dec sinus HR (- chronotropic effect) mainly due to vagal nerve input to SA node; dec AV conduction velocity - prolong refractory period in AV (- dromotropic effect); inc automaticity/excitability in atria, purkinje, ventricles
123
digoxin possible therapeutic benefits
inc CO; improve tissue perfusion; improve diuresis -\> resorption of edema; dec sympathetic tone, vasoconstrction; dec peripheral resistance (afterload); dec preload; dec myocardial overdistension; improve working efficiency -\> favorable; improve symptoms, but NO DEC IN DEATHS
124
digoxin adverse effects
arrhythmia: tachyarrhythmia (premature ventricular contractions, ventricular fibrillation - low K+), bradyarrhythmia (non/paroxysmal atrial tachy, AV-block - high K+); GI - anorexia, nausea, vomiting, diarrhea; CNS - headache, malaise, neuralgias, delirium (Van Gogh Starry Night)
125
digoxin precipitating factors for adverse effects
hypo/hyperkalemia; drug accumulation/overdose; hypomagnesemia, hypercalcemia; hyperthyreosis; abnormal renal fxn; respiratory disease; acid-base imbalances
126
digoxin toxicity treatment
w/draw drug; monitor plasma dig, K levels, ECG; adjust electrolyte status; ventricular tachyarrhythmia - lidocaine, mg2+, adjust K to high normal
127
severe digoxin toxicity
associate with hyperkalemia -\> bradyarrhythmias, suppressed automaticity -\> temp pacemaker; digitalis antibodies (digoxine immune fab, digibind)
128
digoxin indications
chf grade NYHA III/IV; antiarrhythmic therapy for atrial flutter/fibrillation
129
digoxin non-indications
ineffective in myocarditis, corpulmonale; uncontrolled hypertension; bradyarrhythmias; non-responders or intolerance (severe ae's)
130
ACE inhibitors uses
hypertension, chf, MI, progressive renal disease
131
ACE inhibitors uses - CHF
prevent/delay progression of heart failure (can't improve ejection fraction); dec incidence of sudden death, MI; dec hospitalization; improve quality of life
132
ACE inhibitors uses - MI
dec mortality when started in periinfarction period (no later than 16 days post MI)
133
how to use a beta-blocker
start low (10%dose, go slow); clinical assessment b4 every inc in dose (NYHA III - outpatient, NYHA IV - hospitalize); late onset of benefit (3mths - 12/18mths); give w/diuretics, ACE inhibitors, digitalis (keep as constant as possible, manages side effects); only method that can INCREASE EJECTION FRACTION
134
managing side effects of beta-blockers in treating CHF
give w/diuretics, ACE inhibitors, digitalis; try to maintain beta-blocker, consider: sedation, hypotension (to reduce diuretics, ACE inhibitors), edema (inc diuretic), bradycardia, AV-block (dec digitalis)
135
Last resort treatments
inotropic drugs for acute cardiac failure; keep pt alive for few more days/weeks - dopamine (low dose, act on dopamine receptors in kidney); dobutamine (iv; acts on alpha/beta receptors, inc CO w/o affecting HR); amrinone/milrinone (inc myocardial cAMP by inhibiting PDE III, inc contractile system sensitivity to ca; vaso/venodilation -\> potentiates effect of dobutamine -\> kills pt)
136
Class I antiarrhythmic drugs - fast channel blockers (Na)
quinidine, lidocaine, flecainide
137
Class II antiarrhythmic drugs - beta-blockers (Ca)
propranolol (beta antagonist), atenolol (beta1 antagonist), esmolol (short-acting beta1 antagoinst), sotalol (beta antagonist, k-channel blocker)
138
Class III antiarrhythmic drugs - inhibitors of repolarization (K)
prolong AP, ERP; amiodarone, bretylium (indirect sympatholytic, antihypertensive), sotalol, ibutilide (emergencies), dofetilide (like sotalol, less ae's)
139
Class IV antiarrhythmic drugs - calcium channel blockers (Ca)
verapamil, diltiazem
140
unclassified antiarrhythmic drugs
adenosine, atropine, digoxin, magnesium
141
main factors promoting arrhythmias
ischemia/hypoxia; acid-base imbalance; inc autonomic input; drug toxicity (digitalis, antiarrhythmic drugs); overstretching cardiac fibers (chf); impaired tissue (MI survivors)
142
all arrhythmias result from:
disturbance in impulse formation, conduction, or combo of both
143
delayed afterdepolarization
result of ischemia, anything that affects cAMP (E/NE, theophylline), digitalis, tachy
144
early afterdepolarization
result of brady, hypokalemia, action potential delaying drugs
145
principles to therapy of cardiac arrhythmias
eliminate/minimize precipitating factors; define arrhythmia type (brady/tachy? ventricular/supraventricular?); minimize risks of doing drug therapy -\> most cause arrhythmias!
146
goals of therapy of cardiac arrhythmias
terminate ongoing arrhythmia; prevent recurrence
147
class IA antiarrhythmic drugs
inhibits Na AND k channels -\> prolonged repolarization; quinidine, procainamide, disopyramide
148
class IB antiarrhythmic drugs
accelerated repolarization; lidocaine (used for resuscitation), mexiletine, tocainide (phenytoin)
149
class IC antiarrhythmic drugs
little effect - rarely used; flecainide, propafenone
150
quinidine pk
oral, IM, BID, QID (iv - watch for arrhythmia, hypotension)
151
quinidine pd
na channel block in ACTIVATED STATE -\> dec vmax in phase 0; block K channels -\> prolong AP; antimuscarinic (low doses) -\> inc AV-conduction (paradoxically); alpha-blocker (high conc)
152
quinidine cardiac effects
block Na channels in ACTIVATED STATE -\> dec automaticity; dec conduction/excitability; recovering from blockade - slower in depolarized than polarized tissue; RESULT: prolonged refractory period esp in depolarized tissue; block K channels - dec max re-entry frequency -\> prolong AP, ERP
153
quinidine EKG effects
prolong QRS (delays conduction in bundle of His, purkinje); prolong QT, alter T-wave (delays repolarization); variable prolongation of PR (slows AV conduction)
154
quinidine cardiac adverse effects
dec CONTRACTILITY (- inotrope); paradoxical inc sinus rate, av-conduction (antimuscarinic actions) -\> remove protective av-block -\> ventricular tachy; torsade des pointes - polymorphic ventricular tachy -\> could kill, self-limiting (quinidine syncope); excessive dec conduction -\> toxic (AVB, asystolia) - serum K \> 5, quinidine \> 5
155
quinidine extracardiac pd
antimalarial (2nd line, CHOICE for falciparum malaria); hypotensive (alpha-blocker)
156
quinidine extracardiac adverse effects
GI disturbances; CNS - cinchonism (overdose of cinchona) - headache, dizziness, tinnitus
157
quinidine extracardiac drug interactions
compete for CYP450 w/digoxin, verapamil, others
158
quinidine use
supraventricular arrhythmias - paroxysmal supraventricular tachy, wolff-parkinson-white syndrome, convert atrial flutter/fibrillation to sinus rhythm as adjunct/2nd-line treatment; do not use w/o prior digitlization
159
procainamide characteristics
amide of procaine; protected from enzymatic hydrolysis; less cns effects
160
procainamide pk
oral; iv arrythmia, hypotension
161
procainamide pd
LIKE quinidine; block na channels in activated state, block K channels; antimuscarinic (less than quinidine); alpha-sympatholytic
162
procainamide adverse effects
cardiac/GI - like quinidine; cns - mental confusion, psychosis, less frequent than w/lidocaine; hypersensitivity (much more often w/quinidine), lupus-like syndrome (reversible), 70% w/ANAs; hypotension; antimuscarinic - aggravates glaucoma, urinary retention
163
procainamide uses
indications similar to quinidine -\> try other if one doesn't work; 2nd choice after lidocaine for sustained ventricular arrhythmias w/acute MI; oral - sustained release for prolonged therapy; iv - infusion, ECG-monitoring, control plasma levels
164
class IB - lidocaine characteristics
amide local anaesthetic
165
lidocaine pk
ONLY iv
166
lidocaine pd
block IN/ACTIVATED na channels -\> more pronounced effect in tissues w/long plateaus (purkinje, ventricular) and depolarized tissue; little effect on K-channels -\> shorten AP duration (effect depolarized, arrhythmogenic tissue)
167
lidocaine cardiac adverse effects
exacerbate arrhythmias; SA-standstill in pt's w/MI
168
lidocaine cns adverse effects
paresthesias; toxic - convulsions, coma (very high doses)
169
lidocaine drug interactions
agents that interfere w/hepatic perfusion, microsomal metabolism
170
lidocaine uses
CHOICE for ventricular tachy, fibrillation after cardioversion; suppress arrhythmia assoc w/depolarization (post MI, dig toxicity); NOT for prolonged prophylactic use post-MI
171
mexiletine characteristics
orally active congeners of lidocaine
172
mexiletine pk
oral
173
mexiletine pd
same as lidocaine
174
mexiletine adverse effects
frequent w/therapeutic doses; cns - nausea, tremor, blurred vision, lethargy; allergic - rash, fever, agranulocytosis
175
(phenytoin) characteristics
antiepileptic drug similar to phenobarbital
176
(phenytoin) pk
oral, iv
177
(phenytoin) pd
same as lidocaine
178
(phenytoin) adverse effects
cns - sedation, nystagmus, vertigo, loss of mental accuity; gingival hyperplasia
179
class IC - flecainide, propafenone characteristics
very slow dissociation from na channel during recovery; use in life-threatening, refractory arrhythmia; flecainide CAST - inc mortality in post MI pt's treated for premature ventricular contractions -\> use ONLY oral for atrial arrhythmias in hearts otherwise uncompromised
180
class II prototype drug - propranolol cardiovascular effects
dec SA freq -\> sinus brady; dec automaticity in purkinje; prolong ERP of AV-node; suppress ectopic ventricular depolarizations; - inotrope; diverse hemodynamic effects
181
propranolol cardiovascular adverse effects
hypotension, aggravation of chf, asystolia
182
propranolol uses
dec risk of sudden death in post MI; control supraventricular tachy; exercise/stress-precipitated ventricular arrhythmias; ischaemic heart disease, angina pectoris
183
class III - amiodarone pk
2 weeks to reach steady state; 30-120 days half life
184
amiodarone pd
block INACTIVATED na channels - most pronounced in tissues w/long plateaus (purkinje, ventricular), depolarized; block k-channels; weak ca channel, beta blocker
185
amiodarone adverse effects
can deposit in tissues (slowly reversible) -\> pulmonary fibrosis, corneal deposits, photodermatitis, skin discoloration; cns - paresthesias, tremor, ataxia, headache; thyroid dysfxn; GI/liver toxicity
186
amiodarone drug interactions
digoxin, theophylline, warfarin, quinidine
187
class III - sotalol characteristics
racemic mix used
188
sotalol pk
oral, iv
189
sotalol pd
block k-channels; beta blocker
190
sotalol adverse effects
same as beta blockers; proarrhythmic (torsades des pointes)
191
sotalol uses
treat/prophylaxis of severe ventricular tachyarrhythmias, atrial arrhythmias
192
ca channel blockers - verapamil, diltiazem characteristics
block L-type ca-channels in in/activated states; most pronounced effect on AV-conduction
193
verapamil, diltiazem uses
re-entrant supraventricular tachy; dec ventricular rate in atrial fib, flutter; ischaemic heart disease, angina pectoris; hypertension
194
adenosine characteristics
ubiquitous auto/para/endocrine compound
195
adenosine pk
iv infusion
196
adenosine pd
purine-p1 receptor agonist; inc k-conductance, inhibits cAMP-mediated ca influx -\> hyperpolarization, esp in av-node
197
adenosine uses
conversion of narrow complex paroxysmal ventricular tachy (PSVT)
198
adenosine adverse effects
transient (short t1/2) -\> flushing, av-block III, chest pain, atrial fib, bronchoconstriction esp in asthmatics
199
miscellaneous antiarrhythmics
potassium; magnesium (ca-antagonist - treat torsades des pointes, dig-induced arrhythmia, prevent arrhythmia in acute MI); digoxin (slow av conduction); atropine (bradyarrhythmia -\> dec vagal tone)
200
drug therapy for atrial fibrillation
- dromotropic agents -\> digoxin, verapamil/diltiazem, beta-blockers; induce/maintain sinus rhythm - block fast action potentials (class IA, IC, III antiarrhythmics)
201
angina treatment drugs
nitrates, beta-blockers, ca-channel blockers
202
angina combination treatment
nitrate + beta-blocker
203
nitrates
nitroglycerine, isosorbide dinitrate (ISDN), isosorbide mononitrate (ISMN)
204
nitrates pd
relax smooth muscles, including vascular; fast relaxation of venous tone -\> inc capacitance, dec preload; slowly dec arteriolar resistance -\> dec myocardial O2 demand
205
nitrates pk
nitroglycerine - subligual, buccal, transderma, iv; NOT oral
206
nitrates adverse effects
vasodilation -\> headache, flushing; hypotension -\> reflex tachy, dizziness, weakness, cerebral ischaemia; nitrate tolerance
207
nitrates uses
acute/anticipated attacks of angina; prolonged preventative therapy (ISMN, ISDN); paroxysmal nocturnal dyspnea in chf; spasmolytic in colic pain (biliary, renal, intestinal)
208
factors that induce nitrate tolerance
prolonged nitrate exposure (patch, sustained release, iv); large doses; frequent dosing
209
factors that prevent nitrate tolerance
intermittent dosing; small doses; infrequent dosing; nitrate-free intervals
210
sodium nitroprusside characteristics
ferrocyanide compound; limit use to only some hours
211
sodium nitroprusside pd
direct NO donator -\> immediate vasodilation
212
sodium nitroprusside pk
iv infusion; protect from light, converted to cyanide, then thiocyanide
213
sodium nitroprusside uses
ICU/emergencies; controlled hypotension in surgery; some of severest cardiac failure
214
sodium nitroprusside precautions
borderline systolic BP; myocardial ischaemia w/o heart failure; hepatic/renal insufficiency
215
sodium nitroprusside adverse effects
nausea, vomiting, headache, cns disturbances
216
sodium nitroprusside toxicity
cyanide intoxication
217
ca channel blockers
verapamil, diltiazem, nifedipine (and dihydropyridines)
218
verapamil, diltiazem, nifedipine pk
oral, iv
219
verapamil, diltiazem, nifedipine pd
block L-type ca channels -\> cardiodepressant, arteriolar vasodilation
220
verapamil, diltiazem, nifedipine adverse effects
dihydropyridines (excessive vasodilation) -\> dizziness, headache, peripheral edema, reflex tachy; verapamil, diltiazem -\> brady, slow SA/AV conduction
221
beta blockers for angina
propranolol, atenolol, metoprolol
222
beta blockers effects on angina
dec severity/freq in exertional angina; somewhat effective in unstable angina; cardioprotective in post MI (beta1 selective); ineffective in vasospastic angina - may worsen condition
223
antihyperlipidemic drugs
hmg coa reductase inhibitors (statins); niacin; fibrates; bile-acid binding agents; cholesterol absorption inhibitors; combination drug therapy
224
statins
lovastatin, sinvastatin, pravastatin, atorvastatin, fluvastatin, rosuvastatin
225
statins characteristics
CHOICE, most efficacious for inc LDL (hypercholesterolemia)
226
statins pk
cyp450
227
statins pd
inhibit hmg coa reductase (HMG analogs) -\> inc LDL receptor expression (homozygotes for FH -\> no LDL receptors -\> no response); modest dec TGs; small inc HDL
228
statins adverse effects of monotherapy
myopathy, myositis w/rhabdomyolysis; inc transaminase, liver enzymes
229
statins adverse effects of combo therapy
interactions (cyp450); myopathy, myositis, rhabdomyolysis; inc risk of overdose of ther drugs
230
statins contraindications
pregnancy/lactation, hepatic disease, muscular disease
231
statin combinations
w/bile acid binding agent or cholesterol absorption inhibitor (more dec LDL); w/niacin - inc risk of myopathy; w/fibrates - inc risk of rhabdomyolysis (gemfibrozil)
232
bile-acid binding agents
cholestyramine, colestipol, colesevelam
233
cholestyramine, colestipol, colesevalem characteristics
2nd choice for lipid reduction; ensure ample fluid intake to avoid constipation
234
cholestyramine, colestipol, colesevalem pd
cationic resins - bind to negatively charged bile acids in sm intestine -\> prevent reabsorption -\> inc conversion of cholesterol to bile acids; inc LDL receptor
235
cholestyramine, colestipol, colesevalem pk
oral, fat soluble -\> not absorbed/met'd; uncomfortable to ingest; completely excreted in feces
236
cholestyramine, colestipol, colesevalem interactions
acidic drugs, coumadin, vitamin c; dec absorption of fat-soluble vit's, drugs (digoxin, warfarin, antiretrovirals, cyclosporin)
237
cholestyramine, colestipol, colesevelam uses
type IIa/b hyperlipidemias; only w/isolated inc in LDL; hypercholesterolemia in young (s w/biliary obstruction (pancreatic carcinoma)
238
cholestyramine, colestipol, colesevalem adverse effects
GI - constipation, nausea, bloating, flatulence
239
cholestryamine, colestipol, colesevalem combinations
w/statins or niacin -\> more dec LDL
240
cholestyramine, colestipol, colesevalem contraindications
can upregulate vldl, TG synth -\> caution in pt's w/hypertriglyceridemia
241
niacin
nicotinic acid, vitamin b3
242
nicotinic acid, vitamin B3 characteristics
most effective agent to inc hdl
243
nicotinic acid, vitamin b3 pd
dec vldl, ldl, tg; inhibits lipolysis in adipose; dec FA's -\> dec triacylglycerol synth (req'd for vldl); inc HDL
244
nicotinic acid, vitamin b3 pk
oral; converted to nicotinamide -\> used in NAD; niacin/metabolites excreted in urine
245
nicotinic acid, vitamin b3 uses
when statin contraindicated; familial hyperlipidemias; combo w/statins for severe hypercholesterolemias
246
nicotinic acid, vitamin b3 adverse effects
cutaneous flush, pruritus (vasodilator); hyperuricemia; hepatotoxicity; impaired insulin sensitivity (caution diabetics); combo w/statin -\> inc risk of myopathy
247
fibrates
fenofibrate, gemifibrozil
248
fenofibrate, gemfibrozil pk
oral; bound to albumin
249
fenofibrate, gemfibrozil pd
dec vldl, tg's; inc hdl; modest dec ldl; binds, activates PPARalpha (hepatocytes, sk muscle, macrophages, heart);
250
fenofibrate, gemfibrozil uses
hypertriglycerolemias; CHOICE for dysbetalipoproteinemia; pt's not responding to diet/other drugs
251
fenofibrate, gemfibrozil adverse effects
mild GI; CHOLELITHIASIS; myositis
252
fenofibrate, gemfibrozil interactions
compete w/coumarin (warfarin) for plasma binding sites -\> potentiates anticoagulant activity
253
fenofibrate, gemfibrozil contraindications
PREGNANCY safety not established
254
cholesterol absorption inhibitors
ezetimibe, plant sterols
255
ezetimibe, plant sterols pd
dec ldl (small dec tg's, small inc hdl); inhibit absorption of dietary, biliary cholesterol; inhibit hepatic vldl synth; upregulation of ldl receptor
256
ezetimibe, plant sterols pk
oral; met in sm intestine, liver
257
ezetimibe, plant sterols uses
complementary to statins or in combo when statins inadequate; hypercholesterolemia when statin CI'd
258
ezetimibe, plant sterols adverse effects
diarrhea, ab pain, headache, rash, angioedema
259
ezetimibe, plant sterols contraindications
pregnancy, lactation
260
omega-3 fatty acids - fish oils characteristics
dec tg's
261
fish oils pd
dec tg synth; inc fa oxidation
262
fish oils uses
tg \> 500mg/dL
