Pharmacology Flashcards
1
Q
Carbonic anhydrase inhibitors
A
- acetazolamide; methazolamide; dichlorphenamide
- inhibits luminal CA at proximal tubule→ less activity of Na/H antiporter, decreased HCO3 and Na+ (and water) reabsorption
- FeNa=5%
- Contraindicated in cirrhosis
- Tx: glaucoma (decrease IOP and vol), mountain sickness
- side effects: hypokalemia, metabolic acidosis; hepatic encephalopathy, BM depression, skin toxicity, sulfonamide HSR
2
Q
Aminophylline
A
- PDE inhibition and enhanced signalling via cAMP and cGMP; works at proximal tubule; decreased HCO3 and Na (and water) reabsorption
- aminophylline = theophylline + ethyelenediamine (solubility agent)
- Tx: reduce inflammation and bronchospasm in moderate-severe asthma, night symptoms; NOT as diuretic
- FeNa = 5%
- side effects: larger doses→ N/V CNS stimulation or seizures, tachycardia/arrythmias
- metabolized by liver; cimetidine and quinoline increase blood levels
3
Q
Mannitol
A
- osmotic diuretic; opposes H2O and Na reabsorption at proximal tubule→ increased osmolarity of tubular fluid
- Tx: increased drug clearance, minimize renal failure (shock or surgery), decrease IOP/ICP, diagnose oliguria
- FeNa = 5%
- side effects: risk of pulmonary edema
4
Q
Loop diuretics
A
- furosemide, bumetanide, torsemide, ethacrynic acid
- inhibits Cl portion of Na-K-2Cl cotransporter in luminal membrane at medullary and cortical (proximal) talH→ decreased K, Ca and Na reabsorption, resultant K loss
- Tx: crisis edema (pulmonary, CHF, cirrhosis), hypercalcemia, drug toxicity/OD; severe HTN in CHF or cirrhosis (vasodilate via prostaglandins and decrease preload by lowering volume)
- FeNa = 25%; eventually causes increase in PT reabsorption, decreases positive & negative free water clearance; decreases cortex-medulla molarity gradient; avoid NSAIDs, take before salty meals, reduce salt intake; useful in patients with renal insufficiency (GFR < 30)
- side effects: hyper glycemia/ lipidemia (DM!), hyperuricemia (gout!), hyperCa; hypoMg/K; photosensitivity, nephrocalcinosis, Rx interactions; ED
5
Q
Thiazide/thiazide-like diuretics
A
- thiazides: chlorothizide, hydrochlorothiazide
- thiazide-like: chlorthalidone, quinethazone, metolazone, indapamide
- inhibit Cl portion of Na-Cl cotransporter in the luminal membrane at early distal tubule→ decreased Na (and H2O) reabsorption, increased Ca reabsorption, resultant K loss
- Tx: HTN (intravascular contraction), CHF, chronic edema (cardiac insufficiency), idiopathic hypercalciuria (stones), nephrogenic diabetes insipidus
- FeNa = 8%
- side effects: hypoK/hyperCa, contraction alkalosis, decreases positive free water clearance; increased BUN & creatinine; hyperglycemia/lipidemia (DM) hyperuricemia (gout); hypo magnesia /natremia; gout, photosensitivity, ED
- lethal interaction w/quinidine (v. tach→ fib, may be due to hyperK)
- avoid NSAIDs, bile sequestrants
- increased risk of hypoK w/steroids or AmphoB
6
Q
K+ sparing diuretics
A
- amiloride, triamterene
- work on principal cell of collecting duct to blocks ENaC and Na/H antiporter in lumenal membrane→ decreased K secretion and distal tubule acid secretion, increased Ca absorption
- FeNa = 2%
- Tx: use w/ other diuretics to prevent hypokalemia; edema, idiopathic hypercalciuria (stones); Li-induced polyuria/toxicity, Liddle syndrome, mucocilliary clearance
- side effects: hyperkalemia in renal failure or patients on ACEi/ARBs
7
Q
Aquaretics
A
- conivaptan, tolvaptan
- new drug class with unproven clinical benefit
- ADH receptor antagonist working at collecting duct→ increased free water excretion
- Tx: hyponatremia (SIADH, CHF)
8
Q
Eplerenone
A
- K+ sparing diuretic; selective aldosterone receptor blocker devoid of antiandrogenic effect (inhibits Na reabsorption in distal tubule)
- Tx: CHF (30% in NYHA class III and IV); use w/ other diuretics to prevent hypoK; HTN edema; 1’/2’ aldosteronism; anti-testosterone agent
- side effects: hyperK; low incidence of gynecomastia and mennorhagia vs. spironolactone
9
Q
Spironolactone
A
- K sparing diuretic; competes for aldosterone receptor, inhibiting mRNA transcription and translation→ decreased Na and K channels, decreased #/activity of Na-K-ATPase in late distal tubule and collecting duct→ decreased K+ secretion, distal tubule acid secretion
- Tx: CHF mortality (30% in NYHA class III and IV); use w/ other diuretics to prevent hypokalemia; HTN edema; 1’/2’ aldosteronism; anti-testosterone agent
- side effects: hyperK in renal failure or patients on ACEi; gynecomastia, ED, a/oligomenorrhea, breast soreness
10
Q
ACE inhibitors
A
- short acting: capto_pril_
- long acting: lisinopril, benazepril, quinapril, ramipril**
- vasodilating: enalapril**
- blocks ACE conversion of ATI to ATII (potent vasoconstrictor); prevents breakdown of bradykinin (potent vasodilator)
- Tx: 1st line for CHF (reduces afterload), LV hypertrophy, post-MI (prevents LV remodeling); protective of diabetic nephropathy; mild/ moderate HTN, reduces incidence of future CAD events in at risk for or PMH of vascular disease;
- side effects: dry cough, hyperK, angioedema, inhibits renal autoregulation, hypotension
- contraindicated in pregnancy, renal artery stenosis, hyperK, and prior angioedema; caution in ARF; reduces future CAD events; may reduce risk of DM
11
Q
ARBs
A
- losartan, valsartan, irbesartan**
- competitive inhibition of ATII in vascular endothelium→ fall in PVR w/ little change in HR or CO
- Tx: CHF (reduces afterload), LV hypertrophy, post-MI (prevents LV remodeling); protective of diabetic nephropathy; mild/ moderate HTN
- as effective as ACEi; use if cough is an issue
- side effects: angioedema, decreased renal function, hypotension;
- contraindicated in pregnancy, renal artery stenosis, hyperkalemia, and prior angioedema; caution in ARF
12
Q
Aliskiren
A
- renin inhibitor (blocks ATI formation)
- not v. effective
- does not interfere with bradykinin
13
Q
Non-dihydropyridine Ca channel blockers
A
- diltiazem; verapamil (most heart specific)
- blocks L-type Ca channel→ decreased Ca intracellularly→ decreases CO (lowers HR via decrease AV nodal conduction) and decreases TPR (less than dihydropyridine)
- Tx: HTN, angina (esp. vasospastic; - ionotrope→ decreased MO2 demand), SVT (class IV anti-arrhythymic); good to preserve renal function in DM and CKD
- side effects: leg edema, bradycardia, AV nodal blockade, hypotension, worsening HF; constipation (most common), headache, flushing
- contraindicated in overt decompensated HF, bradycardia, sinus node dysfunction, high-degree AV block
14
Q
Dihydropyridine Ca channel blockers
A
- nifedipine, amlodipine**
- L-type Ca channel→ decreased Ca in vascular SM→ decreases TPR; no effect on AV nodal conduction
- Tx: HTN, Raynauds, angina (3rd choice drug); 1st line for coronary vasospasm;
- side effects: leg edema (less than nondihydros), constipation (most common), headache, flushing
- no bradycardia, can use in low HR patients, can use in patients with AV block
15
Q
ß blockers for HTN
A
- lower CO and decrease renin release
- Tx: 1st line for HTN if CHF, post MI/angina, CAD
-
nonselective: propranolol
- bronchospasm, bradycardia (-chronotrope), CHF (- ionotrope), masking hypoglycemia
- decreased exercise capacity, depression (crosses BBB), worsening PVD
-
selective ß1: metoprolol, atenolol, esmolol
- decrease contractility and HR (reduced MO2 demand); prevent MIs, prevent sudden cardiac death, increase survival post-MI (do not stop suddenly)
- less likely to have bronchospasm, hypoglycemic awareness, and depression
- side effects: fatigue, worsening claudication, impotence
-
combined a/ß: labetolol, carvedilol
- ß1 blockage with vasodilatory effects
- Tx: HTN urgency, ACS, CHF
16
Q
Terazosin (Hytrin)
Doxazosin (Cardura)
A
- blocks post-synaptic a1 receptor on vascular SM→ decreased arteriolar and venous resistance
- Tx: BPH (decrease tone of urinary sphincter), 2nd tier med for HTN
- side effects: orthostatic hypotension, fluid retention, worsening angina (2nd to reflex tachy)
17
Q
Clonidine (Catapres)
α-methyldopa (Aldomet)
A
- central α2-agonist→ reduction in symp outflow; inhibition of renin release (2nd to decreased symp tone)
- a methyldopa: only drug for HTN of pregnancy; takes place of dopa, so less NE (methyl-NE also activates α2)
- side effect: rebound HTN if abruptly stopped; moderate orthostatic hypotension; sedation, dry mouth, fatigue, depression
18
Q
Reserpine (Serpalan)
A
- ganglion blocking agent (blocks transport of NE, DA, and 5HIAA vesicles)
- Tx: decreased CO and TPR
- side effects: sedation, depression, Parkinsonism symptoms
19
Q
Hydralazine (Apresoline)
A
- direct vasodilators (prevent oxidation of NO)→ decrease TPR via arteriolar dilation
- Tx: HTN urgency; patients with both CHF and HTN
- side effects: SLE-like syndrome; reflex tachy
20
Q
Minoxidil (Loniten)
A
- direct vasodilators; open K channels→ hyperpolarization of SM→ vasodilation of arterioles
- Tx: refractory HTN; hair loss
- side effects: leg edema, pericardial effusion; hirsutism; reflex tachy
21
Q
Niacin (Niaspan)
A
- nicotinic acid→ reduction of liver TG synthesis→ less hepatic VLDL (thus LDL); decreases lipolysis in adipose→ lowered FFA transport to liver (thus, less TGs); reduced hepatic clearance of ApoAI (raising HDL)
- best agent to increase HDL (30-40%); as good as fibrates and statins at lowering TGs (35-4%); lowers LDL (20-30%)
- Tx: hyperTG and low HDL
- side effects limit compliance (<50%): flushing, pruritis of face and upper trunk (take aspirin), rashes, acanthosis nigricans, hepatotoxicity, hyperuricemia, hyperglycemia; dyspepsia/reactivation of peptic ulcer disease; rarely, toxic ambylopia, tachyarrhythmias, a-fib (in elderly) and myopathy
- contraindicated in DM and gout patients
22
Q
Fibric Acid Derivatives (Fibrates)
A
- Clofibrate, gemfibrozil, fenofibrate
- may interact w/peroxisome proliferator-activated receptor (esp. PPARα) to induce LPL (enhance TG-rich lipoprotein clearance); inhibit apoC III expression (enhance VLDL clearance); stimulation of apoAI and apoAII (increase HDL)
- Marked reduction in VLDL (thus, TGs); variable small effect on LDL; small increase in HDL (10%)
- Tx: severe hyperTG
- side effects: potentiate oral anticoag (displace from albumin), gallstones; myositis flu-like syndrome in 5% (higher risk + statin)
23
Q
Bile acid sequestrants
A
- colestipol, cholestyramine, colesevelam
- v. + resins bind - bile acids, inhibiting reabsorption and increasing CH loss→ increase LDL receptors in liver (to make more CH), decreasing LDL in blood
- Tx: pure hyperCH (decrease LDL (25%), but slight increase (5%) in TG and HDL)
- v. safe (indicated for kids) because not systematically absorbed; impairs vitamin ADKE absorption, binds other drugs (e.g., cardiac glycosides, coumarins)
- standard treatment in combo w/statin; contraindicated in hyperTG
- side effects: bloating, dyspepsia, constipation, gritty/unpleasant taste
