Pharmacology Flashcards
Side effects of ACEI
ACEIs dilate afferent arteriole
Hyperkalemia, cough, angioedema (increased bradykinin)
Furosemide
Sulfonamide loop diuretic: inhibits Na-K-2Cl symporters in the thick ascending limb of the loop of Henle → increased Na and Cl excretion → increased water excretion
Loop diuretics also stimulate renal prostaglandins which dilate the afferent arteriole → increased renal blood flow → increased GFR → increased drug delivery
Concurrent use of NSAIDs will blunt diuretic response
Indicated for edematous states, HTN, hypercalcemia
SA: ototoxicity, hypokalemia, dehydration, slfa allergies, interstitial nephritis, gout
Spironolactone
Competitive aldosterone receptor antagonist in the cortical collecting tubule (K+ sparing diuretic)
Indicated for hyperaldosteronism, K+ depletion, CHF (improves survival)
SA: hyperkalemia → arrhythmias, endocrine effects such as gynecomastia, antiandrogen effects
Eplerenone
Competitive aldosterone receptor antagonist in the cortical collecting tubule (K+ sparing diuretic)
Indicated for hyperaldosteronism, K+ depletion, → CHF (improves survival)
SA: hyperkalemia → arrhythmias; fewer side effects than spironolactone
Triamterene
Na+ channel blockers in the cortical collecting tubule (K+ sparing diuretic)
Indicated for hyperaldosteronism, K+ depletion, CHF
SA: hyperkalemia → arrhythmias
Amiloride
Na+ channel blockers in the cortical collecting tubule (K+ sparing diuretic)
Indicated for hyperaldosteronism, K+ depletion, CHF
SA: hyperkalemia → arrhythmias
Mannitol
Osmotic diuretic → increased tubular fluid osmolarity → increased urine flow → decreased intracranial/intraocular pressure
Indicated for drug overdose, increased intracranial/intraocular pressure
SA: pulmonary edema, dehydration
Contraindicated in anuria, CHF
Acetazolamide
Carbonic anhydrase inhibitor → NaHCO3 diuresis and decreased total body HCO3- stores
Indicated for glaucoma, urinary alkalinization, metabolic alkalosis, altitute sickness, pseudotumor cerebri
SA: hyperchloremic metabolic acidosis, paresthesias, NH3 toxicity, sulfa allergy
Ethnacrynic acid
Phenoxyacetic acid loop diuretic: inhibits Na-K-2Cl symporters in the thick ascending limb of the loop of Henle → increased Na and Cl excretion → increased water excretion
Loop diuretics also stimulate renal prostaglandins which dilate the afferent arteriole → increased renal blood flow → increased GFR → increased drug delivery
Concurrent use of NSAIDs will blunt diuretic response
Indicated for edematous states, HTN, hypercalcemia
SA: ototoxicity, hypokalemia, dehydration, slfa allergies, interstitial nephritis, hyperuricemia → don’t use with gout
Hydrochlorothiazide
Thiazide diuretic: inhibits NaCl reabsorption in early distal tubule → decreased diluting capacity of the nephron; decreased calcium excretion
Indicated for HTN, CHF, idiopathic hypercalciuria, nephrogenic DI, osteoporosis
SA: hypokalemic metabolic alkalosis, hyponatremia, hyperglycemia, hyperlipidemia, hyperuricemia, hypercalcemia, sulfa allergy
Captopril
ACE inhibitor → decreased angiotensin II → dilation of efferent arteriole → decreased GFR
Indicated for HTN, CHF, proteinuria, diabeic nephropathy, prevention of unfavorable remodeling as a result of chronic HTN or MI
SA: cough (ACEI prevent inactivation of bradykinin), angioedema, teratogen, increased creatinine due to decreased GFR, hyperkalemia, hypotension
Contraindicated in bilateral renal stenosis (further decrease in GFR → renal failure)
-sartans
Angiotensin II receptor blockers (ARBs)
Decreased risk of cough or angioedema because it does not increase bradykinin
How do diuretics affect serum calcium concentration?
Loop diuretics can cause hypocalcemia → hypercalciuria (Loops Loose calcium).
Thiazide diuretics can cause hypercalcemia → hypocalciuria
How do diuretics affect serum potassium concentration?
Serum potassium increases with K+ sparing diuretics and decreases with loop and thiazide diuretics.
What effects do diuretics have on acid-base status?
Carbonic anhydrase inhibitors and K+ sparing diruetics may cause acidemia.
Loop and thiazide diuretics may cause alkalemia.
Torsemide
Sulfonamide loop diuretic: inhibits Na-K-2Cl symporters in the thick ascending limb of the loop of Henle → increased Na and Cl excretion → increased water excretion
Loop diuretics also stimulate renal prostaglandins which dilate the afferent arteriole → increased renal blood flow → increased GFR → increased drug delivery
Concurrent use of NSAIDs will blunt diuretic response
Indicated for edematous states, HTN, hypercalcemia
SA: ototoxicity, hypokalemia, dehydration, slfa allergies, interstitial nephritis, gout
Chlorthalidone
Thiazide diuretic: inhibits NaCl reabsorption in early distal tubule → decreased diluting capacity of the nephron; decreased calcium excretion
Indicated for HTN, CHF, idiopathic hypercalciuria, nephrogenic DI, osteoporosis
SA: hypokalemic metabolic alkalosis, hyponatremia, hyperglycemia, hyperlipidemia, hyperuricemia, hypercalcemia, sulfa allergy
Bumetanide
Sulfonamide loop diuretic: inhibits Na-K-2Cl symporters in the thick ascending limb of the loop of Henle → increased Na and Cl excretion → increased water excretion
Loop diuretics also stimulate renal prostaglandins which dilate the afferent arteriole → increased renal blood flow → increased GFR → increased drug delivery
Concurrent use of NSAIDs will blunt diuretic response
Indicated for edematous states, HTN, hypercalcemia when furosemide is ineffective
SA: ototoxicity, hypokalemia, dehydration, slfa allergies, interstitial nephritis, gout
Metolazone
Thiazide-like diuretic
Bethanechol
Cholinergic agonist - activates bowel and bladder smooth muscle, resistant to anticholinesterase
Indicated for postoperative ileus, neurogenic ileus, and urinary retention
Carbachol
Cholinergic agonist
Indicated for glaucoma (↑ aqueous humor outflow via opening of trabecular meshwork), pupillary constriction, and relief of intraocular pressure
Pilocarpine
Cholinergic agonist
I_ndicated for open-angle and closed-angle glaucoma (↑ aqueous humor outflow via opening of trabecular meshwork)_; potent stimulator of sweat, tears, and saliva
Methacholine
Muscarinic receptor agonist → stimulates muscarinic receptors in the airway when inhaled causing bronchoconstriction
Used for asthma challenge tests
Neostigmine
Anticholinesterase with no CNS penetration
Indicated for postoperative and neurogenic ileus and urinary retention, myasthenia gravis, postoperative reversal of neuromuscular junction blockade
Physostigmine
Anticholinesterase with CNS penetration
Indicated for anticholinergic toxicity, glaucoma
Pyridostigmine
Anticholinesterase with no CNS penetration
Indicated for myasthenia gravis (long-acting)
Donepezil
Acetylcholinesterase inhibitor → ↑ acetylcholine
Indicated for Alzheimer disease
Rivastigmine
Acetylcholinesterase inhibitor → ↑ acetylcholine
Indicated for Alzheimer disease
Galantamine
Acetylcholinesterase inhibitor → ↑ acetylcholine
Indicated for Alzheimer disease
Edrophonium
Anticholinesterase
Historically used to diagnose myasthenia gravis because it is extremely short-acting
Anticholinesterase inhibitor poisoning
Commonly caused due to exposure to organophosphates like parathione
Causes diarrhea, urination, miosis, bronchospasm, bradycardia, excitation of skeletal muscle and CNS, lacrimation, sweating, and salivation
Treat with atropine (antimuscarinic) and pralidoxime (regenerates acetylecholinesterase)
Atropine
Muscarinic antagonist that works on the eye to produce mydriasis/dilation via paralysis of ciliary muscles and to treat bradycardia
Also used to treat organophosphate (cholinesterase inhibitor) poisoning
Homatropine
Muscarinic antagonist that works on the eye to produce mydriasis/dilation via paralysis of ciliary muscles
Tropicamide
Muscarinic antagonist that works on the eye to produce mydriasis/dilation via paralysis of ciliary muscles
Benztropine
Muscarinic antagonist that works in the CNS to treat Parkinson disease
Scopolamine
Muscarinic antagonist that works in the CNS to treat motion sickness
Ipratropium
Muscarinic antagonist → prevents bronchoconstriction
Indicated for COPD or asthma
Tiotropium
Muscarinic antagonist → prevents bronchoconstriction
Indicated for COPD or asthma
Longer-acting than ipratropium
Oxybutynin
Muscarinic antagonist that works in the genitourinary system to reduce urgency in mild cystitis and reduce bladder spasms
Darifenacin
Muscarinic antagonist that works in the genitourinary system to reduce urgency in mild cystitis and reduce bladder spasms
Solifenacin
Muscarinic antagonist that works in the genitourinary system to reduce urgency in mild cystitis and reduce bladder spasms
Tolterodine
Muscarinic antagonist that works in the genitourinary system to reduce urgency in mild cystitis and reduce bladder spasms
Fesoterodine
Muscarinic antagonist that works in the genitourinary system to reduce urgency in mild cystitis and reduce bladder spasms
Trospium
Muscarinic antagonist that works in the genitourinary system to reduce urgency in mild cystitis and reduce bladder spasms
Glycopyrrolate
Muscarinic antagonist used in the GI and respiratory systems to reduce airway secretions preoperatively and prevent drooling or peptic ulcers
Anticholinergic toxicity
Hot as a hare, dry as a bone, red as a beet, blind as a bad, mad as a hatter
Epinephrine
Sympathomimetic (β > α) used to treat anaphylaxis, open angle glaucoma (vasoconstriction → ↓ aqueous humor synthesis), asthma, hypotension
Norepinephrine
Sympathomimetic (α1 > α2 > β1)
Indicated for hypotension
Isoproterenol
Sympathomimetic (β1 = β2) used in the electophysiologic evaluation of tachyarrythmias
Indicated for tocolysis (relaxation of uterus) via β2 stimulation
Dopamine
Sympathomimetic (D1 = D2 > β > α) used to treat unstable bradycardia, heart failure, shock
Dobutamine
Sympathomimetic (β1 >> β2, α)
Indicated for refractory systolic heart failure, cardiogenic shock, and cardiac stress testing
Phenylephrine
Sympathomimetic (α1 > α2)
Indicated for hypotension, ocular procedures, rhinitis, and nasal decongestion and opening eustachian tubes as it reduces hyperemia and edema
SA: HTN, CNS stimulation/anxiety
Can also be used illicitly to make methamphetamine
Albuterol
Sympathomimetic (β2 > β1)
Indicated for acute asthma (short-acting) → relaxes bronchial smooth muscles
SA: tremor, arrythmia
Salmeterol
Sympathomimetic (β2 > β1)
Indicated for asthma and COPD (long-acting) prophylaxis
SA: tremor, arrythmia
Terbutaline
Sympathomimetic (β2 > β1) used to reduce premature uterine contractions
Indicated for tocolysis (relaxation of uterus) via β2 stimulation
Drugs that have antimuscarinic effects?
Atropine, TCAs (e.g. amitriptyline), H1 receptor antagonists (e.g. diphenhydramine), neuroleptics, antiparkinsonian drugs
Describe the pharmokinetic effects of competitive vs. non-competitive inhibitors.
Competitive, reversible inhibitors increase Km and decrease potency (increase ED50).
Competitive, irreversible inhibitors and non-competitive inhibitors decrease Vmax and decrease efficacy.
How do you calculate volume of distribution?
Vd = amount of drug in the body/plasma drug concentration
High Vd indicates a small molecular weight drug or a highly lipophilic drug that can easily distribute to tissues other than the plasma
A low Vd indicates a large molecular weight drug, a highy hydrophilic drug (highly positively charged), or a drug that is highly protein-bound which is likely to stay in the plasma
How do you calculate half-life?
For drugs that follow first-order kinetics:
t1/2 = (0.693 x Vd)/CL
It takes 4-5 half-lives to each steady state (3.3 half-lives to reach 90% steady state)
What is the difference between zero-order and first-order elimination?
Zero-order elimination = constant amount of drug eliminated per unit time (Cp decreases linearly with time)
First-order elimination = constant fraction of drug eliminated per unit time (Cp decreases exponentially with time)
How are weak acids and bases eliminated?
Ionized apecies are trapped in urine and cleared quickly; neutral forms can be reabsorbed.
Eliminating weak acids → alkalinize with bicarbonate
Eliminating weak bases → acidify with ammonium chloride
Which drugs should you use with caution in the elderly population?
Anticholinergics (e.g. first-generation antihistamines), alpha blockers, TCAs, benzodiazepines, antipsychotics, most antiarrhythmics, skeletal muscle relaxants
What medications are appropriate to treat high blood pressure during pregnancy?
α-methydopa
Labetaolol
Hydralazine
Nifedipine
Bromocriptine
Dopamine agonist
Indicated for prolactinoma, Parkinsons
Desmopressin (DDAVP)
ADH analog
Used to treat central diabetes insipidus and von Willibrand factor deficiency
Propylthiouracil (PTU)
Inhibits thyroid peroxidase and 5’-doiodinase → decreases T4/T3 production in the thyroid and decreases convertion of T4 to T3 in peripheral tissue
Used to treat hyperthyroidism, esp. in pregnancy
SA: agranulocytosis
Methimazole
Inhibits thyroid peroxidase → decreases T4/T3 production in the thyroid
Used to treat hyperthyroidism
SA: agranulocytosis
Cabergoline
Dopamine agonist
Indicated for prolactinoma
Octreotide
Somatostatin analog
Used to treat excess GH (gigantism, acromegaly), carcinoid tumors, gastrinoma, glucagonoma, VIPomas, acute esophageal variceal bleeding
SA: nausea, cramps, steatorrhea
Lanreotide
Somatostatin analog
Used to treat excess GH (gigantism, acromegaly), carcinoid, gastrinoma, glucagonoma, esophagesl varices
Pegvisomant
Growth hormone receptor antagonist
Used to treat excess GH (gigantism, acromegaly)
Oxytocin
Used to stimulate uterine contractions (starts labor, controls uterine hemorrhage), milk let-down
Demeclocycline
ADH antagonist (member of the tetracycline family)
Used to treat SIADH
SA: nephrogenic DI, photosensitivity, abnormalities of the bone and teeth
Adenosine
Binds α1 receptors on cardiomyocytes → activates potassium channels and inhibits L-type calcium channels → prolonged depolarization time (phase 4) → ↓ HR, slows AV node conduction
Indicated for termination of SVT (first line)
SA: flushing, hypotension, chest pain, effects blocked by theophylline and caffeine
Verapamil
Non-dihydropyridine calcium channel blocker/class IV antiarrhythmics → blocks L-type calcium channels → ↓ contractility, ↑ vasodilation, ↓ conduction velocity
Indicated for HTN, angina, afib/aflutter, prevention of nodal arrhythmias (e.g. SVT)
SA: cardiac depression, AV block, peripheral edema, flushing, dizziness, hyperprolactinemia, constipation
How do calcium channel blockers work?
Non-dihydropyridine calcium channel blocker → blocks L-type calcium channels → prevents calcium influx into cardiomyocytes and vascular smooth muscle → vasodilation, slows phase 4 diastolic depolarization and conduction velocity in the SA and AV nodes, ↓ contractility
Dihydropyridines work more on vascular tissue and non-dihydropyridines work more on cardiac tissue
Does not work on skeletal muscle because mechanical coupling of L-type calcium channels and RyR1 channels on the SR allows release of intracellular calcium without significant calcium influx across the plasma membrane
Diltiazem
Non-dihydropyridine calcium channel blocker/class IV antiarrhythmics → blocks L-type calcium channels → ↓ contractility, ↑ vasodilation, ↓ conduction velocity
Indicated for HTN, angina, afib/aflutter, prevention of nodal arrhythmias (e.g. SVT)
SA: cardiac depression, AV block, peripheral edema, flushing, dizziness, hyperprolactinemia, constipation
Amlodipine
Dihydropyridine calcium channel blocker → blocks L-type calcium channels → ↓ contractility, ↑ vasodilation
Indicated for HTN, angina (including Prinzmetal), Raynaud phenomenon
SA: cardiac depression, AV block, peripheral edema, flushing, dizziness, hyperprolactinemia, constipation
Nimodipine
Dihydropyridine calcium channel blocker → blocks L-type calcium channels → ↓ contractility, ↑ vasodilation
Indicated for subarachnoid hemorrhage (prevents cerebral vasospasm)
SA: cardiac depression, AV block, peripheral edema, flushing, dizziness, hyperprolactinemia, constipation
Nifedipine
Dihydropyridine calcium channel blocker → blocks L-type calcium channels → ↓ contractility, ↑ vasodilation
Indicated for HTN, angina (including Prinzmetal), Raynaud phenomenon
SA: cardiac depression, AV block, peripheral edema, flushing, dizziness, hyperprolactinemia, constipation
Hydralazine
↑ cGMP → smooth muscle relaxation
Vasodilates arterioles > veins (↓ preload, ↓ afterload)
Indicated for severe HTN, esp. in pregnany, CHF
SA: compensatory tachycardia (can co-administer β-blocker), fluid retention, nausea, headache, angina, lupus-like syndrome
Nitroprusside
Stimulates release of NO → ↑ cGMP → vasodilation
Indicated for hypertensive emergency
SA: cyanide toxicity
Fenoldopam
Dopamine D1 receptor agonist → coronary, peripheral, renal, splanchnic vasodilation
Indicated for hypertensive emergency, esp. in patients with AKI
Nitroglycerin
↑ NO in smooth muscles → ↑ cGMP → vasodilation
Dilates veins >> arteries (↓ preload)
Indicated for angina, ACS, pulmonary edema
SA: reflex tachycardia (can co-administer β-blocker), hypotension, flushing, headache, “Monday disease” (increase in side effect on Mondays after developing tolerance over the work week)
Isosorbide dinitrate
↑ NO in smooth muscles → ↑ cGMP → vasodilation
Dilates veins >> arteries (↓ preload)
Indicated for angina, ACS, pulmonary edema
SA: reflex tachycardia (can co-administer β-blocker), hypotension, flushing, headache, “Monday disease” (increase in side effect on Mondays after developing tolerance over the work week)
-statins
HMG-CoA reductase inhibitors prevents conversion of HMG-CoA to mevalonate, a cholesterol precursor → upregulates LDL receptors in the liver
↓↓↓ LDL
↑ HDL
↓ Triglycerides
SA: hepatotoxicity, myalgias → rhabdomyolysis (esp. when used with fibrates and niacin)
Niacin (Vitamin B3)
Inhibits lipolysis in adipose tissue, reduces hepatic VLDL synthesis
↓↓ LDL
↑↑ HDL
↓ Triglycerides
SA: facial flushing mediated by prostaglandins (reduced with long-term use or aspirin), hyperglycemia, hyperuricemia (don’t use with gout)
Cholestyramine
Bile acid resin prevents intestinal absorption of bile acids so liver must use cholesterol to make more
↓↓ LDL
Slight ↑ HDL
Slight ↑ Triglycerides
SA: bad taste, GI discomfort, ↓ absorption of fat-soluble vitamins, cholesterol gallstones
Colestipol
Bile acid resin prevents intestinal absorption of bile acids so liver must use cholesterol to make more
↓↓ LDL
Slight ↑ HDL
Slight ↑ Triglycerides
SA: bad taste, GI discomfort, ↓ absorption of fat-soluble vitamins, cholesterol gallstones
Colesevelam
Bile acid resin prevents intestinal absorption of bile acids so liver must use cholesterol to make more
↓↓ LDL
Slight ↑ HDL
Slight ↑ Triglycerides
SA: bad taste, GI discomfort, ↓ absorption of fat-soluble vitamins, cholesterol gallstones
Gemfibrozil
Fibrate that upregulates lipoprotein lipase → triglyceride clearance, activates PPAR-α in induce HDL synthesis
↓ LDL
↑ HDL
↓↓↓ Triglycerides
SA: myositis, hepatotoxicity, cholesterol gallstones (use with caution because fibrates inhibit 7α-hydroxylase, the rate-limiting step in bile acid synthesis)
Clofibrate
Fibrate that upregulates lipoprotein lipase → triglyceride clearance, activates PPAR-α in induce HDL synthesis
↓ LDL
↑ HDL
↓↓↓ Triglycerides
SA: myositis, hepatotoxicity, cholesterol gallstones (use with caution because fibrates inhibit 7α-hydroxylase, the rate-limiting step in bile acid synthesis)
Bezafibrate
Fibrate that upregulates lipoprotein lipase → triglyceride clearance, activates PPAR-α in induce HDL synthesis
↓ LDL
↑ HDL
↓↓↓ Triglycerides
SA: myositis, hepatotoxicity, cholesterol gallstones (use with caution because fibrates inhibit 7α-hydroxylase, the rate-limiting step in bile acid synthesis)
Fenofibrate
Fibrate that upregulates lipoprotein lipase → triglyceride clearance, activates PPAR-α to induce HDL synthesis
↓ LDL
↑ HDL
↓↓↓ Triglycerides
SA: myositis, hepatotoxicity, cholesterol gallstones (use with caution because fibrates inhibit 7α-hydroxylase, the rate-limiting step in bile acid synthesis)
Ezetimibe
Prevents cholesterol absorption at the small intestine brush border
↓↓ LDL
SA: ↑ LFTs, diarrhea
Which lipid-lowering agents has the greatest effect on increasing HDL?
Niacin (vitmain B3) > HMG-CoA reductase inhibitors = fibrates > bile acid resins
Which lipid-lowering agents has the greatest effect on lowering LDL?
HMG-CoA reductase inhibitors > niacin/vitamin B3 = bile acid resins = cholesterol absoption blockers > fibrates
Which lipid-lowering agents has the greatest effect on decreasing triglyceride?
Fibrates > HMG-CoA reductase inhibitors = niacin/vitamin B3
Bile acid resins acutally slightly increase triglycerides
Quinidine
Class IA antiarrhythmic
Sodium channel blocker → ↓ slope of phase 0 depolarization → slows conduction → increased action potential duration
Indicated for atrial and ventricular arrhythmias, esp. re-entrant and ectopic SVT and VT
SA: cinchonism (headache, tinnitus), thrombocytopenia, ↑ QT interval → torsades de pointes
Procainamide
Class IA antiarrhythmic
Sodium channel blocker → ↓ slope of phase 0 depolarization → slows conduction → increased action potential duration
Indicated for atrial and ventricular arrhythmias, esp. re-entrant and ectopic SVT and VT
SA: SLE-like syndrome, thrombocytopenia, ↑ QT interval → torsades de pointes
Disopyramide
Class IA antiarrhythmic
Sodium channel blocker → ↓ slope of phase 0 depolarization → slows conduction → increased action potential duration
Indicated for atrial and ventricular arrhythmias, esp. re-entrant and ectopic SVT and VT
SA: heart failure, thrombocytopenia, ↑ QT interval → torsades de pointes
Lidocaine
Class IB antiarrhythmic
Sodium channel blocker → ↓ slope of phase 0 depolarization + reduced action potential duration
Indicated for acute ventricular arrhythmias (esp. post-MI), digitalis-induced arrhythmias
SA: CNS stimulation/depression, cardiovascular depression
Mexiletine
Class IB antiarrhythmic
Sodium channel blocker → ↓ slope of phase 0 depolarization + reduced action potential duration
Indicated for acute ventricular arrhythmias (esp. post-MI), digitalis-induced arrhythmias
SA: CNS stimulation/depression, cardiovascular depression
Flecainide
Class IC antiarrhythmic
Sodium channel blocker → greatly ↓ slope of phase 0 depolarization → prolongs refractory period in AV node (action potential duration unchanged)
Indicated for SVTs, including afib
SA: proarrhythmic, especially post-MI (contraindicated in structural and ischemic heart disease)
Propafenone
Class IC antiarrhythmic
Sodium channel blocker → greatly ↓ slope of phase 0 depolarization → prolongs refractory period in AV node (action potential duration unchanged)
Indicated for SVTs, including afib
SA: proarrhythmic, especially post-MI (contraindicated in structural and ischemic heart disease)
β-blockers (-lol)
Class II antiarrhytmic
β-blockers ↓ cAMP → ↓ calcium currents → ↓ slope of phase 4 in AV > SA nodes → ↑ PR interval
Indicated for SVT, slowing ventricular rate during afib and aflutter
SA: impotence, exacerbation of COPD and asthma, bradycardia, AV block, sedation, sleep alterations (treat overdose with glucagon)
Contraindicated in cocaine users 2/2 risk of unopposed α-adrenergic activity)
Esmolol is short acting
Metoprolol can cause dyslipidemia
Propranolol can exacerbate Prinzmetal angina
Amiodarone
Class III antiarrhythmic
Potassium channel blocker → markedly prolonged repolarization → ↑ action potential duration → ↑ QT interval
Indicated for afib, aflutter, ventricular tachycardia
SA: pulmonary fibrosis, hepatotoxicity, thyroid dysfunction (contains iodine), corneal and skin deposits resulting in photodermatitis, neurologic effects, constipation, bradycardia, heart block, CHF
Check PFTs, LFTs, and TFTs before using!!!
Ibutilide
Class III antiarrhythmic
Potassium channel blocker → markedly prolonged repolarization → ↑ action potential duration → ↑ QT interval
Indicated for afib, aflutter
SA: prolonged QT interval → torsades de pointes
Dofetilide
Class III antiarrhythmic
Potassium channel blocker → markedly prolonged repolarization → ↑ action potential duration → ↑ QT interval
Indicated for afib, aflutter
Sotalol
Class III antiarrhythmic
Potassium channel blocker → markedly prolonged repolarization → ↑ action potential duration → ↑ QT interval
Indicated for afib, aflutter, ventricular tachycardia
SA: prolonged QT interval → torsades de pointes, excessive beta-blockade
Digoxin
Inhibits Na+/K+ ATPase which indirectly inhibits Na+/Ca2+ exchanger → ↑ intracellular Ca2+ → + inotropy
Stimulates vagus nerve → ↓ HR
Indicated for CHF, afib
SA: cholinergic toxicity, arrhythmias, AV block, hyperkalemia, nausea, vomiting, color vision alterations
Clopidogrel
Irreversible inhibitor of P2Y12 (component of ADP receptors) on platelets preventing aggregation
Fish oil/Omega-3 fatty acids
Decrease VLDL and apolipoprotein B synthesis
↑ HDL
↓ Triglycerides
SA: fishy taste
What drugs can cause a prolonged QT interval)
Class IA antiarrhythmics (e.g. quinidine)
Class III antiarrhythhmics (sotalol)
Antipsychotics (e.g. risperidone)
Atibiotics (e.g.macrolides)
Chloroquine
Protease inhibitors
Thiazides
Milrinone
Phosphodiesterase 3 inhibitor → ↑ cAMP → ↑ contractility, arterial and venous vasodilation
Indicated for treatment of CHF
SA: hypotension
Inamirinone
Phosphodiesterase 3 inhibitor → ↑ cAMP → ↑ contractility, arterial and venous vasodilation
Indicated for treatment of CHF
SA: hypotension
Which drugs improve survival for CHF?
ACEI/ARBs
Aldosterone antagonists
Beta-blockers
Cilostazol
Phosphodiesterase inhibitor → ↑ cAMP → ↓ platelet activation + vasodilation
Indicated for peripheral artery disease
Abciximab
Monoclonal antibody targets platelet IIb/IIIa receptors to inhibit platelet aggregation
Argatroan
Direct thrombin inhibitor
Indicated to treat heparin-induced thrombocytopenia
Heparin
Potentiates antithrombin III → inactivation of thrombin → anticoagulation
Safe for pregnancy; high water solubility → won’t cross placenta
Warfarin
Competitive inhibitor of vitamin K epoxide reductase → reduces factors II, VII, IX, X, protein C, protein S → anticoagulation (temporary heparin bridge to prevent hypercoagulation 2/2 shorter half-lives of proteins C and S)
Must monitor PT/INR
Contraindicated during pregnancy; high lipid solubility → will cross placenta
Enoxaparin
Low molecular weight heparin
Good for anticoagulation during pregnancy (doesn’t cross the placenta, short half-life)
Dabigatran
Direct thrombin inhibitor
Apixaban
Factor Xa inhibitor
How do β1 agonists work?
β1 agonist → GPCR (Gs) → ↑ cAMP → protein kinase A → ↑ intracellular calcium + inhibition of myosin light-chain kinase
↑ HR
↑ contractility
↑ renin release
↑ lipolysis
How do β2 agonists work?
β1 agonist → GPCR (Gs) → ↑ cAMP → protein kinase A → ↑ intracellular calcium + inhibition of myosin light-chain kinase
Vasodilation (↓ TPR)
Bronchodilation
↑ HR
↑ contractility
↑ lipolysis
↑ insulin release
↑ glycogenolysis
↑ gluconeogenesis
How do α1 agonists work?
α1 agonist → GPCR (Gq) → Phospholipase C → ↑ IP3 → ↑ intracellular calcium
Vascular smooth muscle contraction
How do α2 agonists work?
α2 agonist → GPCR (Gi) → ↓ cAMP → ↓ protein kinase A → ↓ intracellular calcium:
↓ sympathetic outflow
↓ insulin release
↓ lipolysis
↑ platelet aggregation
Cimetidine
Reversible block of H2 receptors → ↓ H+ secretion by parietal cells
Indicated for peptic ulders, gastritis, mild GERD
SA: drug interactions (inhibitor of P-450), antiandrogen effects (prolactin release, gynecomastia, impotence, decreased libido in males), confusion, dizziness, headaches, decreased renal excretion of creatinine
Ranitidine
Reversible block of H2 receptors → ↓ H+ secretion by parietal cells
Indicated for peptic ulders, gastritis, mild GERD
SA: decreased renal excretion of creatinine
Famotidine
Reversible block of H2 receptors → ↓ H+ secretion by parietal cells
Indicated for peptic ulders, gastritis, mild GERD
SA: decreased renal excretion of creatinine
Nizatidine
Reversible block of H2 receptors → ↓ H+ secretion by parietal cells
Indicated for peptic ulders, gastritis, mild GERD
SA: decreased renal excretion of creatinine
Omeprazole and other -prazoles
Proton pump inhibitor
Irreversibly inhibits H+/K+ ATPase in stomach parietal cells
Indicated for peptic ulcers, gastritis, GERD, Zollinger-Ellison syndrome
SA: increased risk of C. difficile infection, pneumonia, long-term use increases risk of hip fractures and hypomagnesemia
Also includes lansoprazole, esomeprazole, pantoprazole, dexlansoprazole
Bismuth, sucralfate
Binds to base of ulcer providing physical rotection and allowing HCO3- secretion to reestablish pH gradient in the mucous layer
Indicated for ulcer healing, travelers’ diarrhea
Misoprostol
PGE1 analog → increases production and secretion of gastric mucous barrier, ↓ acid production
Indicated for NSAID-induced peptic ulcers, maintenance of PDA, ripens cervix
SA: diarrhea
Contraindicated in women of childbearing potential (abortifacient)
Aluminum hydroxide
Antacid that affects absorption, bioavailability, or urinary excretion of other drugs by altering gastric and urinary pH or by delaying gastric emptying
SA: hypokalemia
Overuse: constipation, hypophophatemia, proximal muscle weakness, osteodystrophy, seizures
Calcium carbonate
Antacid that affects absorption, bioavailability, or urinary excretion of other drugs by altering gastric and urinary pH or by delaying gastric emptying
SA: hypokalemia, can chelate and decrease the effectiveness of other drugs
Overuse: hypercalcemia, rebound acid increase
Magnesium hydroxide
Antacid that affects absorption, bioavailability, or urinary excretion of other drugs by altering gastric and urinary pH or by delaying gastric emptying
SA: hypokalemia
Overuse: osmotic diarrhea, hyporeflexia, hypotension, cardiac arrest
Infliximab
Monoclonal antibody to TNF-α
Indicated for Crohn disease, ulcerative colitis, rheumatoid arthritis, ankylosing spondylitis, psoriasis
SA: infection, fever, hypotension
Sulfasalazine
Colonic bacteria activate sulfapyridine (antibacterial) and 5-aminosalicyclic acid (anti-inflammatory)
Indicated for ulcerative colitis, Chron disease
SA: malaise, nausea, sulfonamide toxicity, reversible oligospermia
Ondansetron
5-HT3 antagonist → ↓ vagal stimulation → central-acting anti-emetic
Indicated for postoperative and post chemotherapy nausea and vomiting
SA: headache, constipation
Metclopramide
D2 receptor antagonist → increased resting tone, contractility, LES tone, motility
Indicated for diabetic and post-surgery gastropresis, anti-emetic
SA: Parkinsonian effects (contraindicated in Parkinsons)
Rifaximin
Binds to DNA-dependent RNA polymerase and inhibits bacterial RNA synthesis
Decreased bacterial flora decreases intetinal production and absorption of ammonia (NH3)
Indicated for hepatic encephalopathy and traveler’s diarrhea
Lactulose
Catabolized by intetinal bacterial flora to short chain fatty acids, lowering the colonic pH and increasing cconversion of ammonia (NH3) to ammonium (NH4+)
Indicated for hepatic encephalopathy
Anti-emetics
GI irritation → 5-HT3 antagonists (e.g. odansetron)
Central/Migraines → D2 antagonists (e.g. metoclopramide, prochlorperazine)
Vestibular nausea → H1 antagonists (e.g. diphenhydramine, meclizine) and M1 antagonists (e.g. scopolamine)
Hydroxyzine
First generation H1 antagonist
Indicated for allergies, motion sickness, sleep aid
SA: sedation, anticholinergic/muscarinic (blurry vision, urine retention, delirium), anti-alpha-adrenergic (orthostatis hypotension), serotonergic (appetite stimulation, weight gain)
Diphenhydramine
First generation H1 antagonist
Indicated for allergies, motion sickness, sleep aid
SA: sedation, anticholinergic/muscarinic (blurry vision, urine retention, delirium), anti-alpha-adrenergic (orthostatis hypotension), serotonergic (appetite stimulation, weight gain)
Promethazine
First generation H1 antagonist
Indicated for allergies, motion sickness, sleep aid
SA: sedation, anticholinergic/muscarinic (blurry vision, urine retention, delirium), anti-alpha-adrenergic (orthostatis hypotension), serotonergic (appetite stimulation, weight gain)
Chlorpheniramine
First generation H1 antagonist
Indicated for allergies, motion sickness, sleep aid
SA: sedation, anticholinergic/muscarinic (blurry vision, urine retention, delirium), anti-alpha-adrenergic (orthostatis hypotension), serotonergic (appetite stimulation, weight gain)
Loratadine
Second generation H1 antagonist
Indicated for allergies
Fewer side effects than first generation (less lipopholic → less likely to cross BBB and cause sedation)
Cetirizine
Second generation H1 antagonist
Indicated for allergies
Fewer side effects than first generation (less lipopholic → less likely to cross BBB and cause sedation)
Finasteride
5α-reductase inhibitors prevents convertion of testosterone to DHT
Indicated for BPH (second line as it takes 6-12 months to see an effect) and androgenetic alopecia (male-pattern hair loss)
Succinylcholine
Depolarizing NMJ blocker (2 phases)
Binds to nicotinic acetylcholine receptor → continuous depolarization of the neuromuscular endplate (can’t be broken down by acetylcholinesterase) causes inactivation of sodium channels → flaccid paralysis
Indicated for rapid-sequence intubation
SA: malignant hyperthermia (esp. with halothanes), severe hyperkalemia in patients with burns, myopathies, crush injuries, and denervation, bradycardia or tachycardia
Dimenhydrinate
First generation H1 antagonist
Indicated for allergies, motion sickness, sleep aid
SA: sedation, anticholinergic/muscarinic (blurry vision, urine retention, delirium), anti-alpha-adrenergic (orthostatis hypotension), serotonergic (appetite stimulation, weight gain)
Fexofenadine
Second generation H1 antagonist
Indicated for allergies
Fewer side effects than first generation (less lipopholic → less likely to cross BBB and cause sedation)
Desloratidine
Second generation H1 antagonist
Indicated for allergies
Fewer side effects than first generation (less lipopholic → less likely to cross BBB and cause sedation)
Guaifenesin
Expectorant
Thins respiratory secretions but does not suppress cough
Dextromethorphan
NMD glutamate receptor antagonist → antitussive
Synthetic codeine analog that has mild opioid effect when used in excess → can give naloxone for overdose
N-acetylcystine
Mucolytic
Indicated for thinning mucous plugs in CF patients and as antidote for acetaminophen overdose
Pseudoephedrine
Sympathomimetic α-agonist
OTC indicated for nasal decongestion and opening eustachian tubes as it reduces hyperemia and edema
SA: HTN, CNS stimulation/anxiety
Can also be used illicitly to make methamphetamine
Formoterol
Sympathomimetic (β2 > β1)
Indicated for asthma and COPD (long-acting) prophylaxis
SA: tremor, arrythmia
Theophylline
Methylxanthine → inhibits phosphodiesterase → ↑ cAMP → bronchial smooth muscle relaxation
SA: cardiotoxicity, neurotoxicity, blocks actions of adenosine (limited use due to narrow therapeutic index)
Beclomethasone
Inhibits synthesis of many cytokines, including inactivation of NF-κB (transcription factor) → ↓ TNF-α
Indicated for chronic asthma (first line)
Fluticasone
Inhibits synthesis of many cytokines, including inactivation of NF-κB (transcription factor) → ↓ TNF-α
Indicated for chronic asthma (first line)
Montelukast
Leukotriene receptor blocker
Indicated for asthma, especially aspirin-induced
Zafirlukast
Leukotriene receptor blocker
Indicated for asthma, especially aspirin-induced
Zileuton
5-lipooxygenase inhibitor blocks converstion of arachidonic acid to leukotrienes
Indicated for asthma
Omalizumab
Monoclonal anti-IgE antibody → binds to unbound serum IgE and prevents binding to FcεRI
Indicated for allergic asthma resistant to inhaled steroids and long-acting β2-agonists
Bosentan
Antagonizes endothelin-1 receptors to ↓ pulmonary vascular resistance
Indicated for pulmonary arterial hypertension
Vecuronium
Nondepolarizing NMJ blocker
Competitive inhibitor of postsynaptic acetycholine receptors at the NMJ
Can be reversed with neostigmine
Pancuronium
Nondepolarizing NMJ blocker
Competitive inhibitor of postsynaptic acetycholine receptors at the NMJ
Can be reversed with neostigmine
Turbocurarine
Nondepolarizing NMJ blocker
Competitive inhibitor of postsynaptic acetycholine receptors at the NMJ
Can be reversed with neostigmine
Varenicline
Partial agonist of nicotinic acetylcholine receptors in the CNS → reduces dopamine release → reduces reward pathway of nicotine
Indicated to reduce cravings and attenuate rewarding effects of nicotine to promote cessation
Cromolyn
Nedocromil
Inhibits mast cell degranulation
Indicated for prophylaxis for seasonal symptoms, aspirin hypersensitivity, and exercise-induced asthma
Latanoprost
PGF2α agonist → ↑ outflow of aqueous humor
Indicated for glaucoma
SA: darkens color of iris
Opioid analgesics (morphine, fentanyl, codeine, loperamide, methadone, meperidine, dextrmoethorphan, diphenoxylate)
Opioid receptor agonist
Binds to post-synaptic receptor → opens K+ channels allowing K+ efflux → hyperpolarizes membrane
Binds to pre-synaptic receptor → closes Ca2+ channels preventing Ca2+ influx → ↓ release of neurotransmitters
Indicated for pain suppression, cough, diarrhea, pulmonary edema
SA: addiction, respiratory depression, constipation, miosis
Toxicity treated with naloxone or naltrexone (opioid receptor antagonist)
Butorphanol
Mu-opioid receptor partial agonist and kappa-opioid receptor agonist
Indicated for severe pain, less respiratory depression that full opioid agonist
Overdose not easily reversed with naloxone
Tramadol
Very weak opioid agonist
Indicated for chronic pain
SA: similar to other opioids + decreased seizure threshold, serotonin syndrome
Ethnosuximide
Blocks thalamic T-type Ca2+ channels
Indicated for absence seizures
Phenytoin
Increased sodium channel inactivation
Indicated for tonic-clonic seizures (first line)
SA: gingival hyperplasia, hirsutism, megaloblastic anemia, SLE-like syndrome
Carbamazepine
Increased sodium channel inactivation
Indicated for simple partial, complex partial, and tonic-clonic seizures, trigeminal neuralgia (first line for all)
SA: bone marrow suppression, SIADH
Valproic acid
Increased sodium channel inactivation, inhibits GABA transaminase → ↑ GABA concentration
Indicated for simple partial, complex partial, tonic-clonic, and absense seizures, bipolar disorder
Contraindicated in pregnancy (neural tube defects)
Gabapentin
GABA analog → inhibits high-voltage-activated calcium channels
Indicated for partial simple, partial complex, and tonic-clonic seizures, peripheral neuropathy, postherpetic neuralgia, migraine prophylaxis, bipolar disorder
Barbiturates (phenobarbital, pentobarbital, thiopental, secobarbital)
↑ duration of chloride channel opening → ↑ GABAA action → ↓ neuron firing
SA: respiratory and cardiovascular depression, CNS depression (exacerbated by alcohol)
Benzodiazepines
↑ frequency of chloride channel opening → ↑ GABAA action → ↓ neuron firing
SA: dependence, additive CNS depression effects with alcohol, less risk of respiratory depression and coma than with barbituates
Avoid taking with other CNS depressants (alcohol, barbituates, neuroleptics, 1st generation antihistamines)
Treat overdose with flumazenil (competitive antagonist at GABA benzodiazepine receptor)
Relationship between solubility and induction time and potency for CNS anesthetics
↓ solubility in blood = ↓ blood/gas partition coefficient = rapid induction and recovery times (if a gas is not very soluble in the blood, the blood becomes saturated more quickly and the drug can enter the brain more quickly)
↑ tissue solubility = ↑ AV gradients = slow blood saturation = slow brain uptake = slow onset of action
↑ solubility in lipid = ↑ potency = 1/MAC
Dantrolene
Prevents release of calcium from the sarcoplasmic reticulum of skeletal muscle
Indicated to treat malignant hyperthemia and neuroleptic malignant syndrome
Levodopa/carbidopa
Levodopa is a dopamine precursor that can cross the BBB and is converted to dopamine by dopa decarboxylase in the CNS
Carbidoba inhibits peripheral dopa decarboxylase
Indicated for Parkinsons
SA: arrythmias (↑ peripheral formation of catecholamines), dyskinesia following administration and akinesia between doses, anxiety, agitation, insomnia, confusion, delusions, hallucinations
First line treatment for essential tremor
Propranolol
Essential tremor is familial (autosomal dominant) and worsens while maintaining a particular postures and improves with alcohol consumption
Where are α1 receptors located?
Vascular smooth muscle α1 stimulation = contraction/constriction
Bladder α1 stimulation = contraction of internal urethral sphincter
Eye α1 stimulation = mydriasis (dilation)
Where are β2 receptors located?
Skeletal muscle vasculature β2 stimulation = relaxation/vasodilation
Bronchi β2 stimulation = bronchodilation
Uterus β2 stimulation = relaxation (tocolysis)
Pramipexole
Non-ergot dopamine agonist
Indicated for Parkinsons, restless leg syndrome
Treatment for status epilepticus
Status epilepticus = single seizure lasting > 5 min or multiple discrete seizures with incomplete recovery of consciousness between episodes
IV benzodiazepine (↑ frequency of chloride channel opening) first
IV phenytoin (↓ sodium current in cortical neurons) concurrently to prevent recurrence
Remelteon
Melatonin agonist
Indicated for insomnia, especially in older adults
Short-term use
Sumatriptan
5-HTIB/ID agonist → inhibits trigeminal nerve activation →prevents vasoactive peptide release and induces vasocontriction
Indicated for acute migraine (abortive) and cluster headache attachs
SA: coronary vasospasm (contraindicated in CAD and Prinzmetal angina), increased blood pressure
Cytochrome P-450 inducers
Carbamazepine
Barbiturates
Phenytoin
Rifampin
Griseofulvin
St John’s wort
Modafinil
Cyslophosphamide
OCPs
Cytochrome P-450 inhibitors
Acetaminophen
NSAIDs
Amiodarone
Cimetidine
Fluoroquinolones
Clarithromycin
Azole antifunals
Grapefruit juice
Isoniazid
Ritonavir
Omeprazole
Thyroid hormone
SSRIs
Effects of inhaled anesthetics
Myocardial depression
Respiratory depression
Nausea/emesis
Increased cerebral blood flow
Decreased cerebral metabolic demand
Decreased hepatic blood flow
Decrease GFR (increased renal vascular resistance and decrease renal plasma flow)
SA: hepatotoxicity, malignant hyperthermia
Anticonvulsants indicated for absence seizures
Ethosuximide (first line)
Valproic acid (also indicated for partial smiple, partial complex, and tonic-clonic seizures)
Lamotrigine (also indicated for partial smiple, partial complex, and tonic-clonic seizures)
Organophosphate poisoning
May organophosphates, often found in pesticides, are irreversible inhibitors of acetylcholinesterase in both nicotinic and muscarinic synapses
Characterized by diarrhea, diaphoresis, urination, miosis, bronchospasm, bradycardia, emesis, lacrimation, salivation
Tx: atropine (muscarinic antagonist) + pralidoxime (restores acetylcholinesterase)
Need both because atropine has no effect on nicotinic receptor overstimulation and patient is still at risk of muscle paralysis
Buprenorphine
Partial opioid agonist
Can precipitate withdrawal in opioid-tolerant patients
Baclofen
GABAB receptor agonist
Indicated for treatment of spasticity secondary to brain and spinal cord disease (e.g. MS)
Non-benzodiazepine hypnotics (Z drugs)
Zolpidem
Zaleplon
Eszopiclone
Binds to BZ1 subtype of the GABAA receptor
Indicated for insomnia
Decreased risk of dependence compared to benzodiazepines
Memantine
MDA receptor antagonist helps prevent excitotoxicity (mediated by Ca2+)
Indicated for Alzheimers
Probenecid
Inhibits organic anion transporters in renal tubular cells to inhibit tubular secretion of certain antibiotics (e.g. penicillin)
Also inhibits the urate transporter which increases urinary excretion of uric acid (can be used to treat gout)
Retinoids (tretinoin, adapalene, tazarotene, isotretinoin)
Vitamin A analogs that bind to intranuclear receptors RAR or RXR that act as transcription factors that decrease sebum production and normalize epidermal differentiation → increased cell turnover and shedding from stratum corneum reduces hyperkeratinization, opens blocked pores, and prevents formation of microcomedones
Indicated for severe, refractory, nodulocystic acne, psoriasis
