EXAM 2 Pharm
Unstable patients who require immediate cardioversion
Heparin (IV)
most appropriate pharmacology in pregnant patient with deep vein thrombosis (DVT) .
Heparin, avoid warfarin
ACE inhibitors effect on following - Renin - Angio I - Angio II - Aldosterone - Bradykinin
- Inc. - Inc. - Dec. - Dec. - Inc.
Bethanechol Therapeutic Effects
Relieve constipation and difficulty urination via M3 receptors
Hydralazine
Antihypertensive: arteriolar vasodilator, orally active; used in severe HTN, HF. Tox: tachycardia, salt and water retention, lupus-like syndrome
Theophylline MOA
"PHILLING your lugns!" inhibits PDE so more cAMP! bronchodilation! careful with INHIBITORS of CYP450
A hypertensive emergency is defined as severe hypertension ........................................................... in an otherwise healthy person, or, DBP >120 mm Hg in individuals with pre-existing complications along with signs of damage to target organs.
(DBP >150 mm Hg or SBP >210 mm Hg)
Bronchodilators Used in COPD Short-acting Bronchodilators vs. Long-acting Bronchodilators
(SABAs)(SAMAs)(LABAs)(LAMAs) Used for symptomatic relief and in management of acute exacerbations of COPD vs. Used for long-term control of COPD
Heart failure with preserved ejection fraction (HFpEF)
(also referred to as diastolic heart failure): EF ≥ 50%
Heart failure with reduced ejection fraction (HFrEF)
(also referred to as systolic heart failure): EF ≤ 40%
ADP receptor antagonists
*Clopidogrel (Plavix)* -Number of CYP-dependent steps: 2 -Offset: 5 days -Drug-drug interactions: CYP2C19 inhibitors may decrease effects; avoid omeprazole and esomeprazole; coadministration with NSAIDs increase risk of GIB; coadministration with warfarin increases risk of bleeding -PRODRUG - needs to go through liver for metabolism
Nitrates Tolerance
Develops rapidly (vessels desensitizetovasodilation) •Can be overcome by daily 'nitrate-free interval' (10-12h) eg, nitroglycerin patches: 'on' for 12 h, 'off' for 12h
A 22-year-old pregnant woman currently has a lipid profile of LDL = 222 mg/dL, TAGs = 125 mg/dL and HDL = 40 mg/dL. She is prescribed appropriate treatment for her dyslipidemia based on her current condition. What is the mechanism of action of the drug in question?
*The patient is pregnant, so you absolutely cannot give statins. Colesevelam is Category B, so it is tolerable for pregnancy. It inhibits enterohepatic bile circulation
Modafinil (Provigil)
- inhibits NE and dopamine transporters - inc synaptic concentrations of NE, dopaline, serotonin + glutamate, + dec GABA
Mixed: (D 1 , β 1 , α 1 ), (α 1 , α 2 , β 1 , β 2 ), (α 1 , α 2 , β 1 )
-- Dopamine, -- Epinephrine, -- Norepinephrine
α 1 antagonists: α 2 antagonists: Mixed α antagonists: β 1 (cardioselective) antagonists: β 1 , β 2 (nonselective): α 1 and β antagonists:
-- doxazosin, prazosin, terazosin -- mirtazapine -- phenoxybenzamine, phentolamine -- acebutolol, atenolol, metoprolol -- pindolol, propranolol, timolol -- carvedilol, labetalol
Chronic (preexisting) hypertension in pregnancy is often treated with ................................. while preeclampsia (new-onset hypertension in pregnancy) is treated with .................................
--- Methyldopa --- Hydralazine.
Malignant hyperthermia {possible causes}
Due to excessive release of Ca2+ from the SR. Most incidents due to combination of succinylcholine + halogenated anesthetic
Digoxin- Anti-arrhythmic actions
1) Slows AV conduction HF ( enhance contractility); 2) Prolongs effective refractory period {ERP] of AV node thereby decreasing fraction of atrial impulses that are conducted through the node and increasing PR interval → useful in treating atrial flutter / fibrillation by controlling ventricular rate) Reduce atrial fibrillation ( conduction at AV node and depression of SA node).
Isolated low HDL initial drug + additions
1) Statin 2) Niacin
DRUGS USED IN THE TREATMENT OF GLAUCOMA
1 ) Parasympathomimetics (e.g. Pilocarpine Carbachol) (Echothiophate) 2 ) Sympathomimetics (Brimonidine) 3) β-blockers (Timolol) 4) Carbonic anhydrase inhibitors (Acetazolamide, Dorzolamide) 5) Prostaglandin Analogues (Latanoprost) 6) Osmotic agents (E.g. Glycerol, isosorbide, mannitol)
Isolated severe Hypertriglyceridemia (TG) initial drug + additions
1) Fibrate (or Niacin or w-3 Fattyacid). 2) Statin
Spironolactone: aldosterone-receptor antagonist Use: AE:
1) Hyperaldosteronic state 2) Adjunct to K + -wasting diuretics. 3) Antiandrogenic uses (female hirsutism) 4) Congestive heart failure Side effects: hyperkalemia and acidosis; antiandrogen
Long-term Management of Asthma Intermittent (step 1) mild persistent (step 2) Moderate persistent (step 3) Severe persistent (step 4 or 5)
1) Inhaled SABA (no daily medications) 2) inhaled SABA + low dose ICS 3) inhaled SABA + low dose ICS OR medium dose ICS 4) inhaled SABA + medium dose ICS + LABA OR high dose ICS + LABA
............................... is similar Cholinesterase inhibitor but longer-acting. ............................... is a lipidsoluble plant alkaloid. ............................... is a rarely used organophosphate cholinesterase inhibitor for topical ophthalmic use.
1) Pyridostigmine 2) Physostigmine 3) Echothiophate
Elevated LDL initial drug + additions
1) STATIN 2) Niacin, Resin, Ezetimibe
Elevated LDL and TG initial drug + additions
1) Statins 2) Niacin, Fibrate, w-3 Fattyacid
Amiloride and triamterene: Na + -channel blockers, block aldosterone receptors in collecting tubule Use: AE:
1) adjunct to K -wasting diuretics, l 2) Lithium-induced nephrogenic diabetes insipidus (amiloride) Side effects: hyperkalemia and acidosis;
antihypertensive medication that decreases aldosterone and angiotensin 2 production whilst increasing renin and angiotensin 1 concentrations. Which of the following medications was most likely prescribed?
Captopril
Elevated BP is defined by a systolic blood pressure between ........... and/or a diastolic blood pressure ............
120-139 mm Hg. < 80 mm Hg.
Actions •B1 action increases HR and contractility = increased CO (mild increase SBP) •Pulse pressure rises •B2 action: Dilation of arterioles of skeletal muscle = decreases PVR (decreases DBP) •Decreased DBP= MAP DECREASES= •REFLEX TACHYCARDIA
1so-protereno1
A 72-year-old presents to his physician due to generalized weakness and muscle pain. He has also been noticing that his urine has been appearing darker lately. He has a previous history of hypertension, diabetes, and dyslipidemia. He previously has a lipid profile of LDL = 192 mg/dL, HDL = 40 mg/dL and TAGs = 193 mg/dL. The patient was on first-line monotherapy for his dyslipidemia, but his physician decided to add an additional drug 3 weeks ago, just before his symptoms began occurring. What is likely identity of additional drug?
1st monotherapy for this pt was likely a statin drug and additional drug was likely Gemfibrozil, which can increase levels of stains and itself. This causes an increased risk for myopathy and rhabdomyolysis (weakness, muscle pain, dark urine). It increases expression of LPL [Increae clearance of TG by activating PPAR- Alpha to induce HDL synthesis]
patient is diagnosed with stage 1 hypertension. Comorbidities include diabetes with observed albuminuria. Which of the following drugs would be the most appropriate choice to initiate antihypertensive treatment with?
Captopril
Treatment of patients with stage 2 hypertension ???? In addition all patients with hypertension should be advised on lifestyle modifications.
2-drug combination (thiazide diuretic + ACE inhibitor) on average thiazide diuretics can only reduce blood pressure by ~ 15 mm Hg).
Sumatriptan
5-HT1D receptor agonist: used to abort migraine attacks. Tox: coronary vasospasm, chest pain or pressure.
Sumatriptan taken for migraine. What is pharmacological target?
5HT1d/1b
For patients with stage 1 hypertension and no other cardiovascular risk factors, ...............................can be attempted in the hope that they may be sufficiently effective to make it unnecessary to use antihypertensive agents.
6 to 12 months of lifestyle modifications
Stage 2 hypertension is defined as a systolic blood pressure ................... and/or a diastolic blood pressure............
>140 mmHg > 90 mm Hg.
A 20-year-old woman sees her physician, reporting that she has been experiencing severe, unilateral, throbbing migraines several times each month. She has used ibuprofen in the past but finds it does not control the headaches well. The physician recommends another drug that the patient should take at the immediate onset of her symptoms. What is the mechanism of action of her new medication? A sumo wrestler trips and falls on his head.
A 5-HT 1D/1B receptor agonist. Inhibit trigeminal nerve activation, prevent vasoactive peptide release, induce vasoconstrition. Adverse effects: Coronary vasospasm (contraindicated in patients with CAD or vasospastic angina), mild paresthesia, serotonin syndrome (in combination with other 5-1 IT agonists).
.A 56-year old woman is diagnosed with atrial fibrillation and prescribed a medication to prevent stroke. She develops a lesion, which is shown in the photograph taken six days after the drug is begun. Which of the following drugs is most likely responsible for the findings seen in this patient?
A common adverse effect of warfarin is skin necrosis, due to a reduction of levels of Protein C. This leads to a hypercoagulable state. Warfarin and heparin are by far the most high-yield blood clotting drugs. If you have no idea, these are good guesses.
Cardiovascular effects of a new drug (X) that activates autonomic receptors are shown in the table below: Parameter Control Drug X Systolic BP. 120 mm Hg. 110 mm Hg Diastolic BP 85 mm Hg 55 mm Hg Heart rate 60/min 120/min
A decrease in mean blood pressure, an increase in pulse pressure, plus a marked increase in heart rate are characteristic of a drug such as isoproterenol. PVR and mean BP are decreased because of activation of β 2 receptors in the vasculature. Systolic BP decreases less than diastolic BP because of activation of β 1 receptors in the heart, leading to an increase in stroke volume, as well as the increase in heart rate.
A patient returns to the clinic after 4 weeks and his blood pressure is measured at 137/88 mm Hg. How would you classify the patient's blood pressure?
A diagnosis of Stage 1 hypertension can be made. Stage 1 hypertension is defined by a systolic blood pressure of between 130-139 mm Hg and/or a diastolic blood pressure of between 80-89 mm Hg. Normal BP is defined as <120/<80 mm Hg.
Inhibits insulin release
ALPHA 2 (MAD2 INHIBIT)
A 34-year-old man is undergoing surgery. He is anesthetized with the inhalational general anesthetic halothane. He is also given an intravenous dose of the skeletal muscle relaxant succinylcholine. Within minutes, he develops a HR of 120/min and increasing body temperature. A. What is the most likely explanation for these symptoms? B. Which is the drug of choice for this patient's condition? C. What is the mechanism of action of this drug
A. Malignant hyperthermia B. Dantrolene C. Blocks Ca2+ release from the SR.
•Anticoagulants prevent formation of thrombi but are ineffective against pre-existing clots. •Thrombolytic drugs lyse blood clots andrestore the patency of obstructed vessels before distal tissue necrosis occurs. •Thrombolytic agents act by converting plasminogen to plasmin.
ALTEPLASE RETEPLASE TENECTEPLASE
An EKG shows atrial fibrillation. The physician prescribes an antiarrhythmic medication that has actions in all classes of antiarrhythmics. Which of the following disorders would make this medication contraindicated?
A.Alcoholic cirrhosis
Captopril
ACE inhibitor prototype: used in HTN, diabetic nephropathy, and HF. Tox: hyperkalemia, fetal renal damage, cough ("sore throat").
Drug of choice for the treatment of hypertension in a patient who is also diabetic. They are the preferred choice (alongside ARBs) due to their protective effects on the kidneys. This is regardless of the ethnicity of the patient.
ACE inhibitors
A 67 year old man comes to the physician for a routine examination. He has a 5 year history of hypertension. His only current medication is hydrochlorothiazide. His blood pressure is 148/85 mm Hg and pulse is 85/min. He is administered a drug that works by inhibiting an extracellular enzyme. Which of the following adverse effects is most likely to be seen in this patient?
ACE inhibitors adverse effects Dry hacking cough Fatigue Dizziness Headache Mood changes Impaired taste Possible hyperkalemia Dry, nonproductive cough, which reverses when therapy is stopped Angioedema: rare but potentially fatal Note: First-dose hypotensive effect may occur
Enhancement of the effects of bradykinin is most likely to occur with drugs like
ACE inhibitors prevent the conversion of angiotensin I to angiotensin II and lower blood pressure by decreasing both the formation of aldosterone formation and the vasoconstrictive action of AII at AT-1 receptors. ACEIs also inhibit the metabolism of bradykinin, and this leads to additional hypotensive effects, because bradykinin is an endogenous vasodilator. Unfortunately, increases in bradykinin are associated with side effects, including cough and angioedema. Losartan, which blocks AT-1 receptors, does not increase bradykinin levels.
Pharmacological treatment for Stage C HfrEF
ACEI (or an ARB) and a -blocker. Additionally, diuretics are recommended in patients who have evidence of fluid retention, to improve symptoms. For NYHA class II-IV patients an aldosterone antagonist should be added provided that estimated creatinine >30 mL/min and K < 5.0 mEq/dL.
First line antihypertensive medication for patient with Diabetes
ACEI or ARBs
Rapid hydrolysis by both acetylcholinesterase and plasma butyrylcholinesterase.
ACETYLCHOLINE
Used to obtain rapid miosis after delivery of the lens in cataract surgery and other procedures where rapid miosis is required.
ACETYLCHOLINE
Beta 1 selective blockers name
AMEBBA Atenolol, Metoprolol, Esmolol, Bisoprolol, Betaxolol, Acebutolol BOXED WARNING - Beta blockers should not be withdrawn abruptly (particularly in patients with CAD), gradually taper over 1-2 weeks to avoid acute tachycardia, HTN, and/or ischemia CI - Sinus bradycardia, 2nd or 3rd degree heart block, sick sinus syndrome (unless patient has a functioning artificial pacemaker) or cardiogenic shock. Do not initiate in patients with active asthma exacerbation SE - Decrease in HR, Hypotension, Fatigue, Dizziness, depression, decrease Libido, impotence, Hypertirglycerdiemia, decrease in HDL, etc. Monitoring - HR, BP ,etc.
•Inhibits plasminogen activation. Uses: adjunctive therapy in hemophilia, and therapy for bleeding from fibrinolytic therapy
AMINOCAPROIC ACID & TRANEXAMIC ACID
A 74-year-old man being treated for a supraventricular arrhythmia complains of extreme fatigue since he began treatment. An EKG reveals that QRS, PR and QT intervals are prolonged in this patient. Which of the following antiarrhythmic drugs would account for these changes in the EKG?
Amiodarone
What is a common side effect of nifedipine?
Ankle edema
A farm worker is taken to a clinic after an accidental exposure to an organophosphate insecticide. He is in respiratory distress and bradycardic. He is administered atropine. Which drug would increase the activity of his acetylcholinesterase?
Antidote—atropine (competitive inhibitor) + Pralidoxime (regenerates AChE if given early).
Diphenhydramine
Antihistamine (first-generation) H 1 blocker: used in hay fever, motion sickness, dystonias. Tox: antimuscarinic, a adrenoceptor blocker, strong sedative. Doxylamine is similar.
Chlorpheniramine
Antihistamine first-generation H1 blocker prototype. Tox: less sedation and ANS-blocking action than diphenhydramine.
Niacin
Antihyperlipidemic, vitamin: inhibits VLDL synthesis and release of fatty acids from adipose tissue. Lowers LDL cholesterol and triglycerides and raises HDL cholesterol. Tox: flushing, pruritus, liver dysfunction, increased risk of myopathy when combined with statins.
Cholestyramine
Antihyperlipidemic: bile acid-binding resin prototype that sequesters bile acids in gut and diverts more cholesterol from the liver to bile acids instead of circulating lipoproteins. Used for hypercholesterolemia. Tox: constipation, bloating; interferes with absorption of some drugs. Colestipol and colesevelam are similar.
Physician prescribed a diuretic that works in the distal convoluted tubule. In response to this drug, the serum level of which of the following is most likely to decrease?
Sodium [Hyponatremia]
Ezetimibe
Antihyperlipidemic: cholesterol-lowering drug that inhibits GI transporter of dietary cholesterol and the cholesterol secreted in bile. Used for hypercholesterolemia, usually in combination with a statin. Tox: possible increased risk of hepatic damage when combined with statin
Antidote for Excess Cholinergic agonists.
ATROPINE
Used to prevent clotting after coronary angioplasty and in acute coronary syndrome
Abciximab
The drug of choice for the prophylaxis of mountain sickness is?
Acetazolamide
Used in glaucoma and mountain sickness
Acetazolamide
A 69 year old comes to the emergency department after taking several tablets of his medications in suicide attempt. he has 10 year history of depression and was recently (less than 6 months ago) diagnosed with glaucoma. He appears drowsy and reports feeling of nausea, paresthesias and tiredness. Physical examination shows erythematous skin eruptions. Laboratory tests show hyperchloremic metabolic acidosis. which of the following medications might have caused the patient symptoms?
Acetazolamide Thick ascending Tubule Carbonic anhydrase inhibitor Self limited NaHCO3 diuresis and decrease total body HCO3- stores
Choline ester most susceptible to acetylcholinesterase
Acetylcholine
Spray of Methacholine for diagnosis of asthma
Activation of M3 receptor
Why are non-selective Beta-blockers not recommended for diabetic individuals?
Activation of hepatic B2-receptors leads to stimulation of glycogenolysis (Glycogen breakdown) and, therefore, glucose release into the blood. In an insulin-dependent diabetic, blockade of B2 receptors can lead to pronounced hypoglycemia after insulin injection [Mask typical autonomic symptoms of hypoglycemia (ie. anxiety, tremors, palpitations)
Effect of activation of muscarinic receptors in vasculature?
Activation of non-innervated endothelial M3 receptors leads to enhanced synthesis of nitric oxide and thus to vasodilation and a drop in blood pressure.
DOC for paroxysmal supraventricular tachycardias and AV nodal arrhythmias
Adenosine Side effects: flushing, sedation, dyspnea Adenosine is antagonized by methylxanthines (theophylline and caffeine)
A 61 year old man comes to the emergency department because of 3 day history of palpitations and lightheadedness. He also reports mild chest discomfort. He has 10 year history of hypertension and type 2 diabetes mellitus. Current medications include hydrochlorothiazide and nifedipine. His blood pressure is 99/54 mmHg and his pulse is 180/min. An ECG shows a narrow QRS complex tachyarrhythmia that is irregularly irregular. Which of the following drugs is the most appropriate to try to restore normal sinus rhythm??
Adenosine [Inc] K + out of cells ==> hyperpolarizing the cell and [Dec] ICa , decreasing AV node conduction. Drug of choice in diagnosing/terminating certain forms of SVT. Very short acting (~ 15 sec). Effects blunted by theophylline and caffeine (both are adenosine receptor antagonists). Adverse effects include flushing, hypotension, chest pain, sense of impending doom, bronchospasm.
Tirofiban, ABCIXIMABC
Adjuncts to PCI (Per cutaneous intervention) for prevention of cardiac ischemic complications
Tubocurarine
Adjuvant drugs in anaesthesia during surgery to relax skeletal muscle. Competitive antagonists.
A 56 year old woman is diagnosed with DVT and started on UFH. A week later her platelet count is found to have dropped by 50%. Heparin administration is stopped. Which of the following is the next best step in the management of this patient?
Administer argatroban
Carvedilol
Adrenoceptor blocker: racemic mixture, one isomer is a nonselective b blocker and the other is an a blocker. Used in HTN, prolongs survival in HF. Tox: cardiovascular depression, asthma. Labetalol is similar.
Which of the following drugs would be the most appropriate choice to initiate treatment with if the patient was African-American?
African-American patients (with no comorbidities) are: thiazides and calcium channel blockers. Either of these would be an appropriate drug with which to initiate treatment in this patient.
A 9-year-old boy is brought to the emergency department by his parents because of a 2-day history of coughing and breathing difficulties. Physical examination shows moderate to severe respiratory distress with bilateral expiratory wheezing. His blood pressure is 125/81 mm Hg, pulse is 132/min and respirations are 27/min. Which of the following would be the most appropriate initial pharmacotherapy to rapidly relieve his symptoms?
Albuterol
Inhaled short-acting β2 adrenergic agonists (SABAs)
Albuterol Terbutaline Pirbuterol
A 64-year-old man with a history of chronic obstructive pulmonary disease (COPD) is evaluated in the emergency department for increased dyspnea over the past 3 days. He has obvious difficulty breathing and cannot speak in full sentences. He has been using his inhalers much more than usual but with minimal improvement. He has smoked one pack per day since age 18 and has a history of hyperlipidemia, hypertension and obesity. His respirations are 28/min, pulse is 100/min, blood pressure of 130/90 mm Hg, and temperature is 37.7°C. His O2 saturation is 84% on room air. Breath sounds are diffusely decreased with bilateral expiratory wheezes. Cardiac examination shows no abnormalities. He does not have any peripheral edema. He is administered supplemental O 2 via nasal cannula. Which of the following is the next best step in the management of this patient?
Albuterol and ipratroprium
Acute asthma symptoms (short-acting) vs. Prolonged duration of action - long term asthma/COPD
Albuterol vs. Salmeterol + Formoterol
A 63 year old man comes to the physician for a routine check up. He currently has no physical complaints. At his last visit three months ago, he was started on therapeutic lifestyle changes to decrease his blood pressure, which was measured in the 150s/90s mm Hg on two separate visits. His blood pressure is now 154/93 mm Hg and he agrees to start on antihypertensive medication. The medication prescribed decreases aldosterone production and serum angiotensin I concentration and increases natriuresis. Which of the following medications was most likely prescribed?
Aliskiren Inhibits enzyme activity of Renin Prevents conversion of angiotensinogen into angiotensin I Inhibits production of angiotensin II and aldosterone
Mediates vascular smooth muscle contraction
Alpha 1 - Gq
A 70-year-old man comes to the physician because of a 6-month history of difficulty urinating. Digital rectal exam shows diffuse enlargement of the prostate. Serum PSA are within normal limits and he is diagnosed with benign prostatic hyperplasia. He is prescribed a drug that relaxes the smooth muscle of the prostatic capsule and the prostatic urethra. Which of the following drug-receptor interactions is seen in this patient?
Alpha 1 adrenergic blockade
Which of the following signaling mechanism mediates glycemic effect of phenylephrine ?
Alpha 1 agonist increase IP3, DAG, and Ca2+
Clonidine
Alpha 2 agonist: acts centrally to reduce SANS outflow, lowers BP. Used in HTN and in drug dependency states. Tox: mild sedation in normal doses, rebound HTN if stopped suddenly.
A 74 year old man comes to the physician because of a 3 month history of difficulty urinating. His urine stream is intermittent, and he has recently begun experiencing nocturia and profound urinary urgency. Digital rectal exam shows diffuse enlargement of the prostate. Laboratory studies are within the normal range. He is diagnosed with benign prostatic hyperplasia (BPH). He is prescribed a drug that relaxes smooth muscle in the bladder neck, prostate capsule and prostatic urethra. Which of the following types of drug receptor interactions most likely mediates the effects of the drug used in this patient?
Alpha1 adrenoceptor blockade
Used to recanalize occluded blood vessels in acute MI, severe pulmonary embolism, stroke.
Alteplase (t-PA)
A 19-year-old woman complains of severe dysmenorrhea. A uterine stimulant derived from membrane lipid in the endometrium is
Although serotonin and, in some species, histamine may cause uterine stimulation, these substances are not derived from membrane lipid. Similarly, oxytocin causes uterine contrac tion, but it is a peptide hormone released from the posterior pituitary. Prostacyclin relaxes the uterus.
Reflex tachycardia caused by the systemic administration of albuterol can be blocked by what drug?
Although used primarily via inhalation for asthma, systemic effects of albuterol include vasodilation due to its β 2 receptor activation. This can result in a decrease in TPR and mean BP, which elicits a reflex tachycardia. Reflex tachycardia could be blocked at the heart with a beta blocker such as metoprolol or by ganglion blockers (mecamylamine) which prevent all autonomic reflexes. Dobutamine stimulates beta-1 receptors causing tachycardia. Phenylephrine stimulates alpha-1 receptors which would raise TPR and BP and evoke a reflex bradycardia that doesn't block tachycardia caused by albuterol. Prazosin blocks alpha-1 receptors decreasing TPR and BP and causing a reflex tachycardia. Lowdose epinephrine stimulates beta-1 and beta-2 receptors and will cause tachycardia.
Therapy for bleeding due to thrombolytic therapy
Aminocaproic acid
3-month history of progressive shortness of breath and a dry cough. He also says that over the past few weeks he has noticed his facial skin has become discolored. He has a 4-year history of coronary artery disease and atrial fibrillation but does not remember which drugs he is currently taking. His blood pressure is 150/85 mm Hg, pulse is 90/min and respirations are 18/min. Physical examination shows blue/grey discoloration of the face and hands. Diffuse inspiratory crackles are heard and an x-ray of the chest shows reticular opacities around the lung periphery. Which of the following drugs is the most likely cause of this patient's findings?
Amiodarone
A 52 year old woman is brought to the emergency department after fainting. she is accompanied by her husband who witnessed the event. She was in her usual state of health until she developed palpitations that eventually resulted in her failing to the ground. She was unresponsive and the emergency medical services were called. She had myocardial infarction 3 months ago. physical examination shows an unresponsive patient with no pulse. an ECG shows tachyarrhythmia with irregular QRS complexes of variable amplitude and morphology Immediate treatment should be given with which of the following drugs?
Amiodarone
A 54-year-old woman comes to her physician because of difficulty breathing for the past 3 weeks. These issues are not associated with exertion and does not improve with rest. Physical examination finds clubbing of her fingernails. She has a 10-year history of HTN and was recently diagnosed with a supraventricular arrhythmia 6 weeks ago. She is currently taking lisinopril and an anti-arrhythmic drug for the supraventricular tachycardia. Which of the following anti-arrhythmic drugs is she taking?
Amiodarone
A 56-year-old man visits the ER with symptoms of acute ventricular tachycardia. An EKG confirms your diagnosis. Which of the following drugs would be successful in resolving this condition?
Amiodarone
Adverse effects include pulmonary fibrosis, hypotension, GI upset, peripheral neuropathy, hyper- or hypothyroidism, liver toxicity, photosensitivity, blue skin discoloration and corneal microdeposits. Despite the marked QT prolongation and bradycardia the incidence of torsades de pointes is low
Amiodarone has complex effects, showing class I, II, III and IV actions. It blocks inactivated Na+ channels and has a relatively rapid rate of recovery from block. It also decreases Ca2+ current and transient outward delayed rectifier and inward rectifier K+ currents and exerts a noncompetitive adrenergic blocking effect. Its dominant effect is prolongation of the action potential duration and the refractory period.
Which one of the following drugs is most likely to block K+ channels in the heart responsible for cardiac repolarization, and also blocks calcium channels in the AV node?
Amiodarone is a highly effective antiarrhythmic drug, in part because of its multiple actions, which include Na+ channel block, beta adrenoceptor block, K + channel block, and Ca 2+ channel block. Drugs that block K + channels prolong APD and ERP and predispose toward torsades de pointes ventricular arrhythmias. Quinidine, class Ia, can block both sodium and potassium channels but not calcium channels. Lidocaine, class Ib, blocks only sodium channels. Sotalol is both a beta blocker and a potassium channel blocker. It is a class III drug that also has class II properties Verapamil is a class IV calcium channel blocker with no effect on potassium.
Acute Ventricular Tachycardia [Emergency]
Amiodarone, Lidocaine, Cardioversion
A 44-year-old man presents to his physician presenting with a chronic cough and extreme dyspnea. Medical interviewing reveals that the patient underwent rigorous chemotherapy treatment several years ago for cancer. One particular agent in the patient's former regimen that strikes the physician's interest is the antineoplastic agent busulfan. The main adverse effect of busulfan most similar to a drug from which of the following categories?
Amiodarone, a type III antiarrhythmic, also caused pulmonary fibrosis. Also, just going to mention this here - Digoxin is a common answer choice for many questions, but is rarely the correct answer. This is because it is rather toxic and has limited use. Typically used in systolic heart failure with decreased EF and can control ventricular rate in certain situations. Also, it does not decrease mortality, but is rather for symptomatic treatments.
A 45 year old man comes to the physician for a routine examination. He has a 5 year history of hypertension. Current medications are hydrochlorothiazide and lisinopril. His blood pressure is 155/95 mmHg and pulse is 75/min. An EKG shows 1st degree heart block. Which of the following drugs would be most appropriate to add to this patient's regimen?
Amlodipine (CCB)
Ca2+ channel blockers
Amlodipine, Nifedipine, Diltiazem, Verapamil
SARIN
Among the most potent synthetic toxic agents known.
A 28-year-old man comes to his family physician because of intense episodes of anxiety accompanied by headaches, diaphoresis and palpitations. His blood pressure is 168/100 mm Hg and serum studies show an excess of catecholamine levels. In addition, an MRI of the adrenal glands shows a left adrenal mass. A diagnosis of pheochromocytoma is made by the physician. Which of the following drugs should be administered pre-operatively to control blood pressure in this patient?
An alpha-adrenergic antagonist
A patient with a supraventricular tachycardia has an atrial rate of 280/min with a ventricular rate of 140/min via a 2:1 AV nodal transmission. After treatment with a drug, the atrial rate slowed to 180/min, but the ventricular rate increased to 180/min. Which of the following drugs was most likely to have been given to this patient?
An increase in AV conduction is characteristic of quinidine, which exerts quite marked blocking actions on muscarinic receptors in the heart. Thus, an atrial rate, formerly transmitted to the ventricles in a 2:1 ratio, may be transmitted in a 1:1 ratio after quinidine. This effect of quinidine can be offset by the prior administration of an antiarrhythmic drug that decreases AV nodal conduction, such as digoxin or verapamil. All of the drugs listed (except quinidine) slow AV nodal conduction, but adenosine and esmolol (a beta blocker) are very short-acting agents used IV only.
Zafirlukast, Montelukast
Antagonists of LTD4 receptors
Adenosine
Antiarrhythmic: miscellaneous group; parenteral only. Hyperpolarizes AV nodal tissue, blocks conduction for 10-15 s. Used for nodal reentry arrhythmias. Tox: hypotension, flushing, chest pain.
Heparin Unfractionated heparin LMWHs: dalteparin, enoxaparin, tinzaparin
Anticoagulant: large polymeric molecule with activity against thrombin and factor X. Rapid onset, parenteral administration. LMW heparins (eg, enoxaparin) and fondaparinux have a similar mechanism of action (accelerates activity of antithrombin III), although they are more selective for factor X. Tox: bleeding. Antidote: protamine.
Clopidogrel
Antiplatelet agent: Prodrug, active metabolite irreversibly inhibits platelet ADP receptors and platelet aggregation. Used in transient ischemic attacks and to prevent strokes and restenosis after placement of coronary stents. Tox: bleeding, neutropenia. Prasugrel, ticagrelor, and ticlopidine are similar. Ticagrelor is not a prodrug and ticlopidine has higher risk of neutropenia and thrombotic thrombocytopenic purpura (TTP).
Heparin's anticoagulant effect is a consequence of binding to
Antithrombin III
Can be administered orally
Apixaban
Direct factor Xa inhibitors
Apixaban Rivaroxaban
Treatment of thrombosis in patients with HIT type 2.
Argatroban
A 50-year-old woman with moderately severe arthritis has been treated with non-steroidal anti-inflammatory drugs for 6 mo. She now complains of heartburn and indigestion. You give her a prescription for a drug to be taken along with the anti-inflammatory agent, but 2 d later she calls the office complaining that your last prescription has caused severe diarrhea. Which of the following is most likely to be associated with increased gastrointestinal motility and diarrhea?
Aspirin and zileuton rarely cause diarrhea. LTB is a chemo tactic factor. Famotidine is an H blocker that does not cause diarrhea
Sympathetic (adrenergic) Predominant Tone
Arterioles - alpha 1 Veins - alpha 1
African American woman comes to the physician for a follow up examination. At the last examination, one month ago, she had elevated BP. She has a 3 year history of diabetes. Her only current medication is metformin (oral anti diabetic drug). Her current blood pressure is 145/86 mm Hg and pulse is 80/min. Which of following drugs is the most appropriate initial pharmacotherapy for this patient?
As a selective and competitive, nonpeptide angiotensin II receptor antagonist, losartan blocks the vasoconstrictor and aldosterone-secreting effects of angiotensin II; losartan interacts reversibly at the AT1 and AT2 receptors of many tissues and has slow dissociation kinetics; its affinity for the AT1 receptor is 1000 times greater than the AT2 receptor. Angiotensin II receptor antagonists may induce a more complete inhibition of the renin-angiotensin system than ACE inhibitors, they do not affect the response to bradykinin, and are less likely to be associated with nonrenin-angiotensin effects (eg, cough and angioedema). Losartan increases urinary flow rate and in addition to being natriuretic and kaliuretic, increases excretion of chloride, magnesium, uric acid, calcium, and phosphate.
Neostigmine differs from pilocarpine in having effects on
As an inhibitor of AChE, neostigmine exerts effects to enhance the actions of ACh at all innervated effector sites where ACh is a neurotransmitter. These include all ANS ganglia, PANS postganglionic neuroeffector junctions, and SANS innervation of thermoregulatory sweat glands. Pilocarpine activates M receptors and has no effects at conventional dose levels on nicotinic receptors such as those in ANS ganglia and the skeletal NMJ.
Inhibits TXA2 synthesis
Aspirin
A patient with a bleeding tendency presents in the hematology clinic. He is apparently taking large amounts of an unidentified drug that inhibits platelet activity. Which of the following is taken orally and directly and reversibly inhibits platelet cyclooxygenase?
Aspirin is a direct but irreversible inhibitor of cyclooxygenase. NSAIDs other than aspirin (such as ibuprofen) are reversible inhibitors of COX. Corticosteroids reduce the synthesis of cyclooxygenase.
Effect of atropine on cardiovascular actions of norepinephrine?
Atropine will block cardiac M2 receptors and thus will prevent reflex bradycardia seen with norepinephrine and will expose the direct effects of norepinephrine on the heart (ie. tachycardia).
After deciding to add metoprolol to the patient's treatment regimen, what should you tell the patient regarding what to expect with the addition of this new drug?
At the beginning of therapy with a β-blocker symptoms may be exacerbated due to its negative inotropic effects. However, these symptoms should decrease over the course of therapy in addition to survival being increased.
A 56 year old woman comes to emergency department because of palpitations persisting over the past 12 hours. Her blood pressure is 103/71 mmHg and pulse is 160/min. An ECG shows narrow complex tachycardia and diagnosis of AV nodal reentrant tachycardia is made. Carotid sinus massage is performed but is unsuccessful. Which of the following drugs would be most likely to restore sinus rhythm??
Atenolol
A 69-year-old comes to the emergency department after being woken in the middle of night with intense chest pain, radiating to the left arm and accompanied by breathlessness. He has a 5-year history of hypertension, well managed with hydrochlorothiazide. Laboratory results show no increase in myocardial injury markers and ECG is not suggestive of acute myocardial infarction. After initial treatment which of the following drugs is most appropriate to give to the patient on discharge in order to reduce risk of further events?
Atenolol Anti-arrhythmics β-blockers (class II) Clinical Use SVT, ventricular rate control for atrial fibrillation and atrial flutter.
A 65 year old woman comes to the physician because of shortness of breath when walking short distances. She has 10 year history of hypertension. Current medications include captopril and hydrochlorothiazide. Her BP is 153/90 mmHg, pulse is 80 beat/min and Sp02 is 94%. Physical examination shows elevated jugular venous pressure and 1+ pitting lower extremity edema. An echocardiogram shows systolic dysfunction, mild regurgitation, a dilated left atrium and an ejection fraction of 30%. Which of the following drugs is most appropriate to add to this patient regimen at this current time?
Atenolol Decrease SA and AV nodal activity by [Dec] cAMP, [Dec] Ca 2+ currents. Suppress abnormal pacemakers by [Dec] slope of phase 4. AV node particularly sensitive ==> [Inc] PR interval. Esmolol very short acting Main effect: SVT, ventricular rate control for atrial fibrillation and atrial flutter.
A 61 year old man comes to the emergency department because of shortness of breath, decreased exercise capacity, and distended neck veins. The man has a 3 year history of hypertension. Current medications are hydrochlorothiazide and captopril. His blood pressure is 158/94 mm Hg. After physical examination and laboratory tests, a diagnosis of diastolic ( HFpEF ) cardiac failure is made. Which of the following would be a useful drug to add to the patient's therapeutic regimen?
Atenolol Selective inhibition of beta-1 receptors, with effects including negative chronotropy and inotropy
A 63-year-old woman comes to her physician because of episodes of chest discomfort. She explains that she has been suffering from increasing chest discomfort for the past 1-2 years. At first, she only noticed the discomfort when she experienced extreme exertion, such as running for the bus, and these symptoms always promptly resolved when she stopped or slowed down. About 6-9 months ago, she noted that the chest pain episodes had become more frequent, occurring perhaps once or twice per week and precipitated by stress, either physical or mental, but again always resolved with rest. She has a 5- year history of hypertension, well managed with enalapril. Which of the following combination of drugs is the best choice to initiate treatment with?
Atenolol and nitroglycerin
A 56-year-old man comes to the emergency department because of palpitations over the past few days. He has a 10-year history of both hyperlipidemia and hypertension. Current medications are losartan and hydrochlorothiazide. His blood pressure is 145/95 mm Hg and pulse is 115/min. Physical examination shows a normal ejection fraction. An echocardiogram shows no absence of P waves and irregularly irregular RR intervals with a rapid ventricular response. Which of the following rate-control therapies is most appropriate at this time?
Atenolol and warfarin
A 49-year-old man is discharged after being treated for STEMI. In addition to aspirin, clopidogrel, lisinopril and metoprolol, which of the following medications should he be given at discharge?
Atorvastatin
A 66 year-old man is diagnosed with hypercholesterolemia and started on antihyperlipidemic monotherapy. He returns a week later because of muscle pain and dark brown urine. Which of the following antihyperlipidemic agents was this patient most likely prescribed?
Atorvastatin Inhibit conversion of HMG-CoA to mevalonate, a cholesterol precursor; Reduced mortality in CAD patients Hepatotoxicity ( LFTs),, myopathy (esp. when used with fibrates or niacin)
Digoxin is a good choice of drug for patients with both?
Atrial fibrillation and heart failure
A pharmacologist administers and IV infusion of phenylephrine to an experimental animal. The effects of the infusion on the heart are recorded. Pre-treatment with which of the following drugs would most likely block the effects on the heart of the IV infusion of phenylephrine?
Atropine
Antidote for organophosphate poisoning
Atropine
Activation of this receptor [Inc] renin release from kidneys [Inc] heart rate, [Inc] contractility (one heart), [Inc] $lipolysis
B1 - Gs
Formoterol, Albuterol, Salmeterol
B2 selective agonist
May cause dry mouth, MUSCLE CRAMPS, nausea, vomiting, anemia, WEAKNESS, dizziness, orthostatic hypotension, anorexia, GI distress including diarrhea and constipation, hyperglycemia, photosensitivity, rash, and transient blurred vision
Benztropine, Trihexyphenidyl (Antimuscarinic; improves tremor and rigidity but has little effect on bradykinesia in Parkinson disease)
Atenolol
Beta 1 -selective blocker: low lipid solubility, less CNS effect; used for HTN, angina. Tox: asthma, bradycardia, AV block, heart failure
A 58 year old man comes to the emergency department because of a 2 day history of shortness of breath and confusion. His blood pressure is 75/50 mm Hg, respirations are 22/min and pulse is 112/min. Physical examination shows cool extremities, jugular venous distension and diffuse crackles in the lungs. He is diagnosed with cardiogenic shock and an appropriate drug administered. Which of the following mechanisms of action does the pharmacotherapy target?
Beta 1 receptor agonism
Recommended in all patients (unless contraindicated) with stable angina who have had an ACS or who have left ventricular dysfunction
Beta blockers
Angina Diabetes Heart failure Post-MI BPH Dyslipidemias Chronic kidney disease
Beta blockers, CCBs ACEIs, ARBs ACEIs, ARBs, beta blockers Beta blockers Alpha blockers Alpha blockers, CBs, ACEIs/ARBs ACEI, ARBs
AV Node therapy
Beta-blockers (II), Calcium-channel blockers (IV) & digoxin
SA Node therapy
Beta-blockers (II), Calcium-channel blockers (IV) & digoxin
The patient can only produce 50 mL of urine. Afterwards, ultrasonography shows retention of at least 500 mL of fluid within the bladder. Which of the following is the most appropriate pharmacotherapy for this patient?
Bethanechol The patient presents with neurogenic bladder as a complication of his recent stroke. Unlike the pharmacotherapy for BPH that decreases sympathetic innervation to the sphincters, pharmacotherapy for neurogenic bladder restores the parasympathetic innervation that allows sphincter relaxation and voiding, (D)
Direct Cholinergic activators:
Bethanechol (M), Pilocarpine (M), methacholine (M and N), nicotine (N),
Not absorbed or metabolized.
Bile acid resins [Cholestyramine, colestipol, colesevelam] Prevent intestinal reabsorption of bile acids; liver must use cholesterol to make more
SUCCINYLCHOLINE [type of paralysis]
Binds to the nicotinic receptor and depolarizes the junction. Persists in the synaptic cleft, stimulating the receptor: receptor desensitizes. This leads to flaccid paralysis.
A 68-year-old man presents to the physician with progressive exertional dyspnea and lower extremity edema. Echocardiogram shows biventricular dilation and left ventricular ejection fraction of 35%. After initial stabilization, long-term use of which of the following medications will most likely improve survival in this patient?
Bisoprolol, Carvedilol, Metoprolol (Beta-blockers Curb Mortality) Patient has systolic failure. You can use ACE inhibitors, ARBs, aldosterone antagonists and beta-blockers to improve survival. Loop diuretics and thiazides and digoxin only used for symptomatic relief!
Peptide that is Direct thrombin inhibitors
Bivalirudin (related to hirudin, the anticoagulant used by leeches), Directly inhibits activity of free and clot-associated thrombin Clinical Use: Venous thromboembolism, atrial fibrillation. Can be used in HIT, when heparin is BAD for the patient. Does not require lab monitoring.
A 30-year old man undergoes surgery for a mitral valve replacement. He is given packed red blood cells and fresh frozen plasma during surgery. After surgery, treatment with an anti-coagulant drug is started. 5 days later, he develops non-blanching, darkened and purpuric lesions on his trunk and arms. His temperature is 37oC (98.6oF) pulse is 95/min, respirations are 18/min, and blood pressure is 134/76 mmHg. The remainder of the physical examination is unremarkable. Laboratory studies show WBC is 11, 000/mm3, hemoglobin is 13.5mg/dL, and platelets are 85, 000/mm3. A review of the chart shows normal labs prior to the initiation of anticoagulation five days ago. Administration of which of the following drugs is most appropriate for this patient?
Bivalirudin (related to hirudin, the anticoagulant used by leeches), Argatroban, Dabigatran (only oral agent in class). Directly inhibits activity of free; clot-associated thrombin. Clinical use: Venous thromboembolism, atrial fibrillation. Can be used in Heparin Induced thrombocytopenia (HIT), when heparin is BAD for the patient. Does not require lab monitoring.
A 49 year old woman is admitted to the hospital because of generalized weakness, continuous nausea, and diarrhea. The patient's own report is vague, but notes from her chart from other hospitals revealed that she has a very long history of laxative abuse. Blood test results on admission show pronounced hypokalemia (K+ 2.8mEq/L). An appropriate therapy is started that includes the administration of amiloride. Which of the following actions best explains the potassium sparing effect of this drug?
Blockade of Na channels in the collecting duct. [K sparing diuretic]
Ranolazine (MOA)
Blockade of Na+ current that facilitates Ca2+ entry via Na+/Ca2+ exchanger Decreased intracellular Ca2+ reduces ventricular tension & myocardial O2 demand Thought to also produce myocardial relaxation May modify fatty acid oxidation
Dantrolene [ryanodine receptor antagonist] Usage
Blocks release of Ca2+ from SR. treatment of Malignant hyperthermia: rare, life-threatening condition in which inhaled anesthetics or succinylcholine induce hyperthermia and severe muscle contractions. Susceptibility is often inherited as autosomal dominant with variable penetrance. Mutations in voltage-sensitive ryanodine receptor (RYRJ gene) cause [inc] Ca 2 + release from sarcoplasmic reticulum.
Vesamicol MOA
Blocks the ACh-H+ antiporter for transport ACh into vesicles [preventing the storage of ACh]
Hemicholinium-3 (HC-3)
Blocks the CHT. Prevents uptake of choline required for ACh synthesis. Research tool.
student pre-treats an experimental animal with scopolamine. Subsequently, he injects norepinephrine intravenously. Result?
Blood pressure [INC] Heart rate [INC]
Treatment of pulmonary hypertension
Bosentan Endothelin (ET)-1 is a powerful vasoconstrictor through ET-A and -B receptors. Bosentan is an ET-A receptor antagonist. • Administered orally • Side effects: those associated with vasodilation (headache, flushing, hypotension) • Contraindication: pregnancy Prostacyclin (PGI 2 ): Epoprostenol •Administered via infusion pumps SildenafiL Inhibits type V PDE Increases cGMP Pulmonary artery relaxation Decreases pulmonary hypertension
CARBA CHOLE
Both muscarinic and nicotinic agonist. USES Miosis during surgery. Reduces intraocular pressure after cataract surgery.
Type IA antiarrhythmics are most effective at treating which of the following?
Both supraventricular and ventricular arrhythmias
Type IC antiarrhythmics are most effective at treating which of the following?
Both supraventricular and ventricular arrhythmias
Type III antiarrhythmics (K+) are most effective at treating which of the following?
Both supraventricular and ventricular arrhythmias
Inhibits Ach release
Botulinum toxin
Atropine is most effective at treating which of the following?
Bradycardias
Which drug will utilize the same signaling pathway as endogenous bradykinin on smooth muscle?
Bradykinin binds to endothelial receptors and causes the formation of nitric oxide, which signals through the cGMP pathway to relax smooth muscle. Nitroprusside utilizes nitric oxide and cGMP in a similar fashion to relax smooth muscle.
Selective Alpha 2 agonist used in glaucoma.
Brimonidine --> Reduce aqueous humor synthesis Adverse effects Blurry vision, ocular hyperemia, foreign body sensation, ocular allergic reactions, ocular pruritus
Used in hyperprolactinemia and a rarely used alternative drug in parkinsonism
Bromocriptine
Ergot Alkaloids
Bromocriptine drugs that constrict blood vessels in the brain and provide relief of pain for certain migraine headaches
Drugs Used in the Management of COPD
Bronchodilators (E.g β2 Agonists Anticholinergic) Corticosteroids Mucolytic agents
A 32-year-old man comes to the physician because of intermittent shortness of breath that has been worsening over the past 6 months. He uses a SABA inhaler. He now has intermittent periods of shortness of breath on most days, and he wakes up approximately 2 nights a week with a cough and shortness of breath. His asthma severity is classified as moderate persistent. Which long term therapy should be prescribed to this patient?
Budesonide
Rate control (slowing of ventricular rate) - negative dromotropic agents
Ca2+ channel blockers Beta-blockers Digoxin (in patients with reduced EF or CHF) Amiodarone (when other agents can't be used
Quaternary ammoniums [Impair permeability of cell membranes.]
CHOLINE ESTERS Methacholine, carbachol and bethanechol are more resistant to hydrolysis by cholinesterase.
The drug is available only on a limited basis
CISAPRIDE (prokinetic agent) because of prolonging QT interval
Prophylaxis post-MI and in supraventricular tachyarrhythmias (SVTs)
CLASS II: BETA BLOCKERS Prevent β-receptor activation, which would normally ↑ cAMP ↓ SA and AV nodal activity ↓ Slope of phase 4 (diastolic currents) of AP in pacemakers
when patients smokes, nicotine binds receptors on brain indirectly increasing permeability of which ion?
Calcium (Ca2+)
Verapamil (Calan)
Calcium channel blocker prototype: blocks L-type channels; cardiac depressant and vasodilator; used in HTN, angina, and arrhythmias (group 4). Tox: AV block, HF, constipation.
Which of the following class of drugs have found to be the least useful in HFrEF?
Calcium channel blockers
Mainly Supraventricular Tachycardia (SVT) Therapy
Calcium-channel blockers (IV) & Beta-blockers
Which drug is useful for patients with congestive heart failure because it reduces both preload and afterload, and also inhibits cardiac remodeling?
Captopril and other ACE inhibitors are primary treatment options for congestive heart failure because they reduce preload by dilating veins and reduce afterload by dilating arterioles. They inhibit cardiac remodeling which results in improved survival for patients with heart failure. Hydralazine reduces afterload but does not affect preload. Hydrochlorothiazide reduces preload but does not affect afterload and does not inhibit remodeling. Neither prazosin nor nifedipine has any significant role in heart failure.
Patient with history of hypertension, dyslipidemia, and congestive heart failure comes to the emergency department with acute onset swelling of the lips, eyes, and tongue causing airway obstruction and respiratory distress. Physical examination also shows an urticarial rash. Current medications include captopril, hydrochlorothiazide, atenolol, simvastatin and aspirin. Which of his current medications is the most likely cause of the patient's current symptoms?
Captopril, Enalapril, Lisinopril (ACEI) ACE inhibitors. Reduce levels of angiotensin II and prevent inactivation of bradykinin, a potent vasodilator. Increases renin release Tachycardia, MI, rash, pruritus, gastric irritation, aphthous ulcers, peptic ulcers, dysgeusia, proteinuria, bone marrow suppression, cough
Muscarinic and Nicotinic agonist. Administered as eye drop solution.
Carbachol Constricts pupil and relieves intraocular pressure in open-angle glaucoma. Carbon copy of acetylcholine (but resistant to AChE).
Acetazolamide
Carbonic anhydrase-inhibiting diuretic acting in the proximal convoluted tubule: produces a NaHCO diuresis, results in bicarbonate depletion and metabolic acidosis. Has self-limited diuretic but persistent bicarbonate-depleting action. Tox: paresthesias, hepatic encephalopathy. Dorzolamide and brinzolamide are topical analogs for glaucoma.
A 67-year-old man comes to the physician because of palpitations and fatigue. Further evaluation shows atrial fibrillation, and treatment is begun with a medication that acts by inhibiting sodium-potassium ATPase. Three weeks later he returns to the physician for a follow-up examination with a complaint of yellow/green visual halos, dizziness, and abdominal pain. His serum drug levels are well above the therapeutic range. The patient is at highest risk for developing which of the following?
Cardiac arrhythmia
Digoxin
Cardiac glycoside prototype: positive inotropic drug for HF, half-life 40 h; inhibits Na + /K + -ATPase. Tox: calcium overload arrhythmias, GI upset
Mnemonic: Generic names of b 1 -selective blockers start with A through M except for ....
Carvedilol, Labetalol.
A 45 year old man visits his doctor for a routine appointment. His medical history is significant for heart failure. Current medications include carvedilol, furosemide, enalapril, digoxin and spironolactone. Which of the drugs he is taking has been shown to prolong life in patients with chronic CHF but initially causes a worsening of the patient's symptoms?
Carvedilol, labetalol A1 and B1/2 receptor blocker-->lower bp, lower HR/contractility, bronchoconstriction -->decreased cardiac work Uses = chronic CHF; HTN
Which of the following is true regarding epinephrine structural analog, isoproterenol?
Causes greater drop in total peripheral resistance (TPR) at high doses because of having no effect on alpha 1 receptors as oppose to the epinephrine which act on both Beta (low doses) and alpha (high doses)
A 24-year old woman comes to the emergency department with palpitations. She says that this happens every few years without any identifiable causes. Her pulse is 200/min. An ECG shows narrow complex QRS. Her heart rate is 204/min with a regular rhythm. She is given a drug that activates cardiac potassium channels and causes transient atrioventricular block. Which of the following adverse effects is most likely to occur following administration of this drug?
Chest pain
Adverse effect of adenosine (Activate cardiac K+ Channel and causes transient AV block )
Chest pain [Inc] K + out of cells -> hyperpolarizing the cell and [Dec] I Ca , decreasing AV node conduction. Drug in diagnosing/terminating certain forms of SVT. Very short acting (~ 15 sec). Effects blunted by theophylline and caffeine (both are adenosine receptor antagonists). Adverse effects include flushing, hypotension, chest pain, sense of impending doom, bronchospasm.
•Useful only in hyperlipidemias involving isolated increases in LDL. •In patients who have hypertriglyceridemia as well as elevated LDL levels, VLDL levels may increase.
Cholestyramine Colestipol Colesevelam
Which one of the following is likely to occur following treatment of a hypercholesterolemic patient with cholestyramine?
Cholestyramine and colestipol are resins that sequester bile acids in the gut, preventing their reabsorption. This leads to release of their feedback inhibition of 7-alpha hydroxylase and the diversion of cholesterol toward new synthesis of bile acids. Increase in high-affinity LDL receptors on hepatocyte membranes decreases plasma LDL. These drugs have a small but significant effect to increase plasma HDL rather than decrease it, but their ability to increase TGs precludes their clinical use in the management of hypertriglyceridemias.
Edrophonium
Cholinesterase inhibitor: very short duration of action (15 min).
Pralidoxmine* (2-PAM)
Cholinesterase regenerator for organophosphate insecticide poisoning.
Inhibits P450 enzymes
Cimetidine
cause hypotension and atrial flutter with high ventricular rate.
Class 1C antiarrhythmic. Flecainide+Propafenone is a blocker of Na+ and K+ channels with slow unblocking kinetics. Flecainide suppresses phase 0 upstroke in Purkinje and myocardial fibers. This causes marked slowing of conduction in all cardiac tissue, with a minor effect on the duration of the action potential and refractoriness
Which class of antiarrhythmic drugs are not commonly used clinically due to their high levels of adverse effects?
Class IA
Rhythm control (induction / maintenance of sinus rhythm)
Class IC antiarrhythmics, (flecainide, propafenone) Class III antiarrhythmics, (amiodarone, dofetilide) 47
Dofetilide
Class III
cause QT prolongation and torsades de pointes.
Class III drug. Class III agents block potassium channels and thus diminish the outward potassium current during repolarization of cardiac cells. They prolong duration of the action potential without altering phase 0 of depolarization or the resting membrane potential. Instead, they prolong the effective refractory period.
Atrial myocytes therapy
Class's IA & IC & K+ channels blockers (III)
Ventricular & Supraventricular Therapy
Class's IA & IC & K+ channels blockers (III)
alpha 2 selective agonists
Clonidine Methyldopa Brimonidine
Antagonist at P2Y12 receptors
Clopidogrel
A 64-year-old man comes to office due to exertional chest pain over the last 6 months. He is a lifelong 1-pack-per-day cigarette smoker and has a history of diabetes mellitus and peripheral artery disease. The patient develops chest pain upon moderate exertion one day that is accompanied by ECG changes, which is resolved with rest. The patient has a previous contraindication with aspirin. Which of the following is the best alternate therapy for prevention of cardiovascular disease?
Clopidogrel [ADP receptor inhibitors] Inhibit platelet aggregation by irreversibly blocking ADP (P2Y 12 ) receptor. Prevent expression of glycoproteins IIb/lla on platelet surface. Clinical Use: Acute coronary syndrome; coronary stenting. Iowers incidence or recurrence of thrombotic stroke. Adverse effects: Neutropenia (ticlopidine) . TTP maybe seen
Potentiates the effects of norepinephrine
Cocaine
Reuptake inhibitors
Cocaine, Tricyclic antidepressants (TCA)
cough
Codeine and dextromethorphan •Suppress cough reflex via a direct action on the cough center in the medulla of thebrain. •Adverse effects: constipation and drowsiness. •Dextromethorphan is safer and has lowerabuse potential than codeine.
Contraindicated in hypertryglyceridemia.
Colesevelam
May reduce absorption of several drugs and liposoluble vitamins Constipation Nausea Flatulence Bloating Rise in TG
Colestipol
Patient has a 15year history of laxative abuse. Laboratory results show hypokalemia (K+ 2.8mEq/L). An appropriate therapy is started including a drug that blocks epithelial sodium channels in which of the following locations?
Collecting duct
A 60 year old African American woman comes to the physician because of breathlessness and swelling in her ankles. She has a 7 year history of congestive heart failure. Current medications are lisinopril, atenolol, furosemide and digoxin. Her blood pressure is 143/87 mm Hg and her pulse is 124/min. Physical examination shows 3+ pretibial edema and dyspnea. Which of the following drugs would be most appropriate to add to her regimen at this time?
Combination - Hydralazine Reduce afterload. Artery relax> vein Inc cGMP-> relax smooth muscle -isosorbide dinitrate (Vasodilation)
Spironolactone MOA
Competitive inhibition for aldosterone receptors in distal tubules, leading to increased excretion of fluid and sodium with increased potassium retention
A 32-year-old woman is admitted for gastric bypass surgery. After the procedure she is unable to pass urine. Vital signs are within normal limits. Physical examination shows a distended bladder. A drug with which of the following mechanisms of action would most likely be used to relieve her symptoms?
Competitive inhibition of acetylcholinesterase
Examination reveals medial hypertrophy, intimal fibrosis, and decreased intraluminal diameter of the small branches of the pulmonary artery. Which of the following is the most appropriate pharmacotherapy for this patient's current condition?
Competitively antagonizes endothelin-1 receptors ==> reduce pulmonary vascular resistance.
Recommended for use in patients who cannot tolerate ACEI or ARB, or in African American patients with advanced heart failure as an adjunct to standard therapy
Concurrent use of hydralazine and isosorbide dinitrate
The most common adverse effects of digoxin are
Conduction disturbances, cardiac arrhythmias, nausea, vomiting, confusion, and visual disturbances.
A 44 year old woman comes to physician because of 2 month history of palpitations. Her pulse is 137/min and irregularly irregular. An ECG shows irregularly spaced QRS complexes and no distinct P waves. Treatment is started with drug that increases PR interval and prevents voltage dependent calcium channel entry into myocytes. which of the following adverse effects is she most likely to experience??
Constipation
CONTRAINDICATIONS OF ANTIMUSCARINIC AGENTS
Contraindicated in patients with angle-closure glaucoma. Should be used with caution in patients with prostatic hypertrophy and in the elderly
Oxytocin (OT) Usage
Control of postpartum hemorrhage, but if it is ineffective, ergonovine or methylergonovei IM can be tired.
Verapamil, diltiazem. [Dec] conduction velocity, [Inc] ERP, [Inc] PR interval.
Control of ventricular rate
Anti-inflammatory Drugs
Corticosteroids Release inhibitors Immunomodulators Leukotrienemodifying agents
inhibits mast cell degranulation
Cromolyn
Alternative medications for patientswith mild persistent asthma. Also used to prevent exercise-induced bronchospasm.
Cromolyn and Nedocromil
Useful in management of serotonin syndrome
Cyproheptadine
Dopamine Effects - low dose: ................... activated in renal and vascular beds leading to: vasodilation, inc GFR, inc RBF, inc sodium excretion - intermediate dose: .................... activated in heart, inc CO. Neglible activation of b2. inc SBP, DBP no change. - high dose: ........... activated > vasoconsriction and inc BP. TPR may also inc.
D1 B1 A1
Competitive, direct thrombin inhibitor; thrombin enables fibrinogen conversion to fibrin during the coagulation cascade, thereby preventing thrombus development
Dabigatran
Direct thrombin Inhibitor. Orally active.
Dabigatran
Used in muscle spasm (cerebral palsy, multiple sclerosis, cord injury) and in emergency treatment of malignant hyperthermia.
Dantrolene
pt was diagnosed with Wolff-Parkinson-White syndrome several years ago, and has been taking a medication, but she cannot remember the name. What is the most likely mechanism of action of the drug this patient is taking?
Decreased conduction velocity through the AV node
A 57-year-old man with 2-year history of hypertension managed by diet and exercise comes to the physician for a follow-up examination. His blood pressure is 166/97 mmHg. Laboratory studies show plasma renin activity 3-4 times higher than normal. Treatment with Losartan started. Following administration, which of the following is most likely to be seen?
Decreased plasma uric acid levels ARBs compete with uric acid for URAT1 binding and therefore reduce plasma uric acid. Can be useful in the treatment of gout.
Beta Blockers or Ca2+ channel blockers [CCB]. Decreases what??? Increases what??
Decreases: HR, Arterial Pressure, Contractility Increases: Ejection time, EDV
Nitrates + Beta blockers or C2+ channel blockers Decreases what??? Increases what?
Decreases: HR, Arterial pressure just a little EDV Nothing increases
which of the following effect is mediated by drug used to treat choreactic movement associated with Huntington disease?
Depletion of presynaptic catecholamines
Ergonovine
Diagnosis Of VariantAngina
A 86-year-old woman comes to emergency department because of shortness of breath and palpitations. She has a 13-year history of HFrEF. Current medications include losartan and hydrochlorothiazide. Her BP is 143/81 mm Hg, pulse is 154/min with an irregularly irregular pattern and respirations are 16/min. An ECG shows an absence of P waves and irregular RR intervals. control this patient's ventricular rate????
Digoxin
A 91 year old man comes to the emergency department because of shortness of breath and palpitations. He has 14 year history of hypertension. Current medications include losartan and hydrochlorothiazide. His blood pressure is 143/81 mmHg, pulse is 154/min with an irregularly irregular pattern and respirations are 16/min. An echocardiogram shows normal sized left ventricle with an ejection fraction of 30%. An ECG shows an absence of P waves and irregular RR intervals. which of the following is the most appropriate drug to help control this patient ventricular rate?
Digoxin
Used to decrease the symptoms of heart failure as well as to increase exercise tolerance and to decrease the rate of hospitalization, it does not however, increase survival outcome. It should only be in addition to the standard recommended drugs (ACEI, diuretic and β-blocker).
Digoxin
An 82-year-old man is brought to emergency department with fatigue and palpitations. The patient is administered intravenous digoxin and appears comfortable 2 hours later. Which of following explains the heart-rate lowering effects of medication?
Digoxin stimulates vagal tone and is good for controlling rate control in A-fib.
A 75-year-old patient suffering from congestive heart failure accidentally ingests a toxic dose of digoxin. Clinical consequences due to the toxic effects of cardiac glycosides are likely to include
Digoxin toxicity is associated with CNS consequences including disorientation and visual dysfunctions such as halos around lights and blurry, yellow vision. More serious manifestations include lifethreatening arrhythmias
.................... , like verapamil, has more depressant effect on heart than dihydropyridines (eg, nifedipine)
Diltiazem
A 39 year old woman is brought to the emergency department because of recurrent chest pain and breathlessness. She describes the pain as pressure like the initially worsened with activity. However, recently she has noticed that the pain is still present with decreasing physical activity and even at rest. Physical examination shows an anxious patient who is in pain. An ECG shows sinus bradycardia with no ST changes. Cardiac troponins are not elevated. Her blood pressure is 135/82 mmHg and pulse is 85/min. 24 hotter monitoring shows sinus rhythm with episodes of severe ST elevations. A diagnosis of vasospastic angina is made. In addition to nitroglycerin which of the following drugs should also be administered?
Diltiazem, Verapamil [calcium channel blockers (class IV)] [Dec] conduction velocity, [Inc] ERP, [Inc] PR interval.
A 35-year- old man comes to the physician to request a medication to prevent sea- sickness. Which of the following is the most appropriate pharmacotherapy for this patient?
Dimenhydrinate
Useful in GERD
Ranitidine (Zantac) H2 receptor antagonist. Potent inhiitor of gastric acid secretion Indications: GERD, ulcers, H. pylori, reflux, indigestion ADR: Pain, constipation, diarrhea, headache. Can cause jaundice
First-generation vs. Second-generation Oral Antihistamines:
Diphenhydramine Chlorpheniramine Loratadine Fexofenadine Cetirizine
May cause dry mouth and urinary retention.
Diphenhydramine (Benadryl) First generation
Actions: •Potent inotrope (increase contractility= increased CO •INCREASE SV & DECREASE ESV (high yield for step) •Mild chronotropic effect (mild increase in heart rate) •Mild vasodilation via B2 (decreased TPR= increases CO) OVERALL: MAP FALLS
Dobutamine
B1 selective agonist
Dobutamine - potent inotrope, with mild chronotropic effects. - produces less inc in HR and less dec in PVR - mild vasodilation; inc myocardial O2 consumption - management of acute heart failure + cardiogenic shock
A 25 year- old healthy male volunteer receives an IV infusion of a new drug in a phase 1 clinical trial. It is found that the drug causes an increase in cardiac contractility, a slight increase in heart rate, and no major changes in systemic vascular resistance. Which of the following drugs does the new agent most resemble?
Dobutamine beta 1 agonist -inotropic agent, inc. contractility and CO, does NOT inc HR. -used in acute management of heart failure. -short 1/2 life due to COMT
Both dobutamine and inamrinone increase cardiac contractility by
Dobutamine acts as a beta-1 agonist to activate adenylyl cyclase and increase cAMP. Inamrinone inhibits phosphodiesterase III which increases the amount of cAMP in the heart. In each case, there is an increase in intracellular Ca 2+ being sequestered in the SR which leads to enhance contractility.
A 43 year old man comes to emergency department because of shortness of breath and palpitations. He has 5 year history of hyperlipidemia. Current medications include atorvastatin. His blood pressure is 143/81 mmHg, pulse is 154/min with an irregularly irregular pattern and respirations are 16/min. An echocardiogram shows normal sized left ventricle with an ejection fraction of 60%. An ECG shows an absence of P waves and irregular RR intervals. A drug is prescribed to attempt to revert the patient back to normal sinus rhythm. after administration of the drug the patient ECG shows prolongation of QT interval but no change in PR or QRS is observed. Which of following drugs was the patient most likely administered??
Dofetilide (K+ Channel blockers) [Inc] AP duration, [Inc] ERP, [Inc] QT interval.
A 43-year-old man is treated for a ventricular arrhythmia with an oral drug. After administration of drug patient's EKG shows prolongation of the QT interval but no change in QRS is observed. Which of the following drugs was the patient most likely given?
Dofetilide [Class III]
Used in the treatment of Alzheimer's disease
Donepezil
AChE INHIBITORS USED IN ALZHEIMER DISEASE
Donepezil Rivastigmine Galantamine
NOT used in the chronic management of congestive heart failure. It is indicated in the acute treatment of cardiac decompensation.
Dopamine is a positive inotropic agent Milrinone is a positive inotropic agent (it inhibits PDE3 to cause an increase in cAMP)
A patient with CAD is scheduled to undergo coronary stent implantation. In order to reduce risk of an adverse cardiovascular event after placement of the stent, a combination of aspirin and another drug with similar indications is administered. Following a 2-week period, patient returns and a complete blood count is done because of a potential adverse effect of neutropenia caused by the drug. Which of the following best describes the MOA of this drug?
Drug in question is going to be a platelet aggregation inhibitor. Key thing in the stem is that a potential adverse effect is NEUTROPENIA. Of the drugs in this class from lecture, only Ticlopidine has this adverse effect. Clopidogrel also has a similar mechanism, but has less adverse effects (no neutropenia).
A 67-year-old man has a history of severe hypertriglyceridemia (TG). He was treated with a fibrate medication in the past, but could not tolerate it due to liver toxicity. The physician now prescribes a medication and explains to the patient that he is likely to experience skin flushing and warmth after taking the pills. Which of the following is the primary agent mediating these side effects?
Drug in question is niacin, which increases HDL and causes prostaglandin-mediated flushing. This can be prevented by aspirin
A 41-year-old woman with a history of angle-closure glaucoma begins treatment with a first-line oral drug for this condition. Three weeks later, she returns to the physician for a follow-up examination. Laboratory studies show an arterial pH of 7.34, arterial PCO2 of 29 mmHg, and plasma HCO3- of 15 mEq/L. Which of following is the most likely underlying condition?
Drug is acetazolamide, a first-line treatment for glaucoma and diuretic. Side effect is metabolic acidosis
After the patient's acute symptoms are treated, the physician decides to add a drug that will further control her heart rate. She is counseled that this new medication may cause visual disturbances, as well as nausea, vomiting, and diarrhea. Which of the following factors could predispose this patient to toxicity to this new medication? (A) Hyperkalemia
Drugs that control heart RATE à Beta-blockers, calcium-channel blockers and digoxin. Drug in question is digoxin, because stem specifies visual disturbances.
Atropine adverse effects
Dry mouth, blurred vision, sandy eyes, tachycardia, constipation urinary retention. Effects on CNS: restlessness, confusion, hallucinations, delirium, which may progress to depression, collapse of the circulatory and respiratory systems and death.
Eccenteric Hypertrophy
Duplication of sarcomas in series increase left ventricular end diastolic volume (preload) results in dilation of left ventricle in attempt to increase myocardial contractility to maintain cardiac out. this compensatory mechanism ultimately fail and continue strain of. increase blood o blue in the LV trigger myocardial remodeling that results in eccentric hypertrophic (addition of sarcomas in errs) eventually leading to dilated cardiomyopathy and reduced ejection fraction. most case of dilated cardiomyopathy are idiopathic bugs common identical emus indulge exposure to toxic xustbance metabolic Agnes nd infect pathogens that cause struck damage to myocardium or values
Reverses neuromuscular block produced by NON-depolarizing muscular blockers.
Edrophonium
Used in diagnosis of myasthenia gravis and to distinguish myasthenic crisis from cholinergic crisis.
Edrophonium
A colleague with myasthenia gravis wants you to assist him to the ER because he is experiencing muscle weakness and has found it difficult to titrate his drug dosage because he has had the "flu." You note that he has a slight temperature, shallow respirations, and a gray-blue skin pallor. What would be the most appropriate drug to give to your colleague at this time?
Edrophonium is a very short-acting (reversible) AChE inhibitor that has been used in the diagnosis of myasthenia gravis. The drug is useful for distinguishing between muscle weakness attributable to excessive cholinergic receptor stimulation (usually due to overdose of a AChE inhibitor) and the symptoms of myasthenia (reflecting inadequate treatment). If symptoms improve with a single dose of edrophonium, then an increase in the dose of neostigmine or pyridostigmine is indicated. If symptoms worsen, then the dose of neostigmine should be reduced.
AChE inhibitors reversible—
Edrophonium, physostigmine, neostigmine, pyridostigmine, donepezil, rivastigmine
A 56-year-old man is brought to emergency department by a friend because of altered mental status. His blood pressure is 165/112 mmHg and pulse is 132/min. Physical examination shows an agitated man. His skin is warm and sweaty, and his pupils are dilated. Which of the following is the most likely cause of these symptoms?
Ephedrine
Adenosine mechanism of action
Enhances K+ conductance Inhibits cAMP-mediated Ca2+ influx Leads to hyperpolarization esp. in AV node Clinical Applications IV adenosine = drug of choice for abolishing acute supraventricular tachycardia
Inhibits hepatic uptake of statins
Gemfibrozil
Epinephrine PHYSIOLOGICAL ANTAGONISTS??
Epinephrine has smooth muscle actions opposite to those of histamine, but acting at different receptors.
Specifically used in the treatment of pulmonary hypertension.
Epoprostenol
Bromocriptine
Ergot derivative: prototype dopamine agonist in CNS; inhibits prolactin release. . Tox: Various CNS disturbances, dyskinesias, hypotension.
Cardioselective beta blocker with a short elimination half-life that is administered via the intravenous (IV) route only?
Esmolol
used in acute SVTs
Esmolol (IV)
Anaphylaxis cause and antidote
Exaggerated immune mediated hypersensitivity reaction that leads to systemic histamine release by mast cells, increased vascular permeability, and vasodilation; regardless of the etiology, the presentation and management of anaphylactic reactions are the same ■Treated rapidly with Epinephrine.
■ Activate peroxisome proliferator- activated receptor-a(PPAR-α). ■PPAR-α receptors are expressed in liver + brown adipose tissue. ■ Activation of PPAR-α by fibrates leads to [Dec] in plasma TG levels and [Inc] in plasma HDL levels.
FIBRATES
Decrease in plasma TG levels is caused by increased expression of lipoprotein lipase, decreased hepatic expression ofapoC-III, and increased hepatic oxidation of fattyacids.
FIBRATES: MECHANISM OF ACTION
A 57-year old man is brought to the emergency department because of a sudden onset of shortness of breath and tachycardia. A spiral CT scan of the chest shows a pulmonary embolism. Treatment with a medication that causes an almost immediate inactivation of factor IIa is begun. Which of the following laboratory studies will most likely be used to monitor the effect of the drug administered to this patient?
Factor IIa is also known as thrombin and is part of the intrinsic clotting pathway (factors III, VII are extrinsic). APTT will be increased with problems in the intrinsic pathway.
increased risk of myopathy when combined with statins or niacin
Gemfibrozil
ACE inhibitors adverse effects
Fatigue Dizziness Headache Mood changes Impaired taste Possible hyperkalemia Dry, nonproductive cough, which reverses when therapy is stopped Angioedema: rare but potentially fatal Note: First-dose hypotensive effect may occur
A 76-year-old woman suffers from seasonal allergies that cause irritating rashes, a puffy face, and sneezing. She is prescribed a medication by her physician that acts on a histamine receptor. Which of the following drugs is most appropriate for this woman?
Fexofenadine, Loratadine, , cetirizine. (2nd generation Histamine 1 blocker) Names usually end in "-adine." Adverse effects: Far less sedating than 1st generation because of reduce entry into CNS
Limited use because of proarrhythmogenic effects, leading to ↑ in sudden death post-MI and when used prophylactically in VT
Flecainide
In the treatment of atrial fibrillation which one of the following agents can be used to induce/maintain sinus rhythm?
Flecainide -Class 1C anti-dysrhythmic drugs -Block cardiac sodium channels -Delay ventricular repolarization
organophosphate poisoning. which of the following is adverse effect of most appropriate pharmacotherapy at this time?
Flushing
Used in long-term managementofCOPD
Fluticasone and budesonide
Corticosteroids Used in COPD Inhaled corticosteroids Systemic corticosteroids
Fluticasone and budesonide Oral prednisolone
The least potent statin in lowering LDL.
Fluvastatin
A 12-year-old boy comes to the physician for a follow-up examination. He has a history of moderate asthma and has been using an inhaled corticosteroid daily. He says that over the past 2 months he has needed to use his albuterol inhaler more than 4 times per week. A drug is added to his daily regimen. Which of the following drugs was most likely added to his regimen?
Formoterol
A 76 year old woman comes to clinic with difficulty hearing. She had been admitted to hospital 1 week ago for orthopnea, dyspnea, and bilateral leg swelling. which medications probably led to this patient sensorineural hearing loss?
Furosemide
progressive, bilateral ankle swelling and a cough. She was diagnosed with hypertension 20 years ago and has been frequently noncompliant with prescribed medication. She describes the cough as producing pink frothy sputum. Examination show bilateral pitting edema to the ankles and diffuse crepitations on auscultation. Which of the following medications is most appropriate for relief of this patient's current symptoms?
Furosemide
A 54 year old man comes to the physician for a routine visit. He has a 4 year history of HFrEF. Current medications include lisinopril, hydrochlorothiazide, metoprolol and digoxin. The physician decides to add another drug to the patient's regimen but warns the patient that this drug will increase the risk of digoxin toxicity and close monitoring will be required. Which of the following drugs was the patient likely prescribed?
Furosemide AE hypokalemia; prerenal azotemia
Eptifibatide and Tirofiban
GPIIb/IIIa inhibitors.
To visualize retina, doctor delivers medicine that dilate the iris. What secondary messenger is likely being activated by medication used?
GQ, IP3 (Alpha 1)
Ganglion blocking agents are of little clinical value today but they are important drugs to know for solving cardiovascular drug problems because they can block
Ganglion blockers (hexamethonium, mecamylamine) block N N receptors at autonomic ganglia and the adrenal medulla. As such, they can block all autonomic reflexes including those elicited by changes in blood pressure. They have no effect on nicotinic receptors at the neuromuscular junction (N M ) or on the direct actions of drugs on the blood vessels or heart.
■Myopathy ( risk with statins), ■ cholesterol gallstones (via inhibition of cholesterol 7α-hydroxylase)
GemFIBrozl FenoFIBrate
How to overcome reflex bradycardia of Norepinephrine
Give atropine as a pretreatment before you give NE ·This prevents reflex bradycardia aka the NE will cause tachycardia ·Basically, this kills your baroreceptor reflex o Atropine blocks M2 on heart o M2 is what causes reflex bradycardia o Block M2 then give NE-à baroreceptor will try and send a signal to decrease HR but M2 is already blocked by atropine so you won't have the reflex and thus you will have TACHYCARDIA
A 45 year old man with clinical depression is brought to the emergency department with severe symptoms of cardiac depression. His sister informs you that he has swallowed approximately 25 pills of her blood pressure medication, which you discover to be atenolol. Which of the following drugs is the most appropriate initial treatment for this overdose patient?
Glucagon
overdose of beta blockers cause cold, clammy extremities, low glucose concentration, low pulse low blood pressure, scattered expiratory wheezing heard throughout both lung fields
Glucagon increase intracellular cAMP by activating adenylate cyclase which improve cardiac contractility
First-line treatment for allergic rhinitis.
Glucocorticoids
Amiodarone
Group 3 (and other groups) antiarrhythmic: broad spectrum; blocks sodium, potassium, calcium channels, b receptors. High efficacy and very long half-life (weeks to months). Tox: deposits in tissues; skin coloration; hypo- or hyperthyroidism; pulmonary fibrosis; optic neuritis
inverse agonists.
H1-blockers were considered H1 receptor antagonists.
Cimetidine
H2 blocker prototype: used in acid-peptic disease. Tox: inhibits hepatic drug metabolism; has antian-drogen effects. Less toxic analogs: ranitidine, famotidine, nizatidine
Autonomic receptor coupled to Gq
HAV1 M1M3
A 70-year-old woman comes to the physician because of a 4-month history of exertional chest pain. Physical examination shows a blood pressure of 152/90 mm Hg but is otherwise unremarkable. The ECG is normal. She exercises for 8 minutes, experiences chest pain, and is found to have a 2-mm ST-segment depression in the inferolateral leads at the end of exercise. Treatment is begun with atenolol and isosorbide mononitrate and the patient is also provided with a drug that can be administered in an acute attack that is administered sublingually. Which of the following adverse effects is most likely to occur after administration of the sublingual drug?
Headache
______________________ anticoagulant effect is a consequence of binding to antithrombin III. Antithrombin III is an alpha-globulin. It inhibits clotting factor proteases, especially thrombin, IXa and Xa. The binding of ______________________ to antithrombin III leads to a substantial acceleration in the inhibition of the proteases. A critical sequence of five carbohydrate residues in ______________________ is required for binding to Anti-Thrombin III. ______________________ functions as a cofactor for the Anti-Thrombin-protease reaction without being consumed. Once the Anti-Thrombin-protease complex is formed, ______________________ is released intact.
Heparin
Dofetilide Adverse effects Antiarrhythmic K+ channel blockers (class III)
Headache, chest pain, dizziness, ventricular tachycardia Torsade de Pointes (prolongs QT interval)
Parasympathetic (cholinergic) Predominant tone
Heart (M2) Iris (M3) Ciliary muscle(M3) GI tract(M3) Urinary bladder(M3) Salivary(M3) glands(M3)
Inhibitor of ACh synthesis Inhibitor of Ach storage Inhibitor of Ach release
Hemicholinium-3 Vesamicol Botulinum toxin
Initial anticoagulant therapy for DVT
Heparin
Glucagon
Hormone from pancreatic A cells. Increases blood glucose via a GPCR G s and cAMP. Used in severe hypoglycemia and as an antidote in b-blocker overdose
Which of the following would be caused by atropine intoxication but not by amphetamine intoxication?
Hot as a hare (inc temp), Dry as a bone (dec secretions), Red as a beet (flushed skin), Blind as a bat (cycloplegia), Mad as a hatter
It is a second/third line treatment for hypertension due to it having to be given with both a β-blocker and a diuretic to combat these adverse effects.
Hydralazine
Reflex tachycardia occurs with which of the following drugs?
Hydralazine
6. A 67-year-old African-American man comes to the physician because of difficulty breathing for the past month. He is now having trouble walking around 1 block before feeling too short of breath. A physical exam reveals bilateral pitting edema, visible JVD and palpable heaves. The patient is currently being treated for chronic hypertension with diltiazem, furosemide, and propranolol. Which of the following could be added to this patient's regimen to improve his current condition?
Hydralazine + isosorbide dinitrate
African American woman comes to the physician for an annual checkup. She has a 5 year history of hypertension refractory to thiazide diuretics and ACE inhibitors. Her blood pressure is 170/115 mm Hg and BMI is 31. It is decided to prescribe a drug that works by directly dilating arterioles. The patient should be instructed to return immediately if she experiences which of the following drug adverse effects?
Hydralazine adverse effects Reflex tachycardia Increased blood volume Systemic lupus erythematosus-like syndrome Headache, dizziness, weakness, and fatigue
pt hypertension continues to persist despite the previous administration of several medications. The physician decides to add a drug to his regimen that preferentially dilates arterioles. Which of the following drugs was prescribed?
Hydralazine can also be used to treat hypertension/pre-eclampsia in pregnancy. Other options include drugs like labetalol, methyldopa (sometimes) and magnesium sulfate. I might be forgetting some.
A patient has a genetic polymorphism such that they cannot rapidly metabolize drugs by acetylation. You would be most concerned about this polymorphism if the patient was taking which drug?
Hydralazine is metabolized by N-acetyltransferase (a phase II drug metabolism reaction) associated with a genetic polymorphisms. Patients who are classified as slow acetylators may develop SLE-like symptoms when treated with hydralazine. Other drugs metabolized via N-acetyltransferase, including isoniazid and procainamide, have also been associated with lupus-like symptoms in slow acetylators.
African American woman comes to the physician for a follow up examination. At the last examination, one month ago, she had elevated blood pressure. Her current blood pressure is 139/87 mm Hg and pulse is 80/min. Which of the following drugs is the most appropriate initial pharmacotherapy for this patient?
Hydrochlorothiazide
A 32-year - old woman is brought to the emergency department in severe pain. She describes the acute onset of flank pain which is radiating to the groin accompanied by nausea and vomiting. A CT scan shows a large urinary stone in the right renal pelvis. Laboratory tests are positive for idiopathic. She is scheduled for surgical removal of the calculus. In order to prevent new stone production which of the following would be the most appropriate pharmacotherapy?
Hydrochlorothiazide HTN, CHF, idiopathic hypercalciuria, nephrogenic diabetes insipidus
A 57 year old man comes to the physician for routine examination. He has a 7 year history of stage 2 hypertension, type 2 diabetes and dyslipidemia. Current medications include insulin, hydrochlorothiazide, losartan, simvastatin and fenofibrate. His blood pressure is 129/81 mm Hg and fasting blood glucose is 170 mg/dL (normal: 70-100 mg/dL). All other lab values are within the normal range. The physician suspects that one of the patient's medications may be the cause of the glycemia. Which of the following drugs is most likely responsible?
Hydrochlorothiazide Inhibit sodium reabsorption in the distal tubule side effect -Hyponatremia (with no salt) -Hypokalemia ( or no money) K -Hypercalcemia (bony) -Hyperglycemia (sugary) -Hyperlipidemia (fatty) -Increased uric acid (gouty) -Sexual dysfunction (geek)
inhibits thromboxane synthesis much more effectively than prostacyclin synthesis?
Hydrocortisone and other corticosteroids inhibit phospholipase. Ibuprofen and indomethacin inhibit cyclooxygenase reversibly, whereas zileuton inhibits lipoxygenase. Because aspirin inhibits cyclooxygenase irreversibly, its action is more effective in platelets, which lack the ability to synthesize new enzyme, than in the endothelium.
Physician decides to initiate treatment with a diuretic that works in the distal convoluted tubule. Which of the following adverse effects could be anticipated in this patient?
Hyperglycemia
Digoxin toxicity will result in?
Hyperkalemia
A major precipitating factor for Digoxin toxicity is?
Hypokalemia
A 58-year-old woman being treated for atrial fibrillation and angina complains of dyspnea on exertion. On exam, her heart rate is 115/min and irregularly irregular at rest. You believe her rate control for atrial fibrillation is suboptimal and the likely cause of her dyspnea. You are considering adding verapamil to her current metoprolol for additional rate control. Which of the following adverse effects should you be most concerned about with this additional medication?
Hypotension
Warfarin acts by preventing the post translational modification of some clotting factors. Which clotting factors are affected by the action of warfarin?
II, VII, IX, X
Activation of H1 receptors leads to
IP3 increase
What would have been the best choice of initial treatment if a hypertensive patient had been of African Ancestry?
In black and/or elderly patients, thiazide diuretics and calcium channel blockers (CCB) are the preferred first-line agents. Along with lifestyle modifications, this is the most appropriate combination.
Increasing the concentration of norepinephrine in adrenergic synapses leads to
In sympathetic nerve endings presynaptic α 2 receptors are coupled to inhibitory G-proteins. These receptors serve an autoregulatory function to inhibit further neurotransmitter release and also to decrease the synthesis of norepinephrine.
Which one of the following effects is caused by the ingestion of mushrooms that contain pilocarpine?
In sympathetic nerve endings presynaptic α 2 receptors are coupled to inhibitory G-proteins. These receptors serve an autoregulatory function to inhibit further neurotransmitter release and also to decrease the synthesis of norepinephrine. Bradycardia due to vagal stimulation is elicited by activation of muscarinic receptors in the heart. Atropine, which is an antagonist at M receptors, blocks bradycardia elicited by stimulation of the vagus, including reflex bradycardia due to increases in mean BP caused by vasoconstrictors.
Which of the following drugs will prevent tachycardia evoked by isoproterenol?
In the case of isoproterenol-induced tachycardia, a reflex is evoked by the B2 mediated decrease in blood pressure. This reflex will be processed by the vasomotor center and result in increased sympathetic autonomic nervous system outflow to the sinus node to increase heart rate. This reflex would be blocked by a ganglion blocker such as hexamethonium. However, isoproterenol also induced tachycardia directly by activating B receptors in the sinus node, an effect nor blocked by a ganglion blockers. Only a ß blocker (propranolol) will prevent both the reflex tachycardia and the direct tachycardia induced by isoproterenol.
In the presence of an ACE inhibitor, potassium levels are known to?
Increase
In the presence of an ACE inhibitor, renin levels are known to?
Increase
In the presence of an ARB, renin levels are known to?
Increase
Concenteric Hypertrophy
Increase in sysmatematic vascular resistance
During a routine visit a 67 year old woman is found to have a plasma level of potassium 2.8 mEq /L (normal 3.5-5.0 mEq /L). The woman has been receiving hydrochlorothiazide for 1 month to treat her recently diagnosed essential hypertension. Which of the following actions most likely contributed to the thiazide induced increase in renal excretion of potassium?
Increased Na+ load in the lumen of the collecting tubule
TXA2 triggers platelet aggregation by
Increasing IP3
Amphetamine - inc BP - used for ADHD + narcoplepsy. Methylphenidate - structural analog of amphetamine - treat ADHD in children Tyramine - normally oxidized by MAO - severe hypertension
Indirect releasing agents
A 45-year-old man has recently been the recipient of a heart transplant. Which one of the following drugs is least likely to cause tachycardia in this patient?
Indirect-acting sympathomimetics require innervation of the effector organ to exert effects. In this case, amphetamine would not be effective because the transplanted heart lacks sympathetic innervation; thus, there is no "mobile pool" of NE capable of being released by a drug. However, transplanted hearts retain receptors, including those (β 1 ) responsive to direct-acting sympathomimetics. Heart transplants are not responsive to AChE inhibitors because they, too, are indirect acting and require vagal innervation to exert effects on the heart.
Ephedrine
Indirectly acting sympathomimetic: like amphetamine but less CNS stimulation, more smooth muscle effects. In botanicals (eg, ma huang) and products for weight loss that are banned in the United States. Tox: hypertension, stroke, MI.
Pt experienced a generalized tonic-clonic seizure after ingesting Induction of norepinephrine release overdose of amphetamine. His blood pressure is 160/105 mmHg. MOA for the patient's hypertension?
Induction of norepinephrine release
A newborn infant is diagnosed with transposition of the great vessels, wherein the aorta exits from the right ventricle and the pulmonary artery from the left ventricle. Which of the following drugs is likely to be used in preparation for surgical correction of this anomaly?
Infants with great vessel transposition pump venous blood to the aorta and oxygenated blood back to the lungs. Therefore, they require surgical correction as soon as they are strong enough to withstand the procedure. In the meantime, they are dependent on a patent ductus arteriosus to allow some oxygenated blood to flow from the left ventricle via the pulmonary artery and ductus to the aorta. The ductus can be prevented from closing by infusing the vasodilator PGE1 .
Pathophysiology of asthma
Inflammation of airway results in: • Bronchiolar Smooth muscle spasm • Airway hyper-responsiveness • Airway edema • Increase mucus secretion
most effective long-term control medication in the management of persistent asthma.
Inhaled Corticosteroids
Bronchodilators: Anticholinergics
Inhaled Short-Acting Muscarinic Antagonists (SAMAs) •Ipratropium Inhaled Long-Acting Muscarinic Antagonists (LAMAs) •Tiotropium
A 64-year-old man with a history of chronic obstructive pulmonary disease (COPD) is evaluated in the emergency department for increased dyspnea over the past 3 days. He has obvious difficulty breathing and cannot speak in full sentences. He has been using his inhalers much more than usual but with minimal improvement. He has smoked one pack per day since age 18 and has a history of hyperlipidemia, hypertension and obesity. His respirations are 28/min, pulse is 100/min, blood pressure of 130/90 mm Hg, and temperature is 37.7°C. His O2 saturation is 84% on room air. Breath sounds are diffusely decreased with bilateral expiratory wheezes. Cardiac examination shows no abnormalities. He does not have any peripheral edema. He is administered supplemental O 2 via nasal cannula, albuterol and ipratroprium by nebulizer and oral prednisone. The next day he appears comfortable, with respirations of 14/min and an oxygen saturation of 95%. Which long-term therapy is most appropriate for this patient?
Inhaled budesonide plus formoterol plus albuterol as needed.
Bronchodilators: Anticholinergics MOA
Inhaled ipratropium and tiotropium block muscarinic receptors on the airways causing bronchodilation and reduction of respiratory secretions.
Glucocorticoids MOA
Inhibit PLA2, thus blocking release of arachidonic acid. Inhibit synthesis of COX-2.
Edema occurs premenstrually Site of action does the appropriate pharmacotherapy work at?
Inhibit sodium reabsorption in the distal tubule side effect -Hyponatremia (with no salt) -Hypokalemia ( or no money) K -Hypercalcemia (bony) -Hyperglycemia (sugary) -Hyperlipidemia (fatty) -Increased uric acid (gouty) -Sexual dysfunction (geek)
5-HT1D/1BRECEPTOR AGONISTS:MOA A sumo wrestler trips and falls on your head.
Inhibit trigeminal nerve activation; prevent vasoactive peptide release; induce vasoconstriction. Clinical Use: Acute migraine, cluster headache attacks.
The mechanism of action of loop diuretics is?
Inhibition of Na + /Cl - /K + cotransporter in ascending loop of Henle
The patient returns 6 months later and whilst his blood pressure is stable, he is now suffering from significant peripheral edema. How would it be best to modify his treatment to combat this new symptom?
Loop diuretics are more efficacious diuretics than thiazides and are indicated when edema is present.
A 62 year old man is brought to the emergency department because of 7 hour history of abdominal pain, nausea, vomiting and confusion. Two months ago his wife died, and he has yet to return to work. He has 5 year history of congestive heart failure and atrial fibrillation well controlled with hydrochlorothiazide, lisinopril, and digoxin. His pulse is 57/min and irregular and blood pressure is 120/80 mmHg. An EBG shows premature ventricular beats. of his current medications, which of the following mechanisms of action is most likely responsible for toxicity exhibited?
Inhibition of Na+/K+ ATPase
A 45 year old man is diagnosed with pulmonary embolism and started on enoxaparin. 24 hours later a second drug is administered. Which of the following is the most likely mechanism of action of this second drug?
Inhibition of vitamin K epoxide reductase (Warfarin)
a-methyltyrosine
Inhibitor of of NE synthesis - competitive inhibitor of tyrosine hydroxylase - management of malignant PCC - used in preoperative prep of pts for resection of PCC
Zileuton (Zyflo)
Inhibitors of 5-lypoxygenase
A 26-year-old woman comes to the physician because of shortness of breath and dyspnea when she jogs. A diagnosis of exercise-induced asthma is made after further evaluation, and treatment with Zileuton is begun. What is the mechanism of this drug?
Inhibits 5-lipoxygenase [Antileukotrienes] Blocks conversion of arachidonic acid to leukotrienes. Hepatotoxic.
BOTULINUM TOXIN
Inhibits acetylcholine release. Injected locally into muscles for treatment of several diseases involving muscle spasms. Also approved for cosmetic treatment of facial wrinkles.
Sildenafil Tadalafil and vardenafil are similar.
Inhibits phosphodiesterase (PDE)-5, preventing breakdown of cyclic guanosine monophosphate (cGMP), which promotes vasodilation and smooth muscle relaxation. Used for erectile dysfunction and pulmonary hypertension. Tox: severe hypotension when combined with nitrates, impaired blue-green color vision
A 9-year-old boy is brought to the emergency department by his parents because of a 2-day history of coughing and breathing difficulties. Physical examination shows moderate to severe respiratory distress with bilateral expiratory wheezing. His blood pressure is 125/81 mm Hg, pulse is 132/min and respirations are 27/min. He is administered albuterol but his symptoms of bronchoconstriction are only partially relieved. Which of the following drugs could be given next in order to evoke additional relief?
Ipratropium
DOC for β-blocker-induced bronchospasm.
Ipratropium
Used in treatment of COPD
Ipratropium Muscarinic antagonists competitively block muscarinic receptors, preventing bronchoconstriction. Tiotropium is long acting.
Non-selective b1 + b2 Agonist
Isoprotererenol - inc HR, force of contraction, CO (b1). - dilates arterioles of skeletal m (b2) > dec PVR - diastolic BP falls. Systolic BP remains unchanged - MAP typically falls; causes bronchodilation (b2). - used in emergencies to stimulate HR
Nitrates
Isosorbide dinitrate, Isosorbide mononitrate, Nitroglycerin, Sodium Nitroprusside
Nitrates
Isosorbide dinitrate, Isosorbide mononitrate, Nitroglycerin, SodiumNitroprusside
Post-MI, open-heart surgery, digoxin toxicity-ventricular arrhythmias only
Lidocaine, Mexiletine (ORAL)
Digoxin is not a first-line agent in CHF because?
Its use has not shown to decrease mortality and morbidity
What drug should be administered to J.K. to control his ventricular rate?
J.K. has signs of HF, so digoxin is a reasonable choice. IV verapamil and β- blockers may worsen the signs and symptoms of HF. The goal of rate control should be a resting and an exercising heart rate of <90 and 140 beats/minute, respectively.
Amiloride
K + -sparing diuretic: blocks epithelial Na + channels in cortical collecting tubules. Tox: hyperkalemia.
Lidocaine is an effective antiarrhythmic because it
Lidocaine, a class IB drug, effectively targets ischemic areas of the heart. Its major effect is on sodium channels in fast response fibers such as ventricular muscle. It has no significant effect on the PR or QT intervals.
Enoxaparin
LMW heparin: used parenterally for anticoagulation. Primary effect is on factor Xa, less on thrombin. The aPTT test is unreliable. Other LMW heparins include dalteparin, tinzaparin. Tox: bleeding.
Ergot alkaloid used as an illicit drug
LSD
The new drug blocks both the α-mediated effects (increased diastolic and mean arterial blood pressure) and ß-mediated action (increased cardiac force). In addition, it does not cause epinephrine reversal. Therefore, the drug must have both alpha and Beta-blocking effects
Labetalol (mixed drug) (act on both)
reduces intraocular pressure by increasing outflow of aqueous humor via lowering resistance of flow through uveoscleral pathway
Latanoprost
Abciximab
Monoclonal antibody that inhibits the binding of platelet glycoprotein IIb/IIIa (GPIIb/IIIa) to fibrinogen. e.
Used in the management of NSAID- exacerbated respiratory disease (NERD).
Leukotriene-Modifying Agents: Uses
Leukotriene-Modifying Agents: MOA
Leukotriene-modifying agents (LTMAs)interfere with the pathway of leukotrienemediators, which are released from mast cells, eosinophils, and basophils.
A 45-year-old man is treated for ventricular arrhythmia with an IV drug. After administration of the drug patient's EKG shows QRS to be increased very slightly whereas no significant changes to either PR or QT intervals are observed. Which of the following drugs was most likely given?
Lidocaine
A 60-year old man comes to emergency department with severe chest pain. ECG reveals ventricular tachycardia with occasional normal sinus beats, and ST-segment changes suggestive of ischemia. A diagnosis of myocardial infarction is made, and the man is admitted to the cardiac intensive care unit. His arrhythmia should be treated immediately with
Lidocaine
Mainly Ventricular therapy
Lidocaine (IB) & Mexiletine (IB)
First-generation vs. Second-generation
Lipophilic vs. Hydrophilic Block H1 central receptors: sedation vs. Less likely to block central H1 receptors: little or no sedation Block muscarinic receptors: Anticholinergic adverse effects vs. Less likely to block muscarinic receptors: Minor anticholinergic adverse effects Block α adrenoceptors: Orthostatic hypotension vs. Less likely to block α adrenoceptors: Little or no orthostatichypotension
A 57 year old woman comes to the physician because of shortness of breath. She says that she has been experiencing progressively worsening dyspnea while climbing the stairs in her house. She denies both chest pain and dyspnea at rest. She has a 3 year history of hypertension. Current medications are aspirin and metoprolol. Her blood pressure is 150/80 mm Hg and pulse is 55/min. Physical examination shows a regular heart rate and rhythm and lower extremity edema. Pulmonary exam shows rales at the bases. Echocardiogram shows increased LV filling pressures with a normal ejection fraction. Which of the following drugs is most appropriate to add to this patient's current medications?
Lisinopril Competitive inhibition of angiotensin-converting enzyme (ACE), stopping production of angiotensin II
Ethacrynic acid
Loop diuretic and can be used in case of sulfa allergy and causes less hyperuricemia. It may reduce uric acid levels.
Not usually associated with drowsiness because of lower entry into CNS.
Loratadine 2nd Generation Antihistamines, inhibits H1 receptors
A 22 -year- old man comes to the physician because of a 3 day history of epistaxis secondary to inflamed nasal mucosa. He is diagnosed with allergic rhinitis and prescribed a second generation H1 blocker. Which of the following drugs was he most likely prescribed
Loratadine (Claritin) 2nd generation antihistamine
A 71 year old African American man is diagnosed with stage 1 hypertension. His medical history is positive for Type 2 diabetes and COPD. Urinalysis reveals albuminuria . Which of the following drugs would be the most appropriate choice to initiate antihypertensive therapy with?
Losartan
patient is at risk for a complication involving sarcomeres being added in-series within cardiac myocytes. Which of the following antihypertensive medications is best for preventing this complication in this patient?
Losartan, candesartan, valsartan. Selectively block binding of angiotensin II to AT 1 receptor. Effects similar to ACE inhibitors, but ARBs do not increase bradykinin. Clinical Use: Hypertension, HF, proteinuria, or chronic kidney disease (eg, diabetic nephropathy) with intolerance to ACE inhibitors (eg, cough, angioedema).
Low doses vs. High dose atropine
Low doses: Bradycardia Blockade of presynaptic M2 receptors that normally inhibit release of ACH at SA node . ACH normally binds to M2 presynaptic receptor to stop the release of more ACH Since this receptor is blocked you have more ACH release which activates M2 receptors postsynaptic membrane causing BRADYCARDIA Moderate/high dose: Tachycardia Block M2 receptor on atria Normally M2 slows down pacemaker
Mediates the negative chronotropic effect of acetylcholine (reduce heart rate and contractility of atria)
M2 - Gi
A pharmacologist injects carbachol IV in an experimental animal. The injection evokes a decrease in peripheral vascular resistance and a decrease in mean arterial pressure. Activation of which of the following receptors is most likely responsible for this effect?
M3
Woman comes to physician because of a 3-week history of urinary retention and constipation. She has a history of schizophrenia well controlled with antipsychotic drug. Her clinical presentation is due to blockade of which of following receptors?
M3
Mediates GI smooth muscle contraction
M3 = Gq
Mediates the vasodilating effect of acetylcholine
M3 = Gq
1An ophthalmologist instills a solution of a drug into a 41-year-old woman's eye to dilate her pupils prior to ocular examination. Which of following drugs is most likely being used to achieve this effect?
M3 agonist
ORGANOPHOSPHATES: INSECTICIDES
MALATHION, PARATHION
Ergotamine, Dihydroergotamine
MOA: Ergot alkaloids produced by claviceps purpurea (grain fungus) 5-HT antagonist, alpha antagonist, CNS dopamine antagonist USE: specific for migraines (triptans preferred)
A 30 year old woman in her 3rd trimester of pregnancy is brought to emergency department due to severe headaches. Vital sign examination reveals BP (190/150 mmHg). She is immediately started on IV medication. Which of the following side effects can potentially develop in this patient after administration of this drug?
Maculopapular rash (lupus like) Selective dilation of arterioles, no effect on veins. HR increases
pt recently diagnosed with heart failure with reduced ejection fraction and began taking a drug to alleviate the symptoms. The drug also benefited his controlled atrial fibrillation which he was diagnosed with 2 years ago. Which of the following can be administered to treat the toxicity of this anti-arrhythmic?
Magnesium
What drugs are recommended to prevent seizures in severe preeclampsia or eclampsia?
Magnesium sulfate May cause loss of reflexes, diplopia, flushing, or slurring of speech; higher levels may cause muscular paralysis, ventilatory failure, and circulatory collapse; magnesium may alter cardiac conduction, leading to heart block in digitalized patients; in overdose, calcium gluconate IV can be administered as antidote for clinically significant hypermagnesemia
Used short term for reduction of intracranial pressure or to promote excretion of renal toxins in hemolysis, rhabdomyolysis
Mannitol
Which drugs can be used to achieve cardioversion? Describe their mechanism of action and potential adverse effects.
Many class I and III antiarrhythmic agents have been evaluated for efficacy in conversion of AF or atrial flutter to normal sinus rhythm. Flecainide, propafenone, dofetilide and amiodarone are widely recommended agents.
Useful in motion sickness
Meclizine
Used for diagnosis of bronchial airway hyperreactivity [Challenge test for diagnosis of asthma.]
Metacholine Stimulates muscarinic receptors in airway when inhaled
Pregnant female ( Gravida 2, Para 1) presents to the clinic for a routine visit at 30 weeks. Her blood pressure is 155/86 mm Hg and she is diagnosed with pregnancy - induced hypertension. The physician decides to place her on a drug that inhibits sympathetic outflow. Which of the following drugs was the patient most likely given?
Methyldopa Converted to a-methyldopamine and a-methylnorepinephrine centrally to diminish sympathetic outflow in CNS Causes decreased peripheral resistance and decreased BP (CO NOT decreased) DOES NOT decrease renal blood flow or GFR
Theophylline
Methylxanthine derivative found in tea; used in asthma. Bronchodilator, mild CNS stimulant. Caffeine (coffee) and theobromine (cocoa) are similar. Tox: seizures
Used to stimulate upper GI motility in patients with gastroparesis and used as an antiemetic.
Metoclopramide
Pro kinetic agents for Diabetic and post surgery gastroparesis, antiemetic, persistent GERD.
Metoclopramide D2 receptor antagonist. resting tone, contractility, LES tone, motility, promotes gastric emptying. Does not influence colon transport time.
A 52-year-old man comes to the physician because of severe pain in his first metatarsophalangeal joint. He says that the pain was so bad that it woke him up from sleep. Physical examination shows a tender and erythematous metatarsophalangeal joint. A review of his records shows that the patient was started on a new drug 2 weeks ago. Which of the following drugs is the most likely cause of this patient's symptoms?
Metolazone. Thiazide diuretics can increase plasma uric acid. Remember this pneumonic for the exam. Thiazides cause hyper (excess amounts) of GLUC ==> Glucose, lipidemia, uric acid and calcium. They also cause hypokalemia. Although thiazides cause hypercalcemia, they are actually good for treating calcium oxalate stones because they remove calcium from the urine
A 68 year old man is brought to the emergency department because of sudden onset chest pain and shortness of breath. He describes the pain in his chest as radiating to his left arm and jaw. He has 8 year history of hyperlipidemia and type 2 diabetes. Current medications include aspirin, simvastatin and an oral anti-diabetics drug. His blood pressure is 180/110 mmHg and pulse is 109/min. He is immediately administered aspirin, nitroglycerin , morphine and captopril. Due to its success at reducing post MI mortality rates, which fo the following drugs should also be administered to this patient??
Metoprolol
A 75 year old man comes to the physician because of a 4 month history of shortness of breath and bouts of coughing during rest. He has a 20 year history of hypertension and hyperlipidemia. Current medications include losartan and simvastatin. His blood pressure is 145/81 mm Hg, pulse is 70/min and respirations are 25 breaths/min. Physical examination shows crackles over both lungs and edema of the lower extremities. A diagnosis of congestive heart failure is made. Which of the following drugs should be given to improve his long survival?
Metoprolol
PDE3 inhibitors
Milrinone Inamrinone
A 69 year old man is brought to the emergency department because of 1 day history of shortness of breath and confusion. He has 8 year history of hypertension. Current medications include metolazone. His BP is 75/50 mmHg, respiration are 21/min and pulse is 110/min. Physical examination shows cool extremities, jugular venous distention and diffuse crackles in the lungs. Which of the following drugs is the most appropriate to administer immediately?
Milrinone Selective PDE-3 inhibitor. In cardiomyocytes: [Inc] cAMP accumulation --> [Inc] Ca2+ influx ==> [Inc] inotropy and chronotropy. In vascular smooth muscle: [Inc]cAMP accumulation activity ==> inhibition of MLCK activity ==> general vasodilation. Short-term use in acute decompensated HF. SIDE EFFECTS: Arrhythmias, hypotension.
Nitrates MOA
Mimic the actions of endogenous NO Rapid reduction in myocardial O2 demand (systemic vasodilatation) & relief of symptoms •In CV system, nitrous oxide (NO) is primarily produced by vascular endothelialcells
Carbachol (Miostat) Usage
Miosis during surgery Reduces intraocular pressure
Treatment of narcolepsy
Modafinil (non-amphetamine stimulant)(Uptake inhibitor)
A 6-year-old boy is brought to the physician by his mother for a follow-up examination. He was recently diagnosed with mild persistent asthma and prescribed daily therapy with an inhaled corticosteroid. The mother says that the boy strongly dislikes using the inhaler. She enquires about an oral medication. Which of the following would be the most appropriate alternative for this patient?
Montelukast
beta-blockers (incl. labetalol or propranolol) are not recommended because of risk from unopposed alpha-adrenergic stimulation
Most hypertensive emergencies (especially eclampsia) Avoid in acute CHF, heart block >1st degree Hydralazine, labetalol, methyldopa, nifedipine. "He likes my neonate."
ME THA CHOLINE
Muscarinic agonist. USES Diagnosis of bronchial airway hyperreactivity in subjects who do not have clinically apparent asthma.
BETH ANE CHOLE
Muscarinic agonist. USES Postoperative and postpartum urinary retention. Atony of the urinary bladder.
A 25-year old is brought to the emergency department by ambulance after being found unconscious in the street. He has fever, tachycardia, dilated pupils, facial flushing, xerostomia and dry skin. Which class of drugs is mostly responsible for his symptoms?
Muscarinic antagonist
Woman is brought to emergency department by a concerned friend. Physical examination shows mydriasis, tachycardia, dry and hot skin. She is confused and delirious. classes of drugs is responsible for her clinical presentation?
Muscarinic antagonist
Atropine
Muscarinic cholinoceptor blocker prototype: lipid-soluble, CNS effects; antidote for cholinesterase poisoning. Tox: "red as a beet, dry as a bone, blind as a bat, mad as a hatter," urinary retention, mydriasis. Cyclopentolate, tropicamide: antimuscarinics for ophthalmology; cause cycloplegia and mydriasis. Glycopyrrolate: antimuscarinic with decreased CNS effects.
Benztropine
Muscarinic cholinoceptor blocker: centrally acting antimuscarinic prototype for parkinsonism. Tox: excess antimuscarinic effects.
The activation of muscarinic receptors in bronchiolar smooth muscle is associated with
Muscarinic receptors present in bronchiolar smooth muscle are of the M 3 subtype coupled via G q proteins to phospholipase C. Activation of this enzyme causes hydrolysis of phosphatidylinositol bisphosphate, with release of IP 3 and DAG (the latter activates protein kinase C). Decreased formation of cAMP mediated via a G i protein occurs with activation of M 2 receptors such as those in the heart. Cation channel opening occurs in response to activation of nicotinic receptors.
NMJ blockers uses
Muscle paralysis in surgery or mechanical ventilation. Selective for Nicotinic Muscarinic receptors NMJ but not autonomic Nn receptors
Dantrolene
Muscle relaxant: blocks Ca 2+ release from sarcoplasmic reticulum of skeletal muscle.
Adverse effect of mannitol
Muscle rigidity is an adverse effect of mannitol due to HYPOnatremia (low amount of Na+)
Physical examination shows miosis, excessive sweating and salivation, and wheezing. There is generalized muscle weakness. His blood pressure is 88/58 mm Hg. pulse is 52/min, and respirations are 24/min. He is administered atropine. Which of the following adverse effects of malathion will most likely persist despite the administration of atropine?
Muscle weakness
Effect of a ganglion blocker on pupil size and accommodation? Inhibit division of autonomic nervous system that exercises dominant control of the organ.
Mydriasis (dilation) and inhibit accommodation iris and ciliary muscle are under the control of parasympathetic nervous system, So their inhibition make sympathetic effect (Mydriasis) dominant
instills phenylephrine and tropicamide in each of a patient's eyes as preparation for an ocular examination. Effect of this application?
Mydriasis and cycloplegia
Prior to an eye exam a patient is given a drug that causes mydriasis but has no effect on accommodation. What is the most likely identity of this drug?
Mydriasis can be caused by either a muscarinic antagonist or an alpha-1 agonist. Cycloplegia (paralysis of accommodation) is caused by a muscarinic antagonist, but accommodation is unaffected by an alpha-1 agonist such as phenylephrine. Remember accommodation is a parasympathetic function only. Ganglionic blockade with mecamylamine would cause mydriasis and cycloplegia similar to a muscarinic blocker.
Two nights previously, a 25-year old medical student woke up in the middle of the night with tachycardia, high blood pressure, headache and severe sweating. She has elevated levels of VMA in her urine. Which of the following drugs would be most appropriate for her condition?
Phentolamine
Mucolytic Agents Used in COPD
N-Acetylcysteine •Breaks disulfide linkages in mucus and lowers viscosity.
A 25-year-old woman is brought to the emergency department by her husband after she had a panic attack and severe chest pain following the consumption of cocaine. Physical examination shows a pale, diaphoretic woman. Her blood pressure is 155/90 mmHg, and pulse is 115/min. An ECG shows 2 mm ST-elevation in the inferior leads. Which of the following is contraindicated in this patient?
NEVER give a non-selective beta-blocker to a patient who has a cocaine overdose! One of the main problems of a cocaine overdose is hypertension. If you block beta-receptors, catecholamines released via cocaine can only bind to alpha-receptors. Alpha-1 causes vasoconstriction and will exacerbate the hypertension.
Aspirin
NSAID prototype: inhibits cyclooxygenase (COX)-1 and -2 irreversibly. Antiplatelet agent as well as antipyretic, analgesic and anti-inflammatory drug. Tox: GI ulcers, nephrotoxicity, rash, hypersensitivity leading to bronchoconstriction, salicylism. Other NSAIDs: ibuprofen, indomethacin, ketorolac, and naproxen.
A 76 year old woman comes to the clinic for a follow up visit. She has a 15- year history of hypertension Current medications include atenolol and lovastatin. Her blood pressure is 156/94 mm Hg. It is decided to add prazosin to her antihypertensive regimen. What long effect of prazosin should be expected in this patient?
Na and H2O retention Prazosin [alpha 1 antagonist]
Option for patients who have failed all other antianginal therapies
Na+ channel blockers
ventricular myocytes therapy
Na+ channel blockers (I) & K+ channel blockers (III)
A 69-year-old man is admitted to the intensive care unit after a coronary artery bypass graft. His past history is significant for class 1 heart failure. His temperature is 37.0C (98.6F), pulse is 56/min, respirations are 12/min, and blood pressure is 122/62 mmHg. An EKG of the patient shows that the patient an absence of p-waves. Which of the following drugs is most likely contraindicated in this patient?
No p-waves = A-fib. A-fib is exacerbated by hyperkalemia, which is a side effect of spironolactone.
Verapamil, Diltiazem
Negative inotropes [Prevention of nodal arrhythmias (eg, SVT), rate control in atrial fibrillatioN] Transient decrease in BP CNS effects (headache, fatigue, dizziness) GI effects (constipation, nausea)
A 45-year-old woman comes to the physician because of diplopia, eyelid droop, weakness in her limbs and difficulty swallowing food. These symptoms are more common later in the day and are exacerbated with exercise. The physician suspects myasthenia gravis. Which of the following drugs is prescribed for long-term treatment of the patient's symptoms?
Neostigmine
man undergoes elective hip surgery. 24 hours later he is unable to urinate and experiences painful bladder distension. He is administered an intramuscular injection of a drug that increases contractility of the detrusor muscle. Which of the following drugs was this patient most likely prescribed?
Neostigmine
Montelukast adverse effects
Neuropsychiatric: -Dream abnormalities -Insomnia -Anxiety -Depression -Suicidal idealization -Suicide
May induce insulin-resistance
Niacin
inhibit adenylyl cyclase in adipocytes. leading to inhibition of hormone sensitive lipase
Niacin
•Decreases VLDL, LDL and Lp(a)levels. •It increases HDLlevels. •Most effective agent for increasing HDL and the only agent that may reduceLp(a).
Niacin
May precipitate gout Generalized flushing Abnormal liver enzymes Pruritus IGT Watch glucose control with overt DM
Niacin Inhibits secretion of hepatic VLDL via lipoprotein lipase (LPL) pathway --> decreased VLDL and LDL; decreased clearance of HDL
Activates a G protein-linked receptor
Niacin (vitamin B 3 ) Inhibits lipolysis (hormone sensitive lipase) in adipose tissue; reduces hepatic VLDL synthes
•Calcium-channel blocker •IV infusion for hypertensive emergency •t1/2 = 30 min •Evokes reflex tachycardia
Nicardipine
Drug X caused a 50 mm Hg rise in mean blood pressure in the control animal, no blood pressure change in the ganglion-blocked animal, and a 75 mm mean blood pressure rise in the atropine-pretreated animal. Drug X is probably a drug similar to
Nicotine
The treatment of hyperlipidemic patients with nicotinic acid (niacin) results in
Nicotinic acid inhibits the synthesis of the VLDL apoprotein and decreases VLDL production. Its use results in decreases of both cholesterol and triglycerides, so total cholesterol in the plasma decreases. The drug is not an inhibitor of HMG-CoA reductase, and it increases plasma HDL to a greater extent than any other available antihyperlipidemic drug
pt diagnosed with stage 1 hypertension. She has no comorbid conditions and takes no current medications. Which of the following drugs would be the most appropriate choice to initiate treat with?
Nifedipine
A 52 year old man comes to the emergency department because of increasing chest pain. He describes the pain as pressure like that initially worsened with activity and improved with rest. However, over the past week he noticed that the pain is still present with decreasing physical activity to the point that it persists with rest. Physical examination show patient appearing uncomfortable and anxious. An ECG shows mild ST segment depressions in V1-V2. Cardiac troponin are not elevated. Which of the following drugs is most appropriate to administer immediately in order to alleviate the chest pain?
Nitroglycerin
A 69-year-old comes to the emergency department after being woken in the middle of the night with intense chest pain, radiating to the left arm and accompanied by breathlessness. He has a 5-year history of hypertension, well managed with hydrochlorothiazide. Laboratory results show no increase in myocardial injury markers and ECG is not suggestive of acute myocardial infarction. Which of following drugs should be given in order to see an immediate reduction in associated pain?
Nitroglycerin Vasodilate by [Inc] NO in vascular smooth muscle [Inc] in cGMP and smooth muscle relaxation. Dilate veins >> arteries. [Dec] preload. Adverse effects: Reflex tachycardia (treat with β-blockers), hypotension, flushing, headache, "Monday disease" in industrial exposure: development of tolerance for the vasodilating action during the work week and loss of tolerance over the weekend tachycardia, dizziness, headache upon reexposure. Contraindicated in right ventricular infarction
first-line therapy for treatment of acuteanginalsymptoms
Nitroglycerin (sublingual orspray)
A patient presents with a blood pressure of 160/110 mm Hg. The patient has asthma and has been treated with albuterol, by aerosol. Propranolol is prescribed to manage the hypertension. Is this action appropriate?
No, because propranolol is contraindicated in a patient with asthma.
Leukotriene Receptor Antagonists (LTRAs)
Non-bronchodilating Newer class of asthma medications Currently available drugs montelukast (Singulair) zafirlukast (Accolate)
Only recommended in the treatment of HFpEF due to their negative inotropic effects.
Non-dihydropyridine calcium channel blockers
Tubocurarine Analogs: pancuronium, atracurium, vecuronium, and other "-curiums" and "-oniums."
Nondepolarizing neuromuscular blocking agent prototype: competitive nicotinic blocker. Tox: respiratory paralysis. Releases histamine and may cause hypotension, therefore rarely used. Antidote: cholinesterase inhibitor, for example, neostigmine
. During an investigational study, blood pressure is monitored in an anesthetized experimental animal. The animal is given an intravenous dose of epinephrine, which produces an increase in blood pressure. After the blood pressure returns to baseline 3 minutes later, an unknown drug is given, followed by the readminstration of epinephrine 15 minutes later. Readminstration of epinephrine produces a decrease in blood pressure. To which of the following classes does the unknown drug most likely belong?
Nonselective alpha-receptor antagonist Epinephrine acts on beta-receptors at low doses, but more so on alpha at higher doses. So when it was initially given, it preferentially acted on alpha-1, causing vasoconstriction. However, if you add an alpha-blocker, it acts on beta-2, causing vasodilation. Norepinehprine has very little action on beta-2 (so it will not vasodilate!).
Contraindicated in an asthmatic:
Nonselective antagonists (β 1 = β 2 ) nadolol, pindolol (partial agonist), propranolol, timolol
Agonist at Alpha-1, Alpha2 + Beta1 (little effect on B2)
Norepinephrine - peripheral vasoconstriction (ALPHA-1) - inc cardiac contractility (BETA-1) - inc peripheral vascular resistance, systolic BP and diastolic BP. - CO is unchanged or decreased. - inc in BP --> baroceptor (bradycardia) - if atropine given 1st > tachycardia. ==> treat shock
Alpha > Beta (Very high vasoconstriction) Alpha = Beta (little vasodilation) Beta > Alpha (Very high vasodilation)
Norepinephrine (Reflex bradycardia) Epinephrine (slight increase in HR) Isoproterenol (Reflex tachycardia)
Following pretreatment with a muscarinic receptor blocking agent, the IV administration of norepinephrine is likely to result in
Norepinephrine activates α 1 and β 1 receptors, causing increases in PVR and CO. The increase in mean BP can elicit reflex bradycardia (vagal outflow leads to stimulation of cardiac M receptors), which may overcome the direct stimulatory effects of NE on the heart. However, reflex bradycardia is not possible following pretreatment with an M blocker. Thus, HR increases because of the direct activation of cardiac β 1 receptors by NE
Drug Y caused a marked increase in diastolic pressure, suggesting strong α1 vasoconstrictor effects. It also caused a small increase in pulse pressure suggesting some ß-agonist action. An increase in stroke volume may also result from increased venous return (an α-agonist effect) and stroke volume. The drug that best matches this description ???
Norepinephrine.
Fenofibrate drug interactions Upregulate lipoprotein lipase + apo A1, [Dec] VLDL, [Dec] TG, modest [Dec] LDL, modest [INC] HDL
Not inhibit statin metabolism, and much less likely to increase risk of rhabdomyolysis.
The data in the table below show the effects of four drugs (#1-4) on mean blood pressure administered as individual agents before and after treatment with prazosin. The arrows denote the direction and intensity of drug actions on blood pressure. Condition Before Prazosin After Prazosin Drug #1 ↑↑ ↑ Drug #2 ↑↑ ↑ Drug #3 ↓↓ ↓↓ Drug #4 ↑ ↓
Of the drugs listed, only isoproterenol causes a decrease in mean blood pressure, because it activates beta receptors and has no effect on alpha receptors. This permits identification of drug #3 as isoproterenol. Prazosin is an alpha blocker, so one can anticipate that this drug would antagonize any increases in blood pressure that result from activation of α 1 receptors in the vasculature. Epinephrine (high dose), norepinephrine, and tyramine all exert pressor effects via activation of α 1 receptors. However, only epinephrine is active on β2 receptors, and this action would be revealed by vasodilation and a reversal of its pressor effects following treatment with an alpha blocker—"epinephrine reversal." Thus, drug #4 can be identified as epinephrine.
Used in the management of patients with severe persistent asthma with evidenceof allergy.
Omalizumab
•Monoclonal antibody. •Prevents binding of IgE to basophils and mast cells.
Omalizumab
Used in GI ulcers, Zollinger-Ellison syndrome, gastroesophageal reflux disease (GERD)
Omeprazole . Other "prazoles": esomeprazole, dexlansoprazole, lansoprazole, pantoprazole, rabeprazole. Tox: hypergastrinemia
Acts on a ligand-gated ion channel receptor
Ondansetron
Control vomiting postoperatively and in patients undergoing cancer chemotherapy.
Ondansetron 5-HT 3 antagonist; reduce vagal stimulation. Powerful central-acting antiemetic. Adverse effects: Headache, constipation, QT interval prolongation, serotonin syndrome.
5-HT3 receptor unique feature
Only monoamine neurotransmitter receptor known to functionas a ligand-gated ionchannel.
Naloxone
Opioid μ receptor antagonist: used to reverse CNS depressant effects of opioid analgesics (overdose or when used in anesthesia). Naltrexone (orally active), a related compound, is used in ethanol dependency states.
A 61 year old man is admitted to the hospital with a diagnosis of stroke 5 months after a renal embolism. An intraventricular thrombus is observed. He is administered apixaban. Which of the following best describes the properties of this drug?
Oral direct factor Xa inhibitor Treatment and prophylaxis for DVT and PE; stroke prophylaxis in patients with atrial fibrillation. Oral agents do not usually require coagulation monitoring.
Dabigatran
Oral direct thrombin inhibitor: fixed dosing; no monitoring required, but can be measured with aPTT. Argatroban is a small molecule thrombin inhibitor used parenterally for PCI. Other direct thrombin inhibitors are lepirudin, a recombinant form of a medicinal leech protein, and bivalirudin—both used parenterally. Tox: bleeding; monitor with aPTT.
isosorbide di-nitrate, isosorbide mono-nitrate.
Oral nitrates
Used in the management of acute exacerbations of COPD
Oral prednisolone
Echothiophate
Organophosphate cholinesterase inhibitor: less lipid soluble than most organophosphates; used in glaucoma SALIVATION
Causes Diarrhea, Urination, Miosis, Bronchospasm, Bradycardia, Emesis, Lacrimation, Sweating, and Salivation. May lead to respiratory failure if untreated.
Organophosphates like Parathion {Irreversibly inhibit AChE}
Type IIB familial combined hyperlipidemia
Over-population of VLDL and associated [Inc] LDL 2 o to excess hepatic synthesis of apolipoprotein B Autosomal dominant
Anticoagulant factor released by the endothelium
PGI2
inhibits platelet aggregation and promotes vasodilation, decreases platelet aggregation, vascular tone, bronchial tone, and uterine tone "Platelet grouping inhibitor"
PGI2 (prostacyclin) Side effects: flushing, jaw pain. Examples: epoprostenol, iloprost.
Partial muscarinic agonist. Tertiary amine Stable to hydrolysis by acetylcholinesterase.
PILOCARPINE
H1 vs H2 receptors coupling
PLC (NO) vs. Adenylyl Cyclase (cAMP)
A 24-year-old man presents to the ER with a sudden onset of palpitations. He previously had an episode similar to this a year ago that resolved spontaneously. Blood pressure is 126/74 mmHg and pulse is 164/min. A drug is administered that results in instantaneous resolution of the arrhythmia but is accompanied by flushing, burning in the chest, and dyspnea. Which of the following medications was most likely used to treat this patient's condition?
Patient has paroxysmal supraventricular tachycardia, which is treated by adenosine. Adenosine also fits the side effect profile.
Amiodarone (Cordarone) contraindications
Patients taking: Digoxin, theophylline, warfarin, quinidine Patients with: Bradycardia SA or AV block Severe hypotension Severe respiratory failure
Adjunctive Medications for PCI:
Patients undergoing PCI should receive anti-platelet drugs (aspirin, P2Y12 inhibitor, and GP IIb/IIIa inhibitors), and anticoagulant therapy (IV UFH is typically given to prevent acute vessel closure due to thrombosis).
When nitrates, Beta-blockers & Ca2+-blockers are unsuccessful
Ranolazine Inhibits the late phase of sodium current thereby reducing diastolic wall tension and oxygen consumption. Does not affect heart rate or blood pressure.
Epinephrine reversal phenomenon
Phenoxybenzamine (Irreversible) ) Non specific a1 & a2 blockers •Adrenergic blockers can reverse the a1 effects of epinephrine •Block a1 vasoconstriction à vasodilation via B2 receptors •Systemic BP drops = reversing the effect of epinephrine •EPINERPHRINE WILL INCREASE HR •DECREASE IN MAP (B2 PREDOMINATES)
Chlorpromazine
Phenothiazine antipsychotic drug prototype: blocks most dopamine receptors in CNS. Tox: atropine-like, EPS dysfunction, hyperprolactinemia, postural hypotension, sedation, seizures (in overdose), additive effects with other CNS depressants. Other phenothiazines: fluphenazine, trifluoperazine (antipsychotics), prochlorperazine (antiemetic), promethazine (preoperative sedation).
alpha-antagonists (NON-Selective)
Phenoxybenzamine [irreversible] used for pheochromocytoma Phentolamine [reversible] - pheochromocytoma (control of HT during preoperative prep and surgery) - diagnosis of PCC - prevention of dermal necrosis - hypertensive crisis due to stimulant drug overdose.
Causes epinephrine reversal Give to patients on MAO inhibitors who eat tyramine-containing foods and for severe cocaine-induced hypertension (2nd line)
Phentolamine (non-selective a-blocker)[Reversible] All a-adrenergic blockers reverse a-agonist effects of epinephrine. For example, vasoconstrictive action of epinephrine is blocked, but vasodilation of other vascular beds caused by stimulation of a-receptors is not blocked. Thus, systemic BP decreases in response to epinephrine given in presence of Phenoxybenzamine.
Anaphylactic shock treatment via IV norepinephrine. After few hours doctor notices her peripheral extremities turn blue and almost appear necrotic. what medication should be administered to reveres this side effect?
Phentolamine [Nonselective α-blocker]
A drug interacts with adrenergic receptors to activate phospholipase C and evoke an increase in IP3 and Ca2+ release, resulting in vascular smooth muscle contraction. This drug is most similar to following?
Phenylephrine
ALPHA1-SELECTIVE AGONIST
Phenylephrine - vasoconstriction (hypotension) - nasal decongestant. Given orally or topically. - mydriasis but NO cycloplegia (M3) - used to inc BP from septic shock
Causes mydriasis but not cycloplegia
Phenylephrine (α-adrenergic agonists, used as nasal decongestants.) Adverse Effects Hypertension. Rebound congestion if used more than 4-6 days. Can also cause CNS stimulation/ anxiety (pseudoephedrine).
Reduce hyperemia, Edema, nasal congestion; Open obstructed eustachian tubes.
Phenylephrine Pseudoephedrine Adverse Effects: Hypertension. Rebound congestion if used more than 4-6 days. Can also cause CNS stimulation/ anxiety (pseudoephedrine).
Nasal Decongestants
Phenylephrine Pseudoephedrine •α adrenergic agonists. •Constrict dilated arterioles in the nasalmucosa. •Should be used no longer than 3 days due torisk of rebound nasal congestion.
Actions: • A1 action: vasoconstriction • Vasoconstriction increases PVR (increases DBP) • Increased afterload= decreased CO • Increase in MAP= reflex bradycardia
Phenylephrine Receptor: Alpha 1
When given to a patient, phentolamine blocks which one of the following?
Phenylephrine, an α agonist and induces bradycardia through the baroreceptor reflex. Blockade of this drug's α-mediatedvaso constrictor effect prevents the bradycardia
Cilostazole, dipyridamole
Phosphodiesterase inhibitors; [Inc] cAMP in platelets, resulting in inhibition of platelet aggregation; vasodilators. Indications: Intermittent claudication, coronary vasodilation, prevention of stroke or TIAs (combined with aspirin). Side Effects: Nausea, headache, facial flushing, hypotension, abdominal pain.
Inflammation is a complex tissue reaction that includes the release of cytokines, leukotrienes, prostaglandins, and peptides. Prostaglandins involved in inflammatory processes are typically produced from arachidonic acid by which of the following enzymes?
Phospholipase A converts membrane phospholipid to arachidonic acid. Cyclooxygenases convert arachidonic acid to prostaglandins. COX-1 products appear to be important in normal physiologic processes. COX-2 is the enzyme responsible for this reaction in inflammatory cells.
Anticholinesterase with both peripheral and central effects
Physostigmine
A 38-year-old farmer was working in the fields one morning when she suddenly started feeling hot, flushed, and presented with xerostomia, mydriasis, and disorientation. Her heart rate is highly elevated. What drug would you give to treat this patient?
Physostigmine Patient has atropine poisoning, so you give atropine. Some of you might have picked (B) because you thought she had organophosphate poisoning due to working in the fields. Yes, there are pesticides in crops, but the symptoms are not consistent with organophosphate poisoning. Don't forget that atropine comes from the Belladonna flower, which can also be found in the fields.
which of the following has LEAST effect on vascular tone?
Physostigmine (Anticholinesterse - increases ACh indirectly), no effect on receptors
Used in Sjögren's syndrome, xerostomia, glaucoma.
Pilocarpine
Miotic[ Contracts ciliary muscle of eye ](open-angle glaucoma), pupillary sphincter (closed-angle glaucoma); resistant to AChE, can cross bloodbrain barrier (tertiary amine).
Pilocarpine You cry, drool, and sweat on your 'pilow.
- treatment of dry mouth due to radiotherapy for cancer of head + neck. - treatment of dry mouth caused by Sjogren's Syndrome
Pilocarpine (partial muscarinic agonist, stable to hydrolysis_
Partial β agonist.
Pindolol and acebutolol [ should be used with caution in angina]
Warfarin exhibits large interindividual variability in the dose required for its anticoagulation effect. What are the causes of such variability?
Polymorphisms of CYP2C9 and vitamin K epoxide reductase complex subunit 1 (VKORC1) are largely responsible for the variability.
A pharmacology student studying a new antihypertensive drug finds it can relax vascular smooth muscle to cause vasodilation via inhibition of phosphodiesterase 3(PDE3). Knowing this mechanism of action which other effect would be expected from this drug?
Positive inotropy (increase contractile force of heart --> ventricles empty more completely --> cardiac output improved) Milrinone Inamrinone
Activation of postsynaptic M 2 receptors on the heart is associated with
Postsynaptic muscarinic receptors on the heart (M 2 ) are G i protein coupled to inhibition of adenylyl cyclase and decreased formation of cAMP.
Dofetilide - MOA & Clinical Anti-arrhythmic (class III)
Potent and pure K+ channel blocker [Inc] AP duration, [Inc] ERP, [Inc] QT interval. Clinical Applications Conversion of atrial fibrillation / flutter to normal sinus rhythm Maintenance of normal sinus rhythm in patients with chronic atrial fibrillation / flutter of longer than one week duration who have been converted to normal sinus rhythm
Cimetidine adverse effects
Potent inhibitor of cytochrome P450 (multiple drug interactions) Anti-androgenic effects (prolactin release, gynecomastia, impotence, reduce libido in males) -Cross blood brain barrier (confusion, dizziness, headaches) and placenta. -- Both cimetidine and ranitidine reduce renal excretion of creatinine
Sotalol Mechanism of Action Anti-arrhythmic (class III)
Potent non-selective -blocker Inhibits rapid outward K+ current Prolongs repolarization & duration of action potential Lengthens refractory period torsades de pointes, excessive β blockade.
alpha1-selective adrenergic blocking agents
Prazosin Terazosin - prazosin analog w/longer half life. - used for hypertension and BPH. Doxazosin (same as terazosin) Tamsulosin - approved for BPH, little effect on BP
Which one of the following drugs is least likely to cause reflex tachycardia during long-term therapy?
Prazosin (alpha 1 antagonist)
A 10-year-old boy in respiratory distress is brought to the emergency department by his mother. She says he developed nasal congestion, a sore throat and cough 24 hours previously. He has been experiencing chest pain and has been breathing rapidly. His mother administered albuterol via the nebulizer with no improvement. His respirations are 40/min, oxygen saturation is 88%, pulse is 130/min and blood pressure is 125/79 mm Hg. He is afebrile. He appears drowsy and is using accessory chest muscles to breathe. He is administered oxygen, fluids, an inhaled SABA, and an inhaled SAMA. Which of the following should also be administered to this patient?
Prednisone
A 64-year-old man with a history of chronic obstructive pulmonary disease (COPD) is evaluated in the emergency department for increased dyspnea over the past 3 days. He has obvious difficulty breathing and cannot speak in full sentences. He has been using his inhalers much more than usual but with minimal improvement. He has smoked one pack per day since age 18 and has a history of hyperlipidemia, hypertension and obesity. His respirations are 28/min, pulse is 100/min, blood pressure of 130/90 mm Hg, and temperature is 37.7°C. His O2 saturation is 84% on room air. Breath sounds are diffusely decreased with bilateral expiratory wheezes. Cardiac examination shows no abnormalities. He does not have any peripheral edema. He is administered supplemental O 2 via nasal cannula and albuterol and ipratroprium by nebulizer. Which of the following should also be administered to this patient?
Prednisone
Verapamil contraindications
Preexisting depressed cardiac function or AV conduction abnormalities, Use with caution in patients taking digoxin (increases digoxin levels)
Scopolamine Uses
Prevention of motion sickness. To block short-term memory: sometimes used in anaesthetic procedures.
A 33-year-old woman who recently started treatment for an arrhythmia complains to her family doctor of extreme fatigue, painful joints and fever. The doctor is convinced these symptoms are due to an adverse effect from her medication. Which of the following drugs could explain these symptoms?
Procainamide
Metabolized via N-acetyltransferase (genotypic variation) to N-acetyl procainamide (NAPA), an active metabolite Adverse effects: systemic lupus erythematosus (SLE)-like syndrome (30% incidence) more likely with slow acetylators; hematotoxicity (thrombocytopenia, agranulocytosis); CV effects (torsade)
Procainamide
Wolff-Parkinson-White syndrome treatment Most common type of ventricular pre- excitation syndrome. Abnormal fast accessory conduction pathway from atria to ventricle (bundle of Kent) bypasses the rate-slowing AV node ventricles begin to partially depolarize earlier characteristic delta wave with widened QRS complex and shortened PR interval on ECG. May result in reentry circuit supraventricular tachycardia.
Procainamide
A 10 year old boy is Brough to the physician by his mother for scheduled ECG. his family history includes Wolff Parkinson White Syndrome and sudden cardia death. The mother says that there are currently no other concerns. An ECG shows widened QRS alongside a shortened PR interval, confirming a diagnosis of Wolff Parkinson white (WPW) syndrome. Which of the following drugs is most appropriate for initiating therapy in this patient?
Procainamide Slow or block ([Dec] ) conduction (especially in depolarized cells). [Dec] slope of phase 0 depolarization. Are state dependent (selectively depress tissue that is frequently depolarized [eg, tachycardia]).
Mifepristone
Progestin and glucocorticoid receptor antagonist: used in combination with prostaglandin analogs for medical abortion in early pregnancy
Which of the following drugs should never be discontinued abruptly through fear of rebound hypertension?
Propranolol
Which of the following medications should be avoided in patients suffering from bradycardia?
Propranolol
Which one of the following antiarrhythmic agents would result in a prolongation of the PR interval?
Propranolol
A 46-year-old man is brought to the emergency department because of a 2-week history of episodes of severe headaches, diaphoresis, and palpitations. Physical examination shows an anxious patient. His blood pressure is 192/125 mm Hg, and pulse is 110/min. Laboratory studies are diagnostic for pheochromocytoma. He is scheduled for surgical removal in 10 days. ■ Which of the following is contraindicated in this patient? ■ Which of the following should be administered to this patient?
Propranolol Phenoxybenzamine
Exacerbate vasospasm in Prinzmetal angina. Coronary vasospasm (contraindicated in patients with CAD or Prinzmetal angina), mild paresthesia, serotonin syndrome (in combination with other 5-HT agonists).
Propranolol Sumatriptan (5-HT 1B/1D agonists)
A 46 year old man complains to his physician of insomnia, nightmares, fatigue, diminished libido, and blanching of the fingers when exposed to cold. The man, recently diagnosed with stage 2 hypertension, has been taking antihypertensive drugs for 1 month. Which of the following drugs most likely caused the patient's symptoms?
Propranolol precipitation of heart failure or heart block, can mask tachycardia of hypoglycemia (diabetes) and hyperthyroidism, sedation, sleep disturbances, depression
Following a myocardial infarct, a 40-year-old man is being treated prophylactically with propranolol. You would be concerned about the use of this drug if the patient also had what comorbid condition?
Propranolol is a nonselective beta blocker that causes hypoglycemia by blocking glycogenolysis and gluconeogeneis in the liver and skeletal muscle. This is of particular concern in a patient with diabetes. The other conditions listed are all potential uses for beta blockers, including essential tremor where it is important to use a nonselective beta blocker.
A patient with hypertension also suffers from essential tremor. Optimal treatment of the patient should include management with
Propranolol is a nonselective beta blocker useful in a variety of cardiac conditions including hypertension. The drug is also useful in essential tremor where blocking the beta-2 receptor is beneficial. Metoprolol, beta-1 selective, is useful in hypertension but not essential tremor. Clonidine and prazosin are second-line drugs for hypertension and not effective in essential tremor. Lidocaine, an antiarrhythmic, is not effective in either condition.
A 57-year-old man has severe pulmonary hypertension and right ventricular hypertrophy. Which of the following agents causes vasodilation and may be useful in pulmonary hypertension?
Prostacyclin (PGI ) is a very potent vasodilator. All the other choices in the list are vasoconstrictors.
Latanoprost
Prostaglandin F2 ALPHA analog used topically in glaucoma. Bimatoprost and travoprost are similar.
Heparin antidote
Protamine sulphate
A 56 year old man is diagnosed with DVT. He is started on warfarin. A few days later he develops erythematous skin lesions on his left thigh and his physician suspects that this is an adverse effect of warfarin. This adverse effect is most likely due to reduced activity of which of the following?
Protein C
Hexamethonium
Prototypic ganglion blocker, now obsolete except for research use. Causes marked block of both PANS and SANS, hypotension. Newer analogs trimethaphan, mecamylamine are rarely used.
Albuterol
Prototypic rapid-acting b 2 agonist; important use in acute asthma. Tox: tachycardia, arrhythmias, tremor. Other drugs with similar action: metaproterenol, terbutaline. Slow-acting analogs: formoterol, salmeterol; used for prophylaxis
Which of the following is a potential adverse effect of amiodarone when it is used in high daily dosages?
Pulmonary fibrosis
EDR OrPHONIUM
Quaternary ammonium. Does not enter CNS. USES Used in diagnosis of myasthenia gravis. Edrophonium IV leads to rapid increase in muscle strength. Used to reverse the neuromuscular block produced by non-depolarizing muscular blockers.
A 56-year-old man who has recently been started on pharmacotherapy for an atrial arrhythmia complains of 'ringing in the ears', blurred vision and throbbing headaches. The effect of the drug on the cardiac fast action potential is shown (in red) in the diagram below. Which of the following drugs is the patient most likely taking?
Quinidine
Patient has a 8-year history of congestive heart failure. An echocardiogram shows a wide complex tachycardia with a P-wave rate of 105/min, an R-wave rate of 129/min, and no apparent relation between the two. Intravenous pharmacotherapy is initiated with a drug that prolongs both the QRS and QT intervals. Which of the following drugs was the patient most likely administered?
Quinidine
An ECG is done at this time which finds torsade de points, which is treated with magnesium. Which of the following drugs did she receive initially?
Quinidine Explanation: A- Class 1A- inhibits Na+ (QRS) and K+ (QT), B- Class 1B- rapid, inhibits Na+ only, so increase QRS, decrease QT, Class 1C-slow, inhibits Na+ only, so only increase in QRS, Class 2- little effect on AP, affect mainly nodal tissues, Class 3- inhibits K+ only, therefore only QT increase)
Adverse effects: cinchonism (GI, tinnitus, ocular dysfunction, CNS excitation), hypotension, prolongation of QRS and ↑ QT interval associated with syncope (torsade). º Drug interactions: hyperkalemia enhances effects and vice versa; displaces digoxin from tissue binding sites, enhancing toxicity.
Quinidine is a weak base, and antacids increase its absorption, thus greatly increasing its toxicity.
Which one of the following antiarrhythmic agents would result in a prolongation of the QT interval?
Quinidine, Procainamide, Disopyramide -Class 1A anti-dysrhythmic drugs -Blocks sodium channels, slowing impulse conduction within heart -Delays repolarization and blocks vagal input to heart
Echothiophate
Rarely used for glaucoma.
A 52 year old woman is discharged from the hospital after recovery from an acute MI. Her post discharge medications include lisinopril. Which of the following actions most likely contributes to mortality reduction obtained by the use of ACEI's in MI?
Reduction of preload and afterload
Pretreat w/ Propranolol blocks B1 and B2. If we then add nitric oxide a vasodilator we would expect
Reflex tachycardia. However, we have blocked B1 the pretreatment thus we block the reflex tachycardia and there will be no change/no effect on HR
A novel highly potent, non-selective muscarinic receptor has been developed. This new drug would most likely have which of the following actions?
Release of endothelial NO
A 44 year old man diagnosed with Stage 1 hypertension is prescribed losartan. Which of the following changes in these parameters would you expect to see in this patient following administration of this drug?
Renin (INC) Angiotensin I (INC) Angiotensin II (INC) Serum K+ (INC)
A 44 year old man diagnosed with Stage 1 hypertension is prescribed captopril. Which of the following changes in these parameters would you expect to see in this patient following administration of this drug?
Renin (INC) Angiotensin I (INC) Angiotensin II (dec) Serum K+ (INC)
Beta-blockers have been shown to be useful in the treatment of congestive heart failure primarily due to their actions on?
Renin secretion
Dyslipidemia Medications that is Pregnancy category B
Resins that bind bile acids in intestinal lumen and prevent absorption thereby [Colesevelam]
Predominant signs and symptoms of organophosphate poisoning?
Result of excess acetylcholine at nerve endings, which mimics hyperactivity of the parasympathetic nervous system. • The acronym DUMBELS (diarrhea, urination, miosis, bradycardia, emesis, lacrimation, salivation)
Fibrin Selective Thrombolytics
Reteplase
pt has dyspnea with physical activity and when lying flat. She has a history of an arrhythmia and is compliant with her medications. Physical examination shows a pansystolic murmur. An echocardiogram shows vegetations on the mitral valve. Which of the following medications is she most likely taking?
Reversible SLE-like syndrome Procainamide
Atropine target action
Reversible competitive antagonist at muscarinic receptors. Prevents acetylcholine from binding at muscarinic receptors.
Inhaled Short-Acting β2 Adrenergic Agonists: Uses
SABA are DOC for relief fo acute asthma symptoms and prevention of exercise induced bronchospasm
■ Drugs of choice for LDL reduction. ■ Reduce cardiovascular mortality. ■ Lower LDL levels in all types of hyper lipidemias. ■ Homozygotes for familial hypercholesterolemia lack functional LDL receptors andthus benefit muchless from treatment withstatins. ■ Contraindicated in pregnancy [Category X]
STATINS: USES
DEPOLARIZING BLOCKERS
SUCCINYLCHOLINE
On the first post-op day after hip surgery, a 75-year old woman is unable to urinate and complains of painful bladder distention. She is prescribed a drug that increases the contractility of the detrusor muscle. Which of the following adverse effects may this patient experience?
Salivation
man undergoes elective hip surgery. Twenty four hours later he is unable to urinate and experiences painful bladder distension. He is administered an intramuscular injection of a drug that increases contractility of the detrusor muscle. Which of the following adverse effects may this patient experience?
Salivation
Inhaled long-acting β2 adrenergic agonists (LABAs)
Salmeterol Formoterol
Antiasmathic with prolonged duration of action. Unsuitable for prompt relief of breakthrough attacks of bronchospasm.
Salmeterol [β 2 > β 1]
PI-LO CAR PINE
Second line agent for open angle glaucoma. Management of acute angle-closure glaucoma. Treatment of dry mouth due to radiotherapy for cancer of head and neck. Treatment of dry mouth caused by Sjogren's Syndrome.
H1 RECEPTOR ANTAGONISTS: ADVERSE EFFECTS
Sedation: less common with second generation agents. Dry mouth: due to anticholinergic effects.
A 50-year-old man with a history of asthma and depression is brought to the emergency department by ambulance after admitting that he had ingested an overdose of his theophylline slow release tablets. He has no previous history of self-harm or overdose. He is currently asymptomatic. Which of the following adverse effects may this patient experience?
Seizures & arrhythmias
Celecoxib
Selective COX-2 inhibitor. Less GI toxicity than nonselective NSAIDs. Tox: nephrotoxicity, increased risk of coronary thrombosis and stroke.
Management of COPD Exacerbations
Short acting bronchodilators (SABA or SAMA) Corticosteroids (e.g oral steroids) Antibiotics Oxygen
A 59 year old man comes to the physician because of chest pain. Over past 6 months, he has noticed dull, central chest pain, that radiates to his left arm whilst walking. The pain subsides at rest but quickly return upon walking again. He has 11 year history of hyperlipidemia. Current medications include aspirin and simvastatin. His blood pressure is 135/82 mmHg and pulse is 74/min. He is immediately administered atenolol and nitroglycerin. Which of the following drugs would be contraindicated in this patient?
Sildenafil Inhibit PDE-5 [Inc] cGMP prolonged smooth muscle relaxation in response to NO --> [Inc] blood flow in corpus cavernosum of penis, [Dec] pulmonary vascular resistance.
Sildenafil has been prescribed for years to treat erectile dysfunction. Recently, this drug is also being used for what condition?
Sildenafil (a PDE5 inhibitor) is used for erectile dysfunction but has been recently approved for use in pulmonary hypertension. Other useful drugs in pulmonary hypertension are epoprostenol and bosentan.
Nitrates contraindications
Sildenafil (also increase level of cGMP)
Their effectiveness depends on functional LDL receptors
Simvastatin, ezetimibe colesevelam
man visits the ER with symptoms of atrial tachyarrhythmia. You decide to treat this patient initially by giving him a drug that increases the ERP in the AV node. The goal of this treatment is to?
Slow the ventricular rate
Verapamil and Diltiazem MOA
Slows AV conduction directly → HR, contractility, BP & O2 demand Has greater inotropic effects than dihydropyridines (weaker vasodilator) Adverse Effects Same as other Ca2+ channel blockers Constipation
BP is 245/115 mm Hg and pulse is 85/min and regular. Fundoscopy shows bilateral retinal hemorrhages and exudates. All other laboratory studies are within normal levels. Which of the following drugs is most appropriate at this time?
Sodium Nitroprusside Short acting; increase cGMP via direct release of NO. Can cause cyanide toxicity (releases cyanide)
May increase statins plasma levels and increase the risk of adverse effects.
Sodium valproate Isoniazid Cimetidine Ketoconazole Fluconazole Acute alcohol abuse Chloramphenicol Erythromycin/clarithromycin Sulfonamides Ciprofloxacin Omeprazole Metronidazole Amiodarone Grapefruit juice SICKFACES.COM (when I Am drinking Grapefruit juice)
Somnifacients (hypnotic)
Some first-generation H1 blockers have strong sedative properties and are used in the treatment of insomnia.
A 50-year-old woman is treated for a ventricular arrhythmia with an oral drug. After administration of drug patient's EKG shows both QT and PR intervals are prolonged but no change in QRS is observed. Which of the following drugs was the patient most likely given?
Sotalol
life-threatening ventricular arrhythmia
Sotalol Decreases IK, slowing phase III Non-selective beta blocker: β1 blockade, leading to ↓ HR, ↓ AV conduction
Their utility in heart failure is thought to be due to increased levels of circulating aldosterone
Spironolactone
Used as an add-on drug alongside first-line antihypertensives. It is most useful in the treatment of secondary hypertension caused by hyperaldosteronism or in the treatment of congestive heart failure where it has been shown to decrease morbidity and mortality when combined with standard treatments. It is not an appropriate choice to initiate therapy with.
Spironolactone
Used as an add-on drug to standard therapy (ACEIs, β-blockers, diuretics) to increase survival, however its addition would not significantly decrease edema due to its weak diuretic effect.
Spironolactone
Useful in the treatment of congestive heart failure when combined with standard treatments (ACEI, diuretic and β-blocker) where it has been shown to decrease both morbidity and mortality
Spironolactone
Used as an add-on drug with first-line antihypertensives. It is most useful in the treatment of secondary hypertension caused by hyperaldosteronism or in the treatment of congestive heart failure where it has been shown to decrease morbidity and mortality when combined with standard treatments.
Spironolactone (potassium sparing diuretic)
Which side effect is associated with spironolactone?
Spironolactone blocks aldosterone receptors thereby inhibiting the production of Na + channels in the collecting duct and is used as a K + -sparing agent because the reabsorption of Na + in the CT is coupled (indirectly) to the secretion of K + ions. Hyperkalemia is characteristic of this drug and may lead to clinical consequences at high doses, or if patients fail to discontinue K + supplements or ingest foodstuffs high in K+ . Because Na + reabsorption is associated with secretion of protons, spironolactone causes retention of H + ions, leading to acidosis. It has no significant effect on the renal elimination of Ca 2+ or on the plasma level; of glucose.
Recommended in addition to ACE inhibitors (or ARBs), β-blockers and a diuretic if patients continue to be symptomatic. Clinical studies have shown they can decrease morbidity and mortality.
Spironolactone is
A 56-year old man comes to the physician because of decreased libido. He has a history of myocardial infarction and is taking Lisinopril, metoprolol, hydrochlorothiazide and spironolactone. Physical examination shows a slight increase in breast mass. The drug likely causing these adverse effects has which of the following clinical effects?
Spironolactone is a K-sparing diuretic that can also cause endocrine effects.
Should be prescribed after an MI irrespective of LDL levels.
Statins
A 44 year old woman comes to the physician because of a 3 history of a dry- hacking cough. She has a 4 year history of month hypertension. Current medications include enalapril and amlodipine. Temperature is 36.9° C and her blood pressure is 139/80 mm Hg. Which of the following next steps is the most appropriate in her management?
Stop enalapril and start losartan
Depolarizing neuromuscular blocker Mimics ACh and binds to ACh receptors causing prolonged depolarization; initial fasciculation may be seen, followed by temporary paralysis secondary to blocked ACh receptors by SCh
Succinylcholine Assist intubation Increased risk of aspiration (need rapid paralysis and airway control (e.g. full stomach), hiatus hernia, obesity, pregnancy, trauma) Short procedures Electroconvulsive therapy (ECT) Laryngospasm
May cause coronary vasospasm
Sumatriptan
Agonist at 5HT1 receptors Inhibit trigeminal nerve activation, prevent vasoactive peptide release, induce vasoconstrition.
Sumatriptan [Triptans] Acute migraine, cluster headache attacks.
Adenosine is most effective at treating which of the following?
Supraventricular tachycardias
Outpatient prophylaxis of a patient with an SVT is best accomplished with the administration of
Supraventricular tachycardias (SVTs) are treated effectively by class II and class IV antiarrhythmics. In addition, adenosine is indicated for SVTs and nodal tachycardias but only acutely since it must be administered IV and has an extremely short duration. The primary actions of both beta blockers (esmolol) and CCBs (diltiazem) are at the AV node, but esmolol is too short-acting to be useful as prophylaxis. Lidocaine and mexiletine are both class Ib drugs that are used in ventricular arrhythmias.
Sympathetic (cholinergic) Predominant tone
Sweat glands (M3) Effect of ganglion blockage Anhydrosis
patient has 10 year history of coronary artery disease and systolic heart failure. Current medications include atenolol, captopril and hydrochlorothiazide. Her blood pressure is 145/82 mm Hg. Physical examination shows minimal edema of the lower extremities. Laboratory studies show elevated serum potassium. Which of the following changes to her current medications is most appropriate at this time?
Switch captopril to hydralazine and isosorbide dinitrate
A 55-year old man is brought to the emergency department because of onset of severe, sharp chest pain. His blood pressure is 80/50 mm Hg, pulse is 192/min and respirations are 22 /min. Physical examination shows a pale and dyspneic man who is alert and oriented. Faint rales can be heard in the lower lung fields on both sides on auscultation. An echocardiogram shows persistent ventricular tachycardia. Which of the following is the best next step in the management of this patient?
Synchronized cardioversion
Which of the following set of cardiovascular changes best represents responses to sequential administration of ganglion blocker + norepinephrine ??
TPR (total peripheral resistance) [inc.] HR [inc.] Contractility [inc.]
NON-DEPOLARIZING BLOCKERS
TUBOCURARINE
sequential administration of atropine + norepinephrine
Tachycardia (because of blockage of reflex bradycardia)
α 1 -antagonist used to treat BPH by inhibiting smooth muscle contraction. Selective for α 1A/D receptors (found on prostate) vs vascular α 1B receptors.
Tamsulosin
used only in benign prostatic hyperplasia.
Tamsulosin (Alpha 1 -selective blocker)
Referred to as 'bolus fibrinolytics' since their administration does not require a prolonged intravenous infusion. Because of their simplicity of administration they are the fibrinolytic agents most often recommended.
Tenecteplase and reteplase
PHYSO! STIG MINE
Tertiary amine. Can enter and stimulate CNS. USES Treatment of overdoses of anticholinergic drugs.
NICOTINE
Tertiary amine. Selective agonist of the nicotinic receptor. Depending on the dose, nicotine depolarizes autonomic ganglia, resulting first in stimulation and then in paralysis.
Treatment of chorea associated with Huntington's
Tetrabenazine
Indicated in addition to ACE inhibitors (or ARBs), β-blockers and diuretics in African-American heart failure patients who are still symptomatic.
The combination of hydralazine and isosorbide dinitrate
The drug X dose caused a decrease in diastolic blood pressure and little change in systolic pressure. Thus, there was a large increase in pulse pressure. The decrease in diastolic pressure suggests that the drug decreased vascular resistance, that is, it must have significant muscarinic or beta effect. The fact that it also markedly increased pulse pressure suggests that it strongly increased stroke volume, a b agonist effector.
The drug with these beta effects is isoproterenol
Carvedilol is an effective antihypertensive agent that, like propranolol, is capable of blocking beta receptors. An important difference between the two drugs is that carvedilol
The effectiveness of carvedilol in the management of hypertension and in congestive heart failure appears to be due to a combination of antagonistic actions at both alpha and beta adrenoceptors. Carvedilol is not a β 1 selective blocking agent (unlike atenolol and metoprolol), and (unlike pindolol and acebutolol) it lacks intrinsic sympathomimetic activity.
A new diuretic is being studied in human volunteers. Compared with placebo, the new drug increases urine volume, increases urinary Ca 2+ , increases plasma pH, and decreases serum K + . If this new drug has a similar mechanism of action to an established diuretic, it probably
The effects described are typical of loop diuretics, which inhibit the Na + K + 2Cl − cotransporter in the thick ascending limb. This action prevents the reabsorption of Ca 2+ from the paracellular pathway and provides for the use of these drugs in hypercalcemia. The increased load of Na + in the collecting tubules leads to increased excretion of both K + and H + , so hypokalemia and alkalosis may occur.
After 6 months of lifestyle modifications the patient's blood pressure remains elevated. It is decided that pharmacotherapy must be started. What would be the most appropriate choice of drug to initiate treatment with?
The four classes of antihypertensives that are recommended as first-line drugs are: thiazides, calcium channel blockers, ACEIs (e.g. Captopril) and ARBs (e.g. losartan) Any one of these would be an appropriate drug with which to initiate treatment in this patient.
Which of the following is a component of slow-reacting substance of anaphylaxis (SRS-A)?
The leukotriene C and D series are major components of SRS-A. Leukotriene LTB is a chemotactic eicosanoid
drugs prevents platelet aggregation by blocking ADP receptors, Prevent expression of glycoproteins IIbn lla on platelet surface.?
Ticlopidine(Neutropenia ), Clopidogrel
An 11-year-old boy was brought to the ER by some of his friends because he "started going crazy" after eating seeds from a plant while "trying to get high." The boy was incoherent; his skin was hot and dry. His pupils were dilated and unresponsive to light. Blood pressure was 180/105 mm Hg, pulse 150/min, and rectal temp 40 C (104 F). The presumptive diagnosis was drug toxicity due to the ingestion of a compound similar to
The signs and symptoms experienced by this boy are highly suggestive of the ingestion of a compound with strong muscarinic receptor-blocking actions. The leaves and seeds of jimsonweed (Datura stramonium) contain anticholinergic compounds, including atropine, hyoscyamine, and scopolamine—approximately 50 seeds may cause severe toxicity. In addition to symptomatic support, management of poisoning (or drug overdose) due to M blockers may involve use of the AChE inhibitor physostigmine.
In a patient suffering from angina of effort, nitroglycerin may be given sublingually because this mode of administration
The sublingual administration of a drug avoids its absorption into the portal circulation and hence eliminates the possibility of firstpass metabolism, which can often have a major impact on oral bioavailability. Given sublingually, nitroglycerin is more effectively absorbed into the systemic circulation and has improved effectiveness in angina by this mode of administration. Effective absorption is unlikely to decrease reflex tachycardia or propensity toward methemoglobinemia. There is no bypass of the coronary circulation—nitrates actually decrease coronary vasospasm, which makes them effective in variant angina.
A 5-year-old child becomes ill while visiting relatives who have a farm in Arkansas. His symptoms include severe abdominal cramps with vomiting and diarrhea and profuse lacrimation and salivation. Pupillary constriction is marked. The most likely cause is exposure to
The symptoms of cholinergic excess seen in this child are indicative of exposure to insecticides such as the organophosphate parathion, which cause irreversible inhibition of acetylcholinesterase. Other symptoms may include CNS excitation and stimulation of the skeletal NMJ, ultimately leading to paralysis of respiratory muscles"DUMBBEELSS." In addition to symptomatic support, management of AChE inhibitor poisoning involves the use of atropine and 2-PAM.
Alternative therapy for patients withpersistent asthma.
Theophylline
Thermoregulatory sweat glands in the body utilize what type of pathway?
Thermoregulatory sweat glands are innervated only by the sympathetic nervous system. The pathway is unusual in that the postganglionic neuron releases acetylcholine. Thus, the receptors on sweat glands are muscarinic (M 3 ). The term neurohumoral means "nerve-blood." The only site in the ANS where neurohumoral transmission occurs is the adrenal medulla, where sympathetic nerve activity elicits the release of catecholamines (mostly epinephrine) into the blood. Epinephrine cannot bind to muscarinic receptors.
Physical examination shows JVD, rales are heard bilaterally on auscultation of the chest and there is 3+ bilateral pitting edema of the ankles. The patient's symptoms will improve with administration of a diuretic, but the physician does not want to cause hypercalcemia. Which of the following diuretics are contraindicated for use in this patient?
Thiazides
Used in heparin-induced thrombocytopenia (HIT).
Thrombin inhibitors like Dabigatran
Alteplase (t-PA)
Thrombolytic: human recombinant tissue plasminogen activator. Reteplase and tenecteplase are similar. Streptokinase is a bacterial protein with thrombolytic properties. Tox: bleeding
Indicated for the treatment of glaucoma.
Timolol
May be added to ICS for long-term control of severe persistent asthma.
Tiotropium
A 34-year-old woman comes to the physician for follow-up after a recent medication change for managing intermittent ventricular arrhythmias. She has started experiencing joint pain and has developed a rash on her cheeks. Which of the following complications can be expected with continued use of this medication?
Torsades de pointes Antiarrhythmics Na channel blockers (class I)
Sotalol clinical use Anti-arrhythmic (class III)
Treatment of life-threatening ventricular arrhythmias Maintenance of sinus rhythm in patients with atrial fibrillation & flutter who are currently in sinus rhythm Due to pro-arrhythmic effects - do not use for asymptomatic arrhythmias
Drug that inbhitd both thrombin and factor Xa
Un-fractioned heparin
Causes mydriasis and cycloplegia
Tropicamide, Atropine, homatropine Anticholinergics
A woman on a MAO inhibitor has a hypertensive crisis after a meal. What did she likely ingest?
Tyramine-containing foods.
A 67 year old woman is diagnosed with DVT. Which of the following are the best options for initial anticoagulant therapy in this patient?
UFH, LMWH or fondaparinux
Juan ate some uncooked prawns and consequently got food poisoning, manifested as acute diarrhea. The pharmacist suggested he took a drug which acts by blocking muscarinic receptors. Juan decided to take double the recommended dose. Which of the following side effects is he most likely to suffer from?
Urinary retention
Urination in the human subject is decreased by
Urinary retention is a well known adverse effect of drugs that have antagonist effects on muscarinic receptors. In addition to the prototypic drug atropine, M blockers include drugs used in Parkinson disease, such as benztropine. Acetylcholine directly and AChE inhibitors (edrophonium, physostigmine) indirectly activate M receptors in the GU system, causing bladder contraction with voiding and incontinence. Activation of nicotinic receptors in ANS ganglia would lead to the stimulation of PANS functions.
Latino prost (PGF2a derivative)
Used for glaucoma.
To0l.terodine
Used for overactive bladder.
Eplerenone (Inspra)
Used in HTN and heart failure, is a more selective aldosterone antagonist
Gly.COPY.rrolate Muscarinic anticholinergic Synthetic [4] quaternary ammonium
Used orally to inhibit GI motility. Used parenterally to prevent bradycardia during surgical procedures.
furosemide, torsemide, and ethacrynic acid Mechanism: Na + /K + /2Cl − transporter inhibition, results in: - ↓ intracellular K + in TAL - ↓ back diffusion of K + - ↓ positive potential - ↓ reabsorption of Ca 2+ and Mg 2+ - ↑ diuresis Uses: AE: Drug interaction:
Uses: - Acute pulmonary edema - Heart failure - Hypertension - Refractory edemas - Anion overdose - Hypercalcemic states Side effects: - Sulfonamide hypersensitivity (furosemide) - Hypokalemia and alkalosis - Hypocalcemia - Hypomagnesemia - Hyperuricemia (actively secreted by the OAT) - Ototoxicity (ethacrynic acid > furosemide) Drug interactions - Aminoglycosides (enhanced ototoxicity) - Lithium (chronic loop administration, ↓ clearance) - Digoxin (↑ toxicity due to electrolyte disturbances)
acetazolamide and dorzolamide Mechanism: carbonic anhydrase inhibition, results in: - ↓ H + formation inside PCT cell - ↓ Na + /H + antiport - ↑ Na + and HCO 3 − in lumen - ↑ diuresis Uses: AE: Drug interaction:
Uses: - Glaucoma - Acute mountain sickness - Metabolic alkalosis Side effects: - Bicarbonaturia and acidosis - Hypokalemia - Hyperchloremia - Paresthesias - Renal stones - Sulfonamide hypersensitivity
hydrochlorothiazide, Mechanism: Na + /Cl − transporter inhibition, results in: - ↑ luminal Na + and Cl − in DCT - ↑ diuresis Uses: AE: Drug interaction:
Uses: - Hypertension, CHF - Nephrolithiasis (calcium stones) - Nephrogenic diabetes insipidus Side effects: - Sulfonamide hypersensitivity - Hypokalemia and alkalosis - Hypercalcemia - Hyperuricemia (actively secreted OAT) - Hyperglycemia - Hyperlipidemia (except indapamide) Drug interactions and cautions: - Digoxin (↑ toxicity due to electrolyte disturbances) - Avoid in patients with diabetes mellitus
Coagulation factor with shortest half life
VII
Dihydropyridine calcium channel blockers have a preferential effect on calcium channels in:
Vascular smooth muscle amlodipine, nifedipine
A 60-year-old man is considered for more treatment for his hypertension after his current medication became ineffective. The physician wants to prescribe an additional medication that will dilate his blood vessels. This medication acts on calcium channels on vascular smooth muscles to lower his blood pressure. Which of the following is the physician most likely referring to?
Vascular smooth muscle- amlodipine = nifedipine > diltiazem > verapamil. Heart-verapamil > diltiazem > amlodipine = nifedipine (verapamil = ventricle).
Effect of ganglion blocker on vascular tone and HR?? Inhibit division of autonomic nervous system that exercises dominant control of the organ.
Vasodilation and a decrease in peripheral resistance [TPR]. [Vascular tone is controlled by sympathetic nervous system] increase in heart rate. [heart rate is normally under parasympathetic control]
PYRI,DO? STIG MINE
[4'] Quaternary ammonium. Does not enter CNS. USES Treatment of myasthenia gravis.
Type IB antiarrhythmics are most effective at treating which of the following?
Ventricular arrhythmias
A 56-year-old woman comes to emergency department because she has been experiencing frequent palpitations. Medical history includes severe asthma and stable angina. An EKG show absence of P waves and an 'irregularly irregular' ventricular rate. Which of the following antiarrhythmic drugs is most appropriate to control this patient's ventricular rate?
Verapamil
A 86-year-old woman comes to emergency department with complaints of mild shortness of breath and palpitations. She has a 20- year history of hypertension. Current medication is losartan. Her blood pressure is 143/81 mm Hg, pulse 154 beats/min with an irregularly irregular pattern and RR 16 breaths/min. ECG shows a diagnosis of atrial fibrillation. Which of the following drugs is the most appropriate to help control this patient's ventricular rate?
Verapamil
Can increase concentrations of other cardiovascular drugs such as digoxin, dofetilide, simvastatin, & lovastatin
Verapamil
Which of the following drugs in high doses causes bradycardia?
Verapamil
a 72 year old woman comes to physician because of breathlessness during mild exercise. she has 8 year history of atrial fibrillation and angina. current medications are metoprolol and warfarin. her blood pressure is 134/75 mmHg and her pulse is 115/min and irregularly irregular at rest. The physician decides to add another drug to her current regiment to help control her ventricular rate. which of the following drugs is most appropriate to prescribe at this time?
Verapamil
In the treatment of atrial fibrillation which one of the following agents can be used to control ventricular rate?
Verapamil (CCB)
supraventricular tachycardias
Verapamil and Diltiazem Prototype Ca 2+ -channel blockers Side effects: constipation (verapamil), dizziness, flushing, hypotension, AV block Drug interaction: - Additive AV block with β-blockers, digoxin - Verapamil displaces digoxin from tissue-binding sites
A 65-year-old woman comes to the emergency department with ongoing oppressive chest pain at rest, intensity 7/10, irradiating to the neck, that appeared after emotional distress. She has a 10-year history of hypertension. Current medications include captopril. After 24 hours of IV vasodilators, with the patient hemodynamically stable and free of symptoms, a PCA (percutaneous coronary angioplasty) is performed and shows no significant epicardial stenosis. Transthoracic Echocardiogram shows normal EF (70%), normal valvular apparatus and normal left ventricular outflow tract. A diagnosis of Prinzmetal's angina is made. Which of the following drugs is the most appropriate long-term treatment for this patient?
Verapamil, diltiazem. Antiarrhythmics calcium channel blockers (class IV) [Dec] conduction velocity, [Inc] ERP, [Inc] PR interval.
Hypertensive urgency
Very high blood pressure (eg, diastolic > 120 - 130 mm Hg) without target-organ damage
May cause skin necrosis
Warfarin
Monitored by measuring the PT (Intrinsic pathway)
Warfarin
In stable patients cardioversion should be delayed for 3- 4 weeks until adequate anticoagulation has been achieved
Warfarin (oral)
Initiated within 24 to 48 h of starting heparin
Warfarin [long-term anticoagulation for all patients except pregnant women (who should continue to take heparin)]
Ipratropium, Tiotropium Amine group + Uses
[4] QUATERNARY AMMONIUM MUSCARINIC ANTAGONISTS Used as inhalational drugs in treatment of (COPD) + Asthma.
A 17-year-old patient complains that he develops wheezing and severe shortness of breath whenever he takes aspirin for headache. Increased levels of which of the following may be responsible, in part, for some cases of aspirin hypersensitivity?
When cyclooxygenase is blocked, leukotrienes may be produced in increased amounts by diversion of prostaglandin precursors into the lipoxygenase pathway. In patients with aspirin hypersensitivity, this might precipitate the bronchoconstriction often observed in this condition
Ranolazine (Ranexa) indication
When nitrates, beta blockers and Ca2+ channel blockers are unsuccessful
NEO. STIG MINE
[4'] Quaternary ammonium. Does not enter CNS. USES Postoperative urinary retention. Reversal of effects of non-depolarizing neuromuscular blockers after surgery. Treatment of myasthenia gravis
5-Lipoxygenase Inhibitors
Zileuton
Enzyme inhibitor
Zileuton
a leukotriene receptor blocker? Blocks conversion of arachidonic acid to leukotrienes. Hepatotoxic
Zileuton blocks the synthesis of leukotrienes. Montelukast and zafirlukast block LTD4 receptors. Especially good for aspirin-induced and exercise-induced asthma.
Amine Group of Atropine
[3'] Tertiary amine: both central and peripheral muscarinic blocker.
HomaTROPIne, TROPIicamide
[3] TERTIARY AMINE MUSCARINIC ANTAGONISTS Used as Mydriatic for fundoscopy. Produce Mydriasis with cycloplegia. Preferred to atropine because of shorter duration of action.
BenzTROPIne, TRIHEXYPHENIDYL
[3] TERTIARY AMINE MUSCARINIC ANTAGONISTS Used to treat Parkinson's disease and the extrapyramidal effects of antipsychotic drugs.
Antiarrhythmicsβ-blockers (class II) Metoprolol, propranolol, esmolol, atenolol, timolol, carvedilol.
[Dec] SA and AV nodal activity by [Dec] cAMP, [Dec] Ca 2+ currents. Suppress abnormal pacemakers by [Dec] slope of phase 4. AV node particularly sensitive— increase PR interval.
Metoclopramide adverse effects
[Inc] parkinsonian effects, tardive dyskinesia. Restlessness, drowsiness, fatigue, depression, diarrhea. Drug interaction with digoxin and diabetic agents. Contraindicated in patients with small bowel obstruction or Parkinson disease (due to D 2 -receptor blockade).
Activation of the sympathetic nervous system results in
[αlpha1] [Q] [Inc] vascular smooth muscle contraction, [Inc] pupillary dilator muscle contraction (mydriasis), [Inc] intestinal and bladder sphincter muscle contraction
Pretreat w/ Prazosin an A1 antagonist blocking vasoconstriction. If we then add Nitric oxide a vasodilator we would have
a major drop in BP and would expect reflex tachycardia
argatroban or lepirudin monitoring???
aPTT.
A 32-year old man comes to the emergency room because of intractable vomiting and chest pain for the past 2 days. Physical examination reveals dry mucous membranes and muscle weakness. EKG shows flatted T waves and apparent prolongation of QT intervals. ABG shows pH is 7.7 [HCO3] is 36meq/L, and pCO2 is 52mmHg. He is given fluids as well as a drug to correct his acid/base imbalance. Where does this drug most likely act?
acetazolamide. If you see anything about acid-base imbalance, high altitude, glaucoma or a head injury, think about acetazolamide.
heparin therapy be monitoring??
activated partial thromboplastin time (aPTT) assay. The aPTT is a test of the integrity of the intrinsic and common pathways of coagulation. The aPTT should be measured routinely to guide subsequent dosing adjustments. The aPTT should be evaluated no sooner than 6 hours after loading dose or after any changes in infusion rate, as noted previously. If dosing is stable, the aPTT should be evaluated once daily. Additional monitoring parameters for heparin therapy include evaluation for potential adverse reactions and possible therapeutic failure. Hct and platelet count should be checked every 1 to 2 days. L.N. should be examined for signs of bleeding, as well as for signs and symptoms associated with thrombus extension and PE.
Recreating sinus rhythm
agent that target AV node (reduce Excitability ) Atenolol (Beta blockers) + CCB + Digoxin
can be used IV for rate control in critically ill patients, or to control heart rate acutely in patients with HF.
amiodarone
Omalizumab adverse effects
anaphylaxis
HexaMETHOnium, MeCAMYlamine
antagonism of nicotinic receptors causes ganglion blockage
Decreases synthesis of mevalonatem , Inhibits cholesterol biosynthesis, [Dec] LDL synthesis, [Inc] LDL clearance, modest [Inc] HDL, limited [Dec] VLDL
atorvastatin fluvastatin lovastatin pravastatin rosuvastatin simvastatin
Blocks norepinephrine-induced reflex bradycardia
atropine
Muscarinic blockers:
atropine, benztropine, ipratropium, scopolamine
Increases expression of Lipoprotein Lipase [LPL] [Dec] VLDL, [Dec] TG, modest [Dec] LDL, modest [Inc] HDL
bezafibrate fenofibrate gemfibrozil
Centrally-acting antihypertensive drug
clonidine (alpha 2 antagonist) Application: Hypertensive urgency (limited situations), ADHD, Tourette syndrome, symptom control in opioid withdrawal Adverse Effects CNS depression, bradycardia, hypotension, respiratory depression, miosis, rebound hypertension with abrupt cessation
Management of Stable COPD
started with one long acting bronchodilator (LABA or LAMA) or two depending on dyspnea short acting bronchodilators (SABA or SAMA) should be only if dyspnea is infrequent
Second messenger that keeps platelets dormant
cAMP
A 77-year-old man is transferred to the hospital from a nursing home due to fever and confusion. On arrival the patient's BP is revealed to be 60/40 mmHg despite aggressive intravenous hydration. Intravenous norepinephrine is administered in response to patient's hypertension. Which of the following cellular changes is most likely to occur in direct response to the medication?
cAMP increase in cardiac muscle cells Norepinephrine preferentially acts on alpha receptors. However, none of the options are correct for alpha-1, which is linked to Gq (correct answer could be IP3/DAG/calcium increase in vascular smooth muscle cells). Norepinephrine also has some action on beta-1 (BUT NOT BETA-2!!!), which is described by (b).
Nonselective α- and β-antagonists Nonselective a- and βantagonists have modified suffixes (instead of" -olol")
carvedilol ( reduce mortality), labetalol
A patient with glaucoma who has been using timolol (Timoptic) drops for several days. what is the most likely target of this drug?
ciliary epithelium non-selective beta(1) and beta(2) adrenergic receptor blocking agent Decreases production of aqueous humor by reducing cAMP
Torsades de Pointes treatment • a variant of polymorphic VT that occurs in patients with baseline QT prolongation - "twisting of the points" • looks like usual VT except that QRS complexes "rotate around the baseline" changing their axis and amplitude • ventricular rate >100 bpm, usually 150-300 bpm
magnesium, temporary pacing, isoproterenol and correct underlying cause of prolonged QT, electrical cardioversion if hemodynamic compromise
Type II antiarrhythmics (BB) are most effective at treating which of the following?
maintaining ventricular rate in patient suffering from atrial fibrillation/flutter
Type IV antiarrhythmics (CCB) are most effective at which of the following?
maintaining ventricular rate in patient suffering from atrial fibrillation/flutter
AChE inhibitors: irreversible—
malathion, parathion
LMWH inhibit activated ______________________but have less effect on thrombin than UFH: UFH has an anti-factor Xa/anti-factor IIa ratio of 1:1. LMWH have anti-factor Xa/anti-IIa ratios between 2:1 and 4:1.
factor X
Activates a nuclear receptor
fenofibrate GI upset Skin rashes [Inc] risk of gallstone formation [Inc] risk of rhabdomyolysis when combined with statins
What addition needed to standard therapy in African-American patients who remained symptomatic despite standard therapy significantly reduced mortality and symptoms?
fixed-dose combination of hydralazine and isosorbide dinitrate (BiDil) Its benefit in non-African-American patients is less well established, but the combination can be considered in those intolerant to an ACE inhibitor or an ARB, or in those who need additional blood pressure control despite maximal doses of standard therapy.
Zileuton adverse effects
hepatotoxicity, myalgia
H1 effect on nervous system
histamine powerful stimulant of sensory nerve endings, especially those mediating pain and itching
Long term use of systemic glucocorticoidsmay result in
hypercortisolism and Cushing's syndrome.
Combining K-sparing diuretics with ACEIs or ARBs may cause ......
hyperkalemia
As this patient presents with anaphylactic shock, the best drug to give would be epinephrine. mechanism of action?
non selective beta agonist with some alpha receptor activity that opposes the vasodilatory effects (unlike isoproterenol, (C), that has unopposed beta2 activity). After administration, cardiac output increases through increased heart rate. MAP will increase slightly, which is shown best in (B)
Timolol MOA
non-selective beta(1) and beta(2) adrenergic receptor blocking agent
Reserpine (Serpasil) Tetrabenazine
inhibitors of NE storage
treatment of hypertension during pregnancy
methyldopa
Minoxidil
more powerful antihypertensive, is also used topically in baldness.
hexamethonium - mechanism of action? CAUSE
nicotinic antagonist (put a HEX on smokers/nicotine) - ganglionic blocker Causes Tachycardia
Drugs used to treat angina
nitrates, beta blockers, calcium channel blockers
A hypertensive emergency occurs when hypertension is severe enough to cause end-organ damage. Most commonly, ............................., ..........................., or ........................... is given intravenously as therapy.
nitroprusside, labetalol, or the D1 agonist
Direct acting cholinergic agonists
pilocarpine, methacholine, may be used for xerostomia
A 70 year old African American man comes to the clinic for his regular check up. He has past medical history of severe left heart failure and takes medication for it. He also suffered myocardial infarction 6 months ago and was started on beta blockers after that. on his current visit his BP is found to be 140/80 mmHg. His wife claims his blood pressure has been around that value for past 3 months. The physician decides to add another medicine to his regime. which one??
potassium sparing diuretic (Spironolactone)
Leukotrienes (LTC4, LTD4, LTE4)
potent bronchoconstrictorsand are secreted inasthma and anaphylaxis.
Bosentan, CONTRAINDICATION?? Endothelin (ET)-1 is a powerful vasoconstrictor through ET-A and -B receptors. Bosentan is an ET-A receptor antagonist. • Administered orally • Side effects: those associated with vasodilation (headache, flushing, hypotension)
pregnancy
Metoclopramide
prokinetic agent used to block emesis Diabetic and postsurgery gastroparesis, antiemetic, persistent GERD. D2 receptor antagonist. [Inc] resting tone, contractility, LES tone, motility, promotes gastric emptying. Does not influence colon transport time.
inhibit non dihydropyrdine calcium channels (e.g. Verapamil, diltiazem) action
prolongation of AV node repolarization because depolarization of nodal tissues (SA or AV node) is dependent upon the movement of calcium ions, non-dihydropyridine calcium channel blockers primarily affect these tissue. The end results is prolonged AV node conduction time (decrease in conduction velocity)
Hydralazine is a direct vasodilator that is associated with significant .............................. and ..............................
reflex tachycardia sodium and water retention
Which of the following is a consequence of one of the first line heart failure medications [ACE Inhibitors] that is contraindicated in this patient?
renin [INC] Angio II [Dec] Aldosterone [Dec]
anaphylactic shock treatment via epinephrine by way of intramuscular injection. other effects?
stimulating of lipolysis
Direct, selective and reversible inhibition of factor Xa in both the intrinsic and extrinsic coagulation pathways
rivaroxaban apixaban edoxaban
Atropine main action in clinic
speeding up heart rate Muscarinic antagonist. Used to treat bradycardia and for ophthalmic applications.
In the case of both loop and thiazide diuretics, the blood ph become ???
the associated loss of H + results in alkalosis.
The two classes of antihypertensives that are recommended as first-line drugs in African-American patients (with no comorbidities) are: ___________________________ and ___________________________ Either of these would be an appropriate drug with which to initiate treatment in this patient. The four classes of antihypertensives that are recommended as first-line drugs are: ___________________________ ___________________________ ___________________________ ___________________________ Any one of these would be an appropriate drug with which to initiate treatment in this patient.
thiazides and calcium channel blockers. thiazides, calcium channel blockers (CCB), ACEIs and ARBs. (diabetes)
In the management of a cardiac arrhythmia, lidocaine is to be administered by way of an IV loading dose. What variable must be known to calculate an appropriate loading dose?
to calculate a loading dose you must know volume of distribution and target plasma concentration. Since lidocaine is being given IV, its bioavailability is 100% (f=1) so no adjustment is required to the equation. Renal clearance is needed to calculate a maintenance dose, and time to steady-state applies only when using a maintenance dose. There is no lag time for an IV drug.
IV nitroglycerin
unstable angina ´ heart failure
ergot alkaloids adverse effects
vasospasm
He is started on a medication that inhibits the enzyme that catalyzes the first committed step of cholesterol synthesis. Which of the following studies should be done before starting the medication?
warfarin need Renal function tests
α 1 agonists: α 2 agonists: β agonists: (β 1 = β 2 ), (β 1 > β 2 ) β 2 agonists:
~~ phenylephrine ~~ clonidine, methyldopa ~~ isoproterenol + dobutamine ~~ albuterol, terbutaline, salmeterol
Main Effects of Statins
¯25%-60% reduction of LDL
Third-line antihypertensive drug.
α-blocker
Orthostatic (postural) hypotension results from venular dilation (not arteriolar) and mainly results from ...
α1 blockade or decreased sympathetic tone.
An ophthalmologist instills a solution of a drug into a 35-year-old man's eyes to dilate his pupils prior to ocular examination. Which of the following drugs is most likely being used to achieve this effect?
αlpha-1 agonist [INC] vascular smooth muscle contraction, [INC] pupillary dilator muscle contraction (mydriasis}, [INC] intestinal and bladder sphincter muscle contraction
Only considered first-line for patients with coronary heart disease(CAD), heart failure, or post MI where they have strong clinical outcome benefits.
β-blockers
Second-line drugs in most antihypertensive patients. They are only first-line in hypertensive patients with coronary artery disease, CHF or post-MI.
β-blockers
3 months after starting therapy the patient is not responding adequately to initial 2 drug combo treatment for anti hypertension. What would be the most appropriate add-on medication?
β-blockers are not a first-line option in most people but are a good choice of drug to combine with first-line agents if initial treatment is not successful.
How would you alter the treatment of the patient considering his new diagnosis of heart failure?
β-blockers are recommended in addition to an ACEI (and diuretic) for patients with symptomatic heart failure (as in the case of this patient) or asymptomatic patients who have a decreased LVEF or history of MI. β-blockers have been shown to reverse some of the remodeling of the cardiac tissue that occurs in heart failure and therefore increase survival outcomes.
Selective β-1 blockers are preferred over nonselective beta blockers in some patients because they
β1-selective blockers like atenolol and metoprolol are less likely to block receptors in the bronchiolar smooth muscle and therefore less likely to cause bronchoconstriction, especially in asthmatic patients. Nonselective beta blockers are considered to be equally as effective as selective beta-1 blockers in arrhythmias, migraine prevention, and in post-MI prophylaxis. Both types of drugs are cardiodepressant.
1. A pharmacologist is studying the increase in cAMP evoked by different drugs. Activation of which of the following receptors would be expected to evoke the largest increase in cAMP levels?
β2
Bronchodilators
β2 Adrenergic agonists Anticholinergics Methylxanthines
Glucocorticoids: Adverse Effects
•Local irritation of the nasal mucosa •Nosebleed •Nasal septal perforation •Nasopharyngeal candidiasis
Systemic corticosteroids
•Prednisolone •Dexamethasone
In such patients, class IA and class III antiarrhythmic drugs may increase the risk of torsades. Drugs which cause torsades include:
• Potassium-channel blockers (class 1A and class III) • Antipsychotics (thioridazine) • Tricyclic antidepressants
ACh does not have a direct effect on ........................................................ It INDIRECTLY triggers the release of ..............................................
• Smooth muscle relaxation: • Nitric Oxide. Nitric Oxides causes smooth muscle relaxation ie vasodilation
Atrial fibrillation is the most common arrhythmia in the United States. There are 2 primary goals:
• Ventricular rate control with beta blocker, CCB, or digoxin • Anticoagulation
NO functions as
• vasodilation • anti-thrombotic • anti-inflammatory (all involve NO-stimulated formation ofcGMP)
Cromolyn and Nedocromil MOA
•Act by inhibiting mast cell degranulation, and prevent both antigen- and exercise-induced bronchospasm in asthmaticpatients. •Not useful in managing an acute asthma attack, because they are notbronchodilators.
Niacin adverse effects Antidote
•Administration of aspirin prior to niacin decreases flush, which is prostaglandin(PG)- mediated.
β2 AdrenergicAgonists: AdverseEffects
•Administration of these drug by inhalation decreases the risk of systemic side effects such as tachycardia, tremor, andhypokalemia. •LABAs increase risk of serious asthma- related events (hospitalization, intubation,and death).
Inhaled corticosteroids (ICS)
•Beclomethasone •Budesonide •Flunisolide •Fluticasone
Inhaled β2 Adrenergic Agonists: MOA
•Bind to and activate β2 adrenergic receptors on airway smooth muscle cells. •Activation of β2 receptors stimulates adenylyl cyclase and increases formation of cAMP. •cAMP activates protein kinase A which phosphorylates and inactivates myosin light chain kinase. •This results in relaxation of the airway smooth muscle cells and bronchodilation.
Beta blocker MOA
•Blockb1receptors •Reduce both heart rate & contractility •O2 demand is reduced during exercise and at rest •Reduce frequency and severity of angina attacks
Anti-Inflammatory Drugs: Release Inhibitors
•Cromolyn •Nedocromil
Pharmacotherapy of Allergic Rhinitis
•Glucocorticoid nasal sprays •Oral antihistamines •Cromolyn sodium •Montelukast •Nasal Decongestants
Corticosteroids: MOA
•Glucocorticoids inhibit phospholipase A2 and inhibit transcription of COX-2, resulting in reduced formation of leukotrienes and prostaglandins. •Prolonged use of SABAs results in β2 receptors desensitization. •Corticosteroids prevent or reverse this desensitization.
Inhaled Corticosteroids: Adverse Effects
•ICS have lower bioavailability than systemic corticosteroids: risk of potential adverse effects is reduced. •Local adverse effects include oropharyngeal candidiasis, dysphonia, reflex cough and bronchospasm. •Long term use may result in osteoporosis and cataracts. It may cause deceleration ofvertical growth in children.
allergic rhinitis (hay fever)
•Inflammation of nasal mucosa induced by different allergens. •Characterized by nasal pruritus, sneezing, rhinorrhea, and nasal congestion. •Treatment includes allergen avoidance and pharmacotherapy.
Acute exacerbations are managed with quick relief medications:
•Inhaled (SABAs). •Inhaled (SAMAs). •Systemic corticosteroids.
Bronchodilators: Anticholinergics USES
•Ipratropium is less effective than SABAs. •Ipratropium provides additive benefit to SABAs in the management of moderate to severe exacerbations of asthma.
Longer onset of action & duration of action than nitroglycerin (more useful for long-term prophylaxis)
•Isosorbide mononitrate = >1 h (time to onsetofaction) & nearly 100 % oralbioavailability
Inhaled LONG-Acting β2 Adrenergic Agonists: Uses
•LABAs are combined with inhaled corticosteroids (ICS) for long-term controlin moderate and severe persistentasthma. •LABAs shouldn't be used as monotherapy for long-term control of asthma as they have no anti-inflammatory action. •LABAs are not used in the treatment of acutesymptoms or exacerbations.
Theophylline: Adverse Effects
•Largely replaced by β2 agonists and corticosteroids due to narrow therapeutic window, adverse effects, and potential for drug interactions. •The most common adverse effects are headache, nausea, vomiting, abdominal discomfort, andrestlessness. •At high concentrations: cardiac arrhythmias and seizures.
Misso.prost.ol(PGE1 analog) usage
•Prevention of peptic ulcers inpatients taking high doses of NSAIDs. •To ripen the cervixat or nearterm. •Management of post partum hemorrhage. •Abortifacient in combination with the antiprogestin mifepristone or methotrexate (MTX).
Bronchodilators: Anticholinergics Adverse effects
•These agents are quaternary ammonium compounds. •Low access to the systemic circulation and systemic adverse effects. •Minor anticholinergic effects, e.g. xerostomia, might occur. •Safer than SABAs in patients with cardiovascular disease.
Release Inhibitors: Adverse Effects
•Throat irritation, cough, mouth dryness. •Rarely, chest tightness and wheezing. •Rare side effects include reversible dermatitis, myositis, or gastroenteritis, pulmonaryinfiltration with eosinophilia andanaphylaxis.
Dino prostone(PGE2) usage
•To ripen cervix at or nearterm. •Abortifacient. MOA: uterine smooth muscle contraction
Ca2+ channel blockers - Clinical applications
•Used in combination with b-blockers when initial treatment with b-blocker is not successful or, as a b-blocker substitute when b-blockers are contraindicated Relieve symptoms of Variant Angina
LMWH have replaced UFH for most clinical indications because
■ (1) they can be administered SC, once daily, without laboratory monitoring; ■ (2) they are as effective as and safer than UFH.
Main Effects of Resins
■ 15%-30% reduction of LDL ■ 5%(Bad) INCREASE TG
Main Effects of Fibrates
■ 30%-60% reduction of TG
Stable Angina treatment
■ Acute attack: promptly relieved by rest or nitroglycerin ■ Maintenance therapy: long acting nitrates NITRATES + Beta blockers ■ CCB: When beta blockers are not successful or are contraindicated
Cyproheptadine usage
■ Allergic rhinitis ■ Vasomotorrhinitis ■ Management of serotonin syndrome.
A 69 year old man comes to the emergency department because of a 3 hour history of severe substernal chest pain. An ECG shows a STEMI. The hospital does not have a coronary catheterization laboratory. He is administered a fibrin selective thrombolytic agent. Which of the following drugs was he most likely given?
■ Alteplase (tPA), reteplase (rPA), streptokinase, tenecteplase (TNK-tPA). Directly or indirectly aid conversion of plasminogen to plasmin, which cleaves thrombin and fibrin clots. [INC] PT, [INC] PTT, no change in platelet count. ■ Adverse Effects: Bleeding. Contraindicated in patients with active bleeding, history of intracranial bleeding, recent surgery, known bleeding diatheses, or severe hypertension. Nonspecific reversal with antifibrinolytics (eg, aminocaproic acid, tranexamic acid), platelet transfusions, and factor corrections (eg, cryoprecipitate, FFP, PCC).
Lidocaine
■ Amide local anesthetic, medium-duration amide prototype: highly selective use-dependent group 1B antiarrhythmic; used for nerve block and acute post-MI ischemic ventricular arrhythmias. Parenteral only. ■Tox: CNS excitation. ■Mexiletine: like lidocaine, but orally active, longer duration.
Statins monitoring parameters
■ Aminotransferase activity should be measured at baseline, at 1-2months, and then every 6-12 months. ■ CK should be measured at baseline. If muscle pain, or weakness appears, CK should be measured immediately and drug discontinued if activity is significantly elevated.
Ca2+ channel blockers (CCB)
■ Amlodipine, ■ Nifedipine, ■ Diltiazem, ■ Verapamil
Ondansetron
■ Anti-emetic. ■ Particularly for severe nausea and vomiting that occurs with cancer chemotherapy.
Ipratropium
■ Antimuscarinic agent: aerosol for asthma, chronic obstructive pulmonary disease (COPD). Good bronchodilator in 30-60% of patients. Tiotropium and aclidinium are similar with longer action; approved only for COPD. ■Not as efficacious as b 2 agonists but less toxic in COPD. ■Tox: dry mouth
B-blockers
■ Atenolol, ■ Metoprolol, ■ Propranolol
inhibitors of HMG-CoA reductase, theenzyme that catalyzes the first committed step of cholesterol biosynthesis Adverse effects: Hepatotoxicity ( LFTs), myopathy (esp. when used with fibrates or niacin)
■ AtorvaSTATIN ■ FluvaSTATIN ■ LovaSTATIN. ■ PravaSTATIN ■ RosuvaSTATIN ■ SimvaSTATIN
Prevent intestinal reabsorption of bile acids, liver must use cholesterol to make more
■ Bile acid resins (e.g. cholestyramine, colestipol, colesevelam) ■ AE: GI upset, reduce absorption of other drugs and fat soluble vitamins
Ezetimibe drug interactions
■ Bile-acid sequestrants (e.g. cholestyramine) inhibit absorption of ezetimibe. ■ The two agents should not be administered together.
Ranolazine MOA
■ Blockade of Na+current that facilitates Ca2+ entry via Na+/Ca2+exchanger ■ Decreased intracellular Ca2+reduces ventricular tension& myocardial O2 demand ■ Thought to also produce myocardial relaxation ■ May modify fatty acid oxidation
beta blockers adverse effects
■ Bradycardia ■ Conductiondisturbances ■ Bronchoconstriction ■ Worseningof symptoms of peripheral vasculardisease ■Fatigue, ■ CNSeffects ■ Impotence
• Hexamethonium arrow shows the THE DIRECT EFFECT • Arrow down: • Arrow up: • Hexamethonium no effect:
■ Bradycardia M2 ■ Tachycardia B1 ■ Drug has NO DIRECT effect on the heart (drug doesn't directly at M2 or B1)
Statins MOA
■ By inhibiting cholesterol synthesis statins deplete intracellular supply of cholesterol. ■ Depletion of intracellular cholesterol leads to upregulation of HMG-CoA reductase, and upregulation of the LDL receptor.
COX-1 vs. COX-2 blockade
■ COX-1 > ↓TxA2 > ↓plt aggregation •COX-1 is found in most cells as a constitutive enzyme and the prostaglandinsit produces are involved in normalhomeostasis. ■ COX-2 > ↓ prostacyclin > vasoconstriction (can be pro-thrombotic) COX-2 is found mainly in inflammatory cells and is induced by inflammatorystimuli.
Bile Acid Binding Resins
■ Cholestyramine ■ Colestipol ■ Colesevelam
Farmer with dyspnea, salivation, miosis, diarrhea, cramping, blurry vision. What may have caused these symptoms? What is the mechanism of action? What is the antidote for his condition?
■ Cholinergic excess [organophosphate insecticide poisoning] ■ inhibition acetylcholinesterase. ■ Atropine
quid pro quo Mexican lidocaine Fries please !!!
■ Class IA Quinidine, Procainamide, Disopyramide. "The Queen Proclaims Diso's pyramid." AP duration, effective refractory period (ERP) in ventricular action potential, QT interval, some potassium channel blocking effects. Both atrial and ventricular arrhythmias, especially re-entrant and ectopic SVT and VT. Cinchonism (headache, tinnitus with quinidine), reversible SLE-like syndrome (procainamide), HF (disopyramide), thrombocytopenia, torsades de pointes due to QT interval. ■Class IB Lidocaine, MexileTine. "I'd Buy Liddy's Mexican Tacos." AP duration. Preferentially affect ischemic or depolarized Purkinje and ventricular tissue. Phenytoin can also fall into the IB category. Acute ventricular arrhythmias (especially postMI), digitalis-induced arrhythmias. IB is Best post-MI. CNS stimulation/depression, cardiovascular depression. ■ Class IC Flecainide, Propafenone. "Can I have Fries, Please." Significantly prolongs ERP in AV node and accessory bypass tracts. No effect on ERP in Purkinje and ventricular tissue. Minimal effect on AP duration. SVTs, including atrial fibrillation. Only as a last resort in refractory VT. Proarrhythmic, especially post-MI (contraindicated). IC is Contraindicated in structural and ischemic heart disease.
Accessory Pathways therapy
■ Class IA & K+ channel blockers (III)
Ca2+ channel blockers improve angina symptomsby:
■ Coronary &peripheral vasodilatation ■ Reducing contractility Degree to which above changes occur varies with types of blocker
2 major pathways int synthesis of eicosanoids from arachidonicacid:
■ Cyclo- oxygenases: which initiate the biosynthesis ofprostaglandins,prostacyclins andthromboxanes ■ Lipoxygenases: whichinitiatethesynthesis of leukotrienes,andothercompounds.
Fibrates uses
■ DOC in severe hypertriglyceridemia (TG) ■ Reasonable consideration in moderate hypertriglyceridemia. ■ As monotherapy, fibrates offer highest TG reduction, followed by niacin, w-3-fattyacids, statins, andezetimibe.
B2 Action: Vasodilation [decreased PVR/TRP]
■ Decreases PVR= decreased DBP= Decreased MAP ■ Decreased MAP is sensed by baroreceptor ==> baroreceptor will increase HR (reflex tachycardia) ■Baroreceptor "decreases firing rate" which leads to SNS activation to increase the heart rate & bring up BP
Succinylcholine
■ Depolarizing neuromuscular relaxant prototype: short duration (5 min) if a patient has normal plasma cholinesterase (genetically determined). No antidote (compare with tubocurarine). ■Implicated in malignant hyperthermia.
What is the mechanism of action of argatroban and lepirudin? How is their effect monitored?
■ Direct thrombin inhibitors (DTIs). They exert their anticoagulant effect by directly binding to the active site of thrombin. ■ Their effect is monitored with the aPTT. (intrinsic pathway)
Useful incombination with a statin in patients unable to reach their LDL goal on statin monotherapy.
■ EZETIMIBE ■ 1st non-statin drug should be considered as adjunct to statin. ■ Ezetimibe is only used as monotherapy in patients who do not tolerate statins.
Statins adverse effects
■ Elevation of aminotransferases. Usually not associated with other evidence of liver toxicity. ■ Myopathy and rhabdomyolysis. Rare. Rhabdomyolysis may cause myoglobinuria, leading to renalinjury.
H1 receptors locations
■ Endothelium, ■ Smooth muscles cells ■ Nerve endings
Prevent cholesterol absorption at small intestines brush border
■ Ezetimibe ■ AE: Rare, increase LFT, diarrhea
•IV infusion for hypertensive emergency •t1/2 = 30 min •Maintains or increases renal perfusion as lowers BP •Promotes naturesis •Safe to use in all hypertensive emergencies (particularly beneficial in patients with renalinsufficiency) Contraindications (Glaucoma)
■ Fenoldopam ■ Peripheral dopamine-1 (D1) receptor agonist ■ Evokes arteriolar dilation
Up-regulate LPL ==> Increase TG clearance Activates PPAR-alpha to induce HDL synthesis
■ Fibrates (e.g. Gemfibrozil, Bnezafibrate, Fenofibrate) ■ AE: Myopathy (increase risk with statins), cholesterol gallstones (via inhibition of cholesterol 7 alpha-hydroxylase)
BILE ACID-BINDING RESINS: ADVERSE EFFECTS
■ GI adverse effects: bloating, nausea, cramping, constipation. ■ Colesevelam produces fewer GI adverse effects than cholestyramine or colestipol. ■ May increase TG: contraindicated in hyper tryglyceridemia (TG).
H2 receptor location
■ Gastric mucosa, ■ cardiac muscle cells, ■ vascular smooth muscle ■ some immune cells
Procainamide
■ Group 1A antiarrhythmic drug prototype: short half-life, metabolized by N-acetyltransferase. ■Tox: may cause a lupus-like syndrome and torsades de pointes arrhythmia. Similar to quinidine but more cardiodepressant
Nitrates AE + Contraindications
■ Headache (cerebral vasodilation) ■ Highdoses = postural hypotension, facial flushing, reflex tachycardia ■Contraindications Sildenafil(risk of severe hypotension)
Treatment for HIT type II is a systemic hypercoagulable state
■ Heparin must be stopped and either argatroban or lepirudin must be started. ■ They are direct thrombin inhibitors (DTIs). They exert their anticoagulant effect by directly binding to the active site of thrombin.
H1 receptor activation in blood vessels
■ Histamine induced edema ■ The effect is due to separation of the endothelial cells which permits transudation of fluid and molecules into perivascular tissue. ■ This effect is responsible for urticaria (hives) that signals the release of histamine in the skin
initial therapy for deep venous thrombosis (DVT) treatment
■ IV or SC unfractionated heparin (UFH), ■SC low molecular weight heparin (LMWH) ■ SC fondaparinux
Pleotropic effects of statins
■ Improve endothelial function. ■ Decrease platelet aggregation ■ Stabilize atherosclerotic plaque. ■ Reduce inflammation.
H2 receptor influence on cardiovascular system
■ Increase contractility ■ Increase pacemaker rate
H2 receptors antagonist usage
■ Inhibitors of gastric acid secretion. ■ By competitively blocking H2 receptors, these agents reduce secretion of gastricacid. ■ Peptic ulcers: promote healing of duodenal + gastric ulcers. ■Acute stressulcers ■GERD: effective inprevention and treatment of heart-burn.
Ezetimibe MOA
■ Inhibits intestinal transport protein (NPC1L1), which takes up cholesterol from lumen. ■ Triggers acompensatory increase in cholesterol synthesis (which can be inhibited with astatin). ■ Reduced delivery of intestinal cholesterol to liver leads to upregulation of LDL receptors, which enhances LDL clearance from plasma
Niacin adverse effects
■ Intense cutaneous flush after each dose of niacin when drug is started or dose increased. ■ Pruritus, rashes, dryskin. Acanthosis nigricans. ■ Nausea and abdominal discomfort. ■Most serious adverse effects: hepatotoxicity +hyperglycemia. ■ insulin resistance can cause severe hyperglycemia. ■ Raise uric acid level and may precipitate gout
Large doses VS. Low doses of Epinephrine IV
■ Large doses of Epinephrine IV ==> Anaphylactic shock treatment Increase in BP due to: ■ B1: Increased HR and contractility/ increases CO (increases SBP) ■ A1: Vasoconstriction (increases diastolic blood pressure) Overall effect: Increased SBP and DBP= increased MAP Result of increased MAP: Reflex bradycardia ■ Low Dose of Epinephrine IV BP/MAP does not change ■ B1 activation: increases HR and contractility (increased CO) = increases SBP ■ B2 activation: decreases PVR (vasodilates)= decreases DBP ■ A1 is not very sensitive to low dose of epi so B2 predominates Overall effect: Increased SBP & Decreased DBP= No change in MAP No change in MAP= No baroreceptor reflex INCREASED HR @ LOW DOSE OF EPI
Direct effect of parasympathetic activation
■ M1 == Q == Mediates higher cognitive functions, stimulates enteric nervous system ■ M2 == I == [Dec] heart rate and contractility of atria ■ M3 == Q == [Inc] exocrine gland secretions (eg, lacrimal, sweat, salivary, gastric acid), [Inc] gut peristalsis, [Inc] bladder contraction, bronchoconstriction, [Inc] pupillary sphincter muscle contraction (miosis), ciliary muscle contraction (accommodation), [Inc] insulin release
Cyproheptadine (Periactin)
■ MOA: H1 Histamine receptor antagonist Use: adolescent migraine; weight gain in Cushing's syndrome Side effects: sedation (++), anti-cholinergic activity (+) Notes: 1st generation antihistamine, but lead compound for 2nd generation; anti-serotonin effects
Cromolyn and Nedocromil
■ Mast cell stabilizing agents that inbhit mast cell degranulation independent of stimuli present. ■ Second line (first-line is inhaled glucocorticorids) for treamtnet of allergic rhinitis and bronchial asthma.
What antihypertensives are recommended in pregnancy? [M.L. P.H.N.N]
■ Methyldopa Widely considered the first-line agent for treatment of hypertension during pregnancy. ■Labetalol Reasonable first-line drug. Widely used. Not associated with mild fetal growth restriction (unlike some other β-blockers). ■Pindolol Nonselective β-blocker with ISA. ■Nifedipine Appears safe in pregnancy. Relaxes smooth muscle: used to treat preterm contractions. ■Nitroprusside Restricted to use in cases of severe hypertension not responsive to other drugs listed. ■Hydralazine IV form is useful when treating severe hypertension due to preeclampsia/eclampsia. Long record of safe use during pregnancy.
Fibrates adverse effects
■ Mild GI disturbances. ■ Myositis. Patients with renal insufficiencymay be at risk. Rhabdomyolysis has occurred rarely. ■ Lithiasis. Fibrates increase biliary cholesterol excretion, therefore they may cause cholesterol gallstones.
Inhibit lipolysis (hormone sensitive lipase) in adipose tissue; reduces hepatic VLDL synthesis
■ Niacin (Vitamin B3) ■ AE: Red, flushed face, which is reduce by NSAID or long term use ■ HYperglycemia ■ HYperuricemia
NIACIN(vitamin B 3 ): MOA
■ Niacin increases LPL activity. ■ Inhibits lipolysis (hormone-sensitive lipase) in adipose tissue; reduces hepatic VLDL synthesis ■ Catabolic rate for HDL is decreased→ HDL increases.
Inactivation of LDL-receptor degradation, increasing amount of LDL removed from bloodstream.
■ PCSK9 inhibitors (e.g. Alirocumab, Evolocumab) ■ AE: Myalgias, Delirium, dementia, other neuro-cognitive effect
4 major statin benefit groups
■ Patients withASCVD. ■ Patients with LDL 190 mg/dL or higher. ■ Patients age 40-75 years of age with diabetes and LDL 70-189mg/dL. ■ Patients without ASCVD or diabetes with LDL 70-189 mg/dL and an estimated 10-year risk of ASCVD of 7.5% or higher.
Reactivator of AChE
■ Pralidoxime Regeneration of AChE -> Time Dependent aging requires use of 2-Pam ASAP -> *Aging* is due to hydrolysis of organophosphate and results in a phosphorylated enzyme that cannot be reversed with 2-PAM. Use: -> tx of organophosphate/AChE inhibitor poisoning This is the ONLY med that reverses both the muscarinic AND nicotinic side effects of organophosphates!!! (Atropine only reverses muscarinic side effects) "Have a Parade because your AChE is back"...weeeaak
Verapamil Contraindications
■ Preexisting depressed cardiac function or AV conduction abnormalities, ■ Use with caution in patients taking digoxin (increases digoxinlevels)
Ergot alkaloids contraindications
■ Pregnant women because the drugs may cause fetal distress and miscarriage. ■ patients with peripheral vascular disease, CAD, hypertension,and impaired hepatic or renalfunction.
Nitrates Cardiovascular Impact
■ Prevents/reverses vasospasm ■ Vasodilation ■ Improves subendocardial perfusion ■ Increased oxygen delivery ■ Reduced preload and afterload (decrease wall stress) ■ Decrease oxygen demand
Non-selective beta blockers
■ Propranolol ■ Nadolol ■ Timolol
Ranolazine adverse effects
■ QT interval prolongation (mainconcern with thisnew drug) ■ Nausea ■ Constipation ■ Dizziness
NIACIN: USES
■ Raising HDL. ■ Particularly useful in patients with combined hyperlipidemia and low HDL levels. ■ Effective in combination with statins.
Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) benefits
■ Reduce TG synthesis and increase fatty acid oxidation in liver. ■ HDL levels may modestly [inc]
The most potent statin in lowering LDL + Next most potent one
■ Rosuvastatin > Atorvastatin > Simvastatin.
hypertensive emergency
■ Severe hypertension with signs of damage to target organs (primarily the brain, cardiovascular system, and kidneys). ■Diagnosis is by BP measurement, ECG, urinalysis, and serum BUN and creatinine measurements. Treatment is immediate BP reduction with IV drugs.
Verapamil MOA
■ Slows AV conduction directly→ LOWER HR, contractility, BP & O2 demand ■ Has greater inotropic effects than dihydropyridines (weakervasodilator) ■ AdverseEffects [Constipation]
H2 effect on: Stomach
■ Stimulates parietal cells (increasing gastric hydrochloric acid production and secretion)
unstable angina treatment
■ Symptoms relieved by rest or nitroglycerin ■ In addition, therapy with nitroglycerin and beta blockers
Variant angina (Prinzmetal's angina) treatment
■ Symptoms respond to nitroglycerin & Ca2+ channel blockers ■ All available Ca2+ channel blockers appear to beequally effective. ■ Choice of drug is based on each individual patient
Bile Acid Binding Resins MOA
■ The reduction in bile acid concentration causes hepatocytes to increase conversion of cholesterol to bile acids. Consequently, intracellular cholesterol decreases. •This leads to up-regulation of LDL receptors in theliver. ■ Liver uptake of LDL increases, leading to decrease in plasma LDL levels. ■ This effect is partially offset by increased cholesterolsynthesis due to upregulation of HMG-CoA reductase.
UFH vs. LMWH [Adverse effects] [Monitoring]
■ UFH also binds endothelial cells, platelet factor 4, and platelets, leading to rather unpredictable pharmacokinetic and pharmacodynamic properties. ■ LMWH lack non-specific binding affinities of UFH, therefore they have more predictable pharmacokinetic + pharmacodynamic properties. LMWH have a predictable dose response, therefore usually their anticoagulant activity does not need to be monitored.
UFH vs. LMWH [Clearance Route]
■ UFH is cleared by renal + hepatic routes. UFH may be used instead of LMWH for hospitalized patients and for patients who have renal insufficiency or failure. ■ LMWH are cleared mainly by the renal route, and their half-life is prolonged in patients with renal failure. LMWH have a significant accumulative effect in patients with impaired renal function.
Epo prost enol(PGI2) usage
■ Used in severepulmonaryhypertension ■ To prevent platelet aggregation in dialysis machines.
BILE ACID-BINDING RESINS: USES
■ Used with statins or niacin to increase LDL reduction. ■ Drugs of choice for pregnant women and for children. ■ Little effect inindividual who completely lack functional LDLreceptors.
Nitrates - Clinical applications
■ Variant angina ■ Stable & unstable angina ■ IV nitroglycerin = unstable angina ´ heart failure ■ Nitroglycerin (sublingual orspray) =first-line therapy for treatment of acuteanginalsymptoms ■ Isosorbide mononitrate =orallyforprophylaxis (sustained release prepsavailable)
Beta Blockers Contraindications
■ Variant angina (treatedby Ca2+channel blockers or nitrates) ■ Use with caution in patients with obstructive airway disease or peripheral vascular disease and, initially at very low doses in patients with heartfailure ■ NEVER discontinue abruptly (can cause rebound hypertension orangina)
Nitrates impact on Systematic Vasculature
■ Vasodilation (venous dilation > arterial dilation) ■ Decreased venous pressure ■ Decreased arterial pressure (small effect)
3 days after starting warfarin, erythematous skin lesion, approximately 15 cm by 10 cm, was noted on D.J.'s right hip, and a similar one was noted on her left thigh; she reported intense localized pain bilaterally. What is the diagnosis for her symptoms? What is pathophysiology?
■ Warfarin induced skin necrosis (WISN), a rare, but serious adverse effect of warfarin therapy. Patients present within 3 to 6 days of the initiation of warfarin therapy with painful discoloration of the breast, buttocks, thigh, or penis. The lesions progress to frank necrosis with blackening and eschar
Warfarin induced skin necrosis (WISN) treatment
■ Warfarin is discontinued, IV heparin is started, vitamin K and fresh frozen plasma are administered. Treatment with protein C concentrates may also be helpful. These interventions are aimed at reversing the effects of warfarin quickly.
Antiarrhythmics Ca2+ channel blockers (class IV)
■ [Dec] Conduction Velocity, ■ [Inc] ERP, ■ [Inc] PR interval. ■ Prevention of nodal arrhythmias (eg, SVT), rate control in atrial fibrillation.
A 35 year old woman comes to primary care physician because of recurrent episodes of muscle weakness. she has two year history of lupus and family history of RA. She often has ptosis and diplopia at the end of day. The doctor gives her drug to test this muscle weakness, what is the most likely response in atria during this trial?
■ [Dec] cAMP (Bradycardia) Edrophonium [Anticholinesterse - increases ACh ■Historically used to diagnose myasthenia gravis (MG is now diagnosed by anti-AChR Ab test.
Phenoxybenzamine
■Alpha-blocker prototype (nonselective): irreversible action. ■Phentolamine: similar with competitive action. ■Used in pheochromocytoma. ■Tox: excess hypotension; GI distress.
How can you tell if mydriasis has been induced by the application to the eye of a sympathetic agonist or of a cholinergic antagonist?
■ cholinergic blocking (e.g. tropicamide - Mydriacyl®) ◆ Mydriasis [dilation] plus cycloplegia (loss of accommodation) by paralysis of iris sphincter and the ciliary body ◆ indications: refraction, ophthalmoscopy, therapy for iritis ■ adrenergic stimulating (e.g. phenylephrine HCl 2.5%) ◆ stimulate pupillary dilator muscles [Mydriasis], no effect on accommodation ◆ usually used with tropicamide for additive effects ◆ side effects: HTN, tachycardia, arrhythmias
Torsades de Pointes drug causing it
■ class IA (quinidine), ■ class III (sotalol), ■ phenothiazines (TCAs), ■ erythromycin, quinolones, antihistamines
Eicosanoids MOA
■ contractile effects of eicosanoidson smooth muscle are mediated by Ca2+. ■ Their relaxing effects are mediated by cAMP.
Bromocriptine and Cabergoline
■ dopamine agonists used agianst prolactinoma
Anticoagulant activity of LMWH can be monitored by measuring
■ factor Xa inhibition (anti-factor Xa activity). The aPTT cannot be used to monitor LMWH activity, because LMWH do not significantly affect the aPTT. T
Amiodarone acts primarily by blocking which channels during myocyte depolarization
■ increase AP duration, increase ERP, increase QT interval. ■ Atrial fibrillation, atrial flutter; ventricular tachycardia (amiodarone, sotalol). ■ Sotalol—torsades de pointes, excessive β blockade. ■ Ibutilide—torsades de pointes. ■ Amiodarone—pulmonary fibrosis, hepatotoxicity, hypothyroidism or hyperthyroidism (amiodarone is 40% iodine by weight), acts as hapten (corneal deposits, blue/ gray skin deposits resulting in photodermatitis), neurologic effects, constipation, cardiovascular effects (bradycardia, heart block, HF).
Gemfibrozil interactions
■ inhibits hepatic uptake of statins, thus increasing plasma concentration of statins. ■ competes for the glucuronosyl transferases that metabolize most statins. As a consequence, levels of both drugs may be increased when they are co-administered. ■ Risk of rhabdomyolysis
What happens If muscarinic effects are blocked by a muscarinic antagonist such as atropine??
■ large doses of acetylcholine produce nicotinic effects: ■Increase in blood pressure and vasoconstriction ■ These effects are due to the stimulation of sympathetic ganglia and release of epinephrine from the adrenal medulla.
•If Hexamethonium and control arrows are the SAME ways: •If If Hexamethonium and control arrows are the DIFFERENT ways:
■ no baroreceptor reflex ■ baroreceptor reflex
Cisapride (Propulsid)
■ prokinetic agent ■ Prolongs QT interval [Torsade pointe] ■ Due to serious cardiac adverse effects it is no longer generally available in theUS.
warfarin therapy be monitoring??
■ prothrombin time (PT). Monitoring is performed with prothrombin time (PT). This is a test of the integrity of the extrinsic and common pathways of coagulation. ■ Measurement of the PT is standardized, and is expressed as the International Normalized Ratio (INR) of prothrombin time in patient sample to that in a control sample, normalized for the international sensitivity index (ISI) of laboratory's thromboplastin preparation compared to World Health Organization's reference thromboplastin preparation. The therapeutic goal is an INR of 2.0 to 3.0.
inhibit conversion HMG-CoA to mevalonate (HMG-CoA reductase inhibitors), a cholesterol precursor; reduce mortality in CAD patients
■ statins ■ AE: hepatotoxicity (Increase LFT), myopathy (esp. when used with fibrates or niacin
Agents that should be avoided in treatment of cocaine toxicity in acute setting??
■ β-adrenergic antagonists ■ β-blockers result in unopposed α-adrenergic vasoconstriction, leading to further elevation in BP. ■At discharge, β -blockers should be considered for patients with coronary artery disease or left ventricular dysfunction, in certain situations.
Main Effects of Ezetimibe
■15%-20% reduction of LDL
Main Effects of Niacin
■20%-35% increase of HDL
Main Effects of w-3 Fattyacids
■20%-50% reduction of TG
GP IIb/IIIa inhibitors
■Abciximab ■Eptifibatide ■ Tirofiban MEDICALLY INDUCED Glanzmann thrombasthenia
Pralidoxime
■Acetylcholinesterase regenerator: antidote (with atropine) for organophosphate poisoning; chemical antagonist with very high affinity for phosphorus in organophosphates. T ■tox: neuromuscular weakness
Pretreat Phenoxybenzamine blocks A1 and A2. Adding isoproterenol causes Adding NE causes Adding ACh causes
■Activates B1 & B2 and we would expect and increase in HR ■Vasoconstriction at A1 is already blocked so we wont have a huge drug in BP ■Reflex tachycardia in the presents of a nonselective alpha blocker
Absolute contraindications for fibrinolytic therapy in patients with STEMI include:
■Active internal bleeding ■Prior intracranial hemorrhage ■Structural vascular lesion ■ intracranial neoplasm ■ Ischemic stroke within the past 3 months ■Suspected aortic dissection ■Closed head injury within the past 3 months
Hydrochlorothiazide
■Acts in distal convoluted tubule to block Na + /Cl − transporter; used in HTN, HF, nephrolithiasis. Chlorthalidone is similar. ■Tox: hypersensitivity reactions; increased serum lipids, uric acid, glucose; K + wasting
Norepinephrine
■Adrenoceptor agonist prototype, neurotransmitter: acts at all a adrenoceptors and b 1 adrenoceptors; used as vasoconstrictor. Causes reflex bradycardia. ■Tox: ischemia, arrhythmias, HTN.
Spironolactone
■Aldosterone receptor antagonist: K + -sparing diuretic action in the collecting tubules; used in aldosteronism, HTN, and female hirsutism (androgen receptor-blocking action). ■Tox: hyperkalemia, gynecomastia.
Prazosin
■Alpha 1 -selective blocker prototype: used in HTN and benign prostatic hyperplasia. ■Tox: first-dose orthostatic hypotension but less reflex tachycardia than nonselective a blockers.
Losartan
■Angiotensin AT 1 receptor blocker (ARB) prototype: used in HTN. Effects and toxicity similar to those of ACE inhibitors but causes less cough. ■Other AT 1 blockers: candesartan, eprosartan, irbesartan, olmesartan, telmisartan, valsartan
Nitroglycerin
■Antianginal vasodilator prototype: releases nitric oxide (NO) in veins, less in arteries, and causes smooth muscle relaxation. ■Standard of therapy in angina (both atherosclerotic and variant). ■Tox: tachycardia, orthostatic hypotension, headache.
Lovastatin
■Antihyperlipidemic: HMG-CoA reductase inhibitor prototype used for hypercholesterolemia. Acts in liver to reduce synthesis of cholesterol and indirectly increase LDL receptor synthesis. ■Other statins: atorvastatin, fluvastatin, pravastatin, rosuvastatin, simvastatin. ■Tox: hepatotoxicity (elevated enzymes), muscle damage, teratogen.
Gemfibrozil
■Antihyperlipidemic: fibrate prototype used for hypertriglyceridemia. ■ Lowers serum VLDL and triglycerides and increases HDL by activating peroxisome proliferator-activated receptor-a nuclear receptors. ■Tox: GI distress, cholelithiasis,
Methyldopa
■Antihypertensive: safe during pregnancy, a prodrug of methylnorepinephrine, a CNS-active a 2 agonist. ■Reduces SANS outflow from vasomotor center. See also clonidine. ■Tox: sedation, positive Coombs test, hemolysis.
Lepirudin
■Antithrombotic: recombinant form of a medicinal leech protein that directly inhibits thrombin; rapid onset; parenteral administration. ■Used in heparin-induced thrombocytopenia (HIT). ■Tox: bleeding; monitor with aPTT. ■Bivalirudin is similar, used for PCI. ■Argatroban is a small molecule used parenterally for PCI.
recommended initial management of STEMI [total occlusion of an epicardial vessel causes transmural infarction]
■Aspirin, O2, Nitroglycerin, Clopidogrel ■ β-blockers, Anticoagulation, ACE inhibitors, Angiotensin receptor blockers, Statins, Nonsteroidal anti-inflammatory drugs (NSAIDs)
Unlike patients with ACS unrelated to cocaine use, cocaine users should be provided with
■Benzodiazepines relieve chest pain and beneficial cardiac hemodynamic effects. ■ Resolution of anxiety with benzodiazepine will often lead to resolution of hypertension and tachycardia. ■When sedation is not successful, hypertension can be managed with sodium nitroprusside, nitroglycerin, or intravenous phentolamine.
Isoproterenol
■Beta 1 and b 2 agonist catecholamine prototype: bronchodilator, a cardiac stimulant. ■Always causes tachycardia because both direct and reflex actions increase HR. ■Tox: arrhythmias, tremor, angina
Contraindicated in treatment of hypertension associated with cocaine toxicity.
■Beta-blockers and labetalol
Examples of First Generation:
■Chlorpheniramine ■Diphenhydramine ■Dimenhydrinate ■Hydroxyzine ■Promethazine ■Meclizine ■Cycliezine
Neostigmine
■Cholinesterase inhibitor: prototype synthetic quaternary nitrogen carbamate with little CNS effect. ■Tox: excess cholinomimetic effects.
Compare and contrast the effects of direct- acting and indirect-acting cholinergic agonists on the blood vessels.
■Cholinesterase inhibitors [Indirect acting] have minimal effects on vascular smooth muscle [vascular beds lack cholinergic innervation]. ■Direct-acting agonists are able to activate non-innervated M3 receptors found in endothelium [Significant vasodilation]
H2 RECEPTOR ANTAGONISTS Examples Take H2 blockers before you dine. Think "table for 2" to remember H2 .
■Cimetidine ■Ranitidine ■Famotidine ■Nizatidine
A 65 year old man with acute coronary syndrome undergoes percutaneous coronary intervention with stenting. Before the intervention he is given aspirin, plus a prorodrug which is converted to an active metabolite by CYP2C19. Which of the following is prodrug that was he most likely given?
■Clopidogrel Inhibit platelet aggregation by irreversibly blocking ADP (P2Y 12) receptor. Prevent expression of glycoproteins IIb/IIIa on platelet surface. ■Clinical Use: Acute coronary syndrome; coronary stenting. [Dec] incidence or recurrence of thrombotic stroke. ■Adverse Effects: Neutropenia (ticlopidine). TTP may be seen.
H1 effect on extravascular smooth muscles
■Contraction of GI Tract smooth muscle ■Bronchioconstriction of bronchiole smooth muscle
M2 Action: Decreases HR and Contractility
■Decreased HR & Contractility= decreased cardiac output (CO) ■ Decreased CO= decreased SBP= MAP decreases ■ Decreased MAP is sensed by baroreceptorà baroreceptor will increase HR (reflex tachycardia)
Nitrates.. Decreases what??? Increases what??
■Decreases: Arterial pressure, EDV, ejection time ■Increases: Heart rate (reflex), Contractility (reflex)
Nifedipine
■Dihydropyridine calcium channel blocker prototype: less cardiac depression than verapamil, diltiazem; used in angina, HTN. ■Tox: constipation, headache, tachycardia, arrhythmias (avoid rapid-onset forms, that trigger reflex tachycardia). ■Others in the dihydropyridine group include amlodipine, felodipine, nicardipine
H1 RECEPTOR ANTAGONISTS: USES
■Drugs of choice for allergic rhinitis and urticaria ■Motion sickness and nausea ■ Ineffective in bronchial asthma because histamine is only one of several mediators
Nitric oxide (NO)
■Endogenous vasodilator released from vascular endothelium; neurotransmitter. ■Mediates vasodilating effect of acetylcholine, histamine, and hydralazine. ■Active metabolite of nitroprusside and of nitrates used in angina. ■Used as pulmonary dilator in neonatal hypoxia, pulmonary HTN. ■ Tox: excessive vasodilation, hypotension.
Examples of Second Generation:
■Foxofenadine ■Loratadine ■Cetirizine
Carba mates (3)
■Physostigmine ■Neostigmine ■Pyridostigmine
Metoclopramide (Reglan)
■Prokinetic agent: dopamine D 2 receptor antagonist ■Tox: restlessness, insomnia, agitation, extrapyramidal effects, elevated prolactin.
Beta- blockers are commonly used for both the acute and chronic control of ventricular rates in patients with AtrialF. Contraindications?? x3
■Given their negative inotropic effects, β-blockers should not be used to acutely control the ventricular response in patients with HF. ■Avoided in patients with bronchospasm or COPD because of their β2-blocking properties. ■In patients with diabetes mellitus blood glucose levels should be monitored more closely because beta-blockers can mask signs and symptoms of hypoglycemia (except sweating).
Sotalol Others in group: ibutilide, dofetilide.
■Group 3 antiarrhythmic prototype: blocks I K channels and b receptors. ■Used for atrial and ventricular arrhythmias. ■ Tox: torsades de pointes arrhythmias.
Seven days after admission, L.N.'s platelet count dropped by 50%, and blue discoloration of the toes was noted. What is the most likely diagnosis?
■Heparin-induced thrombocytopenia (HIT) type II, a dangerous condition with a ■mortality rate of 50%.
Used for short-term therapy in patients with intractable heart failure
■Inamrinone1, ■ Milrinone1 ■ Selective PDE-3 inhibitor. ■ In cardiomyocytes: [Inc] cAMP accumulation --> [Inc] Ca2+ influx--> [Inc] inotropy and chronotropy. ■ In vascular smooth muscle: [Inc] cAMP accumulation -->inhibition of MLCK activity --> general vasodilation.
Pretreat w/ Atropine blocks M2 and should cause tachycardia. Adding nitric oxide a vasodilator causes Adding ACh causes.....
■Increase in heart rate d/t reflex tachycardia Atropine is the pretreatment choice to block NE reflex bradycardia No tachycardia or bradycardia can occur because M2 is already blocked •Normally Acetylcholine acts on M2 to decrease heart rate as has reflex tachycardia
•B1 Action (Dobutamine): Increased HR and Contractility
■Increased HR & Contractility= Increased cardiac output (CO) ■Increases CO ==> increased SBP ==> MAP increases ■Increase MAP is sensed by baroreceptor ==> baroreceptor will decrease HR (reflex bradycardia)
Montelukast
■Leukotriene receptor blocker (especially LTD 4 ) used for prophylaxis in asthma. ■Orally active; once daily administration. ■Tox: minimal
Phenobarbital
■Long-acting barbiturate: used as a sedative and for tonic-clonic seizures. ■Facilitates GABA-mediated neuronal inhibition (by increasing duration of channel opening) and may block excitatory neurotransmitters. Partial renal clearance that can be increased by urinary alkalinization. Chronic use leads to induction of liver drug-metabolizing enzymes and ALA synthase. ■Tox: psychological and physiologic dependence; additive effects with other CNS depressants.
Furosemide
■Loop diuretic prototype: blocks Na + /K + /2Cl − transporter in thick ascending limb; high efficacy; used in acute pulmonary edema, refractory edematous states, hypercalcemia, and HTN. ■Tox: ototoxicity, K + wasting, hypovolemia, increased serum uric acid. Bumetanide and torsemide differ only in half-life.
INR > therapeutic range but < 5.0; no significant bleeding INR > 5.0 but < 9.0; no significant bleeding INR > 9.0; no significant bleeding Serious or lifethreatening bleeding
■Lower or omit dose of warfarin. If INR is only minimally prolonged, no dose reduction is required. ■Omit warfarin temporarily. Alternatively, omit warfarin temporarily and give vitamin K1 orally. ■Stop warfarin therapy and give higher dose of vitamin K1, which should reduce INR substantially in 24-48 h. Resume therapy @ lower dose when INR therapeutic. ■Stop warfarin therapy. Give vitamin K1 by slow IV infusion, plus fresh frozen plasma, prothrombin complex concentrate or recombinant factor VIIa.
Selegiline Rasagiline is similar and used more commonly.
■MAO-B inhibitor: selective inhibitor of the enzyme that metabolizes dopamine (no tyramine interactions at normal dosage). ■Used in Parkinson's disease. ■Tox: GI distress, CNS stimulation, dyskinesias, serotonin syndrome if used with selective serotonin reuptake inhibitors.
Pilocarpine
■Muscarinic receptor partial agonist prototype: ■tertiary amine alkaloid. ■May cause paradoxical hypertension by activating muscarinic excitatory postsynaptic receptors in postganglionic sympathetic neurons. ■Tox: muscarinic excess
Propranolol
■Nonselective b-blocker prototype: local anesthetic action but no partial agonist effect. ■Used in HTN, angina, arrhythmias (group 2), migraine, hyperthyroidism, tremor. ■Tox: asthma, AV block, HF
Warfarin
■Oral anticoagulant prototype: causes synthesis of non-functional versions of the vitamin K-dependent clotting factors (II, VII, IX, X). ■Measure with PT test expressed as INR. ■Tox: bleeding, teratogenic. ■Antidote: vitamin K, fresh plasma
Rivaroxaban (Xarelto) Apixaban (Eliquis)
■Oral factor X inhibitor: used for prevention of deep venous thrombosis (DVT), pulmonary embolism (PE), postsurgery, and stroke in atrial fibrillation. Fixed dose, no routine monitoring. ■Side effect: bleeding.
Malathion
■Organophosphate insecticide cholinesterase inhibitor: prodrug converted to malaoxon.. ■Other organophosphates: parathion converted to paraoxon, and the nerve gases (eg, sarin, soman).
Mannitol
■Osmotic diuretic: . ■Tox: initial expansion of extracellular fluid volume with resulting hyponatremia, headache, nausea. With continued use, dehydration and hypernatremia
Prostacyclin
■PGI 2 : endogenous prostaglandin vasodilator and inhibitor of platelet aggregation. ■ An analog, epopro-stenol, is used in primary pulmonary HTN.
Heparin vs warfarin ■Route of Administration ■Site of Action ■Onset of Action ■Mechanisms of Action ■Duration of action ■Agents for reversal ■Monitoring ■Crosses Placenta??
■Parenteral (IV, SC) vs. Oral ■Blood vs. Liver ■Rapid (seconds) vs. Slow, limited by h-f of normal clotting factors ■Activates antithrombin, which the action of IIa (thrombin) and factor Xa vs. Impairs synthesis of vitamin K-dependent clotting factors II, VII, IX, and X, and anticlotting proteins C and S ■Hours vs. Days ■Protamine sulfate vs. Vitamin K, FFP, PCC ■PTT (intrinsic pathway) vs. PT/INR (extrinsic pathway) ■No vs. Yes (teratogenic)
Recommended reperfusion strategy
■Percutaneous coronary intervention (PCI) is the preferred reperfusion method. ■Primary PCI is also associated with a lower risk of stroke than treatment with fibrinolysis.
Misoprostol
■Prostaglandin E 1 derivative: orally active prostaglandin used to prevent GI ulcers caused by NSAIDs. ■Also used with mifepristone as abortifacient. ■Tox: diarrhea.
Omeprazole
■Proton pump inhibitor prototype: ■ irreversible blocker of H + /K + ATPase proton pump in parietal cells of stomach.
A 50-year-old woman is brought to the emergency department after collapsing whilst walking. Her husband says that she had been complaining about indigestion over the past few hours. Her blood pressure is 70/40 mm Hg and her pulse is 180/min. An echocardiogram shows a wide-complex tachycardia (widened QRS) in a left bundle branch block pattern. Immediate treatment is initiated with intravenous amiodarone. Which of the following changes to the ECG are most likely to occur?
■QRS (INC) ■QT. (INC) ■ PR. (INC)
Purple Toe Syndrome
■Rare adverse effect that typically occurs 3 to 8 weeks after the initiation of warfarin therapy. Patients initially present with painful discoloration of the toes that blanches with pressure and fades with elevation. ■ The pathophysiology of this syndrome has been related to cholesterol microembolization from atherosclerotic plaques, leading to arterial obstruction. ■Because cholesterol microembolization has been associated with renal failure and death, warfarin therapy should be discontinued in patients who develop purple toe syndrome.
Loratadine
■Second-generation H 1 antihistamine: used in hay fever. ■Tox: much less sedation than first-generation antihistamines; no ANS effects. Others: desloratadine, cetirizine, fexofenadine.
What fibrinolytics are recommended for reperfusion?
■Streptokinase, alteplase, tenecteplase, and reteplase are approved by FDA for IV use in patients with STEMI. ■act by promoting the conversion of plasminogen to plasmin, which subsequently lyses fibrin thrombi.
Al.prost.adil (PGE1) usage
■To maintain patency of ductus arteriosus. ■Vasodilation; used in male impotence
Sumatriptan (5-HT 1B/1D agonists) A sumo wrestler trips and falls on your head.
■Triptans are 1st-line therapy for acute severe migraine attacks. Adverse Effects ■Triptans may cause coronary vasospasm (contraindicated in patients with CAD or Prinzmetal angina), ■ Mild paresthesia, ■ Serotonin syndrome (in combination with other 5-HT agonists).
•A1 action (Hydralazine): Vasoconstriction
■Vasoconstriction= Increased PVR/TPR ■Increase PVIR= increased DBP= MAP ■ Increase MAP is sensed by baroreceptor ==> baroreceptor will decrease HR (reflex bradycardia)
Antiarrhythmics K+ channel blockers (class III)
■[Inc] AP duration, ■[Inc] ERP, ■ [Inc] QT interval ■ Atrial fibrillation, atrial flutter; ventricular tachycardia
Ergonovine and Ergotamine
■cause prolonged vasoconstriction and uterine contraction. ■Used in migraine and obstetrics. Tox: vasospasm (including coronaries)
Treatment rationale of angina
■•Increase oxygendelivery •Coronaryvasodilators •Anti-thrombotic drugs ■Decrease oxygen demand •Vasodilators (reduce afterload & preload) •Cardiac depressants (reduce heart rate & contractility)