Drugs COPY

Question 1

How do the M odd receptors work?

Answer 1

M1, 3, & 5 (M_odd): ­increased intracellular Ca²⁺ (G_q)

• Activation results in stimulation of phospholipase C → PIP2 hydrolysis to IP3 (which acts on SR to increases [Ca²⁺]_i) + DAG → DAG activates PKC to open Ca²⁺ channels on sarcolemma
• ­increased intracellular Ca²⁺ increases muscle contraction via MLCK

Question 2

How do the M even receptors work?

Answer 2

M2 & 4 (M_even): hyperpolarizes the cell (G_i)

activation results in inhibition of cAMP synthesis → causes K⁺ efflux which hyperpolarizes the cell

Question 3

How can adrenergic transmission be terminated?

Answer 3

Termination of Adrenergic Transmission:

• Reuptake: accounts for about 60%. NE, EPI transported back into nerve terminal. Inhibited by cocaine and drugs used for depression
• Diffusion: accounts for about 20%. NE, EPI diffuse away from synaptic cleft
• Metabolism: accounts for 20%. NE, EPI metabolized to inactive compounds (COMT & MAO)

Question 4

How do alpha1 receptors work?

Answer 4

a₁: increased ­intracellular Ca²⁺(G_q) by increased DAG and IP3

• Vasoconstriction (BP increased­)
• On smooth muscle of vessels, eye, and GI/urinary sphincters
• Smooth muscle contraction by stimulating phospholipase C and Ca²⁺

Question 5

What do alpha 2 receptors do?

Answer 5

a₂: decreased cAMP (G_i), decreased Norepinephrine release (autoreceptor)

• presynaptic nerve terminals and modulate nerve activity
• inhibit cAMP synthesis; inhibits neuron activity by causing K+ efflux which hyperpolarizes the cell

Question 6

What do beta 1 receptors do?

Answer 6

b₁: increased ­cAMP (G_s), ­increased HR, ­increased Myocardial contractility

• Found in heart; activation leads to increased ­contraction increased heart rate; causes renin secretion and lipolysis
• coupled to Gproteins; increases ­adenylyl cyclase and cAMP

Question 7

What do beta 2 receptors do?

Answer 7

b₂: ­increased cAMP (G_s),

• Vasodilation (non-innervated b2) lowering BP, bronchodialation
• located on most tissues; activation leads to relaxation of smooth muscle (uterus, GI, bladder)
• ­increased cAMP → activates PKA → phosphorylates MLCK, preventing it from phosphorylating myosin → decreases contraction

Question 8

What do beta 3 receptors do?

Answer 8

b₃: ­increased cAMP (G_s), ­increased lipolysis

• least defined, but present on adipocytes; cause lipolysis coupled to Gproteins; ­increased adenylyl cyclase and cAMP

Question 9

What are the side effects for muscarinic agonists?

Answer 9

Muscarinic Agonists:

• Overall: “SLUD” (salivation, lacrimation, urination, defication) + hypotension / bronchoconstriction
• Eyes: pupillary constriction (miosis)

Question 10

What are the side effects for muscarinic antagonists?

Answer 10

Muscarinic Antagonists:

• “Red as a beet, dry as a bone, blind as a bat, and mad as a hatter” (opposite of SLUD)
• Eyes: mydriasis (relaxation causes wide pupils) and dry eyes

Question 11

List some muscarinic agonists and antagonists and what are they used for?

Answer 11

Agonist: muscarine, nicotine, varenicline

Antagonist: atropine (treat bradyarrhythmias), ipratropium/tiotropium (treat asthma/COPD)

Question 12

For Norepinephrine:

• What is the receptor specificity?
• What effect does it have/what is it used for?

Answer 12

• alpha1 = alpha2 > beta1 > beta2
• increases blood pressure

Question 13

For Epinephrine:

• What is the receptor specificity?
• What effect does it have/what is it used for?

Answer 13

• beta1 = beta2 > alpha1 = alpha2
• increases HR

Question 14

How does the reflex response occur for norepinephrine?

Answer 14

alpha1 and alpha2 stimulation causes BP to increase, causing baroreceptors to fire more, decreasing CNS response, leading to decrease in HR…beta1 stimulation causes increase in HR… overall neutral response

Question 15

List some of the alpha1 agonists (3).

Answer 15

Phenylephrine, midodrine, methoxamine

Question 16

For Phenylephrine, midodrine, methoxamine:

• What action do they have?
• What receptor do they act on?

Answer 16

Vasoconstriction leading to increased ­ BP

alpha1

Question 17

How does the phenylephrine reflex response with baroreceptors work?

Answer 17

alpha1 stimulation causes BP to increase, causing baroreceptors to fire more, decreasing CNS response, leading to decrease in HR… overall decreased HR

Question 18

What is the mechanism of action of psuedoepherine? What does it lead ot?

Answer 18

Vasoconstriction leading to ­increased BP

• INDIRECT AGONIST: Stimulate release of pre-formed catecholamines, indirectly stimulating alpha1 receptor

Question 19

List two alpha2 agonist drugs.

Answer 19

Clonidine and Methyldopa

Question 20

How does clonidine work?

And what receptor does it act as an agonist for?

What happens if the drug is stopped abruptly?

Answer 20

• Alpha 2
• Blocks synthesis of catecholamines and hyperpolarizes cell to prevent depolarization
• Chronic low [NE] release leads to upregulation of alpha 1 receptors (post-synaptic)
• If drug is stopped abruptly, can lead to hypertension crisis because upregulated post-synaptic receptors will pick up the catecholamines that are being released

Question 21

• How does methyldopa work?
• What are some physiological effects related to this drug?

Answer 21

• PRODRUG analog precursor that is metabolized by the same enzymes as dopamine
• Displaces norepiphrine and dopamine synthesis because it uses same enzymes.
• Has higher affinity for receptor than NE, giving rise to negative feedback preventing synthesis of NE
• Parkinsonian symptoms (tremors)

Question 22

For Isoproterenol:

• what is the receptor specificity?
• What are the basic effects?

Answer 22

• Beta1 = Beta2
• Decreased BP and increased HR

Question 23

How does the basoreceptor reflex work for isoproterenol?

Answer 23

beta2 stimulation causes BP to drop, causing baroreceptors to fire less, allowing CNS to reflexively increase HR…beta1 stimulation causes increase in HR… overall HR is doubly increased

Question 24

• What receptor does dobutamine work on?
• What effect does dobutamine have?
• What occurs with chronic use of beta agonists?

Answer 24

• Beta1
• Increases HR
• Chronic use of beta-agonists will lead to downregulation of receptors

Question 25

How does the basoreceptor reflex work for dobutamine?

Answer 25

Beta1 stimulation causes no change to BP, causing no response by baroreceptors… overall HR increase

Question 26

* What receptor does albuterol (short-acting)/salmeterol (large-acting) work on? * What effect does it have? * What are some physiological effects?

Answer 26

* beta2 * decreased BP; Vasodilation and bronchodialation * Increased blood flow due to smooth muscle relaxation causes hyperglycemia and tremors

Question 27

Name three alpha antagonists.

Answer 27

Phentolamine Phenoxybenzamine Praz**_osin_**

Question 28

For Phentolamine: * IV or oral? Fast or slow? * What is the receptor specificity? * What is its MOA? * What is it used for? * What is a big side effect of the drug?

Answer 28

* IV and short acting (QUICK) * alpha1 = alpha2 ANTAGONIST * MOA: Competitive inhibitor * Hypertensive crisis * Reflex tachycardia due to resulting decreasing BP

Question 29

For Phenoxybenzamine: * IV or oral? Fast or slow? * What is the receptor specificity? * What is its MOA? * What is it used for? * What is a big side effect of the drug?

Answer 29

* Irreversible non-competitive inhibitor * Oral - slow * alpha 1 = alpha 2 ANTAGONIST * MOA: irreversible noncompetitive inhibitor * Use: Hypertensive crisis * Reflex tachycardia due to resulting decreased BP.

Question 30

For Praz**_osin**_ and any other _**-osin_** drugs: * What is the receptor specificity? * What is the use? * What is a possible side effect

Answer 30

* Alpha1 Antagonist * Used for prostatic hypertrophy * Reflex tachycardia

Question 31

Name 4 beta antagonists.

Answer 31

Propanolol Metoprolol Labetolol Carvedilol

Question 32

For propanolol: * What is the receptor specificity? * What are some possible physiological effects (2)? * What are some side effects?

Answer 32

* Beta 1 = beta 2 antagonist * Effects * Negative inotropic (contractility) and chronotropic (HR) actions * Blocks renin release * Side Effects * Slows AV node firing * Crosses blood brain barrier - CNS effects (vivid dreams, depression, decreased libido) * Inhibits glycogenolysis * Vasoconstriction * Bronchoconstriction

Question 33

* What receptor blockage is specific for slowing of AV conduction? * What receptor blockage is specific for inhbiting glycogenolysis? * Bronchoconstriction? * Vasoconstriction?

Answer 33

* slowing of AV conduction: **Beta1** * inhibition of glycogenolysis: **Beta2** * Bronchoconstriction: **Beta2** * Vasoconstriction: **Beta2**

Question 34

For metoprolol: * What is the receptor specificity? * What is it used for? * What is a physiological effect?

Answer 34

* Beta1 selective Antagonist (little beta2 activity) * Slows HR and therefore cardiac output is decreased * Bradycardia

Question 35

For Labetolol and Carvedilol: * What is the receptor specificity? * What is it used in? * Is there a reflex tachycardia present? Why or why not?

Answer 35

* Beta1 = beta2 \> alpha1 = alpha2 antagonist * used in hypertensive crises and in heart failure * Does NOT have reflex tachycardia because beta1 is blocked

Question 36

How are most beta blockers excreted and why is this important?

Answer 36

Most beta blockers are excreted via the liver, making it likely that they have drug interactions due to biotransformation by P450 enzymes.

Question 37

Outline the process from the baroreceptors to renin to aldosterone release.

Answer 37

Question 39

With aldosterone release or inhibition, how can you get hyperkalemia? * Outline what occurs to Na+, H2O, K+ with Aldosterone. * Without aldosterone?

Answer 39

* Normal: with aldosterone → increased expression of Na+ and Na+/K+ ATPase channels * Abnormal: without aldosterone → decreased expression of Na+ and Na+/K+ ATPase channels → excretion of Na+ and retention of K+ and H+ → hyperkalemia and metabolic acidosis

Question 40

What 5 things causes renin release?

Answer 40

* Renin release is stimulated by: * Sympathetic activation * Low pressure in renal vasculature * Sodium diuresis * Decreased blood volume * Decreased renal blood flow

Question 42

In the renin-angiotensin-aldosterone system, what are the 4 classes of drugs used to reduce BP?

Answer 42

* Angiotensin Converting Enzyme (ACE) Inhibitors * Angiotensin Receptor Blockers (ARBs) * Direct Renin Inhibitors * Aldosterone Receptor Antagonists

Question 43

For Angiotensin Converting Enzyme (ACE) Inhbitors: * What are three important drugs to know? * What is the MOA? * What is a secondary MOA that occurs with ACEI's? * What are three side effects? * What are 5 main advantages?

Answer 43

* Lisino**_pril**_, Enala_**pril**_, Capto_**pril_** * MOA: Prevents conversion of ATI to ATII, reducing peripheral resistance (ATII causes vasoconstriction) * Bradykinin (vasodilator) is inactivated via ACE * ACEI: by blocking ATII synthesis and bradykinin inactivation, you get a double whammy of decreasing BP * Side Effects: * Cough/angioedema * Decreases renal function * Hyperkalemia *

Question 44

For Angiotensin Converting Enzyme (ACE) Inhbitors: * What are three side effects? * What are 5 main advantages?

Answer 44

Lisinopril, Enalapril, Captopril * Side effects * Cough/angioedema * Decreases renal function * Hyperkalemia * Advantages * No effects on HR * No reflex actions of the sympathetic nervous systme * Prevents stroke * Beneficial in HF * Slow progression of kidney disease

Question 45

For Angiotensin Receptor Blockers: * What are three drug names? * MOA? * What are two side effects? * What is the main advantage?

Answer 45

* Lo**_sartan_**, Val**_sartan_**, Olme**_sartan_** * MOA * angiotensin I receptor inhibitors * antagonizes angiotensin II through actions at angiotensin I receptor * Side Effects * decreased renal funtion * hyperkalemia * Advantage * Better tolerated than ACE inhbitors * Less likely to cause cough/angioedema

Question 46

For direct renin inhbitor: * What is a drug? * What is the MOA? * What are three side effects? * What is a minor advantage?

Answer 46

* _Drug_: Aliskiren * _MOA_: inhibits renin * _Side effects_: diarrhea, cough, angioedema * _Advantage_: Can be tolerated better

Question 47

For aldosterone receptor antagonists: * Name two drugs. * What is the MOA? * What are three side effects? * What is an advantage of one of the drugs compared to the other?

Answer 47

* Spironolact**_one_**, epleren**_one_** * _MOA**:**_ Inhibits aldosterone receptor → increases Na+ excretion (and H2O) and conserves K+ * _Side Effects:_ * For Spironolactone: Hyperkalemia, Metabolic acidosis, sexual dysfunction * Advantage of Eplerenone: ONLY hyperkalemia

Question 48

All renin, angiotensin, aldosterone system drugs are contraindicated in what two situations and why?

Answer 48

All drugs are contraindicated in: * Renal artery stenosis (because it blocks ATII from causing vasoconstriction → decreases perfusion pressure through glomeruli) * Pregnancy

Question 49

In the renin, angiotensin, aldosterone system drugs: What are the two main prodrugs to know and what class of drug are they? * What is different about prodrugs?

Answer 49

* Enala**_pril_**: ACE Inhibitor * Olme**_sartan_**: ARB (Angiotensin receptor blocker) Must be metabolized before and therefore has a shorter half-life

Question 50

Hydrachlorothiazide/chlorthialidone MOA?

Answer 50

MOA * Inhibit Na+/K+/Cl-/H+ reabsorption in the distal tubule by inhibiting Na+/Cl- symporter → increased excretion of water → lowers BP * Stimulates Ca++ reabsorption

Question 51

Hydrachlorothiazide/chlorthialidone Side Effects?

Answer 51

* Hypokalemia * Glucose intolerance (lower K+ → less depolarization → less insulin release) * Gout * Metabolic alkalosis

Question 52

Triamterene MOA? Side Effects?

Answer 52

MOA * Inhibits sodium reabsorption through ion channels Side Effects * Hyperkalemia * Acidosis

Question 53

Dihydropyridines Nife**_dipine**_, amlo_**dipine_** MOA? Side Effects?

Answer 53

MOA * Causes relaxation of vessels (used for angina, Raynaud’s phenomenon) Side Effects * Peripheral edema * Gingival hyperplasia

Question 54

Non-dihydropyridines: Verapamil, diltiazem MOA? Side Effects?

Answer 54

MOA * Blocks main depolarizing ion in SA and AV nodes to decrease contractions Side Effects * * Contraindicated in patients with HF and conduction defects/SA node arrest Inhibit P450s

Question 55

Non-dihydropyridines: Verapamil, diltiazem MOA? Side Effects?

Answer 55

MOA * Blocks main depolarizing ion in SA and AV nodes to decrease contractions Side Effects * * Contraindicated in patients with HF and conduction defects/SA node arrest Inhibit P450s

Question 56

Hydralazine MOA? Side Effects?

Answer 56

MOA * Relaxes smooth muscle in vasculature to decrease total peripheral resistance * Used in resistant hypertension Side Effects * Lupus-like syndrome

Question 57

Nitroprusside (IV) MOA? Side Effects?

Answer 57

MOA * * Relaxes smooth muscle in vasculature to decrease total peripheral resistance * Prodrug = NO and cyanide Used in hypertensive crises because fast-acting Side Effects * Cyanide toxicity

Question 58

Drug interactions with diuretics

Answer 58

NSAIDs and Steroids cause Na+ retention

Question 59

Why aren’t loop diuretics a first-line choice for hypertension?

Answer 59

Because they must be give 2x daily due to short duration of activity and activation of RAAS

Question 60

Statins MOA Side effects Utility

Answer 60

* MOA: HMG-CoA Reductase inhibitor; thereby increasing LDL clearance * Adverse effects: Myalgias and rhabdomyolysis (muscle breakdown) * Utility: Primary and secondary prevention

Question 61

What is your body's reflex to long term statin use

Answer 61

* Reflex: compensation for statin therapy * GI cholesterol absorption increases * Cellular production of HMG CoA reductase increases * The PCSK9 gene is activated

Question 62

Ezetimibe ## Footnote MOA

Answer 62

* MOA: inhibits cholesterol transport into enterocytes * When given with statins, Ezetimibe has a better effect on preventing CV events

Question 63

Bile acid sequestrants (i.e. Cholesevalam, Choleystyramine) MOA?

Answer 63

* MOA: inhibit bile acid reabsorption in the ileum → more bile is secreted → more LDL is secreted → lower LDL

Question 64

Plant stanols/sterols MOA?

Answer 64

MOA: lowers reabsorption of LDL

Question 65

PCSK-9 inhibitors (Evolocumab) MOA? Drawbacks?

Answer 65

MOA: monoclonal antibodies that bind to PCSK9 → inhibiting LDL receptor degradation → increasing LDL resorption into cells for degradation Negative: $$$$$

Question 66

Explain Unusual therapies for homozygous FH (HoFH) * Lomitapide * Mipomersen * LDLpheresis

Answer 66

* Lomitapide * MOA: blocks the apolipoprotein B from attaching to VLDL * Mipomersen * MOA: blocks the loading of triglycerides on apolipoprotein B * LDLpheresis * MOA: dialysis that removes LDL from your blood

Question 67

For nitroglycerin: * What is the class? * What are the methods of intake and what effects do they have? * What is the mechanism of action?

Answer 67

* Class: Nitrate * Can take sublingually, po, or IV * PO/SL both work on veins * IV works on coronary arteries (hence the Nitro drip post-MI) * MOA: Nitrates → NO @ vessel walls → stimulates guanylate cyclase → produce cGMP → dephosphorylating of MLC → venodilation → decreases preload * REQUIRE THIOL FOR ACTIVATION

Question 68

For nitroglycerin: * What are some side effects? * What are contraindications to worry about?

Answer 68

* Side Effects: * Hypotension with reflex tachycardia * Tolerance can develop * Contraindications * Keep in glass bottle (reacts with plastic) * No Viagra * Inhibits PDE 5, which allows for no way to terminate action of cGMP, causing it to accumulate → fatal hypotension

Question 69

For isosorbide mononitrate: * What is the method of ingestion? * What class is this drug? * What is the MOA? * What are some side effects? * What is a contraindication?

Answer 69

* Ingested po * Class: Nitrate * MOA: NO @ vessel walls → stimulates guanylate cyclase → produce cGMP → dephosphorylating of MLC → venodilation → decreases preload * Completely bioavailable – no need for metabolism * Side Effects: * Hypotension with reflex tachycardia * Tolerance can develop * Contraindications: * No Viagra * Inhibits PDE 5, which allows for no way to terminate action of cGMP, causing it to accumulate → fatal hypotension

Question 70

For -olol drugs: * What class are these drugs? * What is their MOA? * What are some side effects? * Who are they indicated in?

Answer 70

* Beta-blockers * MOA: * Act on beta adrenergic receptors in SA/AV node and vessels * Decreases HR, contractility, BP (Increasing O2 delivery by increasing diastolic time) * Side Effects * Hypotension * Beta2 blockage is bad for several reasons: * Inhibits glycogenolysis (beta 2) * Vasoconstriction * Bronchoconstriction * Indicated in people with cardiac conditions

Question 71

For -DHP drugs: * What class are these drugs? * What is their MOA? * What are some side effects? * Who are they contraindicated in?

Answer 71

* Calcium channel blockers * MOA: Works at vessels: blocks Ca2+ from entering cell → blocking constriction of smooth muscles in vessels → arteodilation * \*decreases afterload * Side Effects: hypotension * Contraindicated in: patients taking beta blockers

Question 72

For non-DHP drugs: * What class are these drugs? * What is their MOA? * What are some side effects? * Who are they contraindicated in?

Answer 72

* Class: calcium channel blockers * MOA: Works at SA/AV nodes: blocks Ca2+ from entering cells → slows contraction of heart → decreased HR * Side Effects: hypotension * Conraindicated in people taking beta blockers

Question 73

For Ranolazine: * What class are these drugs? * What is their MOA? There are two. * Side effects? * Contraindications?

Answer 73

* Class: Metabolic modifier (used for patients with angina) * MOA: 1. Inhibits late sodium currents → decreased Ca channel activation → therefore decrease Ca2+ in the cell → less diastolic stress → improved coronary blood flow 2. Partial fatty oxidation inhibitor → tissues switches to glucose metabolism → creates more ATP 3. \*prolongs QT interval * Side Effects: Dizziness, headaches, nausea * Contraindications: Metabolized by P450s

Question 74

For aspirin: * What is the class? * What is the MOA? * What are some side effects? * What are some contraindications?

Answer 74

* Class: Platelet Aggregation * MOA: Irreversibly inhibits COX-1/2 → reduces TXA → prevents platelet aggregation * \*COX-1 found in platelets * Side Effects: GI bleeding/GI irritation * Contraindications: Patients taking NSAIDS

Question 75

For clopidogrel: * What is the class? * What is the MOA? * What are some side effects? * What are some contraindications?

Answer 75

* Class: Platelet aggregation * MOA: _Prodrug_ that inhibits to the P2Y (ADP receptor) → allows for Prostacyclin to have anti-platelet activity * Side Effects: rash diarreah, bleeding * Contraindication: metabolized by CYP540

Question 76

For Tenecteplase: * What is the class? * What is the MOA? * In what time period should it be administered following an MI? * What are some side effects? * What are some contraindications?

Answer 76

* Class: Thrombolytic: * MOA: Binds to fibrin at clot site → activating plasminogen → degrades fibrous clot * Administer within 70 minutes * Side Effects: Bleeding Thrombocytopenia, allergy/hypotension/fever * Contraindicated: patients with active bleeding

Question 77

Quineidine Type? MOA? Effects? Use? Adverse Effects?

Answer 77

**Type:**Ia **MOA:**Na+ channel blocker and K+ rectifier channel blocker **Effects:** * Prolonged Phase 0 depolarization and prolonged Phase 3 repolarization * QT and QRS prolongation * Raises depolarization threshold **Use**: Historic drug for reentrant arrhythmias **AE:** * QT prolongation – Torsades de Pointes * Anticholinergic properties * Cinchonism – tinnitus, dizziness, blurred vision, headache,

Question 78

Flecainide Type? MOA? Effects? Use? Adverse Effects?

Answer 78

**Type:**Ic **MOA:** Na+ channel blocker (potent) **Effects:** * AV Node: prolonged refractory period * Atrial, ventricular, Purkinje fibers: prolonged Phase 0 with no change in refractory period * Raises depolarization threshold **Use**: * Ventricular arrhythmias * AFIB * Paroxysmal supraventricular arrhythmias **AE:** * Metallic taste * Visual disturbances

Question 79

Beta Blockers Type? MOA? Effects? Use? Adverse Effects?

Answer 79

**Type:** II **MOA:** Blocks beta-adrenergic receptors **Effects:** * Slows conduction velocity * Decreases automaticity, thus increasing PR interval (due to slowed AV conduction) **Use**: * Atrial tachycardia because slows conduction at AV node * Ca++ dependent arrhythmias at AV and SA nodes **AE:**

Question 80

Amiodarone Type? MOA? Effects? Use? Adverse Effects?

Answer 80

**Type:** III **MOA:** Blocks Na+, Ca++, and K+ channels **Effects:** * Delay repolarization (prolonged QT interval) **Use**: * Sustained life-threatening arrhythmias **AE:** * Thyroid issues * “Smurfism”

Question 81

Sotalol Type? MOA? Effects? Use? Adverse Effects?

Answer 81

**Type:** III **MOA:** Blocks K+ channels and beta-blocker **Effects:** * Delay repolarization (prolonged QT interval) **Use**: * Atrial and ventricular tachycardia **AE:** * Bradycardia, bronchospasm

Question 82

Dofetilide Type? MOA? Effects? Use? Adverse Effects?

Answer 82

**Type:** III **MOA:** Blocks K+ channels **Effects:** * Delay repolarization (prolonged QT interval) **Use**: * Continuing atrial tachycardia after ablation **AE:** * QT prolongation – contraindicated for hypokalemia

Question 83

Non-DHP CCBs (verapamil and diltiazem) Type? MOA? Effects? Use? Adverse Effects?

Answer 83

**Type:** IV **MOA:** Blocks calcium channels at SA and AV nodes **Effects:** * Prolonged Phase 0 depolarization in nodal tissue * Prolonged QT interval **Use**: * AFIB **AE:** * Bradycardia * Hypotension

Question 84

Digoxin MOA? Effects? Use? Adverse Effects?

Answer 84

**MOA:** Blocks Na+/K+ ATPase **Effects:** * Increases vagal activity * Slows AV conduction **Use**: * AV reentrant arrhythmias * Chronic AFIB **AE:**

Question 85

Adenosine MOA? Effects? Use? Adverse Effects?

Answer 85

**MOA:** Blocks Ca++ channels at SA and AV nodes **Effects:** * Prolonged QT interval because prolonged Phase 0 depolarization **Use**: * Acute reentrant supraventricular tachycardia **AE:** * Bronchospasm

Question 86

How do you treat Stage A HF?

Answer 86

* Stage A: High risk for developing HF * **Treatment:** * **Treat risk factors (i.e. HTN, smoking, cholesterol, alcohol)**

Question 87

How do you treat Stage B HF?

Answer 87

* Treatment used for A: * Treat risk factors (i.e. HTN, smoking, cholesterol, alcohol) PLUS * **Treatment for B:** * **ACEI (indicated in PMHx of MI or decreased EF)** * **Beta-blockers (indicated in recent MI)** * **ICD** * **Digoxin: reduces progression of HF**

Question 88

How do you treat stage C HF?

Answer 88

Treatment used for A: * Treat risk factors (i.e. HTN, smoking, cholesterol, alcohol) PLUS Treatment for B: * ACEI (indicated in PMHx of MI or decreased EF) * Beta-blockers (indicated in recent MI) * ICD * Digoxin: reduces progression of HF PLUS * **Treatment for C** * **Hydralazine-Isosorbide Dinitrate Combo (balanced vasodilator)** * **Biventricular Pacing/Cardiac Revascularization Therapy (CRT): device placed that stimulates ventricular contraction at same time** * **Indicated in QRS ≥ 120ms and LVEF ≤ 35%** * **Neprilysin inhibitor**

Question 89

How do you treat Stage D HF?

Answer 89

Treatment used for A: * Treat risk factors (i.e. HTN, smoking, cholesterol, alcohol) PLUS Treatment for B: * ACEI (indicated in PMHx of MI or decreased EF) * Beta-blockers (indicated in recent MI) * ICD * Digoxin: reduces progression of HF PLUS Treatment for C * Hydralazine-Isosorbide Dinitrate Combo (balanced vasodilator) * Biventricular Pacing/Cardiac Revascularization Therapy (CRT): device placed that stimulates ventricular contraction at same time * Indicated in QRS ≥ 120ms and LVEF ≤ 35% * Neprilysin inhibitor PLUS * **Treatment/Care for stage D:** * **Surgical therapy: cardiac transplantation, valve repair/replacement** * **Drugs** * **Palliative care**

Question 90

For ACEi, ARB, Aldosterone Antagonists in HF: * What MOA/effect do they have? * What is the rationale of that effect? * What are side effects? * Can you combine ACEI and ARBs?

Answer 90

* What effect do they have? * Balanced vasodilators (dilate arteries and veins both) * What is the rationale of that effect? * Reduces BP * Decreases preload and afterload → reduces myocardial oxygen demand * Limits remodeling (aldosterone) * What are side effects? * Monitor potassium, especially if combining! * CANNOT COMBINE ACEI AND ARBs

Question 91

For Hydralazine/Isosorbide (combo drug), in HF: * What MOA/effect do they have? * What is the rationale of that effect?

Answer 91

MOA: * Hydralazine: vasodilates arteries * Isosorbide: vasodilates veins Rationale * Reduces BP * Decreases preload and afterload → reduces myocardial oxygen demand * Limits remodeling (aldosterone)

Question 92

For Nitroprusside, in HF: * What MOA/effect do they have? * What is the rationale of that effect?

Answer 92

MOA: * Balanced vasodilators (arteries and veins) Rationale: * Reduces BP * Decreases preload and afterload → reduces myocardial oxygen demand * Limits remodeling (aldosterone)

Question 93

For beta blockers (Metoprolol succinate, Carvedilol, bisoprolol), in HF: * What MOA/effect do they have (Acutely and chronically)? * What is the rationale of that effect?

Answer 93

MOA * Acute: decreases contractility and HR * Chronic: increases contractility (due to up-regulation of beta receptors) Rationale * In HF, beta receptors are down-regulated due to chronic compensatory sympathetic stimulation * Beta blockers can up-regulate beta receptors à resulting in increased contractility

Question 94

For loop diuretic like Furosemide, in HF: * What MOA/effect do they have? * What is the rationale of that effect? * What are the side effects of this drug?

Answer 94

*_**\*\*PNEUMONIC ALERT BIATCHES: Furosemide (FURY has no wrath aka potent)\*\***_* MOA: * Inhibits sodium reabsorption at the Loop of Henle blocking Na/K/Cl Rationale * Reduces BP – works well in renal failure * More potent, helps with edema Side Effect * Dehydrating * Hypokalemia * Hyperuricemia * Ototoxicity

Question 95

For digoxin, in HF: * What MOA/effect do they have? LONG * What is the rationale of that effect? * What are the side effects of this drug? * How do you treat digoxin toxicity? TWO WAYS

Answer 95

MOA: * Blocks Na/K ATPase → resulting in greater driving force for Na/Ca exchanger → increased intracellular Ca * Positive Inotrope * Hypokalemia – increases effectiveness (risk Digoxin toxicity) * Hyperkalemia decreases effectiveness Rationale * Increase in contractility → Increase SV and CO → leads to increased reflex vagal tone → reduce O2 demand Side Effects * Chromatopsia * Drug Interaction: * Diuretics * P-glycoprotein inhibitors * Quinidine, Verapamil * Tx toxicity: w/ potassium or Digibind

Question 96

For dobutamine, in HF: * What MOA/effect do they have? * What is the rationale of that effect? * What are the side effects of this drug?

Answer 96

MOA * Beta-1 agonist Rationale * Increases SV by increasing contractility Side Effects * Tachycardia, arrhythmias, angina, myocardial ischemia

Question 97

For dopamine, in HF: * What MOA/effect do they have? * Specifically for Low dose, intermediate dose, high dose! * What is the rationale of that effect? * What are the side effects of this drug?

Answer 97

Dobutamine and dopamine are similar in MOA, Rationale, and Side Effects MOA * Low dose: stimulate dopamine receptors to vasodilate (Ehhh) * Intermediate dose: stimulate beta-1 receptors (GOOD) * High dose: stimulate alpha-1 receptors (BAD) Rationale * Increases SV due to increased contractility Side Effects * Tachycardia, arrhythmias, angina, myocardial ischemia

Question 98

For Milirinone, in HF: * What MOA/effect do they have? * What is the rationale of that effect? * What are the side effects of this drug?

Answer 98

MOA * Increase cAMP by phosphodiesterase-3 → activation of Ca channels → positive inotrope Rationale: * Vasodilation → decrease BP, preload, afterload Side Effects * Teratogenicity, hypotension, hyperkalemia

Question 99

Fluticasone Budesonide Class, MOA, Use, AE

Answer 99

Class:Glucocorticoid MOA:Acts as a nuclear transcription factor to antagonize mucous production and inflammatory mediators Use: Prophylaxis, Upregulation of beta receptor AE: * Thrush (can avoid with water) * Change in vocal chords (can avoid with water) * Decrease in bone density * Abruptly stopping drug is bad because cortisol inhibits HPA

Question 100

Cromyln Class, MOA, Use, AE

Answer 100

Class:Mast cell inhibitor MOA:Stabilize plasma membrane of mast cells and basophils and eosinophils to prevent degranulation and release of histamine and leukotrienes Use: Prevents degranulation and release of histamine and leukotrienes AE: * Well Tolerated

Question 101

Montelukast Class, MOA, Use, AE

Answer 101

Class:Leukotriene modifiers MOA:Acts on leukotriene receptors C4, D4, E4, decreasing LT effect on Gq receptors Use: Decreases bronchoconstriction AE: * Well Tolerated

Question 102

Albuterol (short-acting) Salmeterol (long-acting) Class, MOA, Use, AE

Answer 102

Class:Beta-2 agonists MOA:Beta-2 agonist Use: Bronchodilation AE: * Tachycardia

Question 103

Theophylline, caffeine Class, MOA, Use, AE

Answer 103

Class:Methylxanthines MOA: * Inhibits PDE3, activating PKA and causing vasodilation * Inhibits PDE4, inhibiting inflammatory processes * Enhance catecholamine secretion to work on beta-2 Use: Used if other drugs do not work, Nocturnal asthma AE: * Stimulant * Diuretic affects

Question 104

Ipratropium Tiotropium Class, MOA, Use, AE

Answer 104

Class:Anticholinergics MOA:Block M3 receptors (Gq receptors) Use: Bronchodilation AE: * Dry mouth (opposite of SLUD)

Question 105

Omalizumab Class, MOA, Use, AE

Answer 105

Class:MAB MOA:Binds to IgE Use: allergic asthma AE: * expensive

Question 106

Bupropion MOA, Use, AE

Answer 106

MOA:Inhibits dopamine reuptake (lasting feeling of pleasure) Use: Smoking cessation aid AE: * Tremors * Insomnia

Question 107

Varenicline MOA, Use, AE

Answer 107

MOA:Nicotine receptor agonist Use: Eases withdrawal symptoms and blocks pleasurable effects AE: * Transient nausea

Question 108

Name 5 anti-histamines.

Answer 108

* Diphenhydramine * Hydroxyzine * Fexofenadine * Loratadine * Cetirizine

Question 109

What is the general mechanism of action of antihistamines?

Answer 109

Competitive H1 receptor (Gq receptor); although increase in intracellular Ca2+, histamine stimulation causes production of prostacyclin and NO, outweighing histamine’s vasoconstrictive effects

Question 110

What are the uses of antihistamines? What are the adverse effects of antihistamines?

Answer 110

Use: Allergy-mediated pathologies Adverse Effects: Diphenhydramine and hydroxyzine have anticholinergic effects (aka sedating)

Question 111

Name 2 decongestants

Answer 111

* Pseudoephedrine * Phenylephrine

Question 112

For decongestants (pseudophedrine, phenylepherine): * What is the MOA? * What are the uses? * What are some adverse effects?

Answer 112

* MOA: Alpha 1 agonists (Gq) – vasoconstriction * Uses: Used to decrease mucus production * Adverse effects: Tissue necrosis if use extends past 3 days

Question 113

For intranasal corticosteroid: * Name one. * What is the MOA? * What is its use? * What are 3 adverse effects?

Answer 113

* Example: fluticasone * MOA: Transcription factor that decrease capillary permeability, stabilize lysosomes, decrease mucus production * Uses: Sinusitis * AE: Candida infection, perforation of nasal septum, bone necrosis

Question 114

For expectorant: * Name one. * What is the MOA? * What is its use?

Answer 114

* Guaifenesin * MOA: Increase respiratory tract fluid secretions and helps loosen phlegm * Use: Sinusitis (may help – “expect” it to help)

Question 115

For mucolytic agents: * Name one. * What is the MOA? * What is its use?

Answer 115

* Example: acetylcysteine * MOA: Splits the disulfide linkages that holds mucus together * Use: Reduces sputum viscosity to improve secretion clearance

Question 116

For opioid antitussives: * Name three. * What are the MOAs? * What is its use? * Adverse effects?

Answer 116

* Example: Codeine/Hydrocodone/Dextrmethorphan * MOA: Acts on G_i receptors to hyperpolarize cell membranes – prevents neurotransmitter release * Uses: Decreases cough (so people with colds can sleep) * Adverse effects: Dextromethorphan (seen as DM in cold medications) is very weak; honey more effective

Question 117

For non-opioid antitussives: * Name one. * What is the MOA? * What is its use? * Adverse effects?

Answer 117

* Example: Benzonatate * MOA: Topical anesthetic action on respiratory stretch receptors (blocks sodium channels) * Use: Decreases cough (so people with colds can sleep) * AE: Sedating