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Homeostasis > PEARLS Pharmacology > Flashcards

PEARLS Pharmacology Flashcards

1
Q

Amlodipine

A
  • Class: Calcium channel blocker, dihydropyridine
  • Uses: HTN, angina pectoris, SVT, mild to mod. HF
  • MOA: binds to the L-type calcium channel (responsible for the Ca2+ entry that maintains phase 2 of the action potential or “plateau”) in heart and vascular smooth m. of coronary and peripheral arteriolar vasculature → prevents calcium influx → vascular smooth m. relaxation → arteriolar dilation → ⇡coronary blood flow and ⇣TPR to decrease BP
  • Affinity for vascular Ca channels > affinity for heart Ca channels
  • Have an intrinsic naturietic effect (no need for diuretics in patients w/ DM, angina, etc.)
  • Pharmacokinetics:
    • Very long half-life
    • Metabolized by the the same isoform of
      CYP450 (3A4) that metabolizes statins so
      use of amlopdipine with statins is cautioned due to myopathy and rhabdomyosis that may
      result b/c of the increased levels of statins
    • Renal excretion
  • AEs: acute hypotension, peripheral edema
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2
Q

Hydrochlorothiazide

A
  • Class: thiazide diuretic
  • Uses: HTN, edema due to HF, ascites, or nephrotic syndrome, hypercalcemia, DI
  • MOA: inhibits NaCl cotransporter in the distal tubule → ⇡excretion of sodium and water as well as potassium and magnesium ions
    • It also ⇡reabsorption of calcium ions, so it useful for patients w/ osteoporosis that need a diuretic
    • Also causes reduced TPR → ⇣BP
  • Pharmacokinetics: r​enal excretion as unchanged drug
  • AEs: hypokalemia, hyponatremia, hyperuricemia, orthostatic hypotension, hypercalcemia, hyperglycemia, hyperlipidemia
  • Contraindications: sulfa allergy
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3
Q

Erythromycin

A
  • Macrolide antibiotic (like azithromycin and clarithromycin)
  • It inhibits Ik rapid channels that function during phase 2 and 3 of the myocyte AP → reduced outward K+ current → prolonged repolarization
  • Since it prolong repolarization, erythromycin can cause and increased QT interval and is contraindicated in patients with Long QT Syndrome (LQTS)
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4
Q

Amitryptyline

A
  • Selective Serotonin Reuptake Inhibitor (SSRI)
  • Prevents reuptake of 5HT and NE → ⇡NE → ⇡sympathetic stimulation to the heart →⇡Calcium influx during phase 2 of myocyte AP → prolonged plateau phase → lengthened AP and ∴prolonged QT interval
  • Since they prolong the QT interval, they are contraindicated in LQTS
  • Prolonged plateau phase also ⇡risk of early afterdepolarization, which can trigger ventricular arrythmias
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5
Q

Diphenhydramine

A
  • Anticholinergic antihistamine
  • Anticholinergic → decreased PSNS inhibition w/ unrestricted SNS stimulation → phase 2 calcium influx → prolonged plateau phase →lengthened AP and ∴prolonged QT interval
  • Also ⇡risk of early afterdepolarization
  • At higher concentrations, it inhibits the repolarizing (phase 3) potassium channels → lengthened AP and ∴prolonged QT interval
  • Since it prolongs the QT interval, it is contraindicated in patients with LQTS.
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6
Q

Digitalis/Digoxin

A
  • Class: Cardiac glycoside
  • Uses: atrial fibrillation, heart failure (antiarrhythmic and inotropic agent)
  • MOA: selective inhibitor of plasma membrane Na+/K+ pump of the myocyte, particularly at the AV node → ⇣Na+ being pumped out of cells from ATPase → ⇣activity of Na+/Ca++ exchanger (normally pumps Na+ in, Ca++ out) → ⇡Ca++ intracellularly and stored within SR → more Ca++ ions able to bind TnC in response to AP → more tension dev. and ⇡force of contraction
  • AEs: arrhythmias (esp. atrial) due to ⇣intracellular K+, headache, fatigue, confusion, blurred vision, anorexia, nausea, and vomiting
    • hypokalemia predisposes to digixon toxicity because it results in a further ⇣ in the Na+/K+ pump activity, promoting ⊖ effects
      • therefore, interaction with corticosteroids, loop (furosemide) and thiazide diuretics.
  • Pharmacokinetics:
    • Metabolized via sequential sugar hydrolysis in the stomach or by reduction of lactone ring by intestinal bacteria
    • 50-70% excreted unchanged by the kidney
    • Long half-life (36 hrs) and narrow therapeutic window, which means that the therapeutic endpoint is difficult to quantify and digoxin toxicity may be life-threatening
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7
Q

Digoxin-immune-Fab

A

Digoxin-specific antibody fragments = definitive tx for patients w/ digitalis toxicity

These fragments bind free digoxin, thereby forming digoxin-immune fragment complexes. As the level of free digoxin in plasma falls, the resulting concentration gradient facilitates dissociation of digoxin from the sodium-potassium ATPase. The complexes are then renally excreted.

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8
Q

Metoprolol

A
  • Class: ß1-adrenergic antagonist (Beta1 blocker)
  • Uses: HTN, CHF (⇣mortality), tachyarrhythmias caused by ⇡SNS activity, atrial flutter, afib, angina
  • MOA: Competes with catecholamines to block binding at ß1-adrenergic receptors in the heart → ⇣HR → ⇣CO → ⇣BP
    • also somehow ⇣renin secretion → ⇣BP
  • AE: commonly produces mild 1st degree heart block and may also produce severe 1st, 2nd, or 3rd degree heart block, which is why it is contraindicated in AV block.
    • coadministration with digoxin ⇡the risk of developing high-grade AV heart block
  • Other AEs: bradycardia, hypotension, drug-induced sexual dysfunction (e.g., ⇣libido)
  • Used in patients with HCM because decreasing HR helps ⇡the length of time for ventricular diastolic filling and increasing the inotropic state lessens the myocardial oxygen demand.
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9
Q

Furosemide

A
  • Class: Loop diuretic
  • Uses: pulmonary edema, peripheral edema, CHF, cirrhosis
  • MOA: Inhibitor of Na+/K+/2Cl- cotransporter in the thick ascending loop of Henle → ⇣Na+/K+/Cl- reabsorption in the renal tubule → ⇣circulating volume and BP, but also can contribute to hypokalemia
    • Also ⇡Na+ at distal tubule → Na+ exchanged with K+ → ⇡renal excretion of K+, contributing to hypokalemia
    • Activates RAAS → ⇡aldosterone → promotes further Na+/K+ exchange, contributing to hypokalemia
    • For these reasons, it is dangerous for patients digoxin, since hypokalemia can further ⇡the risk for digoxin toxicity.
  • AEs: electrolyte imbalance, dehydration
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10
Q

Phenylephrine

A
  • “Selective” α1-adrenergic agonist (Gq pathway) of vascular smooth muscle → arterial vasoconstriction → ⇡TPR → ⇡BP
  • Effective for HCM because outflow obstruction is lessened when afterload is increased
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11
Q

Nitroglycerin

A
  • Converted to nitric oxide which activates guanylate cyclase increasing levels of cGMP → ⇡MLCK, causing vasodilation in smooth muscle.
    • Venous vasodilation at low doses increases venous capacitance and decreases preload/end-diastolic volume
    • arteriolar vasodilation (wide-spread) at high doses → reflex tachycardia and hypotension
  • AEs: syncope due to hypotension
  • Decreasing preload is problematic in patients with HCM because it further decreases LV volume causing obstruction of the outflow tract with the anterior mitral valve leaflet due to venturi forces.
  • Helps decrease ischemic chest pain by decreasing preload → ⇣myocardial oxygen demand → ⇣myocardial ischemia
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12
Q

Dobutamine

A
  • Class: synthetic catecholamine
  • MOA: stimulates beta1-adrenergic receptors in the heart to increase contractility
  • AEs: dysrhythmias, coronary atherosclerosis
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13
Q

Treatment for Acute Heart Failure

A
  • Treatment consists of:
    • Decreasing preload → use vasodilators and diuretics → nitroglycerin and furosemide
    • and Increasing contractility → use beta1-adrenergic agonits → dobutamine
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14
Q

Lisinopril

A
  • Class: ACE inhibitors (ACEIs)
    • also: enalapril
  • MOA: inhibits conversion of ANG1 → ANG2 by ACE, ∴ decreasing the effects of ANG2, including the release of ALDO from the adrenal glands, to prevent Na+ and H2O reabsorption → ⇣BP
    • ACE also breaks down bradykinin, so ACEIs → ⇡bradykinin levels → vasodilation
  • Black box warning: pregnancy
  • AEs: dry cough, angioedema, dizziness, syncope, hypotension, hyperkalemia, renal insufficiency
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15
Q

Carvedilol

A
  • Class: Beta blocker
  • **MOA: **non-selective beta1-blocker (→⇣contractility, HR, and BP ) with alpha1-blocking activity → vasodilation → ⇣TPR → ⇣BP
    • Good for long term tx of CHF because it has both alpha and beta blocking activity and because at high doses it is cardioprotective by its antioxidant properties (inhibitions generation of free radicals, preventing LDL oxidation)
  • AEs: AV block
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16
Q

Spirnolactone

A
  • Class: Aldosterone Receptor antagonist, potassium-sparing diuretic
  • **MOA: **blocks the aldosterone receptor → ⇣ sodium and water reabsorption while ⇡potassium reabsorption → reduced preload → ⇣BP
  • Black box warning: tumor risk
  • AEs: hyperkalemia, gynecomastia in men, menstrual irregularities in women
17
Q

Treatment for Chronic Heart Failure

A
  • Treatment consists of agents that decrease preload, BP, and contractility:
    • ACE inhibitors (lisinopril)
    • Beta-blockers (carvedilol or metoprolol; carvedilol also has alpha1 effect that leads to vasodilation)
    • Aldosterone antagonists (spironolactone)
18
Q

Inhaled NO

A
  • Class: Vasodilator
  • MOA: NO activates guanylyl cyclase causing increased levels of cGMP → cGMP activates MLCK → smooth muscle relaxation
  • Inhalation of NO is important because it ensures that the first site of action will be the lungs
    • Inhaled NO is used to treat pulmonary HTN (e.g., in newborn case) because it selectively targets pulmonary vessels causing a potent and sustained vasodilation → ⇡pulmonary blood flow
19
Q

Aspirin

A
  • Class: Non-steroidal anti-inflammatory drugs (NSAIDs), antiplatelet agent
    • also: ketorolac
  • MOA: irreversibly inhibits cyclooxygenases (COX1/2) by acetylating them and ∴ preventing prostaglandin synthesis
    • In platelets (low dose/COX1), this inhibits thromboxane A2 (TxA2) synthesis → inhibition of platelet granule release reaction and platelet aggregation
    • higher doses (COX2) also inhibit the synthesis of prostaglandin I2 (PGI2) in endothelial cells, which normally → vasodilation and inhibition of platelet aggregation
    • For this reason, low dise aspirin is used because it causes loss of TxA2 without losing PGI2
  • AEs: gastric upset, GI bleeding, gastric and duodenal ulcers, hemolysis in G6PD deficiency
  • Can cause acute renal failure by inhibiting prostaglandin synthesis and ∴ the compensatory actions taken against high levels of sympathetic activity, ANGII, and afferent arteriolar vasoconstriction → ⇣peritubular blood flow → ⇡risk of ATN
20
Q

Dypyridamole

A
  • Class: Phosphodiesterase inhibitor, antiplatelet
  • MOA: inhibits phosphodiesterase, preventing the degradation of cAMP in platelets and endothelial cells → ⇡cAMP → ⇡PKA → ⇣platelet aggregability and increased vasodilation (endothelial cells)
    • Also inhibits the uptake of adenosine by the platelets → further reduced platelet aggregation (since ADP is one of the 3 factors released by platelet granules, along with TxA2 and vWF)
  • AEs: vasodilatory effects → ⇣CO → production of angina in CAD patients
  • Pharmacokinetics:
    • half-life= 10 hours
    • Metabolized by liver CYP450
    • Excreted in bile
  • Prescribed to people that are intolerant of aspirin
21
Q

Cilostazol

A
  • Class: phosphodiesterase inhibitor (PDEIs), antiplatelet
  • MOA: inhibits phosphodiesterase 3 → suppressing cAMP degradation → ⇡cAMP → inhibition of platelet aggregation and increased vasodilation, especially in femoral vascular bed
  • Black box: contraindicated in CHF of any severity because several drugs that inhibit PDE3 have caused ⇣survival in class 3-6 CHF
  • AEs: bleeding, anemia, thrombocytopenia, arrhythmias
  • Pharmacokinetics:
    • Half-life = 11-13 hours
    • Metabolized in the liver by CYP450 3A4
    • Urinary (unchanged) and fecal excreiton
22
Q

Clopidogrel

A
  • Class:
  • MOA: Drug that irreversibly blocks ADP receptors on platelets, preventing platelet stickiness and aggregation
    • ADP receptors are coupled to Gi proteins
    • Blocking them → activation of adenylyl cyclase → ⇡[cAMP]in → ⇣expression of GIIb/IIIa receptors on the surface of platelets and preventing platelet aggregation
  • Brand name: Plavix
  • Other class member: Prasugrel, bleeding is more common
23
Q

Prostanoids

A
  • Class: Prostacyclin (PGI2) analogs
  • MOA: mimic the vasodilatory effects of PGI2
    • PGI2 activates adenylyl cyclase → ⇡cAMP → PKA → MLCK → smooth muscle relaxation
24
Q

Endothelin-based drugs

A
  • Class: Endothelin receptor antagonists
  • Uses: treatment of pulmonary arterial hypertension (PAH)
  • MOA: Bind to endothelin-1 (ET1) Gq GPCR receptors (ETA and ETB receptors) on vascular smooth muscle cells, preventing smooth muscle constriction
    • Normal ET1 action: ET1 binds to ETA/ETB → activation of PLC → conversion of PIP2 to IP3 and DAG → ⇡[Ca]in and PKC → smooth muscle contraction through calmodulin-MLCK
  • Examples:
    • bosentan (non-selective antagonist of ETA)
    • ambrisentan (selective antagonist of ETA)
25
Q

Phosphodiesterase 5 inhibitors

A
  • Class: PDE5 inhibitors
  • Uses: Improves gas exchange in severe lung fibrosis and secondary pulmonary arterial HTN
  • MOA: Inhibits PDE5, which increases the cellular levels of cGMP (PDE5 degrades cGMP) → MLCK → vascular smooth muscular relaxation
    • this is effect is particularly potentiated in the lung, where there is a high concentration of PDE5 → preferential pulmonary vasodilation and improved gas exchange
26
Q

Heparin

A
  • Class: anticoagulant; unfractionated & LMW
  • Use: helps limit expansion of thrombi by preventing fibrin formation; tx for acute DVT & PE, postoperative and acute MI prophylaxis
  • MOA: mimics endogenous heparan sulfate, which binds to antithrombin 3 (AT3), an endogenous anticoagulation factor, to help it inactivate thrombin, as well as factors 9, 10, 11, and 12. ​
    • ​unfractionated also binds thrombin and strongly inactivates thrombin
    • LMW heparin only binds AT3, so it poorly inactivates thrombin
  • Choice of treatment in pregnant women
  • Monitored using aPTT (activated Partial Thromboplastin Time), which measures the intrinsic and common pathways (no tissue factor, so the extrinsic pathway is not activated) by adding anticoagulation molecules and excess phospholipids with patient’s blood in a tube and seeing how long it takes a clot to form.
    • Prolonged aPTT: clotting is slow, anticoagulant excess (exogenous or endogenous) or procoagulant deficiency
    • Shortened aPTT: clotting is fast, procoagulant excess or anticoagulant deficiency
27
Q

Warfarin

A
  • Class: Anticoagulant
  • Uses:
  • MOA: blocks epoxide reductase → ⇣production of Vitamin K-dependent procoagulation factors 2, 7, 9, 10 and anticoagulant proteins C & S [epoxide reductase activates Vitamin K]
    • ​Initially some factors remain in body from before administration, but eventually these are degraded. W**arfarin’s onset of action is delayed because it depends on the half-lives of the factors being inactivated (F2, ~3 days)
    • Proteins C & S have the shortest half-life (will be first to degrade)
    • Without them the balance between procoagulant factors and anticoagulant factors will be tipped in favor of procoagulants → ⇡ risk of thrombus during the window in which (factors 2, 7, 9, & 10 have not been degraded)
    • Heparin is co-administered during this window to prevent thrombosis
    • Patients with Proteins C & S deficiency cannot be given warfarin because it further ⇣ protein C/S levels → hypercoagulable state (esp in skin) → warfarin skin necrosis
  • **Monitored by Prothrombin Time (PT), **which puts patients blood with coagulation factors and tissue factor and see how long it takes for a clot to form. Measures extrinsic and common pathways.
  • INR (International Normalized Ratio) = patient PT/standard PT
28
Q

Abciximab

A
  • Class: GIIb/IIIa receptor antagonist monoclonal antibody
  • MOA: blocks the GIIb/GIIIa receptor of platelets and prevents platelet aggregation
29
Q

Morphine

A
  • Decreases ischemic chest pain by ⇣sympathetic response → ⇣HR → ⇣myocardial oxygen demand → myocardial ischemia
30
Q

Albuterol

A
  • Class:“selective” β2-adrenergic receptor agonist, bronchial smooth muscle relaxan
  • Uses: acute exacerbations of asthma
    • Long-acting: salmeterol, formoterol
  • MOA: activates beta2 adrenergic receptors on airway smooth muscle cells → activating the coupled Gs protein -→ activating adenylyl cyclase → ⇡cAMP → a ⇣ in intracellular calcium concentration in lung & activation of PKA → inactvation of MLCK & activates myosin light chain phosphorylase → resulting in bronchodilation
  • AEs: at high doses it can cause cardiac stimulation → tachycardia, palpitations, hypotension, and skeletal muscle tremor
31
Q

Theophylline

A
  • Class: methylxanthines, adenosine receptor blockers, PDEIs
    • also: aminophylline
  • Uses: long term symptoms in mild asthma
  • MOA: exact mechanism unknown, but

likely causes bronchodilation by inhibiting phosphodiesteraseŽ → ⇡cAMP levels due to ⇣cAMP hydrolysis/degradation. It also antagonizes adenosine receptors.

* ⇡cAMP → PKA → phosphorylation and inactivation of MLCK → smooth muscle dilation
* adenosine → ⇡K+ out of cells → Žhyperpolarizing the cell and ⇣[Ca]<sub>in</sub>
  • Less potent than β2-agonists and often used in combination with them
  • Usage is limited because of a narrow therapeutic index (overdose can cause cardiotoxicity and neurotoxicity, see below)
  • AEs: headache, restlessness, convulsions, and life-threatening cardiac arrhythmias
  • Metabolism by cytochrome P450
32
Q

Ipratropium

A
  • Class: Muscarinic (M3) receptor antagonists
    • also: tiotropium, which is a long-acting M3 antagonist
  • Uses: long term treatment of asthma, COPD
  • MOA: competitive block of muscarinic receptors (blocks ACh) → ⇣Gq activity and ∴ preventing parasympathetic bronchoconstriction and decreasing mucus production
  • Administration: inhaled ∴ have no systemic absorption and are generally very safe
  • AEs: blurred vision, dry mouth, tachycardia, constipation
33
Q

Prednisone

A
  • Class: oral corticosteroid
    • also: methylprednisolone
    • inhaled: fluticasone
  • Uses: reduction of inflammation in asthma, COPD
  • MOA: blocks PLA2 → ⇣synthesis of prostaglandins and leukotrienes
    • directly targets underlying airway inflammation by decreasing the inflammatory cascade (eosino- phils, macrophages, and T lymphocytes), reversing mucosal edema, decreasing the permeability of capillaries, and inhibiting the release of leukotrienes
34
Q

Cromolyn

A
  • Class: Mast cell stabilizer
  • MOA: inhibit degranulation of mast cells by blocking calcium channels → ⇣bronchial hyperresponsiveness
  • Administration: inhaled ∴ <1% is absorbed into systemic circulation, which makes them very safe with few side effects
35
Q

Montelukast

A
  • Class: Antileukotrienes/leukotrience receptor antagonists
  • Uses: asthma
  • MOA: prevent the action of leukotrienes → ⇣bronchoconstriction of respiratory smooth muscle
  • AEs: headaches
  • Especially good for aspirin-induced asthma
36
Q

Naloxone

A
  • Class: pure opioid antagonist
  • Uses: opiate overdose-induced respiratory depression and coma
  • MOA: competes and displace opioids at mu-opioid receptor sites
  • AEs: cardiac arrest, hyper- or hypotension, tachycardia, arrhythmias, dyspnea, hypoxia, pulmonary edema, fever
37
Q

Vasopressors v. Inotropes in hypotension

A
  • Vasopressors: adrenergic agonists
    • NE: non-selective, but α1 > α2 > β1 agonist
      • ​preferred for tx of shock
    • Phenylephrine: pure α-adrenergic agonist,

α1 > α2 → vasoconstriction → ⇡BP

    * used when tachycardia or arrhythmias preclude use of β-agonists like NE * Inotropes: beta adrenergic agonists
* Dobutamine: β1 \> β2, α agonist →⇡cardiac contractility → ⇡CO → ⇡BP
    * ​used in patients with refractory shock after fluids and pressors have not worked
38
Q

Varenicline

A
  • Class: smoking cessation drug
  • MOA: partial neuronal α4 β2 nicotinic receptor agonist → prevents nicotine stimulation of mesolimbic dopamine system associated with dopamien addiction
    • Stimulates dopamine, but to a much smalle degree than nicotine, which results in ⇣cravings and withdrawal symptoms
39
Q

Buproprion

A
  • Class: antidepressant smoking cessation drug
  • MOA: not fully understooad, but is a relatively weak inhibitor of the neuronal uptake of NE and dopamine → reduced nicotine cravings

Homeostasis (26 decks)

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