Pharmacology MD2 Flashcards
1
Q
Sertraline
A
SSRI (selective serotonin reuptake inhibitor) for
depression & anxiety tx
sertraline binds serotonin reuptake transporters @ somatodendritic area. prevents reuptake. serotonin binds autoreceptors -> decr serotonin release @ axon.
After TWO WEEKS, autoreceptors are downregulated -> increased serotonin secretion @ axon -> transmission of neuronal impulse.
2
Q
Lorazepam
A
- benzodiazepine
- tx of ANXIETY, epilepsy, etoh withdrawal, sedation
- positive allosteric modulator of GABA receptors-> incr affinity of GABA-> incr frequency of Cl- channel opening-> incr Cl- influx-> hyperpolarization of neuron & decr excitability-> inhibition of neurons in the limbic system-> anxiolytic effects
- AE: drowsiness, confusion
3
Q
Oxycodone
A
- opioid agonist
- analgesic
- binds to opioid receptors in CNS coupled to G proteins, inhibits adenylate cyclase-> decr cAMP->
- closes Ca2+ channels in presynaptic neuron-> decr intracellular Ca2+-> decr release of nociceptive NTs (substance P)
- opens K+ channels in postsynaptic neuron-> incr efflux of K+-> hyperpolarization and decr excitability
- AE: sedation, drowsiness, respiratory depression, abuse
4
Q
Morphine
A
- opioid agonist, analgesic in MI
- lowers pain & anxiety-> decr HR & O2 demand
- binds to G-protein coupled opioid receptors-> inhibition of adenylate cyclase-> decr cAMP->
- (presynaptic) closes Ca2+ channels-> decr intracellular Ca2+-> decr release of nociceptive NTs (substance P)
- (postsynaptic) opens K+ channels-> incr efflux of K+-> hyperpolarization-> decr excitability-> decr transmission of pain signals
- AE: respiratory depression, abuse
5
Q
Nitroglycerin
A
- paste can be wiped off if BP drops too low (vs. sublingual)
- nitrate-> nitrite-> NO-> activates guanylate cyclase-> incr cGMP-> activates protein kinase G-> dephosphorylation of myosin light chains-> smooth muscle relaxation-> vasodilation (veins > arteries)-> decr BP
- coronary artery dilation-> incr myocardial O2 supply
- incr venous capacitance-> decr venous return-> decr preload & ventricular wall stress-> decr myocardial O2 demand
6
Q
Aspirin
A
- antithrombotic
- irreversable acetylation of serine residue on COX-1-> prevents binding of AA-> prevents PG synthesis-> prevents downstream TXA2 synthesis-> prevents vasoconstriction & platelet agonist activity
- also NSAID, action of COX-2 (antipyretic, anti-inflammatory, analgesic)
7
Q
Atorvastatin
A
- statin
- early use s/p MI: plaque stabilization (decr platelet agg.), decr inflammation & oxidative stress, reduce
risk of cardiogenic shock, arrhythmias, cardiac arrest, rupture
- HMG CoA reductase inhibitor prevents conversion of HMG CoA to mevalonate (cholesterol precursor, rate limiting step)->
- decr cholesterol synthesis in hepatocytes, incr LDL receptors & LDL uptake, decr plasma LDL, decr VLDL secretion
AE: liver dz, rhabdomyolysis
8
Q
Heparin
A
- fast acting anticoagulant
- binds to ATIII, induces conform change, accelerates inactivation of thrombin & factor Xa-> prevents fibrin formation-> decr clot stability
- monitored by PTT (intrinsic)
- Heparin-Induced Thrombocytopenia (HIT): antibodies vs. heparin:PF4 complex activate platelets, removed from circulation, lower platelet count
9
Q
Warfarin
A
- coumarin anticoagulant, vitamin K antagonist
- prophylactic for MI, DVT, A-fib
- slow acting, depletion of prev coag factors
- initial hypercoagulable d/t decr activity of anticoagulant proteins C & S
- binds C1 subunit of vitamin k epoxide reductase preventing reformation of vitamin k from vitamin k epoxide, vitamin k req for carboxylation of clot factors (II, VII, X)-> decr clot factor activity & clotting
- AE: bleeding
- Antidote: Vitamin K
10
Q
Metoprolol
A
- B1 selective adrenergic blocker
- (myocardium) decr cAMP & Ca2+-> decr contractility-> decr CO and O2 demand
- (pacemaker) decr HR-> incr refractory period @ AV node-> prevent arrhythmias
- @ high doses, blocks B2 in lungs and vascular smooth muscle-> bronchoconstriction & vasoconstriction
11
Q
Clopidogrel
A
- blood thinner
- irreversable binding of P2Y ADP receptors on platelets prevents binding of ADP-> decr activation of GP IIb/IIIa receptors that bind fibrinogen, fibrinogen cross-links GP receptors on adjacent platelets-> decr platelet agg.
12
Q
Enalapril
A
- ACE inhibitor
- competes w/ ATI for binding to ACE, prevents conversion to ATII.
- Prevents ATII & aldosterone assoc. ventricular remodeling, fibrosis, inflammatory changes.
- reduction in afterload & preload decr ventricular wall stress during systole & end diastole-> less ventricular hypertrophy & dilation
13
Q
Abciximab
A
- monoclonal antibody
- prophylactic MI, s/p coronary procedures
- noncompetitive inhibition of GP IIb/IIIa receptors on platelets, prevents binding of fibrinogen, which cross-links GP receptors on adjacent platelets-> prevents platelet agg.
- expensive
14
Q
Epinephrine
A
- adrenergic agonist
- fast acting, short duration
- low dose: B1: incr HR, contractility-> incr CO
B2: bronchodilation, vasodilation (coronary arteries-> incr O2 supply)
- high dose: a1: vasoconstriction-> incr PVR, BP, shunt blood to heart and brain
a2: negative feedback inhibition of adrenergic NT release.
15
Q
Amiodarone
A
- class III antiarrhythmic, K+ channel blocker
- has effects of other classes too
- blockage of K+ channels (K+ efflux) prolongs phase 3 repolarization-> longer AP & ERP-> prevents re-entry
- AE: prolonged QT-> torsades de pointes, iodine (blue skin)
16
Q
Lidocaine
A
- class IB antiarrhythmic, Na+ channel blocker
- blocks fast Na+ channels in myocytes, prevents phase 0 depolarization-> decr conduction velocity
- decr slope of phase 4 in pacemaker cells, decr excitability/automaticity-> suppress ectopic pacemakers
- AE: vasodilation leads to systemic diffusion (CNS depression), given w/ epinephrine (vasoconstriction)
- incr effect w/ incr HR (binds to open or inactive channels)
17
Q
Erythromycin
A
- macrolide, incr effect on gram +, pts w/ beta-lactam allergy
- irreversable binding to 50S subunit on bacterial ribosome prevents translocation in protein synthesis, bacteriostatic
- AE: CYP450 inhibitor, prolonged QT, ototoxicity
18
Q
Levofloxacin
A
Fluoroquinolone, widespectrum, tx chr bronchitis exac, pna
(vs. Gram -) binds DNA gyrase prevents resealing step after DNA unwinding, dbl stranded DNA breaks-> apoptosis
(vs. Gram +) binds topoisomerase IV, prevents segregation of newly synthesized DNA
- AE: well tolerated, tendon rupture in children, prolonged QT
- prolonged post-antibiotic effect
19
Q
Clindamycin
A
lincosamide, vs gram+ & anaerobic
- binds 50S subunit of bacterial ribosome during translocation step of protein synthesis
- indicated in erythromycin hypersensitive pts
- dental pt prophylaxis of infective endocarditis/
strep mutans (cause of dental caries)
20
Q
Cefuroxime
A
cephalosporin (2nd gen)
- more resistant to beta-lactamases, gram- activity in addition to +, indicated vs. haemophilus & klebsiella
- beta lactam ring binds PBP, inhibits transpeptidation/peptidoglycan crosslinking in 3rd/final stage of bacterial cell wall synthesis-> cell wall instability and apoptosis
- some penicillin cross-reactivity
21
Q
Fluticasone;Salmeterol
A
combo drug for long-term tx of asthma/chr. bronchitis
- CI in acute attacks, ICS can cause oral thrush, salmeterol-> arrhythmias, tremor
- fluticasone: binds glucocorticoid receptor in cytoplasm, translocates to nucleus & binds GREs on DNA-> decr inflam mediators, vasoconstriction/decr permeability causing decr inflam cell influx & edema, decr hyperresponsiveness of airway smooth muscle-> decr inflammation
- salmeterol: lipophilic side chain binds to exosite on B2 receptors, allows continuous binding of active site (long duration of action)-> activates adenylyl cyclase, incr cAMP, protein kinase A, inhibits MLCK, decr Ca2+, dephosphorylation of MLC, smooth muscle relaxation & bronchodilation
22
Q
Quinapril
A
ACEI,
withold if 2ndary HTN suspected (RAS).
In RAS, afferent arteriole stenosed, decr pressure. Relies on efferent arteriole vasoconstriction by ATII for intraglomerular pressure (filtration). If ATII decr by ACEI, intraglomerular pressure decr and GFR is insufficient (renal failure).
23
Q
Propanolol
A
non-selective beta-blocker,
Withhold in possible 2ndary HTN (pheochromocytoma). Tumor secreting catecholamines. If beta receptors blocked, all catecholamines bind a1-> vasoconstriction & severe HTN. Administer a1 blocker first, then beta blocker.
24
Q
Centrally Acting Agents
A
preferential a2 agonists
- initial binding to a1-> peripheral vasoconstriction & incr BP
- preferential binding to a2 receptors in MNTS-> decr SNS activity & catecholamine secretion, incr PSNS activity-> decr HR/CO, vasoconstriction/TPR-> decr BP
- AE: CNS depressant, rebound HTN w/ abrupt discontinuation
- e.g. Clonidine, alpha-methyldopa
25
Losartan
Angiotensin II Receptor Blockers (ARB)
- competes w/ ATII for binding to ATII, type I receptor, prevents vasoconstriction & aldosterone release-\> decr Na+ & H2O reabsorption (decr volume) & TPR-\> decr BP
- no dry cough
- more RAAS blockade vs ACEI (ATI able to be converted to ATII via non-ACE enzymes)
26
Diltiazem
CCB, Class IV antiarrhythmic
- binds a1 subunit of voltage-gated Ca2+ channels in open, depolarized state
- (myocardium) decr Ca2+ influx, decr phase 2 plateau, decr contractility, decr CO and BP
- (smooth muscle) decr MLCK activity, decr phosphorylation of MLC, smooth muscle relaxation, vasodilation ( \> arteries)-\> decr PVR & vasodilation of coronary arteries leading to incr myocardial O2 supply-\> decr BP & improvement of angina
- (pacemaker cells) decr phase 0 depol, incr threshhold @ SA node & decr AV node conduction, decr HR-\> tx arrhythmias (supraventricular/atrial)
- AE: - inotropic (decr cardiac function), bradycardia, hypotension
27
Arterial Vasodilators
- e.g. minoxidil, hydralazine
- open K+ channels on vascular smooth muscle, K+ efflux, hyperpolarization, decr Ca2+ influx, smooth muscle relaxation-\> vasodilation-\> decr BP
- AE: reflex autonomic response-\> incr RAAS (tx w/ diuretics), incr SNS/catecholamines, HR, SV-\> incr myocardial O2 demand (tx w/ beta blockers)
28
Alpha Blockers
non-selective vs. selective
- non-selective rarely used d/t amplified reflex tachycardia (a2 blockade prevents negative feedback inhibition of catecholamine release)
- selective (-osins, prazosin, tamsulosin) blocks a1 only
competes w/ norepinephrine for a1 binding on vascular smooth muscle-\> smooth muscle relaxation, vasodilation (arteries & veins)-\> decr preload & afterload, decr TPR-\> decr BP
- AE of selective: milder reflex tachycardia (d/t no a2 blockade), postural hypotension
- minimal effects on HR, CO, renal blood flow
29
Tiotropium Bromide
anticholinergic, long-term COPD management
- more potent, once daily dosing vs. ipratropium bromide
- competitive, reversible binding to muscarinic receptors, preventing acetylcholine. M3 on bronchial smooth muscle & submucosal glands: decr bronchoconstriction & mucus secretion
- slow dissociation, prolonged duration of action
- AE: anticholinergic: dry mouth, constipation, urinary retention, paradoxical bronchospasm, CI in acute attack
30
Albuterol
SABA (short acting selective B2 agonist), tx of acute asthma/COPD
- binds B2 receptors on bronchial smooth muscle, incr adenylate cyclase activity, incr cAMP, incr cAMP dependent protein kinases, decr MLC phosphorylation, smooth muscle relaxation, bronchodilation
- incr Na/K ATPase, incr intracellular K, hypokalemia
(also tx hyperkalemia)
- can cause cardio AE like arrhythmia, CAD, LQTS
- AE: B2 overactivation (tremor, anxiety)
31
Varenicline
- partial nicotine receptor agonist
- more effective than bupropion
- competitively binds nACh receptors in CNS, decr dopamine release @ nucleus accumbens-\> decr withdrawal sx & nicotine cravings, decr nicotine rewarding effects during relapse
- AE: SI, mood changes, vivid nightmares
32
Bupropion
- antidepressant, smoking cessation
- prevents reuptake of dopamine & norepinephrine
- incr dopamine-\> decr cravings
- incr norepinephrine-\> decr withdrawal sx
- decr wt gain s/p quitting
- CI in sz & eating disorders
- false + for amphetamines on UDS
33
Demeclocycline
- tetracycline antibiotic (binds 30S ribosomal subunit, prevents tRNA access to mRNA:ribosome), ALSO TX IN SIADH
- prevents ADH binding, decr H2O reabsorption @ collecting ducts, incr H2O excretion, tx of SIADH & hyponatremia (nephrogenic diabetes insipidus)
- AE: photosensitivity, stunting in teeth & bone of children
34
Cisplatin
platinum-based, cell cycle nonspecific, IV chemo drug
- binds N7 position on guanine in DNA, forms intra & interstrand cross links, alters DNA conformation, prevents DNA replication & RNA synthesis-\> apoptosis when DNA repair mechanisms fail
- neutral, inactive in presence of Cl- (resistance via thiol containing groups, also w/ incr DNA repair)
- AE: nephrotoxicity d/t ROS generation
35
Etoposide
- cell cycle specific (S & G2) chemo drug
- binds to topoisomerase II:DNA complex, prevents religation of DNA, irreversable dbl strand breaks-\> apoptosis
- cancer cells (rapidly dividing) rely on topoisomerase II to introduce DNA strand breaks to reduce supercoiling
- AE: bone marrow suppression (decr RBC/WBCs), can lead to leukemia
36
Furosemide
- loop diuretic, tx HF & BP
- binds to Cl- site on Na+/K+/2 Cl- cotransporter in ascending loop of Henle, incr excretion of Na, K, Cl, also Ca2+, Mg2+ and H2O
- incr Ca2+ excretion
- most effective diuretic
37
Aldosterone Antagonists
- K+ sparing diuretics, tx HF & HTN
- spironolactone (nonselective), eplerenone (selective, newer): doesnt bind androgen receptors/block testosterone-\> gynecomastia
- competes w/ aldosterone, prevents DNA activation & downstream protein synthesis-\> decr Na/K ATPase activity in collecting duct-\> incr Na excretion, decr K excretion-\> incr H2O excretion
- AE: hyperkalemia
38
Nesiritide
- human recombinant BNP, tx HF & BP
- potent, rapid onset
- binds to guanylate cyclase receptor, incr cGMP-\> activates cGMP-depended protein kinases-\> dephosphorylation of MLCs-\> smooth muscle relaxation-\> vasodilation-\> decr pre&afterload, BP
- decr RAAS & SNS-\> decr aldosterone, incr GFR-\> natriuresis-\>decr intravascular volume & decr remodeling
- AE: hypotension, expensive, ? efficacy
- indicated in unresponsive to other tx
39
Hydrochlorothiazide
thiazide diuretic, 1st line HTN, decr Ca2+ excretion
-blocks Na+/Cl- cotransporter on luminal side of early distal tubule-\> decr Na+ & H2O reabsorption-\> decr blood volume, preload, afterload-\> decr BP
40
Ramipril
ACEI
-indicated in HF
41
LCZ696
-not medically used yet, in phase 3 drug testing, decr
subQ swelling
- ARB/neprilysin inhibitor
- combo of valsartan/sacubitril
- prevents neprilysin degradation of NPs-\> natriuresis & vasodilation
42
Carvedilol
weak a1 blocker, b-blocker (b1 selective), tx HF & HTN
- in chr HF, b1 overstimulated & downregulated, blocking of b1 upregulates it-\> incr response to sympathetic stimulation in heart (incr HR, contractility)
- b-blockade prevents reflex tachycardia
- weak a1 block-\> vasodilation-\> decr pre&afterload
- AE: orthostatic hypotension
43
Digoxin
- cardiac glycoside, + inotropic, tx in supraventricular arrhythmias & HF
- (myocardium) competes w/ K+ for binding to Na/K ATPase, inhibits, incr intracellular Na+-\> incr Na+/Ca2+ exchange, incr Ca2+, incr contractility
- (@ AV node) incr vagal activity, decr AV node conduction, decr ventricular rate
- AE: Digoxin toxicity (narrow therapeutic range) (altered color perception, blurred vision, HA, confusion), can worsen WPW by sending more signals thru accessory path
- CI: hyperkalemia (less effect), hypokalemia (more effect), exacerbates AV node heart blocks
44
Dabigatran
- new anticoagulant, nonvalvular A-Fib prophylaxis
- competitive inhibition of free & clot bound thrombin, prevents conversion of fibrinogen to fibrin (fibrin clot formation) & thrombin mediated platelet agg.
- wider therapeutic range (no monitoring req.), rapid onset, predictable, doesn't req ATIII cofactor (heparin)
- no antidote, not able to monitor in standard labs, CI in valvular dz
45
Rivaroxaban
- new anticoagulant, nonvalvular A-Fib prophylaxis
- competitive inhibition of Factor Xa, prevents conversion of prothrombin to thrombin & downstream fibrin clot formation.
- wider therapeutic range (no monitoring req.), rapid onset, predictable, doesn't req ATIII cofactor (heparin)
- no antidote, not able to monitor in standard labs, CI in valvular dz
46
Apixaban
- new anticoagulant, nonvalvular A-Fib prophylaxis
- competitive inhibition of Factor Xa, prevents conversion of prothrombin to thrombin & downstream fibrin clot formation.
- wider therapeutic range (no monitoring req.), rapid onset, predictable, doesn't req ATIII cofactor (heparin)
- no antidote, not able to monitor in standard labs, CI in valvular dz
47
Robitussin DM
- oral, OTC tx for cough
- Guaifenesin (expectorant): incr volume of sputum/bronchial secretions & decr viscosity & adhesiveness, promotes ciliary action and flow of secretions-\> incr clearance & decr cough freq.
- dextromethorphan (antitussive): non competitive antagonist of NMDA receptors in CNS, decr excitability @ cough center in medulla-\> decr cough freq.
48
Isoniazid
- 1st line tx in TB, specific to mycobacterium
- inhibits mycolic acid synthesis in mycobacterium cell walls by binding to Inh-A-\> inhibits cell wall synthesis-\> bactericidal in fast growing extracellular TB, bacteriostatic in slow growing intracellular TB
- prodrug converted by KatG, resistance from mutations in enzymes
- AE: peripheral neuropathy, P-450 inhibitor, drug induced SLE
49
Rifampin
rifamycin abx, 1st line tx vs TB, but wider spectrum than isoniazid
- binds B subunit of DNA dependent RNA polymerase only in prokaryotes, prevents binding to DNA in initiation step of RNA transcription, prevents RNA transcription-\> apoptosis
- AE: turns secretions orange (sweat, tears, urine, contact lenses)
- drug interaction: CYP450 inducer, promotes metabolism of oral contraceptives, decr efficacy
- resistance from decr affinity of polymerase for rifampin, decr permeability
- TB tx is longer d/t difficult location of bacteria (intracellular, avascular center of large cavities), slow generation time.
50
Ethambutol
- tx in TB, least potent of TB drugs, given to prevent/tx resistance
- only effective vs actively dividing bacilli
- inhibits arabinosyl transferases, prevents polymerization of arabinogalactan, which links mycolic acids to cell wall-\> disrupts cell wall synthesis, decr stability, incr permeability-\>bacteriostasis
- AE: optic neuropathy (decr visual acuity, color blindness), CI in pts who cannot report vision changes
51
Imipenem;Cilistatin
- broad spectrum abx, combo of beta-lactam & dehydropeptidase-1 inhibitor
- (imipenem): binds to PBP-1 preventing peptidoglycan cross-linking in bacterial cell walls in 3rd and final stage of cell wall synthesis-\> decr stability-\> apoptosis
- binding to PBP-2-\> formation of spheroblasts & loss of rod shape-\> decr stability
- (cilistatin): competitively inhibitis dehydropeptidase-1 in proximal tubules, prevents renal metabolism of imipenem-\> decr nephrotoxicity
- AE: sz @ high doses
52
Pyrazinamide (PZA)
- effective vs. slow growing intracellular MTB in early tx
- PZA only active in low pH (macrophage phagosome)
- converted to pyrazinoic acid (POA) by mycobacterial pyrazinamidases-\> ?lowers pH below growth range for MTB, decr FA synthesis req for mycolic acid synthesis?
- AE: hepatotoxicity, CI in pregnancy (US only)
53
Hydrocortisone Cream
- corticosteroid
- anti-inflammatory
- activates lipocortins-\> inhibition of phospholipase A2, decr leukocyte lysosomal membrane breakdown-\> decr AA release, decr PG synthesis, decr inflam.
- decr mast cell degranulation, decr histamine release-\> decr vasodilation & permeability-\> decr leukocyte infiltration
54
Vancomycin
glycopeptide, tx vs MRSA
- binds to D-ala-D-ala terminus on precursor peptide units, inhibits peptidoglycan polymerase, prevents peptidoglycan cross-linking in 2nd stage of bacterial cell wall synthesis-\> incr permeability, apoptosis
- use sparingly to prevent development of bacterial resistance
- fever, phlebitis
55
OTC Antihistamines
- binds to histamine receptors (H1 mainly), prevents response to histamine-\> decr vascular permeability & prevents bronchoconstriction, release of proinflam. cytokines.
- 1st generation (benadryl): crosses BBB-\> CNS sedation
- 2nd generation (claritin, zyrtec): less crossing of BBB-\> less CNS sedation
56
Omalizumab
- monoclonal antibody, anti-IgE, tx allergic asthma
- binds circulating IgE, prevents binding to IgE Fc receptors on mast cells & basophils, prevents release of allergic/inflam. mediators
- indirectly downregulates IgE Fc receptors
- CI: acute asthma, high cost, lack of clinical trial data, dosing limitations
57
Methylprednisolone/Solumedrol
- glucocorticoid, antiinflam.
- slow onset, long duration
- binds to glucocorticoid receptors in cytoplasm, translocates to nucleus, binds to GRE on DNA, regulates transcription & protein synthesis-\>decr leukocyte infiltration, suppress humoral immune response, interfere w/ inflam mediators
- activate lipocortins, decr AA release, decr PG synthesis, antiinflam effects
- AE: iatrogenic cushing syndrome
- taper: long term use-\> decr adrenal cortex release of glucocorticoids, adrenocortical atrophy-\> abrupt cessation-\> adrenal insufficiency
58
Zafirlukast
- leukotriene receptor antagonist, long term asthma tx, less effects than corticosteroids & B2 agonists
- selectively & competitively inhibits binding of leukotrienes to CysLT-1 receptors-\> prevents bronchoconstriction, endothelial permeability (inflammation, edema), and thick mucus secretion
- Not indicated for acute asthma
59
Zileuton
- leukotriene antagonist, 5-lipoxygenase inhibitor, long term tx of asthma
- selectively inhibits 5-lipoxygenase preventing AA conversion to LTs-\> prevents bronchoconstriction, endothelial permeability (inflam, edema), thick mucus secretion
- Not indicated for acute asthma, less effective than corticosteroids & B2 agonists.
60
Cromolyn Sodium
- mast cell stabilizer, asthma prophylaxis
- ?MoA: works @ mast cell surface, prevents influx of Ca2+, prevents release of histamines, LTs, SRS-A, decr bronchial hyperreactivity
- replaced by LTs as non-ICS tx of asthma, frequent dosing d/t short duration of action, poor absorption
- not indicated for acute asthma
61
Theophylline
- alternative long-term tx of asthma
- ?MoA: prevents PDE III/IV degradation of cAMP-\> smooth muscle relaxation, bronchodilation
- ?MoA: binds to adenosine receptor, prevents adenosine-mediated bronchoconstriction, bronchodilation
- previously standard, but used less d/t narrow therapeutic range, OD-\> sz, arrhythmias
- cheap, used more in developing countries
