441-Final

Humalog, rapid-acting

Novorapid, rapid-acting

Apidra, rapid-acting

regular insulin

regular insulin

• neutral protamine hagedorn
• humulin-N, Novolin ge NPH

Lantus, long-acting

Levemir, long-acting

glyburide, glipizide, glimepiride

repaglinide, nateglinide

metformin

pioglitazone, rosiglitazone

acarbose

sitagliptin, exenatide, liraglutide

prava, lova, atorva, simva, fluva, rosuvastatin

bile acid sequestrants (resins)

bile acid sequestrants (resins)

cholesterol absorption inhibitor

nicotinic acid, TGL inhibitor

gemfibrozil, fenofibrate, bezafibrate - PPAR-alpha stimulants

Xenical, gastric/pancreatic lipase inhibitor

E2, most potent natural estrogen, made in ovaries

E1, made in tissues, liver, placenta (during pregs), adipose tissue in postmen

E3, metabolite of both E1 and E2, made in liver and placenta

SERM, 1st line tx of BC in premen, also in px. risk of endometrial cancer

• SERM, px only for postmenopause.
• Osteoporosis: anti-resorptive (anti-catabolic).
• increase BMD in postmen, but less than E or alendronate.
• 50% RR of vertebral fx, no effect on non-vert or hip.
• Also decreases risk of breast cancer.
• May aggravate vasomotor symptoms (due to selective anti-E effect).
• Increase risk of VTE (similar to HRT).

SERM-like, antiestrogenic (blocks - feedback of E at hypo and pit, increases gonadotropins), tx anovulatory infertility

aromatase inhibitor

aromatase inhibitor

aromatase inhibitor

anti-estrogen; bids to ER and competitively inhibits E binding, causes receptor degradation. for metastatic breast cancer

1st gen progestin, potency 1, weak androgenic.

2nd gen progestin, potency 10-20, most androgenic activity

3rd gen progestin, potency 10-20, lower androgenic activity than levonorgestrel

progestin component, analogue of spironolactone; potency 2, no androgenicity, but slight anti-mineralocorticoid (blocks activity of aldosterone)

• anti-progestin; competitive PR inhibitor, blocks ovulation if in F, causes menses if in L.
• abortion pill

• SPRM: binds PR and partial agonist activity
• anti-ovulatory (inhibits LH release and ovulation)decreases endometrial thickness and impairs implantation
• ECP (===planB)

norgestrel + EE

norelgestromin + EE

levonorgestrel

etonorgestrel + EE

• synthetic GnRH
• pulsatile: profertility (LH release)
• continuous: suppress gonadotropin secretion (mostly the agonists though)

GnRH agonist; profertility (pulses) OR suppression of LH/FSH in advanced prostate cancer

GnRH agonist; profertility (pulses) OR suppression of LH/FSH in endometriosis (continuous)

GnRH agonist; profertility (pulses) OR suppression of LH/FSH in advanced prostate cancer

GnRH antag; inhibition of LH/FSH secretion without agonist phase; for in vitro fert or advanced prostate cancer

GnRH antag; inhibition of LH/FSH secretion without agonist phase; for in vitro fert or advanced prostate cancer

• synthetic weak androgen
• decrease GnRH and LH/FSH secretion; decrease sex steroid secretion by ovaries
• tx endometriosis

testosterone ester, PO, absorbed into lymph, bypass hepatic breakdown

test. esters; FFA esterified at 17-beta-OH position

17-alpha-alkylated androgens, anabolic steroid - hepatotoxicity

• pure anti-androgen
• blocks receptors at target, hypo, and pit; but also blocks - feedback so testosterone increases
• for tx advanced prostatic carcinoma
• may be given with GnRH agonist to decrease testosterone

• pure anti-androgen
• blocks receptors at target, hypo, and pit; but also blocks - feedback so testosterone increases
• for tx advanced prostatic carcinoma
• may be given with GnRH agonist to decrease testosterone

• pure anti-androgen
• blocks receptors at target, but also at hypo, and pit: blocks - feedback so testosterone increases
• for tx advanced prostatic carcinoma
• may be given with GnRH agonist to decrease testosterone

• androgen antagonist with progesterone activity
• prog act blocks Gn secretion so no increase in testosterone (maintains - feedback on LH)
• prostatic carcinoma, in Acne

• Proscar, Propecia
• 5-alpha-reductase inhibitor: prevents conversion to DHT
• tx of BPH, androgenetic alopecia, prostate cancer px

• 5-alpha-reductase inhibitor: prevents conversion to DHT
• tx of BPH, androgenetic alopecia, prostate cancer px

• anti-resorptive (anti-catabolic).
• considered for tx of mod-severe vasomotor symptoms of postmenopause only
• osteoporosis prevention is a secondary benefit

• first-gen bisphosphonate, least potent anti-resorptive(anti-catabolic). R1 -CH3, R2 -OH
• Incorporates into bone, released when hydroxyapatite dissolved by osteoclasts
• Preferentially taken up by osteoclasts -> impair recruitment, differentiation, activity of osteoclasts. Increase osteoclast apoptosis.
• Dose that inhibits bone resorption also impairs bone mineralization --> osteomalacia.
• Therefore give: 400mg etid x14d, then 500mg CaCO3 x76d.
• 1o px post-men: no effect
• 2o px post-men: 50% RR vertebral fracture. NSS for non-vert, hip, wrist.

• 2nd gen bisphosphonate. anti-resorptive (anti-catabolic). R1 -OH, R2 -CH2CH2CH2NH2
• Incorporates into bone, released when hydroxyapatite dissolved by osteoclasts
• Preferentially taken up by osteoclasts -> impair recruitment, differentiation, activity of osteoclasts. Increase osteoclast apoptosis.
• 1o px: 45% RR vertebral fracture (vs. NOT risedronate, and zolen was not tested)
• 2o px: 50% RR in vert, non-vert, hip fx (all 3 drugs)
• Orally, poorly absorbed (1-5%). Empty stomach, water only. t1/2 is 1 hour in plasma, 10 years in bone.
• 10mg/d or 70mg/week

• 2nd gen bisphosphonate. anti-resorptive (anti-catabolic). R1 -OH, R2 -CH2N-ring.
• Incorporates into bone, released when hydroxyapatite dissolved by osteoclasts
• Preferentially taken up by osteoclasts -> impair recruitment, differentiation, activity of osteoclasts. Increase osteoclast apoptosis.
• 1o px: no effect
• 2o px: 50% RR in vert, non-vert, hip fx (all 3 drugs)
• Orally, poorly absorbed (1-5%). Empty stomach, water only. t1/2 is 1 hour in plasma, 10 years in bone.
• 5mg/d, or 35mg/week, or 75mg/day x2 days/month.

• 3rd gen bisphosphonate. anti-resorptive (anti-catabolic). R1 -OH, R2 CH2N-ring.
• Incorporates into bone, released when hydroxyapatite dissolved by osteoclasts
• Preferentially taken up by osteoclasts -> impair recruitment, differentiation, activity of osteoclasts. Increase osteoclast apoptosis.
• 1o px: not tested
• 2o px: 50% RR in vert, non-vert, hip fx (all 3 drugs)
• Injected 5mg once/year by IV infusion.

• peptide hormone in calcium homeostasis; decreases Plasma Calcium. Anti-resorptive (anti-catabolic).
• Suppresses activity of osteoclasts, decreases bone resorption.
• 30% RR in vertebral fx, but not non-vertebral.
• May have analgesic effect.
• 2nd line tx for post-men osteo, 1st line tx for pain ass'd with acute vert fx.

• osteoporosis anti-resorptive (anti-catabolic)
• monoclonal Ab to RANKL that mimcs action of OPG, prevents RANKL from binding to RANK.
• Decrease in osteoclast formation and bone resorption.
• Px severe osteoporosis in post-men: 60% RR vertebral, 20% RR non-vertebral, 40% RR hip
• May also be useful in conditions characterized by temporary rapid bone resorp (i.e. aromatase inhib tx)
• Injection: 60mg SC q6mo.

• recombinante human PTH.
• Increases recruitment and differentioatn of osteoblasts and decreases apoptosis.
• Given intermittently, get net bone forming effect: increases bone remodeling, with anabolic window: initial stimulation of bone formation before resorption takes place. Window lasts 12-18 months.
• 2o post-men: 65% RR vert, 53% RR non-vert. No sig decrease in hip fx.
• Also for glucocorticoid-induced osteo in high-risk pts.
• Tx duration limited 2 years.Once daily injections.

• antiplatelet: thromboxane A2 inhibitor.
• Irreversibly inhibits platelet COX1, blocking TXA2 formation (and therefore no platelet shape change, granule release, or aggregation). Overall decreased platelet aggregation (but weakest since blocks only one pathway).
• Low doses (75-325mg) preferentially inhibits platelet COX over endothelial COX2 (which is important in prostacyclin).

• antiplatelet: ADP-inhibitor. pro-drug.
• selectively irreversibly blocks ADP binding to P2Y12 platelet receptor, therefore no ADP-induced platelet aggregation because no activation of GPIIb/IIIa receptors. (Also partially prevents aggregation by other agonists since ADP is released from all activated platelets irrespective of agonist.)
• As save as aspirin.

• antiplatelet: ADP-inhibitor. pro-drug.
• interferes with platelet-fibrinogen binding and platelet-platelet int'n, maybe due to inhibition of ADP to P2Y12.
• Reserved for pts who cannot tolerate ASA.

• antiplatelet: ADP-inhibitor. pro-drug - converted by intestinal and hepatic CYP450.
• irreversibly binds P2Y12 for lifespan, inhibits platelet activation and aggregation.
• Can be taken together with ASA.

• antiplatelet: GPIIb/IIIa receptor antagonist.
• Most potent antiplatelet agents because blocks final common pathway of all stimuli (thrombin, ADP, collagen). Prevents fibrinogen-mediated cross-linkage.
• monoclonal antiplatelet Ab, prevents binding of fibrinogen and VWF to prevent aggregation.
• Max inhibition observed when >80% of receptors blocked.

• antiplatelet: GPIIb/IIIa receptor antagonist.
• Most potent antiplatelet agents because blocks final common pathway of all stimuli (thrombin, ADP, collagen). Prevents fibrinogen-mediated cross-linkage.
• small-molecule peptide, resembles fibrinogen RGD recognition sequence.
• Reversibly inhibits platelet aggreg by preventing binding of fibrinogen and VWF to receptors.

• antiplatelet: GPIIb/IIIa receptor antagonist.
• Most potent antiplatelet agents because blocks final common pathway of all stimuli (thrombin, ADP, collagen). Prevents fibrinogen-mediated cross-linkage.
• non-peptide antagonist of fibrnogen binding to receptor.
• Reversible. Occupies receptor, therefore inhibits binding of fibrinogen and VWF to receptor.

• antiplatelet: phosphodiesterase inhibitor.
• reduces platelet adhesiveness by increasing cAMP --> release prostacyclin. Also vasodilator.

• Anticoagulant: indirect thrombin inhibitor.
• 5,000-30,000 daltons, injectable. Extracted from porcine mucosa. Strongly anionic due to sulfate and carboxyl groups.
• Very polar, does not cross membranes easily. Binds to plasma ANTITHROMBIN III via pentasaccharide sequence. Increases affinity of antithrombin to Xa and thrombin (among others), promotes inhibition of Xa
• Pentasaccharide only (<18 monosac's long, MW<6,000) - only inhibits factor Xa.
• Longer heps (>18ms, MW>6,000) - have stronger inhibitory capacity against thrombin (heparin must bind to both antithrombin AND thrombin [at exosite 2] to form a ternary complex).
• Rapid acting - peak after 2-4 hours.

• Anticoagulant: indirect thrombin inhibitor.
• 4,000-6,000 daltons, injectable. Extracted from porcine mucosa. Strongly anionic due to sulfate and carboxyl groups.
• Better bioavailability (less binding to endothelium and plasma proteins).
• Longer t1/2...predictable anticoagulant response.
• e.g. dalteparin, enoxaparin, nadroparin, tinzaparin.

• Anticoagulant: direct thrombin inhibitor.
• recombinant Hirudin
• Bivalent irreversible binding to thrombin catalytic site and exosite 1.
• inhibits free and bound thrombin.
• No HIT.

• Anticoagulant: direct thrombin inhibitor.
• short synthetic peptide, resembles Hirudin.
• Bivalent reversible binding to thrombin catalytic site and exosite 1.
• inhibits free and bound thrombin.
• No HIT.

• Anticoagulant: direct thrombin inhibitor.
• small molecule, binds only to catalytic site -> monovalent.
• Reversible, inhibits free and bound thrombin.
• No HIT.

• Anticoagulant: direct thrombin inhibitor.
• first oral direct monovalent thrombin (factor IIa) inhibitor.
• Is a prodrug that is converted by esterases in blood.
• Reversible, inhibits free and bound thrombin.
• No HIT.

• Anticoagulant: factor Xa inhibitor, indirect (binds to antithrombin to enhance affinity 300x).
• synthetic pentasaccharide with the sequence of heparin. Parenteral.
• Long t1/2. Lower risk of HIT.

• Anticoagulant: factor Xa inhibitor, DIRECT and oral.
• Competitively, selectively, directly inhibits factor Xa...10,000x greater.
• Prolongs clotting times in human plasma.

• Anticoagulant: vitamin K antagonist
• Structure similar to Vitamin K, therefore competitively inhibits and interferes with hepatic synthesis of Vit K-dependent clotting factors - II, VII, IX, X, anticoagulant protein C. (decreases availability of hydroquinone).
• Substrate of CYP450. No effect on previously synthesized factors...first anticoag effect at 8-12 hours.
• Effective anticoag at least 1 week - due to half-lives of clotting factors.

• Anticoagulant: alternative
• mixture of non-heparin low MW sulfated glycosaminoglycuronans...some affinity to antithrombin...ahtithrombotic.
• Choice for pts with HIT.

• Anticoagulant: alternative
• Protein C, with co-factor protein S, degrades factors Va and VIIIa --> natural anticoag by inhibiting activation of prothrombin and factor X.

plasmin inhibitor, used as necessary to counteract effects of thrombolytic drugs.

• Thrombolytic: 1st gen
• purified from beta-hemolytic streptococci
• forms active complex with plasminogen to convert uncomplexed plasminogen to active plasmin.
• Non-selective between circulating and fibrin-bound plasminogen.
• Non-fibrin selective: also catalyzes degradation of fibrinogen and factors V and VII.
• Given by infusion...need loading dose to over come antibodies.

• Thrombolytic: 2nd gen
• mostly from recombinant DNA, is also a naturally occurring intrinsic compound.
• Low affinity for plasminogen, but rapidly activates plasminogen bound to fibrin in a thrombus or hemostatic plug (specific to stuff at fibrin surface x00 times more than in circulation).
• Fibrin-selective - esp at low doses (no fibrinogen)
• short half-life - administered as initial bolus then infusion.

• Thrombolytic: 3rd gen
• recombinant PA.
• less expensive to make but less fibrin-specific

• Thrombolytic: 3rd gen
• more fibrin specific than t-PA, made by introducing aa modifications to t-PA. longer half-life.

• positive inotropic drug: used for refractory CHF. Also potent anti-arrhythmic (through vagus nerve mediation, release of ACh prolongs AV refractory period)
• reversibly inhibits Na-K ATPase of cardiac muscle membrane, leads to increase in intracellular Na concentration, thereby indirectly inhibiting Na-Ca exchanger (already lots of Na in cell, NCX can't bring more Na in to take out Ca).
• Ca2+ intracellular increases, --> more available for troponin C binding sites, --> increased systolic force of contraction --> increased cardiac output.
• Improves circulation leads to reduced sympathetic activity.
• Also has vagal effects: reduce SA node firing (decreased automaticity), slows AV node conduction (anti-arrhythmic).
• Delayed afterdepolarization problem: from calcium overload in SR, leads to spontaneous Ca release.

• positive inotropic: phosphodiesterase inhibitor: used for refractory CHF. short term therapy.
• Increases cardiac cAMP -> activation of protein kinase allows phosphorylation of cellular proteins (i.e. slow Ca2+ channel) --> increase Ca2+ influx, more Ca in SR --> increased CO.
• In vascular SM, cAMP promotes direct relaxation.

positive inotropic: B-adrenoceptor agonist -> increase cAMP --------> increase cardiac output.

• synthetic brain natriuretic peptide (===ANP)
• increases cGMP in smooth muscle cells -> decrease Ca, decrease force of contraction, leads to SM relaxation.
• Reduces venous and arteriolar tone --> powerful vasodilator.
• Also causes diuresis.

• Class IA antiarrhythmic: Na+ Channel Blocker
• blocks Na+ channel @ open and activated state.
• also blocks K+ channel to prolong AP.
• overall, increases refractory period, decreases re-entry.
• SE: cinchonism, diarrhea, ab cramps, N/V, hypotension, Torsades de Pointes, aggravation of underlying HF, conduction disturbances or ventricular arrhythmias, fever, hepatitis, thrombocytopenia, hemolytic anemia.

• Class IA antiarrhythmic: Na+ Channel Blocker
• blocks Na+ channel @ open and activated state.
• also blocks K+ channel to prolong AP.
• overall, increases refractory period, decreases re-entry.
• SE: systemic lupus erythematosus, diarrhea, nausea, vomiting, Torsades de Pointes, aggravation of underlying HF, conduction disturbances or ventricular arrhythmias, agranulocytosis.

• Class IA antiarrhythmic: Na+ Channel Blocker
• blocks Na+ channel @ open and activated state.
• also blocks K+ channel to prolong AP.overall, increases refractory period, decreases re-entry.

• Class IB antiarrhythmic: Na+ Channel Blocker
• major block Na+ channel @ open and INactivated
• minor block Na+ channel @ open and activated
• shortens depol, quickens repol, and shortens AP
• overall: decreases refractory period, and decreases re-entry.
• SE: dizziness, sedation, slurred speech, blurred vision, paresthesia, muscle twitching, confusion, N/V, seizures, psychosis, sinus arrest, aggravation of underlying conduction disturbances.

• 
• 

• Class IB antiarrhythmic: Na+ Channel Blocker
• major block Na+ channel @ open and INactivated
• minor block Na+ channel @ open and activated
• shortens depol, quickens repol, and shortens AP
• overall: decreases refractory period, and decreases re-entry.
• SE: dizziness, sedation, anxiety, confusion, paresthesia, tremor, ataxia, blurred vision, N/V, anorexia, aggravation of underlying conduction disturbances or vent arrhythmias.

• Class IB antiarrhythmic: Na+ Channel Blocker
• major block Na+ channel @ open and INactivated
• minor block Na+ channel @ open and activated
• shortens depol, quickens repol, and shortens AP
• overall: decreases refractory period, and decreases re-entry.

• Class IC antiarrhythmic: Na+ Channel Blocker
• most significant effect on Na+ channels @ open & activated
• mild effect on Na+ channels @ open & inactivated
• 0 effect on K+ and repol, no change in ERP
• but refractory period of AV node increased.
• for Atrial flutter and fibrillation and VT/VF.
• SE: dizziness, fatigue, bronchospasm, headache, taste disturbances, N/V, bradycardia or AV block, aggravation of underlying HF, conduction disturbances or ventricular arrhythmias.

• Class IC antiarrhythmic: Na+ Channel Blocker
• most significant effect on Na+ channels @ open & activated
• mild effect on Na+ channels @ open & inactivated
• 0 effect on K+ and repol, no change in ERP
• but refractory period of AV node increased.
• for Atrial flutter and fibrillation and VT/VF.
• SE: blurred vision, dizziness, dyspnea, headache, tremor, nausea, aggravation of underlying HF, conduction disturbances or ventricular arrhythmias.

• Class II antiarrhythmic: B-adrenoceptor antagonist
• blocks B1 receptor and SNS stimulation, decreases cAMP
• @ pacemaker cells:
• 1) decrease slope of Phase 4: opposes adrenaline effect at transient Ca2+ channels
• 2) decrease slope of Phase 0: inhibits slow L-type Ca2+ channels, decrease HR
• @ nonpacemaker cells:
• at Phase 0, blocks inward Na+ current - increase ERP, decrease conduction.
• Antihypertensive: B1 selective blocker at low doses
• therefore, less effect on bronchioles

• Class II antiarrhythmic: B-adrenoceptor antagonist
• blocks B1 receptor and SNS stimulation, decreases cAMP
• @ pacemaker cells:
• 1) decrease slope of Phase 4: opposes adrenaline effect at transient Ca2+ channels
• 2) decrease slope of Phase 0: inhibits slow L-type Ca2+ channels, decrease HR
• @ nonpacemaker cells:
• at Phase 0, blocks inward Na+ current - increase ERP, decrease conduction.
• Antihypertensive: non-cardioselective beta-adrenoceptor antagonist
• blocks B1R - less CO, less renin release so fall in angiotensin II levels and decrease in tubular Na reabs.
• block B2R - presynaptically, reduce NE overflow. Also - (bad) - increases risk of bronchoconstriction, peripheral VC, masking of compensatory response ass'd with hypoglyc...etc.

• Class II antiarrhythmic: B-adrenoceptor antagonist
• blocks B1 receptor and SNS stimulation, decreases cAMP
• @ pacemaker cells:
• 1) decrease slope of Phase 4: opposes adrenaline effect at transient Ca2+ channels
• 2) decrease slope of Phase 0: inhibits slow L-type Ca2+ channels, decrease HR
• @ nonpacemaker cells:
• at Phase 0, blocks inward Na+ current - increase ERP, decrease conduction.
• Antihypertensive: B1 selective blocker at low doses
• therefore, less effect on bronchioles

• Class II antiarrhythmic: B-adrenoceptor antagonist
• blocks B1 receptor and SNS stimulation, decreases cAMP
• @ pacemaker cells:
• 1) decrease slope of Phase 4: opposes adrenaline effect at transient Ca2+ channels
• 2) decrease slope of Phase 0: inhibits slow L-type Ca2+ channels, decrease HR
• @ nonpacemaker cells:
• at Phase 0, blocks inward Na+ current - increase ERP, decrease conduction.
• Antihypertensive: B1 selective blocker at low doses
• therefore, less effect on bronchioles

• Class III antiarrhythmic: K+ channel blocker
• blocks K+ in plateau phase & blocks repolarization
• prolongs AP, increases ERP, more risk of TdP
• Amiodarone has characteristics of all Vaughan Williams classes:
• 1) Na+ channel blocker
• 2) non-comp, non-sel B-blocker
• 3) K+ channel blocker
• 4) small degree of Ca2+ blocker activity
• initial action: B-blockade (by blocking Ca2+ currents, block AP initiation by SA)
• chronic: K+ effect, prolonged repolarization.
• SE: tremor, ataxia, paresthesia, insomnia, corneal microdeposits, optic neuropathy/neuritis, nausea, vomiting, anorexia, constipation, TdP, brady or AV block, pulmonary fibrosis, liver fxn test abnorms, hepatitis, hypothyroidism, hyperthyroidism, photosensitivity, blue-gray skin discoloration, hypotension (IV), phlebitis (IV)

• Class III antiarrhythmic: K+ channel blocker
• blocks K+ in plateau phase & blocks repolarization
• prolongs AP, increases ERP, more risk of TdP

• Class III antiarrhythmic: K+ channel blocker
• blocks K+ in plateau phase & blocks repolarization
• prolongs AP, increases ERP, more risk of TdP
• Antihypertensive: non-cardioselective beta-adrenoceptor antagonist
• blocks B1R - less CO, less renin release so fall in angiotensin II levels and decrease in tubular Na reabs.
• blocks B2R - presynaptically, reduce NE overflow. Also - (bad) - increases risk of bronchoconstriction, peripheral VC, masking of compensatory response ass'd with hypoglyc...etc.
• SE: dizziness, weakness, fatigue, N/V, diarrhea, brady, TdP, bronchospasm, aggravation of underlying HF

• Class III antiarrhythmic: K+ channel blocker
• blocks K+ in plateau phase & blocks repolarization
• prolongs AP, increases ERP, more risk of TdP
• SE: headache, dizziness, TdP

• Class III antiarrhythmic: K+ channel blocker
• blocks K+ in plateau phase & blocks repolarization
• prolongs AP, increases ERP, more risk of TdP
• SE: headache, TdP, hypotension

• Class 4 Antiarrhythmic: Ca2+ Channel Blocker
• blocks voltage sensitive Ca2+ current during Phase 2 plateau of non-pacemaker myocytes
• also decreases automaticity and conduction velocity in both SA and AV nodes.
• Calcium Channel Blocker - primary action at the heart muscles (myocardium), some in conducting tissue.
• Decrease Calcium entry into heart muscle, decrease cardiac output.

• weak diuretic: carbonic anhydrase inhibitor
• Used primarily for glaucoma: blocks CA in ciliary cells to prevent HCO3- secretion into aqueous humor...and reduce Na and H2O transport --> decrease IOP)
• Also may be used for acute mountain sickness and epilepsy.
• Very weak diuretic; CA is in luminal membrane of proximal tubule, so by blocking CA, deplete intracellular H+ and Na/H+ exchanger is inhibited so Na+ stays in lumen.
• but 99% of CA must be inhibited before diuretic activity expressed. Even if it is blocked, not much effect because thick ascending limb can compensate for the less effective proximal reabsorption.

• diuretic: loop-acting
• @ thick ascending limb, inhibits Na+/K+/2Cl- co-transporter.
• Inhibits NaCl reabsorption --> increases NaCl, K+, water, Mg2+ and Ca2+ excretion
• (hypokalemia due to diversion of Na+ to be reabsorbed at distal tubule, where K+ can easily be excreted)
• can cause hypomagnesemia.

• diuretic: loop-acting
• @ thick ascending limb, inhibits Na+/K+/2Cl- co-transporter.
• Inhibits NaCl reabsorption --> increases NaCl, K+, water, Mg2+ and Ca2+ excretion
• (hypokalemia due to diversion of Na+ to be reabsorbed at distal tubule, where K+ can easily be excreted)
• can cause hypomagnesemia.

• diuretic: loop-acting
• @ thick ascending limb, inhibits Na+/K+/2Cl- co-transporter.
• Inhibits NaCl reabsorption --> increases NaCl, K+, water, Mg2+ and Ca2+ excretion
• (hypokalemia due to diversion of Na+ to be reabsorbed at distal tubule, where K+ can easily be excreted)
• can cause hypomagnesemia.

• diuretic: thiazide. Diuretic of choice for HTN.
• @ early distal tubule, inhibits Na+/Cl- co-transporter.
• Inhibits reabsorption of NaCl, therefore decreasing urinary excretion of Ca2+ by enhancing Na/Ca exchanger at basolateral membrane to bring Na+ into cell and Ca2+ back into blood. Increases diuresis.
• Also promotes vasodilation (hyperpolarization of smooth muscle, involving EDHF, PGI2, NO).
• can cause hypokalemia, similar to loop diuretics.

• diuretic: thiazide. Diuretic of choice for HTN.
• @ early distal tubule, inhibits Na+/Cl- co-transporter.
• Inhibits reabsorption of NaCl, therefore decreasing urinary excretion of Ca2+ by enhancing Na/Ca exchanger at basolateral membrane to bring Na+ into cell and Ca2+ back into blood.
• Also promotes vasodilation (hyperpolarization of smooth muscle).
• can cause hypokalemia, similar to loop diuretics.

• diuretic: thiazide. Diuretic of choice for HTN.
• @ early distal tubule, inhibits Na+/Cl- co-transporter.
• Inhibits reabsorption of NaCl, therefore decreasing urinary excretion of Ca2+ by enhancing Na/Ca exchanger at basolateral membrane to bring Na+ into cell and Ca2+ back into blood.
• Also promotes vasodilation (hyperpolarization of smooth muscle).
• can cause hypokalemia, similar to loop diuretics.

• diuretic: potassium-sparing, aldosterone antagonist.
• @ late distal tubule & collecting duct, competitive antagonist of aldosterone.
• Competitively inhibits binding of aldosterone to MR (mineralcorticoid receptors), decrease expression of AIP which increase Na+ channels and Na+/K+ ATP-ase and more ATP... therefore increasing Na+, Cl-, water excretion, and decreases K+ and H+ in urine (no more negative lumen voltage from aldosterone-induced increased Na+ conductance).
• i.e. Na+ not coming into cell, so K+ doesn't have to leave. ===potassium sparing.

• diuretic: potassium-sparing, aldosterone antagonist.
• @ late distal tubule & collecting duct, competitive antagonist of aldosterone.
• Competitively inhibits binding of aldosterone to MR (mineralcorticoid receptors), decrease expression of AIP which increase Na+ channels and Na+/K+ ATP-ase and more ATP... therefore increasing Na+, Cl-, water excretion, and decreases K+ and H+ in urine (no more negative lumen voltage from aldosterone-induced increased Na+ conductance).
• i.e. Na+ not coming into cell, so K+ doesn't have to leave. ===potassium sparing.

• diuretic: potassium-sparing, non-aldosterone, direct sodium channel inhibitor.
• @ late distal tubule & collecting duct.
• Inhibits entry of Na+ from tubule lumen side...decreases electrical potential across membrane which is the driving force for K+ exchange, therefore increases Na+, Cl-, water excretion; decreases K+ in urine.

• diuretic: potassium-sparing, non-aldosterone, direct sodium channel inhibitor.
• @ late distal tubule & collecting duct.
• Inhibits entry of Na+ from tubule lumen side...decreases electrical potential across membrane which is the driving force for K+ exchange, therefore increases Na+, Cl-, water excretion; decreases K+ in urine.

• diuretic: osmotic.
• Increases osmotic pressure in tubules, holds water in as passes down proximal tubule and loop of henle.
• Blocks 10-15% filtered Na+.

• Angiotensin-converting enzyme inhibitor
• lowers total peripheral resistance and decreases BP
• inhibits ACE, which converts Angiotensin I to II
• therefore, decreases ATII-mediated VC --> decreased PVR
• and decreases aldosterone secretion --> decreased sodium retention and ECF volume
• and decreases ADH secretion, decreases thirst.
• May also block degradation of bradykinin (==VD in lungs, fluid --> dry cough)

• Angiotensin-II receptor blocker/antagonist
• lowers total peripheral resistance and decreases BP
• competitive antagonist of Angiotensin II at AT1 receptors.
• Prevents: VC sm, aldosterone secretion, release of adrenal catecholamines, thirst, ADH release.
• More complete inhibition of angiotensin action than ACEI because chymase also makes AngII.

• direct renin inhibitor.
• antihypertensive, blocks renin proteolytic activity of ang-> angI. Suppresses whole RAAS system.
• Also can block compensatory rise in Plasma Renin Activity (due to loss of stimulation fo AT1 receptors of JGC, compensatory increase in renin release).

antihypertensive: non-cardioselective B blocker

antihypertensive: non-cardioselective B blocker

• antihypertensive: cardioselective B blocker
• B1 selective at low doses

antihypertensive: mixed B and A antagonism

antihypertensive: mixed B and A antagonism

• antihypertensive: B blocking and partial agonist activity
• lower blood pressure by decreasing cardiac output (B1) and vascular resistance (B2)

• antihypertensive: B blocking and partial agonist activity
• lower blood pressure by decreasing cardiac output (B1) and vascular resistance (B2)

• antihypertensive: alpha-1 specific blocker
• Acts at post-synaptic receptors to prevent phosphorylation/activation of myosin light chain kinase and contraction...
• leads to arteriole and venous sm dilation --> decrease TPR and arteriol pressure.
• therefore, prevents catecholamine-induced vasoconstriction.
• Only acts at vascular smooth muscle.

• antihypertensive: alpha-1 specific blocker
• newer...gradual onset of action.

• vasodilator, not used for treatment of hypertension.
• phosphodiesterase 5 inhibitor, tx erectile dysfunction.
• Prevents breakdown of cGMP to 5'GMP to sustain effect of NO--> cGMP --> relaxation of smooth muscle of corpus cavernosum and blood vessel --> maintain erection.
• Sildenafil may be used to treat primary pulmonary HTN alone OR with endothelin receptor antagonists and prostacyclin.

• vasodilator. prostaglandin E1 analog.
• Used in tx of erectile dysfunction.
• Acts locally, directly increases cAMP in smooth muscle --> decrease calcium --> relaxation. No involvement of NO.
• Initiates erection whether stimulation present or not.

• Class 4 Antiarrhythmic: Ca2+ Channel Blocker
• blocks voltage sensitive Ca2+ current during Phase 2 plateau of non-pacemaker myocytes
• also decreases automaticity and conduction velocity in both SA and AV nodes.
• Antihypertensive. Calcium Channel Blocker: primary action on conducting tissues.
• Decreases flow of Calcium through transmission of nerve impulses. Slows generation of action potentials at SA node, slows conduction of action potentials through AV node.
• decreases conduction, decrease force of contraction.

• antihypertensive.
• Calcium Channel blocker: primarily act on arterioles.
• Decrease Calcium entry into smooth muscles, cause relaxation and therefore decrease TPR.

• antihypertensive, used for severe HTN only.
• decreases TPR, decreases BP.
• Opens K+ channel of smooth muscle
• hyperpolarization
• decreased Ca2+ entry
• relaxation of smooth muscle.
• SE: hypertrichosis.

• antihypertensive, acts directly on smooth muscle of blood vessels, vasodilation as a result of endothelium-derived relaxing factor --> opens K+ channels or NO generation.
• decreases TPR, decreases BP.
• SE: may increase CO...may cause myocardial ischemia...
• Not used alone, when combined with BB and diuretic, drug is better tolerated.

• antihypertensive, mainstay for hypertensive crises
• DIRECT VD of arteries and veins by releasing NO.
• NO--> guanylate cyclase --> cGMP --> cGMP-dependent protein kinase inhibits Calcium influx...Myosin fails to be phosphorylated...decreased contraction.= relaxation
• also: venous pooling (decrease preload) and decrease arteriolar resistance (decrease TPR and BP)
• May cause cyanide poisoning: therefore, must be administered with sodium thiosulfate.

• antihypertensive, organic nitrite. tx of Angina.
• Enzymatically converted (in presence of intracellular sulfhydryl groups) to S-nitrosothiol --> NO.
• Increased NO --> improves coronary blood flow.
• Large first-pass metabolism. Rapid onset.

• antihypertensive, organic nitrite. tx of Angina.
• Enzymatically converted (in presence of intracellular sulfhydryl groups) to S-nitrosothiol --> NO.
• Increased NO --> improves coronary blood flow.
• Large first-pass metabolism. Rapid onset.

• antihypertensive, organic nitrite. tx of Angina.
• Enzymatically converted (in presence of intracellular sulfhydryl groups) to S-nitrosothiol --> NO.
• Increased NO --> improves coronary blood flow.
• No first-pass, longer duration of action.

• acts on A1 receptor of AV node
• decreases cAMP levels, therefore blocks Ca2+ current due to decreased phosphorylation of Ca2+ channel.
• Enhances K+ conductance, causes hyperpolarization
• decreases conducton velosity, increases ERP in AV node
• slows rate of rise of pacemaker potential
• SE: flushing and hypotension, paresthesias, SOB, chest pain (bronchospasm)