-
insulin lispro
Humalog, rapid-acting
-
insulin aspart
Novorapid, rapid-acting
-
insulin glulisine
Apidra, rapid-acting
-
humulin-R
regular insulin
-
novolin ge toronto
regular insulin
-
NPH insulin
- neutral protamine hagedorn
- humulin-N, Novolin ge NPH
-
insulin glargine
Lantus, long-acting
-
insulin detemir
Levemir, long-acting
-
sulfonylureas
glyburide, glipizide, glimepiride
-
meglitinides
repaglinide, nateglinide
-
-
thiazolidinediones
pioglitazone, rosiglitazone
-
alpha-glucosidase inhibitor
acarbose
-
incretin agent
sitagliptin, exenatide, liraglutide
-
HMG-CoA reductase inhibitors
prava, lova, atorva, simva, fluva, rosuvastatin
-
cholestyramine
bile acid sequestrants (resins)
-
colestipol
bile acid sequestrants (resins)
-
ezetimibe
cholesterol absorption inhibitor
-
niacin
nicotinic acid, TGL inhibitor
-
fibrates
gemfibrozil, fenofibrate, bezafibrate - PPAR-alpha stimulants
-
orlistat
Xenical, gastric/pancreatic lipase inhibitor
-
17-beta estradiol
E2, most potent natural estrogen, made in ovaries
-
estrone
E1, made in tissues, liver, placenta (during pregs), adipose tissue in postmen
-
estriol
E3, metabolite of both E1 and E2, made in liver and placenta
-
tamoxifen
SERM, 1st line tx of BC in premen, also in px. risk of endometrial cancer
-
raloxifene
- 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).
-
clomiphene
SERM-like, antiestrogenic (blocks - feedback of E at hypo and pit, increases gonadotropins), tx anovulatory infertility
-
anastrazole
aromatase inhibitor
-
letrozole
aromatase inhibitor
-
ezemestane
aromatase inhibitor
-
fulvestrant
anti-estrogen; bids to ER and competitively inhibits E binding, causes receptor degradation. for metastatic breast cancer
-
norethindrone
1st gen progestin, potency 1, weak androgenic.
-
levonorgestrel
2nd gen progestin, potency 10-20, most androgenic activity
-
desogestrel
3rd gen progestin, potency 10-20, lower androgenic activity than levonorgestrel
-
drospirenone
progestin component, analogue of spironolactone; potency 2, no androgenicity, but slight anti-mineralocorticoid (blocks activity of aldosterone)
-
mifepristone
- anti-progestin; competitive PR inhibitor, blocks ovulation if in F, causes menses if in L.
- abortion pill
-
ulipristal acetate
- SPRM: binds PR and partial agonist activity
- anti-ovulatory (inhibits LH release and ovulation)decreases endometrial thickness and impairs implantation
- ECP (===planB)
-
-
-
-
Nuvaring
etonorgestrel + EE
-
gonadorelin
- synthetic GnRH
- pulsatile: profertility (LH release)
- continuous: suppress gonadotropin secretion (mostly the agonists though)
-
buserelin
GnRH agonist; profertility (pulses) OR suppression of LH/FSH in advanced prostate cancer
-
nafarelin
GnRH agonist; profertility (pulses) OR suppression of LH/FSH in endometriosis (continuous)
-
leuprolide
GnRH agonist; profertility (pulses) OR suppression of LH/FSH in advanced prostate cancer
-
ganirelix
GnRH antag; inhibition of LH/FSH secretion without agonist phase; for in vitro fert or advanced prostate cancer
-
cetrorelix
GnRH antag; inhibition of LH/FSH secretion without agonist phase; for in vitro fert or advanced prostate cancer
-
danazol
- synthetic weak androgen
- decrease GnRH and LH/FSH secretion; decrease sex steroid secretion by ovaries
- tx endometriosis
-
testosterone undecanoate
testosterone ester, PO, absorbed into lymph, bypass hepatic breakdown
-
testosterone cypionate, enanthate
test. esters; FFA esterified at 17-beta-OH position
-
stanozolol
17-alpha-alkylated androgens, anabolic steroid - hepatotoxicity
-
flutamide
- 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
-
bicalutamide
- 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
-
nilutamide
- 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
-
cyproterone acetate
- androgen antagonist with progesterone activity
- prog act blocks Gn secretion so no increase in testosterone (maintains - feedback on LH)
- prostatic carcinoma, in Acne
-
finasteride
- Proscar, Propecia
- 5-alpha-reductase inhibitor: prevents conversion to DHT
- tx of BPH, androgenetic alopecia, prostate cancer px
-
dutasteride
- 5-alpha-reductase inhibitor: prevents conversion to DHT
- tx of BPH, androgenetic alopecia, prostate cancer px
-
HRT
- anti-resorptive (anti-catabolic).
- considered for tx of mod-severe vasomotor symptoms of postmenopause only
- osteoporosis prevention is a secondary benefit
-
Etidronate
- 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.
-
Alendronate
- 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
-
Risedronate:
- 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.
-
Zoledronate:
- 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.
-
Calcitonin
- 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.
-
Denosumab (prolia)
- 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.
-
Teriparatide
- 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.
-
Acetylsalicylic Acid (Aspirin)
- 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).
-
Clopidogrel (Plavix)
- 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.
-
Ticlopidine (Ticlid)
- 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.
-
Prasugrel (effient)
- 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.
-
Abiciximab (ReoPro)
- 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.
-
Eptifibatide (Integrilin)
- 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.
-
Tirofiban (Aggrastat)
- 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.
-
Dipyridamole
- antiplatelet: phosphodiesterase inhibitor.
- reduces platelet adhesiveness by increasing cAMP --> release prostacyclin. Also vasodilator.
-
Heparin (unfractionated)
- 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.
-
Low Molecular Weight Heparin
- 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.
-
Lepirudin
- Anticoagulant: direct thrombin inhibitor.
- recombinant Hirudin
- Bivalent irreversible binding to thrombin catalytic site and exosite 1.
- inhibits free and bound thrombin.
- No HIT.
-
Bivalirudin
- 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.
-
Argatroban.
- Anticoagulant: direct thrombin inhibitor.
- small molecule, binds only to catalytic site -> monovalent.
- Reversible, inhibits free and bound thrombin.
- No HIT.
-
Dabigatran
- 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.
-
Fondaparinux
- 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.
-
Rivaroxaban
- Anticoagulant: factor Xa inhibitor, DIRECT and oral.
- Competitively, selectively, directly inhibits factor Xa...10,000x greater.
- Prolongs clotting times in human plasma.
-
Warfarin, Nicoumalone
- 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.
-
Heparan sulfate-Danaparoid
- Anticoagulant: alternative
- mixture of non-heparin low MW sulfated glycosaminoglycuronans...some affinity to antithrombin...ahtithrombotic.
- Choice for pts with HIT.
-
Xigris - recombinant human protein C - drotrecogin alfa.
- Anticoagulant: alternative
- Protein C, with co-factor protein S, degrades factors Va and VIIIa --> natural anticoag by inhibiting activation of prothrombin and factor X.
-
Aminocaproic acid
plasmin inhibitor, used as necessary to counteract effects of thrombolytic drugs.
-
Streptokinase
- 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.
-
t-PA (tissue plasminogen activator)
- 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.
-
r-PA
- Thrombolytic: 3rd gen
- recombinant PA.
- less expensive to make but less fibrin-specific
-
tenecteplase
- Thrombolytic: 3rd gen
- more fibrin specific than t-PA, made by introducing aa modifications to t-PA. longer half-life.
-
digoxin
- 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.
-
milrinone
- 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.
-
dobutamine
positive inotropic: B-adrenoceptor agonist -> increase cAMP --------> increase cardiac output.
-
Nesiritide
- 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.
-
Quinidine
- 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.
-
Procainamide
- 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.
-
Disopyramide
- 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.
-
Lidocaine
- 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.
-
Mexiletine
- 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.
-
Tocainide
- 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.
-
Propafenone
- 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.
-
Flecainide
- 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.
-
Esmolol
- 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
-
Propranolol
- 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.
-
Metoprolol
- 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
-
Atenolol
- 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
-
Amiodarone
- 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)
-
Dronedarone
- Class III antiarrhythmic: K+ channel blocker
- blocks K+ in plateau phase & blocks repolarization
- prolongs AP, increases ERP, more risk of TdP
-
Sotalol
- 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
-
Dofetilide
- 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
-
Ibutilide
- 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
-
Verapamil
- 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.
-
acetazolamide, methazolamide, dorzolamide, brinzolamide
- 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.
-
furosemide
- 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.
-
ethacrynic acid
- 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.
-
bumetanide
- 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.
-
hydrochlorothiazide
- 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.
-
indapamide
- 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.
-
metolazone
- 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.
-
spironolactone
- 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.
-
eplerenone
- 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.
-
triamterene
- 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.
-
amiloride
- 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.
-
mannitol
- diuretic: osmotic.
- Increases osmotic pressure in tubules, holds water in as passes down proximal tubule and loop of henle.
- Blocks 10-15% filtered Na+.
-
captopril
- 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)
-
losartan
- 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.
-
aliskiren
- 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).
-
timolol
antihypertensive: non-cardioselective B blocker
-
nadolol
antihypertensive: non-cardioselective B blocker
-
bisoprolol
- antihypertensive: cardioselective B blocker
- B1 selective at low doses
-
labetalol
antihypertensive: mixed B and A antagonism
-
carvedilol
antihypertensive: mixed B and A antagonism
-
acebutolol
- antihypertensive: B blocking and partial agonist activity
- lower blood pressure by decreasing cardiac output (B1) and vascular resistance (B2)
-
pindolol
- antihypertensive: B blocking and partial agonist activity
- lower blood pressure by decreasing cardiac output (B1) and vascular resistance (B2)
-
prazosin
- 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.
-
doxazosin
- antihypertensive: alpha-1 specific blocker
- newer...gradual onset of action.
-
sildenafil, tadalafil, vardenafil
- 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.
-
alprostadil
- 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.
-
diltiazem
- 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.
-
nifedipine, amlodipine, felodipine, nimodipine
- antihypertensive.
- Calcium Channel blocker: primarily act on arterioles.
- Decrease Calcium entry into smooth muscles, cause relaxation and therefore decrease TPR.
-
minoxidil
- 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.
-
hydralazine
- 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.
-
sodium nitroprusside
- 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.
-
nitroglycerin (glyceryl trinitrite)
- 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.
-
isosorbide dinitrate
- 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.
-
isosorbide mononitrate
- 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.
-
adenosine (purinergic agonist)
- 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)
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