Bennie Berkvens
Renal module
Pharmacology 2009-2010
Medical Pharmacology Drug List
for Renal/Male Reproductive Module
2009
Keeton says “two exam questions about
immunosuppressive drugs will test your knowledge of their MOA”
For each drug, know the:
1. mechanism of action (MOA)
2. pharmacological effects
3. therapeutic uses
4. toxicity (a.k.a., adverse effects
side effects, untoward effects)
Immunosuppressive Drugs –(use page 317 as a guide) “once the waiter found out I took immunosuppressive drugs my meal was COMPPT)
Cyclosporine (p.323)
Moa: Binds cytoplasmic protein (cyclophilin)—this complex inhibits enzymatic action of calcineurin (calmodulin dependent
derine/threonine phosphatase) in Helper T-cell no dephosphorylation of NFATC no transcription of the genes for IL-2 and IL-2
receptors, TNF-b, and IFN-gBlocks helper T-cell activation, prevents clonal expansion of T-cells and B-cells, and prevents activation
of CTLs (cellular immunity).
Uses: primarily suppresses cellular immunity. B cells are still activated by IL-6 (direct Ag stimulation). Organ transplantation, GVHD,
Autoimmune disease (RA, MG, psoriasis, DM type 1)
S/E: no myelosuppression. Nephrotoxic, hepatotoxic, ↑ viral infections, gingival hyperplasia, neurotoxicity, nausea, vomiting, hirsutism,
diarrhea, abd cramping, anorexia, degraded by CYP450.
OKT-3 (muromonab-CD3)
Moa: Monoclonal Anitbodies directed against CD-3 complex of helper T-cells (Th0) which lies directly next to Ag recognition complex
of the T cell blocks binding of foreign Ag presented by the APC no activation of helper T cellsno IL-2 production blocks fxn of
CTL. T-cells become inactive and are removed from the RES. Blocks direct activation of helper T, B, and plasma cells by f-MHC.
Uses: prophylaxis of early rejection, primary tx for organ rejection, rejection crisis, depletion of T cells from marrow prior to transplant
S/E: Cytokine release syndrome, Pulmonary edema, Nephrotoxicity, Neurologic complications, Viral infections, Neoplasms.
Mycophenolate
Moa: potent inhibitor of the enzyme inosine monophosphate dehydrogenase which is critical in de novo synthesis of the purine
Guanine by B and T lymphocytes (these cells have no alternative pathway, HGPRT, for purine biosythesis) suppress lymph
proliferation and Ab synthesis by B-cells. Prevents leukocyte recruitment by inhibiting glycosylation of lymph glycoproteins involved in
cell adhesion.
Uses: renal, cardiac, hepatic transplants. Oral drug for prevention of acute and chronic rejection of renal allografts esp in pts who
cannot tolerate cyclosporine or tacrolimus.
S/E: sepsis (CMV), diarrhea, leukopenia, GI hemorrhage
Prednisone (p. 317)
Moa: converted to prednisolone by 11-B-hydroxysteroid dehydrogenase. Causes a leukopenia (↓ T& B lymphs, monocytes, eos, and
basophils. ↑ Neutrophils (release from marrow). Interfere w/ APC (macrophage/monocyte/langerhans/dendritic & B cells) fxnblock
expression of IL-1 prevents activation of Helper T-cells blocking IL-2 release no activation of TH1 and TH2 cellsno release of
IL-4 or IL-6 (from APC)no activation of CTLs or B cells. Block of IL-2 also causes block in expression of TNF-b (↓ expression of
adhesion molecules in graft endothelium) and IFN-G (↓ f-MHC II expression in graft).
Uses: suppression of both Cellular and Humoral immunity. Use in organ transplantation (rejection crisis), and smaller doses for
maintenance immunosuppression. Also, use in autoimmune diseases.
S/E: Do NOT cause bone marrow suppression. Hirsutism, acne, PREDNISONE (Pg. 322)
Prednisolone
Moa: SAME AS PREDNISONE
Uses:
S/E:
Tacrolimus
Moa: binds FKBP in T-helper cellsthis complex inhibits calcineurininhibits production of IL-2, IL-2 receptors, TNF-b and IFN-g
Uses: 100X more potent then cyclosporine. prevention of acute rejection, allows withdrawal of tx w/ corticosteroids, rescue therapy
when OKT-3 is ineffective.
S/E: same as cyclosporine
Androgen receptor antagonists –Androgens are my Best Friend (BF)
Bicalutamide
Moa: Competitively block testosterone receptorsloss of feedback inhibition of LH secretion↑ plasma LH and testosterone.
Uses: TX of prostatic carcinoma in combination w/ GnRH analog.
S/E: Less hepatic toxicity then Flutamide and can be takes once a day.
Flutamide
Moa: Competitively block testosterone receptors loss of feedback inhibition of LH secretion↑ plasma LH and testosterone.
Uses:
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Bennie Berkvens
Renal module
Pharmacology 2009-2010
GnRH receptor agonists “for patients with prostatic carcinoma who are takinf GnRH receptor angonists Life’s Good (LG)”
Leuprolide
Moa: Initial stimulation of LSH and LH release in males and femalesinitial ↑ in plasma testosteroneif given continually in nonpulsatile fashion pituitary GnRH receptors become desensitized (downregulated) ↓ secretion of LH plasma testosterone ↓ to about
10% of normal w/In 2 wks.
Uses: 3-4mo depot prep for IM injection. Prostatic carcinoma along w/ androgen receptor antagonist to prevent initial flare up of tumor
activity caused by initial ↑ testosterone. TX of endometriosis and uterine fibroid tumors. TX of central precocious puberty
S/E: Hot flushes and sweating, Edema, gynecomastia, ↓ libido.
Goserelin
Moa: Same as Leuprolide
Uses: 3mo IM inplant
S/E: same as leuprolide
Tx of BPH- “if you have BPH, taking OSIN is a pain in the asteride”
α1adrenoreceptors are abundant in the SM of the prostate, prostatic capsule, prostatic urethra and bladder neck. Blockade of these receptors causes a reversible
relaxation of SM resulting in ↓ urethral resistance to flow. (70% are α-1A subtype)
Doxazosin
Moa: T1/2 of 22hr. alpha-adrenoreceptor blocker
Uses: can be used to TX hypertension and BPH in the same patient!
S/E: dizziness, postural hypotension (block of vascular α1 adrenoreceptors), somnolence, asthenia, nasal congestion, peripheral
edema, impotence (failure to ejaculate, ↓ volume, retrograde ejaculation).
Tamsulosin
Moa: selective α-1A adrenoreceptor antagonist.
Uses: BPH
S/E: less dizziness and orthostatic hypotension then doxazosin. Selectivity for α-1A ↑ incidence of ejaculatory dysfunction.
Finasteride (Five-a)
Moa: 5α-reductase exists in 2 molecular forms (type 1-liver and skin, and type 2-prostate). Finasteride inhibits TYPE 2. inhibition of 5αreductase prevents DHT formation from testosterone (p. 333). Causes plasma DHT to fall 70% and plasma testosterone to ↑ 10%. It
also causes DHT concentration in the prostate gland to ↓ by 70%. Plasma LH is not changed. Inhibition of 5α-reductase prevents
hairloss
Uses: BPH. ↓ size of prostate. (the larger the prostate the greater the response). ↓ need for TURP. Male pattern baldness
S/E: impotence, ↓ libido, 5mg Suppresses Prostate specific Antigen (PSA) by up to 50% (so now require periodic rectal exams), 1mg
does not suppress PSA.
Dutasteride
Moa: Inhibits BOTH type 1 and 2 forms of 5α-reductase forms.
Uses: same as Finasteride
S/E: reduces serum PSA by 40%
Tx voiding dysfunction “all dentists (DDS) take voiding dysfunction drugs”
Solifenacin
Moa: selective M3 muscarinic receptor antagonist (M3 receptors found on the detrusor muscle of the bladder, as well as in the salivary
glands.
Uses: TX of urge incontinence (uninhibited contractions of the urinary bladder that overcome the sphincter). Can be given postprostatectomy to prevent bladder spasms.
S/E: ↑ Q-Tc, few CNS effects, minimal dry mouth.
Darifenacin
Moa: selective M3 muscarinic receptor antagonist.
Uses:
S/E: no CNS or CV effects and no increase in Q-Tc. Minimal dry mouth.
Desmopressin (DDAVP)
Moa: synthetic analog of AVP (ADH) w/ duration of 6-20hr. selective for V2 receptor found in principle cells of the late distal tubule and
collecting duct. ↓ Normal production or urine.
Uses: TX of voiding dysfunction, nocturnal enuresis in children. Can be given as Nasal spray before bed.
S/E: Nasal spray can cause allergic rhinitis or nasal congestion from URI slow absorption.
Tx of erectile dysfunction “ ED drugs should be sold in VATS”
Vardenafil
Moa: onset 60 min, acts 4-5Hr MOA same as sildenafil
Uses: ED
S/E: same as sildenafil
Alprostadil
Moa: PGE1-receptor agonistrelaxation of SM of corpus cavernosa and relaxation of penile SMerection in 5 min (subsides 60-90
min).
Uses: used for patients nor responding to sildenafil.
S/E:
Tadalafil
Moa: onset 30-45 min, acts 24Hr. MOA same as sildenafil
Uses: ED
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Bennie Berkvens
Renal module
Pharmacology 2009-2010
S/E: same as sildenafil
Sildenafil
Moa: onset 30-60 min, acts 4-5Hr PDEase5 inhibitorprevents CGMP degradationCGMP is now converted to CGMP protein
kinaseact of MLC phosphataseprevents MLC phosphorylationrelaxation of vascular SM↑ blood flow erection
Uses: ED
S/E: smurf vision and impaired blue-green color discrimination (partial blockade of PDEase6 in cones of the retina), ↓ BF to the optic
nerveoptic neuropathy, headache and flushing. Severe hypotension when used w/ a nitrate or α-blockers.
Diuretic drugs
acetazolamide
Moa: Proximal Tubule inhibits 80-90% Carbonic anhydrase in PT  inhibts 35% HCO3 reab in PT and EDTprevents reab of Na
and waterurine becomes alkaline. Loop cannot compensate for loss of Na reab DT [Na] and [HCO3] are highthis causes ↑ K
secretion in LDT/CD. CL excretion falls.
Uses: glaucoma, altitude sickness, alkalinization of urine to ↑ loss of acidic drug in drug intoxication.
S/E: Hyperchloremic metabolic acidosis due to loss of HCO3 and impaired H secretion. When body loses HCO3, CL is retained.
Mannitol
Moa: TAL ↓Na reab. Freely filtered, not reabsorbed. ↑ RBF and GFR. ↑ urine flow and prevents reab of water in TDL of loop ↓ [NaCl]
in TAL (relative to water content)↓ Na reab in TAL. Overall ↑ in urinary excretion of Na, K,Mg, Ca, Cl, HCO3, PO4. salt/water loss
directly related to amount of mannitol excreted in urine. (B/c ↑ in urine flow rate, mannitol should be given w/ IV fluid)
Uses: prevent complete renal failure in ARF patients, ↓ intraocular pressure in glaucoma, ↓ intracranial pressure if intracranial bleeding
is not involved, prevent renal toxicity of cisplatin, Ampho-B, cyclosporine, Myoglobin.
S/E: overexpansion of plasma volumeCHF and pulmonary edema. Headache, nausea, hyponatremia.
Furosemide
Moa: TAL ↓Na reab. Filtered and secreted into PT. Activity not effected by acidosis or alkalosis, effective orally or parenterally, rapid
diuresis of short duration, Effective if GFR<25ml/min. Inhibit NA/K/2Cl co-transport in loop↓ reab of NaCl. Distal tubule unable to
resorb all extra NaClmassive diuresis. Na/K/Cl symporter blocked in the macula densa ↑GFR due to tuboglomerular feedback
block, ↑ vasodilatory prostaglandins, ↑ renin secretion (causes secondary hyperaldosteronism). ↑ Ca, Mg, K, Na, Cl, HCO3, PO4
excretion.
Uses: Acute pulmonary edema, edema in cardiac, hepatic, and renal disease. b/c of ↑ GFR and RBF they are useful in TX of CRF and
nephrotic syndrome. Also TX hypercalcemia.
S/E: hypokalemia-hypochloremic metabolic alkalosis. hypoMg cardiac dysrrhythmias, hyperuricemia gouty arthritis, Orthostatic
Hypotension, dilutional hyponatremia, Tinnitis. Hyperglycemia (Furosemide only), Azotemia and coma in renal and hepatic disease.
Bumetanide
Moa: TAL ↓Na reab Same as Furosemide
Uses: same as Furosemide
S/E: same as Furosemide
ethacrynic acid
Moa: TAL ↓Na reab
Uses: same as furosemide
S/E: same as Furosemide but ↑ risk for tinnitus and hearing loss
Hydrochlorothiazide
Moa: EDT inhibit NaCl reab in DT. Rapid onset, long duration. Only 5-6% of filtered Na is excreted, GFR consistently reduced,
Ineffective if GFR <25 ml/min (except for Metolaxone). At larger doses Thiazides inhibit carbonic anhydrase in PT↑ urinary pH. Do
not allow dilute urine production (urine is hypertonic). Enhanced urate reab in PT. ↓ excretion of Ca. ↑ Mg, K, Na, Cl, K, HCO3
excretion. Contraction of ECF volume causes renin secretionsecondary hyperaldosteronism.
Uses: first line for HTN. tx edema due to CHF, renal failure, hepatic cirrhosis, premenstrual wt gain, estrogen therapy. TX
hypercalcinuria in pts w/ renal calculi. Also ↓ urine output in patients that have Diabetes Insipidus (nephrogenic) b/c ↓ plasma volume ↑
solute/water reab in PTless volume to CD.
S/E: secondary hyperaldosteronism, Hypokalemia, HypoMg, Hyperuricemia, dilutional hyponatremia, hyperglycemia (due to block in
insulin secretion), azotemia and coma in severe renal and hepatic disease (hypokalemia stim renal prod of ammonia)
Metolazone
Moa: EDT ↓NaCl reab same as HCTZ
Uses: same as HCTZ. Use w/ loop diuretic when PT is reab too much Na massive Na excretion.
S/E: Same as HCTZ
Spironolactone
Moa: LDT/CD K-sparing ↓Na reab. Block aldosterone receptors in the DT (so diuretic activity requires the presence of aldosterone).
Weak diuretic (only 2-3%of filtered Na is excreted). ↑ excretion of Na, Cl, HCO3. ↓ excretion of K. very long duration of action.
Uses: lessen hypokalemia caused by thiazide (used together). Refractory edema, primary hyperaldosteronism, cirrhosis and nephrotic
syndrome, Heart failure (↓ LV wall thickness).
S/E: hyperkalemia (do not use w/ oral K), gynecomastia, azoospermia in males and menstrual irregularity and hirsutism in females due
to partial agonistic effects at androgen, estrogen, and progesterone receptors.
Amiloride
Moa: LDT/CD K-sparing ↓Na reab by blocking Na channels on luminal (apical) memb of principal cells in DT and CD. Weak diuretics
(2-3% Na excreted). Inhibit secretion of H ion (does not involve CA). ↑ excretion of water, Na, Cl, HCO3 and ↓ excretion of K and H.
Uses: use w/ thiazide to ↑ Na loss and to ↓ hypokalemia. Use in CF inhalation of amiloride slows mucus accumulation.
S/E: hyperkalemia
Triamterene
Moa: LDT/CD K-sparing ↓Na reab same as Amiloride
Uses: Same as Amiloride
S/E: Same as Amiloride
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Bennie Berkvens
Renal module
Pharmacology 2009-2010
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