HLS Drugs and Pharmacology Review

Comprehensive vocabulary review flashcards covering hematologic, antithrombotic, antimalarial, antineoplastic, and antiviral pharmacotherapies from the HLS Drugs lecture.

Ferrous sulfate (hydrated)

An oral iron preparation used for the treatment or prevention of iron deficiency anemia; a $325\,\text{mg}$ tablet contains $65\,\text{mg}$ of elemental iron. About $25\%$ of the dose is absorbed, requiring at least $200\text{--}400\,\text{mg}$ daily for $3\text{--}6\,\text{months}$ after resolving the underlying cause. Common adverse effects include gastrointestinal irritation, constipation, diarrhea, and black stools.

Ferrous gluconate

An oral iron formulation used in the treatment and prevention of iron deficiency anemia; a $325\,\text{mg}$ tablet provides $36\,\text{mg}$ of elemental iron and carries adverse effects of nausea, epigastric discomfort, abdominal pain, constipation, diarrhea, and black stools.

Ferrous fumarate

An oral iron preparation used for the prevention and treatment of iron deficiency anemia; a $325\,\text{mg}$ tablet contains $106\,\text{mg}$ of elemental iron. Adverse effects include stomach irritation, epigastric discomfort, constipation, diarrhea, and black stools.

Iron dextran

A parenteral (IM/IV) stable complex of ferric hydroxide and low-molecular-weight dextran containing $50\,\text{mg}$ elemental iron per $\text{mL}$. Indicated for iron-deficient patients who cannot tolerate or absorb oral iron (e.g., malabsorption syndromes, small bowel resection) or with extensive chronic blood loss. Adverse effects include local pain and tissue staining after IM injection, and headache, fever, arthralgia, flushing, bronchospasm, anaphylaxis, and death following IV administration.

Deferoxamine & Deferasirox

Chelating agents serving as antidotes for iron excess and used in hemochromatosis. ? is administered parenterally and can also chelate lead, whereas ? is administered orally.

Unfractionated heparin (UFH)

An indirect anticoagulant administered by continuous IV infusion that depends on antithrombin to prevent thrombus growth. It forms a ternary complex with antithrombin and thrombin ($\text{Factor IIa}$), while factor $\text{Xa}$ inactivation requires only the pentasaccharide sequence. It has a zero-order, dose-dependent half-life ($30\text{--}90\,\text{min}$), requires aPTT monitoring $4\text{--}6\,\text{hours}$ post-administration, and may cause heparin-induced thrombocytopenia (HIT) and osteoporosis with use beyond $6\,\text{months}$.

Protamine sulfate

A basic antidote that neutralizes unfractionated heparin within $5\,\text{minutes}$, with an action lasting for $2\,\text{hours}$. It is limited to a maximum dose of $50\,\text{mg}$ to avoid causing an undesired anticoagulant effect.

Low molecular weight heparins (LMWH)

Heparin derivatives (e.g., Enoxaparin, Dalteparin) with one-third the mean molecular weight of UFH that act primarily on factor $\text{Xa}$ rather than $\text{IIa}$. They display first-order, dose-independent elimination with a half-life of $3\text{--}6\,\text{hours}$, undergo renal clearance, and achieve $90\%$ bioavailability subcutaneously. Monitored via anti-Xa activity ($0.5\text{--}1$) at $4\text{--}6\,\text{hours}$ post-subcutaneous dose only in obesity, pregnancy, and children.

Fondaparinux

A synthetic pentasaccharide sequence that reversibly binds antithrombin to selectively inhibit factor $\text{Xa}$ without affecting factor $\text{IIa}$. It is rapidly and completely absorbed subcutaneously, has an elimination half-life of $19\,\text{hours}$, exerts anticoagulant effects for $2\text{--}4\,\text{days}$, and has no available antidote.

Lepirudin

A recombinant hirudin derivative produced via DNA technology that irreversibly inactivates fibrin-bound thrombin. Administered IV or SC and eliminated by hepatic and renal pathways, it is monitored by aPTT and serves as an alternative anticoagulant in patients with heparin-induced thrombocytopenia (HIT). It has no antidote.

Bivalirudin

A synthetic direct thrombin inhibitor analog of hirudin that reversibly inhibits both circulating and clot-bound thrombin and suppresses thrombin-mediated platelet activation. Administered IV with an elimination half-life of $25\,\text{minutes}$, it is cleared via hepatic, renal, and proteolytic pathways, is indicated for percutaneous coronary intervention (PCI) and HIT, and is monitored via a thrombin inhibitory assay.

Warfarin

An oral anticoagulant that inhibits the reduction of vitamin K epoxide, blocking synthesis of factors $\text{II}$, $\text{VII}$, $\text{IX}$, and $\text{X}$, as well as proteins C and S. Because its anticoagulant effect requires $6\,\text{days}$, it must initially be overlapped with heparin for at least $5\,\text{days}$ to prevent thrombosis and skin necrosis. Monitored by PT/INR (target $2\text{--}3$); reversed by vitamin K.

Direct oral anticoagulants (DOACs)

Selective, reversible anticoagulants that do not alter the synthesis of clotting factors and exhibit intermediate half-lives. They are partially cleared by the kidneys, interact with CYP450 enzymes and P-glycoprotein, and can be bound by activated charcoal if administered within $2\,\text{hours}$ of ingestion during an overdose.

Rivaroxaban, Apixaban, & Edoxaban

Potent and selective direct inhibitors of both free and clot-bound factor $\text{Xa}$ that do not require antithrombin and have a terminal half-life of approximately $10\,\text{hours}$. are substrates for CYP3A4 and P-glycoprotein and are used to prevent venous thromboembolism before hip/knee replacement surgery or for extended VTE treatment after the initial $6\,\text{months}$.

Dabigatran

An oral prodrug that acts as a selective, reversible, direct factor $\text{IIa}$ (thrombin) inhibitor with a $16\,\text{hour}$ half-life. Used for extended VTE treatment after the initial $6\,\text{months}$; its anticoagulant effect can be reversed by hemodialysis or the specific monoclonal antibody Idarucizumab.

Idarucizumab

A specific reversal agent for dabigatran that binds to dabigatran and its acylglucuronide metabolite with higher affinity than dabigatran's affinity for thrombin, providing rapid IV reversal during life-threatening bleeding or emergency surgery.

Aminocaproic acid & Tranexamic acid

Antidotes for thrombolytic agents that bind to plasminogen and plasmin to inhibit their fibrin-degrading activity. They are contraindicated in disseminated intravascular coagulation (DIC) and upper urinary tract bleeding (kidney or ureters) due to the risk of thrombosis.

Streptokinase

A first-generation, nonenzymatic thrombolytic protein produced by group C streptococci. It forms an allosteric complex with plasminogen to expose its active catalytic site and convert it to plasmin; pre-existing antistreptococcal antibodies may neutralize its activity, requiring a loading dose.

Tissue Plasminogen Activator (tPA)

A fibrin-selective thrombolytic agent (e.g., Alteplase) that exhibits high affinity for clot-bound fibrin and selectively activates plasminogen within the thrombus. Used in acute MI (within $6\,\text{hours}$ of onset) and acute ischemic stroke (within $3\,\text{hours}$ of onset).

Aspirin

An antiplatelet agent administered at low doses ($60\text{--}100\,\text{mg/day}$) that causes irreversible acetylation and inhibition of platelet cyclooxygenase (COX), blocking thromboxane $A_2$ ($\text{TXA}_2$) synthesis for the platelet lifespan ($7\text{--}10\,\text{days}$). Doses higher than $350\,\text{mg}$ are avoided to prevent inhibiting endothelial prostacyclin ($\text{PGI}_2$).

Eicosapentaenoic acid

An omega-3 unsaturated fatty acid derived from cold-water fish used for the prevention (not treatment) of thrombosis. It generates $\text{PGI}_3$ (an active antiaggregatory agent comparable to $\text{PGI}_2$) and $\text{TXA}_3$ (which is far less active at promoting aggregation than $\text{TXA}_2$).

ADP P2Y12 Receptor Blockers

Antiplatelet agents (Clopidogrel, Ticlopidine, Prasugrel) that irreversibly block the Gi protein-coupled $P2Y_{12}$ ADP receptor on platelets, preventing $\text{GPIIb/IIIa}$ expression and fibrinogen binding. Clopidogrel is a prodrug requiring activation by CYP2C19 (inhibited by lansoprazole).

GPIIb/IIIa Receptor Blockers

Parenteral antiplatelet agents (Abciximab, Eptifibatide, Tirofiban) that inhibit the final common pathway of platelet aggregation by blocking the fibrinogen receptor on platelets. Abciximab is a chimeric monoclonal antibody, Eptifibatide is a fibrinogen analog, and Tirofiban is a non-peptide small molecule.

Dipyridamole

A vasodilator and platelet inhibitor that blocks cellular adenosine uptake and cyclic GMP phosphodiesterase activity. It provides minimal benefit when used alone, but is combined with aspirin for cerebrovascular ischemia prophylaxis or with warfarin to prevent thromboemboli from prosthetic heart valves.

Cilostazol

A phosphodiesterase inhibitor that induces vasodilation and suppresses platelet aggregation, indicated for intermittent claudication secondary to atherosclerosis. It may provoke coronary steal syndrome by dilating healthy vessels away from stenosed areas.

Deoxyadenosylcobalamin

An active form of vitamin $B_{12}$ that acts as an essential cofactor for methylmalonyl-CoA mutase, catalyzing the isomerization of methylmalonyl-CoA to succinyl-CoA, which is vital for neuronal myelin formation.

Methylcobalamin

An active coenzyme form of vitamin $B_{12}$ that facilitates the transfer of a methyl group from $N^5\text{-methyltetrahydrofolate}$ to homocysteine to generate methionine and tetrahydrofolate (THF). Oral high doses ($1.5\,\text{mg}$) can be used to manage metformin-induced deficiency.

Hydroxocobalamin

A parenteral formulation of vitamin $B_{12}$ used for the treatment of pernicious anemia; it is preferred over cyanocobalamin because it exhibits higher plasma protein binding, dissociates slowly, and remains in the circulation longer.

Chloroquine

An antimalarial blood schizonticide that accumulates in the acidic food vacuole of Plasmodium, inhibits heme polymerase, and raises vacuolar pH. Safe in pregnancy and effective for clinical attacks of sensitive malaria and amebic liver abscess, its use is limited by adverse effects including retinopathy, QRS/T wave abnormalities, and hemolysis in G6PD deficiency.

Primaquine

A hepatic tissue schizonticide and gametocide that acts by inducing oxidative stress and accumulating hydrogen peroxide ($\text{H}_2\text{O}_2$). Used for causal prophylaxis and radical cure of hypnozoites (e.g., P. vivax, P. ovale) administered for $14\,\text{days}$ following blood schizonticides; contraindicated in pregnancy and causes hemolysis in G6PD deficiency.

Erythropoietin (Epoetin alfa)

A recombinant growth factor used to treat anemia in chronic renal failure. Adverse effects include hypertension and thromboembolic complications triggered by a rapid rise in hematocrit, requiring dosing to keep target hemoglobin at or below $11\,\text{g/dL}$.

Filgrastim

A recombinant human granulocyte colony-stimulating factor (rHuG-CSF) that stimulates the proliferation, differentiation, phagocytic function, and survival of progenitors committed to the neutrophil lineage; indicated for chemotherapy-induced neutropenia.

Sargramostim

A recombinant human granulocyte-macrophage colony-stimulating factor (rHuGM-CSF) that possesses a broader spectrum than filgrastim, stimulating early and late granulocytic, erythroid, and megakaryocyte progenitors.

Romiplostim

A peptibody thrombopoietin receptor agonist indicated for chronic immune thrombocytopenia. Adverse effects include portal vein thrombosis, bone marrow fibrosis, rebound thrombocytopenia upon cessation, and increased blast counts progressing to AML in myelodysplastic syndrome.

Eltrombopag

An orally active small nonpeptide thrombopoietin receptor agonist used as secondary therapy for chronic immune thrombocytopenia refractory to steroids, IVIG, or splenectomy, and in hepatitis C-related thrombocytopenia. Adverse effects include hepatotoxicity and portal vein thrombosis.

Oprelvekin

A recombinant form of interleukin-11 (IL-11) used to stimulate platelet production. Adverse reactions include fatigue, transient atrial arrhythmias, dilutional anemia, pulmonary fluid accumulation (dyspnea), and hypokalemia secondary to diuretic management of fluid retention.

Classic Alkylating Agents

Cytotoxic drugs that transfer alkyl groups to DNA, predominantly attacking the $N^7$ position of guanine to cause intrastrand cross-linking, interstrand cross-linking, depurination, and mispairing with thymine. Toxicities include myelosuppression, alopecia, carcinogenesis (acute leukemias), and vesicant damage.

Cyclophosphamide

A classic alkylating prodrug that requires bioactivation by hepatic microsomal cytochrome P450 enzymes into 4-hydroxycyclophosphamide and aldophosphamide. A distinctive adverse effect is acrolein-induced hemorrhagic cystitis, preventable with aggressive hydration.

Methotrexate (MTX)

A folic acid analog antimetabolite that competitively inhibits dihydrofolate reductase (DHFR), depleting tetrahydrofolate necessary for purine and thymidylate synthesis. It undergoes intracellular polyglutamation, saturates oral absorption above $26\,\text{mg/m}^2$, is cleared renally (inhibited by NSAIDs/penicillins), and is rescued using Leucovorin.

Cytarabine (Ara-C)

An S-phase-specific pyrimidine antimetabolite converted by deoxycytidine kinase to ara-CTP, which competitively inhibits DNA polymerases $\alpha$ and $\beta$ and incorporates into DNA to terminate chain elongation. Toxicities include myelosuppression, mucositis, and cerebellar ataxia.

Vinca Alkaloids

Antimitotic agents (Vinblastine and Vincristine) derived from the periwinkle plant Vinca rosea that bind tubulin and inhibit its polymerization, disrupting the mitotic spindle and causing cell cycle arrest in metaphase. Toxicities include peripheral sensory neuropathy, autonomic dysfunction (orthostatic hypotension, paralytic ileus), SIADH, and vesicant extravasation.

Etoposide

A semisynthetic podophyllotoxin derivative from the Mayapple root that forms a ternary complex with topoisomerase II and DNA, causing irreversible double-stranded DNA breaks and preventing cellular entry into the mitotic phase.

Doxorubicin & Daunorubicin

Cytotoxic anthracycline antitumor antibiotics that intercalate DNA base pairs, inhibit topoisomerase II, and undergo iron-dependent redox cycling to generate semiquinone and reactive oxygen species, leading to acute arrhythmias and dose-dependent chronic dilated cardiotoxicity.

Bleomycin

A cell-cycle specific antitumor antibiotic that contains a DNA-binding region and an iron-binding domain, causing single- and double-strand DNA breaks via free radicals and arresting cells in the $G_2$ phase. Eliminated renally and notable for lacking vesicant activity, but carries high risks of dose-dependent pulmonary toxicity (pneumonitis and fibrosis).

Carboplatin

A platinum coordination analog that binds DNA to create intrastrand and interstrand cross-links predominantly at the $N^7$ position of guanine, inhibiting DNA replication across all phases of the cell cycle. Toxicities include myelosuppression, nausea, vomiting, and peripheral neuropathy.

Imatinib

A small-molecule competitive inhibitor of the ATP-binding kinase domain of the BCR-ABL oncoprotein, indicated for chronic myelogenous leukemia (CML) harboring the $t(9;22)$ Philadelphia chromosome translocation. Notable adverse effects include prominent fluid retention (periorbital and ankle edema), myalgias, and diarrhea.

Asparaginase

An enzyme (L-asparagine aminohydrolase) that hydrolyzes serum L-asparagine into aspartic acid and ammonia, depriving acute lymphoblastic leukemia (ALL) cells—which lack asparagine synthetase—of an essential amino acid. Notable adverse effects include severe hypersensitivity reactions, pancreatitis, and coagulopathies (bleeding and thrombosis).

Bortezomib

A dipeptide boronic acid derivative that acts as a reversible inhibitor of the $26\text{S}$ proteasome, disrupting signaling cascades and protein turnover in multiple myeloma cells. Adverse effects include peripheral neuropathy, severe fatigue, thrombocytopenia, and complete AV block.

Alemtuzumab

A humanized recombinant monoclonal antibody targeting CD52 expressed on mature normal and malignant B and T lymphocytes, natural killer cells, and monocytes. It induces complement-dependent and antibody-dependent cellular cytotoxicity in refractory B-cell chronic lymphocytic leukemia (B-CLL), causing profound pancytopenia.

Rituximab

A chimeric murine-human monoclonal antibody targeting the CD20 antigen found on normal and malignant pre-B and mature B lymphocytes. It triggers complement-mediated lysis, antibody-dependent cell-mediated cytotoxicity (ADCC), and apoptosis in relapsed or refractory low-grade or follicular B-cell non-Hodgkin's lymphoma.

Ganciclovir

An acyclic guanosine analog used for cytomegalovirus (CMV) infections. It undergoes initial monophosphorylation by a viral protein kinase followed by cellular triphosphorylation, competitively inhibiting viral DNA polymerase. Primary toxicities include severe myelosuppression (neutropenia and thrombocytopenia), retinal detachment, and CNS disturbances.

Foscarnet

An inorganic pyrophosphate analog that directly inhibits viral DNA polymerase, RNA polymerase, and HIV reverse transcriptase without requiring intracellular phosphorylation. Up to $30\%$ of the drug deposits into bone with a half-life of months; adverse effects include acute nephrotoxicity, electrolyte shifts (hypo/hypercalcemia, hypo/hyperphosphatemia), and genital ulcerations.

Cidofovir

An acyclic cytosine nucleotide analog that is phosphorylated to cidofovir diphosphate independently of viral enzymes, competitively inhibiting viral DNA polymerase. Administered with oral probenecid and vigorous pre-hydration to mitigate severe proximal tubular nephrotoxicity (Fanconi's syndrome and proteinuria).

Abacavir

A guanosine-derived nucleoside reverse transcriptase inhibitor (NRTI) that competitively inhibits HIV-1 RT to cause viral DNA chain termination. It can induce mitochondrial toxicity and lactic acidosis, and requires prior screening for the $HLA\text{-}B^*5701$ allele to avoid fatal multiorgan hypersensitivity reactions.

Delavirdine

A non-nucleoside reverse transcriptase inhibitor (NNRTI) that binds directly to an allosteric pocket of HIV-1 reverse transcriptase without intracellular phosphorylation. Highly metabolized by CYP3A4, its major adverse effects include diffuse maculopapular cutaneous rash, erythema multiforme, and Stevens-Johnson syndrome.

Atazanavir

An HIV-1 and HIV-2 protease inhibitor that prevents post-translational cleavage of viral polyproteins, producing noninfectious, immature virions. Notable adverse effects include lipodystrophy (buffalo hump and central obesity), unconjugated hyperbilirubinemia/jaundice via UGT1A1 inhibition, and PR/QTc interval prolongation.

Enfuvirtide

A synthetic 36-amino-acid peptide fusion inhibitor administered subcutaneously that binds to the gp41 subunit of the HIV viral envelope, preventing the structural changes needed for membrane fusion with host cells. Adverse reactions include subcutaneous injection-site reactions, hypersensitivity, and an increased incidence of bacterial pneumonia.

Raltegravir

An integrase strand transfer inhibitor (INSTI) that binds the catalytic site of HIV-1 and HIV-2 integrase, blocking proviral integration into the host genome. Its oral absorption is impaired by chelation with polyvalent metal cations ($\text{Ca}^{2+}$, $\text{Mg}^{2+}$, $\text{Fe}^{2+}$), and it is associated with elevations in creatine phosphokinase.