Pulmonary Drugs

Front 1

Amantadine/Rimantadine

Back 1

influenza A prophylaxis, block viral uncoating preventing replication. No protection against influenza B, should be taken in 48h of symptoms, commonly GI and CNS side effects, resistant influenza strains emerging

Front 2

Oseltamivir (Tamiflu)

Back 2

inflluenza treatment/prophylaxis, neuraminidase inhibitor, oral dosing

Front 3

Zanamivir (Relenza)

Back 3

influenza treatment/prophylaxis, poor bioavailability (inhaled only)

Front 4

Peramivir

Back 4

influenza treatment, neuraminidase inhibitor, compassionate use only

Front 5

Ribavirin

Back 5

RSV treatment, mechanism unknown (GTP depletion?), aerosol for infants (can cause bronchospasm), oral for transplant patient, both need supportive care

Front 6

Cidofovir

Back 6

disseminated adenovirus, nucleoside analogue, not recommended for pulmonary disease

Front 7

doxycycline, minocycline

Back 7

Class: tetracycline derivatives
Mechanism: bind 30S ribosome preventing binding of tRNA during elongation
Toxicities: GI upset (nausea, vomiting, diarrhea, esophagitis), teratogenic (fetal teeth and bone deformity, discoloration), photosensitivity

Front 8

Ipratopium

Back 8

- alternative asthma therapy, targets the parasympathetic vagal nerve reflex
- mechanism: antagonizes bronchiole SM M1-muscarinic receptors preventing activation (which triggers ACh release and bronchoconstriction)
- Aerosol only (charged so does not cross the membrane well)
- Individualized efficacy but very good for some (esp. exercise and nocturnal asthma)
- Very few side-effects due to limited absorption

Front 9

Pseudoephedrine, phenylpropanolamine

Back 9

- mechanism: binds to reuptake (NET) and vesicular transporters (VMAT) causing reverse catecholamine transport and release. Does not effectively cross BBB so few CNS effects.
- Functional effect: respiratory mucosa vasoconstriction, bronchial relaxation, increased heart rate and contractility
- Indications: nasal decongestant (cold, allergies, sinusitis)
- Side effects: high dose may cause hemorrhagic stroke

Front 10

Phenylephrine

Back 10

- mechanism: selective α₁ agonist (high effect on vascular smooth muscle, moderate CNS). T1/2 of several hours
- Functional effect: potent vasoconstrictor therefore decreases the volume of the nasal mucosa reducing airflow resistance
- Indications: nasal decongestant (oral or spray)
- Contraindications: hypertension, MAOI use (sustained increase in BP)

Front 11

Epinephrine

Back 11

Mechanism: preferentially activates β receptors (vasodilation) but also α receptors (dominant at high dose, vasoconstriction). Rapidly metabolized by MAO (T1/2 <1min)
Functional Effects: induces profound bronchodilation, ↑ cardiac output, ↑ blood pressure (↑ HR, ↑ strength of contraction, ↑ vasoconstriction (α receptors)), at low doses vasodilation (β receptors)
Therapeutic potential: Emergency medicine for cardiac arrest, acute bronchospasm, shock. Must by IV (degraded orally)

Front 12

Atropine

Back 12

- indications: acute MI w/ sinus bradycardia (blocks SA nodes, increasing HR which prevents ventricular pacemaking), slit-lamp eye exam (block contraction of iris sphinter and clilary muscles→dilation and paralysis of accomodation), organophosphate/AChE/parasympathetic poisoning (antagonizes high level ACh)
- Side effect: decreased bladder motor activity (problem in prostatic hypertrophy), decreased exocrine glad secretions (dry eyes, mouth, skin), decreased GI motility (constipation)

Front 13

Scopolamine

Back 13

- indications: motion sickness prophylaxis (crosses CNS readily)
- side effects: at high dose can cause hallucinations, disorientation, coma, death

Front 14

Rifampin

Back 14

- mainstay of TB therapy

- inhibits DNA-dependent RNA polymerase (4 subunits/4 genes), bactericidal
- resistance: single mutations in rpo B gene (81 bp) can cause resistance, scanned for by GeneXpert
- side effects: Hepatitis, orange secretions, GI upset, bleeding, flu-like symptoms, rash, many drug interactions (induction of P450-3A: methadone, coumadin, OCP, azoles, steroids, protease inhibitors, etc)

Front 15

Isoniazid

Back 15

- Mainstay of TB therapy

- interferes with mycolic acid synthesis
- side effects: hepatitis, peripheral neuropathy (give pyridozine to prevent), CNS effects

Front 16

Pyrazinamide

Back 16

- TB therapy
- - unknown mechanism, may interfere with fatty acid synthetase I
- side effects: hepatitis, GI upset, hyperuricemia, arthralgias

Front 17

Ethambutol

Back 17

- TB therapy
- disrupts cell wall synthesis
- side effects: optic neuritis

Front 18

Dobutamine

Back 18

Mechanism: selective β₁ receptor agonist
Functional effects: ↑ cardiac contractility, ↑ HR
Indications: EM for shock and cardiac arrest, short-term treatment for heart failure. Sometimes used in stress tests for cardiac abnormalities

Front 19

Clonidine

Back 19

- Mechanism: selective α₂ agonist, binds mostly presynaptic α₂ receptors providing feedback to slow catecholamine release
- Functional effects: (oral or patch) suppresses sympathetic output in the CNS, decreasing overall tone, peripheral resistance, HR and BP
Indications: HTN (less popular), glaucoma eyedrop (vasoconstricts b/c high receptor population), ADHD
- Side effects: cotton mouth and sedation

Front 20

erythromycin, clarithromycin, azithromycin

Back 20

Class: Macrolides
Mechanism: inhibit bacterial protein synthesis by binding 50S ribosome and dislocating tRNA during elongation
Toxicities: phlebitis, pain at infusion site (avoid with central IV), GI upset (cramps, nausea, emesis, diarrhea due to increase motility), during pregnancy chronic cholestatic hepatitis, associated w/ transient sensorineural hearing loss and polyventricular tachycardia
Spectrum:
- gram + (s. pyogenes, s. pneumo, s. aureus, corynebacterium diptheria), gram - (legionella, B. pertussis, Camypylobater jejuni, B. henselae, H. ducreyi, M. catarrhalis), mycoplasma, chlamydia
Indications: pneumonia (typical, atypical), skin and soft tissue infections, CAP, pertussis, diphtheria, chlamydia, patients w/ beta-lactam allergy, MAC prophylaxis w/ azithromycin in AIDS

Front 21

Reserpine

Back 21

- indirectly acting sympatholytic: binds to and blocks vesicular monoamine transporter (VMAT) preventing vesicular packaging and release of catecholamines (taken orally, T1/2 of 36hrs)
- Functional effect: total shut-down of sympathetic nervous system (no release of catecholamines)
- Indications: refractory Raynaud's Syndrome, HTN (not currently used b/c of side effects)
- Side effects: severe CNS effects including depression and impaired cognition

Front 22

Albuterol (short-acting) & Salmeterol (long-acting)

Back 22

- β2 selective, targeting bronchial SM: simulated GPCR β2 receptors to release cAMP and relax SM/bronchodilate
- Aerosol and oral forms
- concerns: tolerance (leading to continued self-medication and crisis), increased risk of exacerbation with long acting
- side effects: cardiac stimulation, tremors, etc (especially oral)

Front 23

Theophylline

Back 23

- Mechanism: not entirely understood, believed to antagonize adenosine receptors (which activate mast cells) causing bronchodilation (unlikely to be phosphodiesterase inhibitor, due to low therapeutic doses)
Major limitations: low therapeutic index (no separation between therapeutic and side-effect curves), high toxicity, many food/drug interactions (metabolized by P450's and competes for binding with plasma proteins)
- Caffeine is very similar to theophylline but 35% less potent

Front 24

Omalizumab

Back 24

- mechanism: IgE antibody which prevents it from binding receptor: prevents mast cell activation and production of inflammatory mediators
- Infusion only
- can be very efficacious but only for allergen-based asthma
- side effect: anaphylaxis

Front 25

Zilueton, montelukast

Back 25

- leukotriene modifiers used in asthma
- inhibits the formation of leukotrienes later in the production pathway than steroids (which inhibit phospholipase A2 via lipocortin)
- Zilueton: inhibits 5-LPO, which normally converts essential fatty acids to LTs
- Montelukast (singulair): inhibits leukotriene receptors to prevent action
- Currently tablet only, may be aersol soon
- good efficacy but individualized and variable
- Side effects: montelukast: few, generally well tolerate, zileuton: elevates hepatic enzymes, numerous drug interactions (warfarin, theophylline, etc)

Front 26

Propranolol

Back 26

- non-selective β receptor antagonist (blocks 1 and 2 receptors). Typically oral, T1/2 of several hours
- Functional effects: decreases HR, strength of contraction (so decreases stress on the heart, can stabilize arrythmias), reduces BP (blocks β1 in kidney effecting renin/angiotensin)
- Indications: HTN, heart disease, angina, arrhythmias, muscle tremor
- contraindications: asthma (inhibtion of B2 in lung causing bronchoconstriction)
- used off label by muscians, competitive shooters, surgeons to reduce tremors

Front 27

Ivacaftor "Kalydeco"

Back 27

- targets CFTR class III mutations (5%), acts to open the ion channel and stimulate Cl- transport

Front 28

Physostigmine (Antilirium), Neostigmine (Prostigmin)

Back 28

Class: reversible indirect acting cholinomimetics

Mechanism: targets active site of AChE (to prevent ACh degradation and prolong signaling) and either competitively binds (Edrophonium) or undergoes reversible carbamylation (spontaneously degrades covalent bond)
Indications: glaucoma, antidote for OD of anti-muscarinics (causing muscle paralysis), myasthenia gravis (diagnosis and treatment)

Front 29

Organophosphates

Back 29

Class: irreversible indirect acting cholinomimetic
mechanism: serves as AChE substrate and irreversibly binds (enzyme cleavage leaves serine residue in binding pocket), very lipophilic (can cross all barriers)
Indications: insecticides (accidental poisoning), glaucoma, military nerve gas
Overdose: too much parasympathetic action SLUDGE (salivation, lacrimation, urination, diaphoresis, gastrointestinal, emesis). Treated with cholinesterase reactivators (Pralidoxime) reactivate AChE by attacking phosphate bond in the binding pocket

Front 30

Prazosin

Back 30

- selective α1 antagonist. Given orally, T1/2 several hours
- Functional effects: reduces BP (by blocking vascular SM constriction)
- indications: HTN, benign prostatic hyperplasia (targets α1 receptors on prostate, preferred is Tamsulosin which doesn't cause hypotension)
- Side effects: postural hypotension and fainting upon standing (normally there would be a sympathetic spike on postural change to vasoconstrict and prevent BP drop in the brain--inhibited)

Front 31

cyclophosphamide

Back 31

- bifunctional alkylating agent (nitrogenous mustard)
- inhibits cancer growth by covalently attaching alkyl groups to bases in DNA, leading to cross-linking and inhibition of replication resulting in apoptosis.
- administered as a prodrug which is activated by p450s in the liver .
- Side effects: hemorrhagic cystitis (managed with MENSA: releases sulfhydryl bond) nausea, emesis, myleosuppression.

Front 32

Carmustine (BNCU), Loumustine (CCNU), Streptozocin

Back 32

- Nitrourea alkylating agents for cancer therapy:
- mechanism: undergo non-enzymatic decomposition to reactive alkylating metabolite and isocyanate compounds (carbamoylating agents) which have several effects on dividing cells, especially inhibition of DNA replication through cross-linking
Indications: BCNU/CCNU: highly lipid soluble so good for primary brain tumors; Streptozocin good for pancreatic islet cell tumors
Toxicity: BCNU/CCNU profound, delayed myelosuppression (dose limiting). Streptozocin is not myelosuppressive

Front 33

Cisplatin

Back 33

class: alkylating anti-cancer agent
mechanism: binds DNA to form intra and inter-strand cross links this prevent replication
Indications: first line treatment for testicular, ovarian, and bladder cancer, some melanoma
Toxicity: nephrotoxic (controlled w/ hydration, diuresis), SEVERE nausea and vomiting (requires ondansetron)

Front 34

Methotrexate

Back 34

class: antimetabolite
mechanism: folate analogue that irreversibly binds dihydrofolate reductase (which reduces FH2 to FH4) inhibiting denovo purine synthesis and dUMP from dTMP inhibiting DNA synthesis
indications: broad spectrum, uterine, bladder, breast, ALL, some inflammatory disease
- Overdose rescued by leucovorin calcium (folinic acid)
- tumore resistance: impaired transport into cells, impaired drug modification (required for activation), increased or altered dihydrofolate reductase
- toxicity: bone marrow suppression, mucosal ulceration

Front 35

5-fluorouracil

Back 35

Class: antimetabolite
mechanism: pyrimidine analogue, is metabolized to F-dUMP and F-UTP which inhibits thymidilate synthase (normally converts dUMP to dTMP). F-UTP is incorporated into RNA and interferes with function
indications: Exclusively solid tumors: breast, colorectal, gastric, non-invasive skin cancers
toxicity: myelosuppression, mucosal damage

Front 36

Doxorubicin, Daunorubicin

Back 36

class: anthracycline, cytotoxic antibiotic
mechanism: inhibit topoisomerase II, intercalate DNA (interferes with DNA/RNA synthesis), cause protein-associated DNA breaks (via topoisomerase II), generate free radicals
indications: BREAST CANCER (most active agent), hodgkins's lymphoma, bladder, ovarian, gastric, non-lymphocytic leukemia
Toxicity: cumulative/dose-related cardiac damage, severe/total hair loss

Front 37

Bleomycin (Blenoxane)

Back 37

class: cytotoxic antibiotic
mechanism: metal-chelating glycopeptide, causes DNA fragmentation through free radicals (esp. in G2 phase)
indications: testicular, hodgkin's
toxicity: pulmonary fibrosis, no myelosuppression (so used in combination therapy b/c limited tox overlap + unique mechanism)

Front 38

Vincristine, viblastine

Back 38

class: vinca alkaloids (M-phase specific)
mechanism: bind to tubulin and inhibit polymerization into microtubules preventing spindle formation in metaphase)
indications: leukemia, lymphoma, solid tumors
tox: neuropathy, dose-related myelosuppression

Front 39

Taxol

Back 39

class: vinca alkaloid
mechanism: over stabilizes microutubules by binding beta-tubulin and promoting assembly but preventing depolymerization. Disrupts mitosis.
indications: ovarian, breast, lung, bladder, head/neck carcinoma
tox: myelosuppression, alopecia, peripheral neuropathy, mild muscle/joint ache

Front 40

Tamoxifen

Back 40

class: hormonal agent
mechanism: anti-estrogen agent
indications: estrogen-dependent breast cancer

Front 41

Anastrozole

Back 41

class: hormonal agent
mechanism: competitive inhibition of aromatase blocking estrogens synthesis from androgens
indications: post-menopausal metastatic breast cancer

Front 42

Aldesleukin

Back 42

class: biological response modifier
mechanism: activates IL-2 receptor to promote B and T cell proliferation
indications: renal, colorectal, melanoma

Front 43

Gleevec

Back 43

mechanism: inhibits Bcr-Abl. c-kit, PDGFR mutated tyrosine kinase receptors
indications: CML, GI stromal tumor
tox: nausea, vomiting, muscle cramp, rash, diarrhea

Front 44

Herceptin (Trastuzumab)

Back 44

mechanism: targets HER2 mutatiosn in GFR2
indications: metastatic breast cancer (20-30%)
tox: cardiotoxicity

Front 45

Gefitinab (Iressa)

Back 45

mechanism: reversible small molecule inhibitor of EGFR tyrosine kinase
indications: NSCLC

Front 46

Avastin

Back 46

class: anti-angiogenesis agent
mechanism: inhibits VEGF
indications: colorectal, lung, breast, renal, glioblastoma

Front 47

Phenelzine (tranylcypromine, selegine)

Back 47

- MAO inhibitor: inhibits catcholamine degradation by monoamine oxidase propagating existing neural impulse (indirect action)
- Indications: (oral,T1/2 24hrs) depression, parkinson's disease (enhances dopaminergic tone, prolonging action)
- Contraindications: other sympathomimetics or rich foods (wine, beer, cheese, chocolate, etc which are normally degraded by gut MAO) which may cause potentially fatal hypertensive crisis

Front 48

Streptokinase

Back 48

- class: antithrombolytic
- mechanism: non-enzymatic plasminogen activator promoting auto-catalysis to plasmin which cleaves fibrin
- indications: EM for clot lysis: MI, extensive DVT, acute/massive PE, acute ischmeic stroke, throbotic occlusion, intravascular cannulas/catheters
- Adverse Effects: systemic proteolysis of fibrinogen--bleeds (treat with aminocaproic acid--binds plasminogen and plasmin to suppress fibrin degradation), elicits anti-bacterial antibodies

Front 49

Alteplase

Back 49

- class thrombolytics
- mechanism: recombinant human tissue plasminogen activator, clot specific (kinetically active when bound to fibrin, concentrates in clot region)
- indications: EM for clot lysis: MI, extensive DVT, acute/massive PE, acute ischmeic stroke, throbotic occlusion, intravascular cannulas/catheters
- Adverse Effects: Bleeds (treat with aminocaproic acid--binds plasminogen and plasmin to suppress fibrin degradation)

Front 50

Yohimbine

Back 50

- selective α2 receptor antagonist. Prepared from bark of African tree, herbal or prescription forms. Taken orally, T1/2 of several hours
- Functional effect: inhibits CNS α2 receptors preventing presynaptic feedback, resulting in upregulation of endogenous E, increasing BP and flow to genitals
- Indications: erectile dysfunction
- Side effects: HTN, sleep disturbances
- Contraindications: uses with sympathomimetics and MAOIs

Front 51

Warfarin

Back 51

Mechanism:
- in vivo inhibition of vitamin K epoxide reductase, which limits vit-k dependent synthesis (carboxylation) of factors 2,7,9,10 in the liver
Use: thrombus prophylaxis, reduction (long term)
Indications: DVT, cerebral vascular thrombosis, A. fib, rheumatic heart disease, valvular heart disease, MI, unstable angina. Contraindicated by pregnancy
Adminstration: oral, long lag time before onset of action and prolonged activation after termination, narrow therapeutic window
- Effects monitored with prothrombin time, INR 2-3 min
- Adverse effects: excessive bleeding (treat OD w/ vit K or plasma transfusion), drug interactions (P450 inhibitors, estrogen), possible rebound effect after termination