CNS Pharm

<Anxiolytics, Hypnotics & sadatives>

Benzodiazepine, Azapirones-Buspirone, Zolpidem
Benzodiazepine Antagonized by flumazenil
Alpraxolam, Clonazepam
o Sedative effect
o Tx Panic disorder & phobias
Buspirone
o Binds 5-HT1A receptors
o Minimal abuse potential
Diazepam (Valilum)
o Binds to GABAa receptor
o Incr. freq of Cl- channel opening
o Tx. Anxiety & ethanol dependence, Status epilepticus
o Tx. Status epilepticus
Zolpidem
o NOT BENZODIAZEPINE but similar effects
o Used as hypnotic
o Less amnesia, less muscle relaxation
<Anti-psychotics> Schizophrenia, delusions
- Dopamine receptor block
Traditional antipsychotics: Thioridazine (low potent), Fluphenazine (high pot),
chlorpromazine, Haloperidol
o Thioridazine
SE: Torsade de pointes arrhythmias & retinal deposits
Cause postural hypotension, sedation, CNS depression
o Haloperidol, Droperidol
SE: Extrapyramidal- parkinsonian, motor restlessness, Tardive dyskinesia
Tardive dyskinesia- After prolonged therapy, rhythmic involuntary tongue,
jaw, lip movement
Active dystonic rxn- Muscle spasms of tongue, neck, face
Neuroleptic malignant syndrome- Rigidity, altered mental status, cardiac
arrhythmia, HTN
o Rx- Dantrolene
Atypical Antipsychotic Drugs- Clozapine, Risperidone, Olanzapine
o Clozapine
Second-line TX for schizophrenia
Better for negative symptoms of dz
Blocks D4 receptor
a/w agranulocytosis
o Risperidone (1st line for schizophrenia)
Largest # of extrapyramidal side effects of all atypical antipsychotics
Blocks D2 & 5-HT receptors
High sedation
sd<Anti-depressant & mania>
Tricyclic antidepressants- Amitriptyline, nortriptyline, imipramine, desipramine
Inhibits reabsorption of norepi & serotonin within synapse
SE- sedation, orthostatic hypotension, cardiac arrhythmias
Selective serotonin reuptake inhibitors (SSRI)- Fluoxetine, sertraline, paroxetine, citalopram
SE: headache, insomnia, nausea, sexual dysfunction
Management of obsessive compulsive disorder (OCD), social phobias, bulimia & alcohol
dependence
Monoamine oxidase inhibitors (MAOI)- Phenelzine, Tranylcypromine (REVERSIBLE),
Isocarboxazid, selegiline
Cheese, which contain tyramine (indirect-acting sympathomimetic) while on MAOIs
o Results hypertensive crisis

 Taken w. SSRIs, serotonin syndrome (life-threatening)

Heterocyclic (Atypical)- Trazadone, Bupropion
Bupropion
o Inhibits reuptake of norepinephrine
o Nicotine withdrawal
<Anticonvulsants (seizures)>
Partial seizure- simple & complex
Simple- focal neurological symptom sensory (auditory, visual hallucination), motor, psychomotor,
o Conscious retained
Complex- loss of consciousness, postictal confusion (coordinated motor activity, mental distortion,
sensory hallu)
o Originates from temporal lobe
Generalized tonic-clonic seizure
Entire cerebral cortex
Tonic phase- loss of consciousness, rigidity, loss of bowel & bladder control
Clonic phase- jerking movement of entire body
Status epilepticus
Continuous seizures not separated by any periods of regained consciousness. Rx- Diazepam,
Lorazepam
Absence seizures
In children 2-12
Very brief few seconds of loss of consciousness
Epilepsy
Group of chronic syndromes characterized by recurrent seizures w. periods of consciousness
Phenytoin
Tx. Partial & tonic-clonic seizures (1st line) & status epilepticus (1st line), class IB
antiarrhythmic
SE: gingival hyperplasia, hirsuitism, anemia & birth defects bc it interferes w. folate
absorption
Carbamazepine
Tx. Partial 1st line (simple & complex) & generalized seizures 1st line (tonic-clonic), Tx of Trigeminal
neuralgia
Inhibits Na+ channels
Result in idiosyncratic blood disorders
o Aplastic anemia & agranulocytosis
Phenobarbital
Sedative
1st line drug for tonic-clonic seizures in children
Tx. Of Crigler-Najjar syndrome type II
Long lasting, prototypic barbiturate
Binds to GABA receptor
Incr. duration of Cl- channel opening w/ neuronal inhibition
Valproic Acid
Tx. Most forms of epilepsy
Tx. Bipolar disorder as well
a/w development of neural tube defects when administered to pregnant women
Ethosuximide
Absence seizures (1st line)
Inhibiting T-type calcium channels in thalamic neurons
a/w Stevens-Johnson syndrome
Gabapentin
Analog of GABA
Tx. Partial seizures & peripheral neuropathy
Iamotrigine
o Cause life-threatening Stevens-Johnson syndrome, epidermal necrolysis,
vigabatrin which inhibits GABA transaminases

Baclofen
Orally active antispasmolytic agent
GABAb receptor agonist functions on inhibitory pathways in spinal cord
Lithium
Mood stabilizer
1st line drug for TX of bipolar affective disorder
Inhibits IP2, DAG
Causes tremor, hypothyroidism, polydipsia, polyuria
<Parkinson disease>
Benzotropine
Antimuscarinics
Contraindications: prostatic hyperplasia, GI obstruction, closed-angle glaucoma
Improving tremors & rigidity, but does little for bradycardia
Bromocriptine
Tx. Prolactinoma as well as Parkinson disease
Ergot derivative; D2 agonist
Inhibits prolactin release
Maintains its effectiveness over time unlike pergolide
Entacapone
Inhibit catechol-0-methyltransferase (COMT)
Inhibits conversion of levodopa to 3-0-methyldopa
Tolcapone- a/w acute liver failure
L-dapa (Levodopa)
Precursor closing BBB & converted to dopamine
Admin w. decarboxylase inhibitor carbidopa to incr. bioavailability & to limit peripheral SEs
Ropinirole (or Pramipexole)
Used when Ldopa is not working
Not ergot derivative
Lower incidence of postural hypotension, dyskinesia, vomiting, hallucination, unlike dopamine
agonists
Selegiline
Inhibits degradation of dopamine
Used as adjuvant to levodopa
Inhibits monoamine oxidase B, which selectively degrades dopamine
Methylphenidate
Amphetamine used for ADD & narcolepsy
Incr. alertness, decr. Appetite by stimulating catecholamine release
Anesthetics
Benzocaine
Ester-type, like cocaine, it has surface activity
Other types: Short-acting procaine & long-acting tetracaine
Low toxicity
Used on large surface area
OTC Ointment
Bupivacaine
Long-acting amide-type local anesthetic severe hypotension & arrhythmias
Bind to Na+ channel
Slow recovery
Cocaine
Only local anesthetic w. vasoconstrictor activity
Fentanyl

Opioid used in induction of anesthesia & post-op analgesia

If used conjunction w. droperidol & Nitrous oxide neuroleptanesthesia
o Resulting in both analgesia & amnesia
Ketamine
Dissociative anesthetic causing hallucinations & disorientation on recovery
SE: incr. cerebral BF
o Can be reduced by pre-op benzodiazepine
Halothane
Most potent inhaled anesthetic
Lowest minimal alveolar conc (MAC)
Used in children & asthmatics
Nitrous Oxide
Never reaches surgical anesthesia level
Safe & induction & recovery are extremely rapid
High MAC, low blood/gas partition
Admin w. IV anesthetic such as thiopental
Dental procedures
Thiopental
Ultra-short-acting barbiturate
High lipid solubility
Short surgical procedures
Rapidly redistributes to other tissues
Tramadol- partially stimulates mu receptors

Antimicrobial
1. Cell wall synthesis inhibitors
Penicillins, cycloserine, cephalosporines, vancomycin
2. Protein synthesis inhibitors
Tetracycline, erythromycin, clindamycin, chloramphenicol
Bind to bact. Ribosomes
3. DNA synthesis inhibitors
Quinolones & floroquinolones
o Block nucleic acid synthesis
Rifampin
o Inhibits DNA dependent RNA polymerase
Sulfonamides
o Inhibit synthesis of folate, which critical component of DNA
4. Cell membrane disrupters
Polyene antimicrobial such as amphotericin B
Bacteriostatic drugs- Arrest growth & replication of bact. Giving bodys immune system a chance to
destroy & remove pathogen
Bactericidal drugs- Bactericidal drugs kill bacteria outright
Penicillin
- Penicillin G (IV, IM), penicillin V (oral), prototype B-lactam antibiotics
Bind penicillin-binding proteins
Block transpeptidase cross-linking of peptidoglycan
o Similar to mech of cephalosporin
Used for gram positive : S. pneumonia, S. Pyogenes, Actinomyces
For Neisseria meningitides, Treponema pallidum & syphilis
Toxicity: Hypersensitivity reaction, hemolytic anemia
Oxacillin, nafcillin, dicloxacillin (Penicillinase-resistant penicillins)
Narrow spectrum, penicillinase-resistant
Penicillinase resistant bc bulky R group blocks access of B-lactamase to B-lactam ring, prevent
degradation by penicillinases
Tx. S. aureus (except MRSA)
Ampicillin, amoxicillin (aminopenicillins)
Combine w. clavulanic acid to protect against B-lactamase
Extended-spectrum of penicillin
Gram neg- Haemophilus spp., E. coli, Listeria, Proteus, Salmonella, Shigella
Greater oral bioavailability & decr. Gastrointestinal irritability
Carbenicillin, Piperacillin, Ticarcillin
Work synergistically w. aminoglycosides
Pseudomonas & enterobacter spp.
Extended spectrum
B-lactamase inhibitors
Clavulanic Acid, Sulbactam, Tazobactam
Often added to penicillin to protect antibiotic from destruction by B-lactamase (penicillinase)
Cephalosporin
- B-lactam drugs inhibiting cell wall synthesis but less susceptible to penicillinases

- Bactericidal
1st gen. cefaxolin, cephalexin
o Gram positive- PEcK Proteus mirabilis, E. coli, Klebsiella pneumonia
2nd gen.- Cefoxitin, cefaclor, cefuroxime
o HEN PEcKS Haemophilus influenzae, Enterobacter aerogenes, Neisseria, Proteus, E.coli,
Klebsiella, Serratia
rd
3 gen- ceftriaxone, cefotaxime, ceftazidime
o Serious gram negative infections; meningitis, gonorrhea, pseudomonas
o Ceftriaxone- TX septic meningitis
Good penetration into CNS
Strep pneumonia, Neisseria miningitidis, H. influenzae, N. Gonorrhea
4th gen. cefepime; incr. activity against Pseudomonas & gram-positive
Polymyxin B
Disrupts bact. Membranes ; too toxic for systemic admin, Topically safe
Systemic use neurotoxicity & acute tubular necrosis
Aztreonam
Work similarly to penicillins & cephalosporins
Resistant to B-lactamases
Ineffective against gram positive or anaerobics
Synergistically w. aminoglycosides against gram negative rods (E coli, pseudomonas)
For penicillin-allergic pts & who cant tolerate aminoglycosides
Imipenem/cilastatin, meropenem
Broad spectrum B-lactamase resistant carbapenem
Always admin w. cilastatin
Against gram positive cocci, gram negative rods, anaerobes
Metabolized by renal dihydropeptidase which blocked by cilastatin
Toxicity- GI distress, skin rash, CNS toxicity
Vancomycin
Inhibits cell wall peptidoglycan formation by binding D-ala D-ala portion of cell wall precursors
Rapid IV infusion a/w diffuse flushing
o Red man syndrome
For Gram positive ONLY- S. aureus (MRSA), pseudomembranous colitis (due to Clostridium
difficile)
Toxicity- Nephrotoxicity, Ototoxicity, Thrombophleobitis, diffuse flushing
SE can be limited by infusion over long time & coadmin of antihistamines
Bacitracin
Inhibitor of bact cell wall synthesis in gram positive
Topical in OTC antibacterial ointment
Severe nephrotoxicity if used systematically
Protein synthesis inhibitors
30S inhibitors Aminoglycosides (Bactericidal), Tetracyclines (Bacteriostatic)
50S inhibitors
Chloramphenicol, Clindamycin (bacteriostatic), Erythromycin (bacteriostatic), Linezolid
Aminoglycosides
Gentamicin, streptomycin, tobramycin, amikacin, neomycin
Bactericidal inhibitors of mRNA translation at 30S ribosome
a/w nephrotoxicity & ototoxicity& Teratogen
Ineffective for anaerobes, bc of requirement for oxygen to be taken up by organism
For gram negative rod infection
Synergistic w. B-lactam antibiotics like ampicillin + gentamicin
Neomycin
o Orally for phophylaxis in bowel surgery & hepatic encephalopathy
o Prevents GI flora growth & accumulation of nitrogenous microbial metabolites
o Too toxic for IV, Topically in OTC antibiotic ointment

Tetracyclines
Tetracycline, doxycycline, demeclocycline, minocycline
Bacteriostatic, inhibit 30S ribosome, protein synthesis
Doxycycline can be used w. pts w. renal failure
Do not take w. milk, antacids or iron containing preps
For Borrelia burgdorferi, M. pneumonia, Rickettsia, Chlamydia, mycoplasma, Vibrio
cholera
Contraindicated in pregnant & children bc of bone dysplasia & defects in dental enamel
Erythromycin
Macrolides, Azithromycin, Clarithromycin
Bacteriostatic inhibitor of protein synthesis; 50S ribosome
Mycoplasma, Corynebacterium, Chlamydia (STDs), Legionella Bordetella
SE: GI irritation, hypersensitivity-based acute cholestatic hepatitis, Arrhythmia, Rash,
Eosinophilia
Safe in pregnancy
Chloramphenicol
Bacteriostatic inhibitor of protein synthesis; blocking peptidyl transferase activity at 50S
ribosome
For meningitis (H. influenza, Neisseria meningitides, S. pneumonia)
SE: Anemia, Aplastic anemia, Gray baby syndrome (cyanosis & cardiovascular collapse, lack
liver UDP glucuronyl transf.)
o Inhibition of RBC maturation, rarely used systemically
Clindamycin
Bacteriostatic inhibitor of protein synthesis, 50S ribosomal subunit
Tx: serious anaerobic infections (Bacteroides fragilis, Clostridium perfringens)
Toxicity- Pseudomembranous colitis (C. difficile overgrowth), fever, diarrhea
Treats anaerobes above diaphragm vs. Metronidazole treat anaerobes below diaphragm
Sulfonamides
Trimethoprim, Sulfamethoxazole (TMP-SMX)
Create block in successive rxn for folate synthesis
Often used for UTI, Shigella, Salmonella, Pneumocystis jirovecii
Trimethoprim- blocks bact Dihydrofolate reductatse
o Can cause megaloblastic anemia
Sulfamethoxazole- blocks Dihydropteroate synthase
o Can cause hypersensitivity & hemolysis in pts w. G6PDH deficiency
Fluoroquinolones
Ciprofloxacin, Norfloxacin
Bactericidal inhibitor of DNA gyrase (topoisomerase II)
Used for gram negative rods (BONE infection), Neisseria, some gram positive organisms
Can Cause tendon damage, contraindicated in children & pregnant women, develop
seizures
Metronidazole
Activation by anaerobes & parasites interfere w. nucleic acid synthesis
Resulting in cytotoxicity
Treats Giardia, Entamoeba, Trichomonas, Gardnerella vaginalis, Anarobes (Bacteroides,
C. difficle), H. pylori, Pseudomembranous colitis
Treats anaerobes below diaphragm vs. Clindamycin tx above diaphragm
Antimycobacterial drugs
M. tuberculosis- via Rifampin, Isoniazid, Pyrazinamide, Ethambutol
M. avium- via Azithromycin, rifampin, ethambutol, streptomycin
M. leprae- via Dapsone & Rifampin
Isoniazid(INH)
Prophylaxis of TB
Inhibits synthesis of mycolic acid in cell wall
SE- peripheral neuritis in slow acetylators & hepatitis in fast acetylators
Multidrug regimens with Ethambutol, pyrazinamide, rifampin, streptomycin

Rifampin
Rarely used alone, except for meningococcal carrier state (prophylactically)
o Chemoprophylaxis in contacts of children with Haemophilus influenzae type B
Imparts red-orange color to secretions
Inhibits DNA dependent RNA polymerase
Rapid resistance if used alone
Used in combined drug regimen
Antimicrobial prophylaxis
Ciprofloxacin, rifampin for children Meningococcal infection
Ceftriaxone- gonorrhea
Benzathine penicillin G- syphilis
TMP-SMX- recurrent UTI
Penicillin- endocarditis w. surgical or dental procedures
Cefazolin- prevention of postsurgical infection due to S. aureus
Erythromycin ointment- prevention of gonococcal or chlamydial conjunctivitis in newborn
MRSA- vancomycin
VRE- Linezolid & strptogramins
Streptogramins
Effective in tx of methicillin-resistant MRSA &VRE
Synercid- mix of quinupristin & dalfopristin
a/w arthralgias & myalgias; inhibition of P450
Antifungal therapy
Amphotericin B
Polyene antifungal for systemic mycosis & intrathecally for fungal meningitis
o Cryptococcus, Blastomyces, Coccidioides, Histoplasma, Candida
Disrupts fungal membranes by binding ergosterol
SE- chills, fever, hypotension, dose limiting nephrotoxicity, drug-induced parkinsonism
o All are less severe when using liposomal formulations
Nystatin
Swish & swallow tx for oral candidiasis or topically for diaper rash
Disrupts fungal membrane permeability by binding to ergosterol
Azoles
Ketoconazole, Itraconazole, Fluconazole
TX mycotic infections
Interfere w. fungal cell wall synthesis , by inhibiting P450 that converts lanosterol to
ergosterol
Inhibit hormone prod gynecomastia
Fluconazole
o Imidazole antifungal used for Tx of fungal meningitis, bc it can cross BBB
o Inhibits formation of ergosterol & Lacks antiendocrine effects seen w. ketoconazole
o Prophylaxis for Cryptococcus neoformans
o Tx of candidiasis
Terbinafine
Inhibits fungal enzyme squalene epoxidase
Tx dermatophytosis (onychomycosis)
Griseofulvin
Oral, accumulates in keratinized tissue
Effective against dermatophyte infections such as ringworm
Binds to tubulin
Inhibiting mitosis
SE- teratogenic, carcinogenic, Incr. P450 & warfarin metabolism
Antiprotozoan therapy

Pyrimethamine (toxoplasmosis)
Suramin & melarsoprol (Trypanosoma brucei)
Nifurtimox (Trypanosoma. cruzi)- Chagas disease, African trypanosomiasis
Sodium stibogluconate (leishmaniasis)

Chloroquine
Primary drug for acute attacks & prophylaxis of malarial infection
o Plasmodial species other than P. falciparum
Kills parasites in erythrocytes (Schizonticidal)
Disrupts hemoglobin breakdown
Quinine
Used for tx of chloroquine-resistant malarial infection due to Plasmodium falciparum
Blocks DNA replication & RNA transcription within erythrocytes
SE: cinchonism, headache, vertigo, blurred vision, tinnitus
Mefloquine- fewer SE used as prophylaxis in chloroquine-resistant areas

Antihelminthic therapy
Mebendazole (related as albendazole, thiabendazole)
For Pinworms- most common in the US
Inhibiting microtubule synthesis & glucose uptake
Pyrantel Pamoate
Used w. mebendazole for roundworm, pinworm, hookworm
Stimulates nicotinic receptors in nematode spastic paralysis
Ivermectin
For river blindness (by Onchocerca volvulus) & treadworm (strongyloides stercoralis)
Incr. GABA mediated neurotransmission paralysis of worm
Praziquantel
Tx trematode (fluke), cestode (tapeworm)
Incr. calcium in worm, niclosamide which functions by uncoupling oxidative phosphorylation
or by activating ATPases, often used w. praziquantel in cestode infection
Antiviral therapy
Oseltamivir, Zanamivir
Oseltamivir- Oral, Decr duration & symptoms of influenza A
Zanamivir- intranasally
Both function as neuraminidase inhibitors, preventing spread of virus from cell to cell
Amentadine , remantadine
Prophylaxis of influenza A & rubella viral
Tx Parkinson disease
Longer half-life
Inhibit fusion of viral particles
Amentadine- not effective for influenza B, which lacks M2 protein
Ribavirin
Admin as aerosol
For respiratory syncytial virus (RSV), Chronic Hep C, viral hemorrhagic fevers
Guanosine analog; capping of viral mRNA, viral RNA-dependent RNA polymerase activity
SE- Hemolytic anemia, severe teratogen
Acyclovir- Oral, topical, IV
Reduce herpes simplex virus (HSV)
No inhibition of reactivation of herpes
Guanosine analog activated by thymidine kinase of herpes virus
o Herpes simplex, Varicella zoster, Epstein-Barr
Functions as chain terminator
Ganciclovir

For Retinitis & Cytomegalovirus (CMV)

Guanosine analog converted by CMV to triphosphorylated form which inhibits viral
polymerase
Good penetration to eye & CNS
Toxicity- neutropenia, leukopenia, thrombocytopenia, renal toxicity
Foscarnet
Back up drug for CMV in immunocompromised pts when resisent to ganciclovir
No require of phosphorylation by viral kinases
Inhibits viral DNA polymerase at diff. site than ganciclovir
Not metabolized by viral transferases which render ganciclovir ineffective
Nephrotoxicity

HIV therapy
Zidovudine (ZDT)/ AZT
Used part of HAART
Prophylaxis of needlestick transmition & transmission to neonates from infected mother during birth
Phosphorylation of this by host cell enzymes inhibiting viral reverse transcriptase, chain
terminator
Protease inhibitors (-navir)
Indinavir, Ritonavir, Saquinavir, Nelfinavir
Combined txt regimens for HIV
Required for prudction of infectious virions
Metabolized by CYT P450
Nucleoside reverse transcriptase inhibitors (NRTI)
Didanosine (ddI), zidovudine (ZDT), zalcitabine (ddC), Iamivudine (3TC), Stavudine (d4T)
Iamivudine- also inhibits reverse transcriptase of Hep B
a/w dose limiting pancreatitis
Nonnucleoside reverse-transcriptase inhibitors (NNRTIs)
Nevirapine, Delavirdine, Efavirenz
Managing HIV infection
No cross-resistance w. NRTIs
Nitrofurantoin
Urinary antiseptic
Ineffective systemically
Can accumulate in pts with renal failure
Cause GI side effects, rash, hemolysis in G6PD deficiency pts

Endocrine
DIABETIC DRUGS (KNOW MECHANISM)
Insulin
Lispro (Rapid acting), Aspart, Glulistine, Regular (short acting), Glargine, Detemir (long-acting)
Immediately before meal
Altered form of insulin entering circulation more rapidly than crystalline zinc (Regularemergency dx) insulin
Bind to insulin receptor (tyrosine kinase activity)
Liver: Incr. glucose stored as glycogen
Muscle: Incr. glycogen & protein synthesis, K+ uptake
Fat: aids TG storage
Type 1 & 2 DM
Toxicity- Hypoglycemia, very rarely hypersensitivity rxn
Ultralente insulin- Supplemented through day with insulin lispro
Given in the morning and in the evening, to maintain basal levels of insulin for 12-24hrs
Biguanides
Metformin (1st line for DM type II)
Oral hypoglycemic agent; NOT require functional pancreatic islet cells
Decr. Postprandial glucose levels w/o hypoglycemia or weight gain
Incr. peripheral glycolysis hepatic gluconeogenesis Decr
Toxicity- Lactic acidosis (contraindicated in renal failure)
Sulfonylureas
1st gen- Tolbutamide, Chloropropamide
2nd gen- Glyburide, Glipizide, Glimepiride
Closure of K+ channel depolarization of B cell & release of preformed insulin
Toxicity- Hypoglycemia
Glitazones/thiazolidinediones (TEDs)
Pioglitazone, Rosiglitazone
Incr. cell sensitivity to insulin, by stimulating PPAR (peroxisomal proliferator gamma)
o Regulates genes in carbohydrate metabolism
Toxicity- Hepatotoxicicy, HF, weight gain, edema
a-glucosidase inhibitors
Acarbose, Miglitol
Oral hypoglycemic agent
Functions in intestinal lumen
Decr. Postprandial hyperglycemia; no effect on fasting sugar
Inhibits a-galactosidase

Toxicity- GI disturbances

Propylthiouracil, methimazole
For Hyperthyroidism
Inhibits iodination & Coupling rxns in thyroid hormone synthesis
Methimazole- cross placenta & enter breast milk
Toxicity- agranulocytosis, aplastic anemia, hepatotoxicity
Levothyroxine (T4), triiodothyronine
For hyPOthyroidism seen in Hashimoto thyroiditis, myxedema, pts in lithium
Thyroxine replacement; Converts T4T3
Toxicity- Tachycardia, heat intolerance, tremor, arrhythmias

Hypothaloamic/pituitary drugs
Somatostatin (Octreotide)
Octreotide- analog of somatostatin
Tx- endocrine tumors, carcinoid, gastrinoma, somatropic pituitary adenoma
Oxytocin
From Posterior pituitary
Stimulate labor, milk ejection
Contraction of uterine SM, contraction of myoepithelial cells to eject milk
Antidiuretic hormone (ADH)Desmopressin, vasopressin
Tx. Diabetes Insipidis
Desmopressin
o V2 agonist facilitating water reabsorption from collecting tubules
Vasopressin
o V1 +V2 agonist
o Tx Esophageal varices; V1 activity incr. vascular smooth muscle tone
Demeclocycline
ADH antagonist
For SIADH
Toxicity- Nephrogenic DI, photosensitivity, abnormality of bone & teeth
Glucocorticoids (regulate gene expression)- hydrocortisone, prednisone, triamcinolone,
dexamethasone, beclomethasone
Decr. Leukotrenes &PG by inhibiting phospholipase A2 & expression of COX-2
Tx. Addisons disease, inflammation, immune suppression, asthma
Toxicity- Iatrogenic Cushings syndrome
Cosyntropin
Synthetic analog of ACTH (adrenocorticotropin) used to Dx pts with abnormalities of cortisol
production
o E.g., Addisons disease
Proteolytic cleavage of preproopiomelanocortin (POMC) forms ACTH & melanocytestimulating hormone (MSH),
Beta-endorphin & metenkephalin
Calcitonin
Tx for osteoporosis, decr. Bone breakdown, decr. Serum calcium & phosphate levels

Tx. Of acute hypercalcemia & paget disease, Salmon calcitonin used bc it is more potent &
longer half-life

Bisphosphonates
Alendronate, Etidronate, Pamidronate, Risedronate
Reduce bone resorption & formation
Used in osteoporosis- postmenopausal, senile, or glucocorticoid-induced, paget disease
Poor oral availability, CANNOT take with food may cause esophageal ulceration, take
with lots of water
Clomiphene
Fertility drug to induce ovulation
Blocks negative feedback to pituitary
Incr. release of FSH & LH

Cardiovascular
Antihypertensive therapy
Essential hypertension
Diuretics (-thiazide), ACE inhibitors, angiotensin II receptor blocker (ARBs), Calcium
channel blocker
CHF
Diuretics (-loop: lose Ca2+ serum incr. in urine), ACE inhibitors/ARBs, B-blockers
(compensated CHF), K-sparing diuretics
Diabetes mellitus
ACE inhibitors/ARBs, Ca2+ channel blockers, diuretics, B-blockers, a-blockers
Calcium channel blockers
Verapamil, Diltiazem, Amlodipine, Nifedipine
Block Volt-dependent L-type calcium channels of cardiac & smooth muscle reduce muscle
contractility
Vascular sm-amlodipine=nifedipine
Heart- verapamil, diltiazem
For HTN, angina, arrhythmias, prinzmetals angina, Raynauds
Toxicity- Cardiac depress, AV block, peripheral edema, flushing, dizziness, constipation
Hydralazine
Incr. cGMP smooth m. relaxation
Vasodilates arterioles>veins; afterload reduction
For Severe HTN, CHF, 1st line for HTN in pregnancy
Co-admin w. B-blocker to prevent reflex tachycardia
Toxicity- Compensatory tachycardia (contraindicated in angina/CAD), fluid retention, nausea,
headache, angina, SLE
Malignant hypertension Tx
Nitropusside, nicardipine, clevidipine, labetalol, fenoldopam
Nitropusside- Short acting; Incr. cGMP via direct release of NO
o Causes cyanide toxicity
Fenoldopam- D1 receptor agonist
o Coronary, peripheral, renal, splanchnic vasodilation

Decr. BP, Incr. natriuresis

Nitroglycerine
For angina, pulmonary edema
Vasodilate by nitric oxide in smooth m.
Causes incr. in cGMP Decr. Preload in ht & Decr. BP
Admin as sublingual patch to decr 1st-pass metabolism
SE- Cyanide poisoning, postural hypotension, headache, flushing
Statin - Lovastatin, Pravastatin
Inhibits rate-limiting enzyme of cholesterol synthesis, HMG-CoA reductase Decreased LDL
May cause Elevated liver enzymes, myositis w. increased creatine kinase from skeletal
muscle
Rarely rhabdomyolysis
Niacin
Lipid-lowering agent causing cutaneous flushing, which can be avoided by admin w. aspirin
Reduces secretion of VLDLs
Increase HDLs
Cholestyramine, Colestipol
Bile acid-biding resins
Used in hyperlipidemia
Prevent enterohepatic recycling diverting hepatic efforts to renew bile acids instead of
producing plasma lipids
Gemfibrozil, Fenofibrate, Clofibrate
Decr. Triglycerides by lipoprotein lipase
Clofibrate a/w gallstones & hepatobiliary neoplasms
Cardiac glycosides
Digitoxin, Digoxin
For congestive Heart failure, atrial fibrillation
Reversible inhibitors of Na/K ATPase Decr. HR, prolong PR interval; Incr. contractility
Unlike digitoxin, digoxin is shorter acting & excreted by kidney
Pts w. low K, low Mg, high Na or high Ca can experience arrhythmias;
Toxicity- Cholinergic- nausea, vomiting, diarrhea, blurry yellow vision; Hyperkalemia
Antidote- K+, Lidocaine, Mg2+
Antiarrhythmics- Na+ channel blockers (Class I)
Local anesthetics, Slow or block conduction (in depolarized cells)
Hyperkalemia causes Incr toxicity for all class I drugs
Class IA- Quinidine, Procainamide, Disopyramide Police Department Questioned
Slow conduction velocity by slowing rate & Rise AP
Maintain SA rhythm after cardioconversion for A. fib
Cause torsade de pointes arrhythmias
Toxicity- Quinidine may cause cinchonism- type of poisoning causes headache, vertigo, tinnitus
o Procainamide- reversible SLE-like syndrome
o Disopyramide- Heart failure
Class

IB- Lidocaine, Mexiletine, Tocainide The Little Men

Decr. AP duration by shortening repolarization phase
Tx. Ventricular arrhythmias, digitoxin-induced arrhythmias
Lidocaine (IV)- Tx ventricular arrhythmias, myocardial infarction bc it only works on ischemic
tissue
Toxicity- local anesthetic, CNS stimulation/depression, cardiovascular depression

Class IC- Flecainide, Propafenone For Pushing Ecstacy

No AP, slow conduction velocity in atrial & ventricular cells

Tx. Refractory Ventricular arrhythmias, rapid A. arrhythmias a/w Wolff-Parkinson-White
syndrome

Class

II (B-blockers)- Propranolol, Esmolol

Decr. SA & AV nodal activity, Slower heart rate
B-blockers Decr. cAMP Reduced Na, Ca currents
NOT use for congestive HF
Toxicity- impotence, exacerbation of asthma, cardiovascular effects (bradycardia, AV block, CHF)

Class

III- K+ channel blockers- Amiodarone, Sotalol, Ibutilide, Dofetilide AIDS

Tx. Recurrent Ventricular arrhythmias
Toxicity- torsade de pointe arrhythmias
Amiodarone- Pulmonary fibrosis, hepatotoxicity, hypothyroidism/hyperthyroidism
photodermatitis, neurologic effects, constipation, CV effects

Class

IV Ca2+ channel blockers: Verapamil, Diltiazem

Tx. Atrial arrhythmias & nodal re-entry, hypertension, angina
Decr. Conduction velocity
Only for hypertension & angina
Toxicity- constipation, flushing, edema, CV effects (CHF, AV block)

Adenosine
Short-acting agent admin IV for AV nodal arrhythmias
SE- Flushing & hypotension
Clonidine
Centrally acting a2 agonist reduces sympathetic ANS Decr. BP
SE- rebound hypertension, abrupt discontinuation
Carvedilol, Labetalol
Tx. CHF
Nonselective B & a1 blocking
Reserpine
Rarely used antihypertensive
Blocks storage & release of catecholamines & serotonin
Can cause suicidal depression, Parkinsonian symptoms
Methyldopa
A2 agonist
Decr. Adrenergic outflow decreased peripheral resistance & decreased BP
Can result in autoimmune hemolytic anemia
Guanethidine
Antihypertensive drug
Blocks norepinephrine release
SE- orthostatic hypotension
Antagonized by tricyclic antidepressants

GI drugs
H2 blockers
Cimetidine, Ranitidine, Famotidine, Nizatidine
Tx. GERD (gastroesophageal reflux disease)
Cimetidine
o Histamine blocker a/w gynecomastia & galactorrhea
o Inhibit hepatic P450 Antiandrogenic effects
Other dines- No inhibition of P450 and No antiandrogenic effects
Proton pump inhibitors
Omeprazole, Iansoprazole, -prazole
Tx. GERD, gastic & duodenal ulcers, H. pylori gastritis, Zollinger-Ellison syndrome
(gastrinoma)
Inhibits H/K ATPase on luminal side of parietal cells
Bismuth subsalicylate,
Tx. Travelers diarrhea
Used with metronidazole & tetracycline for tx of H. pylori a/w peptic ulcer
Sucralfate
Tx. Peptic ulcers, bc it polymerizes & selectively coats necrotic ulcerated tissue
Requires acidic environment to polymerize
o Cannot be used w. antacids or H2 blockers
Misoprostol
Prevent NSAID-induced peptic ulcer for conditions like Rheumatoid arthritis
Used to induce labor
Prostaglandin E analog
Decr. Gastric acid prod & incr. mucus production protecting lining of stomach
Toxicity- Diarrhea

Antacids
- Affect absorption, bioavailability or urinary excretion of other drugs
- Causes hypokalemia
Sodium bicarbonate- systemic antacid
Aluminum hydroxide
Causes constipation
Magnesium hydroxide
Strong laxative, diarrhea
Calcium Carbonate
Causes hypercalcemic alkalosis w. development of renal calculi
Chronic ingestion of this antacid w. milk induce milk-alkali syndrome
Can chelate & Reduce effect of other drugs (e.g, tetracycline)
Ondansetron
Antiemetic to control post-op vomiting & vomiting in chemotherapy pts
5-HT3 inhibitor functions at chemoreceptive area of area postrema
Metoclopramide
Prevent emesis ex. Post-anesthesia or cancer chemotherapy
o Bc. Blocks D2 receptor
Facilitate acetylcholine, antagonizing action of dopamine on enteric N.S.
Toxicity- Incr. parkinsonian effects, Restlessness, drowsiness, sedation, diarrhea, extrapyramidal
symptoms
Infliximab
Tx. Crohns disease, ulcerative colitis, RA
Monoclonal ABx to TNF-a

Sulfasalazine
Tx. Crohns disease, ulcerative colitis
Combination of sulfapyridine (antibacterial) & 5-aminosalicylic acid (anti-inflammatory)
Activated by colonic bacteria
Cisapride
Tx. Of upper GI dysfunction, like GERD or gastroparesis w. delayed gastric emptying
Stimulates peristalsis by promoting release of acetylcholine from postganglionic nns of
myenteric plexis
Diphenoxylate, Loperamide
Opioid derivatives Tx of diarrhea bc they suppress GI motility
Diphenoxylate formulated w. antimuscarinic alkaloids
Dronabinol
Tx. Emesis & nausea a/w chemotherapy & contains active ingredient in marijuana
Schedule III drug contains tetrahydrocannabinol (THC), controlled substance
Ipecac syrup
Proemetic agent used in cases of ingestion of caustic substances or mineral oils
Oral, acts on chemoreceptor trigger zone in medulla

ANTI- INFLAMMATORY DRUGS

Aspirin (acetylsalicyclic acid)
Irreversibly inhibits both COX1 & 2
Inhibits formation of PGE
Incr. bleeding time; Can decrease uric acid secretion
Decr. Pain & fever
Antiplatelet, anti-inflammatory properties
Predisposing acute gastritis
NSAIDS
Ibuprofen, naproxen, Piroxicam
Reversible inhibitor of cyclooxygenase (COX1&2)
Block PG synthesis
More efficacious analgesics & anti-inflammatories, antipyretic
Lack antiplatelet effects
Indomethacin
High potency NSAID
TX ACUTE GOUT & ARTHRITIS & Closure of ductus arteriosus (PDA)
Ketorolac
Only parenteral NSAID
Primarily for its analgesic
Substantially decreases GI irritation
COX-2 inhibitors
Celecoxib
Tx. RA & chronic conditions
Decr. Risk of ulcers & other GI bleeds

Selectively inhibit COX-2 only in leukocytes

No inhibition of COX-1 which produces protective PG in stomach
Sulfa drugs hypersensitivity In some pts

Acetaminophen
Commonly for analgesic & antipyretic but NO anti-inflammatory properties
Reversibly inhibit cyclooxygenase, inhibits PG synthesis
Mostly in CNS
Used instead of aspirin to avoid Reyes syndrome in children w. viral infection
Prodrug- phenacetin
Antidote- N-acetylcystein
Toxicity- nephrotoxicity, hepatic necrosis
Bisphosphonates
Alendronate (-dronates)
Pyrophosphate analog; Inhibiting osteoclast activity
For osteoporosis, hypercalcemia, Pagets disease of bone
Toxicity- corrosive esophagitis, osteonecrosis of jaw
TNF-a inhibitors
- Predispose to infection including reactivation of latent TB
Etanercept- for Rheumatoid arthritis, psoriasis, ankylosing spondylitis
Infliximab, adalimumab- For Crohns disease, RA, ankylosing spondylitis, psoriasis

GOUT DRUGS
NSAIDs & Indomethacin above
Allopurinol
For Chronic gout
Inhibits xanthine oxidase Incr. xanthine & hypoxanthine
o Both are soluble & less likely from crystals than uric acid
Febuxostat
Inhibits xanthine oxidase
Probenecid
Uricosuric agent for Chronic gout
Incr. effective conc. of weakly acidic drugs like penicillin
Compete w. uric acid for reabsorption in proximal tubules of kidney
Inhibit secretion of weak acids
Colchicine
For Acute gout, impairs leukocyte function
Inhibits microtubule assembly leukocyte migration & phagocytosis of uric acid
crystals
o No effect on biosynthesis or excretion of uric acid
Toxicity- GI SE, diarrhea
ETC
Gold salts
Tx. Severe Rheumatoid arthritis, decr. Lysosomal & macrophage function
SE- dermatitis, hematotoxicity & nephrotoxicity
Capsaicin
Topically used for RA, bc it depletes substance P
Potent NT for pain sensation
Thalidomide

 Tx. SLE, multiple myeloma, leprosy

Suppress TNF-a
Causing teratogenic effects (phocomelia flipper limb)
Sumatriptan
Serotonin agonist
Tx. Migraines & cluster headaches
Binds to HT1d receptor vasoconstriction of cerebral vasculature
Methylsergide
Prevention of migraines
Ergot derivative, no value in Tx of acute migraine attacks
Blocks serotonin (5HT) receptor
Tx of carcinoid tumors
SE- Retroperitoneal & subendocardial fibroplasia
Meperidine
Opioid agonist
Analgesic for pancreatitis, cholecystitis
Cause biliary spasms
Relaxation of sphincter of Oddi
Contraindicated in cases of head injury, bc they cause increased intracranial pressure
Cyclosporine
Used in Tx of transplant pts & pts w. autoimmune disease
Impairs T cell production of IL-2
Inhibits transcription of cytokine genes
Tacrolimus
o Similar agent, binds to immunophilin FK-binding protein (FKBP)
Toxicity- dose-limiting nephrotoxicity
Daclizumab
Monoclonal AB used in management of pts with renal allografts
Binds to high affinity IL2 receptor expressed on activated T cells
Respiratory Drugs
H1 Blocker
1st gen: Diphenhydramine, Chlorpheniramine, Dimenhydranate (-en/-ine or en/-ate)
Anti-histaminic for Tx. Allergic (hay fever, urticarial, atopy)
Also Tx. Motion sickness
Inhibit H1 receptors
Anticholinergic effects
SE- sedative
2nd gen: Loratadine, Fexofenadine (-adine)
Nonsedating antihistamic
Do not enter CNS
Asthma drugs
Acebutolol, Atenolol, Metoprolol
B-adrenergic antagonists
Tx- HTN for pts w. asthma or COPD, smokers
B1 Blockers Decr. BP w. no bronchoconstriction at low doses
Albuterol
Adrenergic agonist
Management of bronchospasm in asthmatics
B2 agonists- include metaproterenol, terbutaline, salmeterol
Salmeterol
o Long-acting B2 agonist for prophylaxis of asthma
o Works for 12 hrs or more
o SE- tremors & arrhythmias
Theophylline
Methylxanthine for asthma for its bronchodilatory effects & Status asthmaticus (life-threatening)

 Inhibits phosphodiesterase Inhibiting degradation of cAMP AMP

Cimetidine & Erythromycin incr. theophylline plasma levels
Phenytoin decreases theophylline plasma level
Ipratropium
Aerosolized Anti-muscarinic agent
For COPD & asthma
SE- Dry mouth
Beclomethasone
Synthetic glucocorticoid penetrates airway mucosa
Short lives in blood stream
1st line for chronic asthma & chronic rhinitis
Less systemic effects than other glucocorticoid
Zileutin, Zafirlukast & Montelucast
Selectively inhibit leukotriene synthesis, NOT beneficial in acute bronchospasm
Leukotrienes inhibited by LTD4 & LTE4 antagonists Zafirlukast & Montelucast (sounds like
last step of leukotriene)
o These are especially good for aspirin-induced asthma
Omalizumab
Monoclonal anti-IgE AB
Used in allergic asthma resistant to inhaled steroids & long-acting B2-agonists
Cromolyn Sodium
Stabilizes mast cell & basophil membranes, preventing release of histamine in asthmatics
For prophylaxis ONLY & Rhinitis
NOT for Acute asthma attacks
Dextromethorphan
Opioid agonist in OTC cough syrups
Antitussive agent depresses cough center in medulla
Codeine- for analgesia & higher abuse potential; tolerance from chronic use
Ephedrine & pseudoephedrine
a-adrenergic agonists constrict dilated arterioles in nasal mucosa to tx rhinitis
Diuretics
Mannitol
In Prox. Convoluted tubules
Maintain high urine output in cases of hemolysis or rhabdomyolysis
Extracting water from tissues blood
Tx. Hydrocephalus & incr. intracranial pressure
Toxicity- Pulmonary edema, dehydration, contraindicated in anuria, CHF
Acetazolamide
Inhibits carbonic anhydrase in Prox. Convoluted tubule
Maintain glaucoma, acute mountain sickness
Alkalinize urine in aspirin toxicity
SE- Metabolic acidosis, sulfa allergy
Loop Diuretics
Flurosemide/Butamide
Sulfa drugs, can cause hypercalcemia, ototoxicity, hyperuricemia, hypokalemia,
metabolic alkalosis
Most potent class of diuretics
Inhibit Na/K/Cl co-transporter in thick ascending loop
Incr. Ca excretion, prevent conc. of urine
Stimulate PG,
Inhibited by NSAIDs
Ethacrynic acid
Non-sulfa drug
Never use to tx gout

Hydrochlorothiazide
In Distal convoluted tubule
Inhibit NaCl reabsorption, Decr. Ca excretion
For hypertension, CHF, nephrogenic diabetes insipidus (Excessive free H2O loss)
SE- hypokalemia, alkalosis, hyperuricemia, hyperlipidemia
K-sparing diuretics (At Collecting Tubule) Keep K+
For Hyperaldosteronism, K depletion, CHF (Rx. Aldosterone antagonist, B blocker, ACE
inhibitor, Diuretics, aspirin)
Spironolactone & eplerenone
Aldosterone antagonist
SE- Incr. P450 gynecomastia & other Antiandrogenic effects
Amiloride & Triamterne
Blocking Na channel/ not aldosterone antagonist
No Anti-androgenic effects
SE- hyperkalemic metabolic acidosis
Calcium Salts- cause milk alkalis syndrome but tastes the best
ACE inhibitors (@ collecting tubule)
Captopril, Enalapril, Lisinopril
Anti-hypertensive drugs
Inhibit conversion of Angiotensin I II
Inhibit breakdown of bradykinin COUGH & potent vasodilator
SE- cough, angioedema, teratogen, hyperkalemia, creatine incr.

Losartan
NO COUGH SE
Teratogenic Contraindicated for pregnancy
Angiotensin II receptor antagonist
Anti-HTN drug
Nitroprusside; Minoxidii (topical antiHTN agent; Beneficial SE of hypertrichosis-abnormal hair
growth)
Stimulate guanyl cyclase w. incr. in cGMP within smooth mm
Potent vasodilator used in malignant HTN
SE- Cyanide poisoning due to release of CN-; postural hypotension
Diuretics: electrolyte changes
Urine NaCl
Incr. (All diuretics)
Urine K+
Incr. (All except K+ sparing diuretics)
Blood pH
Decr. (Acidemia)
o Carbonic anhydrase inhibitors- Decr. HCO3- reabsorption
o K+ sparing-aldosterone blockade prevents K+ secretion & H+ secretion
o Hyperkalemia leads to K+ entering all cells (via H/K exchanger) in exchange for H existing
cells
Incr. (Alkalemia)
o Loop diuretics & thiazides alkalemia

Volume contraction Incr. ATII Incr. Na/H exchange in prox. Tubule Incr. HCO3reabsorption
K+ loss leads to K+ exciting all cells in exchange for H+ entering cells
In low K state, H exchanged for Na in collecting tubule alkalosis & paradoxical
aciduria

Urine Ca2+
Incr. w. loop diuretics
o Decr. Paracellular Ca reabsorption hypocalcemia
Decr. W. Thiazides
o Enhanced paracelullar Ca reabsorption in prox. Tubule & loop of Henle

Blood
Heparin
Activates antithrombin III
Rapid acting, IV anticoagulant
For acute MI & DVT prevention
Results in inactivation of thrombin and other clotting factors
DOES NOT CROSS PLACENTA unlike warfarin
o Used during pregnancy
Protamine sulfate used to reverse heparin effect
Toxicity- bleeding, osteoporosis
Act on factor Xa, better bioavailability with LOW DOSE
Warfarin (Coumadin)
Interferes Vit K-dependent carboxylation of clotting factors 10, 9, 7, 2 (1972)
Effect on Extrinsic pathway & Incr. PT (WEPT)
PO anticoagulant
For Prophylaxis of venous thrombosis, myocardial infarction, stroke
NOT during pregnancy
Thrombolytics
Alteplase/Reteplase (Tissue Plasminogen Activator/t-PA)
Converts fibrin-bound plasminogen to plasmin, Incr PT & PTT

 Thrombi dissolution
Created thru recombinant DNA
For coronary artery thrombosis & ischemic stroke
Toxicity- Bleeding, Tx with aminocaproic acid
Streptokinase
Catalyzes plasminogen plasmin
Sign. Cheaper than tPA
Strep. Pyogenes product
For Tx. For coronary a. thrombosis
Aspirin
Irreversibly inhibit both COX1, 2 by covalent acetylation
Incr. bleeding time, Decr. TXA2 & PG
For antipyretic, analgesic, anti-inflammatory, antiplatelet
Toxicity- Gastric ulceration, tinnitus, acute renal failure
ASPIRIN- Asthma, Salicylism, Peptic ulcer, Intestinal Blood loss, Reyes syndrome, Idiosyncratic rxn,
Noise (tinnitus)
ADP receptor inhibitors
Clopidogrel, Ticlopidine, Prasugrel, Ticagrelor
Inhibit platelet aggregation by irreversibly blocking ADP receptor
For acute coronary syndrome
Toxicity- neutropenia
GP IIb/IIIa inhibitors (on Platelets)
Abciximab, eptifibatide, tirofiban
Bind to glycoprotein receptor IIb,IIIa on activated platelets, preventing aggregation
Monoclonal AB
Used in anticoagulant, preventing restenosis after coronary angioplasty
Ticlopidine
Interferes w. binding of fibrin to glycoprotein IIb/IIIa receptor on platelets
Platelet antiaggregant
For prevention of transient ischemic attacks (TIA) in pts w. aspirin sensitivity

Folic Acid
Vit B12 deficiency must be ruled out before treating megablastic anemia w. folic acid
Only correct anemia but not neurologic deficits
Erythropoietin (Epoetin Alfa)
Tx anemia a/w bone marrow transplants or toxic drug rxns
Recombinant product used in tx anemia a/w renal failure
Aminocaproic acid
Tx. Acute bleeding in pts with hemophilia & coagulopathies
Orally active inhibitor of plasminogen activation
Inhibit fibrinolysis
Tranexamic acid
Hydroxyurea
For management of sickle cell anemia & myeloid neoplasms
Decr. Sickle cell crisis by increasing level of fetal Hb (HbF)
Inhibits DNA synthesis by blocking conversion of ribonucleotides to deoxyribonucleotide

Cancer
Antimetabolites
Methotrexate (MTX)
Folic acid analog
o S phase inhibitor of dihydrofolate reductase
Decr. DNA & Protein synthesis
For leukemia, non-Hodgkin lymphoma, RA, Therapeutic abortions, psoriasis
Toxicity- myelosuppression (Tx w. leucovorin)
Fluorouracil (5-FU)
Pyrimidine analog, Inhibits thymidylate synthase
For colon cancer, superficial tumors such as basal cell carcinoma
S-phase antimetabolite causes myelosuppression
Cytarabine
Pyrimidine analog inhibition of DNA polymerase
For leukemia, lymphomas
Azathioprine, Mercaptopurine (6-MP), Thioguanin (6-TG)
Purine metabolites
For leukemia, lymphomas
Requires activation by hypoxanthine-guanine phosphoribosyltrasferase (HGPRT)
Inhibits many enzymes involved in purine metabolism

Antitumor antibiotics
Dactinomycin (Actinomycin D)
Intercalates in DNA
For wilms tumor, Ewings sarcoma, rhabdomyosarcoma, Childhood tumors
Doxorubicin (Adriamycin), Daunorubicin
Intercalates in DNA Decr. Replication & transcription
For myelomas, sarcomas, lymphomas
Toxicity- Cardiotoxicity, dilated cardiomyopathy,
Daunorubicin- for acute myelogenous leukemia (AML)
Bleomycin
Induces free radical formation causes breaks in DNA strands
G2 phase inhibitor
ABVD regimen- Adriamycin, Bleomycin, Vinblastin, Dacarbazine for Hodgkin disease
For testicular cancer, Hodgkins lymphoma
Toxicity- Pulmonary fibrosis
Alkylating agents
Cyclophosphamide
For Tx of non-Hodgkin lymphoma & breast & ovarian carcinomas
SE- hemorrhagic cystitis
o Decreased by hydration & use of mesna
Nitrosoureas- (Carmustine, Lomustine)
Highly lipophilic nitrosoureas crossing BBB
For Tx. Of many brain tumor
DNA cross-linking & strand breaks
Busulfan
CML
Ablate pts bone marrow before transplantation
Toxicity- pulmonary fibrosis, hyperpigmentation
Microtubule inhibitors
Vincristine,
Part of MOPP regimen for lymphomas, Wilms tumor, Choriocarcinomas
o MOPP- Mechlorethamine, Oncovin (vincristine), Procarbazine, Prednisone
M phase inhibitor blocks microtubule polymerization & spindle formation
Toxicity- Neurotoxicity
Vinblastin
Part of ABVD regimen
o Adriamycin, Bleomycin, Vinblastine, Dacarbazine
Toxicity- Blasts bone marrow suppression
Paclitaxel
Microtubule stabilizing agent
For ovarian & breast carcinomas
From yew tree
M phase agent prevents mitotic spindle from breaking down inhibits completion of anaphase
Toxicity- myelosuppresion & hypersensitivity
Cisplatin, carboplatin
Tx. Testicular & lung carcinomas
SE- nephrotoxicity, acoustic nerve damage
Carboplastin- less nephrotoxicity & neurotoxicity but greater myelosuppression
Etoposide

Inhibitor of topoisomerase II for tx. Small cell carcinoma of lung, prostate, testicular cancers
G2 phase-specific inhibition
DNA breaks & degradation

Presdnisone
Glucocorticoid for tx. Leukemias & lymphomas, RA, Asthma
Triggers apoptosis lead to hypercoticolism w. Cushing-like symptoms
Must be tapered gradually to prevent life-threatening adrenal insufficiency
Toxicity- Cushing-like symptoms, immunosuppression, cataracts, acne, osteoporosis, HTN,
hyperglycemia, psychosis
Tamoxifen
Primary agent for estrogen receptor- Breast cancer
Toxicity- Endometrial carcinoma
Trastuzumab (Herceptin)
Monoclonal AB for metastatic breast cancer
Binds to receptor tyrosine kinase Erb-B2 (HER-2)
Rituximab
Monoclonal AB for tx of low-grade non-Hodgkin lymphoma
Binds to CD20 antigen on B cells
Adverse reaction- infusion, fever, chills, headache, nausea
Interferon Alpha
Recombinantly produced cytokine
For Hairy cell leukemia
Tx. Chronic myelogenous leukemia (CML), malignant melanoma, Kaposi sarcoma
Normally produced by virally infected cells to prevent infection of adj. cells

Toxicology
Dantrolene
Antispamodic
For Malignant hyperthermia & neuroleptic malignant syndrome
Decreases Ca2+ release from sarcoplasmic reticulum
Muscle relaxant w. minimal sedation SE
N-Acetylcysteine
Tx. Acetaminophen overdose
May protect fulminant hepatic failure
Deferoxamine
Tx. Iron toxicity
A/W hypotensive shock
Digibind
Fab fragment AB for Tx. Digitalis toxicity
Also Tx. Mg2+, K+ correction, Lidocaine for arrhythmias
Dimercaprol
Tx. Heavy metal poisoning, Lead poisoning, arsenic, mercury poisoning
Chelates metals
Succimer- PO available

Ethylene Glycol
Ingestion, industrial inhalation, or absorption thru skin causes metabolic acidosis &
precipitation of damaging oxalate crystals in kidney
Component of antifreeze
Toxicity managed by ethanol
Flumazenil
For benzodiazepine overdose
Antagonizes benzodiazepines & zolpidem although it doesnt block actions of barbiturates
Methanol
Cause retinol damage, blindness along w. metabolic acidosis & coma
Damage due to conversion to formaladehyde by liver
Tx. Ethanol which competes for alcohol dehydrogenase
Naltrexone, naloxone
Tx. Opioid overdose
Antagonists Mu opioid receptors
Organophosphates (Isoflurophate/Echothiophate/Parathion)
Anticholinesterases used as insecticides
Agents of chemical warfare, motor paralysis, respiratory depression, convulsions
Antidote- Atropine, acetylcholinesterase regenerators such as pralidoxime
Penicillamaine
Derivative of penicillin w. ability to chelate copper ions
For Tx. Copper toxicity

Tx. Wilson disease

Adjunct therapy for rheumatoid arthritis

MISC
Disulfiram- Tx. Alcoholism
Naproxen
o Dysmenorrheal pain & in acute gouty attacks but decreases diuretic action of furosemide
Lorazepam
o Sudden status epilepticus
o Best IV drug
Lopramide- doesnt cross BBB

Drugs of abuse
Amphetamines
Causes feelings of euphoria, self-confidence
Chronic doses- Delusions & paranoia
Function indirect sympathomimetic by releasing stored catecholamines
Cocaine
Overdose often results in fatalities from arrhythmias, myocardial infarctions, seizures
Inhibits catecholamine reuptake
Resulting in cardiotoxicity & hypertensive episodes
Disulfiram
Used to tx alcoholism
Causing flushing, vomiting, hypertension when alcohol consumed
Inhibits aldehyde dehydrogenase
o Toxic accumulation of acetaldehyde
Ecstasy
congener of amphetamine results in increased intrapersonal communications & incr. sexual
drive
Flunitrazepam
rapidly acting benzodiazepine used as date-rape drug
Due to amnestic properties, this added to alcohol, making victim incapable of resisting or
remembering being raped
LSD (Lysergic Acid Diethylamide)

Hallucinogenic agent causes psychedelic perceptual effects

Panic attack
a/w somatic effects such as nausea, paresthesias & weakness
o seen w. use of mescaline & psilocybin

Marijuana
High a/w euphoria, disinhibition, laughter, changes in perception, hunger
Tetrahydrocannabinol (THC) can be used medically to lower intraocular pressure in
glaucoma
MPTP
By-product of incorrectly synthesized illicit street opioids,
o This can cause irreversible parkinsonism
Causes destruction of Dopaminergic neurons of nigrostriatal tract
Phencyclidine (PCP)
Hallucinogen often causes psychotic rxns & impaired judgment leading to reckless behavior
Aka angel dust
OD- nystagmus, life-treatening hypertension & seizures
Methadone
Used in management of opioid withdrawal & addicts
Tx. Nausea, chills, sweats, lacrimation, cramps, rhinorrhea, yawning, piloerection,
diarrhea, tremor
Opioids (Heroin/Morphine/Meperidin/Fentanyl)
OD constricted pupils, clammy skin, nausea, drowsiness, respiratory depression w. possible coma
& death
Modulate synaptic transmission by binding mu (morphine), delta (encephalin), kappa (dynorphin)
receptors

Shared effect
Aminoglycosides (antibiotics)
Loop Diuretics
Cisplatin (Antineoplastic)
Causes sign. Ototoxicity & nephrotoxicity
Vancomycin rarely a/w mild ototoxicity & nephrotoxicity
o although both may become sign. When used in conjunction w. aminoglycosides
Bleomycin (Antineoplastic)
Amiodarone (Class IA Antiarrhythmic)
Busulfan (Antineoplastic)
Drugs leading to pulmonary fibrosis & subsequent restrictive lung disease
Pts may manifest w. dyspnea, tachypnea, cyanosis
o w. decr. Forced expiratory vol. at 1 sec (FEV1) & decr. Forced vital capacity (FVC)
Cimetidine (Antiulcer)
Ketoconazole (Antifungal)
Spironolactone (Antihypertensive)
Cause gynecomastia
All compete for androgen receptors, leading to antiandrogenic effects
Cimetidine (Antiulcer)
Ketoconazole (Antifungal)

Erythromycin (Antibiotic)
Common drugs inhibiting hepatic P450 system
Potentiate action of other drugs which normally metabolized by P450
Doses must be lowered when such drugs used together
Helothane (anesthetic)
Acetaminophen (Analgesic)
Valproic Acid (Anticonvulsant)
Drugs can cause massive hepatic necrosis
Hydralazine (Vasodilator)
Procainamide (Class IA Antiarrhythmic)
Isoniazid (Antituberculoid)
Phenytoin (Anticonvulsant)
Cause SLE-like syndrome
Symptoms- arthralgias, myalgias, skin rashes, fever
Mebendazole, Thiabendazole (Antihelminthic)
Paclitaxel, Vincristine (Antineoplastic)
Colchicine (Antigout)
Griseofulvin (Antifungal)
Inhibit microtubule function
Either block intracellular transport, interfere locomotion, disrupt formation of mitotic
spindle
Metronidazole, Cephalosporins (Antibiotic)
Procarbazine (Antineoplastic)
Cause disulfiram-like rxn
Cause flushing, headache, nausea, sweats, hypotension, confusion

Niacin (Antihyperlipidemic)
Calcium Channel Blockers
Adenosin (Antiarrhythmic)
Vancomycin (Antibiotic)
Cause cutaneous flushing on admin
Often SE controlled by slow infusion or coadmin w. histamine blockers
Penicillins, Cephalosporins, Vancomycin, Aminoglycosides, Fluoroquinolones, Metronidazole
Bactericidal antibiotics
Most other antibiotics are bacteriostatic
Phenytoin, Carbamazepine (Anticonvulsant)
Griseofulvin (Antifungal)
Rifampin (Antituberculoid)
Barbiturates
Chronic ethanol use
Induce hepatic P450 system
Hepatic P450 microsomal mixed function oxidase system involved in phase I metabolism
of many drugs
Sulfonamides (Antibiotic)
Ethosuximide, Lamotrigine (Anticonvulsant)

Drugs cause Steven-Johnson syndrome, febril, erosive hemorrhagic crusting on lips & oral
mucosa of children
Penicillins, barbiturates, salicylates, hydantoins, antimalarials
o a/w less severe form of erythema multiforme
o w. macules, papules, vesicles, bullae

Sulfonamides (antibiotic)
Isoniazid (Antituberculoid)
Primaquine (Antimalarial)
Cause hemolysis in pts w. glucose-6 phosphate dehydrogenase (G6PDH) deficiency
In pts w. G6PDH deficiency , these drugs will causes
o Oxidative stress on RBCs bc of deficit of reducing equivalents of NADPH
Normally generated by hexose monophosphate shunt
Tetracycline (Antibiotics)
Amiodarone (Class IA antiarrhythmic)
Sulfonamides (Antibiotics)
Cause photosensitivity
Barbiturates can precipitate photosensitivity in pts w. acute intermittent porphyria