Drug Mechanism

Antifungals
Clincal Use Side Effects
-Binds ergosterol – DOC -Systemic mycoses Neurologic imbalance
ANTIFUNGAL Amphote
(animals sterol) Anemia – decreases erythropoiet
ricin B -Pores in membrane Broad spectrum Electrolyte imbalance
(increases permeability)
-Low therapeutic index Nephrotoxic
-IV (intrathecal in
meningitis)
Fever, chills, pain, N/V – pre-tx
steroid/NSAID
Flucytosine -Pro-Drug Combo w/ Ampho B to decrease BM depression
-Deaminate  5- toxic effects of Ampho B
fluorouracil -Synergistic b/c also increases
-Fxnal/strxral flucytosine penetrance
instability -Meningitis – crypto or candida
-Inhibits thymidine UTI- candida
synthetase Torulopsis glabrata
-Enters CSF
Nystatin -Structurally similar to Candidiasis Rare – lack of absorption
(topical) Ampho B -Vaginal N/V
-Same mechanism -Skin Topical b/c too toxic
-Not well-absorbed -Oral for topical tx of GI
fungi (thrush)
IMIDAZOLES Ketaconazole -All work by blocking DOC – non-meningeal -N/V, anorexia
(itraconazole fungi cyt P450 blastomycosis, -Allergic rash
) -Inhibits ergosterol paracoccidiomycosis, -Inhibits steroid synthesis
production coccidiomycosis -Decreased libido, gynecomasti
-Disrupts membrane -Mucocutaneous candidiasis -Liver dysfxn
-Increased permeability -Vaginal candida -Teratogenic
-Also inhibits -Cushings Syndrome -Increases cycloserine/warfarin
-gonadal/adrenal Testicular Ca (anti-androgenic levels (x-rxn w/ human Cyt P450
steroid synthesis effect) -Nephrotoxic
Oral -
Fluconazole -Similar to -Esophageal candidiasis Steven’s-Johnson’s syndrome –
ketaconazole -Prevents relapse of bullous erythema formae
-Enters CSF cryptococcal meningitis -Thrombocytopenia in AIDS pt.
-Slow metabolism -DOC – cryptococcal -Co-administration w/ phenytoin,
-No endocrine side meningitis, candidemia, sulfonylurea, warfarin cyclospori
effects coccidiomycosis increases plasma concentration
- Enters CNS readily
Clotrimazole Topical only -DOC – oral thrush
-Tinea
-Otomycosis
-Cutaneous/vulvar candida
-Versicolor
Econazole Water-soluble cream -Candida Local erythema
-Dermatophytes Burning/itching
Miconazole Dermatological & Tenia pedis (athletes foot),
(monistat) vaginal cream cruris, versicolor

Vulvovaginal candidiasis

Trichophyton
Griseofulvin -Microtubule interxn Dermatophytes - Superficial -Barbituataes decrease absorpt
-Disrupts mitotic -Microsporum -Hepatotoxic – increase metaboli
spindles -Epidermophyton of warfarin, contraceptives (BC)

29
-Keratin-containing -Trichophyton -H/a post-discontinuation
tissues & may take -Peripheral neuritis
months -Teratogenic /carcinogenic
-Can be given IV to tx
Candidas if allergic to
ampho B
-Must given w/ fatty
meal

30
 Drug Mechanism Clincal Use Side Effects

ANTIVIRALS Amantadine -increase endosomal pH Prophylactic for Reswpiratory -CNS affects

Bockage of Rimantidine (blockage of uncoating) viruses -teratogenic
adsorption, -enters CNS -Influenza A -contraindicated in psychiatric disorders,
penetration, & -oral Antivirals
-Rubella epilepsy, CAD
uncoating -Parkinson’s disease (amantidine) -renal failure  toxicity
Nucleic acid Acyclovir -activiated by VIRAL -HSV-1,2 -local irritation (topical)
synthesis thymidine kinase -VZV -h/a, diarrhea, n/v (oral)
-premature chain -DOC – HSV encephalitis -renal dysfxn(crystallization), seizure, delirium
termination -prophylaxis immunocompromised hypotension (hi IV dose)
-disseminated seropositive
throughout body – oral, -CMV resistant – no thymidine kinase
topical, IV
-irreversibly binds
template primer to
viral DNA polymerase
-competes w/
deoxyguanosine
-only viral infected
cells affected
Gancyclovir -acyclovir analog DOC – CMV (disseminated -reversible neutropenia
-inhibits Viral DNA Pol /retinitis) -thrombocytpenia
-prophylaxis in BM suppression -renal dysfxn
-seizures
Trifluoridine -phosphorylated by Topical only Ocular irritation
idoxuridine HOST kinases Edema
cytarabine -incorporated to host -HSV keratitis Photophobia
& infected cells Pain
-inhibit DNA to
DOC – keratoconjunctivitis w/
disrupt fxn Systemically
respect to HSV
-Bone marrow suppression
-renal damage
-acyclovir resistance (2nd line)
-AML
Vidarabine -adenosine analog -HSV keratitis/encephalitis GI irritation
-inhibits DNA pol Hepatic dysfxn
-topical or systemic -in immunocompromised Convulsions
DOC -neonatal herpes
-VZV, HSV-1,2
Azidothymidi -Phosphorylated inhibits HIV -BM toxicity
ne (AZT) RT -CNS – h/a, insomnia, agitation, seizure
-terminates DNA -toxicity – precipitated by acetaminophen,
synth/replication lorazepam, indomethacin, sulfa’s, probenecid,
cimetidine
Interferons -induce protein kinase -Herpes zoster -FLU-like (h/a, fever, muscle aches)
--oligoadenylate -CV – dysfxn
kinase, protein kinase, -HBV -neurotoxic
phosphodiesterase -Kaposi’s sarcoma -BM suppression
(blocks peptide chain) -Hairy cell leukemia -GI irritation
-inhibitory on -HPV – (genital warts) –gamma-INF
DNA/RNA synth
-glycoprotein
Foscarnet -inorganic phosphate -acyclovir – resistant strains Renal impairment
analog Tremors & seizures
-inhibits DNA pol w/o -CMV 2nd to gancyclovir Hypocalcemia
being phosphorylated – CMV retinitis-in immunosuppressed Anemia
Ribavirin -synthetic guanosine DOC – RSV – children – aerosol Interferes w/ AZT
analog Anemia in Lassa fever
-inhibits viral coded -Influenza A, B Elevates bilirubin
RNA Pol (inhibits viral Lassa/hemorrhagic fever Electrolyte dysfxn
mRNA synth) Contraindicated in pregnancy

31
 DDC -Converted to ddCTP Peripheral neuritis
LATE Methisazone -late -Alters
(dideoxycytosine) structural protein
DNA synth AZT-resistant HIV
PROTEIN/ synthesis inhibition
PROTEASE Saquinovir -Blocks aspartate -small-Given
pox (eradicated)
in high dose to completely
VIRAL -
INHIBITORS indinovir ritinovir proteinase to prevent stop replication of virus
ASSEMBLY
cleavage of gag-pol -too low or monotherapy 
precursor protein resistance
-Blocks packaging &
assembly

32
 o
Gaseous Anesthetics

Drug type Drug Mechanism Clinical Use Side Effects

Inhaled Nitrous oxide MAC 100 Potent analgesic!!!! -Safest

anesthetics -Weak; used w/ No anesthetic -Diffusional hypoxia
others Give w/ 20% O2 -Vit B12 def.
-Rapid onset, rapid -2nd gas effect (enhance solubility of
recovery 2nd)
-< CV & resp. -Little muscle relaxant
depression
Desflurane MAC 8.0 Ambulatory surgery Bronchial irritation
Irritating
Not very soluble
Rapid onset &
recovery
-Less potent
Isoflurane MAC 1.4 -No arrhythmias Irritating
-No problems w/ catecholes
Enflurane MAC 1.68 -More potent muscle relaxant SEIZURE (assoc. w/ hypercarbia)
-Rapid onset & Malignant hyperthermia
recovery Renal toxicity (fluoride ion)
<Hepatotoxic
Halothane MAC .75 Pediatric anesthetic – not Hepatotoxicity
-Resp. & CV hepatotoxic to kids Lo threshold for catecholamine-
depression induced arrhythmia
-Vasodilation  MALIGNANT HYPERTHERMIA
relaxing SM (uterine) Carcinogenic
-Increase intracranial Increased risk of miscarriage
pressure
Methoxymethane MAC.16 -Reserved for OB -Metabolism releases fluoride
-Excellent skeletal -Most potent inhalant (RENAL DAMAGE)
muscle relaxation
-Slow onset &
awakening

33
Neuromuscular Blockers:

Two Types:

I. Non-depolarizing-Competitively inhibits the NMJ receptors by binding without

activation of pre and postsynaptic sites. These cannot enter CNS due the charge of
thei ammonium ions.
a. Presynaptic inhibition- Release of Ach diminishes and contraction “fades”

b. Postsynaptic inhibition- Blocks Ach at receptor. This is a competitive block

therefore increased Ach can reverse this.

II. Depolarizing-Competitive agonist that binds to and activates the NMJ receptor but
it by keeping the ion channel open (IE the
inactivates
receptor is prevented from cycling back to it’s closed
state).

Duration Drug Mechanism Clinical Use Adverse Effects

Long Tubocurarie Nondepolarizing Muscle parplysis Histamine release

Acting
(1.5 hrs) Gallamine Nondepolarizing Muscle parplysis Vagal Blockade

Pancuronium Nondepolarizing Muscle parplysis Indirect sympathomimetic effect

Short surgical
Medium Atracurium Nondepolarizing procedure Safe for organ failure due to
Acting nonenzymantic metabolism
(30 min) Vent patients (long
Vecurium term) Toxic metabolite will build up with
long-term infusion in pts with
organ failure.
Muscle soreness
Very Succinylcholine Depolarizing Intubations
Short Malignant Hyperthermia

Mivacurium Nondepolarizing Not used due to favor

of succinylcholine

34
35
 Drug Carmustine Liphophilic
Mechanism
(BBB-CNS -Malignant
Cancer therapy
glioma Clincal Use Delayed hematopoietic
Side Effects
dep.
Nitrosurias tumors) Brain cancers Aplastic marrow
CANCER Non-phase specific Hodgkin’s disease Severe vomiting
Lomustine -Penetrates CNS Renal toxicity
THERAPY Mechlorethamine -Alkylation of N7 Bone marrow suppression
-Alkylate DNA CNS toxicity
Guanine in DNA Solid tumors Latent viral infxn
inhibiting replication
Alkalating -Cross-linkage between Extravasation is serious
-CML BMSAdrenal suppression
Agents chains & depurination
Methane Busulfam Methane
-NO DNAsulfate
duplication
sulfonates IV or IA Pulmonary fibrosis
Cyclophosphamide Alkylating-like
Pro-Drug -Testicular ca
-Burkitt’s lymphoma (Ondestron) cystitis w/ fibrosis of
-Hemorrhagic
Other Cisplatin -Complexes w/ guanine --Combo -- vinblastine, bleomycin,
-BRCA Limiting:
bladder dueNephrotoxic
to acrolein (active
in DNA cisplatin,
-Nephroticetoposide
syndrome (mannitol/hydration)
metabolite)
Chlorambucil -Activated via
-Binds to proteins – -Ovarian ca
-RA (intractable Acoustic nerve damage
-Tx w/ MESNA, hydration & mannitol)
hydroxylation via Cyt
cross-linkage -Bladder ca Lo Ca++/Mg++
BMS
P450
-Cytotoxic to all cell Neurotoxic
-oral/liver metabolism w/ toxicity @ all
-Covalent x-link
stages Sterility
dose levels
guanine
Newer form of cisplatin Same as platin Less toxic/nauseating than cis-platin
-Oral;
Carboplatin -No protein binding
Slow-acting
(chlorambucil) Limiting – myelosuppression
(thrombocytopenia)
ANTI- Methotrexate -Dihydrofolate ALL-children Bone marrow toxicity
METABOLITE reductase inhibition
INHIBITORS (W/ leukovorin) -Decrease THF Choriocarcinoma – w/ dactinomycin GI disturbances
-Inhibit conversion of Burkitt’s Urticaria
S-phase dUMP to TMP -BRCA Alopecia
specific -Hi doeses 7-OH  -Head/neck ca Renal damage-Hi dose - 90%unchanged in
crystaluria -Long-term use in psoriasis/RA  urine Lo—50%--liver can only detoxify so
-CSF only Hi doses hepatic fibrosis/cirrhosis much @ a time – measure blood/renal fxn
-Abortion when used w/ misoprostol in Hepatic fibrosis – in low doses (mostly
Leucovorin Rescue 3rd term long-term for immunosuppression)- also
recirculates in biliary stasis -

GI toxicity
-Pyrimidine analog that Slow growing solid tumors (colon, Ulceration of oral & GI mucosa
Arabinosyl
5-fluorauracil interferes
Pyrimidine w/
antagonist breast, ovarian, pancreatic, gastric)
AML-myelogenous BMS
N/V/D
Cytidine conversion of
ara-CTP – competitive Superficial basal cell Anorexia
Myelosuppression
deoxuyurdylic acid Pol
inhibitor for DNA  N/V/D
Hepatic dysfxn
Combo w/ t-TG+daumorubicin
thymic acid
-Chain termination upon Hand/foot syndrome
(Cytarabine/ARA-
-F-dUMP competes w/
incorporation
C)
dUMP (thymidilate
Adriamycin Broadest antitumor Solid tumors Cardiotoxic – ECG changes – cumulative
synthetase)
ANTIBIOTICS (doxorubicin) spectrum dose dependent (unique)(give Fe++
-Decreases TMP &
-Competitive ALL & granulocytic leukemias chelator)
inhibits DNA synthesis
substrate/DNA pol Hodgkins BMS
Purine analog – N/V
inhibitor Kaposi’s sarcoma (liposomal prep Alopecia
6-mercaptopurine activated by HGPRT ALL—maintain remissions Thrombocytopenia
-INTERCALATION— decreasescardiac toxicity) Myelotoxicity
topoisomerse II
-Inhibits
interference
amidotransferase
-Superoxide/ (via
-Blocks
quinone moiety) free
IMPAMP/GMP
radicals fragmenting
-CAREFUL
DNA – allopurinol
—(xanthine
-Preferenceoxidase)
for
inhibits
Sphase drug
(not specific)
metabolismtoxic
Same Acute lymphocytic & agranulocytic
levels) leukemias
Daunorubicin
-Not as effective against solid tumors
Intercalates w/ GC or Small cell lung ca Pulmonary fibrosis – low levels of
Bleomycin GT Testicular ca (w/ vinblastine & deactivating enzyme in this tissue
cisplastin)
-Free radicals Lymphomas -Tachypnea/dyspnea
-Splits DNA -Rash-hypertrophic skin change
G2-phase specific -Anaphylactoid rxn
-Complexes w/ Fe++
No BMS
-Intercalates in small Childhood tumors BMS 36
Actinomycin D groove
(dactinomycin) -Interferes w/ DNA-
dep RNA pol
 Vincristine -Microtubule assembly -Vincristine – (childhood tumors) –some Neurotoxic (axonal transport)
MITOTIC (oncovin) inhibitor adult leukemias & solid tumors
INHIBITORS vinblastine -Blocks mitosis Vinblastine – testicular ca((now Vincristine: neurotoxic
etoposide preferred), (bleomycin & Vinblastine: BM suppression (blasts
(Vinca alkaloids) M-phase specific cisplatin), lymphomas, Kaposi’s, breast marrow)
Resistance: export (P-glycoprotein)
M-phase spec. Breast ca Neutropenia
Paclitaxel (Taxol) Hyperstablizes
microtubule Ovarian ca, Hypersens. Rxn (dyspnea, urticaria,
hypotension)
--Good to give w/ dexamethosone,
diphenhydramine, & H2 blocker
Cardiac toxicity
Topoisomerase II Small cell ca Leukopenia – limiting
OTHER Epipidophyllotoxin inhibitor
(Etoposide) – -Strand breakage Hodgkins
VP16 Effecfts in S & G2 CNS malignancies
-Now used in combo w/ Testicular ca
bleomycin & cisplatin Leukemia

37
 Immunosuppression
CANCER: Lymphomas Adrenal suppression
STEROIDS Prednisone (Also General anti-lymphocytic DOC for: Growth inhibition
immunosuppressive) effect -ITP Decreased muscle tone
-Triggers apoptosis -Autoimmune hemolytic anemia Osteoporosis
IMMUNOSUPPRESSION: -Acute glomerulonephritis Cushing’s syndrome
Toxic to some T-cell G vs. H disease Immune suppression
lines
-Suppress immunity &
inhibits production of
mediators
-Ameliorate drug
toxicity/inflammation
Decreases rapidly-growing ALL – esp. childhood Hypersensitivity rxn
Asparaginase leukemias that show Decreases clotting factors
nutritional requirement Hepatotoxic
for asparagines Pancreatitis
Seizures, coma
Pro-drug Autoimmune disease BMS
IMMUNOSUPPRESSIVES Azothioprine Renal transplants Gi irritation
-Precursor for **Caution allopurinol toxicity Skin rash
mercaptopurine Hypersensitivity rxn
-Actively dividing cells
-Amidotransferase
inhibition
(IMPAMP/GMP)
-Incorporated into DNA
Particularly active Prophylaxis against G vs. H in Hepatic fibrosis/cirrhosis (not
Methotrexate against lymphoid cells BMT BM suppression)
-See cancer Abortion in combo w/ misoprostol
chemotherapy Severe RA (PGE1 analog)
Psoriasis
Leucovorin rescue
-2nd line to azothioprine Autoimmune -doesn’t cause side effects of
Cyclophosphamide -Hi dose  tolerance to steroids/anti ca drugs
new antigen -RBC hemolysis, Ab RBC
dyscrasia, BM suppression
BM transplant @ hi doses
Interferes w/ early Organ transplants Nephrotoxicity is limiting factor
Cyclosporin A antigen response G vs H disease
-Inhibits T-helper cells RA Neurotoxic – hi in liver transplant
-Inhibits calmodulin, Il- Glomerulonephritis Infxn
Lymphomas
2, RBC dysplasia
Hirsutism
-Cyt P450 Inflammatory bowel disease Gingival hyperplasia
Psoriasis Hypertension

Similar to Cyclosporin A Liver transplant NO gingival hyperplasia, less

FK509 (tacrolimus) hypertension
-Higher potency & fewer -Rescue in other organ -Otherwise similar to Cyclosporin
side effects transplants A
-P450 metabolism -avoid use w/ NSAID –
interferes w/ renal blood flow
Rxn against T-cell (poly or G vs. H disease Hypersensitivity rxn/serum
-Antibodies Antilymphocyte monoclonal) sickness
Globin Organ transplants
-Serological immunity not
impaired
Anti-OKT-3 Monoclonal, mature T-cell- Renal transplant/allograft crisis Hypersensitivity rxn
directed Ab
(Muromonab-CD3) -Blocks killer T-cells
Converted to Kidney transplant
Mycophenotate mycophenolic acid (MPA) 38
39
 Mechanism Clincal Use Side Effects

Isoniazid -inhibits synthesis of -bacteriostatic/ -cidal Peripheral neuritis (inhibits pyridoxal

(INH) mycolic acid phosphate kinase)
-intracellular/ TB- resistance if used alone
extracellular organisms --given w/ pyridoxine (Vit. B6)
-acetylated -hepatotoxic (hydrazine metabolite)
M. Kanasii
-affects synth. Of -allergic rash/drug fever
lipids/ nucleic acids -potentiates effects of phenytoin & warfarin
Prophylactically – given alone
-hemolysis in G6PD deficiency
Rifampin -inhibits DNA-dep Bacteriocidal -GI irritation
RNA pol -TB -Hepatotoxic
-decreaase RNA synth -atypical mycobacteria -Thrombocytopenia
-CNS penetration -M. Leprae – in combo -induces P450 (increase metabolism of steroids
-prokaryocytes -meningitis – prophylactic (h. & oral contraceptives)
-red/orange urine, influenza, N. Meningitidis) -Flu-like syndrome
sweat, tears etc.
Ethambutol Mechanism u/k Bacteriostatic Decreased visual acuity/optic neuritis
-TB, M. kansasii (reversible)
-atypical mycobacteria -peripheral neuritis
-h/a, confusion
Second line Pyrazinamide Mech u/k Bacteriocidal GI irritation
drugs TB Hepatitis  death
Hyperuricemia  gout

Photosensitivity
Streptomycin 30s inhibitor TB (advanced & military) Optic nerve dysfxn
Tularemia, plague, meningitis
Ethionamide -Structurally similar to - GI irritation – due to dose
isoniazid Impotence
-diff mechanism Mental disturbance
-large doses required
LEPROSY Para-amino -competitive inhibitor GI irritation
salicylic acid for PABA in Folate Hemolysis in G6PD def
(PAS) synth Hypersensitivity
Cycloserine Inhibits cell wall 2nd line for TB/atypical Exacerbate epileptic seizures
synthesis by mycobacteria
competitively inhibiting -nocardia infection if sulfa’s fail CNS disturbance
conversion of L-ala to -renal TB – 70% excreted in urine
D-ala, then linking D-
Peripheral neuropathies
form
Dapsone Bacteriostatic agent Leprosy Allergic rxn
inhibiting folate – Alternate tx for P. carinii in AIDS
(PABA-antagonist) pt. Peripheral neuritis
dihydropterate --recommended therapy = dapsone
synthase (similar to +clofazimine + rifampin
Hemolysis in G6PD def
sulfonamides)
-acetylation
-excreted via kidneys Lepra rxn (erythema Nodosum; similar to
jarisch herxheimer rxn w/ penicillin & syphilis)
Clofazimine Phenazine dye binds to -dapsone resistant leprosy Discoloration of skin
DNA to inhibit bacteriocidal to M. leprae
template fxn anti-inflammatory effect Eosinophilic enteritis
tx lepra rxn of dapsone

GI irritation
Amithiozone Alternate drug to Hepatotoxicity
dapsone Dapsone-resistant replacement GI irritation
Thiosemicarbazone

40
 Primaquine 8-aminoquinolone 1. Liver stage 1. GI irritation
Tissue
-liver phase of Antimalarials
infxn (exoerythrocytic) 2. H/A
schozont -“Tissue shizonticide” 2. Primary Falciparum, 3. Agranulocytosis
-extensive metabolism Malariae 4. Pruritis
icide
Drug Mechanism (oxidation/ Clincal Use3. Secondary Vivax, Ovale 5. Methemaglobinemia
Side Effects
demethylation) (latent hypnozoite) – only 6. Hemolysis in G6PD def.
Blood Cloroquine -DOC for all types -DOC – prophylaxis of all types
agent to cure b/c1. they
Short term – GI disturbance
schizonticide except falciparum (except resistant falciparum)remain in liver 2. Long-term – SIGHT, HEARING
-blocks enzymatic synth -persistent liver stage 4. (w/ Gametocidal for all 4 DAMAGE
–
of RNA & DNA primaquine) interrupted transmission
-buffers cellular pH to -amebiasis (cemetine) amebic liver
decrease cellular abcess
invasion -collagen disorders/autoimmune like
-concentration: liver, lupus & RA b/c anti-inflammatory
idney, lung, blood, brain effect
-RBC – bindsw/ -gametocide
ferriprotopphorphyrin
IX  damages
membrane  lysis of
parasite/RBC
- erythrocytic phase
Amiodaquine Similar to cloroquine 1. Agranulocytosis
2. Photosensitivity
3. Dermatitis
4. GI disturbances
5. H/A
Pyrimethamine Inhibits dihydrofolate Prophylaxis of resistant falciparum 1. Megaloblastic anemia
reductase of parasite (w/ cloroquine & pyrimethamine) 2. Sulfa-skin rashes
Decreases P. Malariae & toxoplasma (w/ 3. GI distress
purin/pyrimidine synth sulfadiazine) 4. Hemolysis
Works @ lower -synergistic w/sulfadoxine in folate 5. Kidney damage
concentration than pthway 6. Steven-Johnson syndrome
required for mammalian
enzyme
Fansidar: pyrimethamine
+ sulfadoxine
Quinine Inhibits DNA Gyrase P. falciparum infxn resistant to 1. Cinchonism (h/a, tinnitus, blurred
mefloquine - prevent DNA strand chloroquine vision)
separation Relieve leg cramps 2. Cardiac conduction disturbances
Blocks DNA replication Myotonia congenital 3. Black water fever, (intravascular
& RNA transcription Sclerosing agent hemolysis)
-20% excreted 4. GI distresss
unchanged 5. Hemolysis in G6PD def

41
 Aminoglycosides

Drug Mechanism Clincal Use Side Effects

AMINOGLYCOSIDES Gentamycin -Inhibits 30s AEROBIC ONLY Ototoxic (vestibular & cochlear)
Amikacin -enters microbe via Gram – Nephrotoxic
Tobramycin O2-dep active E. Coli
transport Proteus NM blockade
-interferes w/ Klebsiella
assembly of fxnal Serratia
Hypersensitivity rxns
ribosome Pseudomonase
Superinfxn
-misreading of mRNA Enterobacteriaceae
-No CNS action TB (streptomycin)
Amikacin: resistant to
aminoglycoside
inactivity enzyme
produced by Gram (-)
Streptomycin Not effective in Gram TB – advanced & military
(-) rods Optic nerve dysfxn
Tularemia

Y. Pestis – plague
Meningitis
Spectinomycin Very limited spectrum Penicillin-resistant gonococcal Not ototoxic or nephrototoxic

Allergic penicillin gonococcal (not

effective against syphilis)
Netilmycin -Similar to amikacin Good for gentamycin-resistant Less ototoxic & nephrotoxoc
-Slight resistant to organisms (as is amikacin)
-aminoglycoside
inactivating enzymes
Neomycin -too toxic for systemic GI infxn Cochlear toxicity
(topical) use Sterilization for bowel surgery Nephrotoxic
(paramomycin -only used topically & Hepatic coma to reduce ammonia Hypersensitivity
) (kanamycin) sometimes orally intoxication Allergic rxn
-kanamycin/Paramycin Pottentiates action of NM blockers
is antiamebic
POLYMYXINS Polymixin B, -interacts w/ Ophthalmic Nephrotoxicity severely limits use
E (Colistin) phospholipids Skin Neurotoxic – parasthesia, dizziness, ataxia
-penetrates Ear Acute renal tubular necrosis
-disrupts cell Mucous membranes
membranes
-lyses cell
TOPICAL only

42
 Drug Mechanism Clincal Use Side Effects

AMEBIASIS metronidazole -undergoes reductive -severe intestinal & extra- Teratogenic /carcinogenic
bioactivation intestinal amebiasis
-cytotoxic products binds -UG trichomonas Seizures
protein/DNA Pseudomembranous colitis Ataxia
- cell death via pyrvate, Amebiasis Disulfiram- like
ferridoxin Giardiasis N/V/D
oxodoreductase in Dry mouth/stomatitis
anaerobic infxn Insomnia
Gardnerella vaginalis
Anaerobic infxn – esp B. fragilis Weakness
Acute ulcerative gingivitis Urethral burning
Cancrum oris
Cutaneous leishmania

Decubitis ulcers

Anaerobic infxns – esp. B.

Fragilis
Emetine -Blocks Ribosome (prot. Intestinal & extra-intestinal Heart: cloudy swelling & necrosis, hypotension,
Dehydroemetine synth) amebiasis CHF , arrhythmia
-IM injection Balantidium coli
Narrow therapeutic Fasciiola hepatica Pain/abcess @ injxn site
range Pargonimus westermani
Only given in hospital
Urticaria/ pruritic eruption
Concentration: liver,
N/V/D
spleen, kidney heart
Weakness & fatigue
--cumulative effect
Disulfiram-like rxn w/ alcohol

Potentiate coumadin
Diloxanide Mechanism u/k DOC - asymptomatic carriers of Mild
furoate Oral cysts N/V
Hydrolyzed in gut Abd cramps
diloxanide Moderate/severe intestinal Esophagitis
-oral, - 90% amebiasis Dry mouth urticaria
absorbedconjugated Proteinuria
inliver, urine excretion
Iodoquinol Mechanism u/k Alternate in asymptomatic Nephrotoxicity – high doses
Oral carriers Optic atrophy
Peripheral neuropathy
N/V
Mild-severe intestinal amebiasis Thyroid enlargement
Agranulocytosis
ANTI- Mebendazole -inhibits microtubule DOC: Nematodes GI irritation
HELMINTHS synth 1. Whip worm (trichuris Contraindicated in pregnancy
Nematodes -depletes helminth trichuria); prolapsed Rapid metabolization
energy stores by rectum
decreasing glucose uptake 2. Pin worm (enterobius
-hi therapeutic index vermicularis)
3. Eichonococcus granulosis
Also:
Ascaris
hookworm
Thiabendazole Congener of DOC: Vertigo
mebendazole Threadworm (strongyloides)
Larvicidal & ovicidal Trichinosis Crystalluria/hematuria
Inactivated by liver Larva migrans; ancylostoma
hydroxylation (creeping eruptions; cutaneous)
Hypotension
-excreted urine/liver
Note: killed parasites  fever, chills, rigors,
skin rash & lymphadenopathy (like Steven-
Johnson syndrome)
Pyrantel Depolarizing NM blockage DOC: Ascaris (Oxantel doesn’t Rash & fever
pamoate block of nicotinic work) GI irritation
Oxantel receptors  paralyze Hookworm H/A
pamoate worm expelled from GI Enterobius infection Dizziness 43
tract Weakness
 Ivermectin -enhanced GABA- DOC – onchocerciasis (river Lymph node nelargement & tenderne
mediated blindness) Arthralgia
neurotransmission in
nematodes (paralysis) Filiarisis
-facilitates removal by Strongyloidiasis Hypotension
RES Scabies tachycardia
-doesn’t cross BBB

Other Diethyl Mech u/k DOC: filiariasis (w. Bancrofti) Mazzoti rxn – acute rash post-tx
carbamazine Violent allergic rxn Onchocerciasis (river blindness) –
(dying parasite proteins) alternate drug (tx w/ antihistamines or steroids)
Kills microfiliriae & adult -pyrexia
-resp. distress
-hypotension
-prostration
Albendazole -Blocks glucose uptake  Alternate Teratogenic
decreased ATP -Neurocystercosis BM suppression
production -Echinococcus
-inhibits microtubular Also: Hookworm, enterobius, Hepatitis
assembly (similar to strongyloides, trichuris
mebendazole )
Alopecia
Piperazine -paralysis of worm via Alternate: Contraindications:
Citrate non-depol blockade -Ascaris -Hepatic & renal insufficiency
-Enterobius -Epilepsy
Cestodes Niclosamide -Inhibits oxidative DOC: T. Solium (followed by Nausea
phosphorylation in purge) Abd pain
mitochondria t. saginata (tapeworm) Pruruitis
-ineffective against ova Diphyllobothrium (fish tape worm, Fever
present in segments B12 def)
-follw by purge
Trematodes Praziquantel Increased permeability to DOC: schistomiasis Increased rates of abortion
Ca++
-Muscular spasticity DOC cystercercosis (larval T. H/a
/paralysis) of worm Solium) Sedation
Vacuolization of cells Tapeworms N/V
death Paragonimus wetermani Fever/Rash
Broad spectrum

44
 AMEBIASIS/ANTIHELMINTHS

Drug Mechanism Clincal Use Side Effects

ANTIHELMINTHS Levamisole Depolarizing NM Alternate: Vasculitis

blocker -Ascaris Agranulocytosis
-Hookworm Proteinuria
Improves T-cell fxn in Restores depressedT-cell fxn of:
RA -RA
-Recurrent apthous stomitis
-herpes etc
Niridazole Concentrates in the Schistosomiasis - alternate drug Carcinogenic/ teratogenic
worm to cause glycogen Causes hemolysis in G6PD def
depletion Anti-inflammatory effect Psychiatric problems
Pulmonary infiltration
Eosinophilia

Immunosuppression/anti-inflammatory
Metrifonate Organophosphate Alternate Cholinergic stimulation @ hi dose
compound inhibiting -Schistosoma hematobium
actylcholinesterase -S. mansoni
Nifurtimox T. cruzi; Chaga’s disease

Sodium Leishmaniasis
Stibogluconate
(pentavalent
antimony)

45
DIABETES:

Diabetes Type I (IDDM) Diabetes Type II (NIDDM)

Mechanism Insulin is defective or is never formed. Insulin resistance; down-regulation of insulin
Antibodies against pancreatic beta- receptors; failure of pancreas to release insulin even
cells. though it being formed.
Survival Insulin is absolutely required for Patient will survive without insulin
survival.
Synonyms Ketosis-Prone Diabetes Ketosis-Resistant Diabetes

Juvenile-Onset Diabetes Adult-Onset Diabetes

Onset Sudden, often discovered by Gradual, insidious. Often discovered incidentally, or
ketoacidosis. Childhood polydipsia, when chronic complications arise.
polyphagia, polyuria.
Nutrition Often thin. Failure of action of insulin. Usually obese.
Ketoacidosis Frequent Seldom or never
Treatment (order of Insulin always required Diet and exercise
importance)
Diet Oral hypoglycemics

Never oral hypoglycemics Insulin

46
 Diabetes
Drug Mechanism Clincal Use Side Effects

RAPID ACTING CZI “Regular Insulin” -subcutaneous -hypoglycemia (poor dosing)

crystalline -pork, beef, human -IV (emergency) -general insulin allergy
zinc insulin recombinant -lowers blood sugar w/in minutes -local fat atrophy/hypertrophy
-4 hr. peak
-ONLY one IV
Semilente -suspension of -subcutaneous
insulin amorphous insulin
(portk/beef)
-supplement for
intermediate or
prolonged forms
Lyspro -doesn’t complex w/
zinc
-very soluble & rapid
acting
INTERMEDIATE NPH insulin -delayed absorption -sub cutaneous
-conjugation w/ -tx all forms of diabetes (except
protamine (less soluble) ketoacidosis or emergency
-16 hour peak hyperglycemia)
Lente Insulin Like NPH -previously untx diabetic who
(similar requires insulin Rx
onset/duration)
PROLONGED Ultralente -Poorly soluble
Insulin -Delayed onset w/
prolonged duration
-peak ~20 hours
ORAL Tolbutamine -enhance pancreatic Type II (NIDDM) Neutropenia
HYPOGLYCEMICS Chlopropamide insulin Neuronal (tinnitus/h/a)
1st generation Tolazamide -close ATP-dep K+ Cutaneous lesions
acetohexamide channels
-depolarization Chlorpropamide
-decrease serum -enhanced ADH secretion
glucagons -disulfiram-like rxn
concentrations -granulocytopenia
-cholestatic jaundice
-photosensitivity
2nd generation Glipizide -100x more potent Type II (NIDDM) Hypoglycemic crisis
Glyburide -longer duration
-shorter life -NO agranulocytpopenia
-LESS disulfiram-like rxn
Biguanidines Phenformin Metformin – new form -fatal lactic acidosis
Metformin -NO effect on insulin -contraindication in prior MI or other
production or release metabolic problems
-enhances peripheral
glucose utilization
Acarbose Starch blocker: -used in fat people Flatulence
inhibits alpha Osmotic diarrhea
glucosidase
-decrease starch
absorption from the GI

47
 Drug Mechanism Clincal Use Side Effects

STRONG -opioid receptor in CNS & GI GOLD STANDARD Addiction

AGONIST morphine
-hyperpolarizes nerve cells (inhibit -analgesia Respiratory depression
neuronal firing & presynaptic
inhibition of NT release)
Rx’s diarrhea (decrease GI Vomiting
-Mu receptors in substantia motility) Dysphoria
gelatinosa decrease(Sub P release) -relieves cough (suppress central Decreased blood volume
-inhibits release of excitatory
transmitters from neurons
cough reflex) Increases intracranial pressure
carrying pain stimuli -spinal anesthesia Urinary retention – in hypertrophic prostate
-Liver  6-glucuronide  kidney MI, Post-op pain Histamine release (hypotension, sweating,
excretion
Pulmonary edema itching)
Diacetyl-morphine No medical use Addiction
Heroin
-3x more potent than morphine
-metabolized to form morphine
/acetyl morphine
-enters CNS better
-more exaggerated euphoria
K receptors Analgesia (post-op) Less urinary retention than morphine
-enters CNS better than morphine -addictive
Meperidine -metabolite (normeperidine) has -doesn’t cause pinpoint pupils (acts more like atropine)
extremely long t1/2 Pulmonary edema
(Demerol)
-kidney/liver dysfxn, clonus
twitching & seizures -less peripheral effects
-Mu Post-op pain -
Methadone -potency = morphine Heroin addiction – maintenance
-<euphoria therapy
-longer action Helps w/ heroin w/d
-oral -prevents heroin high
-long duration of action
-80x potency of Anesthetic – decreased amt. cerebral vasodilation – increase intracranial
Fentanyl morphine Needed pressure (contraindicated in head injury)
-rapid onset, short -combo w/ droperidol -stiff man phenom; need to give succinyl
duration “dissociative/ neuroleptic Choline
-doesn’t release histamine analgesia”
(unlike morphine) -w/ dropieridol & NO “neuroleptic
anesthesia”
Diphenoxylate Very insoluble
Sometimes combined w/ atropine
Loperamide Decreases addiction even more Anti diarrhetic Very little addiction b/c lack of solubility
WEAK Propoxyphene -derivative of methadone Analgesia Constipation
Respiratory depression
AGONISTS (nalbuphine) -similar to morphine/ Anti-tussive (cough) Convulsions
(darvon) codeine Hallucinations
-only oral Confusion
-magnified w/ alcohol/CNS depressants
-weaker -high dose causes psychotic episodes

Codeine Methylmorphine Cough Itching

less potent than morphine w/ Analgesia

higher oral efficacy

-low abuse potential

-less euphoria
Dextromethorp -replaced cough in cough Cough (OTC) Non-addictive
han -most non-prescription
cough meds
MIXED Pentazocine Partial agonist of k receptors Analgesia – chronic severe pain Respiratory depression
-weak agonst to m & d -given w/ naloxone – if used orally, then Constipation
ACTION -spinal chord to promote analgesia naloxone is destroyed but if injected will Nightmares
-preciptate w/d if user is addict induce w/d sx in abuser Tachycardia
-binds PCP site also Dizziness

Buprenorphine -partial agonist @ mu

-antagonize morphine
-long duration of action
-
OPIOID Naloxone Rapidly displaces all receptor Reverse coma & respiratory depression of Precipitates w/d sx in morphine & heroin users
bound opioid molecules opioid overdose
ANTAGONIST -enables reversal of heroin -decreases pain tolerance
overdose -blocks analgesic effect of placebo
-competitive antagonist of mu, k, -blocks stress-produced analgesia
receptors
Naltrexone Similar to naloxone Used in opioid-dependence maintenance
48
-longer duration of action programs(not as good as methadone)
-now used to reduce alcohol craving (fairly
successful)
 Drug Mechanism Clinical Use Side Effects
ENDOCRINE Somatostatin analog that modulates 1. Acromegaly -Nausea, cramps, diarrhea
Growth Hormones Octreotide neurotrans- 2. TSH/ACTH secreting -low glucose tolerance
-more selective for GH over insulin tumors -fat malabsorption
3. Islet cell tumors including -flatulence
those secreting: VIP, glucagons -gall stones (w/ long term
4. Carcinoid therapy)
5. GI; variceal bleeding
Prolactin Bromocriptine DA receptor agonist -DOC: M & F -Cold induced digital
-D1 antagonist, D2 agonist Hyperprolactinemia vasospasm(at higher doses)
-1st pass -Parkinson’s Disease -nausea, constipation
-Breast engorgement (after -orthostatic hypotension
abortion) -neuropsychiatric prob’s
-Excess GH (octreotide better)
THYROID Iodide -inhibit Thyroid hormone release Presurgery – firm gland -angioedema
-rapid onset, but short duration -larynx swelling,
Problems: delay radioiodine tx, hemorrhage
action of thioamides serum sickness
Thioamides Propylthiouracil Peroxidase inhibitor Iodide PTU-1st drug in emergencies
(PTU) ===X==>iodine “thydoid storm” -Agranulocytosis
Methimazole (US) PTU: Hyperthroidism -Rash
Carbimazole -protein bound, used in pregnancy, -jt. Pain/stiffness
(EUR) avoid in lactation PTU is highly protein bound vs. -parasthesia
-pro-drug for -inhibits T4-T3 conversion methimazole which is not -h/a
methimazole -hair pigment loss
Methimazole – 10 hr. t ½ , not protein
bound, doesn’t affect T4-T3
conversion
Propranolol Beta blocker. -Hyperthyroidism – tx’s sx See autonomics
-blocks sympathomimetic
manifestations
-may reduce peripheral T4 T3

49
 ADRENAL- Hydrocortisone Has extremely low anti-inflammoatory -Addison’s disease -Cushing syndrome
CORTICO- (Cortisol) and mineralocorticoid potentices. -Replacement therapy for -Diabetogenic action
STEROIDS Duration of action is 8-12 hours. secondary or tertiary -Protein catabolism with
Orally, i.m. or i.v. Higher excretion of adrenocortical insufficiency sketetal atrophy
Short Acting Ca and poor intestinal absorption. -Congenital adrenal hyperplasia -Perforation of ulcers
-Immunosuppression -Osteroporosis
-Cancer -Cardiovascular
-CNS-psychosis
-Fluid retention (HPT, CHF)
-Cataracts& Glaucoma

Prednisone Has low anti-inflammatory action with Same as above Same as above
Intermediate
Prednisolone extremely low mineralcorticoid action.
Triamcinolone Duration of action is 12-36 hours.
Triamcinolone is not administered I.V.
Long Acting Betamethasone -crosses placenta -Relieve inflammation, -masks symptoms
Dexamethasone -used for fetal lung maturation (RDS) hypersensitivity (RA, -cushing’s syndrome etc…
(betamethasone) osteroarthritis, skin see cortisol
inflammation)
-Diagnosis of Cushing’s syn.
(Dexamethasone Suppression
Test)
Beclomethasone -inhalers Asthma - inhalation
Budesonide -hi first pass (no adrenal suppression)
-large anti-inflammatory w/ no
mineralcorticoid action.
Steroid synth Aminoglutethimide -Chol-pregnenolone conversion -estrogen-dep breast cancer GI & Neurological side
inhibitor blocked (cyt P450) effects
-aromatase blocked rash
-inhibits all sterid synth
Ketokonazole -inhibits P450 -hepatic dysfunction
Diethystilbestrol Very potent&effective synthetic Same as above. Associated w/ vaginal
(DES) steroid. Has less first pass -Prostatic carcinoma (clear cell) carcinoma in
metabolism. -Prevent abortion daughters of mothers who
took it during pregnancy
ESTROGENS Estrone -excreted as glucuronides -replacement -Nausea, breast tenderness
Estriol -pregnancy – made in placenta -contraception -vascular:
-puberty, secondary sexual charact., -menopause – hot flash, thrombophlebitis, embolism
reproductive cycle, brain development vaginitis -cholestatic jaundice
-suppress FSH preventing ovulation -osteoporosis -postmenopausal bleeding
-hyperpigmentation
-hypertension
-depression

Cancer:
-increased endometrial
(prevented by concomitant
progestin)
ANTI-ESTROGENS Clomiphene -antagonist Infertility assoc. w/ -Ovarian enlargement
-pituitary/hypothalamus anovulatory cycles (Reversible))
-blocks (-) feedback on GnRH/FSH
increased FSH release (follicular
stimulation)

50
 Tamoxifen -estrogen receptor partial agonist -estrogen-dependent tumor
-prevent/treat breast ca cells

Raloxifene -supposedly better @

prophylaxis in postmenopausal
osteoporosis
PROGESTINS Progestin -secretory phase of menstrual cycle -Contraceptive component -Weight gain
-suppress LH & prevent luteal -Anovulation/oligoovulation; -Hair growth
changes induces bleeding -Depression, fatigue
-Early or mid-cycle
bleeding
CONTRACEPTIVES Ethinyl estradiol -cause same effect as pregnancy Long-term:
Norethindrone -derivatives of estrogen -same effects as pregnancy
-increase T4 binding, HT,
throbosis

Other:
-Nausea, breast
tenderness, edema
-mid-cycle spot bleeding
(decrease estr & increase
Prog)
-wt. gain, hair growth,
depression (decrease prog)
-excess bleeding in late
cycle (increase Prog,
decrease Estr)

-
ANTI-PROGESTINS Mifeprostone Binds to (antagonizes) the -Abortions -Uterine bleeding
(RU-486) cytoplasmic progestin receptor-lose -Cushing’s disease (NEW -Possibility of incomplete
support for the conceptus & lose therapy b/c of its anti- abortion
inhibition of uterine contractions; glucocorticoid action)
also blocks glucocorticoid actions.
CALCIUM Calcifediol (25OH) Calcifediol -kidney & skeletal muscle.
REGULATING Calcitrol (1,25 OH) Calcitrol - GI & bone
-forms of Vit D.
-Calcitriol - most potent - high Ca
transport across the brush border
membranes - enhance Ca resorption
from the kidney
Calcitonin -parafollicular -Paget’s disease No significant effects
-decreases renal Ca++/PO4- -Osteoporosis -Nausea
resorption & bone -Hypercalcemia -Hypersensitivity
-decreases serum Ca++
Glucocorticoids -antagonize Vit D stimulated GI -Intermediate Rx of
absorption hypercalcemia due to
-prevent bone resorption sarcoidosis, lymphoma,
myeloma, D-hypervitaminosis
Estrogens Prevent bone loss after menopause. -Prevent osteoporosis (no
Probably antagonists of PTH. enhancement of bone
formation)

51
 Raloxifene -estrogen agonist in bone New
-antagonist in uterus/breast -have to see what fracture
rate is
Diphosphonates -Retard the formation and dissolution -Hypercalcemia -Osteomalacia
(Etidronate & of hydroxyapatite crystals in bone -Osteroporosis -Hypophosphatemia
Pamidronate) -Inhibits osteoclastic activity -High Arthralgia
Mithramycin -DNA-binding cytostatic drug -Paget’s disease Since it’s given in such low
(intereferes w/ osteoclasts) -Hypercalcemia due to doses, no real effects
-1/10 cytotoxic dose malignancies
Gallium Nitrate -inhibit bone resorption (decrease -ca (osteoporosis, pagets) nephrotoxic
hydroxyapatite solubility)
Fluoride -Stablizes hydroxyapatite crystals Osteroporosis
MINERALCORT- Fludrocortisone -Very potent
ICOIDS Deoxycorticosterone -Act similar to aldosterone in the
kidney
-Deoxycorticosterone is the
precursor to aldosterone
INHIBITORS OF Metyrapone Inhibits 11-hydroxylation (final step -Cushing’s Syndrome -Water retention
STEROID BIOSYN in cortisol synthesis & the synthesis -Tests adrenal cortex function -Hirsutism
of corticosterone—the precursor of -Ectopic ACTH syndrome -Transient citizens
aldosterone -Adrenal syndrome -GI disturbances
Ketoconazole Anti-fungal, strongly inhibits gonadol -Cushing’s
& adrenal steroid synthesis at high -Testicular Cancer, anti-fungal
conc.
Aminoglutethimide Blocks the first step (cholestrol- -Cushing’s
pregnenolone) of glucocorticoid -Breast Cancer (low estrogens
synthesis. ALL adrenal steroid and androgens)
synthesis is suppressed **Must be used in combo w/
dexamethasone
-Adrenal Cortex tumors
GONADO-TROPINS GnRH Stimulate the pituitary release of & -Hypogonadism or delayed
& SEX STEROIDS (gonadorelin) FSH. puberty, infertility
Must be in given in pulsatile fashion -Cryptochidism
to be therapeutic. If given in -Endometriosis
constant dosing, you get -Hypothalamic ammenorrhea
desensitization
FSH/LH Menotropin FSH & LH like actions. Menotropin is -Female infertility (IVF); -Multiple pregnancy
Preparations HCG derived from the urine of normally given in combo w/ -Ovarian
HMG postmenopausal women; it contains a GnRH or Clomiphen Hyperstimmulation
Urofillotropin mixture of FSH & LH. -pituitary insufficiency Syndrome: Massive ovarian
-cryptorchidism enlargement, vascular fluid
Urofillotropin: into the peritoneum,
-only FSH (from pregnant women) hypovolemia, ascites, death

HCG:
-LH-like

HMG:
-postmenopausal urine
Leuprolide -slow release Prostate Cancer
-suppress FSH/LH (estrogen &
testosterone)

Estradiol Naturally occurring steroids. High -Post menopausal therapy -Vascular

Estriol first pass metabolism. Given IM. (osteroporosis & hot flashes) (thrombophlebitis,
Estrone -Development of secondary pulmonary embolism)
characteristics -Nausea

52
-Breast cancer -Cholestatic jaundice
-Contraception -Depression
-Breast tenderness
-Post-menopausal bleeding
-Hyperpigmentation
-Hypertension

53
 EPILEPSY DRUGS
Drug Mechanism Clinical Use Side Effects
EPILEPSY Phenytoin -alters ionic flux (Na, K, Ca) Grand-mal Gingival hyperplasia
Decrease Na+ -membrane stabilizing Partial Hirsutism, coarsening facial
current -prevents spread of discharge Status epilepticus (IV) feat.
-shifts from 1st to 0 order 2nd choice – trigeminal Megaloblastic anemia
neuralgia(1 st carbamazepine) Osteomalia (increased Vit. D
digitalis-induced arrhythmia metabolism -interfere w/
Ca++ metabolism)

Pregnancy – fetal hydantoin

(cleft palate, microcephaly,
hypoplastic phalanges)
Carbamazepine -related to TCA Psychomotor, grand mal -hyponatremia
-antimuscarinic effects Trigeminal neuralgia -H2O retention enhancing
-enzyme inducer Psychosis (alternative to Li+) effect of ADH on DCT
-Neurotoxic
-Hypersensitivity –
photosensitivity, lupus,
agranulocytosis
Valproate -blocks Na & “T” channel -petit mal -neural tube defect
-blocks PTZ seizure better than ECT -2nd choice grand mal -fulminant hepatitis (<3 yo)
-plasma protein-bound (inhibits met of -akinetic epilepsy
phenytoin, phenobarbitone,
lamotrigine)
Lamotrigine -Na+ channel blocker -partial seizures

Chloride current Phenobarbital -too sedative -increased porphyrin synth

increase -anticonvulsant (genetically susceptible)
Barbituates -long t ½ (less addictive)
-alkalinization of urine CI: liver, kidney diseases,
-microsomal inducer pulmonary insufficiency
Primidone -prodrug (deoxybarbituate ==> -same as phenobarb
phenobarbitone + phenylethyl
malonamide (PEMA))
Benzodiazepine -short-term tx for epilepsy Thrombophlebitis
(sedation) Drop in BP
-DOC – emergency - convulsion, Resp. depression
status epilepticus, tetanus,
eclampsia, convulsant poisoning
Clonazepam -blocks PTZ (little sedation) -Petit mal Tolerance – <6 mths
clorazepate -adjuvant in myoclonic &
akinetic epilepsy
Vigabatrin -structural similar to GABA Partial seizure
-irreversible inhibition GABA
transaminase
-increases GABA concentration
-DOES NOT INDUCE MICROSOME
Tigabine -inhibits reuptake of GABA
-used in partial seizure
“T” Ca++ blockers Valproate -blocks PTZ seizure Toxic metabolite:
-potentiates GABA -hepatic biotransformation
-competes for phenytoin, phenobarb, ==>fulminant hepatitis
lamotrigine protein-bindings sites
Ethosuximide -antagonize PTZ - absence seizures GI intolerance

54
 Neurological:
-tiredness
agitation, mood change
drowsiness
Excitatory Felbamate -blocks glutamate -intractable partial seizure -aplastic anemia
transmittor blocker -hepatotoxicity
Gabapentin -GABA analog -~GABA -sedation
-behavior change in children
-movement disorders
Topiramate -enhance GABA Partial seizures -sedation
-weak block of glutamate -mental dulling
-voltage sensitive Na+ channels -renal stones
-wt. loss
parasthesia
Acetazolamide CA inhibitor Absence -rapid tolerance
-produces acidosis
Bromide -useful in refractory cases Sedation

CHOICE OF Phenytoin Generalized tonic clonic (grand

ANTICONVULSANT Carbamazepine mal)
Valproate Absence (petit mal)
Ethosuximide
Carbamazepine Partial-complex
Phenytoin
Valproate
Vigabatrine
Valproate Akinetic
Primodone
Clonazepam
Diazepam Febrile seizure
Phenobarbitone
Diazepam
Phenytoin
phenobarbitone

55
 ALCOHOL
Drug Mechanism Clinical Use Side Effects
ALCOHOLS ETOH -absorbed same as H2O -decrease fever -all the good/bad CNS
-some metabolization in gut -nerve block effects
-mostly in liver -antiseptic -hypoglycemia
-minor elimination via lungs -solvent -hyperuricemia
-may facilitate GABA -relaxes uterine SM
-Alcohol dehydrogenase – NAD-dep – -vasodilation ==>
==> acetaldehyde + antabuse + NAD ==> Withdrawal: hypothermia
acetic acid -physical dep . / DT’s -decreased cardiac
-MEOS (microsome ETOH Oxidizing -Tx – diazepam w/ tapering contractility
System) – mitochondria in liver -acute – glucose, thiamin -diuresis
-NADH shuttles pyruvate from glucose -antabuse – induces disulfiram
(hypoglycemia) rxn also, metronidazole, fulfas, Chronic
griseofulvin, cephalosporin, Liver – fatty ==> cirrhosis
phenylbutazone, phenothiazine GI – gastritis, nutritional
defects
-Naltrexone – opioid antagonist CVS/blood – HPT, MI,
– prevents craving cardiomyopathy
-poor immune response
-increase brca
P450 induction – testicular
feminization gynecomastia,
impotence, sterility
CNS – polyneuritis,
Wernicke’s, Korsakoff’s
(Thiamine tx)
Fetus – teratogenic, retard,
growth def
Methanol -competes w/ alcohol dehydrogenase Substitue for ETOH by Visual dysfxn
for elimination alcoholics GI distress
Coma
Toxicity – give ETOH w/ Acidosis - death
dialysis
Ethylene Glycol -also uses alcohol dehydrogenase Toxicity – ETOH Renal damage/death
-oxalic acid is elimination by-product

56
 
Drug Mechanism Clinical Use Side Effects
THROMBOLYTIC Streptokinase Bacterial culture DVT
AGENTS Generates plasmin PE
Coronary throbus
Urokinase Human kidney cells Same
Generates plasmin
TPA Recombinant Same
Generates plasmin
ANTI-PLATELET Aspirin Inhibits TXA2
Increases bleeding time

Dipyridamole Prevent thrombosis on artificial valves

ANTICOAGULANT Heparin Activates antithrombin III Can be used in pregnancy Bleeding  1st sign
Anti-thrombin inactivates IX, X, XI, Long-acting hematuria
XII Suppress aldosterone
Parenteral Antidote: Protamine Hypersensitivity
Renal excretion Osteoporosis
Doesn’t cross BBB or placenta Reversible alopecia
Immediate action Thrombocytopenia

A mucopolysaccharide B SHORT
CI:
Bleeding disorder
Ulcer, hemorrhoid,
threatened abortion
Surgery
Aspirin or antiplatelets
Warfarin Vit. K-dep. Clotting factors – II, VII, CI in pregnancy -GI Bleed
IX, X Prophylaxis use -Petechiae
Lipid soluble – oral -Adrenal insufficiency
Secreted in milk Antidote:give fresh plasma / -Low Therapeutic index –
Protein-bound Vit. K drug interactions
-Pregnancy

B PAL
Vit. K Causes synth. of clotting factors For Warfarin overdose & CI: Synthetic analogs
SYNTH. newborns
ANALOG Menadione – H2O soluble Hemolysis – G6PD
Phytonadione Kernicterus – newborn
Menadione (hyperbilirubinemia)
menadiol
Deficiency
-decrease prothrombin/
clotting factors
-ecchymoses, bleeding
PRO-CLOTTING VIII Hemophilia A
IX From dried human plasma Hemophilia B (Christmas)
Has several Vit. K-dep. factors
Tranexamic Inhibit conversion of plasminogen to
acid plasmin
Aminocaproic acid Post-tPA , urokinase,
streptokinase
i.e. bleeding due to fibrinolysis
Antihemophilic hemophiliacs
Globulin

57
 Thrombin Clots fibrinogen Topical hemostat (capillary
bleeding)
OTHER Protamine Heparin antagonist
From fish sperm

58