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PharmacologyPharmacology
JeopardyJeopardyBlock 2 - Part IBlock 2 - Part I
Peter O. Beaumont, Peter O. Beaumont, M.Sc. (Pharm)M.Sc. (Pharm)
St. Vinnie’s Fall 2000St. Vinnie’s Fall 2000
AntibioticsAntibiotics
It is thought that a It is thought that a cell Tx with cell Tx with
penicillin may have penicillin may have to produce these in to produce these in
order to be order to be bactericidalbactericidal
What are…What are…
AutolysinsAutolysins
– This is part of the reasoning why you should not mix tetracyclines with cell wall synthesis inhibitors
The estimated rate The estimated rate of resistance of of resistance of
S. aureus to S. aureus to
penicillin Gpenicillin G
What is…What is…
90%90%
– You should always be cognizant of this when prescribing antibiotics for Staph infections
This ‘prophylactic’ This ‘prophylactic’ acronym reminds acronym reminds you what drugs to you what drugs to
use for many staph use for many staph infectionsinfections
What is…What is…
CONDoMCONDoM
– recall, all the penicillins with ‘ox’ in them can be taken orally.
– Naficillin, can be oral, but abs is variable
– Methicilin is definitely not oral
For P. aeruginosa, For P. aeruginosa, choose one of choose one of
these penicillinsthese penicillins
What are…What are…MMezlocillinezlocillin
CCarbenicillinarbenicillin
AAzlocillinzlocillin
TTicarcillinicarcillin
PPiperacilliniperacillin
This penicillin is This penicillin is cleared by the kidney, cleared by the kidney,
but spends time in but spends time in the bile, making it the bile, making it useful against this useful against this
‘fishy’ organism‘fishy’ organism
What is…What is…
Ampicillin & Ampicillin & Salmonella Salmonella (Carrier (Carrier
state)state)
This aminopenicillin This aminopenicillin is not affected by is not affected by food when taken food when taken
orallyorally
What is…What is…
AmoxicillinAmoxicillin
Penicillin G does not Penicillin G does not penetrate well into penetrate well into
these 3 organsthese 3 organs
What are…What are…
The eye, prostate The eye, prostate and meninges and meninges (uninflammed)(uninflammed)
The only penicillin to The only penicillin to be used in patients be used in patients with Renal Failurewith Renal Failure
What is…What is…
NaficillinNaficillin
– It is the only one cleared mainly be the liver
Match the beta-lactam ADRMatch the beta-lactam ADR
NaficillinNaficillin
OxacillinOxacillin
MethicillinMethicillin
AmpicillinAmpicillin
neutropenianeutropenia
hepatitishepatitis
nephritisnephritis
allergic rash in allergic rash in MonoMono
Fever chills, rigors Fever chills, rigors and arthralgia due and arthralgia due
to release of to release of spirochete toxinsspirochete toxins
What is…What is…
The Herxheimer The Herxheimer ReactionReaction
– Occurs with most spirochetes, and is independent of the antibiotic used
While 1st-Gen Cephs While 1st-Gen Cephs are known for their are known for their activity for G-pos, activity for G-pos,
organisms they are organisms they are still active against still active against
these G-negs...these G-negs...
What is…What is…• Proteus mirabilis
• Enterobacter
• E. coli
• Klebsiella pneumoia
• Mloraxlla catarrhalis
These drugs have in These drugs have in common the side common the side
effect of effect of hypoprothombinemia hypoprothombinemia and a disulfiram-like and a disulfiram-like
reactionreaction
What are…What are…
CefopeCefoperazrazone, one, MoMoxolactam and xolactam and
CefoCefomanmandoledole
– 3rd, 3rd and 2nd gen agents
The main difference The main difference between 3rd and between 3rd and 4th-Gen cephs..,4th-Gen cephs..,
What is…What is…
more resistance to more resistance to beta-lactamasebeta-lactamase
– Especially chromosomal lactamase produced by Enterobacter
Type of Type of superinfection superinfection
likely in 3rd-Gen likely in 3rd-Gen cephscephs
What is…What is…
Gram-positive Gram-positive organismsorganisms
– recall, as you move from 1st to 3rd Gen, there is more G-neg activity and less G-pos activity
Don’t ask me why, Don’t ask me why, but this common but this common
lab test may lab test may become positive become positive with the use of with the use of cephalosporinscephalosporins
What is…What is…
Urine test for Urine test for glucoseglucose
– Apparently, this is for all classes of cephs.
The First Gen Cephs
Parenteral Oral
Cefazolin (Ancef™) Cephalexin (Keflex™)
Cephalothin Cefadroxil
Cephapirin Cephadrine
Cephradine
Radical Zoltan lothes rox-star pirsonalities whodrive lexuses
The spectrum of this The spectrum of this class of beta-class of beta-
lactams is just like lactams is just like the the
aminoglycosidesaminoglycosides
What are…What are…
MonobactamsMonobactams
– Active against G-negs
– No activity against G-pos or anaerobes
– Aztreonam is the only drug in the class
This beta-lactam has This beta-lactam has the broadest the broadest
spectrum of all and spectrum of all and greatest resistance greatest resistance
to lactamaseto lactamase
What is…What is…
ImipenemImipenem
– Think Omni-potent imipenem
– Cilastin makes it resistant to dihydropeptidase in the kidney
The only iv drug The only iv drug studied that is studied that is
limited solely to limited solely to
G-pos organisms G-pos organisms
What is…What is…
VancomycinVancomycin
– iv for Tx of MRSA (usually with an aminoglycoside)
– po for Tx of C.difficile
– one exception is G-neg Flavobacterium - but I don’t think we studied it
This antibiotic works This antibiotic works only in the only in the
periplasmic spaceperiplasmic space
What is…What is…
BacitracinBacitracin
– Interferes with cycling of the lipid transporter Bactoprenol
– too toxic for systemic use
– G-pos organisms only
Inhibits the Inhibits the conversion of L-ala conversion of L-ala
to D-alato D-ala
What is…What is…
CycloserineCycloserine
– Inhibits alanine racemase
– almost exclusively used as 2nd line Tx for TB due to toxicity
– “Psycho-serine”
Sulfas used in Sulfas used in bowel-prep, based bowel-prep, based on the absorption on the absorption
profileprofile
What are…What are…Phthalylsulfathiazole Phthalylsulfathiazole Succinylsulfathizole Succinylsulfathizole
and Sulfaquanineand Sulfaquanine
– Neomycin is also effective in this regard
Acidity in the urine Acidity in the urine causes causes
precipitation of this precipitation of this drug class drug class
What are…What are…
Sulfa drugsSulfa drugs
Mechanisms of Mechanisms of resistance to sulfa resistance to sulfa
drugs...drugs...
What are…What are…• decreased affinity for decreased affinity for
dihydropteroate synthasedihydropteroate synthase
• overproductoin of PABAoverproductoin of PABA
• increased acetylationincreased acetylation
– Plasmid mediate
The crossing of The crossing of unconjugated unconjugated
bilirubin into the bilirubin into the CNS in newborns CNS in newborns
What is…What is…
kernicteruskernicterus
– Occurs in sulfonamides and other drugs that are normally highly bound to albumin in adults
This drug is supposed This drug is supposed to release to release
formaldehyde as part formaldehyde as part of its mechanism of of its mechanism of
actionaction
What is…What is…methanamine methanamine
mandelatemandelate
– forms insoluble complex with sulfas– not active against Proteus due to
urea splitting activity - pH must be below 5.5
With this drug... your With this drug... your patient might say, patient might say,
“Thanks Doc, I don’t “Thanks Doc, I don’t have to pee so often, have to pee so often, but it sure comes out but it sure comes out
funny looking”funny looking”
What is…What is…
phenazopyridinephenazopyridine
– urinary anaesthetic
– produces red-orange urine
– no antibacterial effect on its own
The common ADR of The common ADR of Trimethoprim, Trimethoprim,
pyrimethamine, and pyrimethamine, and sulfassulfas
What is…What is…
dose-dependent dose-dependent bone marrow bone marrow
depression due to depression due to lack of folatelack of folate
The enzymes The enzymes inhibited by sulfa inhibited by sulfa
drugs, drugs, pyrimethamine, pyrimethamine,
Trimethoprim and Trimethoprim and MethotrexateMethotrexate
What are…What are…
Dihydropteroate Dihydropteroate synthase, synthase, parasiticparasitic, ,
bacterialbacterial and and mammalianmammalian DHFR, DHFR,
respectivelyrespectively
At therapeutic, At therapeutic, bacteriostatic bacteriostatic
concentrations, the concentrations, the degree of degree of toxicitytoxicity in in
Fast acetylatorsFast acetylators
What is…What is…
potentially morepotentially more
– fast acetylators have fewer incidences of immune mediated ADRs (SJS, SLE, etc.)
– acetylation blocks antibacterial activity, but not the other toxicities. To achieve Tx levels, you need more drug in these patients!
DOC in AIDS PCPDOC in AIDS PCP
What is…What is…
Sulfmethoxazole - Sulfmethoxazole - TrimethoprimTrimethoprim
– Also effective in acute toxoplasmosis, and malaria but pyrimethamine might be better if that is all you are treating
These drugs block These drugs block relaxation of relaxation of
positively positively supercoiled DNAsupercoiled DNA
What are…What are…
FluoroquinolonesFluoroquinolones
– effective in UTI caused by MDR Psuedomonas
– Concentrations higher in prostate, kidney, bile and stool
This drug is only This drug is only good for UTI and good for UTI and specifically not specifically not
pseudomonas or pseudomonas or proteusproteus
What is…What is…
NitrofurantoinNitrofurantoin
– No systemic activity
– bacteria reduce the agent to reactive intermediate, but require pH below 5.5
Bacteriostatic drug Bacteriostatic drug working at the 30S working at the 30S
subunitsubunit
What is…What is…
tetracyclinestetracyclines
– Aminoglycosides also work at the 30S subunit, but they are bacteriostatic
The only important The only important cause of atypical cause of atypical CAP, not covered CAP, not covered by tetracyclinesby tetracyclines
What is…What is…
LegionellaLegionella
– Tetracyclines are active against Mycoplasma & Chlamydia
– Also includes: G-pos, G-neg, and Spirochetes
Two agents used to Two agents used to Tx SIADHTx SIADH
What are…What are…
demeclocycline and demeclocycline and LiLi++
– Impt ADR of demeclocycline is photosensitivity
Renal tubular Renal tubular acidosis, acidosis,
aminoaciduria, aminoaciduria, glycosuria, glycosuria, proteinuria, proteinuria, polydipsiapolydipsia
What is…What is…
Fanconi SyndromeFanconi Syndrome
– impt ADR from ingesting OUTDATED (expired) tetracyclines
The two main The two main antibiotics used in antibiotics used in
the Tx of Acnethe Tx of Acne
What are…What are…
Tetracyclines and Tetracyclines and ClindamycinClindamycin
– Tretinoin (Accutane™) is used too, but it is not an antibiotic, it is a retinoid
– Some macrolides and sulfas are also used occasionally
Broad spectrum, Broad spectrum, bacteriostatic agent bacteriostatic agent working at the 50S working at the 50S
subunitsubunit
What is…What is…
ChloramphenicolChloramphenicol
– Inhibits peptidyl transferase
– Macrolides also work at the 50S, but according to Dr. Reddy they are not broad spectrum
– Bacteroides are highly susceptible
Impt dose-related Impt dose-related ADR of ADR of
Chloramphenicol Chloramphenicol seen in all age seen in all age
groupsgroups
What is…What is…
Bone Marrow Bone Marrow SuppressionSuppression
– Aplastic anaemia is idiosyncratic
– Grey-baby syndrome is only in newborns
Generally, a Generally, a substitute for Pen substitute for Pen
G (in allergy), and a G (in allergy), and a DOC for atypical DOC for atypical
CAPCAP
What is…What is…
ErythromycinErythromycin
– I
Chief reason for Chief reason for discontinuance of discontinuance of
erythromycinerythromycin
What is…What is…
Gastrointestinal Gastrointestinal intoleranceintolerance
– Direct stimulation of gastric motility.This is a significant problem, albeit with minimal morbidity
– incidence of liver tox is increased in pregnancy
Increased acid stability, Increased acid stability, less GIT upset andless GIT upset and
activity agasinst M-activity agasinst M-aviumavium, , lepraeleprae & T. & T.gondiigondii
What is…What is…
ClarithromycinClarithromycin
– also has a longer T1/2 than erythromycin
– Azithromycin adds an even longer T1/2, permitting once-daily dosing
Same mechanism of Same mechanism of action as the action as the
macrolides, but an macrolides, but an entirely different entirely different
structurestructure
What is…What is…
ClindamycinClindamycin
– Main indication is severe Bacteroides infection
– high incidence of resistance in C. difficile --> Pseudomembranous colitis
– Supplanted Erythro in prophylaxis of endocarditis peri-operatively
Interferes with 30S Interferes with 30S ribosome and ribosome and
causes misreading causes misreading of mRNAof mRNA
What are…What are…
AminoglycosidesAminoglycosides
– Main clinical indication in Tx aerobic, G-neg organisms (PPEEKS)
– No activity in anaerobes
– Synergy with cell-wall agents
Aminoglycoside Aminoglycoside withoutwithout activity for activity for
G-neg rodsG-neg rods
What is…What is…
StreptomycinStreptomycin
– Ancient Drug for ancient bug
– Plague, TB and tularemia
Aminoglycoside Aminoglycoside used as 2nd line Tx used as 2nd line Tx
in Pen resistant in Pen resistant gonorrheagonorrhea
What is…What is…
SpectinomycinSpectinomycin
– Use a ‘speculum’ before you Rx spectinomycin
– Not ototoxic or nephrotoxic like other aminoglycosides
Indicated in pre-op Indicated in pre-op bowel prep and bowel prep and hepatic comahepatic coma
What is…What is…
NeomycinNeomycin
– Sterilizes the bowel, eliminating bacterial source of ammonia in liver - which exacerbates liver failure
Use this Use this aminoglycoside for aminoglycoside for parasite infectionparasite infection
What is…What is…
ParomycinParomycin
– Too toxic for systemic use
– Given po as a luminal amebicidial agent
– crypto, visceral leish, and cestodes
The other major side The other major side effect everyone effect everyone
forgets about with forgets about with aminoglycosidesaminoglycosides
What is…What is…
NMJ blockadeNMJ blockade
– curare-like, reversible with neostigmine and Ca gluconate
Topical agents with Topical agents with G-neg activity, that G-neg activity, that
interact with interact with membrane membrane
phospholipidsphospholipids
What are…What are…
polymixinspolymixins
– commonly used in ophthalmic and otic preparations
– combined with Bacitracin to cover G-pos or neomycin for additional G-neg
AntifungalsAntifungals
These 2 drugs….These 2 drugs….Are antifungals that both Are antifungals that both
have efficacy against have efficacy against cryptococus cryptococus
neoformans meningitis neoformans meningitis and are given and are given p.o.p.o.
What are…What are…
Flucytosine and Flucytosine and FluconazoleFluconazole
– if you said Amphotericin B, remember, it is only given iv!
The amphipathic The amphipathic nature of these nature of these
polyene drugs….polyene drugs….
Allow them to create Allow them to create pores in fungal pores in fungal
membranesmembranes
What are…What are…
Amphotericin B and Amphotericin B and NystatinNystatin
– both of these agents bind to ergosterol and are amphipathic (a hydophobic side and a hydrophilic side) - wanna guess where amphoteracin got its name?
These 4 drugs….These 4 drugs….
All affect All affect microtubule microtubule
formation as part of formation as part of their mechanism of their mechanism of
actionaction
What are…What are…
ColchicineColchicine
GriseofulvinGriseofulvin
VincristineVincristine
Albendazole (et al)Albendazole (et al)
Better take this drug Better take this drug with a Big Mac, with a Big Mac,
fries and a shake, fries and a shake, but not your but not your sleeping aidssleeping aids
What is…What is…
GriseofulvinGriseofulvin
– absorption increased by fat, and decreased by barbiturates
Drug A inhibits the Drug A inhibits the absorption of B, but absorption of B, but
B inhibits the B inhibits the metabolism of A. metabolism of A. Hint: ulcers and Hint: ulcers and
fungifungi
What are…What are…
A: A: CimetidineCimetidine
B: B: KetoconazoleKetoconazole
– ketoconazole requires and acid environment for absorption and competes for CYP3A4 with cimetidine
These drugs….These drugs….
Provide induction Provide induction and maintenance and maintenance Tx of Cryptococus Tx of Cryptococus neoformans, neoformans, respectivelyrespectively
What are…What are…
Amphotericin B and Amphotericin B and fluconazolefluconazole
This drug….This drug….
Is used for topical Is used for topical Tx of Candida, but Tx of Candida, but not dermatophytesnot dermatophytes
What is…What is…
NystatinNystatin
– only miconazole, clotrimazole and econazole affect dermatophytes topically
– Giseofulvin gets, them, but does so systemically
This antifungal….This antifungal….
Plus the right Plus the right bacteria, will bacteria, will
depress your bone depress your bone marrowmarrow
What is…What is…
FlucytosineFlucytosine
– Some intestinal bacteria will deaminate 5-fluorocytosine to 5-fluorouracil, an effective antineoplastic agent in mammalian cells
CANCER CANCER CHEMOTHERAPYCHEMOTHERAPY
If a drug killed If a drug killed 99.99% of all cells 99.99% of all cells in a 100g tumour; in a 100g tumour;
this many cells this many cells would remainwould remain
What is…What is…
101077
– A 100 g tumour = ~1011 cells, there fore, you would lose 4-orders of magnitude
An effective route of An effective route of admin for admin for
mechlorethamine, mechlorethamine, but not but not
cyclophosphamidecyclophosphamide
What is…What is…
intra-arterialintra-arterial
– Cyclophosphamide requires metabolic activation
By definition, these By definition, these antineoplastics antineoplastics
work best in the work best in the
M-phase of the cell M-phase of the cell cyclecycle
What are…What are…
Vinca Alkaloids and Vinca Alkaloids and paclitaxelpaclitaxel
– Both affect microtubule assembly and hence the mitotic spindle
Decreasing order of Decreasing order of toxicity of the 3 toxicity of the 3 main alkylating main alkylating agents in the agents in the
handouthandout
What are…What are…
mechlorethamine > mechlorethamine > cyclophosphamide cyclophosphamide
> chlorambucil> chlorambucil
– Chlorambucil is safe enough to be used as an immunosuppressant
This metabolite of This metabolite of Cyclophosphamide Cyclophosphamide
is toxic to the is toxic to the bladderbladder
What is…What is…
acroleinacrolein
– Causes hemorrhagic cystitis and is Tx with sulfhydryl agents like MESNA (2-mercapotethane sulfate)
– Considered most useful alkylating agent
This class of This class of alkylating agents alkylating agents
have better efficacy have better efficacy in CNS tumoursin CNS tumours
What are…What are…
NitrosoureasNitrosoureas
– Carmustine (BCNU) and Lomustine (CCNU) are more lipophilic than the other agents
This alkylating agent This alkylating agent is said to have is said to have
efficacy in efficacy in suppressing bone suppressing bone
marrow prior to marrow prior to transplanttransplant
What is…What is…
BusulfanBusulfan
If in doubt, the If in doubt, the limiting toxicity of limiting toxicity of any anti-CA agent any anti-CA agent
is:is:
What is…What is…
Bone Marrow Bone Marrow SuppressionSuppression
– However, there are some very notable exceptions to follow…..
An important result An important result of mass destruction of mass destruction
of CA cells.of CA cells.
Hint: think DNA Hint: think DNA breakdown breakdown productsproducts
What is…What is…
HyperuricemiaHyperuricemia
– release of purines from damaged cells leads to increases in uric acid after metabolism by xanthine oxidase
This agent acts like This agent acts like an alkylating agent, an alkylating agent, but is structurally but is structurally
dissimilar.dissimilar.
What is…What is…
Cisplatin or Cisplatin or CarboplatinCarboplatin
The limiting toxicity The limiting toxicity of cisplatin, which of cisplatin, which is reduced by IV is reduced by IV
fluids and mannitolfluids and mannitol
What is…What is…
nephrotoxicitynephrotoxicity
– ototoxicity and peripheral neuropathy are not affected
By decreasing protein By decreasing protein binding, this happens binding, this happens quicker in Caroplatin quicker in Caroplatin and hence returns the and hence returns the limiting toxicity back limiting toxicity back
to bone marrowto bone marrow
What is…What is…
renal eliminationrenal elimination
– Carboplatin is used in many patients who cannot tolerate the nephrotoxicity of cisplatin
These 4 agents are These 4 agents are by definition S-by definition S-phase specificphase specific
What are…What are…
5-FU, Methotrexate, 5-FU, Methotrexate, mercaptopurine & mercaptopurine &
Ara-CAra-C– These agents are either
antimetabolites, or interfere with purine or pyrimadine synthesis
Inhibition of this Inhibition of this enzyme leads to enzyme leads to lack of dTMP and lack of dTMP and
reduced reduced components for components for
purine synthesis purine synthesis
What is…What is…
DHFRDHFR
This drugs inhibits This drugs inhibits the previous the previous
enzymeenzyme
What is…What is…
MethotrexateMethotrexate
This agent is This agent is regarded by many regarded by many
as having the as having the broadest anticancer broadest anticancer
spectrumspectrum
What is…What is…
DoxorubicinDoxorubicin
– Daunorubicin is only used against leukemias
MechanismMechanismss of of action of action of
DoxorubicinDoxorubicin
What are…What are…
Intercalatoin of DNA, Intercalatoin of DNA, effects on Topo II, effects on Topo II, toxic free radicaltoxic free radical
– Partly cell-cycle specific, partly not
– H. Baer packet says not
This agent, This agent, combined with combined with etoposide and etoposide and
cisplatin is effective cisplatin is effective in Testicular CAin Testicular CA
What is…What is…
BleomycinBleomycin
– Significant lung toxicity
Dose-limiting Dose-limiting toxicity of toxicity of
doxorubicindoxorubicin
What is…What is…
cardiomyopathycardiomyopathy
– Dose-related, occurs beyond (cummulative) 500mg/m2
Mechanism of the Mechanism of the podophyllotoxinspodophyllotoxins
What is…What is…
inhibit Topo IIinhibit Topo II
– Cause DNA strand breaks
– work in late 2-G2
– Etoposide & Teniposide
GASTROINTESTINAL GASTROINTESTINAL PHARMCOLOGYPHARMCOLOGY
The general Tx The general Tx regimen for regimen for
established H.pylori established H.pylori mediated PUDmediated PUD
What is…What is…PPI or H2 or bismuthPPI or H2 or bismuth
++
Metrondazole & 2nd Metrondazole & 2nd AntibioticAntibiotic
selectively binds the selectively binds the ulcer AND may ulcer AND may
have antibacterial have antibacterial effectseffects
What is…What is…
Bismuth Bismuth
– ADR: black mouth and stool, salicylism
This H2 receptor This H2 receptor antagonist antagonist
prototype drug prototype drug affects the affects the
metabolism of metabolism of many other drugsmany other drugs
What is…What is…
CimetidineCimetidine
– Competatively inhibits P450
– Cause estrogenic effects
The difference in The difference in efficacy among the efficacy among the
newer H2 newer H2 antagonistantagonist
What is…What is…
Essentially noneEssentially none
– Longer lasting, few SE, more $$
The active The active metabolite of this metabolite of this
class of “antacids” class of “antacids” irreversibly inhibits irreversibly inhibits
the H/K ATPasethe H/K ATPase
What are…What are…
proton pump proton pump inhibitorsinhibitors
– Omeprazole and lansoprazole
– effect remains until new pump is synthesised
– Generally well tolerated
PGEPGE22
analogueanalogue
What is…What is…
misoprostolmisoprostol
3 effects of 3 effects of misoprostolmisoprostol
What are…What are…
inhibit acid inhibit acid secretion, stimulate secretion, stimulate
bicarb secretion, bicarb secretion, increase mucus increase mucus
secretionsecretion
Major Major contraindication for contraindication for
misoprostolmisoprostol
What is…What is…
pregnancypregnancy
– pro-abortificant actions
This agent This agent preferentially binds preferentially binds
the ulcer base to the ulcer base to protect itprotect it
What is…What is…
SucralfateSucralfate
– absorbs acid, pepsin and bile
Common ingredient Common ingredient of Nytol, of Nytol,
Dramamine and Dramamine and DimetapDimetap
What is…What is…
DimenhydrinateDimenhydrinate
– 1st Generation H1 blockers
– block both H1 and ACH receptors to produce anti-emtic effect
One of the original One of the original “truth serums”, “truth serums”, now used as a now used as a
patch to prevent patch to prevent sea sicknesssea sickness
What is…What is…
ScopolamineScopolamine
– Primary action is Anti-cholinergic effect on CTZ zone
– major SE of sedation
– Benztropine (Cogentin) and cyclizine are congeners
These agents should These agents should be “high” on your be “high” on your list of list of adjunctsadjuncts in in
Cancer TxCancer Tx
What are…What are…
CannabinoidsCannabinoids
– Dronabinol and nabilone (derivatives of tetrahydrocannabinol)
– You can figure out the SE
Predictable SE of Predictable SE of Prochlorperazine & Prochlorperazine &
promethazine promethazine (Compazine and Phergan for (Compazine and Phergan for
you clinicians out there)you clinicians out there)
What is…What is…
ParkinsonismParkinsonism
– Upsets the DA - ACh balancein the basal ganglia
Treatment of the SE Treatment of the SE of above with this, of above with this, actually enhances actually enhances
the anti-emetic the anti-emetic effect!effect!
What is…What is…
DiphenhydramineDiphenhydramine
– Additional anti-ACh effect restores the ratio in the BG
– benztropine may also be commonly used
Anti-serotonin agent Anti-serotonin agent with good efficacy with good efficacy in N&V associated in N&V associated with Chemo and with Chemo and
RadRad
What is…What is…
OndansetronOndansetron
– blocks the 5-HT3 receptor (which is the only ion channel of the HT receptor group)
Amazing combo of Amazing combo of CNS anti-emetic CNS anti-emetic
and gut promotility and gut promotility make this agent make this agent
very usefulvery useful
What is…What is…
MetoclopromideMetoclopromide
– Anti-DA and anti-5-HT3 in CNS
– muscarinic agonist in the GIT
SE of the above SE of the above agent… based on agent… based on
mechanism of mechanism of actionaction
What is…What is…
Also causes Also causes ParkinsonismParkinsonism
– Specific effect mentioned in class is occulogyral crisis
Medical reason for Medical reason for not using mineral not using mineral
oil laxatives oil laxatives
What is…What is…
fat soluble vit fat soluble vit dificiency and lipid dificiency and lipid
pneumonitis if pneumonitis if aspiratedaspirated
Social reason to not Social reason to not use mineral oil use mineral oil
laxativeslaxatives
What is…What is…
They leak out you They leak out you bum!bum!
Mech of Act of Ex-Mech of Act of Ex-lax, etc.lax, etc.
What is…What is…
irritant to Auerbach’s irritant to Auerbach’s plexus in the colonplexus in the colon
– phenolphthalein turns stools pink - remember CHEM 101?
– May cause post-use constipation
These agents have a These agents have a positive effect on positive effect on the G.I. Ward, that the G.I. Ward, that
is a SE on the is a SE on the orthopedics wardorthopedics ward
What are…What are…
OpiodsOpiods
– Diphenoxylate is a weak analogue of meperidine (Demerol)
– direct action on the ENS: fewer propulsive waves
This agent is This agent is commonly added to commonly added to anti-diarrhea opiod anti-diarrhea opiod
preparationspreparations
What is…What is…
AtropineAtropine
– unpleasant CNS SE limit addictive potential of diphenoxylate
This anti-diarrheal This anti-diarrheal requires no requires no
addition of atropineaddition of atropine
What is…What is…
LoperamideLoperamide
– Does not cross the BBB in significant amounts
Class of agents Class of agents used to decrease used to decrease
GIT tone and GIT tone and motilitymotility
What are…What are…
Anti-cholinergicsAnti-cholinergics
– Dicyclomine mentioned in the notes
– Reportedly, has less anti-ACh side effects than atropine
END of Part IEND of Part I