Pharmacology Jeopardy Block 2 - Part I Peter O. Beaumont, M.Sc. (Pharm) St. Vinnie’s Fall 2000.

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


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


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


AmoxicillinAmoxicillin

Penicillin G does not Penicillin G does not penetrate well into penetrate well into

these 3 organsthese 3 organs


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


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


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


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..,


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


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


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


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


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


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


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


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


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


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”


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


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


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


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


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


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


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


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


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


demeclocycline and demeclocycline and LiLi++

– Impt ADR of demeclocycline is photosensitivity

Renal tubular Renal tubular acidosis, acidosis,

aminoaciduria, aminoaciduria, glycosuria, glycosuria, proteinuria, proteinuria, polydipsiapolydipsia


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


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


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


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


ErythromycinErythromycin

– I

Chief reason for Chief reason for discontinuance of discontinuance of

erythromycinerythromycin


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


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


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


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


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


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


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


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


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


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.


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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:


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


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.


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


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


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


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


DHFRDHFR

This drugs inhibits This drugs inhibits the previous the previous

enzymeenzyme


MethotrexateMethotrexate

This agent is This agent is regarded by many regarded by many

as having the as having the broadest anticancer broadest anticancer

spectrumspectrum


DoxorubicinDoxorubicin

– Daunorubicin is only used against leukemias

MechanismMechanismss of of action of action of

DoxorubicinDoxorubicin


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


BleomycinBleomycin

– Significant lung toxicity

Dose-limiting Dose-limiting toxicity of toxicity of

doxorubicindoxorubicin


cardiomyopathycardiomyopathy

– Dose-related, occurs beyond (cummulative) 500mg/m2

Mechanism of the Mechanism of the podophyllotoxinspodophyllotoxins


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


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


CimetidineCimetidine

– Competatively inhibits P450

– Cause estrogenic effects

The difference in The difference in efficacy among the efficacy among the

newer H2 newer H2 antagonistantagonist


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


proton pump proton pump inhibitorsinhibitors

– Omeprazole and lansoprazole

– effect remains until new pump is synthesised

– Generally well tolerated

PGEPGE22

analogueanalogue


misoprostolmisoprostol

3 effects of 3 effects of misoprostolmisoprostol


inhibit acid inhibit acid secretion, stimulate secretion, stimulate

bicarb secretion, bicarb secretion, increase mucus increase mucus

secretionsecretion

Major Major contraindication for contraindication for

misoprostolmisoprostol


pregnancypregnancy

– pro-abortificant actions

This agent This agent preferentially binds preferentially binds

the ulcer base to the ulcer base to protect itprotect it


SucralfateSucralfate

– absorbs acid, pepsin and bile

Common ingredient Common ingredient of Nytol, of Nytol,

Dramamine and Dramamine and DimetapDimetap


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


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


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)


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!


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


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


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


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


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


They leak out you They leak out you bum!bum!

Mech of Act of Ex-Mech of Act of Ex-lax, etc.lax, etc.


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


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


AtropineAtropine

– unpleasant CNS SE limit addictive potential of diphenoxylate

This anti-diarrheal This anti-diarrheal requires no requires no

addition of atropineaddition of atropine


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


Anti-cholinergicsAnti-cholinergics

– Dicyclomine mentioned in the notes

– Reportedly, has less anti-ACh side effects than atropine

END of Part IEND of Part I

Pharmacology Jeopardy Block 2 - Part I Peter O. Beaumont, M.Sc. (Pharm) St. Vinnie’s Fall 2000.

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Transcript of Pharmacology Jeopardy Block 2 - Part I Peter O. Beaumont, M.Sc. (Pharm) St. Vinnie’s Fall 2000.