pharmacology jeopardy block 2 part ii peter o. beaumont, m.sc. (pharm) st. vinnie’s fall 2000
TRANSCRIPT
PharmacologyPharmacology
JeopardyJeopardyBlock 2 Part IIBlock 2 Part II
Peter O. Beaumont, Peter O. Beaumont, M.Sc. (Pharm)M.Sc. (Pharm)
St. Vinnie’s Fall 2000St. Vinnie’s Fall 2000
Local and General Local and General AnaesthesiaAnaesthesia
The Five Goals of The Five Goals of General General
AnaesthesiaAnaesthesia
What are…What are…Analgesia, amnesia, Analgesia, amnesia,
muscle relaxation, LOC muscle relaxation, LOC and Loss of somatic & and Loss of somatic &
visceral reflexesvisceral reflexes–The first three are universal, the last
two are somewhat secondary
The Surgical Stage The Surgical Stage of Anaesthesia,and of Anaesthesia,and the easiest test to the easiest test to
determine itdetermine it
What are…What are…
Stage III, and the Stage III, and the eyelash reflex testeyelash reflex test
The greatest medical The greatest medical concern in concern in
Guedel’s stage II of Guedel’s stage II of anaesthesiaanaesthesia
What is…What is…
Aspiration of vomitAspiration of vomit
–During this stage, delirium and excitement are often accompanied by retching,vomiting and incontinence.
– Intubation must unfortunately wait until the patient loses gag reflexes
The earliest feature The earliest feature of Guedel’s stage Iof Guedel’s stage I
What is…What is…
analgesiaanalgesia
– this is soon accompanied by amnesia, but consciousness is not lost.–Remember, not all anaesthetics show
all stages, and further, not all agents are good analgesics e.g. halothane
The only true The only true anaesthetic ‘gas’ anaesthetic ‘gas’
What is…What is…
Nitrous OxideNitrous Oxide
–The others are all volatile liquids
The rate of onset of The rate of onset of an excellently an excellently
soluble anaestheticsoluble anaesthetic
What is…What is…
Very slowlyVery slowly
–The sooner the point of saturation is reached, the sooner the blood is willing to give up the agent to the brain tissues
The rate of onset of The rate of onset of anaesthesia in a anaesthesia in a
patient with heart patient with heart failurefailure
What is…What is…
Faster than normalFaster than normal
–This is is a tough concept
–slowly flowing blood will reach its saturation sooner than fast flowing blood
–A greater fraction of the CO goes to the brain in failure
Once you stop the Once you stop the flow of Nitrous and flow of Nitrous and oxygen, this may oxygen, this may
happen to the happen to the patient post-oppatient post-op
What is…What is…
Diffusion HypoxiaDiffusion Hypoxia
– A high partial pressure of gas coming out of solution dilutes oxygen in the lungs in the post-op patient
– Only happens with nitrous oxide, others are used a too low partial pressure
When 1/2 your When 1/2 your patients do not patients do not
jump off the table jump off the table following induction, following induction,
this point is this point is reachedreached
What is…What is…
MACMAC
–By definition… when 50% of patients do not respond to a painful stimulus–highly dependent on degree of
stimulation–Elderly and children have lower MAC
This prototypic GA This prototypic GA has good effect, but has good effect, but
high metabolism high metabolism makes it makes it
undesirable these undesirable these daysdays
What is…What is…
HalothaneHalothane
–Release of halogens can cause hepatotoxicity (methoxyflurane does this as well, so it is rarely used)
If you use halothane If you use halothane for a D&C, you for a D&C, you must also use must also use
these these twotwo adjuncts adjuncts
What are…What are…
Opiods and oxytocinOpiods and oxytocin
–Halothane has virtually no analgesic effect
–oxytocin causes uterine contraction to counteract the relaxant effect of halothane
Were it not for Were it not for concurrent muscle concurrent muscle paralysis, patients paralysis, patients induced with this induced with this agent might hurt agent might hurt
themselvesthemselves
What is…What is…
EnfluraneEnflurane
–Seizure complexes on EEG
–EEG goes with Enflurane
This GA is great for This GA is great for maintenance, but maintenance, but
rarely used for rarely used for inductioninduction
What is…What is…
DesfluraneDesflurane
–Extreme sympathetic stimulation during induction. Also has a sharp irritating odour
–Rapid post-op recovery
Some consider this Some consider this GA to be the GA to be the
‘Cadillac’ inhalation ‘Cadillac’ inhalation agent for short agent for short
proceduresprocedures
What is…What is…
SevofluraneSevoflurane
– rapid onset and recovery
– little airway irritation
–2-5% hepatic metabolism makes it less desirable for long procedures
–Sevo is the “Seville”
Were it not for a Were it not for a high MAC, this high MAC, this
agent would be a agent would be a nearly ideal GAnearly ideal GA
What is…What is…
Nitrous OxideNitrous Oxide
–No CV depression, excellent analgesia
–Must be used with a second GA and paralytic agent
This class of IV GA’s This class of IV GA’s are the prototypical are the prototypical
induction agentsinduction agents
What are…What are…
BarbituratesBarbiturates
–Thiopental was the first - Still used widely today
–Onset in 1 minute
While inhalation While inhalation agents terminate agents terminate
their effect by their effect by exhalation, this is exhalation, this is the mechanism for the mechanism for
barbituratesbarbiturates
What is…What is…
RedistributionRedistribution
–Also known as gamma phase redistribution
–99% hepatic metabolism to inactive compound AFTER termination of sedation effect
Incapable or Incapable or reaching stage III reaching stage III themselves, these themselves, these
agents provide agents provide sedation and sedation and
amnesiaamnesia
What are…What are…
benzodiazepinesbenzodiazepines
–Diazepam, lorazepam and midazolam are short acting agents
–Slower onset than barbiturates
–used as part of “balanced anaesthesia”
Occasionally used Occasionally used alone in Cardiac Sx, alone in Cardiac Sx,
these agents these agents typically support typically support GA agents with GA agents with
analgesiaanalgesia
What is…What is…
OpiodsOpiods
–patient may be ‘aware’ of or recall the Sx
–Chest tightness impairing ventilation may occur
Opiod + neuroleptic Opiod + neuroleptic + Nitrous Oxide =+ Nitrous Oxide =
What is…What is…
NeuroleptanesthesiaNeuroleptanesthesia
– Important for painful, invasive procedures requiring patient cooperation
Dr’s and patients Dr’s and patients agree, this drug is agree, this drug is the ‘real the ‘real Pro’Pro’ of the of the induction agentsinduction agents
What is…What is…
PropafolPropafol
–Similar induction to barbiturates, but faster recovery
–Patients feel much better post-op
–May even have anti-emetic properties
–much much more expensive than thiopental
Catatonia, amnesia Catatonia, amnesia and analgesia and analgesia without LOCwithout LOC
What is…What is…
dissociative dissociative anesthesiaanesthesia
–Produced by ketamine alone–Similar to PCP–only CVS stimulant–good for Sx on patients in shock
This untoward effect This untoward effect of ketamine is of ketamine is
obviated by pre-obviated by pre-medication with medication with
diazepam or diazepam or fentanylfentanyl
What is…What is…
Emergence Emergence PhenomenonPhenomenon
–hallucinations and perceptual illusions
This iv induction This iv induction agents shares one agents shares one shortcoming with shortcoming with halothane and one halothane and one with nitrous oxidewith nitrous oxide
What is…What is…
EtomidateEtomidate
–No analgesia (halothane), no muscle relaxant effect (nitrous)
This effect makes This effect makes Etomidate Etomidate
unsuitable for long unsuitable for long Sx and ICU Sx and ICU
sedationsedation
What is…What is…
inhibition of adrenal inhibition of adrenal steroid synthesissteroid synthesis
–produces hypotension, electrolyte imbalance and oliguria
The two chemical The two chemical groups required for groups required for
effect as a local effect as a local anaestheticanaesthetic
What is…What is…
lipophilic group and lipophilic group and ionizable groupionizable group
–Must be able to readily pass through lipid bilayer, yet interact with ion channel
Relative Relative effectiveness of effectiveness of
locals on locals on infectedinfected tissuetissue
What is…What is…
DecreasedDecreased
– lower pH of tissue causes more ionized agent, which is unable to enter the cell
Major benefit of Major benefit of cocaine as a Local cocaine as a Local
anaestheticanaesthetic
What is…What is…
vasoconstrictionvasoconstriction
–All other agents are vasodilators
– functions through blocked NE reuptake
–prolongs anaesthetic effect
–used in URT and ear
CocaineCocaine
TetracaineTetracaine
BenzocaineBenzocaine
What are…What are…
The ‘ester’ localsThe ‘ester’ locals
–Typically shorter T1/2 due to hydrolysis by plasma cholinesterase
Mechanism of action Mechanism of action of the local of the local
anaestheticsanaesthetics
What is…What is…
blockade of voltage-blockade of voltage-dependent Na dependent Na
channelschannels
–Use-dependent
–blocks from inside
Characteristics of Characteristics of the earliest blocked the earliest blocked
nerve fibresnerve fibres
What are…What are…small, myelinated, rapidly small, myelinated, rapidly
firing, peripherally firing, peripherally located on the bundlelocated on the bundle
–why myelinated first - I don’t know!–Use-dependent means rapidly firing
sensory fibres blocked before motor fibres
CNS sedation, CNS sedation, restlessness, restlessness, nystagmus, nystagmus,
seizuresseizures
What is…What is…
Toxic effects of local Toxic effects of local anaestheticsanaesthetics
–Premedication with benzos, and hyperoxemia are prophylactic for these symptoms
Local that does not Local that does not permeate the skin permeate the skin
when applied when applied topicallytopically
What is…What is…
benzocainebenzocaine
Three LA agents that Three LA agents that cross mucous cross mucous membranes in membranes in
therapeutic therapeutic amountsamounts
What is…What is…
tetracaine, lidocaine tetracaine, lidocaine and cocaineand cocaine
– tetracaine suitable for ophthalmic use - no irritation (cocaine too?)–epinephrine cannot be used in topical
preps.
Rationale for use of Rationale for use of nerve blocksnerve blocks
What is…What is…
Covers larger area, Covers larger area, with smaller amount with smaller amount
of drugof drug
–prevents systemic toxicity– (also, prevents distortion of wound
when suturing!)
Three techniques to Three techniques to prevent cephalad prevent cephalad diffusion of spinal diffusion of spinal
anaesthesiaanaesthesia
What are…What are…
Tilt the patients, use Tilt the patients, use small amount, use small amount, use
‘heavy’ diluent‘heavy’ diluent
–Specific gravity determines whether agent will rise, sink or remain static
Small muscles, Small muscles, trunk muscles, trunk muscles,
diaphragmdiaphragm
What is…What is…
Order of effect of Order of effect of NMJ blockersNMJ blockers
Effect of pre-Effect of pre-synaptic NMJ synaptic NMJ blockade of blockade of
nicotinic receptorsnicotinic receptors
What is…What is…
‘‘Fade’Fade’
–These receptors normally cause increased release of ACh required to maintain repetitive firing
AChE inhibitors AChE inhibitors have this effect on have this effect on non-depolarising non-depolarising
NMJ blockersNMJ blockers
What is…What is…
antagonismantagonism
–non-depol agents are essentially pharmacological antagonists. AChE inhibitors increase the amount of ACh–On the other hand, they would
enhance depolarising blockade
Primary use of Primary use of depolarising NMJ depolarising NMJ
blockersblockers
What is…What is…
temporary paralysis to temporary paralysis to allow intubationallow intubation
–Succinylcholine is the only agent in use
–onset < 1 min, duration 5-10 min - rapid metab by plasma cholinesterase
These two classes These two classes of agents are of agents are
known to cause known to cause malignant malignant
hyperthermiahyperthermia
What are…What are…
volatile anaesthetics volatile anaesthetics and succinylcholineand succinylcholine
–Causes over-release of Ca from SR - Tx with Dantrolene–Genetic susceptibility
Basis for emesis Basis for emesis due to due to
succinylcholinesuccinylcholine
What is…What is…Increased intragastric Increased intragastric psi due to abdominal psi due to abdominal muscle contractionmuscle contraction
–Not triggered by CTZ
inhalation, local and inhalation, local and IV anaesthetics, IV anaesthetics,
and and aminoglycosidesaminoglycosides
What are…What are…
agents that agents that potentiate NMJ potentiate NMJ
blockadeblockade
Goal of Tx with Goal of Tx with spasmolyticsspasmolytics
What is…What is…
reduction in tone, reduction in tone, without reduction without reduction
in strengthin strength
–Useful in CP, MS and stroke
Facilitates GABA-Facilitates GABA-mediated pre-syn mediated pre-syn
inhibitioninhibition
What are…What are…
benzodiazepines benzodiazepines (diazepem)(diazepem)
–muscle spasms of any origin
–marked sedation
GABA-mimetic at GABA-mimetic at GABAGABABB receptors receptors
What is…What is…
baclofenbaclofen
–hyper-polarises pre-syn afferent of reflex arch
–decreases transmitter release
–works in brainstem
–equally effective as diazepam - less sedation
spasmolytic with 3 spasmolytic with 3 month duration of month duration of
actionaction
What is…What is…
botulinum toxinbotulinum toxin
–effective in blepharospasm, dystonia and achalasia
–admin by local injection
Tuberculosis Tuberculosis and Leprosyand Leprosy
Guess the first-line Guess the first-line drugs for Tx of TB drugs for Tx of TB
and win the and win the P.R.I.S.E.P.R.I.S.E.
What is…What is…
Pyrazinamide, Pyrazinamide, Rifampin, Isoniazid, Rifampin, Isoniazid,
Streptomycin & Streptomycin & EthambutolEthambutol
Slow growth, Slow growth, intracellular, intracellular, resistanceresistance
What are…What are…
Three reasons for Three reasons for difficulty in Tx TBdifficulty in Tx TB
–Combination Tx is often used to ovecome these problems
Mechanism of action Mechanism of action of the most import of the most import
drug in the Tx of TBdrug in the Tx of TB
What is…What is…
inhibition of mycolic inhibition of mycolic acid synthesis by acid synthesis by
INHINH
–Pyridoxine congener
The dose-limiting The dose-limiting toxicity of INHtoxicity of INH
What is…What is…
hepatotoxicityhepatotoxicity
–“INH: Injures Neurons and Hepatocytes
–peripheral neuritis is easily Tx with B6 - so, technically, not ‘dose-limiting’
–significant (1%) incidence of severe hepatitis; even greater in alcoholics
This TB agent is an This TB agent is an inhibitor of DNA-inhibitor of DNA-
dep-RNA - dep-RNA - polymerasepolymerase
What is…What is…
RifampinRifampin
–Effective in all mycobacteria and many other agents
–good CSF penetration - exposure/carrier prophylaxis in meningococci and H.flu
Rifampin and Rifampin and phenazopyridine phenazopyridine
have this in have this in commoncommon
(think back to UTI)(think back to UTI)
What is…What is…
colours body fluids colours body fluids REDRED
–4 R’s
–RNA-poly, Reves P450, Red fluid, Rapid Resistance used alone
If you took this TB If you took this TB drug, you may not drug, you may not
know that your know that your urine was red from urine was red from
rifampinrifampin
What is…What is…
EthambutolEthambutol
–Causes loss of red-green discrimination
– relative contraindication in children
–2nd TB agent that causes hepatitis
This TB agent may This TB agent may precipitate gout in precipitate gout in
susceptible susceptible individualsindividuals
What is…What is…
pyrazinamidepyrazinamide
–Hyperuricemia occurs in all patients, but only some are symptomatic
INH, rifampin, INH, rifampin, pyrazinamide, but pyrazinamide, but not ethambutol or not ethambutol or
streptomycinstreptomycin
What is…What is…
First-line TB agents First-line TB agents that cause that cause
hepatotoxicityhepatotoxicity
–Ethambutol does, not… as may have been stated in class
This quasi-first line This quasi-first line agent is still used agent is still used for life-threatening for life-threatening
TBTB
What is…What is…
StreptomycinStreptomycin
–Especially useful in meningitis and milliary TB
–some do not consider it 1st-line for TB anymore
Mech of act of this Mech of act of this primary Tx for primary Tx for
LeprosyLeprosy
What is…What is…Inhibition of Inhibition of
dihydropteroate dihydropteroate synthase by Dapsonesynthase by Dapsone
–Just like all of the other PABA analogues
This dapsone ADR This dapsone ADR is similar to that is similar to that seen in the Tx of seen in the Tx of
spirochete infectionspirochete infection
What is…What is…
the Lepra Reactionthe Lepra Reaction
–somewhat like Jarisch-Herxheimer reaction (erythema nodosum leprosum)
–Tx with thalidomide, chloroquine and clofazime (not in G&G)
Perhaps the most Perhaps the most effective drug in effective drug in leprosy, it can leprosy, it can never be used never be used
alonealone
What is…What is…
RifampinRifampin
–Resistance is a major concern
The main ADR of the The main ADR of the main Dapsone main Dapsone alternative in alternative in
resistant Leprosyresistant Leprosy
What is…What is…
Skin discolourationSkin discolouration
–Clofazime is an ‘azo’ dye that discolours the skin
Malarial parasites Malarial parasites with more than one with more than one
exoerythrocytic exoerythrocytic cyclecycle
What are…What are…
Vivax and OvaleVivax and Ovale
–Falciparum and Malariae have only one cycle before proceeding to RBCs
–Basis for dormant infection in V & O
Stages of the Stages of the lifecycle taken up lifecycle taken up by the mosquito, by the mosquito, and later injected, and later injected,
respectivelyrespectively
What are…What are…
Gametocytes and Gametocytes and sporozoitessporozoites
DOC for Tx and DOC for Tx and prophylaxis of P. prophylaxis of P. falciparum (area falciparum (area
without resistance)without resistance)
What is…What is…
ChloroquineChloroquine
–often used in combo with pyrimethamine
DOC for prophylaxis DOC for prophylaxis of P. falciparum, in of P. falciparum, in
resistant areasresistant areas
What is…What is…Melfoquine Melfoquine oror
Chloroquine + pyrimethamineChloroquine + pyrimethamine(Depending on your source)(Depending on your source)
–2nd choice doxycycline, 3rd chloroquine + proguanil (Katzung and G&G agreee)–Can also be used for the other plasmodia too
DOC for Tx ofDOC for Tx of
chloroquine-resistant chloroquine-resistant P. falciparumP. falciparum
What is…What is…
QuinineQuinine
–given with a tetracycline or antifolate
–Mefloquine is used in some geographic areas
Drug that would Drug that would have made Dr. have made Dr. McPhearson a McPhearson a millionare, and millionare, and which was not which was not
covered in class!covered in class!
What is…What is…
ArtemisininArtemisinin
–Effective blood schizontacide in all types of malaria, including resistant P.f.
–Not good for prophylaxis
–Not available in US… yet.
Only drug for Only drug for eradication of eradication of
tissue schizontstissue schizonts
What is…What is…
PrimaquinePrimaquine
–One of the few indications that is absolute
–only required in Ovale and Vivax
Enzyme deficiency Enzyme deficiency associated with associated with
ADRs in ADRs in primaquine and primaquine and
quininequinine
What is…What is…
Glucose-6-Glucose-6-phosphate DeHasephosphate DeHase
–Produces hemolysis and methmoglobin - toxic to kidneys
Antiviral Antiviral PharmacologyPharmacology
Amantadine is used Amantadine is used in the Tx of: in the Tx of:
Influenza A, and...Influenza A, and...
What is…What is…
Parkinson’s Disease Parkinson’s Disease
– I hope you didn’t guess Influenza B or C!
This drug….This drug….
Is an excellent Is an excellent prophylactic for the prophylactic for the Flu, but won’t make Flu, but won’t make you feel any better you feel any better
once you get itonce you get it
What is…What is…
amantadine or amantadine or rimantadinerimantadine
– these agents block uncoating of the viral particle in the cytosol, but by the time you feel sick, you already have lots of viral particle in your system
These agents limit These agents limit the abilitiy of the abilitiy of
viruses to enter viruses to enter cellscells
What are…What are…
Gamma-globulinsGamma-globulins
–Temporary, passive immunity
–duration about 3 wks
Mech of Act of Mech of Act of amantadine amantadine (for viruses)(for viruses)
What is…What is…
blocks uncoating of blocks uncoating of the virusthe virus
–Raises pH of endosome to alkaline levels–SE are all neuro related (increased
release of DA)
Agents that require Agents that require HSV viral thymidine HSV viral thymidine
kinase to be kinase to be effectiveeffective
What are…What are…
All of the “__ciclovirs”All of the “__ciclovirs”
–Applies to Tx of HSV 1, 2, and 3 (VCV)–acyclovir, famciclovir, ganciclovir,
valaciclovir, etc.
Key difference in Key difference in phosphorylation of phosphorylation of
GanciclovirGanciclovir
What is…What is…
phosphorylated by phosphorylated by CMV-specific kinaseCMV-specific kinase
–uses regular thymidine kinase for HSV, but a different one in CMV
Mech of Act of Mech of Act of acycloviracyclovir
What is…What is…
comp inhibit viral comp inhibit viral DNA polymerase & DNA polymerase &
causes chain causes chain terminationtermination
–May cause some renaldysfxn, but generally well tolerated
Key indication for Key indication for use of Gancicloviruse of Ganciclovir
What are…What are…CMV retinitis, CMV retinitis, pneumonitis, pneumonitis,
esophagitis, and colitisesophagitis, and colitis
–SE: reversible neutropenia and renal dysfxn
Spectrum of action Spectrum of action of inhaled Ribavirinof inhaled Ribavirin
What is…What is…
RSV, Influenza A & BRSV, Influenza A & B
Spectrum of action Spectrum of action of oral/IV Ribavirinof oral/IV Ribavirin
What is…What is…
Lassa feverLassa fever
–HCV effects are debatable
–many more SE when given systemically - cytopenias and suppressoin
Mech of Act of Mech of Act of RibavirinRibavirin
What is…What is…
Inibits RNA-dep-RNA Inibits RNA-dep-RNA polymerasepolymerase
–May interfere with GTP synthesis and the cap on mRNA as well–effective in BOTH DNA and RNA
viruses
Phosphorylated by Phosphorylated by Host cell kinasesHost cell kinases
What are…What are…Idoxuridine, cytarabine, Idoxuridine, cytarabine, Vidarabine, TrifluridineVidarabine, Trifluridine
– Inhibit viral DNA poly
– too toxic for systemic use, except Vidara for neonatal herpes in immunocompromised
HSV /VCV drug HSV /VCV drug requiring no host or requiring no host or viral kinase activityviral kinase activity
What is…What is…
FoscarnetFoscarnet
– Inhibits viral DNA & RNA poly AND HIV reverse transcriptase
Key uses of Key uses of FoscarnetFoscarnet
What are…What are…• AIDS-related CMVAIDS-related CMV
• Acyclovir resistant / Acyclovir resistant / thymidine kinase def HSVthymidine kinase def HSV
• Gancicovir-resistant CMVGancicovir-resistant CMV
–Limited resistance has been observed
3 mechanisms of 3 mechanisms of action of action of
interferonsinterferons
What are…What are…• synth of protein kinases to synth of protein kinases to
inhibit further protein synthinhibit further protein synth
• oligoadenylate synthase oligoadenylate synthase activates RNAaseactivates RNAase
• PDE degrades tRNAPDE degrades tRNA
Major indications for Major indications for interferon Txinterferon Tx
What are…What are…• Pv disseminated HSC, Pv disseminated HSC,
relapse CMV, and relapse CMV, and trigeminal HSV trigeminal HSV
• Hep B & CHep B & C
• Kaposi’s and wartsKaposi’s and warts
...to name a few...to name a few
Major SE of Major SE of interferon Txinterferon Tx
What is…What is…
Constitutional Constitutional symptomssymptoms
–Fever, malaise, chills, etc.
Type of kinases Type of kinases used on 5 out of 6 used on 5 out of 6
HIV reverse HIV reverse transcriptase transcriptase
inhibitorsinhibitors
What are…What are…
Host cell kinasesHost cell kinases
–All 3 phosphorylation steps, c.f. just the last two step for antiherpes drugs
Primary means of Primary means of resistance to AZT, resistance to AZT,
et alet al
What is…What is…
mutation of RT genemutation of RT gene
–Much more common in mono Tx and in advanced disease
Basis for selective Basis for selective toxicity of the RT toxicity of the RT
inhibitorsinhibitors
What is…What is…
our cells do not our cells do not have RT!have RT!
–Simple point, but commonly overlooked
Indications for AZTIndications for AZT
What are…What are…• CD4 count < 200 (500 w CD4 count < 200 (500 w
symptoms)symptoms)
• 3rd trimester (with 3TC)3rd trimester (with 3TC)
• Prophylaxis for needle Prophylaxis for needle stickstick
Major toxicity of AZTMajor toxicity of AZT
What is…What is…
Bone marrow Bone marrow suppressionsuppression
– increased by Rx that undergo glucuronidation, and decerased by rifampin
Two RTI’s that cause Two RTI’s that cause pancreatitispancreatitis
What are…What are…
ddIddI and ddC and ddC
–More common in alcoholics
–also cause peripheral neuropathy
Claim to fame of Claim to fame of NevirpapineNevirpapine
What is…What is…
NNOONN--nnucleoside RTIucleoside RTI
–potentiallife threatening rash
The function of HIV The function of HIV aspartate proteaseaspartate protease
What is…What is…
Final protein cleavage Final protein cleavage into mature, into mature,
infectious particlesinfectious particles
–SE: kidney stones and unconjugated hypernilirubinemia
General formulae for General formulae for HIV TxHIV Tx
What is…What is…
AZT + 2nd RTI + AZT + 2nd RTI + Protease inhibitorProtease inhibitor
HypertensionHypertension
Long term Mech of Long term Mech of Act of diureticsAct of diuretics
What is…What is…
Reduction in Na Reduction in Na altering vascular altering vascular
tonetone
–Volume reduction occurs early, but is abated over 6-8 weks in mild essential HTN
Location and Location and Mechanism of Mechanism of
Action of ClonidineAction of Clonidine
What is…What is…
Central and peripheral Central and peripheral alpha-2 alpha-2
sympathomimeticsympathomimetic
–blocks NE release–SE: sedation and dry mouth
Major caution in Major caution in clonidine useclonidine use
What is…What is…withdrawal syndromewithdrawal syndrome
–Rebound HTN, tachcardia, sweating
–As little as one or two missed doses
–Tx with alpha and beta blockers
Direct vasodilators Direct vasodilators must be used with must be used with
these drugsthese drugs
What are…What are…
Beta blockersBeta blockers
–No sympathoplegia, so reflex response to a decreased BP is still present
Orally active direct Orally active direct vasodilatorsvasodilators
What are…What are…
Hydralazine and Hydralazine and minoxidilminoxidil
–work through opening K channels and hyperpolarises arteriolar SMCs
Fast acting, IV Fast acting, IV arteriolar and arteriolar and venous dilatorvenous dilator
What is…What is…
Na NitroprussideNa Nitroprusside
–high dose > 1 hr assoc w cyanide toxicity
–onset in 1-10 minutes
–activate guanylyl cyclase - not a K channel agent
The other IV only The other IV only direct vasodilatordirect vasodilator
What is…What is…
DiazoxideDiazoxide
–much longer acting means less precise control
– inhibits insulin release
1st-line Tx in an 1st-line Tx in an elderly, black elderly, black
patient with CHF patient with CHF and CRFand CRF
What is…What is…
A loop diureticA loop diuretic
–Without the RF (GFR < 30 ml/min) a thiazide would be first choice
–beta blockers have little efficacy in black patients
Anti-HTN agent Anti-HTN agent contraindicated in contraindicated in
pregnancypregnancy
What is…What is…
ACE-I and AgII ACE-I and AgII receptor blockersreceptor blockers
– fetal hypotension and risk of malformation
Rationale not to use Rationale not to use direct dilators or direct dilators or alpha blockers in alpha blockers in coronary artery coronary artery
diseasedisease
What is…What is…
Coronary stealCoronary steal
–provokation of angine
Patients in who you Patients in who you should not use should not use
amiloride or ACE-I amiloride or ACE-I for HTNfor HTN
Whe are…Whe are…
Patients in renal Patients in renal failurefailure
–both tend to exacerbate hyperkalemia
Drugs not to be Drugs not to be used for HTN in used for HTN in
diabetesdiabetes
What are…What are…
thiazides and non-thiazides and non-selective beta selective beta
blockersblockers
Tx of HTN assoc Tx of HTN assoc with kidney stoneswith kidney stones
What is…What is…
Analgesia and Analgesia and hydrationhydration
–Different stories in different small groups–Texts indicate no benefit of diuretics
or anti-spasmodics
Management of HTN Management of HTN crisiscrisis
What is…What is…
decrease psi by < decrease psi by < 25%, and diastolic 25%, and diastolic not less than 100-not less than 100-
110110
–according to Katzung
BP at which to BP at which to initiate Drug Txinitiate Drug Tx
What is…What is…
140/90140/90(open for discussion)(open for discussion)
–For stage I patients, after 6-12 months of lifestyle change
Why Why hydrochlorothiazide hydrochlorothiazide
and alpha-and alpha-methyldopa are used methyldopa are used
in preg assoc HTNin preg assoc HTN
What is…What is…
““fetal friendly”fetal friendly”
–May not be the best agents, but there are proven safe.
–Hard to test new Rx on mothers.
Basis for pulmonary Basis for pulmonary edema in our case edema in our case
studystudy
What is…What is…Albuterol activates RAS via Albuterol activates RAS via
beta-2 receptors & the beta-2 receptors & the ‘infusion’ may have volume ‘infusion’ may have volume
overloaded the patientoverloaded the patient –Discussion….–MgSO4 may have been better, but
fetus old enough to deliver
Two causes for red Two causes for red urine in our case urine in our case
studystudy
What are…What are…
Hemorrhagic cystitis Hemorrhagic cystitis & doxorubcin die & doxorubcin die
effecteffect
Two causes of the Two causes of the erythematous erythematous
response at the response at the injection siteinjection site
What are…What are…extravasation of extravasation of
vesicant vesicant antineoplastics & the antineoplastics & the
“Adriamycin-flare”“Adriamycin-flare”
Best of LuckBest of Luck to you All! to you All!
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