Pharm Review Class Version

8/17/2019 Pharm Review Class Version

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I Love pharm

A love/hate relationship story

narrated by Monica andMariam


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OTHER CNS DRUGS

Anti-Smoking


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Nicotine Replacements

• Nicorette – Nicotine Gum

– ransdermal !atch

• "-#igarettes

• Nasal Spray

•

Nicotine Inhalers


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Nicotine M$A


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%upropion &'yban(

• M$A) *A and N" reuptake inhibition decreasesre+arding e,ects o nicotine

• S" and #autions) – Sei.ure prone patients

• 0 o sei.ures

• Anore0ia/bulimia

• ead trauma

• #NS tremor

• #irrhosis

– Increased suicidal thinking – #aution in patients +ith &especially when using transdermal

patch))• #1 *isease

• N

• #A*


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1arenicline hanti0(


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#hanti0

• S" and #autions – Increased suicidal thinking

– Increased incidence o stroke and heart attacks

–Aggression/violence

– A,ects vision2 cognition2 and motor control• rouble operating machinery

– N/1

– Strange dreams

– Sei.ures

– Need to ad3ust dose or renal dysunction

– **I +ith alcohol


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OTHER CNS DRUGS

Migraines


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*iagnosis

• 4ive headaches marked by pain and t+o o theollo+ing) – $ne-sided

– !ulsating

– Moderate to severe intensity

– Aggravated by routine physical activity

• !lus one) – N/1 or both

– Abnormal sensitivity to light and sound• $ther criteria

– Last rom 5-67 hours

– No underlying cause +hen evaluated medically

–Not be attributable to any condition other than migraine


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Acute reatment

• $#) aspirin2 ylenol2 NSAI*S

• Midrin – Acetaminophen 8 Isometheptene 8 *ichloralphena.one

• !rescription strength NSAI*s – *icloenac

– Indomethacin

– oradol

• Triptans – Abortive

– 5-HT 1B/1D receptor agonists


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!reventive Medications

• %! Meds – %eta-blockers &propranolol(

– ##%s &1erapamil 9 cluster headaches(

• Anti-sei.ure Meds – *epakote

– opama0

– Gabapentin

• #As – Amitriptyline

– Nortriptyline

– !rotriptyline


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$ther Medications

• %utalbital preparations – #ombine sedative butalbital +ith aspirin

and ca,eine

– #an be addictive and may cause reboundheadaches

• $pioids such as codeine

• #orticosteroids2 especially or migrainesthat last or : days or more


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OTHER CNS DRUGS

Anti-!arkinson;s


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$vervie+

• !rogressive disease that a,ectsnerve cells in the part o the braincontrolling muscle movement

• #ause) damage o nerve cells insubstantia nigra that typicallyrelease *A

– *A transmits signals bet+een substantianigra and corpus striatum allo+ingmuscles to make smooth2 controlledmovements


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reatment

• Medications) – Sinemet &Levodopa and #arbidopa(

• #arbidopa blocks destruction o levodopa by dopa-%


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$ther Medications

• Mirape0

– Synthetic *A receptor agonist

– #an cause compulsive gambling

• Selegiline &"ldepyrl( – MA$-% Inhibitor

– !revents breakdo+n o *A by MA$-%

– #an also be used as an antidepressant

• #ogentin – Anticholinergic

– Reduces Ach to reduce tremoring caused by

e0cessive Ach activity


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Implications or *entistry

• >erostomia

• "namel erosion rom N/1

•*i?culty brushing teeth

• I oral tremor2 dental care di?cult

– Schedule @-B minutes ater levodopadose +hen symptoms are ma0imallyreduced2 ho+ever levodopa can causedyskinesias


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**Is

• Levodopa may sensiti.e heart to epi inducedarrhythmias – #aution +ith epi

• #$M inhibitors) – Increase %! and sensiti.e myocardium to arrhythmias

• #aution +ith epi

– "rythromycin and Ampicillin can reduce biliaryelimination o "ntacapone

• Selegilene – Metaboli.ed to amphetamine and methamphetamine

• Avoid epi

– his is an MA$I 9 avoid Meperidine• #auses buildup o to0ic metabolites o Meperidine

ypertensive crisis2 convulsions2 symptoms o opioid $* suchas respiratory depression


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UEST!ONS

$ther #NS *rugs


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Match the anti-!arkinson drug +ith M$A

CD MA$-% inhibitor

7D #rosses the %%% and converts to *A bynerve cells in the brain

:D Synthetic *A receptor agonist5D #$M inhibitor

ED Anticholinergic2 reducing Ach

AD#ogentin%DMirape0#D"ntacapone*DSinemet

"DSelegiline


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All o the ollo+ing are used ormigraine prevention ">#"!

AD Gabapentin

%D !ropranolol#D *epakote

*D riptans

"D Amitriptyline


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/4) 'yban acts as a nicotine receptor

antagonist2 decreasing re+ardinge,ects o nicotineD #hanti0 inhibits *Aand N" reuptake2 decreasing re+arding

e,ects o nicotineD


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Migraine diagnosis includes Fve headachesmarked by pain and t+o o the ollo+ing ">#"!)

AD !ulsating%D Moderate-severe intensity

#D Aggravated by routine physical

activity*D %ilateral


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#arbidopa is used as a treatment o!arkinson;s because it

AD !otentiates the central action o dopamine

%D !otentiates the central action o N"

#D *ecreases the peripheral metabolism olevodopa

*D Inhibits the peripheral stimulatory Fbersrom the #NS

"D Increases the permeability o the %%% toLevodopa


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#ontrol o %lood !ressure

• 7 systems control %!)

CD Sympathetic NS

7D Renin-Angiotensin-Aldosterone system

Sympathetic

RAAS


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%lood !ressure

%! < otal !eripheral Resistance &!R( 0 #ardiac$utput $(

– *rugs that a,ect !R)• Alpha C blockers

• *iuretics

• A#" Inhibitors

• AR%S

•##% type II

– *rugs that a,ect #$)• %eta %lockers

• ##% type I

• *iuretics


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%eta %lockers

• "nd in -$L$LH• 5 types)

CD SpeciFc %eta blockers)• Atenolol/Metoprolol &%C blockers(

7D Non speciFc %eta blockers)• !ropranolol &%C and %7 blockers(

– #auses bronchoconstriction

– Not good or asthmatics

:D Intrinsic Sympathomimetic Activity &ISA(• !indelol2 Acebutolol

– !artial agonists) Stimulate heart a little2 but not as much as body +ould normallystimulate heart Lo+er #$ than normal

– Good or athletes

5D Alpha/beta %lockers• Labetolol

– AA) vasodilating beta blockers

– Lo+ers !R and #$ Good or #4 patients


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%eta %lockers

• Adverse e,ects) – Mask signs o hypoglycemia JJJJ

– "levate blood lipids

– 4atigue2 sleep disturbance

– Impotence

– Korsens bronchoconstriction in

asthmatics &nonselective %%( – Induces hypoglycemia &nonselective %%(


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AlphaC blockers

• "nd in -osinH – !ra.osin2 era.osin2 *o0a.osin

• Lo+er !R Lo+er %!

• Advantages) – Good or elderly patients +ho have a

lo+ #$ but still have high %! due to

elevated !R – *oesn;t a,ect blood lipids like %%

– Also used or %enign !rostate

ypertrophy


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AlphaC %lockers

• Adverse e,ects) – !ostural hypotension

– *ry mouth2 di..iness2 headache2

dro+siness2 nausea

• **I) – "pi reversal


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#entral Acting Alpha7Agonists

• Methyldopa2 #lonidine – Kork #"NRALL

– Khen alpha7 receptors are activated2 it

tells the neuron to S$! releasing theN &N"(

– Activating alpha7 less N" reduced

sympathetic outo+ in #NS reduced%!


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REN!N-ANG!OTENS!NS$STE%


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A#" Inhibitors

• %lock conversion o Ang I Ang II – %locks breakdo+n o %radykinin

– *ecreases sympathetic activation

– *ecreases aldosterone release&decreases uid retention(

• "nd in -prilH

– Lisinopril2 "nalapril2 #aptopril


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Lisinopril

• A#"-I

• reatment) – N

– #4

– MI

– !revents renal/ retinal complication o

diabetes


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A i i II R


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Angiotensin II Receptor%lockers

• "nd in -SartanH – Losartan2 1alsartan &*iovan(

– y.aar) &Losartan 8 #'(

• !revent Angiotensin II rom binding toreceptor

• Results in)

– *ecreased Aldosterone secretion

– *ecreased vasoconstriction – *ecreased sympathetic activation

*ecreased %! *$ N$ a,ect %radykinin


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#a #hannel %lockers

• ype I) – Kork on #a8 channels in the heart to lo+er cardiac output

– "0) 1erapamil

• ype II) – Kork on #a8 channels in vascular smooth muscle to vasodilate

+hich reduces peripheral resistance• &reduces aterloadH(

– "nd in -!ineH• Niedipine

• Amlodipine

• Advantages) – =seul or N patients that also have)

• Asthma2 diabetes2 angina2 peripheral vascular disease2 blacks2 elderly

• Adverse ",ects) – Gingival yperplasia JJJ &espD Niedipine(

– "dema


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Calcium Channel Blockers

Ca+ Ca+

Reduced

Peripheral

Resistance

Reduced

cardiac

output

Type I:

verapamil

diltiazem

Type II:

Nifedipine


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Amlodipine

• Aka) Norvasc

• #a8 channel blocker- ype II

• =ses)

– ypertension – Angina !ectoris

• Least likely to cause gingival hyperplasia

• Metaboli.ed by :A5 – Macrolides 8 antiungals decrease metabolism

o Amlodipine increase to0icity


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ekalmo

• Aliskiren &ekturna( 8 Amlodipine – eturna) targets RAAS by inhibiting

Renin

• Renin is responsible or the Cst step in RAAS+hich is the conversion o Angiotensin Angiotensin I

– Amlodipine) ##% &type II(


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*iuretics

• #ause person to lose Na8 and 7$ by impairing thereabsorption o Na8 in the renal tubules

• ypes)

CD hia.ides) ydrochlorothia.ide &#'(• Korks in the distal tubule

7D igh-ceiling/ Loop diuretics) 4urosemide &Lasi0(• Korks in the loop o enle

:D !otassium sparing) Spironolacton2 Amiloride

• Cst line drug or NJJ

• =ses) –. #4

–. N

• Adverse e,ect) –. ypokalemia &e0cept the potassium sparing(

• #an be used in combo +ith other N drugs to enhance their

e,ect


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hia.ide *iuretics

• #'

• M$A) – Inhibit Na8 reabsorption in distal tubule

and thereore increase the e0cretion oNa82 #l-2 and 7$

• Adverse e,ects)

– ypokalemia +eakness2 atigue2di..iness2 leg cramps


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Loop *iuretics

• 4urosemide &Lasi0(

• More potent than hia.ide diurectics

• =se) – Khen use o hia.ide diuretics is #/I due

to impaired renal unction because thesediuretics preserve renal blood o+

– Good or elderly2 blacks• Adverse e,ects)

– ypokalemia2 dehydration


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!otassium Sparing *iuretics

• Spironolactone2 riamterene2Amiloride – Spironolactone M$A)

• #ompetitive antagonist at aldosteronereceptor

– riamterene M$A)• %locks apical membrane Na8 channel

• =sually used as a combo +ith otherdiuretics to reduce 8 loss rom theFrst diuretic

•


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Diuretics and N%&ID%

Fluid

volumeFluid

volume

Diuretics act in 'idneys

Na+

H!

"+

Reduced

Peripheral

Resistance

#P

decrease

Reduced C$

N%&ID% act via P(inhi)ition in the

renal

system to reduce

renal perfusion*

causin Na+

and H! retention*

thus reducindiuretic effect

#ombo Antihypertensive


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#ombo AntihypertensiveMeds

• =sually a thia.ide diuretic 8 another Nmed

• "0amples)

– Lotensin #) %ena.epril 8 #' – 'estoretic) Lisinopril 8 #'

– riben.or) $lmesartan medo0omil 8Amlodipine 8 #'

– y.aar) Losartan 8 #'

– eklamo) Amlodipine 8 ekturna &direct renininhibitor(

!h l i l i i h


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!harmacological issues +ith

ypertensive patients

• =se "pi +ith caution – Avoid epi cords

• NSAI*s can reduce antihypertensive

e,ect o drugs

• Katch out or additive sedativee,ects

• Katch out or orthostatichypotension

&ntihypertensive Drus %ummary Ta)le


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Class Agents Mechanism Of Action Adverse SideEects

Drug:Drug nteractions

alpha-Cblockers

pra.osintera.osin

alpha-C block rela0es smoothmuscles in vascular epitheliumcausing vasodilation

orthostatichypotension

epi reversal

beta-blockers

propranolol2nadololatenolol2

metoprololpindolol2acebutolollabetolol2carvediol

beta-C P beta-7 blockspeciFc beta-C blockISA activity

alphaC and %C2 %7 block reduction o cardiac output2reduction in renin output anddecrease in sympathetic outo+rom #NS

all) elevationo blood lipids2masking o

signs ohypoglycemiain diabetics2GI upset2atigueD!ropranolol)bronchoconstriction

•NSAI*S may decreasehypotensive e,ects•potential hypertensive crisis +ith

epi2 especially +ith propranolol•propranolol decreasesmetabolism o lidocaine2dia.epam2 morphine viacompetition or en.ymes#entrally

actingsympatholytics

clonidine methyldopa

direct alpha-7 agonist converted to alphamethylN"2 adirect a-7 agonistQboth reduce sympathetic outo+rom #NS

sedation additive #NS depression) %*'s2alcohol2 narcotic analgesics

A#"Inhibitors

captorpril2enalaprillisinopril

•blocks conversion o angiotensin C toangiotensin-7 &a potentvasoconstrictor(Q•also decreased rate o bradykinininactivation &bradykinin is potentvasodilator( these actions result in

peripheral vasodilation• hese drugs are less e,ective in ArianAmerican patients

coughangioedema&captopril(altered taste

NSAI*S may decreasehypotensive e,ects

Angiotensin Receptor%lockers

Losartan$'AAR(1alsartan&*I$!AN(

competitive anatagonists at theangiotensin-C &A-C( receptorD heseblock the action o angiotensins II andIII2 blocking the vasoconstrictor andaldosterone secreting e,ects oangiotensin II producing a reduction inblood pressure similar to the A#"-inhibitorsD hese drugs are lesse,ective in Arian American patients

heir increasedselectivity oaction vsD theolder A#"inhibitors2ho+ever2 resultsin their lackingthe adverse sidee,ectsassociated +iththese drugs suchas coughing andangioedemaD

same as A#"-Inhibitors

#alcium#hannel%lockers

niedipine2amlodipine&ype I I( verapamil2diltia.em

&ype I(

peripheral arterial vasodilationvia direct action on vascularsmooth muscle

+ork mainly via negative

inotropic e,ect on myocardiumQalso dilates areterioles

gingivalhyperplasia&niedipine( All) edema2 GIupset2

headache

NSAI*S may decreasehypotensive e,ects niedipine can increase digo0inlevels

*iuretics urosemide&loop acting( hydrochlorothia.ide &distaltubules( spironolactone&potassiumsparing(

reduces %! by causing uidreduction via increased sodiume0cretionQ also via vasodilatoryaction

•ypokalemia•Increased risko arrythmias•hypokalemia2alteration oglucose levels •hyperkalemia

may increase the oto0icity oaminoglycosides NSAI*S may decreasehypotensive e,ects Increased chance o hypotension+ith sedatives or opioids

*irect-actingvasodilators

mino0idilhydrala.ine

vasodilation via direct rela0ationo precapillary sphincters

mino0idil)tachycardia2hypertrichosis hydrala.ine)ree0

tachycardia

t ype te s e us %u a y a) e


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UEST!ONS

Antihypertensive drugs


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Su?0

• Remember) – Alpha C blockers -osinH

– %eta blockers -ololH

– A#"-I -prilH

– AR%s -sartanH

– #a8 #% type II -pineH#aliornia a( has a lot o !IN" trees

Sartan sounds like Sultanhe Sultan is an ARa

he A#" takes !ILLS &pril(


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Match the drug +ith its M$A

CD Spironolactone

7D Losartan

:D !ropranolol

5D Lisinopril

ED #lonidine

@D 4urosemide

6D Atenolol

D !ra.osin

BD Labetolol

CD1erapamilCCDAmiloride

C7DNiedipine

C:Dydrochlorothia.ide

AD Alpha-C blocker

%D Alpha-7 agonist

#D Non speciFc beta blocker

*D SpeciFc betaC blocker

"D 1asodilating beta blocker4D A#"-I

GD AR%

D ##% type I

ID ##% type II

TD hia.ide diuretic

D Loop acting diuretic

LD 8 sparing diuretic


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Khich o the ollo+ing drugs is acombination o an A#" inhibitor 8 adiureticU

AD 'estoretic

%D y.aar

#D Lotrel

*D eklamo


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Khich antihypertensive medication+orks in the #NS to reduce bloodpressureU

AD !ra.osin

%D #'

#D 1erapamil

*D #lonidine


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Khich o the ollo+ing diuretics cancause hyperkalemiaU

AD #'

%D 4urosemide

#D Lisinopril

*D Spironolactone


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All o the ollo+ing antihypertensivemedications +ork by lo+ering !Re0cept)

AD !ra.osin

%D Atenolol

#D #'

*D 1erapamil


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Khich o the ollo+ingantihypertensive medications iscontraindicated or asthmatics and

diabeticsUAD Lisinopril

%D Losartan

#D !ropranolol*D !ra.osin


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Khich o the ollo+ingantihypertensive medications is alsoused to treat benign prostate

hypertrophyUAD Atenolol

%D Labetolol

#D #lonidine

*D !ra.osin


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Khich o the ollo+ing is not acomplication o A#"-IU

AD ypokalemia

%D Angioedema

#D yperkalemia

*D *ry cough


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Khich o the ollo+ing drugscommonly causes gingivalhyperplasiaU

AD 4urosemide

%D Niedipine

#D Lisinopril

*D Atenolol


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Khich o the ollo+ing diuretics +orksin the distal tubuleU

AD #'

%D 4urosemide

#D Spironolactone

*D Amiloride


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• Khich o the ollo+ing drugs iscontraindicated +ith "pi because itcauses an epi-reversal reactionU

AD !ra.osin%D !ropranolol

#D #lonidine

*D Losartan


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STAT!NS


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Lipid *isorders

• "levated cholesterolatherosclerosis coronary arterydisease

• #omplications due to atherosclerosis) – $bstructed blood o+2 aneurysms

• reatment or hypercholesteromia)

– Statins

• *iabetics) automatically placed onStatins


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Statins)

• Impair cholesterol synthesis) – Atorvastatin &Lipitor( J

– Simvastatin &'ocor(

– Rosuvastatin restor(

• M$A) – Inhibit MG #oA reductase +hich inhibits

cholesterol synthesis

– Increases V o L*L receptors in liver cell

increased removal o L*L rom blood

• !otency ranking) – #restor W Lipitor W Simvastatin


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Statins

• Advantages) – !revents #1 disease

– reats pts +ith hyperlipidemia

– Anti-inammatory) =seul in treating !eriodontal disease

• Adverse e,ects) – Myopathies

– Rhabdomyelosis

– Memory clouding

–

*iabetesU• **Is)

– :A5 inhibitors &macrolides( increase plasma conc incrisk o rhabdomyelosis


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1ytorin

• 'etia 8 Simvastatin – *ual inhibititon o cholesterol synthesis

8 absorption

1ytorin) 'etia and Simvastatin


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!#SB inhibitors

• Ne+ therapeutic alternative tostatins – !#SB reduce L*L receptors

• Inhibitors block !#SB so you have M$R"L*L receptors more uptake o L*L out oblood and into Liver to be broken do+n


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CARD!O"ASCU#AR DRUGS

Anti-Angina


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ypes o Angina

• ",ort induced2 classic or stable – Most common

– Atherosclerosis coronary artery obstruction reducedblood supply and hence o0ygen delivery to heart

– 0) nitrates2 ##%2 beta-blockers• =nstable

– Increased reXuency and duration and intensityprecipitated by less e,ort

– Symptoms not relieved by rest or nitrates

• !rin.metal2 variant2 vasospastic or rest angina – Least common

– $ccurs at rest due to coronary artery spasm

– 0) nitrates and ##


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reatment - Nitrates

• Nitroglycerin &sublingual2 oral2 patches(

• Isosorbide mononitrate &oral(

• Acute episodes) sublingual

• !rophyla0is) patches2 paste2 oral• M$A)

– Re&'ces pre(oa& reduced o0ygen demand

–*ilates coronary vasculature increaseso0ygenation and perusion to the heart

• **I) 1iagra &potent vasodilator( – hypotension bad

l k


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reatment 9 %eta %lockers

• !ropranolol &non-speciFc(

• Metroprolol2 Atenolol &%C speciFc(

• M$A) Reduces – o0ygen demand o the heart

– cardiac output

– %!

• =sed or prophyla0is taken chronically

•#ontraindications) – Asthma

– *iabetes

– #$!*

–1asospastic angina

##


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reatment 9 ##%s

• 1erapamil – *ecreases R2 contractility2 %!2 and o0ygen demand

• Niedipine2 Amlodipine – Arteriolar vasodilators

• M$A) Decreases a)ter(oa& – %locks calcium entry into cardiac and smooth mm

cells o coronary arteriolar vasodilation reduces myocardial demand P consumption

• Side ",ects – Gingival yperplasia &mainly Niedipine(

– "dema

reatment 9 Ranola0ine


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reatment Ranola0ine&Rane0a(

• #hronic angina

• M$A) Reduces elevated calcium levels reducescardiac output reduces o0ygen demand o theheart

• Sae +ith 1iagra

• **Is – Macrolides and Antiungals

• :A5 substrate) Macrolides and Antiungals +ill inhibit

metabolism o Rane0a to0ic levels and lo+ere,ectiveness

– #odeine• 7*@ inhibitor) Inhibits codeine conversion to morphine

reduces e,ectiveness o #odeine


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%ite of &ction of &nti&ninal Drus

,eins &rteriesHeart -uscle

Before Nitrates(high preload)áBP

After Nitrates (low dose causes

venodilation. reduces preload)âBP

Before Ca++ ChannelBlockers (high afterload) áBP

After Ca++ ChannelBlockers(reduced afterload)âBP

#eta.)loc'ers*HR+ *o'tp't+*B,

Ca++

Ca++

verapamildiltiazem

* contractility*HR+ vaso&i(ation

nifedipine/vasodilation0

Nitrolycerin/Hih dose reducesafterload via dilation

of coronary arteries0

S'..ar/ Tab(e O) Dr'gs Use& To Treat Angina0


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S'..ar/ Tab(e O) Dr'gs Use& To Treat Angina0

Dr'g C(ass %ain Dr'gs %ecanis. o) Action Si&e E))ects

Nitrates

2ac'te terap/-pi((3Cronic terap/ 4 patc3

Nitrog(/cerin Re&'ction o) ./ocar&ia(

o5/gen &e.an&+ pri.ari(/via veno&i(ation 2re&'cing

6pre(oa&738 a(so arteria(

vaso&i(ation

Ortostatic /potension+

ea&aces

Beta-B(oc9ers

2cronic terap/3

,roprano(o(+

Ateno(o(+

%etopro(o(+

,in&o(o(+

Aceb'ta(o(

Re&'ction o) ./ocar&ia(

o5/gen &e.an& via

re&'ction o) eart rate

an& contracti(it/ o)

./ocar&i'. via beta-1

./ocar&ia( receptor b(oc9

Ortostatic /potension+

&i::iness; Ateno(o( acts

peripera((/+ t's &oes

not pro&'ce CNS e))ects

associate&


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UEST!ONS

Anti-Angina


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Khich o the ollo+ing is most useul intreating or preventing angina pectorisU

AD *igo0in

%D Yuinidine#D !ropranolol

*D Lisinopril

"D All the above

"ach o the ollo+ing can be used in


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"ach o the ollo+ing can be used inprevention and treatment o angina ">#"!)

AD *igo0in

%D !ropranolol#D Nitroglycerin

*D 1erapamil

Khich anti-angina medication


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Khich anti angina medicationreduces preloadU

AD Niedipine

%D !ropranolol

#D Nitroglycerin

*D 1erapamil

Khich anti-angina medication


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Khich anti angina medicationdecreases aterloadU

AD Niedipine

%D !ropranolol

#D Nitroglycerin

*D Atenolol


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eart 4ailure

$ i


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$vervie+

• eart is unable to pump enoughblood to meet the body;s needs blood backs up builds up in lungs

and legs edema heart tries torespond to increased demands constant increased preload volume

and aterload pressure ventricularremodeling

#auses


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#auses

• yperthyroidism – Metabolic demands greatly e0ceed #$

• #ongestive eart 4ailure

– eart is diseased typically rom heartattacks killing cardiac muscle

– eart ine?cient at pumping blood

throughout body ventricles havereduced orce o contraction

t t !h th G l


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reatment 9 !harmacotherapy Goals

• o get rid o the e0cess uid thatbuilds up in the body reducesvolume o uid that +eakened heart

has to pump• Advanced cases) Glycoside therapy

– o increase contractility o the heart

reatment


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reatment

• A#" inhibitors – Reduce L ventricular volume and Flling

pressure +hile decreasing !R

prevents enlargement o the heart• *iuretics &loop acting() reduces

preload –

Increases sodium and +ater e0cretion reduces uid backup/edema

• 1asodilating beta-blockers – Reduce R and vasodilate

reatment 9 Glycosides)


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y*igo0in

• Inhibits Na82 8 A!AS" increased calciuminu0 increases orce o contraction omyocardium &positive inotropic e,ect(

• Korks to reduce compensatory changes associated

+ith #4 such as increased heart si.e2 rate2 edema• 4or advanced stages o heart ailure

• Narro+ therapeutic +indo+

• **I

– Macrolides• *ecrease GI bacteria that metaboli.e digo0in increased

plasma levels

• :A5 substrate) :A5 inhibitors +ill decrease metabolism increased plasma levels

reatment AR%s


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reatment 9 AR%s

• 1alsartan/Sacubitril &"ntresto() Reduce !R – Sacubitril) prodrug converted to sacubitrilat

inhibits neprilysin en.yme preventsbreakdo+n o vasoactive peptides increased

level o these peptides vasodilation andreduction o "#4 volume via sodium e0cretion

– 1alsartan) blocks angiotensin II receptor vasodilation and reduction o "#4 volume

• **Is – NSAI*S and #$>-7 inhibitors 9 potential renal

ailure


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UEST!ONS

eart 4ailure

*igo0in e0erts its positive inotropic


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g p p

e,ect by

AD Activation o adenylcyclase

%D An agonist e,ect o beta-receptors

#D Inhibition o Na82 8 A!ase leadingto increased calcium inu0

*D *ecreasing the amount o calcium

available or e0citation-contractioncoupling

Khich o the ollo+ing is N$ used


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gin treatment o heart ailureU

AD Lisinopril

%D #'#D 1alsartan

*DLasi0

"D Labetolol


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he cardiac glycosides +ill increase the concentrationo +hich ion in an active heart muscleU

AD Sodium

%D !otassium

#D #hloride

*D #alcium


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Antiarrhythmics

$vervie+


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$vervie+

• Arrhythmias) abnormalities in impulseormation and conduction in themyocardium

• #an result in) – %radycardia &R Z@ bpm(

– achycardia &R W C bpm(

– 4ibrillation &irregular heart beat(

• ypes – 1entricular Arrhythmia

– Supraventricular Arrhythmia


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SA No&e

• 4unctions as thepacemakerH o heart

• Automaticallygenerates impulses2telling heart to beat

• Sets the pace o heart

beat• #onducts impulses

directly into both atia

A" no&e

• 4unctions as pacesetterH o heart

• Located bt+ atriumand ventricles

• Relays and intensiFesimpulse rom SA node

• 4ibers e0tend rom A1node to ventricles&perkin3e Fbers( – elp ventricles contract

Arrhythmias


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Arrhythmias

• Supraventricular arrhythmias) originate abovethe A1 node – Supraventricular tachycardia)

• Rapid2 regular R &CE-7bpm(

• #an be caused by ca,eine2 alcohol2 etc• Less serious than 1entricular arrythmias

• No t0 reXuired

– A 4ib)• Rapid2 irregular heart rhythm

• Main cause o stroke J &blood pools in the heart and clots(

• reatment) – Anticoagulants

– %eta blockers/ #a channel blockers

– "lectrical cardioversion therapy to restore normal sinus rhythm

Arrhythmias


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Arrhythmias

• 1entricular arrhythmias – 1entricular tachycardia)

• SA node not controlling beating o ventricles

– !remature 1entricular #ontractions &!1#()

• 1entricles contract too soon/ out o seXuence +ithnormal heartbeat

• can be caused by ca,eine2 $# cold meds

• %enign

– 1entricular 4ibrillation)• Lie threatening

• =ncontrolled2 irregular heart beat W :bpm

• atal heart attack


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reatment


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reatment

#lassed by Mechanism• ype I 9 Na channel blockers

– Ia) Xuinidine

– Ib) Lidocaine2 phenytoin – Ic) ecainide

• ype II 9 %eta-blockers) propranolol2metoprolol

• ype III 9 channel blockers) amiodarone

• ype I1 9 #a channel blockers) verapamil2diltia.em

*rug Induced Arrhythmias


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*rug Induced Arrhythmias

• Some drugs can prolong Y interval ventricular arrhythmias

• "0 include) –

Some antiarrhythmics2 especially channelblockers• Amiodarone

– Macrolides

– A.ole antiungals – #A antidepressants

– Atypical antipsychotics

ype I *rugs) block Na channels• Ia) Yuinidine


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• Ia) Yuinidine – M$A) Increases the reractory period o cardiac muscle reduces conduction

velocity o heart

–

0)• A-Fb• ventricular tachyarrhythmias

– as some #lass III activity &can cause ventricular arrhythmias(

– **Is• 7*@ Inhibitor) Lo+ers #odeine e,ectiveness

• Additive e,ects +ith muscaranic antisialogogues

• Ib) Lidocaine – M$A) *ecrease cardiac e0citability

– Acute ventricular arrhythmias arising during MI

– Given I1

– JJdrug o choice or pts hospitali.ed due to 1D Arrhythmia

•

Ic) 4lecainide &ambacor( – M$A) !rolongs cardiac action potential – !revent and treat tachyarrhythmias &supraventricular and ventricular(

– #autions• 7*@ substrate) due to genetic variations in 7*@ e0pression2 patient monitoring o drug e,ects

and dose titration reXuired

• #an aggravate pree0isting arrhythmias or induce lie-threatening ventricular tachycardia

• Increases mortality in pts +ho have had an MI

ype II *rugs) %eta-blockers


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ype II *rugs) %eta-blockers

• !ropranolol P Metoprolol – Reduces incidence o arrhythmias ater

MI

– !revents supraventriculartachyarrhythmias

• "smolol –

Short acting – I1

– Acute arrhythmias occurring duringsurgeries

•

#lass III *rugs 9 channel


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blockers• Amiodarone• !rolong A! duration by slo+ing rate o

repolari.ation

• Severe reractory supraventricular and

ventricular tachyarrhythmias• 0)

– A-Fb

• S"/**I – %lue skin discoloration due to iodine accumulation

ound in drug

– 7*@ inhibitor) Lo+ers #odeine e,ectiveness

#lass I1 *rugs) ##%s


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#lass I1 *rugs) ##%s

• 1erapamil and *iltia.em• Slo+s conduction and prolongs

reractory period

• Atrial arrhythmias W 1entriculararrhythmias

Supraventricular *rugs o


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#hoice

• "erapa.i(• Digoin

– *ecreases the rate o A1 conduction

• %eta blockers

• Yuinidine

• ospitali.ed patients) lidocaine is the

Frst line o treatment

*entistry Implications


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*entistry Implications

• $rthostatic hypotension can be anissue since #1 unction depressed

• Stress can provoke arrhythmias

• #aution +ith epi – Avoid +ith propranolol

• 7*@ inhibitors

– Yuinidine – Amiodarone


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UEST!ONS

Anti-Arrhythmics


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Khich o the ollo+ing anti-arrhythmicdrugs are contraindicated +ith#odeineU

AD Yuinidine%D Lidocaine

#D Amiodarone

*D 1erapamil


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Khich antiarrhythmic drug class mostcommonly causes arrhythmiasU

AD ype I

%D ype II

#D ype III

*D ype I1


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Khat is the antiarrhythmic drug ochoice used to treat 1-arrhythmias inthe hospitalU

AD Yuinidine%D Lidocaine

#D 4lecainide

*D 1erapamil


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Antiplatelets


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• Aspirin – Most +idely used anti-platelet

– Inhibits thrombo0ane synthetase irreversibly inhibits !Gsynthesis

– !rophyla0is against stroke and MI

– *aily baby aspirin Cmg dose

• #lopidogrel &!lavi0(2 iclopidine &iclid(2 !rasugrel

– inhibits platelet aggregation mediated by A*!

– Given or patients +ith aspirin allergy

– Atherosclerotic patients to prevent A2 strokes2 coronary arteryclosure in pts underdoing angioplasty

– *o not stop !lavi0 prior to surgery or patients +ith cardiac stents

– **Is/#autions• 7#CB Substrate) people di,er genetically +ith this gene

– !rasugrel is alternative2 as it is not a 7#CB substrate

• Avoid heartburn meds can reduce e,ectiveness o !lavi0 and increaseMI risk

• %oth used or unstable angina

eparin !roducts


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• eparin Sodium2 eparin #alcium

– hrombin Inhibitors

– Acts in bloodstream &I1(

– %lock conversion o prothrombin thrombin

– Measured by !

– S") increased bleeding and thrombocytopenia• "no0aparin &Loveno0(2 *alteparin &4ragmin(

– LMK

– SY

– More selective

– Monitoring not necessary

• *12 pulmonary embolus2 unstable angina2 acuteMI2 prosthetic heart valves

#oumarin !roducts


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#oumarin !roducts

• Kararin Sodium oumadin(• #ompetitively inhibits the synthesis o 1itamin- dependent

coagulation actors in the liver

• Stroke prevention in patients +ith A-Fb2 stroke2 *1

•

Measured by !/INR• Narro+ therapeutic +indo+

• Should not be stopped beore routine dental surgery

• **Is 9 Increased bleeding – 7#B inhibitors &Metronida.ole2 macrolides2 a.oles(

• Inhibit metabolic breakdo+n o Kararin accumulation increasedbleeding

– Antibiotics &etracycline( diminish gut ora responsible or 1it synthesis can increase bleeding

– Acetaminophen2 Aspirin2 NSAI*s) compete or plasma sites on

protein

*irect hrombin Inhibitors


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• *abigatran &!rada0a(

• #ompetitive direct thrombin inhibitor 9 preventsconversion o Fbrinogen to Fbrin

• #linical advantage vs Kararin – No blood monitoring

– Korks Xuicker – 4e+er **Is

– =na,ected by ood

• Advantage) Reversal agent &!ra0bind( 9 binds

directly to drug• Kararin alternative or or *1 prophyla0is ater 3oint

replacement

• Also used as orally administered Loveno0 alternative

4actor >a Inhibitors


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4actor >a Inhibitors

• Rivora0aban &>arelto(• Api0aban &"liXuis(

• "do0aban &Savaysa(

• *1 and non-valvular A-Fb• $ral administration

• Inhibits actor >a preventing Fbrinproduction decreased blood coagulation

• Antidote in development

• **Is – :A5 Substrate) Avoid :A5 inhibitors

increased bleeding

*ental #onsiderations


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*ental #onsiderations

• #onsult +ith physician on +hether ornot to discontinue anticoagulanttherapy

• #onsider prophylactic antibiotics• NSAI*S cause gastric erosion and GI

bleeding increased bleeding +ith

all the above anticoagulants


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UEST!ONS

Anticoagulants

Match the anticoagulantith M$A


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+ith M$ACD Inhibits synthesis o 1it- dependent coagulation

actors

7D 4actor >a inhibitor

:D Inhibits thrombo0ane synthetase

5D !revents conversion o prothrombin thrombin

ED *irect thrombin inhibitor

@D Inhibits platelet aggregation mediated by A*!

AD !lavi0%D Kararin#D !rada0a*Deparin"D Aspirin

4D Rivora0aban

Khich anticoagulant is a 7#CB

substrateU


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substrateU

AD Kararin

%D Aspirin

#D Rivora0aban*D!lavi0

"D !rada0a


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!atients on eparin reXuire !/INR

monitoringD !atients on KararinreXuire ! monitoringD

AD %oth statements true

%D %oth statements alse

#D 4irst statement true2 second

statement alse

*D 4irst statement alse2 secondstatement true

Khich anticoagulant has theadvantage o an antidote availableU


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advantage o an antidote availableU

AD Kararin

%D Aspirin

#D Rivora0aban

*D!lavi0

"D *abigatran

Khich anticoagulant is a :A5 substrate and


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Khich anticoagulant is a :A5 substrate andshould not be combined +ith a :A5 inhibitorU

AD Kararin

%D Aspirin#D Rivora0aban

*D!lavi0

"D *abigatran


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DRUG-DRUG!NTERACT!ONS

Antibiotic **Is


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CD #idal-Static **I – #idal Abs target actively gro+ing bacteria cell +allD Static Abs inhibit

bacterial gro+thD hereore Static Abs decrease e,ectiveness o cidal Abs

7D etracycline)

– Metal cations &e0) ums2 rolaids() orm comple0 +ith etracycline andinhibit absorption rom GI tract

– *igo0in) etracycline +ipes out bacterial ora in GI +hich is responsibleor metaboli.ing *igo0in increase in digo0in to0icity

– Kararin) etracycline +ipes out bacterial ora in GI +hich is involved in1it synthesis additive bleeding

:D Metronida.ole)

– Alcohol) *isulFram- r0nD Metronida.ole inhibits acetaldehyde

dehydrogenase +hich is needed to metaboli.e alcohol build up oalcohol acetalaldehyde N/1

– Kararin) Metronida.ole inhibits 7#B +hich is needed to metaboli.eKararin increase in Kararin increased bleeding and INR

Antibiotic **Is


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• Macrolides- :A5 inhibition **Is)CD %en.os) increases duration o action o ben.os

7D >arelto/ "liXuis) increased bleeding

:D Lipitor) increased risk o rhabdomyelosis

resulting in mm pain2 +eakness2 kidney ailure5D #arbame.epine/ !henytoin) increases plasma

levels increased to0icity o anticonvulsants

ED Anticancer agents) increased to0icity

@D Antianginal drugs &Rane0a() increased to0icity

Jsame **Is +ith A.ole antiungals

Antibiotic **Is


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• Macrolides) non :A5 **I interactions)CD Kararin- "rythromycin)

aD Kararin is metaboli.ed by 7#BD "rythromycininhibits 7#B increased bleeding

7D *igo0in-"rythromycin/#larithromycin)aD "rythromycin +ipes out GI bacteria that

metaboli.es *igo0in increased *igo0into0icity &same **I as tetracyclines-*igo0in(

bD "rythro/#larithro inhibits !-gp drug e[u0 pump increases oral absorption and decreasesclearance o *igo0in *igo0in to0icity

Analgesic **Is


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g

• Aspirin 8 plasma protein bounddrugs) – Aspirin competes +ith protein binding o

Kararin &results in increased bleeding(and !henytoin &results in antisei.ureto0icity( leading to increased blood conco these drugs

• Acetaminophen)CD %arbiturate/ Alcohol **I) IN#R"AS"

metabolism o tylenol to its

hepatoto0ic orm

NSAI* **Is


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• **Is that increase bleeding)CD Anticoagulants) increases INR and GI bleeding

7D !a0il/ !ro.ac &SSRIs() Increased upper GI bleeding

:D erbals) additive bleeding due to altered plateles &anyherbal that starts +ith G(

5D Alcohol) increased GI bleeding2 ulcerations• $ther **Is)

CD Aspirin) ibuproen INI%IS blood thinning action o Aspirin+hen taken beore aspirinD ake aspirin 7 hrs beore NSAI*

7D Lithium) NSAI* reduces renal clearance o lithium lithium

to0icity:D Antihypertensive drugs) NSAI*s increase Na8/7$ retention decreased e,ectiveness o antihypertensive drugs

$pioid **Is


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p

• #NS depressants) cause additive #NS depression – Include %en.os2 %arbs2 anticonvulsants2 antihistamines2 etc

• Respiratory depressants) cause additive respiratorydepression

– Include ben.os2 barbs

• 7*@ inhibitors 8 #odeine) inhibit conversion o codeineto morphine decreases e,ectiveness o #odeine

– 7*@ inhibitors include)• SSRIs &!a0il/ !ro.ac(

• Antiarrhymic drugs &Yuinidine/ Amiodarone(

• Antianginal drugs &Ranola0ine(

– Also e,ects $0ycodone/ hydrocodone but to a lesser degree

• Nalo0one/ Naltere0one) these are opioid antagonists decrease e,ectiveness o $pioids

Local Anesthetic **Is


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• #As/ SNRIs/ #ocaine – %lock reuptake o N"/" hypertensive crisis due

to too much "pi

• Non speciFc % %lockers

– "pi acts on alpha and beta receptorsD Khen betais blocked2 "pi can only +ork on alpha receptorsresulting in too much vasoconstriction Ncrisis ollo+ed by ree0 bradycardia

• Antipsychotic agents/ Alpha C blockers) – "pi reversalD $rthostatic hypotension ollo+ed by

Documents

Pharm Review Class Version