MS2_PHARM

THREE SILLY PAPA CALFS

• THREOPHYLLINE
• SILDENAFIL
• PAPAVERINE
• CAFFEINE

MOA -- TPC Prevents phosphodiesterase from changing cAMP back à 5´-AMP.

SIL -- Prevents phosphodiesterase from changing cGMP back → 5´-GMP

• THEO --bronchodilator (Not used as much anymore). Relieves airflow obstruction
• of chronic asthma. *Seizures *Poss fatal arrhythmias

PDE INH

MOA -- PREVENTS PDE FROM CHANGING cAMP BACK TO 5'-AMP

PHARM -- BRONCH-DILATOR

THERA -- INFREQ USED; RELIEVES AIRFLOW OBST OF CHRONIC ASTHMA

ADVERSE -- SEIZURES, POSS FATAL ARRHYTHMIAS

PDE INH

MOA -- PREVENTS PDE FROM CHANGING cAMP TO 5'-AMP (SIMILAR TO THREO

THERA -- RELAX SMOOTH MUSC OF BRONCHs IN ASTHMA Pt

PDE INH

MOA --PREVENTS PDE FROM CHANGING cAMP BACK TO 5'-AMP

PDE INH

MOA --PREVENTS PDE FROM CHANGING cGMP BACK TO 5'GMP

• PHARM -- cGMP produces smooth muscle
• relaxation → inc blood flow into corpus cavernosa

THERA -- IMPOTENCE

• ACETAZOLAMIDE (MORE BASIC / ALKALINE)
• -GLAUCOMA (CARBONIC ANHYD INH)

AMMONIUM CHLORIDE (MORE ACIDIC)

BOTULINUM TOXIN (-)

*HEMICHOLINIUM: prevents ACh synthesis by blocking choline uptake in parasympathetic fiber.

*TETANUS TOXIN: prevents inhibitory NT --> increase ACh --> spastic paralysis

*Black widow spider toxin (α-latrotoxin): binds to neurexins --> excessive ACh release

--Drugs affecting degradation of ACh

• •Slowly reversible carbamate inhibitors (neostigmine)
• •Irreversible organophosphate inhibitors (malathion)

BOTOX

Transported into cholinergic receptor via receptor mediated endocytosis (Local i.m. injection)

Light chain of botox (protease) → hydrolyzes proteins involved in the synaptic storage & exocytotic release of ACh

→ No more cholinergic transmission at NMJ

→ muscle paralysis (FLOPPY BABY)

• THERAPEUTIC -->
• *blepharospasm
• *strabismus
• *cervical dystonia
• *spasmodic torticollis
• *laryngeal dystonia
• *hemifacial spasm
• *myofacial pain syndrome

• **all require multiple treatments b/c hydrolyzed
• enzymes are replaced -->regain function

CHOLINERGIC AGONIST

• MOA -- GIVEN IV
• 1^o M EFFECTS (N EFFECTS ONLY AFTER M RECEPTORS BLOCKED BY ATROPINE)

PHARM -- AFTER IV INJ: RAPID & TRANSIENT DEC IN BP VIA NO FROM ENDO CELLS --> BAROREFLEX TACHYCARDIA. NO DIRECT CARDIAC SUPPRESSION

AFTER RX WITH ATROPINE, MUCH LARGER DOSE AF ACh --> INC BP & HR BY SYMP GANG

THERA -- NOT USED SYSTEMICALLY BC EFFECTS MULTI ORGANS.

RAPIDLY DEGRADED BY HYDROLYSIS (PLASMA PSEUDO-CHOLINESTERASE)

USED TO PROD RAPID & COMPLETE MIOSIS (20-60 min) BEFORE OR AFTER SURGERY INVing ANT EYE

CHOLINERGIC AGONIST

MOA -- GIVEN P.O. BUT F IS LOW

M RECEPTOR AGONIST W/ SELECTIVE GI & GU EFFECTS

• PHARM --
• INC ACID SECRETION
• INC MOTILITY & TONE
• RELAX SPHINC
• STIM SECRETION IN GI
• CONTRACT DETRUSOR MUSC
• RELAX EXTERNAL SPHINC

• THERA --
• BOWEL STASIS
• POST-OP PARALYTIC ILEUS
• URINARY RETENTION (POST-OP OR NEURO)
• *TREATS PROBS W/ BOWEL/BLADDER

• CONTRA --
• ASTHMA
• COPD
• PEPTIC ULCER
• CHF
• HYPERTHYROIDISM

CHOLINERGIC AGONIST

MOA -- SINGLE IV INJ

INITIAL SINGLE CONTRACTION OF SKEL MUSC --> 3-5 MINS FLACCID PARALYSIS

N2 CHOL RECEPTORS AT NMJ OF SKEL MUSC

PHARM -- FLACCID PARALYSIS: CONSTANT DEPOL OF MEP = DEPOL BLOCKADE = NON-COMP BLOCKADE

MOST OF IV DOSE DEGRADED BY PLASMA CHOLase BEFORE REACHING NMJ. NOT DEGRADED BY TISSUE ACE

PARTIAL REPOL POSS WHILE SUCC STILL PRESENT BUT NMJ BLOCKADE PERSISTS

PEEPS WITH GENETIC VARIANT OF PLASMA ACE SEE EFFECTS LASTING 1-3hr LONGER

THERA -- MUSC RELAXATION & SHORT TERM PARALYSIS

CHOL AGONIST

MOA -- 3* AMINE

SELECTIVE M AGONIST OF BOTANICAL ORIGIN

DEGRADED BY HEP ENZs (NOT BY ACE OR pseudo-ACE)

PHARM -- CONTRACTION OF MERIDIONAL FIBERS OF CILIARY MUSC

• --> INC IRIDIOCORNEAL ANGLE AND/OR TONE AND ALIGN OF TRABECULAE
• --> AQ FLOW BETTER INTO CANAL OF SCHLEMM

• THERA -- GLAUCOMA: LOWER IOP BY 20%
• DRY MOUTH ASSIC W/ SJORGREN'S SYND

ADVERSE -- GLAUCOMA --> LENS FIXATION IMPAIRS FAR VISION. PERSISTANT MIOSIS CAUSES POOR NIGHT VISION

• CONTRAINDICATION --
• ASTHMA & COPD (BRONCH-CONSTRICT)

PEPTIC ULCER (INC GASTRIC ACID)

HYPERTHYROIDISM (ATRIAL FLUTTER OR FIB)

DIALATED HEART (ATRIAL FLUTTER OR FIB)

CHOL AGONIST

MOA -- SYNTHETIC M AGONIST

PHARM -- INC SALIVATION

THERA -- DRY MOUTH & EYES ASSOC W. SJOGREN'S SYND

• ADVERSE --
• GI CRAMPING
• SWEATING
• UTI
• RHINITIS

CHOLINERGIC AGONIST

MOA -- M RECEPTOR AGONIST

PHARM -- CONTRICTION OF BRONCH MUSC

THERA -- PROVOCATIVE AGENT IN Dx OF BRONCH ASTHMA (meTHAcholine IS FOR asTHMA)

CHOLINERGIC AGONIST

MOA -- N & M RECEPTOR AGONIST

PHARM -- SLOW ONSET MIOSIS (4-8 hr)

THERA -- MIOSIS AFTER SURGERY ON THE ANT CHAMBER OF EYE. EYE DROPS

"AMC BETHANNE SUCCS PILO"

• ACh
• METHACHOLINE
• CARBACHOL (CARBAMYCHOLINE)
• BETHANECHOL
• SUCCINYLCHOLINE (nicotinic also)
• PILOCARPINE

• ACh -- Given i.v.
• Exerts 1^o Muscr effects
• (Nicotinic effects seen only after Muscr receptors are blocked by atropine)

• After i.v. injection:
• Rapid & transient decr in BP (via NO from endothelial cells) → baroreflex tachycardia
• (No direct cardiac suppression)

• After Rx w/ atropine, a much larger dose of ACh →
• incr BP & HR by stim N1-chol receptors at sympathetic ganglia

• THERA --> Not used systemically b/c:
• *Affects multiple organs
• *Rapidly degraded by hydrolysis (plasma
• pseudo-cholinesterase)

Used to produce rapid & complete miosis (20-60 min) before or after surgery involving ant. part of eye

• CARBACHOL
• MOA -- N&M RECEPTOR AGONIST
• PHARM -- SLOW ONSET MIOSIS (4-8hr)
• THER -- CAUSED MIOSIS AFTER SURGERY ON THE ANT CHAMBER OF THE EYE -- EYE DROPS

• METHACHOLINE
• MOA -- M RECEPTOR AGONIST
• PHARM -- CONTRACTION OF BRONCH MUSC
• THER -- PROVOCATIVE AGENT IN Dx OF BRONCH ASTHMA (meTHAchol IS FOR asTHMa

• BETHANECHOL
• MOA -- GIVEN p.o. BUT F IS LOW. M RECEPTOR AG W/ SELECTIVE GI & GU EFFECTS
• PHARM -- INC ACID SECRETION, INC MOTILITY & TONE, RELAX SPHINCs, STIM SEC IN GI, CONTRACT DETRUSOR MUSC, RELAX EXT SPHINC
• THER -- BOWEL STASIS, POST-OP PARALYTIC ILEUS, URINARY RETENTION (POST-OP OR NEURO)
• CONTRAIND -- ASTHMA, COPD, PEPTIC ULCER, CHF, HYPERTHYROIDISM

• SUCC
• MOA -- IV SINGLE INJ. INITIAL SINGLE CONTRAC OF SKEL MUSC --> 3-5 MIN FLACID PARALYSIS. N2 CHOL RECEPTORS AT NMJ
• PHARM -- FLACCID PARAL: CONSTANT DEPOL OF MEP = DEPOL BLOCKADE = NONCOMP BLOCKADE.

MOST IV DOSE DEGRADED BY PLASMA CHOLase BEFORE REACHING NMJ.

PARTIAL REPOL POSS WHILE SUCC STILL PRESENT BUT NMJ BLOCKADE PERSISTS.

NMJ BLOCKADE TERMINATED BY DRUG DIFFUSING AWAY FROM NMJ

THER -- MUSC RELAXATION & SHORT TERM PARALYSIS

• PILO
• MOA -- 3^o AMINE. SELECTIVE M AGONIST OF BOTANICAL ORIGIN

DEGRADED BY HEP ENZs

NOT METABed BY AChase OR PSEUDO-AChase

PHARM -- CONTRACTION OF MERIDONAL FIBERS OF CILIARY MUSC --> INC IRIDIOCORNEAL ANGLE AND/OR TONE AND ALIGNMENT OF TRABECULAE --> AQUEOUS HUM FLOW MORE EASILY INTO CANAL OF SCHLEMM

THER -- GLAUCOMA, LOWER IOP BY 20%

DRY MOUTH ASSOC W/ SJOGREN'S SYND

FOR GLAUCOMA CAN CAUSE LENS FIXATION IMPAIRING FAR VISION AND PERSIST MIOSIS CAUSING POOR NIGHT VISION

• CONTRAIND -- ASTHMA & COPD (BRONCHOCONSTRIC)
• PEPTIC ULCER (INC GASTRIC ACID)
• HYPERTHYROIDISM (ATRIAL FLUTTER OR FIB)
• DILATED HEART (ATRIAL FLUTTER OR FIB)

GLAUCOMA

• EPI
• MOA -- a1 AGONIST

PHARM -- a1 RECEPTOR STIM --> INC OUTFLOW OF AQ HUM VIA PRESS DEP NORMAL PATHWAY. MYDRIASIS VIA RADIAL MUSC DIPIVEFRIN TOO (HYDROed TO EPIN

THER -- GLAUCOMA

ADVERSE -- MYDRIASIS VIA a1 STIM OF RADIAL MUSC OR IRIS

"EPIN BUYs, MAN BETA PILO APRON LANTERNS that TIM ACE's ECHO ISO DORABLE!"

• EPINEPHRINE
• BI-MATO-PROST
• MANNITOL
• BETAX-OLOL
• PILOCARPINE
• APRA-CLONI-DINE
• LAN-TANO-PROST
• TIM-OLOL (b-adren antagonist)
• ACETA-ZOLA-MIDE
• ECHO-THIO-PHATE (op AChase inh also)
• ISO-FLUO-PHATE (DFP)
• DOR-ZOLA-MIDE

Tx OPEN-ANGLE GLAUCOMA

• LATANOPROST (PGF2a ANALOG)
• BIMATOPROST - EYELASHES

Tx FOR OPEN-ANGLE GLAUCOMA

PILOCARPINE (m AGONIST)

EPINEPHRINE (a1-BLOCKER)

• ISOFLUROPHATE (OP ACE INH)
• ECHOTHIOPHATE ''

Tx FOR OPEN-ANGLE GLAUCOMA

• BETAXOLOL (b-BLOCKER)
• TIMOLOL ''
• --NOT PROPRANOLOL BC ANESTHETIC EFFECT

APRACLONIDINE (a2-BLOCKER)

• ACETAZOLAMIDE (CARB ANH INH, MANY Sx)
• DORZOLAMIDE '' -- USE

GLAUCOMA

MOA -- STABLE ANALOG OF PGF-2a

PHARM -- INC UVEOSCLERAL OUTFLOW

THER -- LATANO LOWERS IOP BY 20-25%. BIMATO INC LENGTH/THICKNESS OF EYELASHES

"EPIN BUYs, MAN BETA PILO APRON LANTERNS that TIM ACE's ECHO ISO DORABLE!"

• EPINEPHRINE
• BI-MATO-PROST
• MANNITOL
• BETAX-OLOL
• PILOCARPINE
• APRA-CLONI-DINE
• LAN-TANO-PROST
• TIM-OLOL (b-adren antagonist)
• ACETA-ZOLA-MIDE
• ECHO-THIO-PHATE (op AChase inh also)
• ISO-FLUO-PHATE (DFP)
• DOR-ZOLA-MIDE

GLAUCOMA -- ACUTE ATTACK OF ANGLE CLOSURE

MOA -- OSMOTIC DIURETIC AGENTS

PHARM -- HYPEROSMOLAR ECF CAUSES CELLULAR DEHYDRATION --> FALL IN IOP

THERA -- ACUTE ATTACKS OF ANGLE-CLOSURE GLAUCOMA

COMBINE GLAUCOMA DRUGS WITH DIFF MOA FOR COMBO EFFECT:

MANN, ACETA, PILO

"EPIN BUYs, MAN BETA PILO APRON LANTERNS that TIM ACE's ECHO ISO DORABLE!"

GLAUCOMA & b-BLOCKER

• BETAX MOA
• --SELECTIVE b1-ANTAGONIST (CARDIO SELECTIVE AT LOW DOSE).

--b-BLOCKERS HAVE NO EFFECT ON PUPIL SIZE OR VISUAL ACCOMODATION

PHARM -- DEC PROD OF AQ HUM BY UNKNOWN MECH (20-30%)

THERA -- SYSTEMIC ABS --> TIMOLOL BRONCH-CONSTRICT b2 & BRADYCARDIA

"EPIN BUYs, MAN BETA PILO APRON LANTERNS that TIM ACE's ECHO ISO DORABLE!"

GLAUCOMA

MOA -- SELECTIVE a2 AGONIST

PHARM -- SELECTIVE a2 STIM --> DEC PROD OF AQ HUM

THERA -- PREVENTS POST-SURGICAL OCULAR HYPERTENSION AFTER LASER TRABECULOPLASTY

"EPIN BUYs, MAN BETA PILO APRON LANTERNS that TIM ACE's ECHO ISO DORABLE!"

GLAUCOMA

MOA -- GIVEN P.O. & TOPICAL.

CARBONIC ANHYDRASE INH (DORZOLAMIDE TOO)

*ALSO INC URINE pH!

• PHARM -- DEC PROD OF AQ HUM.
• CARBONIC ANHYD IN CILIARY BODIES PROD AQ HUM --> INH CARB ANHYD STOPS AQ HUM PROD

THERA -- GLAUCOMA

• ADVERSE ACETA -- DON'T GIVE P.O. IF:
• HEADACHE
• DEC LIBIDO
• METALLIC TASTE
• KIDNEY STONES
• URINARY FREQ

"EPIN BUYs, MAN BETA PILO APRON LANTERNS that TIM ACE's ECHO ISO DORABLE!"

GLAUCOMA

MOA -- TOPICAL OP AChase INH

PHARM -- LOWER IOP BY INC AMT OF ACh AVAILABLE TO CONTRACT CILIARY MUSC

THERA -- GLAUCOMA (TOPICAL Rx)

AVERSIVE -- LAST RESORT DRUG IN Pt WHEN OTHER Rx FAIL --> CONTRACTS & GENERAL TOXICITY

"EPIN BUYs, MAN BETA PILO APRON LANTERNS that TIM ACE's ECHO ISO DORABLE!"

GLAUCOMA (SAME AS ECHOTHIOPHATE)

MOA -- TOPICAL OP CHOLase INH

PHARM -- LOWER IOP BY INC AMT OF ACh AVAILABLE TO CONTRACT CILIARY MUSC

THERA -- GLAUCOMA (TOPICAL Rx)

AVERSIVE -- LAST RESORT DRUG IN Pt WHEN OTHER Rx FAIL --> CONTRACTS & GENERAL TOXICITY

"EPIN BUYs, MAN BETA PILO APRON LANTERNS that TIM ACE's ECHO ISO DORABLE!"

GLAUCOMA

• MOA -- TOPICAL. CARBONIC ANHYD INH
• (ACETAZOLAMIDE TOO)

PHARM -- TOPICAL DEC PROD OF AQ HUM

THERA -- GLAUCOMA. LOWER IOP BY 10-20%

"EPIN BUYs, MAN BETA PILO APRON LANTERNS that TIM ACE's ECHO ISO DORABLE!"

"EPIN BUYs, MAN BETA PILO APRON LANTERNS that TIM ACE's ECHO ISO DORABLE!"

• EPINEPHRINE
• BI-MATO-PROST
• MANNITOL
• BETAX-OLOL
• PILOCARPINE
• APRA-CLONI-DINE
• LAN-TANO-PROST
• TIM-OLOL (b-adren antagonist)
• ACETA-ZOLA-MIDE
• ECHO-THIO-PHATE (op AChase inh also)
• ISO-FLUO-PHATE (DFP)
• DOR-ZOLA-MIDE
• ----------------

• FORMATION:
• b-ADREN ANTAGONISTS
• CARB ANHYD
• a2-ADREN AGONISTS

• OUTFLOW:
• PGF-2a
• a1-ADREN AGONIST
• PILO, ISO

MEMANTINE

ALZ Tx

GLUTAMATE NMDA ANTAGONIST -- EXCESS NMDA STIM --> Na + Ca ENTRY --> EXCITOTOXICITY AND NEURONAL CELL DEATH

CARBAMATE AChase INH (REVERSIBLE)

MOA -- 3*AMINE; FREELY ENTERS CNS

NON-COMP SLOWLY REVERSIBLE INH OF AChase

--CARBAMOYLATION RATHER THAN NL ACETYLATION OF ACTIVE SITE OF AChase

HYDROL OF CARBAMOYL ENZ OCCURS SPONT W/ t1/2 OF 15-30 min

NO DIRECT EFFECT AT ACh RECEPTORS

PHARM -- INH ACTION OF AChase --> ACh WILL STAY LONGER

THERA -- NOT USED BC SIDE EFFECTS. ALZ BUT NEWER DRUGS USED (DONEPEZIL = ARICEPT)

OVERDOSE & POISONING W/ ANTI-CHOL AGENTS

ADVERSE -- NUMEROUS CNS EFFECTS

CARBAMATE AChase INH (REVERSIBLE)

MOA -- CARBAMATE COMPOUND

PHARM -- INH ACTION OF AChase

THERA -- DOC FOR ALZ BC MORE SELECTIVE OF CNS

• DECREASES:
• APATHY
• ANX
• HALLUCINATIONS
• BEH PROBS

• ADVERSE -- PNS STIM:
• DIARRHEA
• MUSC CRAMPS
• FATIGUE / BRADYCARDIA
• INSOMNIA
• ANOREXIA
• N/V

CARBAMATE AChase INH (REVERSIBLE)

• MOA -- 4*AMINE
• DIRECT AGONIST AT N2 RECEPTOR

INH AChase BY CARBAMOYLATION AT ALL PERIPH SITES

• PHARM -- INH OF AChase
• INC THE CONC OF ACh AT N2 OF NMJ

INC CONC OF ACh AT M SITES (ex HEART, SALIVARY GLAND, etc)

• THERA -- POST-OP PATALYTIC ILEUS
• ATONIA OF GI & GU

MYASTHENIA GRAVIS

REVERSAL OF MUSC PARALYSIS CAUSED BY COMP NEUROMUSC BLOCKING AGENTS (d-TUBOCURARE)

ADVERSE -- NO CNS EFFECTS. INC CONC OF ACh AT M SITES (HEART, SAL, etc)

ATROPINE GIVEN TO PREVENT THESE UNWANTED EFFECTS

CARBAMATE AChase INH (REVERSIBLE)

MOA -- LIKE NEOSTIG. 4*AMINE

DIRECT AGONIST AT N2 RECEPTOR

INH AChase BY CARBAMOYLATION AT ALL PERIPH SITES

PHARM -- INH ACTION OF AChase

• THERA --
• LONG TERM p.o. DOSING Rx MYASTHENIA GRAVIS

MILD OCULAR Sx (+ CORTICOSTEROIDS)

MILD/MOD GENERAL Sx (+ THYMECTOMY)

MOD/SEVERE GENERAL Sx (+ AZATHIOPRINE IMMUNOSUPPRESSANT)

CARBAMATE AChase INH (REVERSIBLE)

USED TO Dx MYASTHENIA GRAVIS

GIVEN IM OR IV BC VERY SHORT t1/2

• MOA -- 4*AMINE
• INH AChase AT ALL PERIPH CHOL NERVE JUNCTION BUT MOST ACTION AT NMJ FROM DIRECT STIM OF CHOL N2 RECEPTORS

PHARM -- ?

THERA --MYASTHENIA GRAVIS

• UNDER Rx --> MYASTHENIC CRISIS
• OVER Rx --> CHOLINERGIC CRISIS

• BETTER W/ EDRO --> MYASTHENIC
• WORSE W/ EDRO --> CHOLINERGIC

COMBO IV ATROPINE --> REVERSE COMP NEUROMUSC BLOCKADE BY DRUGS (ex d-TUBOCURARINE)

ADVERSE -- NO CNS EFFECTS

EXCESSIVE SALIVATION

RHINITIS

BRADYCARDIA

BRONCHOSPASM

BOWEL CRAMPING

DIARRHEA / VOM

URINARY INCONTINENCE

CARBAMATE INSECTICIDE (REVERSIBLE)

AChase INH

MOA -- CARBAMATE INSECTICIDE USED AROUND HOUSE (LIPID SOLUBLE)

PHARM -- GROUPED W/ OP AChase INH BC POISINING W/ CARBARYL --> SIMILAR EFFECTS OF OP

THERA -- CARBARYL POISONING ONLY W/ ATROPINE (3*M ANTAGONIST)

ADVERSIVE -- CNS EFFECTS!!!

INDIRECT REVERSIBLE INH OF AChase (CARBAMATE)

EXELON -- PATCH

INDIRECT REVERSIBLE INH OF AChase (CARBAMATE)

MEMANTINE (NMDA)

PHYSOSTIGMINE (CARB)

TACRINE (CARB)

DONEPEZIL (DOC -- CARB)

GALANTAMINE (CARB)

RIVASTIGMINE (CARB -- EXELON PATCH)

DON RIVA'S GAL PHYS ED a NEW CAR-BAR-ATOR PIE

**NEGATED BY DRUGS THAT BLOCK CENTRAL M RECEPTORS:

ANTI-CHOL INCLUDING OLDER HISTAMINES DIPHENHYDRAMINE,

URGE INCONT TOLTERODINE

TRICYC ANTI-DEP IMIPRAMINE

----------------------------------------------

• DONEPEZIL
• RIVASTIGMINE
• GALANTAMINE
• PHYSOSTIGMINE
• EDROPHONIUM
• a
• NEOSTIGMINE
• CARBARYL
• PYRIDOSTIGMINE

OP AChase INH (DIP ME)

MOA -- INSEC LAWN & GARDEN

PHOS AChase ACTIVE SITE

SPONT RATE OF HYDROL OF PHOS ENZ IS SUPER LOW

OP AChase INH (IRREVERS) (DIP ME)

MOA -- GIVEN LOCALLY, TOPICAL

PHARM -- LOWER IOP BY INC AMT OF ACh AVAILABLE TO CONTACT CILIARY MUSC

THERA -- GLAUCOMA

ADVERSE -- LAST RESORT Rx --> CATARACTS & GENERAL TOXICITY

SAME AS ECHOTHIOPHATE

OP AChase INH (IRREVERS) "DIP ME"

MOA -- GIVEN LOCALLY, TOPICAL

PHARM -- LOWER IOP BY INC AMT OF ACh AVAILABLE TO CONTACT CILIARY MUSC

THERA -- GLAUCOMA

ADVERSE -- LAST RESORT Rx --> CATARACTS & GENERAL TOXICITY

SAME AS ISOFLUOPHATE (DFP)

OP AChase INH (IRREVERS) "DIP ME"

MOA -- INSECTICIDE CONVERTED TO ACTIVE METABOLITE PARAOXON BY CYP450

ADVERSE -- ACCIDENTAL POISONING / DEATH

OP AChase INH (IRREVERS) (DIP ME)

MOA -- INSECTICIDE, MAMMALS & BIRDS HAVE PLASMA CARBOXYESTERASES WHICH DESTROY MALATHION

THERA -- SPRAY FOR MOSQ. DERM PREP TO KILL HEAD LICE

ADVERSE -- MUCH SAFER THAN PARATHION

• DIM-PYL-ATE
• ISO-FLUO-PHATE
• PARATHION
• MALATHION
• ECHO-THIO-PHATE (glaucoma also)

Tx OF OP POISONING

PRALI-DOX-IME (2-PAM)

MOA -- 4*PRALI DOCKS THE ORGANOPHOS TO TAKE IT AWAY FROM AChase TO ALLOW NORMAL FUNCTION

GREATLY INC RATE OF HYDROLYSIS OF PHOSED ENZ, ESP AT NMJ

LESS EFFECTIVE IF "AGING" OF PHOSED AChase HAS OCCURED (NEED Rx IMMEDIATELY)

NOT USED FOR CARBAMATE POISONING BC WILL NOT INC RATE OF HYDROL OF CARBAMOYLATED AChase

ADVERSE -- DOSN'T ENTER CNS. PROB IF SEVERE CNS EFFECTS

3* M ANTAGONIST

PHARM -- VARIOUS SENSITIVITIES PER ORGAN

• SMALL DOSE --> --> --> LARGE DOSE
• GLANDS -> HRT -> BWL, BLADR -> EYE

AT THERA DOSE --> NO CNS EFFECTS (UNLIKE SCOPOLAMINE)

THERA -- PERIOPERATIVE USE (ALSO GLYCOPYRROLATE)

DEC PROD OF SALIV/PULM SECRETIONS

• COUNTERACT BRADYCARDIA FROM:
• OCULAR PRESSURE
• VISCERAL TRACTION
• CAROTID SINUS STIM
• INJ OF MULTI DOSES OF SUCC

OP POISONING (REV CNS/PNS TOX)

IV ATROPINE + EDRO --> REV COMPETITIVE NEUROMUSC BLOCKADE

CONJUNCTIVAL "SAC" SCOPE, CYCLOPENT, & ATROPINE --> MYDRIASIS & CYCLOPLEGIA TO DET REFRACTIVE ERROR OF LENS & CATARACT SRGY

• ADVERSE -- TOXICITY
• RED AS A BEET
• MAD AS A HATTER
• DRY AS A BONE
• HOT AS A PISTOL

• Tx FOR OVERDOSE:
• GASTRIC LAVAGE
• RESP & CIRC SUPPORT
• SPONGE BATH
• FOLEY CATH
• DARK ROOM
• BENZO FOR SEDATION

• CNS Sx:
• NERVOUSNESS
• EXCITIATION
• CONF
• HALL
• WEAKNESS
• GIDDINESS
• MUSC
• INCOORD
• HYPERTENSE
• MANIA

• PNS:
• DRY MOUTH / THIRST
• HOT, DRY, FLUSHED SKIN
• MYDRIASIS / BLURRED VISION
• TACHYCARDIA

3* M ANTAGONIST

BELLADONNA ALKALOIDS

MIX ATRO + EDRO OR GLYCOPYR + NEOSTIG GIVEN IV

ATRO + GLYCOPYR PREVENT UNWANTED M STIM RESULTING FROM AChase INH AT PARASYMP SITES

MOA -- LITTLE EFFECT ON HR

REVERSE EFFECTS FROM d-TUBOCURARE

• PHARM --
• IRIS - RELAX SPHINC MUSC

CILIARY MUSC - RELAX FOR FAR VISION

ATRIA & VENT - INC dp/dt

SA NODE - INC HR

ATRIA - INC CONDUCTION VELOCITY

AV NODE - INC CONDUCTION VELOCITY & AUTOMATICITY. DEC APD & ERP

GI - DEC MOT & TONE

GU, DETRUSOR, BRONCH - RELAX

SALIVERY, LACRIMAL, SWEAT, BRONCH, GASTRIC GLANDS --> DEC SECRETION

THERA -- INDUCE MYDRIASIS & CYCLOLEGIA BY "SAC": SCOPE, ATRO, CYCLOPENT

DOC (ALSO ATROPINE) --> RELAX SPHINC & CIL MUSC --> DEC PAIN

MOTION SICKNESS (VESTIB NUC & RETIC FORMATION) -- TRANSDERMAL PATCH

AMNESIA esp DURING PARTUITION

ADVERSE -- CNS EFFECTS AT THERA DOSES (UNLIKE ATROPINE)

• SOMNOLENCE
• AMNESIA
• REDUCED REM SLEEP
• ANT-GRADE AMNESIA (WORSE W/ ETOH)

3* M ANTAGONIST

• PHARM --
• IRIS - RELAX SPHINC MUSC

DOC FOR REFRACTIVE ERROR -- SHORT DURATION

CILIARY MUSC - RELAX FOR FAR VISION. CAUSES "PUPLILARY BLOCK"

ATRIA & VENT - INC dp/dt

SA NODE - INC HR

ATRIA - INC CONDUCTION VELOCITY

AV NODE - INC CONDUCTION VELOCITY & AUTOMATICITY. DEC APD & ERP

GI - DEC MOT & TONE

GU, DETRUSOR, BRONCH - RELAX

SALIVERY, LACRIMAL, SWEAT, BRONCH, GASTRIC GLANDS --> DEC SECRETION

THERA -- DOC "SAC" MYDRIASIS & CYCLOPLEGIA

3*M ANTAGONIST

MOA -- AT EYE. "SUNGLASSES IN TROPICS"

PHARM -- SAME AS ATROPINE / SCOPE

THERA -- DOC FOR MYDRIASIS FOR FUNDOSCOPIC EXAM OF RETINA & OPTIC DISK (SHORT t1/2)

3*M ANTAGONIST

MOA -- AT CENTRAL M RECEPTOR

PHARM -- SAME AS ATROPINE & SCOPE

THERA -- PARKINSON'S

3*M ANTAGONIST

MOA -- AT CENTRAL M RECEPTOR

PHARM -- SAME AT ATROPINE & SCOPE

THERA -- PARKINSON'S

3*M ANTAGONIST

MOA -- AT GI TRACT

PHARM -- SAME AS ATROPINE & SCOPE

THERA -- PREVENT BOWEL SPASM & DEC PAIN W/ IBS

3*M ANTAGONIST

MOA -- AT GI TRACT

PHARM -- SAME AS ATROPINE & SCOPE

THERA -- PREVENT BOWEL SPASM & DEC PAIN W/ IBS

3*M₃ ANTAGONIST

URGE INCONTINENCE

"DOTTS"

MOA -- DIRECT ANTISPASMODIC EFFECT AT DETRUSOR MUSCLE

PHARM -- SAME AS ATROPINE & SCOPE

THERA -- URGE INCONTINENCE (OAB)

ADVERSE -- DROWSINESS, SOMNOLENCE, DIZZINESS

3*M3 ANTAGONIST

"DOTTS"

MOA -- ?

PHARM -- SAME AS ATROPINE & SCOPE

THERA -- URGE INCONTINENCE (OAB)

ADVERSE -- DRY MOUTH, BLURRED VISION, CONSTIP & SOMNOLENCE

3*M3 ANTAGONIST

"DOTTS"

MOA -- SELECTIVE M3 ANTAGONIST (DETRUSOR)

PHARM -- SAME AS ATROPINE & SCOPE

THERA -- URGE INCONTINENCE (OAB)

ADVERSE -- FEWER CNS EFFECTS.

LESS DRY MOUTH THAN OXYBUTIN, TOLTERIDINE TROSPIUM?

3*M3 ANTAGONIST

"DOTTS"

MOA -- SELECTIVE M3 ANTAGONIST

PHARM -- SAME AS ATROPINE & SCOPE

THERA -- URGE INCONTINENCE (OAB)

ADVERSE -- NO CNS OR CV EFFECTS!

LESS DRY MOUTH THAN OXYBUTIN, TOLTERIDINE, TROSPIUM

• VIRUSES:
• CAUSE HYPER-SECTRECTION OF UPPER RESP WHICH IS DEC BY M RECEPTOR ANTAGONISTS

RELIEF BY ANTI-HIST FOUND IN OTC "COLD" MEDS (ex CHOLRPHENIRAMINE) RESULTS FROM THEIR ANTI-M RATHER THAN ANTI-HIST PROPERTIES

• COPD:
• BRONCHITIS + EMPHISEMA.

TIOTROPIUM AND IPRATROPIUM IMPROVES VENT BY RELAXING BRONCH SMOOTH MUSC (M ANTAGONIST)

GIVE N2 AGONIST NEOSTIGMINE AND PYRIDOSTIGMINE WHICH ALSO BLOCK AChase.

EFFECT NMJ AND PERIPH SITES --> SAL, RHINITIS, BRADYCARDIA, BRONCHSPASM, BOWEL CRAMP, DIARRHEA, AND URINARY INCONT

GIVE M ANTAGONIST ATROPINE TO PREVENT S/E

LACK OF DA STIM AND RESULTANT INC M STIM IN NIGROSTRIATAL TRACK OF BRAIN

INH OF AChase WHICH ENTER CNS LIKE PHYSOSTIGMINE WORSEN Sx

• "BBAT!" -- BLOCK CENTRAL M RECEPTORS
• 1) BENZTROPINE (COGENTIN)
• 2) BIPERIDEN (AKINETON)
• 3) ATROPINE
• 4) TRIHEXYPHENIDYL (ARTANE)
• 5) DIPHENHYDRAMINE (ANTI-HIST BENADRYL)

MOST EFFECTIVE AGAINST TREMOR, SOME AGAINTS RIGIDITY, AND LITTLE AGAINST AKINESIA/DYSKINESIA

S/E -- CYCLOPLEGIA, CONSTIP, URINARY RET, DRY MOUTH

M ANTAGONISTS

• RED AS A BEET
• MAD AS A HATTER
• DRY AS A BONE
• HOT AS A PISTOL

• Tx FOR OVERDOSE:
• GASTRIC LAVAGE
• RESP & CIRC SUPPORT
• SPONGE BATH
• FOLEY CATH
• DARK ROOM
• BENZO FOR SEDATION

• CNS Sx:
• NERVOUSNESS
• EXCITIATION
• CONF
• HALL
• WEAKNESS
• GIDDINESS
• MUSC INCOORD
• HYPERTENSE
• MANIA

• PNS:
• DRY MOUTH / THIRST
• HOT, DRY, FLUSHED SKIN
• MYDRIASIS / BLURRED VISION
• TACHYCARDIA
• URINE RET
• ABSENT BOWEL SOUNDS

CAUSED BY EXCESSIVE M RECEPTORS IN VEST NUC AND RET FORMATION

SCOPOLAMINE (PATCH) -- CAUSES ANTEROGRADE AMNESIA! ACCENTUATED BY ETHANOL

DIPHENHYDRAMINE (DRAMAMINE)

BENADRYL

3*M ANTAGONIST

MOA -- AT CENTRAL M RECEPTORS & ANTIHIST

PHARM -- SAME AS ATROPINE & SCOPE

THERA -- CAN BE USED FOR PARKINSON'S

"DOTTS"

3*M ANTAGONISTS

• DARIFENACIN
• OXYBUTYNIN
• TOLTERODINE
• TROSPIUM (4*M)
• SOLIFENACIN

"ABC 3D TRIPLE-T HOSS"

• ATROPINE
• BENZTROPINE
• CYCLO-PENTO-LATE

• DI-CYCLOMINE
• DI-PHEN-HYDRA-MINE
• DAR-IDEN-ACIN

• TRI-HEXY-PHEN-IDYL
• TOL-TERO-DINE
• TROPIC-AMIDE

• HY-OSCY-AMINE
• OXY-BUTY-NIN
• SCOPOLAMINE
• SOLI-FEN-ACIN

4*M ANTAGONIST

PHARM -- SAME AS 3*M. DOES NOT ENTER CNS!

4*M ANTAGONIST

PHARM -- SAME AS 3*M. DOES NOT ENTER CNS

4*M ANTAGONIST

PHARM -- SAME AS 3*M ANT. DOES NOT ENTER CNS

4*M ANTAGONIST

"DOTTS" OVER-ACTIVE BLADDER DRUG

MOA -- NON-SELECTIVE MUSC ANTAGONIST

THERA -- URGE INCONTINENCE (OAB)

ADVERSE -- PERIPH ANTI-M Sx

4*M ANTAGONIST

4*M ANTAGONIST

MOA -- ALSO PREVENTS UNWANTED M STIM RESULTING FROM AChase INH AT SITES INNERVATED BY PNS. LIKE ATROPINE

PHARM -- SAME AS 3*M ANT. DOES NOT ENTER CNS

THERA -- PERI-OP USE

DEC PROD OF SALIV / PULM SECRETIONS

• COUNTER BRADYCARDIA CAUSED BY:
• OCULAR PRESSURE
• VISCERAL TRACTION
• CAROTID SINUS STIM
• INJ OF MULTI DOSES OF SUCC

COMBO IV GLYCOPYRROLATE + NEOSTIG: REVERSE COMPETITIVE NEUROMUSC BLOCKADE CAUSED BY DRUGS (ex d-TUBOCURARINE)

4*M ANTAGONIST

• N-METHYL-ATROPINE
• METH-SCOPOLAMINE
• TIO-TROP-IUM
• IPRA-TROP-IUM
• GLYCO-PYROL-ATE

N RECEPTOR AGONIST

MOA -- DIRECT STIM OF PERIPH N1 & N2 CHOL RECEPTORS

BENZOPYRENE IN CIG SMOKE INDUCES HEP CYP450

CNS: DIRECT STIM N1 --> RELEASES NA & DA. MAY INC/DEC RELEASE OF ACh

*ADDICTION -- DA RELEASE FROM NUC ACCUMB

• PHARM -- SMOKING:
• ACUTE CNS EFFECTS:
• INC ALERTING PATTERN ON EEG,

FAC OF ATTENTION & MEM,

DEC AGGRESSION,

DEC APPETITE,

DEC SKEL MUSC TONE & DTR VIA STIM OF RENSHAW INTERNEURONS,

INC PHYSIO TREMOR

• ACUTE CARDIO EFFECTS:
• INC SBP, DBP, PP, HR VIA STIM OF SYMP GANG & AORTIC CHEMORECEPTORS

TOLERANCE DEVS RAPIDLY --> LONG-TERM EFFECTS ON BP & HR ARE SLIGHT

DEC SKIN TEMP & DIGITAL BLOOD FLOW

• SNUFF:
• CARDIO -- INC CV DISEASE esp HYPERTNSN, INC PLASMA INSULIN & FIBRINOGEN. SNUFF FEWER CNS EFFECTS THAN SMOKING

• ORAL CANCER
• -ORAL LEUKOPLAKIA
• -LOCAL PERIODONTAL DISEASE (GUMS)
• -SMOKELESS TOB DOES NOT INC RISK OF ORAL/DIGEST CANCER, BUT CIGS & ALC --> HI RISK; PROPORTIONAL TO USE
• ADVERSE -- VERY H20 SOLUBLE --> PASSES QUICK FROM BLOOD TO BRAIN. RAPIDLY ABS FROM BUCCAL, RESP, & SKIN

• **ACUTE TOX:
• ORAL INGESTION --> VOMITING INDUCED BY CNS EFFECTS OF NICOTINE --> ELIMS MOST OF TOBACCO & LIMITS TOX

INSECTICIDES, N/V ABDOM CRAMPING & DIARRHEA, SAL & SWEAT, HEADACH, DIZZY, DISORIENTATION, MUSC WEAK, BP FALLS, HR IRREG, SHALLOW BREATHING, CARDIO COLLAPSE & CONVULSIONS OFTEN PRECEDE DEATH FROM RESP FAILURE

• **CHRONIC TOX:
• INC LDL AND TG, LOWER HDL

DEC PGI2 AND NO --> CONSTRIC ARTERIOLS & PLATELET AGGREGATION

NEUTROPHIL ACTIVATION AND AGG --> INFLAM DAMAGE

CARDIAC DYSRHYTHMIA VIA CO

CANCER --> BENZOPRENES DAMAGE p53 TUMORE SUPPRESSOR

COPD & ASTHMA (REDUCE CILIARY ACTIVITY)

SMOKER'S FACE: WRINKLING

TREATMENT -- GASTRIC LAVAGE OR DRUG-INDUCED EMESIS, INTUBATION & ARTIFICIAL RESP, DRUG THERA FOR SHOCK & CONVULSIONS

N AGONIST

• MOA --
• GIVEN IV

INITIAL SINGLE CONTRACTION OF SKEL MUSC FOLLOWED BY 3-5 MINS OF FLACCID PARALYSIS

PHARM -- FLACCID PARALYSIS

MOST OF IV DOSE DEGRADED BY PLASMA CHOLase BEFORE REACHING NMJ

NOT METABOLIZED BY TISSUE AChase

PARTIAL REPOL POSS WHILE SUCC STILL PRESENT BUT NMJ BLOCKADE PERSISTS

NMJ BLOCKADE IS TERMINATED BY DRUG DIFFUSING AWAY

NICOTINE SUCCS!

• NICOTINE
• SUCCINYL-CHOLINE (cholinergic also)

N₁-RECEPTOR ANTAGONISTS

TRIMETHAPHAN -- CONTROLLED HYPER TENSION DURING HEAD & NECK SURGERY. CAN ALSO CAUSE HIST RELEASE --> FURTHER VASODILATION

MECAMYLAMINE -- FOR AUTONOMIC HYPER-REFLEXIA -- CONTROLS BY PREVENTING PAROXYSMAL INC IN SYMP ACTIVITY

N1 ANTAGONIST

GANGLIONIC BLOCKING DRUG

MOA -- GIVEN P.O.

COMP BLOCKADE N1-CHOLINERGIC RECEPTORS IN AUTONOMIC GANGLIA

-->PREVENTS ALL SYMP & PARASYMP NERVE ACTIVITY FROM REACHING THE EFFECTOR ORGAN

PHARM -- KNOW IF SYMP OR PARASYMP IS DOMINANT IN EACH ORGAN

BLOCKADE OF SYMP:

ARTERIODILATION --> DEC TPRVENODILATION --> DEC PRELOAD

DEC CARDIAC dp/dt

DEC CO --> HYPOTENSION (DEC TPR ALSO)

DEC SWEATING

IMPOTENCE

• BLOCKADE OF PARA GANGLIA:
• TACHYCARDIA

MYDRIASIS & CYCLOPLEGIA

DEC SAL & LACRIM

DEC GI SEC, MOT, TONE

DEC GASTRIC ACID SEC

DEC RELEASE OF PANC ENZ & BILE

CONSTIP & URINARY RETENSION

IMPOTENCE

THERA -- PROD CONTROLLED HYPOTENSION DURING HEAD & NECK SURGERY

CAUSE HIST RELEASE --> FURTHER VASODILATION

AUTONOMIC HYPERREFLEXIA IN pt W/ HI LEVEL SPINAL INJURIES (T5 & ABOVE)

• Sx:
• HYPERTENSION --> POSS MI, HEMORR STROKE & RENAL HEMORR

BRADYCARDIA (2* TO HYPERTN)

SWEATING

PILOERECTION

*CONTROLS Sx BY PREVENTING PAROXYSMAL INC IN SYMP (MECAMYLAMINE)

N1 ANTAGONIST

GANGLIONIC BLOCKING DRUG

MOA -- GIVEN IV

COMP BLOCKADE N1-CHOLINERGIC RECEPTORS IN AUTONOMIC GANGLIA -->

PREVENTS ALL SYMP & PARASYMP NERVE ACTIVITY FROM REACHING THE EFFECTOR ORGAN

PHARM -- KNOW IF SYMP OR PARASYMP IS DOMINANT IN EACH ORGAN

• BLOCKADE OF SYMP:
• ARTERIODILATION --> DEC TPR

VENODILATION --> DEC PRELOAD

DEC CARDIAC dp/dt

DEC CO --> HYPOTENSION (DEC TPR ALSO)

DEC SWEATING

IMPOTENCE

• BLOCKADE OF PARA GANGLIA:
• TACHYCARDIA

MYDRIASIS & CYCLOPLEGIA

DEC SAL & LACRIM

DEC GI SEC, MOT, TONE

DEC GASTRIC ACID SEC

DEC RELEASE OF PANC ENZ & BILE

CONSTIP & URINARY RETENSION

IMPOTENCE

THERA -- PROD CONTROLLED HYPOTENSION DURING HEAD & NECK SURGERY

CAUSE HIST RELEASE --> FURTHER VASODILATION

AUTONOMIC HYPERREFLEXIA IN pt W/ HI LEVEL SPINAL INJURIES (T5 & ABOVE)

• Sx:
• HYPERTENSION --> POSS MI, HEMMORRHAGIC STROKE & RENAL HEMORR

BRADYCARDIA (2* TO HYPERTN)

SWEATING

PILOERECTION

*CONTROLS Sx BY PREVENTING PAROXYSMAL INC IN SYMP (MECAMYLAMINE)

DIRECT ADRENERGIC AGONIST

LOCAL (NOT A CIRC HORMONE)

IN PLASMA, CLEARED BY LIVER (PHASE I - COMT, MAO & PHASE II (CONJ) & LUNGS

MOA -- a & b AGONIST

a > b1 > B2

VASOCONSTRICT --> ARTERIOLES IN SKIN, KID, & GI TRACT CONTAIN PRIMARILY a RECEPTORS

VASODILATE --> ARTERIOLES IN LIVER & SKEL MUSC CONTAIN PRIMARILY b2 RECEPTORS

PHARM -- ONLY b EFFECTS ARE INC CARDIAC dp/dt, INC VENOUS RETURN VIA DEC HEP VENOUS RESISTANCE

ENDOG NE RELEASE --> DIRECT b1 STIM --> INC HR

vs.

NE GIVEN IV --> INC BP --> BAROREFLEX MEDIATED DEC HR

MOSTLY a EFFECTS:

DIRECT

ARTERIOLAR VASOCONSTRICTION (a1) --> INC TPR --> INC DBP

DEC BLOOD FLOW TO CUTANEOUS, KID, GI, & SKEL MUSC

INDIRECT

INC DBP --> BAROREFLEX MEDIATED BRADYCARDIA VIA INC VAGAL TONE

SV UNCHANGED (STARLING) EVEN THOUGH INC AFTERLOAD

DEC HR --> INC SV DESPITE NO CHANGE OR SLIGHT DEC IN CO

INC DBP PREVENTS INC SV & CO WHICH OCCURS WHEN dp/dp & VENOUS RETURN INC

THERA -- DIRECT AGONIST: VASOPRESSOR AGENT WHEN CO & TISSUE PERFUSION ARE RELATIVELY NORMAL (ex SPINAL SHOCK)

VASOCONSTRICTOR AGENT W/ LOCAL ANESTHETIC DRUGS

ADVERSE -- CARDIAC ARRHYTHMIAS (b)

ANGINA IN pt W/ CAD (b)

CEREBROVASC HEMORR (INC BP)

PULM EDEMA (INC TPR)

TREMOR (b2)

DIRECT ADRENERGIC AGONIST

CIRCULATING HORMONE

MET BY PHASE I - COMT, MAO & PHASE II IN LIVER

NOT CLEARED BY LUNGS

SEC IN VENA CAVA --> BYPASS LIVER IN ROUTE TO HRT

FIGHT OR FLIGHT

MOA -- a & b AGONIST

b2 > b1 > a

VASOCONSTRICT --> ARTERIOLES IN SKIN, KID & GI CONTAIN PRIMARILY a RECEPTORS

VASODILATE --> ARTERIOLES IN LIVER & SKEL MUSC CONTAIN PRIMARILY b2

PHARM --

SMALL IV DOSE: PHYSIO PLASMA LEVELS

DEC TPR --> SLIGHT DEC DBP

NET VASODIL VIA b2 STIM (LIVER, SKEL MUSC > a --> KID, GI

LARGE IV DOSE:

INC TPR --> INC DBP

NET VASOCONST VIA a STIM

• b1 STIM --> INC dp/dt --> INC PP
• ------------------

BOTH SMALL & LARGE IV DOSES:

• INC CARDIAC dp/dt
• INC HR
• INC SV --> INC PP & SBP
• DEC BLOOD FLOW TO KID, GI, SKIN

• INC HRT WORK (O2 DEMAND) --> INC COR BLOOD FLOW
• ------------------------

GIVEN S.C. TO Rx ANAPHYLACTIC rxn:

• INC PP
• INC SBP
• INC DBP

Dec DBP to produce max incr in SV/CO for incr tissue perfusion w/o incr BP (DBP falls)

Incr blood flow to lungs, liver & brain

THERA -- DOC FOR ANAPHYL rxn: REVERSE BRONCH-CONST & LARYNG EDEMA

DOC PRIAPISM INJECTION OF DILUTE SOLUTION INTO CORPORA CAVERNOSA --> a STIM --> CONTRACTS SMOOTH MUSC

BRONCH-DIL IN pt W. ASTHMA & COPD

TOPICAL: LOWERS IOP BY INC OUTFLOW OF AQ HUM (a1)

VASOCONST AGENT W/ LOCAL ANESTHETIC DRUGS. PREVENTS ANESTH FROM FLOWING AWAY. PREVENTS BLEEDING

USED AS + INOTROPIC & CHRONOTROPIC AGENT IN CARDIAC ARREST pts (1/3 SAVED W/ EPI; 2/3 W/ DC COUNTERSHOCK

ADVERSE -- CARDIAC ARRHYTHMIAS (b)

ANGINA IN pts W/ CAD (b)

CEREBROVASC HEMORR (INC BP)

PULM EDEMA (INC TPR)

TREMOR (b2)

ANX

ADRENERGIC AGONIST

STIM IS DOSE DEPENDENT (D1 > b1 > a1)

• MOA --
• SMALL DOSE (0.5 - 2)
• D1 -- DILATE RENAL AFFERENT ARTERIOLS --> INC RBF

--> INC GFR & Na SEC VIA DEC IN FILT FRAC (HEMODYNAMIC DIURESIS)

SMALL DEC OR NO CHANGE IN DBP FROM DEC RENAL VASC RESISTANCE

• MEDIUM DOSE:
• D1 (RENAL) & b1 (HRT) STIM --> INC dp/dt w/ LITTLE EFFECT ON HR

INC dp/dt --> INC SV/CO --> FURTHER INC RBF & GFR --> FURTHER INC Na/H2O EXCRETION

• LARGE DOSE:
• BEGINS TO STIM a RECs IN RESISTANCE ARTERIOLES & VENULES

INC TPR --> INC AFTERLEAD (DBP) --> DEC SV/CO B/C HRT DAMAGED BY MI (STARLING MECH) DESPITE DA STIM STILL INCREASING dp/dt

VENOCONST --> INC VENO RETURN & CARD FILLING PRESSURE:

INC AFTERLOAD --> (-) EFFECT ON SV SO LV WALL TENSION INC DURING DIASTOLE

--> INC O2 DEMAND --> FURTHER ISCHEMIA TO ALREADY DAMAGED MYOCARDIUM

PREVENT/REVERSE VIA IV OF DOBUTAMINE OR SODIAM NITROPRUSSIDE (VIA RELEASE NO TO DIL ART & VEN (BALANCED VASODILATION))

• PHARM --
• INC CO POST MI

INC BP IN SEPTIC & HEMORRHAGIC SHOCK

INC CO IN CHF WHICH IS REFRACTORY TO DIGOXIN PLUS DIURETICS

INC URINE FLOW IN Rx OF BARBITURATE & SALICYCLATE POISONING

SMALL DOSE USED TO MAINTAIN URINE FLOW IN ICU

• ADVERSE --
• SMALL & MEDIUM: LITTLE EFFECT ON HR

LARGE: TACHYCARDIA --> WORSEN ISCH & POSS PRECIPITATE DYSRHYTHMIAS

ALSO INC TPR

PULMONARY EDEMA (INC TPR)

CARDIAC ARRHYTHMIAS (b)

ANGINA IN PTs W/ CAD (b)

PT POSS DEV TOLERENCE TO (+) INOTROPIC EFFECTS OF DA & DOBUTAMINE (DOWN REG RECs)

ADREN AGONIST

MOA -- SELECTIVE b2

b2 >> b1

PHARM -- RELAX BRONC MUSC

THERA -- ASTHMA COPD, BRONCHITIS

• ADVERSE --
• *Cardiac arrhythmias (β)

*Angina in pts w/ CAD (β)

*Tremor (β2)

ADREN AGONIST

MOA -- SELECTIVE b2

b2 >> b1

PHARM -- RELAX BRONC MUSC

THERA -- ASTHMA COPD, BRONCHITIS

EVENTUALLY DESENSITIZE (RECEPTOR DOWN REG). USE CORTICOSTEROIDS FOR CHRONIC TREATMENT AND ALB FOR ACUTE.

• ADVERSE --
• *Cardiac arrhythmias (β)

*Angina in pts w/ CAD (β)

*Tremor (β2)

ADREN AGONIST

MOA -- a ONLY

THERA -- NASAL DECONG

OXYMETAZOLINE LONGER DURATION OF ACTION > PHENYLEPHRINE

• ADVERSE --
• RENAL & MESENTERIC ISCH (a)

REBOUND NASAL CONG (NASAL VC)

INDIRECT ADREN AGONIST

MOA -- RELEASE OF STORED ENDOGENOUS NE FROM NORADREN FIBERS

• PHARM --
• INC BP TO SOME EXTENT BC RELEASE NE FROM SYMP NERVES WHICH INNERVATE BLD VESS
• --NATURAL CONSTITUENT OF MANY FOODS, esp FERMENTED LIKE CHEESE WINE BEER PICLED HERRING

--EFFECTS ARE CONFINED TO PERIPH BC QUARTERNARY

THERA -- NOT USED AS A THERA AGENT

ADVERSE -- CEREBROVASC HEMORR (INC BP)

MIXED ADREN AGONISTS

STERIOISOMERS OF EPHEDRINE

MOA -- DIRECT AGONIST AT ADRENO

CAUSE RELEASE OF ENDO NE

PHARM -- LIPID SOL AGENT ENTERS CNS

CAUSES LESS CNS EXCITIATION & LESS INC IN HR & BP THAN EPHEDRINE

THERA -- NASAL & SINUS DECONG

DEC NASAL BLD VESS SWELLING & DEC FEELING OF PRESSURE

• ADVERSE --
• --INSOMNIA
• --*cardiac arrhythmias (β)
• --*Angina in pts w/ CAD (β)
• --*Cerebrovasc hemorrhage (incr BP)
• --*Tremor (β2)
• --*Rebound nasal congestion (nasal VC

MIXED ADREN AGONIST

MOA -- DIRECT AGONIST AT b1 & b2

RELEASE OF ENDOG NE --> STIM a&b ADREN RECs

PHARM -- LIPID SOL AGENT --> ENTERS CNS

• DIRECT b STIM:
• --BRONCHDIL IN ASTHMA
• --INC AV COND IN AV BLOCK

• INDIRECT a ACTION:
• --MYDRIASIS
• --INC BP
• --NASAL DECONG

• USED AS PRESSOR AGENT TO REVERSE HYPOTENSE DURING ANESTHESIA
• --BOLUS GIVEN IV INC BP BY 10-20 MMHg IN 60sec
• --INC BP PERSISTES FOR 60 mins

• NE IN BRAIN:
• --CENTRAL EXCITATION, MILDER < AMPHETAMINE

• NET EFFECT:
• --INC BP, HR, CO, AV COND
• --BRONCH-DIL w/ INC FEV1
• --MYDRIASIS
• --INSOMNIA

THERA --

• DIRECT b
• --ASTHMA
• --INC AV COND IN AV BLOCK

• INDIRECT a
• --MYDRIASIS
• --INC BP
• --NASAL DECONG
• --HYPERTENSE DURING ANESTHESIA

--ON PROSCRIBED LIST FOR ATHLETES

ADVERSE --

• DIET DRUG
• --ACUTE PSYCHOTIC REACTION
• --INC HTN
• --INSOMNIA
• --CARDIAC ARRYTHMIA (b)
• --ANGINA IN pt w/ CAD (b)
• --CEREBROVASC HEMORR (INC BP)
• --TREMOR (b2)
• --REBOUND NASAL CONG (NASAL VC)

INDIRECT ADREN AGONIST ("TAP")

MOA -- RELEASE OF STORED NE FROM NORADREN FIBERS

ALSO BLOCKS UPTAKE

PHARM -- INC BP TO SOME EXT BC RELEASE NE FROM SYMP NERVES WHICH INNERVATE BLD VESS

• LIPID SOL AGENT:
• ENTERS CNS --> CENTRAL & PERIPH RELEASE OF NE

THERA -- ADHD & ADD

• ADVERSE -- ENTERS CNS
• --INSOMNIA

--CEREBRAVASC HEMORR (INC BP)

--PSYCH DISTURBANCES AFTER PROLONGED USE!!!

ADREN AGONIST

MOA -- a1 SELECTIVE

GIVEN IV

PHARM -- "PURE a"

• GIVEN IV --> NE EFFECTS:
• --INC DBP & INC SBP
• --SV UNCHANGED
• --DEC HR VIA BAROREFLEX

• CV EFFECTS ARE SAME AS NE:
• --ART VASOCONST --> INC TPR --> INC DBP
• --BAROREFLEX-MEDIATED BRADYCARDIA
• --DEC BLD FLOW TO ALL ORGANS

• THERA --
• --SYSTEMIC VASOCONST AGENT

--LOCAL APP RELIEVES NASAL CONG BY CONST BLD VESS IN MUCOSA

--OXYMETAZOLINE LONGER DURATION OF ACTION > PHENYLEPHRINE

--LOCAL APP PRODs MYDRIASIS BY CONTRACTION OF RADIAL MUSC OF IRIS. USED FOR FUNDO EXAMS & OCULAR APPEARANCE

• ADVERSE --
• --RENAL & MESENTERIC ISCH (a)

--CEREBROVASC HEMORR (INC BP)

--REBOUND NASAL CONG (NASAL VC)

--??PULMONARY EDEMA (INC TPR)

ADREN AGONIST

MOA -- SELECTIVE b2

b2 >> b1

PHARM -- RELAX UTERINE SMOOTH MUSC

THERA -- DELAY PARTURITION (NOT USED MUCH ANYMORE)

MOVE FETUS OUT OF BREECH POS (EXT VERSION OF FETUS TO A VERTEX POSITION PRIOR TO BIRTH

• ADVERSE --
• *Cardiac arrhythmias (β)

*Angina in pts w/CAD (β)

*Tremor (β2)

ADREN AGONIST

MOA -- SELECTIVE b2

b2 >> b1

• ADVERSE --
• *Cardiac arrhythmias (β)

*Angina in pts w/ CAD (β)

*Tremor (β2)

ADREN AGONIST

MOA -- SELECTIVE b2

b2 >> b1

PHARM -- RELAX BRONC MUSC

THERA -- ASTHMA COPD, BRONCHITIS

• ADVERSE --
• *Cardiac arrhythmias (β)

*Angina in pts w/ CAD (β)

*Tremor (β2)

ADREN AGONIST

MOA -- GIVEN IV

PURE b STIM (b1 = b2)

• PHARM --
• LIKE EPI EXCEPT NO a STIM

b1 STIM --> INC dp/dt, HR, SV --> INC PP

INC PP FROM DEC DBP. SBP UNCHANGED / DEC DESPITE INC SV

b2 STIM --> VASODIL @ ALL VASC --> DEC TPR & DEC DBP

?? INC FALL IN TPR & DBP & INC IN BLD FLOW THRU KIDNEY, GI, SKEL MUSC, LIVER

• THERA --
• INC AV CONDUCTION IN AV BLOCK

USED AS (+) INOTROPIC (INFLUENCE dp/dt) & CHRONOTROPIC (AFFECT HB) AGENT IN CARDIAC ARREST

• ADVERSE --
• CARDIA ARRHYTHMIAS (b)

ANGINA IN pts w/ CAD (b)

TREMOR (b2)

TACHYCARDIA (ISOPROTERENOL > ALBUTEROL)

ADREN AGONIST

MOA -- RACEMIC MIX OF (+) (-) ENANTIOMERS --> BOTH STIM b1 & b2

• (-) = a1 AGONIST
• (+) = a2 ANTAGONIST
• (+/-) CANCEL OUT

b1 >= b2

• PHARM --
• (+) ENANT BLOCK VASOCONST CAUSED BY (-)

b1 STIM --> INC SV

• b2 STIM:
• --ARTERIODILATION --> DEC TPR --> POSS DEC DBP

--VENODIL --> DEC VENOUS RETURN & DEC CARDIAC FILLING PRESSURE IN pt w/ MI

INC GFR SOLELY FROM INC CO.

NO EFFECT @ RENAL D1 RECs

• THERA --
• ***DOBUTAMINE >> DOPA***
• DISTINCT ADVANTAGES IN Rx MI

• 1) DOBUT DOSNT INC DBP
• 2) DOBUT IS LESS LIKELY TO CAUSE TACHYCARDIA
• 3) DOBUT CAUSES VENODIL --> DEC VEN RET, SO CARDIAC FILLING PRESSURE IS DEC

INC CO AFTER MI

INC CO IN SEPTIC & CARDIOGENIC SHOCK

a-BLOCK & b2 STIM --> PREVENTS/REVERSES INC TPR CAUSED BY INC DOSE DA

• ADVERSE --
• EXCESSIVE DOSE:

TACHYCARDIA

CARDIA DYSRYTHMIAS

CARDIAC ARRHYTHMIAS (b)

ANGINA IN pts w/ CAD (b)

TREMOR (b2)

pt POSS DEV TOLERANCE TO (+) INOTROPIC EFFECTS OF DA & DOBUTAMINE (DOWN REG RECs)

NED PEA DUMB-BUTT ISO TERRIBLE, RIGHT? PHEN EFFRINE ALL-BUTT TRIED OXY-SALMON

• NOREPINEPHRINE
• EPINEPHRINE
• DOPAMINE
• PSEUDO-EPHEDRINE
• EPHEDRINE
• AMPHETAMINE
• DOBUTAMINE
• ISO-PROTER-ENOL
• TERBUTALINE
• RITODRINE
• PHENYL-EPHRINE
• ALBUTEROL
• TYRAMINE
• OXY-META-ZOLINE
• SALMETEROL

a BLOCKER

MOA -- NONCOMP REC BLOCKADE DUE TO COVALENT BINDING (ALKYLATION) OF RECs

a1 >> a2

• PHARM --
• --DEC TPR & BP
• --INC VENOUS CAPACITANCE
• --INC HR
• --INC dp/dt

NET EFFECT -- NO CHANGE IN CO

THERA -- CONTROL BP IN pts w/ MAL TUMORS

• ADVERSE --
• --*angina → produce baroreflex incr in HR, dp/dt & O2 demand
• --*tachycardia
• --* Miosis (α1)
• --*Inhb of ejaculation (α1)
• --*Incr insulin release (α2)

a BLOCKER

a1 = a2

• PHARM
• --DEC TPR & BP
• --INC VENOUS CAPACITANCE
• --INC HR
• --INC dp/dt

• THERA
• --PERI-OP w/ NONSELECTIVE b-BLOCKER TO CTR BP DURING MANIP OF PHEOCHROMOCYTOMA TUMOR

--LOCAL USE TO REVERSE ISCH & TISS NEC CAUSED BY EXTRAVASATION OF DA FROM VEINS DURING IV (DA CAUSES MAJOR VC AT INC DOSE)

--IMPOTENSE (INJ INTO CORP CAV)

• ADVERSE
• --*angina → produce baroreflex incr in HR, dp/dt & O2 demand
• --*tachycardia
• --* Miosis (α1)
• --*Inhb of ejaculation (α1)
• --*Incr insulin release (α2)

a BLOCKER

MOA -- ONLY a1 BLOCK

• PHARM
• --DEC TPR & BP
• --INC VENOUS CAPACITANCE

• NET EFFECT
• --NO CHANGE HR, dp/dt & CO!!!

• THERA
• --1st LINE IN MILD TO MOD HTN

--PERI-OP w/ NONSELECT b-BLOCKER FOR BP DURING MANIP OF PHEOCHROMOCYTOMA

--MOST USEFUL IN Rx OF CONDITIONS ASSOC W/ MARKED VASOCONST (RAYNAUD'S SYND, FROSTBITE & CHRON VASOSPASM)

--SMALL DOSE CAN RELIEVE URINARY OBST TO INC URINE FLOW RATE IN pt W/ PROSTATIC HYPERTROPHY

• ADVERSE
• --MIOSIS (a1)
• --INH OF EJEC (a1)

a BLOCKER

MOA -- ONLY a1A BLOCK

THERA -- DOC FOR BPH

SMALL DOSE CAN RELIEVE URINARY OBST TO INC URINE FLOW RATE (FLOMAX) IN pt w PROSTATIC HYPERTROPHY

NON-SELECTIVE b-BLOCKER:

PROPRANOLOL OR TIMOLOL

ENHANCED BY EXCESSIVE INTAKE OF CAFFEINE, LACK OF SLEEP, ALC, HANGOVER AND STREN EXCERSISE.

• PRAZOSIN (a1)
• OR
• PHENTOLAMINE (a1 = a2)

+

NON-SELECTIVE b ANATAGONIST (PROPRANOLOL)

a BLOCKER

MOA -- BLOCKS a1, b1 & PARTIAL AGONIST FOR b2 (intrinsic sympathomimetic activity)

• PHARM
• --DEC TPR, BP, dp/dt
• --DEC NO CHANGE HR
• --NO CHANGE CO

• THERA
• -1st LINE IN MILD TO NED HTN
• --LOWER BP SLOWLY IN pt w HTN EMERGENCY
• --NOT EFFECTIVE IN CTR BP IN pt w PHEOCHROMOCYTOMA

• ADVERSE
• --MIOSIS (a1)
• --INH OF EJAC (a1)

Tx OF IMPOTENCE

MOA -- PDE INH

(SILDENAFIL ALSO)

Tx OF IMPOTENCE

MOA -- TOPICAL OR INJ INTO CORPUS CAVERNOSA

PGE-1 ANALOG

IMPOTENCE Tx

MOA -- INJ INTO CORPUS CAVERNOSA

COMPET BLOCK OF a1 & a2 REC (a1 = a2)

• PHARM
• --DEC TPR & BP
• --INC VENOUS CAPACITANCE
• --INC HR & dp/dt

NET EFFECT -- NO CHANGE IN CO

• THERA
• --USED PERI-OP w NON-SPECIFIC b-BLOCKER TO ctr BP DURING MANIP OF PHEOCHROMOCYTOMA TUMOR

--LOCAL USE TO REVERSE ISCH & TISS NEC CAUSED BY EXTRAVASATION OF DA FROM VEINS DURING IV

• --ORTHOSTATIC HYPOTENSION
• --FAILURE TO EJAC / RETRO-EJAC
• --MIOSIS (UNOPPOSED PARASYMP)
• --NASAL CONG (UNOPPOSED PARASYMP)
• --ABDOM CRAMPING (UNOPPOSED PARASYMP)

--SOME pt SLOWLY RETAIN Na/H2O TO INC ECF VOLUME

a BLOCKER (really partial a agonist)

ALSO DIHYDROERGOTAMINE

MOA -- PARTIAL a AGONIST

PHARM -- SLIGHTLY CONSTIC CEREBRAL BLD VESS --> DEC MIGRAINE PAIN

THERA -- MIGRAINE

• ADVERSE
• --SPONT ABORT
• --MUSC PAIN
• --PARESTHESIAS
• --DIGITAL VASOSPASM
• --GANGRENE

• --MIOSIS (a1)
• INH OF EJAC (a1)
• INH INSULIN (a2)

a BLOCKER

MOA -- a2 >> a1

PHARM -- VERY LIPID SOL

• CENTRAL a2 BLOCKADE IN THE BAROREFLEX ARC --> INC PREGANG SYMP ACTIVITY
• --TACHYCARDIA
• --TREMOR
• --SLIGHT INC IN BP

THERA -- NOT EFFECTIVE FOR ERECTILE DYSF

• ADVERSE
• --TACHYCARDIA
• --TREMOR
• --SLIGHT INC IN BP
• --RESTLESSNESS
• --IRRITABILITY
• --ANX
• --INC INSULIN RELEASE (a2)

• PHEN-OXY-BENZ-AMINE
• PHEN-TOL-AMINE
• PRAZOSIN
• TERAZOSIN
• DOXAZOSIN
• TAMSULOSIN
• LABETALOL
• YOHIMBINE
• ERGOTAMINE
• DIHYDRO-ERGOTAMINE

"FUN PAPA SOLD ALL"

• PHENTOLAMINE
• PAPAVERINE
• SILDENAFIL
• ALPROSTADIL

b-BLOCKER

MOA -- CARDIO SELECTIVE (b1)

--BAM! BETAX, ATEN, METOPRO

• ------------------------------------------------
• REST SAME FOR ALL b-BLOCKERS

• PHARM
• --DEC BASAL HR, CO, dp/dt
• --MYOCARDIAL O2 DEMAND & CORONARY BLD FLOW

--PREVENT TACHYCARDIA CAUSED BY EXCERCISE, STRESS, ANTI-HTN & ANTI ANGINAL VD DRUGS, & VALSALVA

--DEC CONDUC VELICITY IN AV NODE, ATRIA & VENTs

• NOT EFFECT
• --SLOWLY DEV DEC BP EVEN IN NORMOTENSIVE pts

--BASAL RENIN RELEASE DEC BY 30-50% --> PRA & PLASMA AngII CONC DEC

--IN HTN, pts DEC IN BP MAY INC Na/H2O RET & INC ECF

--DEC IOP BY DEC PROD OF AQ HUM BY UNKNOWN MECH (not propanolol bc of anesth of eye)

--BLOCK LIPOLYSIS (b1 ADIPOCYTES)

--BLOCK GLYCOGENOLYSIS (b2 LIVER & SKEL MUSC) --> ATTENUATED INC IN PLASMA GLUC & LAC CONC BY EPI

• WITH NON-SELECTIVE ANTAGONIST:
• --DEC FEV-1
• --RED DIGITAL BLD FLOW

• THERA:
• --*cardiac dysrhythmias, esp supraventricular arrhythmias assot’d w/ anxiety, stress,hyperthyroidism (Grave’s disease)

--*may prevent stress-induced PVC

--*post-MI (w/ aspirin) to prevent sudden death fr catcholamine-induced ventr dysrhythmia

--*angina pectoris: decr O2 demand

--*HTN: decr BP w/o ortho. hypo.

--*heart failure: incr CO (i.e. metoprolol)

--*hyperthyroidism (Grave’s): Blocks tremor, tachy & atrial fib

--*pheochromocytoma: non-selectv before & during surgery in combo w/ α blocker.

--*essential tremor: non-selectv (β2)

--*portal hypertension: decr CO (i.e., propanolol)

--*Migraine headache (prophylactic)

• Glaucoma:
• --Local use to lower IOP by decr aqueous humor
• production.
• --W/o miosis or cyclopledia.
• (i.e., Betaxolol, Timolol)
• (except Propanolol→ anesth.of eye)

• ADVERSE
• *decr dp/dt ((-) inotropic) --> heart failure & global edema

*bradycardia → contraindicated in AV block by digoxin.

• * Up-regulation of β recptrs
• --sudden withdrawal of Rx (propanol w/d syndrome) → cardiac palpitations & tremor --> angina or MI

*Contraindicated in pts w/ DM type 2

*Impotence (No erection)

---- Non-selective agents ----

Contraindicated: Raynaud’s & Bueger’s

Contraindicated in asthma, COPD & chronic bronchitis (b/c incr airway resistance → decr FEV1)

*Exercise intolerance in non-anginal pts

• *Decr digital blood flow (β2)
• (smoking worsens)

• *DM type 1 pts: mask signs of hypoglycemia &
• HTN in presence of hi plasma EPI

LIKE 3* CHOL AGONIST

ACTS IN CNS TO INC VAGAL TONE --> AV BLOCK

COUNTER WITH ATROPINE

b-BLOCKER "BAM!"

MOA -- CARDIOSELECTIVE (b1) REC

• ---------------------------------------------------
• REST SAME FOR ALL b-BLOCKERS

• PHARM
• --DEC BASAL HR, CO, dp/dt
• --MYOCARDIAL O2 DEMAND & CORONARY BLD FLOW

--PREVENT TACHYCARDIA CAUSED BY EXCERCISE, STRESS, ANTI-HTN & ANTI ANGINAL VD DRUGS, & VALSALVA

--DEC CONDUC VELICITY IN AV NODE, ATRIA & VENTs

• NOT EFFECT
• --SLOWLY DEV DEC BP EVEN IN NORMOTENSIVE pts

--BASAL RENIN RELEASE DEC BY 30-50% --> PRA & PLASMA AngII CONC DEC

--IN HTN, pts DEC IN BP MAY INC Na/H2O RET & INC ECF

--DEC IOP BY DEC PROD OF AQ HUM BY UNKNOWN MECH (not propanolol bc of anesth of eye)

--BLOCK LIPOLYSIS (b1 ADIPOCYTES)

--BLOCK GLYCOGENOLYSIS (b2 LIVER & SKEL MUSC) --> ATTENUATED INC IN PLASMA GLUC & LAC CONC BY EPI

• WITH NON-SELECTIVE ANTAGONIST:
• --DEC FEV-1
• --RED DIGITAL BLD FLOW

• THERA:
• --*cardiac dysrhythmias, esp supraventricular arrhythmias assot’d w/ anxiety, stress,hyperthyroidism (Grave’s disease)

--*may prevent stress-induced PVC

--*post-MI (w/ aspirin) to prevent sudden death fr catcholamine-induced ventr dysrhythmia

--*angina pectoris: decr O2 demand

--*HTN: decr BP w/o ortho. hypo.

--*heart failure: incr CO (i.e. metoprolol)

--*hyperthyroidism (Grave’s): Blocks tremor, tachy & atrial fib

--*pheochromocytoma: non-selectv before & during surgery in combo w/ α blocker.

--*essential tremor: non-selectv (β2)

--*portal hypertension: decr CO (i.e., propanolol)

--*Migraine headache (prophylactic)

• Glaucoma:
• --Local use to lower IOP by decr aqueous humor
• production.
• --W/o miosis or cyclopledia.
• (i.e., Betaxolol, Timolol)
• (except Propanolol→ anesth.of eye)

• ADVERSE
• *decr dp/dt ((-) inotropic) --> heart failure & global edema

*bradycardia → contraindicated in AV block by digoxin.

• * Up-regulation of β recptrs
• --sudden withdrawal of Rx (propanol w/d syndrome) → cardiac palpitations & tremor --> angina or MI

*Contraindicated in pts w/ DM type 2

*Impotence (No erection)

---- Non-selective agents ----

Contraindicated: Raynaud’s & Bueger’s

Contraindicated in asthma, COPD & chronic bronchitis (b/c incr airway resistance → decr FEV1)

*Exercise intolerance in non-anginal pts

• *Decr digital blood flow (β2)
• (smoking worsens)

• *DM type 1 pts: mask signs of hypoglycemia &
• HTN in presence of hi plasma EPI

b-BLOCKER

MOA -- CARDIOSELECTIVE (b1)

USED VIA IV IN ER OF SHORT TERM BLOCKADE (t1/2 9 mins)

• ----------------------------------------------
• REST SAME FOR ALL b-BLOCKERS

• PHARM
• --DEC BASAL HR, CO, dp/dt
• --MYOCARDIAL O2 DEMAND & CORONARY BLD FLOW

--PREVENT TACHYCARDIA CAUSED BY EXCERCISE, STRESS, ANTI-HTN & ANTI ANGINAL VD DRUGS, & VALSALVA

--DEC CONDUC VELICITY IN AV NODE, ATRIA & VENTs

• NOT EFFECT
• --SLOWLY DEV DEC BP EVEN IN NORMOTENSIVE pts

--BASAL RENIN RELEASE DEC BY 30-50% --> PRA & PLASMA AngII CONC DEC

--IN HTN, pts DEC IN BP MAY INC Na/H2O RET & INC ECF

--DEC IOP BY DEC PROD OF AQ HUM BY UNKNOWN MECH (not propanolol bc of anesth of eye)

--BLOCK LIPOLYSIS (b1 ADIPOCYTES)

--BLOCK GLYCOGENOLYSIS (b2 LIVER & SKEL MUSC) --> ATTENUATED INC IN PLASMA GLUC & LAC CONC BY EPI

• WITH NON-SELECTIVE ANTAGONIST:
• --DEC FEV-1
• --RED DIGITAL BLD FLOW

• THERA:
• --*cardiac dysrhythmias, esp supraventricular arrhythmias assot’d w/ anxiety, stress,hyperthyroidism (Grave’s disease)

--*may prevent stress-induced PVC

--*post-MI (w/ aspirin) to prevent sudden death fr catcholamine-induced ventr dysrhythmia

--*angina pectoris: decr O2 demand

--*HTN: decr BP w/o ortho. hypo.

--*heart failure: incr CO (i.e. metoprolol)

--*hyperthyroidism (Grave’s): Blocks tremor, tachy & atrial fib

--*pheochromocytoma: non-selectv before & during surgery in combo w/ α blocker.

--*essential tremor: non-selectv (β2)

--*portal hypertension: decr CO (i.e., propanolol)

--*Migraine headache (prophylactic)

• Glaucoma:
• --Local use to lower IOP by decr aqueous humor
• production.
• --W/o miosis or cyclopledia.
• (i.e., Betaxolol, Timolol)
• (except Propanolol→ anesth.of eye)

• ADVERSE
• *decr dp/dt ((-) inotropic) --> heart failure & global edema

*bradycardia → contraindicated in AV block by digoxin.

• * Up-regulation of β recptrs
• --sudden withdrawal of Rx (propanol w/d syndrome) → cardiac palpitations & tremor --> angina or MI

*Contraindicated in pts w/ DM type 2

*Impotence (No erection)

---- Non-selective agents ----

Contraindicated: Raynaud’s & Bueger’s

Contraindicated in asthma, COPD & chronic bronchitis (b/c incr airway resistance → decr FEV1)

*Exercise intolerance in non-anginal pts

• *Decr digital blood flow (β2)
• (smoking worsens)

• *DM type 1 pts: mask signs of hypoglycemia &
• HTN in presence of hi plasma EPI

b-BLOCKER

MOA -- NONSELECTIVE (b1 & b2)

LIKE TIMOLOL

• ------------------------------------------
• REST SAME FOR ALL b-BLOCKERS

• PHARM
• --DEC BASAL HR, CO, dp/dt
• --MYOCARDIAL O2 DEMAND & CORONARY BLD FLOW

--PREVENT TACHYCARDIA CAUSED BY EXCERCISE, STRESS, ANTI-HTN & ANTI ANGINAL VD DRUGS, & VALSALVA

--DEC CONDUC VELICITY IN AV NODE, ATRIA & VENTs

• NOT EFFECT
• --SLOWLY DEV DEC BP EVEN IN NORMOTENSIVE pts

--BASAL RENIN RELEASE DEC BY 30-50% --> PRA & PLASMA AngII CONC DEC

--IN HTN, pts DEC IN BP MAY INC Na/H2O RET & INC ECF

--DEC IOP BY DEC PROD OF AQ HUM BY UNKNOWN MECH (not propanolol bc of anesth of eye)

--BLOCK LIPOLYSIS (b1 ADIPOCYTES)

--BLOCK GLYCOGENOLYSIS (b2 LIVER & SKEL MUSC) --> ATTENUATED INC IN PLASMA GLUC & LAC CONC BY EPI

• WITH NON-SELECTIVE ANTAGONIST:
• --DEC FEV-1
• --RED DIGITAL BLD FLOW

• THERA:
• --*cardiac dysrhythmias, esp supraventricular arrhythmias assot’d w/ anxiety, stress,hyperthyroidism (Grave’s disease)

--*may prevent stress-induced PVC

--*post-MI (w/ aspirin) to prevent sudden death fr catcholamine-induced ventr dysrhythmia

--*angina pectoris: decr O2 demand

--*HTN: decr BP w/o ortho. hypo.

--*heart failure: incr CO (i.e. metoprolol)

--*hyperthyroidism (Grave’s): Blocks tremor, tachy & atrial fib

--*pheochromocytoma: non-selectv before & during surgery in combo w/ α blocker.

--*essential tremor: non-selectv (β2)

--*portal hypertension: decr CO (i.e., propanolol)

--*Migraine headache (prophylactic)

• Glaucoma:
• --Local use to lower IOP by decr aqueous humor
• production.
• --W/o miosis or cyclopledia.
• (i.e., Betaxolol, Timolol)
• (except Propanolol→ anesth.of eye)

• ADVERSE
• *decr dp/dt ((-) inotropic) --> heart failure & global edema

*bradycardia → contraindicated in AV block by digoxin.

• * Up-regulation of β recptrs
• --sudden withdrawal of Rx (propanol w/d syndrome) → cardiac palpitations & tremor --> angina or MI

*Contraindicated in pts w/ DM type 2

*Impotence (No erection)

---- Non-selective agents ----

Contraindicated: Raynaud’s & Bueger’s

Contraindicated in asthma, COPD & chronic bronchitis (b/c incr airway resistance → decr FEV1)

*Exercise intolerance in non-anginal pts

• *Decr digital blood flow (β2)
• (smoking worsens)

• *DM type 1 pts: mask signs of hypoglycemia &
• HTN in presence of hi plasma EPI

b-BLOCKER

MOA -- NONSELECTIVE (b1 & b2)

LIKE PROPANOLOL

• -----------------------------------------
• REST SAME FOR ALL b-BLOCKERS

• PHARM
• --DEC BASAL HR, CO, dp/dt
• --MYOCARDIAL O2 DEMAND & CORONARY BLD FLOW

--PREVENT TACHYCARDIA CAUSED BY EXCERCISE, STRESS, ANTI-HTN & ANTI ANGINAL VD DRUGS, & VALSALVA

--DEC CONDUC VELICITY IN AV NODE, ATRIA & VENTs

• NOT EFFECT
• --SLOWLY DEV DEC BP EVEN IN NORMOTENSIVE pts

--BASAL RENIN RELEASE DEC BY 30-50% --> PRA & PLASMA AngII CONC DEC

--IN HTN, pts DEC IN BP MAY INC Na/H2O RET & INC ECF

--DEC IOP BY DEC PROD OF AQ HUM BY UNKNOWN MECH (not propanolol bc of anesth of eye)

--BLOCK LIPOLYSIS (b1 ADIPOCYTES)

--BLOCK GLYCOGENOLYSIS (b2 LIVER & SKEL MUSC) --> ATTENUATED INC IN PLASMA GLUC & LAC CONC BY EPI

• WITH NON-SELECTIVE ANTAGONIST:
• --DEC FEV-1
• --RED DIGITAL BLD FLOW

• THERA:
• --*cardiac dysrhythmias, esp supraventricular arrhythmias assot’d w/ anxiety, stress,hyperthyroidism (Grave’s disease)

--*may prevent stress-induced PVC

--*post-MI (w/ aspirin) to prevent sudden death fr catcholamine-induced ventr dysrhythmia

--*angina pectoris: decr O2 demand

--*HTN: decr BP w/o ortho. hypo.

--*heart failure: incr CO (i.e. metoprolol)

--*hyperthyroidism (Grave’s): Blocks tremor, tachy & atrial fib

--*pheochromocytoma: non-selectv before & during surgery in combo w/ α blocker.

--*essential tremor: non-selectv (β2)

--*portal hypertension: decr CO (i.e., propanolol)

--*Migraine headache (prophylactic)

• Glaucoma:
• --Local use to lower IOP by decr aqueous humor
• production.
• --W/o miosis or cyclopledia.
• (i.e., Betaxolol, Timolol)
• (except Propanolol→ anesth.of eye)

• ADVERSE
• *decr dp/dt ((-) inotropic) --> heart failure & global edema

*bradycardia → contraindicated in AV block by digoxin.

• * Up-regulation of β recptrs
• --sudden withdrawal of Rx (propanol w/d syndrome) → cardiac palpitations & tremor --> angina or MI

*Contraindicated in pts w/ DM type 2

*Impotence (No erection)

---- Non-selective agents ----

Contraindicated: Raynaud’s & Bueger’s

Contraindicated in asthma, COPD & chronic bronchitis (b/c incr airway resistance → decr FEV1)

*Exercise intolerance in non-anginal pts

• *Decr digital blood flow (β2)
• (smoking worsens)

• *DM type 1 pts: mask signs of hypoglycemia &
• HTN in presence of hi plasma EPI

b-BLOCKER

MOA -- NONSELECTIVE (b1, b2, & a)

SEE ALSO a-BLOCKER

• ----------------------------------------------
• REST SAME FOR ALL b-BLOCKERS

• PHARM
• --DEC BASAL HR, CO, dp/dt
• --MYOCARDIAL O2 DEMAND & CORONARY BLD FLOW

--PREVENT TACHYCARDIA CAUSED BY EXCERCISE, STRESS, ANTI-HTN & ANTI ANGINAL VD DRUGS, & VALSALVA

--DEC CONDUC VELICITY IN AV NODE, ATRIA & VENTs

• NOT EFFECT
• --SLOWLY DEV DEC BP EVEN IN NORMOTENSIVE pts

--BASAL RENIN RELEASE DEC BY 30-50% --> PRA & PLASMA AngII CONC DEC

--IN HTN, pts DEC IN BP MAY INC Na/H2O RET & INC ECF

--DEC IOP BY DEC PROD OF AQ HUM BY UNKNOWN MECH (not propanolol bc of anesth of eye)

--BLOCK LIPOLYSIS (b1 ADIPOCYTES)

--BLOCK GLYCOGENOLYSIS (b2 LIVER & SKEL MUSC) --> ATTENUATED INC IN PLASMA GLUC & LAC CONC BY EPI

• WITH NON-SELECTIVE ANTAGONIST:
• --DEC FEV-1
• --RED DIGITAL BLD FLOW

• THERA:
• --*cardiac dysrhythmias, esp supraventricular arrhythmias assot’d w/ anxiety, stress,hyperthyroidism (Grave’s disease)

--*may prevent stress-induced PVC

--*post-MI (w/ aspirin) to prevent sudden death fr catcholamine-induced ventr dysrhythmia

--*angina pectoris: decr O2 demand

--*HTN: decr BP w/o ortho. hypo.

--*heart failure: incr CO (i.e. metoprolol)

--*hyperthyroidism (Grave’s): Blocks tremor, tachy & atrial fib

--*pheochromocytoma: non-selectv before & during surgery in combo w/ α blocker.

--*essential tremor: non-selectv (β2)

--*portal hypertension: decr CO (i.e., propanolol)

--*Migraine headache (prophylactic)

• Glaucoma:
• --Local use to lower IOP by decr aqueous humor
• production.
• --W/o miosis or cyclopledia.
• (i.e., Betaxolol, Timolol)
• (except Propanolol→ anesth.of eye)

• ADVERSE
• *decr dp/dt ((-) inotropic) --> heart failure & global edema

*bradycardia → contraindicated in AV block by digoxin.

• * Up-regulation of β recptrs
• --sudden withdrawal of Rx (propanol w/d syndrome) → cardiac palpitations & tremor --> angina or MI

*Contraindicated in pts w/ DM type 2

*Impotence (No erection)

---- Non-selective agents ----

Contraindicated: Raynaud’s & Bueger’s

Contraindicated in asthma, COPD & chronic bronchitis (b/c incr airway resistance → decr FEV1)

*Exercise intolerance in non-anginal pts

• *Decr digital blood flow (β2)
• (smoking worsens)

• *DM type 1 pts: mask signs of hypoglycemia &
• HTN in presence of hi plasma EPI

"ATENsion, BET TIM's LAB MET ES a PRO!"

• BETAXOLOL
• ATENOLOL
• METOPROLOL
• ESMOLOL
• PROPANOLOL
• TIMOLOL (glaucoma)
• LABETALOL

ALTER NE METABOLISM

• COCAIN HCl
• --SNORTED
• --INJ
• --P.O.
• --LOCAL APP TO SUBLING, VAG, URETH, RECT MUCOSA

• MOA
• --LOCAL ANESTH --> BLOCKS Na CHN IN NEURONAL MEM OF SENSORY PAIN FIBERS

--NON-COMP BLOCKADE OF MAO UPTAKE-1 TRANPORTER IN CENT/PERIPH NEURONS

-->AMPs POSTJUNC EFFECTS OF NE, DA, EPI, & 5-HT

--ACTS CENTRALLY TO INC PERIPH SYMP OUTFLOW

• CNS
• --EUPHORIA & ADDICTIVE PROP RESULT FROM INC DA RELEASE IN NUC ACCUMB

(ACTUALLY: PREVENT DA REUPTAKE --> BUILD UP IN NERVE JUNC

• PHARM
• --LOCAL ANASTHET & INTENSE VC

--LOCAL HEMOSTASIS WHEN USED AS A TOPICAL ANESTH

--CNS: EUPH & VERY ADDICTIVE

• --DOSE RELATED
• ----INC BP & HR

• --INDIR VC ACT
• ----NON-COMP BLOCK OF UPTAKE-1 --> INC NE CONC IN NERVE JUNC --> NE STIM a1 @ ADVENTITIAL SURFACE OF VSM

• THERA
• --LOCAL ANESTH IN OCULAR & NASAL SURGERY

ADVERSE

*cardiac dysrhythmias:

• 1. Blockade of cardia Na channels → impairs
• ventr impulse conduction

2. Incr NE release (central effect)

3. potentiates cardiac actions of NE (block uptake-1)

*MI: poss w/ pt w/ normal coronary arteries

*chest pain (sim to MI)

*pulmonary edema: From direct decr dp/dt & incr afterload

*CVA: subarachnoid hemorrhage or ischemic stroke

*respiratory disease: barotrauma, pulmonary hemorrhage & hypersenstv pneumonia

*seizures

*sudden death

* “crack” burns of larynx

*necrosis of nasal septum

SYMPATHOLYTIC

MOA -- ADREN NEURONAL BLACKING DRUG

DIRECTLY INH NERVE-STIMULATED NE RELEASE

***MAIN ACTION IS INH OF NERVE-STIM RELEASE FROM PERIPH SYMP NEURONS

INH VESICULAR STORAGE OF NE

INH EXOCYTOTIC RELEASE OF NE BY ACTION POTENTIAL

• PHARM
• --POORLY LIPID SOL --> NO CNS

• NET EFFECT
• --BALANCED VD --> PASSIVE VD
• ----@ ARTERIOLES; DEC TPR --> DEC DBP
• ----@ VENULES; INC VEN CAP --> DEC VEN RETURN

--UNCHANGED / SLIGHT DEC IN HR

--UNCHANGED / SLIGHT DEC IN CO

--DEC RENAL PERF --> INC FILT FRAC --> Na/H2O RET

• THERA
• --NOT USED TO Rx HTN ANYMORE

ADVERSE

*orthostatic hypotension

*edema

*No/retrograde ejaculation

• *SUPERSENSITIVITY to directly-acting sympathomimetic amines due to
• UPREGULATION of adrenoceptors

• *Unopposed parasymp activity can cause:
• --Bradycardia
• --Diarrhea
• --incr secretion of gastric acid
• --nasal congestion

SYMPATHOLYTIC "aRG!"

MOA -- ALKALOID OF BOTANICAL ORIGIN

**DESTROYS INTRACELL STORAGE VESICLES FOR NT IN CENTRAL & PERIPH MONOAMINERGIC NEURONS

SMALL DOSES AFFECT ONLY PERIPH SYMP NEURONS

INH VESICULAR STORAGE OF NE

• PHARM
• --SLOWED DEPLETION OF NE --> DEC NE RELEASE BY NERVE IMPULSES @ BLD VESS

--DOES NOT SUPPRESS TONIC SYMP ACT TO BLD VESS (LIKE a-MD) BUT LESS NE RELEASED --> SAME END RESULT

• --*BALANCED VASODIL --> PASSIVE VD
• ----AT ARTERIOLES, DEC TPR --> DEC DBP
• ----AT VENULES, INC VENOUS CAP --> DEC VENOUS RET

--DEC HR

--UNCHANGED / SLIGHTLY DEC CO

--DEC RENAL PERF --> INC FILT FRAC --> Na/H2O RET

--INC MOTILITY & TONE IN GI FROM UNOPPOSED PARASYM NERVE ACT

--INC PROLACTIN SEC FROM PIT VIA DEC RELEASE OF DA (DA --> TONIC PRL INH)

• THERA
• --NOT USED TO Rx HTN ANYMORE

ADVERSE

• Contraindicated:
• 1. Pregnant ♀
• 2. Hx of depression

*TERATOGENIC

*sedation

*depression w/ suicidal tendencies

*Parkinsonian-like movements!!!

*orthostatic hypotension!

*No/retrograde ejaculation

*hyperprolactinemia (DA)!!

• *SUPERSENSITIVITY to direct-acting sympathomimetic amines! (Up-regulation
• of periph α & β)

• *Unopposed parasymp activity can cause:
• --Bradycardia
• --Diarrhea
• --incr secretion of gastric acid
• --nasal congestion

• SYMPATHOLYTIC
• --DIR OR IND DEC RELEASE OF NE FROM PERIPH SYMP NEURONS --> DEC BP 1* BY DEC TPR

VIA NE & DOPA SYNTH enz --> a-METHYL-NE

--Stored as a ntr in vseicles of central & peripheral noradrenergic neurons → released by action potential.

--NOT degraded by MAO → stored in cytoplasm & NE vesicles

MOA -- INDIR BLOCKS RELEASE OF NE FROM SYMP NEURONS

**STIMS a2 @ ROSTRAL VL MEDULLA --> DEC PREGANG SYMP ACTIVITY (ACTS CENTRALLY TO MIMIC INC BARORECEPTOR INPUT FROM CAROTID SINUS

**DEC SYMP ACTIVITY --> DEC AMOUNT OF NE @ a-METHYL-NE RELEASED FROM PERIPH SYMP FIBERS WHICH INNERV HRT & BLD VESSs

• PHARM
• --VASOCONST IN BLD VESS (as effecacious as NE)

--NET BALANCED VASO-DIL. DEC TONIC SYMP VC --> PASSIVE VD. ARTERIOLES DEC DBP

--SLIGHT DEC HR

--ATTENUATED INC IN HR THAT OCC WHEN MOVING FROM A SUPINE TO STANDING POS

--UNCHANGED/SLIGHT DEC CO

--DEC BYOCARDIAL O2 DEMAND

--DEC IN RENAL PERF --> POSS INC FILT FRAC --> SLOWLY CAUSE Na/H2O RET

-DEC PLASMA RENIN ACT

--DEC PLASMA AngII CONC

--INC PROLACTIN SEC FROM PIT VIA DEC RELEASE OF DA (DA --> TONIC PRL INH)

• THERA
• --DOC FOR HTN IN CHILDREN & PREG bc NOT TERATOGINIC

• ADVERSE
• --SEDATION & SOMN
• --DRY MOUTH & NASAL CONG
• --EDEMA
• --SOME ORTHOSTATIC INTOLERANCE
• --FLU-LIKE SYND
• --(+) COOMB'S TEST
• --HEP (HYPERSENSITIVITY rxn)

• --HYPERPROLACTINEMIA
• ----MALES: GYNECOMASTIA, OLIGOSPERMIA & IMP / DEC LIBIDO

----FEMALES: AMENORRHEA & GALACTORRHEA

ARG!

• a-METHYLDOPA
• RESERPINE
• GUAN-ETH-IDINE

COCAINE

DYNAMICS - WHAT A DRUG DOES TO THE BODY

KINETICS - WHAT THE BODY DOES TO A DRUG. THE STUDY STUDY OF THE TIME COURSE OF THE ABSORPTION, DISTRIBUTION, METABOLISM, AND ELIMINATION OF DRUGS

BUCCAL

PER OS (p.o) -- SLOW ABS & SUBJECT TO HIGH FIRST PASS FILTERING

RECTAL - DELAYED FIRST PASS. USED WHEN pt IS NAUSEATED

• INJECTION:
• IV -- RAPID ACTION (4 SEC). DRUGS WITH SHORT HALF LIFE --> PEPTIDES AND INSOLUBLE DRUGS

IM -- FAIRLY RAPID ABS. DEPOT FORMS (PEN)

SUBCUTANEOUS -- RAPID ABS WITH AQUEOUS PREPS. FAIRLY RAPID VASOACTIVE DRUGS WHICH ARE DANGEROUS TO GIVE IV (EP FOR ANAPHYLACTIC REACTION)

PULMONARY -- LARGE SURFACE AREA AND HIGH BLOOD FLOW ALLOW RAPID ABS OF GASSES (ANESTHETIC ENFLURANE)

TOPICAL -- LOCAL EFFECT (EYE, SKIN, NOSE, THROAT, VAG, RECTUM, LUNG)

TRANSDERMAL (PATCH) -- SLOW ABS LEADS TO CONSTANT AMT OF DRUG IN BLOOD FOR PERIODS AS LONG AS ONE WEEK (NITROGLYCERINE, SCOPOLAMINE, CLONIDINE, ESTROGEN)

ALMOST ALL ARE LOW MOL WEIGHT AND EITHER ACIDIC OR BASIC

ACIDIC -- ANION FORMING (CONTAIN CARBOXYL GRP -COOH). USUALLY HAVE pKa > 7 BUT EXCEPTIONS (PHENYTOIN, HYDROCLOROTHIOZIDE, PENTAZOCINE)

BASIC -- CATION FORMING (CONTAIN AMINE GRP -NH2). USUALLY HAVE pKa < 7 BUT EXCEPTIONS (VINCRISTINE, DIAZEPAM, METFORMIN)

MOST ABS BY PASSIVE DIFFUSION DRIVEN BY CONC GRADIENT

PASSIVE DIFF OCCURS THROUGH AQ COMPARTMENTS AND LIPID MEMS

LIPID SOLUBILITY MAJOR CHAR OF PASSIVE DIFF --> ELECTRICAL CHARGE OR NOT

UNCHARGED FORM IS BEST ABS -- ELEC CHARGE DETERMINED BY pKa AND pH

• HH USED TO CALC FRACTION OF NONIONIZED DRUG IF THE pKa AND pH ARE KNOWN: LOG (PROT/UNPROT) = pKa - pH
• WHEN pKa = pH, CONC HALF IONIZED

• LOW pH --> HIGH ABS OF ACIDIC DRUGS (STOM)
• HIGH pH --> HIGH ABS OF BASIC DRUGS (SMALL BOWEL)

OIL/WATER PARTITION COEF: 10 IF VERY LIPID SOL (WILL PASS THROUGH LIPID MEM) AND 0.1 IF POORLY LIPID SOL

*REAL WORLD -- REGARLESS OF pKa, MAJORITY OF ANY DRUG WILL ABS IN SMALL INT BC OF LARGE SURFACE AREA

MUST PRODUCE PLASMA CONC VS. TIME CURVE AFTER p.o. DOSING COMPARABLE TO PROPRIETARY.

BIOEQ IS PRIMARILY A FUNC OF BIOAVAILABILITY

BT = METABOLISM

HEPATIC BT MAKES DRUGS MORE WATER SOL SO EXCRETED BY KIDNEYS

MAINLY BY LIVER: DETERMINED BY CONC, HEP EXTRACTION RATION (FRAC OF DRUG REMOVED FROM BLOOD), HEP BLOOD FLOW

• 2 ENZ REACTIONS:
• PHASE I -- CHANGE CHM STRUCT BY OX, HYDROX, DEAM, AND DEALK

PHASE II -- CONJUGACTION OR COUPLING TO ENDOGENOUS COMPOUNDS (GLUCURONIDATION, ACETYLATION, SULFATION)

• MAY ACTIVATE PRODRUGS
• ENALAPRIL --> ENALAPRILAT
• MINOXIDIL --> MINOXIDIL SULFATE
• LORATADINE (CLARATIN) --> DESCARB OETHOXYLORATADINE (DESLORATADINE OR CLARINEX)

CHANGE CHM STRUCT

CYP450 PRIMARILY RESPONSIBLE FOR FOR PHASE I BT. 11 ISOZYMES; BIG ONE IS 3A4 (FOUND IN LIVER & BRUSH BORDER)

INDUCERS & INH AFFECT DIFF ISOZYMES IN DIFF WAYS

PHASE I REACTIONS USUALLY PROD INACTIVE METABOLITES, BUT ACTIVE METABOLITES (WITH HALF LIVES AND EFFICACIES DIFF FROM PARENT) MAY BE PROD

• PHENOBARBITOL & OTHER BARBS
• RIFAMPIN
• PHENYTOIN
• CARBAMAZEPINE
• ETHANOL (CHRONIC ONLY)
• BENZOPRENE (CIG SMOKE)

• QUEEN
• *BARB
• STEALS
• *PHEN-PHEN
• *REFUSES
• GREASY
• *CARBS
• *ETHANOL (chronic)
• *MARCEDES-BENZ-OPREIN

• dioxin (tccd) present in agent orange
• ddt (insecticide)
• polychorinated biphenyls (pcb)

EFFECTS OF OTHER DRUGS DIMINISHED

MAJOR CAUSE OF PHARMACOKINETIC TOLERANCE

• KETOCONAZOLE
• ISONIAZID (TB)
• CIMETIDINE
• ERYTHROMYCIN
• ETHANOL (acute only)
• FURANOCOUMARIN (GF JUICE)

• KEETON
• IS
• CIMPLE
• he
• EATS
• ETHANOL (ACUTE)
• GRAPEFRUIT JUICE (FURANOCOUMARIN)

EFFECTS OF OTHER DRUGS ENHANCED

MAJOR CAUSE OF DRUG TOXICITY

CONJUGATION OF DRUG TO CREATE IONIZED FORM IN PHYS pH --> EXCRETION

EITHER PARENT OR PHASE I METABOLITE CAN UNDERGO PII REACTION

MAY FORM ACTIVE METABOLITES (PROCAINAMIDE --> N-ACETYLPROCAINAMIDE)

CYP450 IN SER OR CYTOSOL. METABOLISM THROUGH CYTO ENZ N-ACETYLTRANSFERASE

• "SHIP" -- RATE OF N-ACE IS BIMODAL, THUS FAST OR SLOW ACETYLATORS:
• SULFAPYRIDINE (hep damage and blood dyscrasia)
• HYDRALIZINE (lupus-like synd)
• ISONIAZID (peripheral neuropathy)
• PROCAINAMIDE (lupus-like synd)

COMPOUND SECRETED INTO BILE AND ENTERS GI

RE-ABS FROM GI --> LIVER --> BACK TO BILE

DRUG CONJUGATES HYDROLYZED BY BAC ENZ IN LARGE INT TO RELEASE PARENT DRUG WHICH IS THEN RE-ABS (ex ESTROGENIC COMPONENTS IN ORAL CONTRACEPTIVES)

GLOMERULAR FILTRATION = PASSIVE

SECRETION = ACTIVE TRANSPORT INTO PROX TUBULE

ONLY FREE DRUGS NOT BOUND BY PLASMA PROTS FILTERED/SECRETED. DRUG CAN THEN BE RE-ABS FROM TUBULAR URINE IF NOT IONIZED BY pH

RATE OF ACIDIC AND BASIC DRUG EXCRETION CAN BE TWEEKED BY MANIPULATING URINE pH --> "ION TRAPPING"

INCREASE EXCRETION OF BASIC AMPHETAMINE BY LOWERING URINE pH WITH AMMONIOM CHOLIDE

ACIDIC SALICYCLIC ACID EXCRETION BY MAKING URINE MORE ALKALINE (BASIC, INC pH) BY GIVING CARBONIC ANHYDRASE INH ACETAZOLAMIDE OR SODIUM BICARB

REVOLVES DAROUND FREE DRUG (NOT BOUND TO PLASMA OR TISSUE PROTS)

ALL CALCULATIONS BASED ON THE PLASMA CONC

PLASMA CONC REPORTED BY LAB IS THE TOTAL CONC AND DOES NOT REVEAL HOW MUCH OF TOTAL CONC IS FREE/BOUND

SOME PORTION OF ALL DRUGS ARE BOUND TO PLASMA PROTS. ACIDIC DRUGS BIND MOSTLY TO ALBUMIN AND OTHERS LIKE a-1 ACID GLYCOPROT. MANY DRUG-DRUG INTERACTIONS INVOLVE DISPLACEMENT OF FIRST DRUG FROM PLASMA PROTS BY A 2ND

ONLY FREE DRUGS PASS THROUGH BIO-MEMS. BUT, CELL MEMs IMPERMIABLE TO LOTS EXCEPT WATER SO MUST BE ACTIVELY TRANSed OR VERY LIPID SOL TO PASS

LIVE PRIMARY SITE OF BIO-TRANSFORMATION. ONLY FREE DRUG IS MET BY LIVER DURING FIRST PASS AND RECIRCULATION

ONLY FREE DRUG IS FILTERED BY GLOM OR SECRETED BY KIDNEYS

ONLY FREE DRUG PASSES INTO TISSUE FOR STORAGE (MAINLY MUSCLE AND ADIPOSE)

ONLY FREE DRUGS ACTIVATE RECEPTORS

BODY DEPICTED AS SINGLE HOMOGENOUS COMPARTMENT

ABS AND DISTRIBUTION IS INSTANTANEOUS

ELIMINATION OF ALMOST ALL DRUGS OCCURS AS A FIRST-ORDER RATE CONSTANT (ex TOTAL DRUG IN BODY x k(1/h) = mg/h k(1/h)=elim frac

• BIOAVAILABILITY (F) IS FRAC OF DRUG DOSE THAT REACHES SYSTEMIC
• CIRCULATION UNCHANGED FOLLOWING EXTRAVASCULAR DOSING. DOES NOT APPLY TO IV INJECTIONS.

• (F) GIVEN BY P.O. DETERMINED BY:
• 1. % ABS FROM GI
• 2. % MET BY BUT WALL ENZs
• 3. % REMOVED BY FIRST PASS

F= (P.O. AUC) / (IV AUC). AUC DETERMINED BY (Cp X TIME) GRAPH

HYPOTHETICAL VOL

DOES NOT REFER TO REAL VOL BUT MAY CORRESPOND TO VOL OF ONE OF THE FLUID COMPARTMENTS OF THE BODY

EXPRESSED IN L, L/Kg, OR L/m^2.

Vd = (Xo x F) / (Cp at time zero). Xo is dose administered in mg.

USED TO CALC LOADING DOSE

ONE OF 2 MAJOR DETERMINANTS OF HALF LIFE

ESTIMATE Cp AT TIME ZERO

• USED TO CALC CLEARANCE
• HIGH Vd MEANS MUCH OF THE DRUG IS ABS INTO THE TISSUES

PROBLEMS GIVEN WITH Vd AS L/Kg. WEIGHT OF Pt CAN BE DETERMINED BY (Vd = L/Kg X Kg = L)

• K = (0.7) / (t_1/2)
• INC K, DEC t1/2

t1/2 = 0.7 (Vd/Cl)

(K)tot = Krenal + Knon-renal

FIRST-ORDER RATE PROCESS BY WHICH A CONSTANT FRACTION OR % OF DRUG IS REMOVED FROM THE BODY PER UNIT TIME

BODY ABLE TO REMOVE A CONSTANT FRAC PER UNIT TIME bc ENZ SYSTEMS RARELY SATURATE

ACTUAL AMOUNT OF DRUG REMOVED PER UNIT TIME (RATEout = RATE OF ELIMINATION) IS DEPENDENT ON TOTAL AMOUNT OF DRUG IN BODY

K AND RATE OF ELIM ARE RELATED BUT NOT THE SAME THING

PLASMA CONC OF DRUG AT STEADY STATE

REMAINS CONSTANT bc RATE IN (DOSING RATE) = RATEout (RATE OF ELIMINATION)

Cpss IS ALWAYS GREATER THAN Cp PRODUCED BY SINGLE p.o. DOSE

TIME NEEDED TO ATTAIN Cpss IS INDEPENDENT OF DOSAGE

Cpss IS PROPORTIONAL TO THE DOSING RATE -- GIVING A DRUG DOSE MORE FQly WILL RESULT IN A HIGHER Cpss

RELATIONSHIP BETWEEN t1/2 AND CONSTANT DOSING RATE

93% Cpss OCCURS AFTER 4 T1/2

FIXED DOSE x 4(t1/2) = 93% Cpss

AMOUNT OF BLOOD OR PLASMA CLEARED OF PARENT DRUG PER UNIT TIME

Cl = RATEout / Cp = L/h

Cp ~ TOTAL DRUG IN BODY

Cl = K x Vd

Cl = X / (Cp x DOSE INT)

• Cl -- THINK FLOW
• RATEout -- THINK ACTUAL AMOUNT AT THAT TIME

IF Cp IS DOUBLED, Cl REMAINS THE SAME BECAUSE RATEout ALSO DOUBLES

0-120 FILTERED AND PARTIALLY RE-ABS

120 FILTERED AND NOT RE-ABS (CREATININE & INULIN)

120-600 SECRETED AND PARTIALLY RE-ABS

600 SECRETED AND NOT RE-ABS (PAH)

GET Cp WITHING THERAPEUTIC WINDOW AS FAST AS POSSIBLE

USUALLY 2-2.5 LARGER THAN MAINENANCE DOSE

XL = (Cp x Vd) / F

AFTER LOADING DOSE IS GIVEN TO REACH THERAPEUTIC WINDOW, A PERIOD OF 4 t1/2 IS STILL REQUIRED TO REACH Cpss

Cpo = (Xo x F) / Vd

USE TO CALC Vd AND Xo ALSO

Vd MUST BE IN L, SO IF GIVEN IN L/Kg -- MUST MULTIPLY BY Pt WEIGHT IN Kg

"SHIP"

LIKELY TO DEV TOXICITY

• Sulfapyridine
• - hepatic damage & blood dyscrasias

• Hydralazine
• - lupus-like syndrome

• Isoniazid
• - peripheral neuropathy

Procainamide - lupus-like syndrome

MAKES URINE MORE BASIC (ALKALINE)

THERA -- Rx OVERDOSE: INC EXCRETION OF WEAK ACIDS (ex ASPRIN)

MAKES URINE MORE ACIDIC

THERA -- Rx OVERDOSE --> INC EXCRETION OF WEAK BASES (ex amphetamine)

Ammonium chloride -- Makes urine more acidic. THERAPEUTIC --> Rx overdose: Incr excretion of weak BASES (e.g. amphetamine)

Acetazolamide -- Makes urine more alkaline. THERAPEUTIC --> Rx overdose: Incr excretion of weak ACIDS (e.g. aspirin)

• POSTJUNCTIONAL SITES:
• EFFECTOR ORGANS, TISSUES AND GLANDS INNERVATED BY SYMP NERVES

INC INTRACELLULAR INH OF ADEN CYCL --> DEC cAMP

SIGNAL BY IP3 & DAG

• 1. POSTJUNCTIONAL SITES:
• EFFECTOR ORGANS, TISSUES AND GLANDS INNERVATED BY SYMP NERVES

INC INTRACELLULAR INH OF ADEN CYCL --> DEC cAMPIP3 & DAG

• 2. PREJUCTIONAL SITES:
• SYMP NEURONS (AUTO --> Gi INC K)

PARASYMP NEURONS OF SA, SPHINC OF IRIS, GI, (HETERO --> Gi INC K)

• POSTJUNCIONAL SITES:
• CARDIAC MUSCLES

CARDIAC CONDUCTION TISSUE

ADIPOCYTES

JG CELLS OF RENAL AFFERENT ARTERIOL

• POSTJUNTIONAL SITES:
• ARTERIOLS AND VENULES

BRONCHIOLS

UTERUS

GI

LIVER

• PREJUNCTIONAL SITES:
• SYMP NEURONS (HETERO)

RADIAL, IRIS -- a1

SMOOTH MUSC OF EYELID --a?

CANAL OF SCHLEMM -- NOT INERVATED BUT:

• a1 -- ENHANCED OUTFLOW
• a2 -- DEC PROD

b2 PREDOMINATE IN SKEL MUSC

a PREDOMINATE IN GI AND KIDNEY

GRAVE'S DISEASE

EXCESSIVE THYROXINE INC THE SYNTH OF b-RECEPTORS

USE b-BLOCKERS TO DEC THE SYMP-MEDIATED MANIFESTATIONS SUCH AS TREMOR, TACHYCARDIA, AND A-FIB

• EPI -- b2 > b1 > a
• NE -- a > b1 > b2
• PE -- a1 ONLY

PE = PHENYLEPHRINE

• Arterioles
• constriction

• Eye
• enhanced normal
• outflow of canal of schlemm

• Eye
• radial muscle
• contraction of iris (dilation, mydriasis)

• Kidney
• proximal tubule
• increased sodium/water reabsorption

• Lung
• bronchial gland
• secretion decrease

• Salivary Glands
• water and K+ secretion (viscous and sticky)

• Skin
• pilomotor muscle
• contraction

• Urethra
• contraction

• Venules
• constriction

• --a1a--
• Male Sex Organs
• vas deferens, ampulla, prostate gland and seminal vesicles emission and ejaculation

• Urinary Tract
• trigone and ext. sphincter
• contraction

• Arterioles
• constriction

• Eye
• decreased production of aq fluid in eye

• Pancreas
• islet (B) cells
• (insulin) decreased secretion

• Platelets
• aggregation

• Stomach and Intestines
• motility and tone decreased

• Stomach and Intestines
• secretion is inhibited

• Venules
• constriction

• Arterioles
• dilation (via circulating Epi)

• Gallbladder and ducts
• relaxation

• Liver
• glycogenolysis and gluconeogenesis increase

• Lung
• bronchial muscle
• relaxation

• Skeletal Muscle
• glycogenolysis, K+ uptake, tremor, and increased contractility

• Uterus
• relaxation for pregnant and nonpregnant women

• Venules
• dilation (via circulating Epi)