-
PHOSPHODIESTERASE INHIBITORS
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
-
THEOPHYLLINE
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
-
CAFFEINE
PDE INH
MOA -- PREVENTS PDE FROM CHANGING cAMP TO 5'-AMP (SIMILAR TO THREO
THERA -- RELAX SMOOTH MUSC OF BRONCHs IN ASTHMA Pt
-
PAPAVERINE
PDE INH
MOA --PREVENTS PDE FROM CHANGING cAMP BACK TO 5'-AMP
-
SILDENAFIL
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
-
INC/DEC URINARY pH
- ACETAZOLAMIDE (MORE BASIC / ALKALINE)
- -GLAUCOMA (CARBONIC ANHYD INH)
AMMONIUM CHLORIDE (MORE ACIDIC)
-
ACh SYNTH / RELEASE
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
-
ACh
CHOLINERGIC AGONIST
- MOA -- GIVEN IV
- 1o 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
-
BETHANECHOL
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
-
SUCCINYLCHOLINE
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
-
PILOCARPINE
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)
-
CEVIMELINE
CHOL AGONIST
MOA -- SYNTHETIC M AGONIST
PHARM -- INC SALIVATION
THERA -- DRY MOUTH & EYES ASSOC W. SJOGREN'S SYND
- ADVERSE --
- GI CRAMPING
- SWEATING
- UTI
- RHINITIS
-
METHACHOLINE
CHOLINERGIC AGONIST
MOA -- M RECEPTOR AGONIST
PHARM -- CONTRICTION OF BRONCH MUSC
THERA -- PROVOCATIVE AGENT IN Dx OF BRONCH ASTHMA (meTHAcholine IS FOR asTHMA)
-
CARBACHOL / CARBAMYLCHOLINE
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
-
CHOLINERGIC AGONISTS
"AMC BETHANNE SUCCS PILO"
- ACh
- METHACHOLINE
- CARBACHOL (CARBAMYCHOLINE)
- BETHANECHOL
- SUCCINYLCHOLINE (nicotinic also)
- PILOCARPINE
- ACh -- Given i.v.
- Exerts 1o 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 -- 3o 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)
-
EPINEPHRINE
GLAUCOMA
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
-
DRUGS THAT INC OUTFLOW OF AQ HUM THROUGH THE UVEOSCLERAL PATHWAY
Tx OPEN-ANGLE GLAUCOMA
- LATANOPROST (PGF2a ANALOG)
- BIMATOPROST - EYELASHES
-
DRUGS THAT INC AQ HUM OUTFLOW THROUGH THE NORMAL PRESSURE-DEPENDENT PATHWAY
Tx FOR OPEN-ANGLE GLAUCOMA
PILOCARPINE (m AGONIST)
EPINEPHRINE (a1-BLOCKER)
- ISOFLUROPHATE (OP ACE INH)
- ECHOTHIOPHATE ''
-
DRUGS THAT DECREASE RATE OF AQ HUM PRODUCTION
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
-
BIMATOPROST & LATANOPROST
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
-
MANNITOL
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!"
-
BETAXOLOL & TIMOLOL
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!"
-
APRACLONIDINE
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!"
-
ACETAZOLAMIDE
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!"
-
ECHOTHIOPHATE
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!"
-
ISOFLUOPHATE (DFP)
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!"
-
DORZOLAMIDE
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!"
-
TREATMENT OF GLAUCOMA
"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: CLASSES OF DRUGS TO TREAT FORMATION OF AQ HUM & OUTFLOW
- FORMATION:
- b-ADREN ANTAGONISTS
- CARB ANHYD
- a2-ADREN AGONISTS
- OUTFLOW:
- PGF-2a
- a1-ADREN AGONIST
- PILO, ISO
-
NMDA RECEPTOR AGONIST
MEMANTINE
ALZ Tx
GLUTAMATE NMDA ANTAGONIST -- EXCESS NMDA STIM --> Na + Ca ENTRY --> EXCITOTOXICITY AND NEURONAL CELL DEATH
-
PHYSOSTIGMINE
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
-
DONEPEZIL
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
-
NEOSTIGMINE
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
-
PYRIDOSTIGMINE (given p.o.)
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)
-
EDROPHONIUM
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
-
Sx OF INH OF AChase AT MUSCARINIC SITES
EXCESSIVE SALIVATION
RHINITIS
BRADYCARDIA
BRONCHOSPASM
BOWEL CRAMPING
DIARRHEA / VOM
URINARY INCONTINENCE
-
CARBARYL
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!!!
-
RIVASTIGMINE
INDIRECT REVERSIBLE INH OF AChase (CARBAMATE)
EXELON -- PATCH
-
GALANTAMINE
INDIRECT REVERSIBLE INH OF AChase (CARBAMATE)
-
Dx FOR COGNITIVE LOSS
MEMANTINE (NMDA)
PHYSOSTIGMINE (CARB)
TACRINE (CARB)
DONEPEZIL (DOC -- CARB)
GALANTAMINE (CARB)
RIVASTIGMINE (CARB -- EXELON PATCH)
-
CARBAMATE REVERSIBLE AChase INHIBITORS
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
-
DIMPYLATE
OP AChase INH (DIP ME)
MOA -- INSEC LAWN & GARDEN
PHOS AChase ACTIVE SITE
SPONT RATE OF HYDROL OF PHOS ENZ IS SUPER LOW
-
ISOFLUOPHATE (DFP)
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
-
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)
-
PARATHION
OP AChase INH (IRREVERS) "DIP ME"
MOA -- INSECTICIDE CONVERTED TO ACTIVE METABOLITE PARAOXON BY CYP450
ADVERSE -- ACCIDENTAL POISONING / DEATH
-
MALATHION
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
-
ORGANOPHOSPHATE AChase INHIBITORS
- DIM-PYL-ATE
- ISO-FLUO-PHATE
- PARATHION
- MALATHION
- ECHO-THIO-PHATE (glaucoma also)
-
PRALIDOXIME
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
-
ATROPINE
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
-
SCOPOLAMINE
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)
-
CYCLOPENTOLATE
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
-
TROPICAMIDE
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)
-
BENZOTROPINE
3*M ANTAGONIST
MOA -- AT CENTRAL M RECEPTOR
PHARM -- SAME AS ATROPINE & SCOPE
THERA -- PARKINSON'S
-
TRIHEXYPHENIDYL
3*M ANTAGONIST
MOA -- AT CENTRAL M RECEPTOR
PHARM -- SAME AT ATROPINE & SCOPE
THERA -- PARKINSON'S
-
DICYCLOMINE
3*M ANTAGONIST
MOA -- AT GI TRACT
PHARM -- SAME AS ATROPINE & SCOPE
THERA -- PREVENT BOWEL SPASM & DEC PAIN W/ IBS
-
HYOSCYAMINE
3*M ANTAGONIST
MOA -- AT GI TRACT
PHARM -- SAME AS ATROPINE & SCOPE
THERA -- PREVENT BOWEL SPASM & DEC PAIN W/ IBS
-
OXYBUTYNIN
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
-
TOLTERODINE
3*M3 ANTAGONIST
"DOTTS"
MOA -- ?
PHARM -- SAME AS ATROPINE & SCOPE
THERA -- URGE INCONTINENCE (OAB)
ADVERSE -- DRY MOUTH, BLURRED VISION, CONSTIP & SOMNOLENCE
-
SOLIFENACIN
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?
-
DARIFENACIN
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
-
RESPIRATORY DISEASES
- 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)
-
MYASTHEMIA GRAVIS
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
-
PARKINSONS
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
-
S/E OF ATROPINE-LIKE DRUGS
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
-
MOTION SICKNESS
CAUSED BY EXCESSIVE M RECEPTORS IN VEST NUC AND RET FORMATION
SCOPOLAMINE (PATCH) -- CAUSES ANTEROGRADE AMNESIA! ACCENTUATED BY ETHANOL
DIPHENHYDRAMINE (DRAMAMINE)
-
DIPHENHYDRAMINE
BENADRYL
3*M ANTAGONIST
MOA -- AT CENTRAL M RECEPTORS & ANTIHIST
PHARM -- SAME AS ATROPINE & SCOPE
THERA -- CAN BE USED FOR PARKINSON'S
-
OVERACTIVE BLADDER DRUGS
"DOTTS"
3*M ANTAGONISTS
- DARIFENACIN
- OXYBUTYNIN
- TOLTERODINE
- TROSPIUM (4*M)
- SOLIFENACIN
-
TERTIARY MUSCARINIC RECEPTOR ANTAGONISTS
"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
-
N-METHYLATROPINE
4*M ANTAGONIST
PHARM -- SAME AS 3*M. DOES NOT ENTER CNS!
-
METHSCOPOLAMINE
4*M ANTAGONIST
PHARM -- SAME AS 3*M. DOES NOT ENTER CNS
-
N-METHYLHOMATROPINE
4*M ANTAGONIST
PHARM -- SAME AS 3*M ANT. DOES NOT ENTER CNS
-
TROSPIUM
4*M ANTAGONIST
"DOTTS" OVER-ACTIVE BLADDER DRUG
MOA -- NON-SELECTIVE MUSC ANTAGONIST
THERA -- URGE INCONTINENCE (OAB)
ADVERSE -- PERIPH ANTI-M Sx
-
IPRATROPIUM
4*M ANTAGONIST
-
GLYCOPYRROLATE
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)
-
TIOTROPIUM
4*M ANTAGONIST
-
QUATERNARY MUSCARINIC RECEPTOR ANTAGONIST
- N-METHYL-ATROPINE
- METH-SCOPOLAMINE
- TIO-TROP-IUM
- IPRA-TROP-IUM
- GLYCO-PYROL-ATE
-
NICOTINE
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
-
SUCCINYLCHOLINE
N AGONIST
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
-
NICOTINIC RECEPTOR AGONIST
NICOTINE SUCCS!
- NICOTINE
- SUCCINYL-CHOLINE (cholinergic also)
-
GANGLIONIC BLOCKING DRUGS
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
-
MECAMYLAMINE
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)
-
TRIMETHAPHAN
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)
-
NE
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)
-
EPI
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:
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
-
DOPAMINE
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))
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)
-
TERBUTALINE
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)
-
ALBUTEROL
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)
-
OXYMETAZOLINE
ADREN AGONIST
MOA -- a ONLY
THERA -- NASAL DECONG
OXYMETAZOLINE LONGER DURATION OF ACTION > PHENYLEPHRINE
- ADVERSE --
- RENAL & MESENTERIC ISCH (a)
REBOUND NASAL CONG (NASAL VC)
-
TYRAMINE
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)
-
PSEUDOEPHEDRINE
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
-
EPHEDRINE
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)
-
AMPHETAMINE
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!!!
-
PHENYLEPHRINE
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)
-
RITODRINE
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)
-
PIRBUTEROL
ADREN AGONIST
MOA -- SELECTIVE b2
b2 >> b1
- ADVERSE --
- *Cardiac arrhythmias (β)
*Angina in pts w/ CAD (β)
*Tremor (β2)
-
SALMETEROL
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)
-
ISOPROTERENOL
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)
-
DOBUTAMINE
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)
-
ADRENERGIC AGONISTS
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
-
PHENOXYBENZAMINE
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)
-
PHENTOLAMINE
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)
-
PRAZOSIN (terazosin, doxazosin)
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)
-
TAMSULOSIN
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
-
Tx OF ESSENTIAL TREMOR
NON-SELECTIVE b-BLOCKER:
PROPRANOLOL OR TIMOLOL
ENHANCED BY EXCESSIVE INTAKE OF CAFFEINE, LACK OF SLEEP, ALC, HANGOVER AND STREN EXCERSISE.
-
DRUGS FOR PHEOCHROMOCYTOMA TO CONTROL BP DURING SURGERY
- PRAZOSIN (a1)
- OR
- PHENTOLAMINE (a1 = a2)
+
NON-SELECTIVE b ANATAGONIST (PROPRANOLOL)
-
LABETALOL
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)
-
PAPAVERINE
Tx OF IMPOTENCE
MOA -- PDE INH
(SILDENAFIL ALSO)
-
ALPROSTADIL
Tx OF IMPOTENCE
MOA -- TOPICAL OR INJ INTO CORPUS CAVERNOSA
PGE-1 ANALOG
-
PHENTOLAMINE
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
-
POSSIBLE S/E OF ALL a-BLOCKERS
- --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
-
ERGOTAMINE
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)
-
YOHIMBINE
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)
-
a-ADRENOCEPTOR ANTAGONISTS
- PHEN-OXY-BENZ-AMINE
- PHEN-TOL-AMINE
- PRAZOSIN
- TERAZOSIN
- DOXAZOSIN
- TAMSULOSIN
- LABETALOL
- YOHIMBINE
- ERGOTAMINE
- DIHYDRO-ERGOTAMINE
-
Tx OF IMPOTENCE
"FUN PAPA SOLD ALL"
- PHENTOLAMINE
- PAPAVERINE
- SILDENAFIL
- ALPROSTADIL
-
ATENOLOL
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
-
DIGOXIN
LIKE 3* CHOL AGONIST
ACTS IN CNS TO INC VAGAL TONE --> AV BLOCK
COUNTER WITH ATROPINE
-
METOPROLOL
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
-
ESMOLOL
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
-
PROPANOLOL
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
-
TIMOLOL
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
-
LABETOLOL
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
-
NAME THE b-ADRENOCEPTOR ANTAGONISTS (b-BLOCKERS)
"ATENsion, BET TIM's LAB MET ES a PRO!"
- BETAXOLOL
- ATENOLOL
- METOPROLOL
- ESMOLOL
- PROPANOLOL
- TIMOLOL (glaucoma)
- LABETALOL
-
COCAIN
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
-
GUANETHIDINE
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
-
RESERPINE
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
-
a-METHYLDOPA
- 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
-
SYMPATHOLYTIC DRUGS
ARG!
- a-METHYLDOPA
- RESERPINE
- GUAN-ETH-IDINE
-
NEURONAL NE UPTAKE 1
COCAINE
-
PHARMACODYNAMICS & KINETICS
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
-
ENTERAL ROUTES
BUCCAL
PER OS (p.o) -- SLOW ABS & SUBJECT TO HIGH FIRST PASS FILTERING
RECTAL - DELAYED FIRST PASS. USED WHEN pt IS NAUSEATED
-
PARENTERAL ROUTES
- 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)
-
ROUTES OTHER THAN ENTERAL/PARENTERAL
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)
-
CHEMICAL NATURE OF DRUGS
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)
-
DRUG ABS IN GI
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
-
BIOEQUIVALENCE OF GENERIC DRUGS
MUST PRODUCE PLASMA CONC VS. TIME CURVE AFTER p.o. DOSING COMPARABLE TO PROPRIETARY.
BIOEQ IS PRIMARILY A FUNC OF BIOAVAILABILITY
-
DRUG BIOTRANSFORMATION
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)
-
PHASE I REACTIONS
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
-
INDUCERS OF HEPATIC CYP450 AND CLINICAL SIG
- 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
-
INHIBITORS OF CYP450 AND CLINICAL SIG
- 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
-
PHASE II REACTIONS
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)
-
ENTEROHEPATIC SECRETION
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)
-
RENAL EXCRETION
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
-
GENERAL PHARMICOKINETIC MODEL
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
-
ONE-COMPARTMENT OPEN MODEL
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)
- 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
-
APPARENT VOLUME OF DISTRIBUTION (Vd)
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)
-
ELIMINATION RATE CONSTANT
- K = (0.7) / (t1/2)
- 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
-
Cpss
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
-
RULE OF 4s
RELATIONSHIP BETWEEN t1/2 AND CONSTANT DOSING RATE
93% Cpss OCCURS AFTER 4 T1/2
FIXED DOSE x 4(t1/2) = 93% Cpss
-
CLEARANCE (Cl)
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
-
RENAL CLEARANCE VALUES: FILTERED vs. SECRETED AND RE-ABS vs. NOT
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)
-
LOADING DOSE
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
-
CALCULATE Cpo
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
-
SLOW ACETYLATORS
"SHIP"
LIKELY TO DEV TOXICITY
- Sulfapyridine
- - hepatic damage & blood dyscrasias
- Hydralazine
- - lupus-like syndrome
- Isoniazid
- - peripheral neuropathy
Procainamide - lupus-like syndrome
-
ACETAZOLAMIDE
MAKES URINE MORE BASIC (ALKALINE)
THERA -- Rx OVERDOSE: INC EXCRETION OF WEAK ACIDS (ex ASPRIN)
-
AMMONIUM CHLORIDE
MAKES URINE MORE ACIDIC
THERA -- Rx OVERDOSE --> INC EXCRETION OF WEAK BASES (ex amphetamine)
-
DRUGS USED TO AFFECT URINARY pH
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)
-
a1-ADRENORECEPTORS FOUND IN:
- POSTJUNCTIONAL SITES:
- EFFECTOR ORGANS, TISSUES AND GLANDS INNERVATED BY SYMP NERVES
INC INTRACELLULAR INH OF ADEN CYCL --> DEC cAMP
SIGNAL BY IP3 & DAG
-
a2 - ADRENORECEPTORS FOUND AT
- 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)
-
b1-ADRENORECEPTORS FOUND AT
- POSTJUNCIONAL SITES:
- CARDIAC MUSCLES
CARDIAC CONDUCTION TISSUE
ADIPOCYTES
JG CELLS OF RENAL AFFERENT ARTERIOL
-
b2-ADRENORECEPTORS FOUND AT
- POSTJUNTIONAL SITES:
- ARTERIOLS AND VENULES
BRONCHIOLS
UTERUS
GI
LIVER
- PREJUNCTIONAL SITES:
- SYMP NEURONS (HETERO)
-
SYMP MUSCLES OF EYE
RADIAL, IRIS -- a1
SMOOTH MUSC OF EYELID --a?
CANAL OF SCHLEMM -- NOT INERVATED BUT:
- a1 -- ENHANCED OUTFLOW
- a2 -- DEC PROD
-
DISTRIBUTION OF a AND b2 IN ARTERIOL BEDS
b2 PREDOMINATE IN SKEL MUSC
a PREDOMINATE IN GI AND KIDNEY
-
HYPERTHYROIDISM
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, NE, AND PE SELECTIVITY
- EPI -- b2 > b1 > a
- NE -- a > b1 > b2
- PE -- a1 ONLY
PE = PHENYLEPHRINE
-
a1 RECEPTOR: LOCATIONS AND ACTION
- 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
- --a1a--
- Male Sex Organs
- vas deferens, ampulla, prostate gland and seminal vesicles emission and ejaculation
- Urinary Tract
- trigone and ext. sphincter
- contraction
-
a2 RECEPTOR: LOCATIONS AND ACTION
- Eye
- decreased production of aq fluid in eye
- Pancreas
- islet (B) cells
- (insulin) decreased secretion
- Stomach and Intestines
- motility and tone decreased
- Stomach and Intestines
- secretion is inhibited
-
b2 RECEPTOR: LOCATIONS AND ACTION
- 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)
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