Rx including some antiAchE

myasthemia gravis = autoimmunity to Nm receptors causing fatigue on activity /w recovers on rest.  Rx:

• neostigmine, pyridostigmine -incr ms contr [ADRs -Meffects]
• corticosteroids, azathioprine, cyclosporin -decr antibody prod.
• plasmapheresis -remove antibodies
• thymectomy.

glaucoma = IOP>21 mm causing optic damage. Rx:

1. open angle[ciliary ms]/ chr simple - βblockers, bimoridine/latanoprost, miotic, CAinh
2. narrow angle[circular ms]/ acute congestive[IOP emergent incr w/mydriatic] - βblocker,miotic, osmotic decong-mannitol/glycerol, CAinh, α agonist.

decr AqH secr  from ciliary body –>

• β blockers[first choice,1-2doses/day, decr by 1mos][ ADRs: pupil constr, myopia, brow pain, IOP, mild burn/red/dry, punctate keratitis,decr HR, incr asthma & CHF]
• α agonists – Atropine/dipivefrine[more consistent], brimonidine[2 selective]
• Carbonic anhydrase inh -acetazolamide[shortterm use before/after surgery], dorzolamide [longtterm use -no sys effects]

incr AqH drainage –>

• contr circular ms[narrow angle] -miotics: pilocarpine[many daily doses + ADRs- constr pupil(dim light,cataract), myopia esp young-brow pain, IOP changes, sys:nausea,diarrhoea,sweating,brconstr] physostigmine[adjunct]
• trabecular-90%drianage [lost after midage -->open angle] =
  • contr ciliary[open angle] ms -miotics
  • incr conductivity -α agonist, PG:latanoprost
• 10% uveoscleral drainage -α agonist, PG:latanoprost

parasympathetic nervous system – food metabolism,growth,energy

somatic ns – has synapses inside CNS[brain & spinalcord]. outside CNS mylinated[prone to paralysis,atrophy] post fibres  without plexus formation supply skeletal ms [ Nm receptors -Ach].

autonomic ns -[SNS-TL & PNS-CS originated] pre myelinated fibres synapse at ganglia outside CNS [SNS-paravertebral & PNS-near organs : Nn & M1 receptors] .  post [SNS-long & PNS -short] nonmyelinated fibres form plexuses supply viscera [SNS-widely & PNS-locally to head neck trunk [SNS-NA,A,Ach &  PNS-Ach]

most tissues have both SNS & PNS innervation but only:

* SNS -  bv[most α β2 , some M3-Ach], M3 : sweat gl, hair follicles, spleen.
* PNS – gastric gl, pancreatic gl, ciliary ms[trabecular] of eye.

PARASYMPATHETIC ns :

Nm – NMJ –>skeletal ms contr.

Nn - all autonomic ganglia, adrmed, CNS.

M1 stimulatory – gastric gl -HCl secretion , LES relax , CNS inj stimulates later depresses, all autonomic ganglia[high doses-stimulates -icr HR & BP]

M2 inh – heart [ventricles have less receptors], autoinh receptors on cholinergic nerves.

M3 stimulates metabolic stores & excretion – vasodil, visceral smms contr , exo gl secretion [sweat,lacrym,gastric,pancreatic,salivary] , eye – circular ms contr[miosis] & ciliary ms contr[accomm spasm ->myopia]

ANTI AchE = inh enz hydrolysis of Ach + [R-Achmimetic]

Carbamates -

• lipid sol [orally active,cross BBB,penetrate cornea-contr ciliary & circular ms(miotic-glaucoma,refraction test mydriasis, iritis corneal ulcer adhesions)] =tertiary N  –>physostigmine[natural alkaloid]–>more marked M(peripheral) & CNS(central) effects [poisoning: atropine,anticholinergics,antiH,tricyantiDepr,phenothiazines; CNS depr from diazepams,Ganaesth]

• lipid insol [im/sc inj]=quarternary N+ –>neostigmine[synthetic] –>(no central action) more marked skms effects + cholinomimeticR direct action [myasthemia gravis, decurarization,cobra venom, post operative paralytic ileus & urinary retention].

Organophosphates -[except echotiophate] highly lipid sol -penetrate skin & lungs.

MOA:

AchE sites binding with Ach:

• aromatic anionic site[-] –>attach to N+choline
• esteritic site –>attach to acetly

this acetylated AchE  +water  —>in msec regenerates enz.

reversible inhibitors also bind to anionic site =carbamylated AchE on hydrolysis –>in 30 sec [<synthesis] regenerates enz.

irreversible inhibitors bind only esteritic site =phosphorylated AchE —> regenereated by oximes.   hydrolysis with water takes longer than synthesis & after 24hrs undergoes irreversible aging by loss of alkyl gr.

ADRs of ANTI AchE: sick sinus,AVblock,hypotension,peptic ulcer,asthma,COPD,seizure.

uses of  ANTI AchE:

• MIOTIC [pilocarpine,physostigmine]–>Rx glaucoma[3rd choice to contr circular & ciliary ms], counter mydriasis after refraction test, break adhesions of iritis & corneal ulcer by alt w/ mydriatic.
• incr ms contr [neostigmine,pyridostigmine]–>Rx myasthemia gravis [autoimmune inj to NmR at NMJ causing fatigue on activity /w recovers from rest]
• [Nm action] neostigmine+ atropine[M action] –>Rx postoperative paralytic ileus, urinary retention, decurarization[competit NM blocker], cobra venom resp paralysis.
• cerebroselective stimulants [rivastigmine,donepezil] –>Rx alzeihmers disease.

Anti AchE poisoning:

M effects-

• ingestion- vomiting,diarrhoea
• inhalational- cough,secretions,brconstr-breathlessness,pulm edema
• eye- irritation,myopia,miosis,lacrym,blurring

Nm effects- ms twitch,fascicul,weakness,paralysis

Autonomic ganglia- incr HR, arhthym, vasocons

CNS effects- anxiety,convulsions. later resp depr,coma.

Rx:

• wash skin,mm, shift to fresh air.
• gastric lavage
• patent airway
• BP- hydration
• convulsions -diazepam
• atropine till pupil dilates  -M + CNS[high dose]
• oximes[obidoxime,prali] -Nm effects.

anticholinergics/parasympatholytics/atropinic

ADRs -dry mouth/skin, fever, difficult swallow/talk, urinary retention, photophobis,blurring, CVS[HR,BP] & resp depr, mania,delirium,hallucination,later convulsions,coma.

CIs -BPH in old males, acute congestive narrow glaucoma.

interactions: their absorb/metabolism blocked by antacids,MAOinh.

• delays gastric emptying –>incr absorb of tetracycline,digoxin;   decr absorb of most drugs.
• incr peripheral degradation of levadopa.
• potentiation w/ other antiM: TCAdepr, phenothiazine, antiH, disopyramide.

ATROPIC SUBSTITUTES:

• tertiary compounds -lipid sol – orallyactive, penetrate CNS & cornea.  short acting.
• quaternary – water sol,longer action, less oral/BBB/cornea. [ADRs: ganglionic[N] blockage -postural hypotension,impotence, at high dose Nm block]

actions:

• high doses cause CNS stimulation[depr of vestibular,tremor,rigidity]–>resp,temp-HTh,vaso,vagal,excit,restless,halluc,delirium, later depr & coma.
• depr vestibular vertigo -HYOSCINE –>prohylaxis[4hrs before] for motion sickness [ADRs-sedation,drymouth]
• sedation,amnesia -HYOSCINE –>labor, mania, lie detection.
• decr saliva, decr sweat[incr temp -M3block+hypothalamus stimulation], depr CNS tremor & rigidity -BENZHEXOL, PROCYCLIDINE, BIPERIDEN,BENZTROPINE, CYCRIMINE,ETHOPROPAZINE –>Adjuvant in parkinsonusm, drug induced extrapyramidal syndromes.
• initial bradycardia by M1 autoreceptors. incr HR prominently in  high vagal tone young adults.
• counter bradycardia,Hblock from incr vagal tone -ATROPINE [ADRs -arryth,ischemia]–>MI induced/digitalis induced.
• no marked/consistent effect on BP. high dose decr BP[M3 vasodil],  incr BP[incr BP, CNS vasomotor centre stimul]
• mydriasis[no light reflex,photophobia] + cycloplegia-loss of accommodation[blurring] , incr IOP.
• mydriasis+cyclopegia[loss of accommdtn] -TROPICAMIDE [adults-quick action], ATROPINE/HYOSCINE [children-high tone ciliary ms in cycloplegia (ADRs- behavior abn  by enter nasolacrimal  duct)] –>diagnostic refraction testing.
• only midriasis -PHENLYEPHRINE [elders since glaucoma], TROPICAMIDE –>fundoscopy.
• relax eye ms + anodyne[spasm pain] -ATROPINE [long action] –>iritis,corneal ulcer,keratitis, alt w/ miotic for breaking adhesions.
• decr gastric secretions -M1 selective=PIRENZEPINE,TELENZEPINE [others replaced by H2 blockers] –>Rx peptic ulcer.
• relives spasm, hypermotility [no complete suppression of peristalsis due to local 5HT,encephalins - so rare constipation] -ATROPmethN,HYObutybr, PROPANTHALINE, OXYPHENONIUM, CLIDINIUM, PIPENZOLATE,  ISOPROPAMIDE[esp psyc disorders] –>Rx dyspepsia,gastritis, hypermotility, pylorospasm, irritable bowel, functional/nervous/drug induced diarrhoea, spastic constipation, renal colic. [not biliary colic from opiates (Rx with NITRATES)]
• decr secretions, central brdilation [<adr β2 agonists] -ATROPINEmethN, IPRTROPIUM,THIOTROPIUM[selective M1M3] br[no alv collapse/inf from dry secretions, no impaired cilia, no sysADRs from GI absorb] –>Prophylaxsis[slow onset] COPD , Asthamatic Bronchitis.
• relieves incontinence  [CI in elderly males-BPH -->urinary retention] -[bladder affinity]OXYBUTININ,FLEVOXATINE –>Rx nocturnal enuresis,neurogenic bladder,spina bifida.
• decr reflex secr from pulm emboli, decr saliva, trbroncial scecr, reflex laryngospasm [irritant ether]; [halothane] arrythmia,vasovagal attack -ATROPINE, GLYCOPYROLATE [anti M, no CNS effects]–>preanaesth,anaesthetic.
• antispasmodic + antiemetic -DICYCLOMINE[not very effective] –>Rx morning sickness, dysmenorrhoea.
• antidote[block M&CNS effects] toxicity from ANTI AchE,mushrooms.

Rx of atropine overdose: PHYSOSTIGMINE [central+peripheral effects]

• tannic acid lavage
• dark quiet room
• cold sponging
• artificial resp
• diazepam for convulsions
• hydration to correct BP

sympethetic nervous system

SNS [flight,fright,fight  -stress]:

thoracolumbar origin –>short pre -Ach –>paravertebral ganglia[Nn receptor] –>long post —> wide diffuse actions:

• major -NA,[DA -D1D2 also in basalganglia,limbicsys,CTZ,antpituitary] – α, β1
• minor -Ach -M3
• Adr med -A – weak β1,α  [A more predominant than NA],β2   [β2 more predominant than α]

supplied only bu SNS are:

• most bv [α1 β2 M3],
• M3 -sweatgl, hair follicles, spleen.

phenylalanine —>tyrosine hydroxylase –> [DA-NA in synaptic vesicles]-[A in adrmed] –>

• release modulated by α2 presynaptic inh or  diffusion/displacement by indirect sympathomimetics.
• axonal uptake1 inh by cocaine,guanithidine,H1antagonists. granular uptake inh by reserpine.
• CAs are given by slow i.v, orally inactive since metabolised by MAO,COMT in tissues. orally active agents are ephedrine,amphetamine,mephentermine,isoxsuprine.

sympathomimetics, agonists -

direct action on receptors:

• αβ -A,NA,DA
• α1 -phenylephrine, methoxamine
• α2 -xylometazoline
• β -isoprenaline
• β2 -salbutomol

indirect action by diffusion/displacement of NA: tyramine.

mixed action: ephedrine, amphetamine, mephentermine.

α receptors –

• stronger action :  A > NA.
• inhibitory action.

α1 actions-

• sm ms contr

α1A contr-bladder trigone, prostrate,sphincter. uterus.
α1B vasoconstr of bv of skin mucosa kidney -HTN.
mydriasis -iris radial ms.
heart -arrhythmia.

• git relaxn.
• exo gl secretion.

α2 actions-

• presynaptic inh -NA reuptake .
• inh central sympathetic vasomotor tone.
• inh insulin from pancreas -inh hunger.
• inh adipose lipolysis.
• plt agg -inh bleeding.
• vasoconstr fron circulating CAs.

β receptors-

• β1 -NA,DA -stimulate heart -contr,vel,rate,JG cells to secrete renin.
• β2 -A  -vasodil of  bv of skms,liver,heart[incr O2 demand]; relaxn of smms of br,git,ut,eye;  secr of glucagon –hyperglycemia,glycogenolysis [incr calorigenesis].
• β3  -incr lipolysis.

sysBP= heart CO β1 ; diaBP= Presis vasocons α β2

• NA -incr Fcontr CO & Presis –> incr both sysdiaBP & this is more than that of NA. this incr in BP causes reflex bradycardia[decr HR]
• A -β1 incr in CO but β2 predominant vasodil than α vasocons –> incr sysBP but decr diaBP [high dose/rapid i.v --> α>β2 -->vasocons-incr Presis-initail short incr in diaBP till high dose decr].  α blocker [no incr Presis diaBP] + A –> fall in BP without the short incr in diaBP : VASOMOTOR REVERSAL OF DALE.

ADRs of CAs -

• local necrosis from extravasation,
• slow absorption from sc/im inj vasocons,
• rapid/high dose i.v causes arrhythmia [CI with halothane] –> use slow i.v in emergency.
• HTN [CI with βblocker],
• incr O2 demand by incr HR in angina,CHF,
• incr calorigenesis in thyrotoxicosis.

pharmocological actions of CAs therapeutic uses:

A -α [stronger cation than NA], predominant β2, weak β1

• A [physiologic antagonist of H]–>immediate hypersensitivityIgE urticaria, angioedema, laryngeal edema, anaphylactic shock [incr BP + doesnt cause brcons/laryngeal edema]
• A+ mech/electrical defibrillation –>cardiac arrest form drowning,electrocution ; stoke adams syndrome heart block.
• A+ LA[infiltrate/Nblock,spinal anaesthesia] –>decr systemic toxicity & incr duration of actrion by vasocons.

NA -α, β1  [no β2 action]   used in gastric erosion & stress ulcers.

Isoprenaline -β  used for heart block, stoke adams syndrome.

DA –

• D1 -vasodil of renal[incr GFR -incr urine exr of Nawater],coronary,mesentric bv -used in cardiogenic/septic shock.
• β1 -incr CO & sysBP [pressor agent in severe CHF].
• [α vasocons incr diaBP by large doses]
• doesnt cross BBB -no CNS effects.

Dobutamine [less arhythmogenic than A]- Cardiac stimulant for acuteMI, SEVERE CHF, cardiac surgery.

• β1 incr in contr,CO.
• α vasoconst causes reflex bradycardia -so no incr in BP.

EPHEDRINE [orally active, low CNS effects] -mixed action:

• indirect NA release treats hypotension from postural/spinal anaesthesia.
• receptor action -treats mild chr asthma.

Mephentrermine [orally active, crosses BBB, mixed action -incr sys&diaBP, Rx-hypotension from spinal anaesthesia,surgery,MIshock.

Amphetamine/dextro/meth [mixed action,orally active, CNS stimulant-pschychological dependence, less periheral effects -no physical dependence]]

• incr conc, work capacity
• RAS-incr wakefulness, incr resp.
• anticonvulsant,antiemetic, antimotionsick, analgesic.
• ADRs -temporary euphoria, talketiveness, hallucinations, later anxiety,agitation,decr hunger, high doses cause arrythmia,vomiting,convulsions,death  Rx-chlorpromazine.
• uses – nocturnal enuresis & incontinence, attention deficit[no tolerance dev but decr appetite-growth retardation], narcolepsy after trying imipramine[tolerance,abuse,behavioral abn], adjuvant in parkinsonism,epilepsy & sedation from antiepileptics.

phenylephrine -predominant α1 -vasocons –>

• incr Presis -incr diaBP [+reflex bradycardia],
• mydriasis for fundus ex & decr iop in glaucoma,
• nasal decongestion.

pressor agent [sysdiaBP -ephedrine mephentermine, diaBP-phenylephrine methoxamine, sysBP -DA]

• mixed pressor agent –> hypotension from shock, spinal anaesthesia, antiHTN drugs.
• ephedrine + elastic stockings & fludrocortisone –>postural hypotension[NA release on standing] from autonomic neuropathy [diabetis,parkinsonism],old age
• pressor agent + vol replacement –>neurogenic & hmrrgic shock.
• DOBUTAMINE -cardiogenic shock [incr BP,CO by β action but no incr in cardiac workload by α vasocons],

relative α2 agonists -vasocons –>topical nasal decongestants [cold,rhinitis,blocked ET]

• naphazoline, xylometazoline, oxymetazoline -long acting , initial stinging,  ADRs-chr use impairs ciliary function,atrophy,anosmia; children low dose since sys effects of CNS depression, incr BP.  CI-HTN,MAOi, elderly males.
• EPISTAXIS –>compresses of A + phenylephrine [ADR-incr BP]/pseudoephedrine [less CNS stimulation]
• phenylpropanolamine [decr appetite, hmrrgic stroke]

selective β2 agonists -

• brdilators -salbutamol,terbutaline,salmotorol,formotorol.
• uterine relax [Rx for premature labor, dysmenorrhoea] + vasodil [ not so effective in PVD-beurger, raynauds, gangrene, frostbite, ischemic ulcers, night leg cramps, diabetic & cerebral vascular insufficiency] -ritodrine,isoxsuprine.

anorexics- severe obesity Rx for <3mos.

• seratonergic -fenfluramine [CNS depression]
• NAdrenergic -phenylpropanolamine [sleep interference, hmrrgic shock]
• 5HT+NA -sibutramine [ADRs- tolerance dev, deaths from CV events incr BP HR, insomnia, anxiety, mood swings, dry mouth, chest pain, constipation]

Adrenergic neurone (membrane release) blockers

RESERPINE, GUANITHEDINE, BRETYLIUM

• cause more complete sympathetic blockage than adrenergic receptor antagonists [α β blockers].

alpha blockers

α blockers -

• actions mostly manifest as sideeffects.
• have additional individual drug actions + relative receptor type(1/2) action + central action.

α1 block causes–>

• vasodil, decr Presist, decr Vreturn, decr CO, fall BP–>postural hypotension.
• decr CO –>decr GFR – sod+water retention – β1 renin stimulation.
• nasal congestion.
• miosis.
• diarrhoea from incr peristalsis.
• BPH -incr urine flow.
• impotence -decr vasdef ejaculation.

α2 block causes–>

• central vasomotor tone not inh – rises BP. but taken over by more predominant β2 A action of vasodil – fall BP VASOMOTOR REVERSAL OF DALE.
• no presyn inh –> NA incr –>fall BP –>cardiac stimulation -reflex techycardia-palpitation.

NONEQUILIBRIUM/IRREVERSIBLE[3-4days] BLOCKAGE – phenoxybenzamine

• decr BP -Rx for inoperable/malignant pheochromocytoma[Adrmed tumor]. pre&intraoperative(1-2wks)-reverse CA ECF shift, outpouring CA during surgery, restore blood vol so can counter fall in BP after surgery.
• shifts blood from pulm to systemic -peripheral vascular disease [but not organic burgers & ischemic intermittent claudication].
• more post cap dil -ECF to vascular compartment shift decr pulm edema – incr CO & tissue perfusion–>WITH IV FLUIDS  for Rx secondary shock[reflex vasoconstr-cold pale extremities, low pulse, incr venous pressure].

ADRs- palpitation, post hypoTN[but recumbent incr CO], im/sc inj causes pain, lipid soluble -enters brain -[rapid iv -cns stimulatn & vomiting] [oral erratic & causes cns depr] , chronic use accumulates in adipose.

natural ergots

• more agonistic than antagonist.
• causes gangrene in peripheral vascular insufficiency.

hydrogenated ergots[short action]

• more antagonistic than agonistic
• Rx of mod/severe migraine, diagnostic ppt for ECG in ischemia, cognitive enhancer.

phentolamine -iv infusion decr BP in min

• diagnosis fall 35:25/more+management of pheochromocytoma.
• Rx of HTN on clonidine withdrawl/MAOi cheese rxn.
• local vasoconstr from extravasation of NA/DA.

α1 selective -

prazosin [6-8hrs][ADR -mild palpitation,postural hypoTN -start with low dose at bedtime to dev tolerance], terazosin/doxazosin [24hrs] ;

• 1B : decr BP  + phosphodiesterase inh rising cAMP in sm ms –> antiHTN,
• 1B: decr CO -short term before ACEi for CHF uncontrolled by diuretics/digitalis,
• 1B: raynauds disease, acrocyanosis.
• 1A : decr tone not size(finasteride-alpha reductase inh -onset 6mos) – relieves BPH in 2wks [hesistency,dribbling,residual]

1A uroselective -tamsulosin -no ADRs from cardiac stimulation/postural hypoTN.

beta blockers

β receptors-

• β1 -NA,DA -stimulate heart,JG cells.
• β2 -A  -reax/secr  bv of skms,liver,heart; smms of br,git,ut,eye.
• β3  -incr lipolysis.

β blockers- actions/uses-

• decr heart rate,contr, CO –>no incr in oxygen demand–>no ischemia,  so incr stress tolerance[exercise,emotional] of heart esp in angina.
• β BLOCKER WITHOUT INTRINSIC SYMPATHOMIMETIC [propranolo,sotalol,timolol,nodalol] for secondary prophylaxis in MI w/ HR>50 HblockPR int<0.24sec[prevent reinfarct & fibrillation], intravenously to salvage in 4-6 hrs [decr O2 demand & arrhythm]
• no β2 vasodil –>initially incr Presis –>decreasing CO with little change in BP –>later adaptation to decr CO with no incr Presis –> fall in sys&dia BP -mild antiHTN [first choice drug since Pt acceptibility].
• most effective chr prophylaxis for migraine.
• suppress A/anaesthesia/digitalis [not digoxin/Ca/glucagon/methylxanthine] induced tachycardia/extrasystoles/fibrillation. –>after α blocker antiHTN is given for pheochromocytoma.
• decr Fcontr & aortic pulsation in dissecting aortic aneurysm.
• low doses benefit hemodynamics by preventing overactivity in dilated cardiomyopathy & after restoration of mild-mod CHF w/ no fluid retention/iv vasodilator/ionotropic drugs.
• incr br resis esp in COPD & asthma.
• blocks lipolysis [incr TG,LDL & decr HDL,FFA]
• blocks insulin release –>hypoglycemia but no warning  tachycardia/tremor –>A release –>decr glycogenolysis & incr BP.
• NONSELECTIVE BLOCKER- decr FFA & glycogenolysis –>no fuel to Skms  +  decr blood to skms from no vasodil –>decr physical exercise performance –>decr essential tremor.
• decr peripheral T3 formation –>initially[for tremor,palpitation,sweating,nervous,myopathy,stare] in Rx w/ antithyroid drugs & preoperative thyrotoxicosis
• decr AqH & iop in chr simple wide angle glaucoma [first choise -topical timolol,nodolal-long t1/2].
• short term decr anxiety[palpitation,tremor not neurosis] during exams/public appearance.
• long term subtle lack of drive,forgetfulness,nightmares, rare hallucinations.

ADRs-

• ppt CHF, Hblock & edema.
• ppt vasospastic angina by unopposed coronary vasoconstr.
• lipid profile risk in Coronary artery disease.
• rebound HTN from sudden withdrawl due to suprasensitive adaptation of βreceptor to A.
• bradycardia<60 esp in sick sinus.
• decr exercise performance –>tiredness.
• decr carb tolerance in prediabetics; no warning hypoglycemia signs & rises BP from A release; delayed recovery from hypoglycemic drugs.
• worsens COPD & asthma by incr br resis.
• worsens peripheral vascular disease [cold extremities] by no vasodil.
• chronic use -lack drive, forgetfulness, nightmares, rarely hallucinations.
• simultaneous Rx w/ cold medication α agonists: ephidrine,pseudoephrine causes rise in BP.
• NSAIDs block antiHTN action.
• prolongs lignocaine,chlorpromozanine.

NONSELECTIVE

WITHOUT intrinsic sympathomimetic -

• propranolol[lipid soluble-brain, oral w/ food to decr first pass metabolism-short t1/2],
• sotalol [class 3 antiarhythmic , pot blocker]
• timolol,nodalol.

PARTIAL AGONIST=WITH intrisic sympathomimetic

prevents exercise tachycardia but no bradycardia at rest –>so antiHTN in bradycardia prone elderly/sick sinus.
due to continued agonistic action – no rebound HTN.
no lipid risk.
dilate cerebral bv.
no renin decr.

• pindolol,oxy,alpre,cart,
• acebutolol.

with α blocking - decr both CO & Presis –> decr BP [pheochromocytoma,clonidine withdrawl,essentialHTN] but incr limb blood flow , no lipid risk, inh NA reuptake so no palpitations [ADRs- postural hypoTN,impotence,liver damage,rash]

• labetalol
• carvedilol -antioxidant.

CARDIO selective at low doses[HTN,Angina]= β1[ asthamatics,diabetics,PvascD,lipid risk, no tiredness] [β2 tremor persists]

• metoprolol,
• atenolol [most commom antiHTN & antianginal]
• acebu [partial agonist & antiarhythm]
• esmolol iv ultrashort<10min [supra ventr tachy, fibrillation/arythm, early Rx of MI, decr HR&BP during cardiac surgery]
• bisopro,beto,celipro.

lipid insoluble[oral absorp less but no first pass metabolism-so long t1/2]=no CNS effects -atenolol,sotalol.

membrane stabilizing antiarhyth at high doses -propranolol,oxy,acebu.