LIST B Flashcards
B/1 CHOLINERGIC TRANSMISSION & ITS PRESYNAPTIC MODIFICATION
- Extracellular Ca2+
- 4-aminopyridin (voltage
dependent K+ channel
inhibitor) - Activation of presynaptic
activator receptors (M1,
Beta-2, AT1 - Inhibition of presynaptic
inhibitor receptors (M2,
alpha-2, D2, MOR) - Alpha-latrotoxin
Presynaptic Inhibition: 1. Local anesthetics, tetrodotoxin (-VG Na) 2. Low EC. Ca2+ level, omega-conotoxin 3. vesamicol (VAT inhibitor) 4. botulinum toxin 5. Inhibition of presynaptic enhancer receptors (M1, beta-2, AT1) 6. Enhance the presynaptic ihibitory receptors (M2, alpha-2, D2, MOR) 7. hemicholinolytics (CHT inhibitors)
B/2. ADRENERGIC TRANSMISSION & ITS PRESYNAPTIC MODIFICATION
-Synthesis: Precursor substance - levodopa
-Release
1. Depolarization: 4-aminopyridine (Fampridine)
(K+ channel blocker)
2. Increased Ca2+ concentration
3. Latrotoxin - causes explosive
release of norepinephrine
4. Presynaptic receptors:
+ stimulatory pre synaptic Beta2R & AT1(heteroR)
- of inhibitory pre sy alpha2
autoreceptors (yohimbine, mianserin)
- Indirectly acting sympathomimetics
(tyramine, ephedrine, amphetamine) -promote transmitter release
-Reuptake inhibitors
(cocaine, tricyclic antidepressants: amitryptyline, desipramine)
PRESYNAPTIC INHIBITION:
- Alpha-Methyltyrosine (methyrosine) ± blocks
the tyrosine hydroxylase enzyme - Reserpine ± prevents transmitter storage
- Tetrodotoxin, saxitoxin, local anaesthetics
(blockade of voltage sensitive Na+ channels) - omega-Conotoxin ± blocks
calcium channels - Inhibitory presynaptic alpha2 autoreceptors (clonidine, methyldopa)
- Activation of presynaptic inhibitory
heteroreceptors (M2, D2, H3, adenosine,
neuropeptide Y, EP3 prostaglandine, Mu/kappa/lambda Opoid R - Adrenergic neuron blockers (guanethidine,
bretylium) - inhibit transmitter release - 6-OH-dopamine -destroys the nerve
B/3. CHOLINOMIMETICS
Direct agonists:
-methacholine: M-selective
Diagnostical tests for bronchial reactivity
-carbachol: resistant to AchE
1. glaucoma. 2. surgery on eyes
3. atonic gut or bladder - ORAL, I.M, S.C.
D=0.5-2hr
-betanechol: M-selective agonist (increases IP3+DAG), resistant to AchE
(atonic gut or bladder eg after surgery/spinal
injury)
ORAL, IM , S.C (poor lipid solubility, DOESNT enter cns)
D=0.3-2hr
SE: cyclospasm, diarrhea, urination, vasodialation, reflex tachy, sweating
*M-R on most endothelial cells are NOT innervated; respond only to Direct-acting drugs
-pilocarpine(3): M-selective ( increases IP3+DAG)
(1. sjogren syndrome, 2. was used for glaucoma “miosis, cyclospasm”) 3. xerostomia
D=0.5-2hr
ORAL, IM , good lipid solubility , topical activity in eye
SE: similar to bethanechol but also VASOCONSTRICTION via ganglionic effect( +EPSP via M-R in ganglia)
ACh esterase blocker:
- edrophonium(4): inhibit AchE , amplifies endogenously released Ach
1. Reversal of Neuromuscular block caused by
non-depolarising agent
2. diagnosis of MG (tensilon test I.V, I.M)
Highly polar, used IV. D=5-10min
SE: increased parasym effect, nausea, vomit, diarrhea, urination
-donepezil, rivastigmine(3), galantamine: used in alzhiemers , lipid soluble
T1/2= 1.5-70 hrs
SE: nausea , vomit
-physostigmine(3): ;enter cns
1. Atropine poisoning (IV)
2. Acute glaucoma (topical)
lipid soluble
D=2-4hr
SE: parasymp effect but longer duration than edroph
+ seizures
-neostigmine(4): inhibits AchE+ direct nicotinic agonist action
1. Reverses Neuromuscular block,
2. treatment of MG
3,glaucoma
4. Stops muscle relaxant agent effects (I.V)
5.gut/bladder atonia (S.C, I.M, I.V)
polar, but orally active
D=2-4hr
SE: parasym effect, longer duration than edroph
-pyridostigmine: (4)
1. treatment of MG,
2.Gut atonia
3. stops muscle relaxant agent effects (I.V)
D=4-8hr, polar but orally active
SE: increased parasym effects, longer duration than neo
Pralidoxime= chemical antagonist of organo-p
regenerates P-enzyme
-organophosphate:
parathion: Irreversible AchE inhibitor
insecticide, highly lipid soluble D= days-weeks
SE: parasymp effect+ muscle paralysis, coma
Malathion: insecticide + scabicide (topical)
highly lipid soluble, but metabolised to inactive products in mammals and birds
D= days
SE: safer than parathion
Sarin, tabun: nerve gases, terrorist threat
highly lipid soluble, more rapid action
SE: rapidly lethal
Ecothiopate= rarely used in glaucoma
B/4. MUSCARINIC-r BLOCKING DRUGS
Tropeins:
*atropine(3) : competitive antagonist(Inverse ag) at ALL MR
-1. mydriatic & cycloplegic 2. antidote for cholinesterase-inhibitor toxicity 3.bradycardia
4. AVblock. 5. smooth.m spasm
lipid soluble, D=2-4 hr except in eye >72hrs
SE: sedation, hyperthermia, flushing, delerium
*scopolamine: antimotion sickness via transdermal patch (alters endolymph pro in cochlear-vestibular )
- butyl-scopolamine(4) used in smooth m spasm
- ipratropium
- tiotropium
- benztropine: somewhat M1 selective for treating resting tremor in parkinson
Non-tropeins:
- oxybutynin: oral, transdermal used for urinary urgency, incontinence
-solifenacine, darifenacine: modest M3R antagonist
1. urinary urgency, incontinence
2.hyper reactive bladder sy
D=12-24 hr , ORAL
se: excessive parasympatholytic effects
- cyclopentolate: topical opthalmic use to produce mydriasis , cycloplegia (D=2-12hr)
- tropicamide: D=0.5-4hr
-procyclidine(3) I.V, PARENTERAL used in parkinsons
-pirenzepine, telenzepine: M1 antagonist
1. peptic disease
ORAL,
B/5. CATECHOLAMINES
Epinephrine: +ino,chrono. , PARENTERAL, TOPICAL
IND: 1. Anaphylactic shock
2. emergency management of complete heart block, cardiac arrest
3.asthmatic
4.inhaled E treats croup
5. reduction of blood flow
SE: HTN, arrythmia, stroke, MI, pulmonary edema
norepinephrine(mainly alpha-1) - IV only
1. neurogenic/septic/cardiogenic shock
4.locally to reduce blood flow
SE: vasospasm, tissue necrosis, BP increase, arrhythmia, infarction
isoproterenol (isoprenaline): potent selective B-agonist
+ino/chrono
IND: bradycardia, AV block (I.V), acute asthma (nebulizer)
dopamine: D1, a1, a2, b1, b3 agonist, IV only
low dose: + D1 (vasodilation increases renal blood flow)
medium dose: +B1r
High dose: +a1 , loses selectivity, acts like epinephrin
IND: 1. cardiogenic shock esp w/renal shutdown
2. sometimes in HF
SE: tachy, tolerance, arrythmia, CV disturbance
dobutamine : selective beta-1 agonist inotropy IND: 1. cardiogenic shock 2. used in acute HF to increase CO SE: tachy
B/6. INDIRECT SYMPATHOMIMETICS
-Release-inducing agents: displaces stored catecholamines from nerve endings
- amphetamine, methamphetamine:
(ADHD, narcolepsy, anorexiant loss of apetite)
oral, parenteral. D=>4-6HR
SE: addiction, paranoia, aggression, HTN, insomnia, seizure
*methylphenidate,
*tyramine: found in fermented food
(very high first pass metabolism, unless pts taking MAO-I
SE: HTN, stoke, MI, arrhythmia
*ephedrine: displacer + some direct activity (ORAL, D=4-6hr) less addictive 1. sometimes for narcolepsy 2. idiopathic postural hypotension 2. enuresis (CANNOT control urination)
-Reuptake inhibitors:
*cocaine: blocks NET,DAT
(local anasthetic w/ intrinsic hemostatic action)
Parenteral (topical, IV , local injection)
D=2hr
SE: addictive, HTN , arrythmia, seizure
- TCA, atomoxetine, modafinil
- MAO inhibitors: tranylcypromine, selegiline, moclobemide
-Alpha1 agonists: phenylephedrine( a1, a2)
decongestant, mydriatic , neurogenic hypotension
SE : rebound hyperemia, Ischemic change of mucosa
swallowing>systemic SE
-Alpha2 agonists:
clonidine: decreases SYM
treat htn
oral(d=2-3d), transdermal(d=1w)
se: sedation, severe rebound htn if suddenly stopped,
dry mouth, brady, orthostatic hypo, depression
Methyl-Dopa: HTN, HTN in pregnancy
oral, d=12-24hr
se=sedation, hemolytic ab
oxymetazoline: eye redness
Rilmenidine, moxonidin: imidazoline-derivative
treat HTN
binds selectively to I1-R (less affinity for a-2)
SE: sedation, dry mouth (less than clonidine)
B/7. ALPHA ANTAGONISTS
*Non-selective:
-phentolamine : competitive alpha-R antagonist (pheochromacytoma, antidote for alpha agonist overdose)
Oral, IV short T1/2 (duration=2-4hr)
SE: orthostatic hypotension, reflex tachy
-phenoxybenzamine, (irreversible covalent alpha antagonist) (pheochromocytoma, carcinoid, mastocytosis, Raynaud ph)
(Oral short T1/2 but long duration of action=24-48 hr)
SE: orthostatic hypo, reflex tachy, GI irritation
-tolazoline: vasodilator in peripheral vascular disease
-ergot alkaloids : agonist/ partial agonist / antagonist actions on several receptors
especially: alpha, 5-HT, D(bromocriptine, LSD)
- toxication in bread , ORAL
1. postpartum hemorrhage (ergometrine, ergotamine);
NEVER before delivery!
2. migraine therapy (ergotamine) D=10-12hr
SE: nausea , vomit, diarrhea , prolonged vasospasm,
*Alpha1-blockers: competitive a-1 antagonist
prazosin: ( BPH , HTN) oral, D=8hr
doxazosin,terazosin : longer D=12-24HR
tamsulosin, silodosin: selective a-1A blocker(in urinary tract) approved only for BPH
SE: orthostatic hypo(esp at first dose) little reflex tachy
*Alpha1-antagonist, weak alpha2-antagonist, weak 5-HT agonist, beta-antagonist: urapidil
antihypertensive crisis
*Alpha2-blockers: mirtazapin,
yohimbine: competitive a2 antagonist (OUTDATED for erectile dysfunction, research use only)
oral, parenteral
se: TACHY, GI upset
*Combined alpha/beta-blocker:
carvedilol (2 isomers) decreases mortality in HF
labetalol (4 isomers: 2 bind and block both alpha +beta)
-ORAL, IV. D=5hr
1. HTN 2, hypertensive emergency (IV)
SE: CNS sedation, lethargy, AV block, less danger of bronchospasm (beta blockade, asthmatics)
selective alpha1 receptor antagonists cause less tachycardia than the non-selective alpha blockers.
B/8. BETA ANTAGONISTS
Non-selective: competitive block of alpha-r
-propranolol: local anasthetic effect
(angina, arrhythmia, HTN, Thyrotoxicosis, tremor, migraine) ORAL, IV D=4-6HR readily enter to CNS
- timolol : lacks local anasthetic, USED in glaucoma
- pindolol: partial agonist, possibly safer in asthma
- sotalol,
-cavedilol, labetalol: HTN, Hypertensive emergency(IV)
oral D=5HR
-Nadolol: like propranolol but longer D=24hr , less CNS effect
SE: excessive beta block> bronchospasm fatal in asthmatic, AV-BLOCK, CNS sedation, lethargy
sleep disturbance
Cardioselective: competitive beta 1 blocker
-Atenolol: HTN, angina, arrhythmia
oral D=6-9 hr ( SE like propranolol but less bronchospasm)
-acebutol, Bisoprolol, betaxolol,
- metoprolol: like atenolol, oral, decreases mortality in HF
- esmolol: IV for 1. perioperative and 2. thyroid storm arrhythmia 2. hypertensive emergency
-nebivolol(+NO): oral
Combined alpha1/beta-blocker: carvedilol, labetalol
BB w/ISA : acebutol , pindolol (less bradycardia, less lipid plasma abnormality)
beta1 selective blockers cause less
1. bronchoconstriction, 2. hypoglycaemia
and 3. peripheral circulatory problems.
beta 1 selectivity is never absolute!
B/9. SPASMOLYTICS
-Diazepam (benzodiazepine):
GABA-A agonist,
increases interneuron inhibition of primary motor aff in spinal cord
hepatic metabolism, D=12-24HR
IND: 1. chronic spasm due to cerebral palsy, stroke, spinal injury
3.acute spasm due to muscle injury
SE: CNS dep, tolerance, dependance
- Baclofen, : GABA-b agonist
pre and post-synaptic inhibition of motor output in spinal cord
oral, intrathecal
IND: severe spasticity, spasms due to cerebral palsy, Multiple sclerosis, stroke
SE: sedation, weakness
-Botulinum toxin: inhibits SNAREs in presyn n terminal>flaccid paralysis
direct injection into muscle
D=2-3month
SE: upper/lower limb spasm due to cerebral palsy, MS
cervical dystonia
migraine
overactive bladder
-Dantrolene: RyR1 antagonist> blocks Ca release ch in SR of skeletal m> reduces actin-myosin interaction I.V, ORAL D=4-6hr IND: Acute and chronic spasm (oral) malignant hyperthermia(IV) SE: muscle weakness
-Tizanidine: alpha-2 agonist in spinal cord
pre and post synaptic inhibition of reflex motor output in spinal cord
oral
renal and hepatic elimination
D=3-6hr
ind: acute and chronic vasospasm
SE: weak, sedation, hypotension
-Tolperisone: inhibition of muscle stretch reflex in spinal cord & brainstem> reduction of muscle reflexes
inhibits Na & Ca ch
oral
Hungarian development
IND: acute vasospasm due to muscle injury
SE: sedation, confusion, ocular effect,
anti-muscarinic effect
B/10. SKELETAL MUSCLE RELAXANTS ACTING ON NMJ
Non-depolarizing agents:
*competitive antagonist at skeletal m Ach nicotinic receptors (Nm)
*parenteral
indications:
1. prolonged relaxation for surgical pro
2.relaxation of respiratory m to facilitate mechanical ventilation in icu
3. Epileptic seizure not responding to anti-epileptics
4. intoxication with theophylline, amphetamine
SE: prolonged apnea(muscle weakness)
-(cis)atracurium,(less laudanosine)
intermediate action(25-45mins)
spontaneous metabolism
- mivacurium, ( withdrawn due to his release, metabolised by pseudocholinesterase) short acting (10-15mins)
-pipecuronium:
-rocuronium(steroid): endotrach intubation (most rapid onset 60-120s) intermediate action(25-45min) hepatic metabolism
-Pancuronium: SE: cardiac M-block
renal elimination
- doxacurium( no effect on autonomic or histamine release)
renal elimination
Depolarizing agents:
*agonist at skeletal m Ach nicotinic R(Nm)
*stimulate ANS ganglia nicotinic Ach R(Nn)
*+ cardiac M3R
phase 1: membrane dep> initial discharge produces transient contraction, followed by flaccid paralysis
note: transient contraction can be prevented w/ small dose of non-dep)
phase 2: membrane repolarises, but receptor is desensitized to Ach effects (Succinyl choline still bound to receptor)
succinylcholine (SUXAMETHONIUM)
parenteral, D=5mins
rapid metabolism by butyryl-cholinesterase or Pseudocholinesterase in liver +plasma
resistant to AchE
indications: 1. surgical procedures where brief duration is needed ( intubation, endoscopy, CT)
2. Epilepsy (rarely used)
SE: Hyperkalemia , muscle pain , malignant hyperthermia
transient increase intra-abdominal and intraocular P
B/11. SELECTIVE BETA2-AGONISTS & OTHER BRONCHODILATORS (COPD & ASTHMA)
Beta2-agonists(Gs):
*SABA: albuterol (salbutamol) , terbutaline(relax of pregnant uterus). fenoterol
D=2-6hr
- acute bronchospasm
-inhaled via aerosol canister, nebulizer, parenteral
SE: tachy, tremor
*LABA , salmeterol, formoterol inhalation/ nebulizer/parenteral/oral -slow onset, long action, D=12-24 -NOT useful in acute bronchospasm -USED only w/ CS for prophylaxis of asthma OR (LABA+ Antimuscarinics) for COPD
Muscarinic antagonists(M3 Gq) for bronchodialation:
-good surface activity in airways
-bronchodialation in asthma+copd
-inhaled
-: Less likely to cause tachycardia and arrhythmias, less effective than Beta
SE: drying of oropharyngeal mucous mem
*SAMA: ipratropium( Asthma + COPD)
*LAMA: tiotropium,
newer LAMA :aclidinium, umeclidium ( available in combo with long-acting B2-R agonist, inhaled for COPD)
Methylxanthines:
*theophylline (inhibits adenosine-receptor(Gi); blocks bronchoconstriction, inhibit PDE which changes cAMP to AMP)
D=12hr
hepatic metabolism by cyp450
B/12. ANTIINFLAMMATORY AGENTS, ANTITUSSIVE AGENTS & EXPECTORANTS (ASTHMA)
Corticosteroids: reversible PLA2 inhibitor + reduces synthesis of COX, LOX
- Prednisolone( active metabolite of prednisone)
I.V for asthmatics
-Methylprednisolone,
-dexamethasone(oral)
-Budesonide(inhaled, D=10-12hr) SE: orophary candiasis
-Fluticasone(inhaled)
Leukotriene antagonists: montelukast, Zafirlukast
LTD4-R antagonist (prophylaxis of Asthma)
oral, duration=12-24hr
minimal SE
Anti-IgE antibody:
omalizumab
(prophylaxis of severe ASTHMA) binds IgE preventing them from binding to mast cells; inhibit degranulation (reduces rxn to inhaled Ag)
Parenteral , several courses of injections
- very expensive, long term toxicity not well documented
Antitussive agents:
-codeine: weak MOR agonist, inhibits NE, 5-HT transporter)
Acute dry cough
D=0.5-1hr , oral
SE: toxic in overdose, supress cough reflex
-butamirate: (non-opioid centrally-acting) oral
peripheral effects: bronchodialation,
suppress inflammation
-prenoxdiazine (peripherally-acting anti-tussive)
Mucoactive agents:
- used in 1. Cystic fibrosis
2. chronic bronchitis
3. bronchiectasis (permanently damaged and widened bronchi) - acetylcysteine(mucolytic=loosens mucous secretion): breaks disulfide bonds in mucus; decreases mucus viscosity
-bromhexine(expectorant=promote sputum excretion): increases serous fluid pro in RT, thinner phlegm. , oral
(SE: lacrimation, rhinorrhea)
-Ambroxol(mucolytic)
- secretolytic compunds: dilutes mucous; easier to remove from bronchi
- vagus stimulators: Ibecachuana (plant-derived) helps in removal of secretion
- bronchial stimulators: essential oils
B/13. TREATMENT OF PERIPHERAL VASCULAR DISEASE
*Cilostazol: PDE-3 inhibitor> decreases PLT agg, increases LPL, vasodilation
oral
acts on corpuscular elements of blood ( PLT agg, RBC deformity)
IND: intermittent claudication (PAD)
SE: headache, palpitation, vertigo, coronary steal sy
CI: CHF
*calcium dobesilate: decreases microvascular permeability, decreased PLT agg, anti-inflammatory and antiox oral ind: 1. chronic venous insuffiency(CVI) 2. diabetic retinopathy 3. symptomatic hemmorhoidal disease se: nausea, vomit, diarrhea
*vinpocetine: inhibits Na and Ca ch, glutamate-r and PLT agg> increases cerebral perfusion and glu utilization
inhibits PDE-1
ORAL, PARENTERAL
INDL: 1. cerebral perfusion deficit (vascular dementia)
2. alzhiemers, 3, post stroke. 4. virtigo
SE: hypotension, tachy, GI
CI: PREGNANCY, nursing
*nicergoline: (alpha-1 antagonist)
enhances cholinergic and catecholaminergic NT func
decreases PLT agg
promotes metabolic activity (o2 and glu utilization)
neurotrophic, antioxidant
-Ergot derivative
ORAL, PARENTERAL
IND: 1. cerebral perfusion deficit
2. vascular dementia
3. peripheral perfusion deficit
4, ischemic stroke. 5. migraine. 6. balance disturbance
SE: nausea, flushing, GI
CI: pregnancy, MI, arrythmia, lactation, acute bleeding
*pentoxyphylline: competitive nonselective PDE-inhibtior
rheological agent> reduces viscosity and increases deformability of RBC> blood flows easily through obstructed vessel
-Methyl xanthine derivative
-ORAL, I.V
IND: atherosclerotic circulatory disease
diabetic circulatory disease
se: GI, tachy, angina, flushing, allergy
B/13. TREATMENT OF MIGRAINE
Abortive therapy:
1. sumatriptan: 5-HT1( 1D/1B) agonist causes vasoconstriction + modulates NT release
( Migraine+ cluster headache)
Oral, Inhaled, Parenteral
D=2-4hr
SE: Paresthesia, dizziness, chest pain, coronary vasospasm
2. Eletriptan,naratriptan : oral only 2-27hr
- ergotamine (ergot alkaloid):
-Partial agonist at 5-HT and alpha-R ( can block alpha-agonist effect; epinephrin reversal
esp in blood vessel and uterus : prolonged a-mediated vasoconstriction
-used for : Migraine, cluster headache, postpartum bleeding
Oral , D= 10-12hr
SE: nausea, vomit, diarrhea, severe vasospasm
Prophylactic therapy:
-galcanezumab (CGRP-R antagonist antibody) binds peptide itself
S.C , D=1 month
se: injection site rxn
-cinnarizine= CCB
improves cerebral circulation
-propranolol: non selective BB, local anasthetic effect
(angina, arrhythmia, HTN, migraine, thyrotoxicosis, tremor) ORAL, IV duration=4-6 hrs readily enters CNS
-verapamil: Blocks L-type Ca ch in smooth m and heart
(angina, HTN, AV-nodal arrhytmia, migraine)
oral, parenteral. D=6-8hr
SE: constipation, pretibial edema, flushing, dizzy
higher doses: cardiac depression, hypotension
-carbamazepine: (Tricyclics)
blocks VG-Na ch + decreases glutamate release
1. Generalised tonic-clonic seizure
2. focal seizures
well absorbed, active metabolite , many drug interactions
SE: ataxia, diplopia, headache, nausea
-valproic acid: Blocks high frequency firing
1. generalized tonic-clonic
2. focal
3. myoclonic seizures
excessive protein binding and metabolism, many drug interactions
SE: nausea , alopecia, weight gain, teratogenic
-imipramine (TCA) blocks NE and 5-HT transporter
1. major depression
2. chronic pain
longer half life
SE: alpha block, M-block, sedation, weight gain
overdose: arrhythmia + seizures
B/14. HF - DRUGS DECREASING THE LOAD ON THE HEART
- drugs of acute failure
- drugs of chronic failure (add them)
*Diuretics:(1st line in sys+dias failure)
-hydrochlorothiazide( -Na/Cl transporter in DCT)
moderate diuresis, decreased excretion of Ca
SE: Metabolic hypokalemic alkalosis,
early decrease in Na,
increased glu, lipid, uric acid, Sulfonamide allergy(rare)
CI: decreased efficacy w/ NSAIDS
-furosemide: NKCC- in TAL strong diuresis, increased Ca excretion oral, parenteral d=2-4hr SE: ototoxic, hypovolemia, hypokalemia alkalosis CI: NSAIDS , Sulfonamide allergy(rare)
-spironolactone(steroid inhibitor of aldosterone-r in cortical CD) decreases K excretion oral decrease mortality in CHF SE:hyperkalemia, gynecomasia
*ACEi:
IND: chronic failure, HTN, diabetic renal disease
SE:cough, teratogenic, renal damage
CI: Pregnancy
-captopril (oral, D=12-24hr)
-enalapril, perindopril, ramipril (longer half life)
*ARB: losartan, valsartan, irbesartan
ind: HTN, used in combo in HF
CI: Pregnancy
SE: hyperkalemia, teratogenic
- Beta1-blocker: metoprolol
- Beta- and alpha-blocker: carvedilol
