2 Pharm: Adrenergic

Front 1

apraclonidine

Back 1

apraclonidine:
- glaucoma
- reduces intraocular P by reducing production of aqueous humor

Front 2

clonidine: therapeutic uses

Back 2

clonidine: therapeutic uses
- hypertension
- preoperative sedation, drying of secretions and analgesia
- differential diagnosis of hypertension and pheochromocytoma

Front 3

adrenal tumor

Back 3

adrenal tumor:
- NT:
1. vasoconstriction
2. H contraction
3. metabolic
- NO hypertension

Front 4

clonidine: adverse effects

Back 4

clonidine: adverse effects:
- dry mouth and sedation
- rebound hypertension occurs on abrupt withdrawl of drug
- sexual dysfunction
- marked bradycardia

Front 5

isoproterenol

Back 5

isoproterenol:
- synthetic catecholamine
- potent, non-selective beta agonist
- inotropic (beta 1 mediated)
- increases myocardial contractile force, HR and CO
- beta 2: skeletal m vasodilation, uterine relaxation

Front 6

dobutamine: adverse effects

Back 6

dobutamine: adverse effects:
- used with caution in atrial fibrilation as increases AV conduction
- tachyphylaxis (tolerance): common in chronic beta agonists

Front 7

ephedrine: actions

Back 7

ephedrine actions:
- Ephedra vulgaris
- stimulates HR and CO
- increases BP
- bronchodilation
- CNS stimulation

Front 8

ephedrine: adverse effects

Back 8

ephedrine: adverse effects:
- hypertension
- cardiac arrhythmias
- insomnia
- tachphylaxis

Front 9

adrenergic antagonists

Back 9

adrenergic antagonists:
- bind to adrenoreceptors but do not trigger the receptor-mediated intracellular effects
- either reversibly or irreversibly attach to receptor, preventing activation by endogenous catecholamines

Front 10

phenoxybenzamine uses

Back 10

phenoxybenzamine uses:
1. pheochromocytoma: catecholamine secreting tumor of adrenal medulla
- before sx removal to treat hypertensive crisis
2. management of benign prostatic obstruction

Front 11

phenoxybenzamine: adverse effects

Back 11

phenoxybenzamine: adverse effects:
- postural hypotension accompanied by reflex tachycardia and other arrhythmias
- nasal stuffiness
- nausea, vomiting
- inhibits ejaculation and aspermia

Front 12

tolazoline

Back 12

tolazoline:
- treats persistent pulmonary hypertension of newborns
- aid in visualizing distal peripheral vessels during arteriography

Front 13

prazosin

Back 13

prazosin:
- alpha 1 antagonist
- reflex tachycardia less prominent that non-selective alpha blockers
- related drugs: terazosin, doxazosin
- cardio effects: dec peripheral resistance, lowers BP

Front 14

ephedrine therapy

Back 14

ephedrine therapy:
1. bronchodilator
2. hypotension: spinal anesthesia
3. nasal decongestant
4. adjuvant in myasthenia gravis

Front 15

agonists/ sympathomimetics

Back 15

agonists/ sympathomimetics:
- produces responses like endogenous adrenergic mediators (E, NE):
1. directly: stim adrenergic receptors
2. indirectly: release of cathecholamines from adrenergic neurons

Front 16

adrenergic neuron

Back 16

adrenergic neuron:
- release NE as NT
- adrenoceptor:
1. presynaptically on neuron -or-
2. postsynaptically on effector organ

Front 17

neurotransmission of adrenergic neuron

Back 17

neurotransmission of adrenergic neuron:
1. synthesis
2. storage
3. release
4. receptor binding
- of NE followed by removal from synaptic gap

Front 18

synthesis of NE

Back 18

synthesis of NE:
- cytoplams of adrenergic neuron
1. tyrosine transp by Na-linked carrier to axoplasm of adrenergic neuron
2. rate-limiting step: tyr --> DOPA by tyrosine hydroxylase
3. DOPA --> dopamine by DOPA decarboxylase

Front 19

storage of NE in vesicle

Back 19

storage of NE in vesicles:
1. dopamine transp into synaptic vesicle by anion transporter system
2. dopamine --> NE by dopamine beta hydroxylase

Front 20

release of NE

Back 20

release of NE:
1. AP reaches nerve terminal
2. influx of Ca from ECF into cytoplasm of neurons
3. vesicles fuse with adrenergic cell mem
4. release NT by exocytosis

Front 21

NE binding by receptor

Back 21

NE binding by receptor:
1. NE rel into synaptic cleft
2. NE binds adrenergic receptors: pre or post synaptically
3. active reuptake of free NE back into axon terminal

Front 22

alpha adrenergic receptors

Back 22

alpha adrenergic receptors:
- divided into 1 and 2, based upon affinity for alpha agonist and blocking drugs
- potency: E> NE> isoproterenol

Front 23

alpha 1 adrenergic receptors

Back 23

alpha 1 adrenergic receptors:
- post-synaptic mem of effector organ
-activation:
1. G-protein activation of phospholipase C
2. gen of IP3 from phosphatidylinositol
3. rel of Ca from endoplasmic reticulum into cytosol

Front 24

alpha 2 adrenergic receptors

Back 24

alpha 2 adrenergic receptors:
1. primarily pre-synaptic nerve endings
2. also post-synaptically on beta cells of pancreas
- causes feedback inhibition of rel of NR from adrenergic nerve terminal
- effects mediated by inhibition of adenylyl cyclase: decrease cAMP

Front 25

beta 1 adrenergic receptors

Back 25

beta 1 adrenergic receptors:
- heart, JG apparatus, fat cells
- equal affinity for E and NE

Front 26

beta 2 adrenergic receptors

Back 26

beta 2 adrenergic receptors:
- blood vessels of skeletal m, liver
- smooth m of bronchus, genitourinary system, uterus
- affinity E> NE

Front 27

beta 1 heart

Back 27

beta 1 heart:
1. E: inc HR, contractility and CO
2. NE: dec HR
- inc contractility and CO

Front 28

BP

Back 28

BP:
1. systolic: inc E> NE
2. diastolic: no change in E
- NE inc

Front 29

alpha blood vessels

Back 29

alpha blood vessels:
- skin, mucosa, splanchnic, renal
- constriction with E and NE

Front 30

beta 2 blood vessels

Back 30

beta 2 blood vessels:
- coronary, skeletal m
- dilation withE and NE

Front 31

beta 2 bronchial smooth m

Back 31

beta 2 bronchial smooth m:
- relaxation with E and NE

Front 32

adrenergic in GIT smooth m

Back 32

adrenergic in GIT smooth m:
1. dec motility, tone: alphas, beta 2 with NE and E
2. sphincter contraction: alpha 1 with NE and E

Front 33

adrenergic urinary bladder

Back 33

adrenergic urinary bladder:
1. beta 2: detrustor m relaxation with E only
2. alpha 1: sphincter contraction with NE and E

Front 34

adrenergic uterus

Back 34

adrenergic uterus:
- alphas, beta 2:
1. E: relaxation
2. NE: contraction

Front 35

alpha 1 ductus deferens

Back 35

alpha 1 ductus deferens:
- ejalculation with E and NE

Front 36

alpha 1 splenic capsule

Back 36

alpha 1 splenic capsule:
- contraction with E and NE

Front 37

alpha 1 skin pilomotor m

Back 37

alpha 1 skin pilomotor m:
- contraction with E and NE

Front 38

alpha 1 radial m, iris

Back 38

alpha 1 radial m, iris:
- dilitation with E and NE

Front 39

beta 2 ciliary m

Back 39

beta 2 ciliary m:
- E: relaxation for far vision

Front 40

alpha 1, beta 2 liver

Back 40

alpha 1, beta 2 liver:
- glycogenolysis with E and NE

Front 41

alpha 2, beta 1 fat

Back 41

alpha 2, beta 1 fat:
- lipolysis with E and NE

Front 42

alpha 2, beta pancreas beta cells

Back 42

alpha 2, beta pancreas beta cells:
1. E: decreased secretion
2. NE: increased secretion

Front 43

absorption and biotransformation

Back 43

absorption and biotransformation:
- not effective orally: undergoes met by conjugation and oxidation in GI mucosa and liver
- SQ abs slower, causes local vasoconstriction
- E met by:
1. COMT: cathechol O-methyl transferase
2. MAO: monoamine oxidase
- met excreted in urine

Front 44

preparations

Back 44

preparations:
- E solns 1: 1K and 10K
- 1% (1:100) avail for inhalation
- E bitartrate: aerosol, opthalamic
- NE bitartrate: 0.2%

Front 45

therapy

Back 45

therapy:
1. respiratory distress: bronchospasm
2. hypotension
3. cardiac arrest, partial/ complete AV block
4. hypersensitivity to drugs, allergens: rapid relief
5. prolongs local anesthetics: local vasoconstriction delaying abs, 1: 100K
6. topical hemostatic agent

Front 46

adverse effects

Back 46

adverse effects:
1. fear, anxiety, restlessness, headache, tremor, weakness, dizziness, palor, respiratory difficulty, palpitation, hypertension,
2. serious: cerebral hemhorrhage, cardiac arrhythmias, ruptured aneurysms
3. inj sites: necrosis, sloughing

Front 47

myocardial toxicity

Back 47

myocardial toxicity predisposition w:
1. hyperthyroidism
2. halogenated hydrocarbon anest
3. hypertension

Front 48

contraindication

Back 48

contraindication:
- pregnancy: induces contraction of uterus

Front 49

dopamine gen

Back 49

dopamine gen:
- met precursor of E and NE
- central NT: motor regulation
- substrate of MAO and COMT

Front 50

dopamine low conc

Back 50

dopamine low conc:
- D1 dopaminergic receptors esp in renal, mesenteric, coronary beds: vasodilation
1. inc GFR, renal BF, Na excretion
2. management of low CO w/ compromised renal fx: cardiogenic, hypovolemic shock

Front 51

dopamine high dose

Back 51

dopamine high dose works on beta 1: 1. positive inotropic
2. tachycardia less prom
3. high conc: alpha 1 vasoconstriction
- release of NE from nerve terminals: cardio effects

Front 52

dopamine dose and route

Back 52

dopamine dose and route:
- IV: HCl, 2-5 gradually inc to 20-50 microg/kg/min
- level of termination: dec urine flow, tachycardia, arrhythmias

Front 53

dopamine therapy

Back 53

dopamine therapy:
1. shock: cardio and septic
2. oliguria and low/normal peripheral vascular resistance: Fenoldopam (D1 selective agonist), dopexamine (synthetic analog)

Front 54

dopamine precautions

Back 54

dopamine precautions:
1. shock, hypovolemia: first transfuse whole blood, plasma or fluids
2. extravasation during infusion: ischemic necrosis, sloughing
3. avoid with MAO inhibitors, tricylic anti-depressants

Front 55

direct-acting adrenergic agonists

Back 55

direct-acting adrenergic agonists:
- alpha and beta receptors
- effects similar to stim of S nerves or release of E from adrenal medulla
1. E, NE
2. dopamine
3. phenylephrine
4. clonidine
5. methoxamine

Front 56

indirect acting adrenergic agonists

Back 56

indirect acting adrenergic agonists:
- into presynaptic neuron: release of NE from cytoplasmic pools or vesicles of adrenergic neuron
1. amphetamine
2. tyramine

Front 57

mixed-action adrenergic agonists

Back 57

mixed-action adrenergic agonists:
- capable of directly stim adrenoceptors and rel NE from adrenergic neuron
1. ephedrine
2. metaraminol

Front 58

methoxamine

Back 58

methoxamine:
- alpha 1 agonist
- direct sympathomimetic amine
- causes arteriolar vasoconstriction:
1. inc BP
2. inc peripheral resistance
3. reflex bradycardia
- IV: rapid pressor resp up to 1hr
- IM: 15 min for pressor resp but lasts 1-1.5 hours

Front 59

methoxamine uses, adverse

Back 59

methoxamine uses, adverse:
- use in sx hypotension
- adverse hypotension headache, vomiting

Front 60

metaraminol

Back 60

metaraminol:
- alpha 1 agonist
- indirect sympathomimetic
- tx hypotension

Front 61

alpha 1 adrenergic agonist agents

Back 61

alpha 1 adrenergic agonist agents:
1. methoxamine
2. metaraminol
3. mephentermine
4. phenylephrine

Front 62

mephentermine

Back 62

mephentermine:
- alpha 1 agonist
- direct and indirect
- prevents hypotension during spinal anesthesia

Front 63

phenylephrine

Back 63

phenylephrine:
- similar to methoxamine
1. nasal decongestant (1-2%): allergy, hay fever, acute rhinitis, otitis media, sinusitis media
2. mydriatic (1-2%): no loss of light reflex or rise in intraocular tension (glaucoma)
3. vasopressor: SQ/IM 5-10 mg, IV 0.5 mg

Front 64

clonidine

Back 64

clonidine:
- alpha 2 agonist in cardio centers of CNS: suppress S outflow
- CNS alpha 2 also modulates pain perception, sedation level
- good PO abs, 100% bioavail
- no dec renal BF or GFR: can be used in hypotension and renal dz

Front 65

alpha 2 agonists

Back 65

alpha 2 agonists:
1. clonidine
2. apraclonidine
3. xylazine
4. detomadine
5. methyl dopa

Front 66

xylazine

Back 66

xylazine:
- alpha 2 agonist
- sedation, anesthesia, muscle relax, analgesia
- large animal
- adverse: bradycardia, conduction prob, myocardial depression

Front 67

detomadine

Back 67

detomadine:
- alpha 2 agonist
- large animal
- sedative, analgesic, anasthetic premed
- w/ butorphanol: inc analgesia, depth of sedation
- w/ ketamine: IV short duration anesthetic
- normally IV: fastest, most efficient, 2-5 min onset, 20-40 microg/ kg

Front 68

methyl dopa

Back 68

methyl dopa:
- alpha 2 agonist
- anti-hypertensive (action similar to clonidine)
- met to alpha methyl NE in brain and acts on central alpha 2

Front 69

isoproterenol therapy, adverse

Back 69

isoproterenol:
1. therapy: emergency stim HR or heart block, asthma
2. adverse: palpitations, tachycardia, headache
- cardiac dz: cardiac ischemia, arrhythmias

Front 70

beta agonists

Back 70

beta agonists:
1. isoproterenol

Front 71

dobutamine

Back 71

dobutamine:
- beta 1 agonist, synthetic catecholamine
- cardio selective: positive inotropic
without effecting HR, rhythmicity, BP
- IV 5-20 microg/kg/min

Front 72

dobutamine therapy

Back 72

dobutamine therapy:
- congestive heart failure
- doesn't sig inc O2 demand of myocardium: advantageous over other sympathomimetics

Front 73

beta 2 agonists

Back 73

beta 2 agonists:
1. metaproterenol
2. terbutaline
3. albuterol
4. salbutamol
5. ritodrine

Front 74

metaproterenol

Back 74

metaproterenol:
- beta 2 agonist
- PO, inhalation
- bronchodilation, improves airway fx

Front 75

terbutalene

Back 75

terbutalene:
- beta 2 agonist
- long-term tx obstructive airway dz

Front 76

salbutamol

Back 76

salbutamol:
- beta 2 agonist
- prolonged duration ~12 hr
- slow onset after inhalation

Front 77

ritodrine

Back 77

ritodrine:
- beta 2 agonist
- uterine relaxant
- IV: arrest premature labor
- adverse: muscle tremors, pulmonary edema, down regulation of receptors with chronic use

Front 78

amphetamine

Back 78

amphetamine:
- alpha and beta agonist
- CNS stim
- peripheral actions mediated through rel of stored cathecholamines

Front 79

amphetamine adverse

Back 79

amphetamine adverse:
- insomnia, tremors, restlessness, excitment, agitation
- cardiac: arrhythmias
- GI: dry mouth, anorexia, metallic taste, nausea, vomiting, diarrhea, cramps
- dependence with chronic use

Front 80

adrenergic drug therapy

Back 80

adrenergic drug therapy:
1. allergies
2. cardiac: CHF
3. vascular: local anest, hemostasis
4. bronchial asthma
5. premature labor
6. mydriatic
7. met: hypoglycemia

Front 81

direct-acting alpha antagonists

Back 81

direct-acting alpha antagonists:
1. phenoxybenzamine
2. phentolamine
3. tolazoline
4. prazosin
5. terazosin
6. yohimbine
7. ergotoxime

Front 82

direct-acting beta antagonists

Back 82

direct-acting beta antagonists:
1. non-selective: propanolol, nadolol, timolol, pindolol
2. beta 1 selective: metoprolol, atenolol, esmolol, acebutolol
3. beta 2 selective: butoxamine

Front 83

indirect-acting adrenergic antagonists

Back 83

indirect-acting adrenergic antagonists:
- interfere with transmitter release, fx of neurotransmission or adrenergic neurons such as
1. catecholamine syn: methyl dopa, alpha methyl tyrosine
2. NE storage: reserpine
3. NE release: guanethidine, guanadrel
4. dec central S outflow: clonidine, guanabenz, guanafacine

Front 84

phenoxybenzamine

Back 84

phenoxybenzamine:
- covalent bond w/ alpha: irreversible inhibition for 14-48 hr
- non-selective
- inhibits reuptake of release NE by presynaptic nerve terminals

Front 85

phenoxybenzamine actions

Back 85

phenoxybenzamine actions:
1. prevents peripheral vasoconstriction: dec resistance causing reflex tachycardia
2. blocks heart alpha 2: inc CO
3. epi reversal

Front 86

alpha blockers

Back 86

alpha blockers:
1. phenoxybenzamine
2. phentolamine
3. tolazoline
4. ergot alkaloids

Front 87

phenoxybenzamine toxicity

Back 87

phenoxybenzamine toxicity:
- mutagenic
- peritoneal sarcomas
- lung tumors

Front 88

phentolamine

Back 88

phentolamine:
- non-selective, competitive alpha blocker
- poor GI abs
- similar to phenoxybenzamine
- causes postural hypotension, reflex tachycardia, diarrhea
- inc GI secretion: antagonist at muscarinic

Front 89

phentolamine indications

Back 89

phentolamine indications:
1. hypotension assoc w/ pheochromocytoma
2. relieve pseudo bowl obstruction
3. local prevention of dermal necrosis on extravasation of alpha agonist

Front 90

phentolamine adverse

Back 90

phentolamine adverse:
1. postural hypotension
2. reflex tachycardia
3. arrhythmias
4. anginal pain

Front 91

tolazoline adverse

Back 91

tolazoline adverse:
1. cardia arrhythmias
2. GI stim: abd pain, nausea, exacerbation of peptic ulcers

Front 92

ergot alkaloids

Back 92

ergot alkaloids:
- alpha blockers
- fungus Claviceps purpurea
- ergotamine, ergonovine: deriv of lysergic acid
- oxytocic activity
- semi-synthetic hydrogenated deriv: dihydroergotamine, hydergine, devoid of oxytocic and partial alpha agonist activity (vasconconstriction), primary alpha blockers

Front 93

ergot alkaloids therapy

Back 93

ergot alkaloids therapy:
- stim postpartum uterine contraction
- migraine relief

Front 94

prazosin therapy, adverse

Back 94

prazosin:
1. therapy: hypertension, benign prostate hypertrophy
2. adverse: dizziness, nasal congestion, headache, drowsiness, orthostatic hypotension

Front 95

yohimbine

Back 95

yohimbine:
- selective alpha 2 antagonist
- facilitates rel of NE at synaptic cleft
- enters brain

Front 96

yohimbine therapy

Back 96

yohimbine therapy:
1. aphrodisiac
2. dx pheochromocytoma
3. hypertension
4. migraine
5. benign prostate hyperplasia

Front 97

propanalol

Back 97

propanalol:
- non-selective beta antagonist
1. neg inotropic, chronotropic
2. periph vasoconstriction
3. bronchoconstriction
4. inc Na retention
5. dec glc met: dec glycogenolysis, glucagon sec
6. CNS: anxiety, sedation

Front 98

propanalol therapy

Back 98

propanalol therapy:
1. hypertension
2. glaucoma
3. migraine
4. hyperthyroidism: prevent cardia arrhythmias
5. angina pectoris: dec O2 demand in ischemic cardiac m
6. myocardial infarction

Front 99

propanalol adverse

Back 99

propanolol adverse:
1. bronchoconstriction
2. arrhythmias: taper off dose
3. met disturbances: hypoglycemia

Front 100

non- selective beta antagonists

Back 100

non-selective beta antagonists:
1. timolol: wide angle glaucoma, dec aq humor sec
2. pindolol

Front 101

selective beta blockers

Back 101

selective beta blockers:
1. atenolol
2. acebutolol
3. metoprolol
4. esmolol: ultra short acting (10min), safer in myocardial infarct

Front 102

beta blocker therapy

Back 102

beta blocker therapy:
1. hypertension
2. ischemia heart dz
3. cardiac arr
4. thyrotoxicosis
5. pheochromocytoma
6. glaucoma
7. neuro disorders, migraine
8. sedation, anti-anxiety

Front 103

labetalol

Back 103

labetalol:
- mixed alpha beta antagonist (1:3)
- pregnancy induced hypertension
- pheochromocytoma
- adverse: drowsiness, fatigue, weakness, dec sexual fx, resp distress
- contraindic: asthma, CHF, heart block, bradycardia