Adrenergic Pharmacology Flashcards
Alpha 1 receptors: general
mostly smooth muscle of the vasculature, bladder base, urethral sphincter and prostate
activation: leads to arterial and venous vasoconstriction → increased BP
in normal pts if BP is increased baroreflex will kick in and counteract ⇒ need to be careful with pts with impaired autonomic functions as giving an alpha 1 agonist will lead to uncompensated vasoconstriction = HIGH BP
Alpha 2 Receptors: general
- Peripheral vasculature: when activated → vasoconstriction (similar effeccts as alpha 1)
- CNS (on presynaptic neurons): pure central alpha 2 agonist introduced → sympatholytic response (less sympathetic neurotransmitters) and inhibition of sympathetic tone which lowers BP i.e. clonidine
a. pts with autonomic failure that are given a central alpha 2 agonist can cause increase BP
* decrease secretion from beta islet cells of pancreas
Chronotropy
heart rate
inotropy
contractility
dromotropy
conduction between AV node
positive dromotropy = increased cardiac output
Beta receptor: general
- Beta-1 in heart:
- activation = increased HR, contractility, conductivity
- beta -2: bronchioles and peripheral vasculature
- activation = bronchodilation
- Beta-3: bladder and adipose tissue, urethral smooth muscle (sphincter)
- activation =relaxation of sphincter
- allows bladder to fully empty
- used for overactive bladder
- activation =relaxation of sphincter
Epinephrine
- agonist at both alpha and beta receptors
- very potent vasoconstrictor and cardiac stimulant
- positive inotropy (contractility) and chronotropy (HR)
- vascular bed vasoconstriction = increased BP
- Toxicities:
- STROKE
- restlessness
- throbbing HA
- tremor
- palpitations
- cardiac arrhythmias
- cerebral hemorrhage
Norepinephrine
- acts most on Alpha 1, 2, and 1; less on beta 2
- increases peripheral resistance and BP (both diastolic and systolic)
- Contraindications:
- severe volume depletion
- vascular thrombosis
- use of MAO inhibitor
- extravasation → necrosis
- SE:
- HA, anxiety
- tachycardia
- severe HTN →stroke
- asthma exacerbation
Differences in effects of Epi and Norepi
- Cardiac: Epi >NE
- HR: Epi>NE
- Cardiac Output: Epi >>> NE
- Peripheral Circulation:
- Total peripheral resistance NE>Epi
- Cerebral blood flow and muscle blood flow Epi >>> NE
- Splanchnic blood flow Epi >>> NE
- Metabolic effects: Epi > NE
- oxygen consumption
- blood glucose
- blood lactic acid
- eosinpenic response
Dopamine: general
- Functions: precursor of norepi and epi
- CNS -reward system ⇒addiction
- regulating Na excretion and renal function
- regulation of movements
- deficiency in basal ganglia in Parkinson’s disease
- When stimulating the peripheral dopamine receptors = vasodilation
- Contraindications:
- pheochromocytoma: tumor in adreal glands and associated with high BP
- tachyarrhythmias
- occlusive vascular disease
- SE:
- tachycardia/angina/HTN
- HA/N/V/anxiety
- Extravasation →tissue necrosis
Dopamine effects at low, intermediate, and high dose
- 0.5-2 mcg/kg/min = only dopaminergic response
- 2-10mcg/kg/min = both dopaminergic and beta 1 response
- increase HR, increase contractility, increase urine output
- >10mcg/kg/min = mostly affect alpha 1 as well as Beta 1 and dopaminergic
- increased BP
Phenylephrine
- selective alpha 1 agonist
- can increase BP affecting HR
- less side effects on the heart as it avoids beta 1 stimulation
Midodrine
- selective alpha 1 agonist
- prodrug
- indication: orthostatic hypotension
- Blackbox warning: may induce supine BP elevation
clonidine
- central acting alpha 2 agonist
- suppressses outflow of sympathetic activity → lowers BP
- well PO absorption (~100% bioavailability)
- Indications:
- HTN
- relieve withdrawal (w/d) sxs of narcotics, alcohol, and tobacco addiction →decreases cravings
- SE: dry mouth
- sedation
- sexual dysfunction
-
Caution:
- w/d rxn following abrupt d/c of long-term therapy
- need to taper off drug
- can use phentolamine for this w/d
- w/d rxn following abrupt d/c of long-term therapy
Non-selective Alpha receptor antagonists
phenoxybenzamine
phentoalmine
Alpha 1 selective blockers
- “osin”
- prazosin
- terazosin
- doxazosin
- alufzosin
- tamsulosin
- indoramin
- urapidil
- bunazosin
alpha 2 selective blocker
yohimbine
non-selective (first generation) beta blocker
- nadolol
- penbutolol
- pindolol
- propranolol
- timolol
- sotalol
- levobunolol
- metipranolol
Beta 1 selective blockers (second generation)
- acebutolol
- atenolol
- bisporolol-long half life
- esmolol-shortest half life
- metoprolol– lipid solublility is moderate
non-selective beta blockers (third generation)
- carteolol
- carvedilol
- bucindolol
- labetalol
- alpha 1 and beta 1 selective:
- carvedilol and labetalol
- carvedilol = ca2+ ebntry blockage and antioxidant activity
- also have systemic effects → peripheral vasodilation
Beta 1 selective blockers(3rd generation)
- betaxolol
- celiprolol
- nebivolol
highly lipid soluble beta blockers
- Non-selective:
- penbutolol
- pindolol
- beta 1-selective:
- metoprolol
Sympathetic postanglionic nerves that use acetycholine or dopamine instead of adrenergic neurotransmitters
sweat glands: acetycholine
renal vascular smooth muscle: dopamine
pheochromocytoma
- rare, benign tumor on the adrenal gland that increases the release of Epi and NE
- can be treated with alpha 1 antagonists →phenoxybenzamene and phentolamine
tocolytic
- suppress premature labor
- beta 2 sympathomimetics are tocolytics
*
isoproterenol
- beta 1 and beta 2 non selective agonist
- relaxaes almost all smooth muscles especially bronchial and GI
oxymetazoline
- alpha 1 and alpha 2 nonselective agonist
- peripheral acting
- topical nasal spray decongestant
long acting beta 2 agonists
- formoterol
- long duration → bronchial dilation may persist for 12 hours
- tx: asthma and COPD
- Arformoterol:
- twice as potent as formoterol
Reserpine
- indications: HTN and psychosis
- blocks the action of VMAT (vesicular monoamine transporter)
- prevents dopamine from entering the vesicles
- depletes the storage of NE which leads to lowered blood pressure
Tyramine, amphetamines and ephedrine
- high affinity for NET (NE transporter: which brings NE back into the cell)
- NE gets displaced and remains in the synaptic cleft for action
- higher sympathetic tone = increase HR, BP, bronchodilation
Dopamine Receptors
mostly in brain and the smooth muscle of the renal vascular bed
MAO and COMT
enzymes that break down the catecholamines (epi, norepi, and dopamine)
Stimulation of beta receptors and effects on NE
- increased release of norepi
stimulation of alpha 2 receptors and effect on NE
slows down the release of NE
mydriasis
- eye dilation due to contraction of radial muscle of iris
- sympathetic response
miosis
- constriction of iris due to contraction of sphincter muscle of the iris
- parasympathetic response
ciliary muscle
- controls the lens of the eye
- when relaxed = far vision = sympathetic
- when contracted = near vision = parasympathetic
Antimuscarinic Agents Toxicity and Cautions
- Toxicity:
- dry mouth
- mydriasis
- tachycardia
- hot flushed skin
- agitation
- delirium
- Cautions:
- glaucoma
- BPH (benign prostatic hyperplasia)
- urinary retention
- PUD (peptic ulcer disease)
- slow emptying of the stomach can worsen
Dicyclomine
- muscarinic antagonist
- treatment for IBS
Beta receptors
- Beta 1: increased HR, contractility, and conductivity
- increased renin secretion
- Beta 2: bronchodilation and peripheral vasodilation
- relaxation of uterus
- Beta 3: bladder and adipose tissue
- relaxation of sphincter, allows bladder to fully empty
- used for overactive bladder
Phentolamine Indications and SE
Alpha blocker
- pheochromocytoma and HTN crisis follow abrupt withdrawal of clonidine
- SE:
- hypotension
- tachycardia (reflex)
- arrythmias
- MI
indications and side effects of alpha 1 blockers
Indications: HTN, BPH
SE: orthostatic hypotension, syncope, HA, dizziness, impaired ejaculation
Beta Blocker Effects and SE
- Effects:
- Lower the BP
- increase airway resistance
- reduce intraocular pressure
- SE:
- bradycardia
- mild sedation
- cold hands
- vivid dreams
- worsen preexisting asthma (nonselective)
- decreased mycocardial contractility and excitability (not good in CHF!!)
Indirect Acting Adrenergic Agonists
Releasing agents: amphetamine, tyramine
Uptake inhibitor: cocaine
MOA inhibitors: selegiline
COMT inhibitors: entacapone
