blood pressure Diarrhea Weakness Slowed heart rate Weight gain Erectile dysfunction Carvedilol is not recommended for people with uncontrolled bronchospastic disease (e.g. current asthma symptoms) as it can block receptors that assist in opening the airways. Carvedilol may mask symptoms of low blood sugar, resulting in hypoglycemia unawareness. This is termed beta blocker induced hypoglycemia unawareness. Pharmacology Pharmacodynamics Carvedilol is both a non-selective β-adrenergic receptor antagonist (β1, β2) and an α-adrenergic receptor antagonist (α1). The S(–) enantiomer accounts for the beta-blocking activity whereas the S(–) and R(+) enantiomers have alpha-blocking activity. The affinity (Ki) of carvedilol for the β-adrenergic receptors is 0.32 nM for the human β1-adrenergic receptor and 0.13 to 0.40 nM for the β2-adrenergic receptor. Using rat proteins, carvedilol has shown affinity for a variety of targets including the β1-adrenergic receptor (Ki = 0.24–0.43 nM), β2-adrenergic receptor (Ki = 0.19–0.25 nM), α1-adrenergic receptor (Ki = 3.4 nM), α2-adrenergic receptor (Ki = 2,168 nM), 5-HT1A receptor (Ki = 3.4 nM), 5-HT2 receptor (Ki = 207 nM), H1 receptor (Ki = 3,034 nM), D2 receptor (Ki = 213 nM), μ-opioid receptor (Ki = 2,700 nM), veratridine site of voltage-gated sodium channels (IC50 = 1,260 nM), serotonin transporter (Ki = 528 nM), norepinephrine transporter (Ki = 2,406 nM), and dopamine transporter (Ki = 627 nM). It is an antagonist of the human 5-HT2A receptors with moderate affinity (Ki = 547 nM), although it is unclear if this is significant for its pharmacological actions given its much stronger activity at adrenergic receptors. Carvedilol reversibly binds to β-adrenergic receptors on cardiac myocytes. Inhibition of these receptors prevents a response to the sympathetic nervous system, leading to decreased heart rate and contractility. This action is beneficial in heart failure patients where the sympathetic nervous system is activated as a compensatory mechanism. Carvedilol blockade of α1-adrenergic receptors causes vasodilation of blood vessels. This inhibition leads to decreased peripheral vascular resistance and an antihypertensive effect. There is no reflex tachycardia response due to carvedilol blockade of β1-adrenergic receptors on the heart. Pharmacokinetics Carvedilol is about 25% to 35% bioavailable following oral administration due to extensive first-pass metabolism. Absorption is slowed when administered with food, however, it does not show a significant difference in bioavailability. Taking carvedilol with food decreases the risk of orthostatic hypotension. The majority of carvedilol is bound to plasma proteins (98%), mainly to albumin. Carvedilol is a basic, hydrophobic compound with a steady-state