Pharmacology trans - Adrenceptor Agonists/Sympathomimetic Drugs II

Study Notes

OAB involves involuntary contractions of the detrusor muscle, leading to urinary urgency and frequency.
PVR pertains to the resistance that blood vessels offer against blood flow; influenced by adrenergic receptors.

Dopamine (DA) selectively activates D1 receptors and is utilized in appropriate therapeutic doses.
DA actions include blocking enzymes that metabolize catecholamines to enhance effects.
Key enzyme inhibitors:
- MAO inhibitors: pargyline and selegiline
- COMT inhibitor: entacapone

Activation of β3 receptors on detrusor muscle leads to muscle relaxation.
Activation of α1 receptors results in mydriasis (pupil dilation) without cycloplegia (loss of accommodation).

Drug Z (Norepinephrine - NE):
- Activates β1 receptors, causing an increase in heart rate (↑HR).
- Activates α1 receptors leading to peripheral vascular resistance (↑PVR) through intense vasoconstriction, raising blood pressure (↑BP).
- Reflex bradycardia occurs as a compensatory response to increased BP.
Drug Y (Epinephrine - EPI):
- Exhibits a biphasic response; at certain doses, both α1 and β2 receptors are activated.
- At higher doses, may cause elevated stroke volume (↑SP) due to positive inotropic and chronotropic effects.

Capable of direct receptor activation and indirect release of norepinephrine from sympathetic nerve terminals.
Mechanisms include:
- Displacing NE from nerve terminals.
- Inhibiting NE reuptake via NET.
- Blocking metabolizing enzymes MAO and COMT.

Two main groups of sympathomimetics:
- Non-catecholamines:
  - Generally lipid-soluble, orally bioavailable, with a longer duration of action.
  - Not degraded by COMT, leading to higher oral bioavailability.
  - Can cause tachyphylaxis, a rapid decrease in drug effectiveness.