1. Adrenergic Antagonists

2. α-Adrenergic Blocking Agents
Affect BP decreased PVR reflex tachycardia

3. Phenoxybenzamine Nonselective, irreversible, noncompetitive
Decrease PVR reflex tachycardia
α2 block increased CO ?????
Pretreatment with phenoxybenzamine followed by Epi???
Used in Pheochromocytoma (before surgery or inoperable tumor) & in Raynaud disease
SEs: postural hypotension, nasal stuffiness, NV, sexual disturbances, & reflex tachycardia

4. Phentolamine Competitive, nonselective α-blocker (4 hrs)
Postural hypotension
Reflex cardiac stimulation
CI in patients with coronary artery disease
Used locally to prevent T necrosis
Used for short term treatment of Pheochromacytoma
Useful in hypertensive crisis due to clonidine abrupt withdrawal & in (tyamine + MAOIs)

5. Prazocin, Terazocin, Doxazocin, Tamsulosin, Alfuzocin
Selective, competitive α1-blockers useful in hypertension
Tamsolosin & alfuzocin used in benign prostatic hyperplasia (BPH)
Metabolized & excreted in urine except for doxazocin
Doxazocin have long duration of action
Decreases PVR, BP (venous & arterial effect)
Minimum effect on CO, RBF, & glomer. Filtration rate
Tamsulosin has the least vascular effect (α1B) & higher effect on prostate (α1A)

6. α-blockers cont. 1st dose effect
Modest improvement in lipid profile & glucose metabolism in hypertension
SEs: dizziness, lack of energy, headache, orthostatic hypotension, Floppy iris syndrome
α-blockers + vasodilators (ex. Nitrates or PDEIs)???
Sexual dysfunction

7. Yohimbine Selective, copmetetive α2-blocker Treat erectile dysfunction
Increases CNS sympathetic out flow
CI in CVDs, psychiatric conditions & renal dysfunction

8. β-Adrenergic Blocking Agents
Competetive, nonselective β1 & β2
Differ in intrinsic sympathomimetic activity, CNS effects, blockade of sympathetic Rs, vasodilation & kinetics
Decrease BP
No postural hypotension ???
Used in Hpertension, Angina, Arrhythmia, MI, HF, Hyperthyroidism, Glaucoma & prophylaxis of Migraine headache
All cpds end with (– olol)

9. Propranolol (nonselective)
CVS:
Decrease CO, -ve inotropic, chronotropic, & AV & SA inhibition-----
Decrease CO, workload, & oxygen consumption
Useful in supravent. Arrhythmia but not in vent. arrhythmia
Peripheral vasoconstriction(β2, reflex response
Increase PVR -----
Reflex vasoconst.-----
In Hypertensive patients, total PVR return to normal ore below
Gradual decreasae in syst. & diast. BP

10. Propranolol (cont.) Bronchoconstriction (precipitate COPD)
Glucose metabolism (glycogenolysis, Glucagon)
Prop. + Isoproterenol
Prop + Epi ???
Prop + NE ???

12. Therapeutic uses: Hypertension (normotensive ???) Decrease CO
Inhibit renin release from kidney
Decrease total PVR
Decrease sympathetic outflow
Angina, (chronic management of stable angina)
Myocardial infarction
Prophylactic
Immediate administration, …..?
Reduce incidence of sudden arrhythmic death after MI
Migraine (prophylactic, lipid soluble)
Hyperthyroidism

13. Propranolol (cont.)
Kinetics (absorption, metabolism, BBB)
Adverse effects:
Bronchoconstriction
Arrhythmia (upregulation, ppt arrhythmia)
Sexual impairment
Metabolic disturbances:
Glycogenolysis, glucagon
ppt symptoms of hypoglycemia -----?
Mobilize energy molecules ex. FFA(lipase activation, β2, β3 , bad, good cholesterol, selective β1 )
CNS effects (CNS dep., fatigue, weakness,------, selective β1 antag.)

14. Drug interaction
Inhibitors: cimetidine, fluoxetine, paroxetine, and ritonavir
Inducers: barbiturates, phenytoin, and rifampin

15. Nadolol, Timolol: non-selective β agents
More potent than prop.
Nadolol: long duration
Timolol, betaxolol, carteolol------glaucoma (open-angle glaucoma, piloarpine???)

17. Acebutolol, Atenolol, Betaxolol, Bisoprolol, Esmolol, Metaprolol, & Nebivolol Selective β1 antagonists
Β1 selective, no bronchoconstriction (β2)
This occurs at doses 50 – 100 fold less than β1
This effect disappear at high doses
So SEs are predictable
Used for hypertension & to increase exercise tolerance in angina
Esmolol given IV, short duration of action???
Fewer effects on pulmonary system, PVR, & CHO metabolism ???
nevibolol releases NO from endothelial SMs------?
Uses ???

18. Therapeutic uses:
 hypertensive patients with impaired pulmonary function
first-line therapy for chronic stable angina
Bisoprolol and the extended-release formulation of metoprolol are indicated for the management of chronic heart failure
Raynaud phenomenon) is less frequent???

19. Acebutolol, Pindolol: antagonists with Partial Agonist Activity
Acebutolol β1 selective antagonist
Pindolol nonselective β blocker
With Intrinsic Sympathomimetic Activity (ISA)???
Diminished effect on heart
Β blockers with ISA minimize disturbances in lipid & CHO metabolism compared with other β blockers
Effective in hypertensive patients with bradycardia

20. Labetalol & Carvedilol: antagonists of both α & β adrenoceptors
Labetalol, carvedilol: nonselective β-blocker with α1 blocking effect------
Decrease BP
Carvedilol decrease lipid peroxidation, vascular wall thickening, so useful in HF
Labetalol replaced methyldopa in pregnancy hypertension & used in hypertensive crisis (IV)
SEs include orthostatic hypot. & dizziness

21. Clinical Uses of β-blockers

22. Drugs Affecting Neurotransmitter Reuptake or Release
EMT: extraneuronal MAO transporter, NET: neuronal noradrenal;ine transporter

24. Drugs Affecting Neurotransmitter Release or Uptake
Reserpine (plant alkaloid):
Blocks Mg/adenosine triphosphate (biogenic amine transporter)
Slow onset of action, long duration of action
Used in hypertension replaced with newer drugs