9. Termination of action
1) Reuptake into nerve terminals by NET
(Na+ dependent )
2)Dilution by diffusion out of Jn: cleft followed by Extra-neuronal
uptake (not Na+ dependent )
3) Metabolic transformation by MAO & COMT
39. USES
1) Acute Bronchial Asthma
0.3-0.5 ml of a 1/1000,given S/C, 1/100 (N)
2)Cardiac arrest, resuscitation
0.2-0.5 ml of a 1/1000,given I/T
3) Anaphylactic shock – DOC
0.2-0.5 ml of a 1/1000,given IM
40. 4) Local Haemostatic- after tonsillectomy,
Tooth extraction etc.
Epinephrine pack dipped in 1/10000,1/20000 solution
5) Along with LA- 1/20000,1/100000 solution
(prolongs action, decreases toxicity)
6) Glaucoma- Prodrug –Dipivefrine
after absorption converted into Epinephrine
AH formation
45. USE
• Treatment of refractory Hypotension (neurogenic)
• Effect disappear 1-2’ after stopping infusion
So taper it off gradually.
46. DOPAMINE
(3,4 di OH phenyl ethylamine) MIXED ACTING
D1, β1, α1, Indirect Action
ACTIONS
Central - neurotransmitter involved in the
regulation of movement
Periphery - synthesized in the PCT ( local diuretic & natriuretic
effect)
On BP - ↑ SBP & PP, no effect on DBP.
48. Moderate doses (2-10µg/kg/mt)
D1 + β1 & release NE (contribute -effect on the heart)
• ↑β1 : +ve inotropic action
• ↑ in BP due to + inotropic action. Also ↑ blood flow to vital organs
• little chronotropic & ↓ arrhythmogenic.
High doses (10-20 µg/kg/mt)
α1
• ↑ BP by VC &
• ↓ blood flow to vital organs
50. USES
Severe CCF in patients with oliguria & low or normal PR
Improves physiological parameters in the Rx of
cardiogenic & septic shock
Improve cardiac & renal function in severely ill patients
with chronic heart d/s or renal failure
56. Clonidine
• Imidazoline derivative
• Rapid I/V infusion - acute rise in BP
( activation of post synaptic α2 in vascular smooth muscles )
Mechanism of action
-(1) activation of α2 receptors in the VMC.
(2) Imidazoline receptors (GPCR) I 1,2,3
(3) activates presynaptic α2 to ↓ NE release
57. Clonidine
• Pharmacokinetics
- well absorbed orally
- t ½- 8-12 hour
- max. hypotensive effect after 2-4 hrs.
Preparations
- oral
- i/v
- Epidural
- TD patch
59. USES
1) Antihypertensive (moderate HTN) – 100 µg BD
2) opioid & nicotine withdrawal symptoms
(↓ craving )
(3) Prophylaxis of Migraine
(4) Along with anesthetics
(5) ↓ Pain in severe painful conditions like cancer, post –op,
labor etc
60. CLONIDINE- T/D- Menopausal syndrome for ↓ hot
flashes
Miscellaneous uses of clonidine
Atrial Fibrillation
Attention Deficit Hyperactivity Disorder
Hyperhidrosis
Mania
Post Herpetic Neuralgia
Ulcerative Colitis, etc
61. α Methyl DOPA
• central action - similar to clonidine in action
• Peripheral - “false transmitter” (α methyl NE)
• Not as potent as NE
• Used in PIH
67. Prenalterol
• Moderate inotropic action (sympathetic – low)
• Marked inotropic action ( symp activity high) – during exercise
• Use –
for short term control of mild to moderate heart failure
( i/v infusion)
75. Mech. of CNS action
Release of
• NE (alerting & anorectic actions)
• Dopamine ( locomotor activity & stereotype behavior)
• 5HT (disturbance of perception & overt psychotic
behavior)
76. ACTIONS
• CNS - Produces alertness, initiative,
• ↑ concentration & self confidence.
• delays onset of fatigue
• Improves physical performance, ( due to cortical action)
• Produce wakefulness by ↑ RAS
• CVS - Cardiac stimulation, ↑ BP - β1
• Smooth muscle- contract sphincters – α1
• Others- Respiratory stimulant, suppress appetite
77. ADR
Anxiety, restlessness, tremor, irritability, delirium,
psychosis, tachycardia, palpitation, angina, arrhythmia
Dry mouth , metallic taste, N,V, D, Urine retension
Fatal doses- convulsions, coma & cerebral H’ages
Use – seldom used due to addiction liability & risk of
psychosis
Narcolepsy, obesity, ADHD,
78. Tyramine
• By product of tyrosine metabolism
• Metabolized by MAO ( liver )
• High first-pass effect
• Spectrum of action is similar to that of norepinephrine
• Patients taking MAO inhibitors must be very careful to avoid tyramine-
containing foods
79. Catecholamine Reuptake Inhibitors
• Atomoxetine ( norepinephrine reuptake transporter)
• Reboxetine
• Sibutramine - NE & 5 HT reuptake (-)
- appetite suppressant for long-term treatment of obesity
80. Catecholamine Reuptake Inhibitors
• Duloxetine
serotonin and norepinephrine transporter
• Milnacipran
• Cocaine
- produces an amphetamine-like psychological effect
- inhibit dopamine reuptake into neurons in the “pleasure
centers
85. TACHYPHYLAXIS
acute tolerance
With drugs like Ephedrine, Tyramine, Amphetamine, 5HT,
Isoprenaline when administered repeatedly, at very short intervals,
the pharmacological response elicited decreases progressively.
87. VASCULAR
• Hypotensive states -
• ( adrenaline in anaphylactic shock)
• Along with local anaesthetics
• Control of local bleeding
• Nasal decongestant
• Peripheral vascular disease