1. Adrenergic Drugs

2. ADRENERGIC TRANSMISSION
Noradrenaline (NA) It acts as transmitter at postganglionic sympathetic sites (except sweat glands, hair follicles and some vasodilator fibres) and in certain areas of brain.
Adrenaline (Adr) It is secreted by adrenal medulla.

4. Adrenergic receptors
There are two main groups of adrenergic receptors, α and β, with several subtypes.
α receptors have the subtypes α1 and α2.
β receptors have the subtypes β1, β2 and β3.

5. α1 adrenergic receptors
Smooth muscle
Vessels (skin, GI system, kidney and brain)
Glands
Gut
Liver
Muscle contraction
Mydriasis
Vasoconstriction in the skin, mucosa etc.
Gland secretion
Gut relaxation but sphincter contraction
Glycogenolysis

7. α2 adrenergic receptors
Prejunctional on nerve ending
Postjunctional in brain, pancreatic β cells, etc.
Extrajunctional in blood vessels, platelets
Negative feedback in the neuronal synapses - presynaptic inhibition of NA release
Inhibition of insulin release
Induction of glucagon release from the pancreas.
Increased thrombocyte aggregation
Vasoconstriction of veins and coronary arteries
Decrease motility of smooth muscle in GIT

8. β1 receptors Increase heart rate
Increase force of cardiac contractility
Increases conduction of atrioventricular node (AV node)
Renin release from juxtaglomerular cells

9. β2 receptor Smooth muscle relaxation, e.g. in bronchi,GI tract
Relax non-pregnant uterus
Relax detrusor urinae muscle of bladder wall
Dilate arteries to skeletal muscle (in contrast to vasoconstriction caused by α1 and α 2 adrenoceptors). Coronary arteries have only β2 receptors.
Relaxation of Bronchioles

10. β2 receptor

11. β3 receptor
It is located mainly in adipose tissue and is involved in the regulation of lipolysis
β3 activating drugs could theoretically be used as weight-loss agents, but are limited by the side effect of tremors.

14. Epinephrine (adrenaline)
Epinephrine, also known as adrenaline, is a medication and hormone.
As a medication it is given intravenously, by injection into a muscle, by inhalation, or by injection just under the skin.
Epinephrine is normally produced by both the adrenal glands and certain neurons and plays an important role in the “fight-or-flight” response.

15. Norepinephrine
Norepinephrine (noradrenaline) is catecholamine that functions in the human brain and body as a hormone and neurotransmitter.
Norepinephrine is synthesized and released by the central nervous system and also by the sympathetic nervous system.
In the sympathetic nervous system norepinephrine is used as a neurotransmitter.

16. Epinephrine vs Norepinephrine
Adr : α1 + α2 + β1 + β2
NA : α1 + α2 + β1 but no β2 action

17. Comparative effects of intravenous infusion of adrenaline and noradrenaline
Adr NA 1. Heart rate ↑ ↓(reflex bradycardia) 2. Cardiac output ↑↑ – 3. BP—Systolic ↑↑ ↑↑ Diastolic ↓ ↑↑ Mean ↑ ↑↑ 4. Blood flow Skin and mm ↓ ↓ Sk. muscle ↑↑ ↓ 5. Bronchial muscle ↓↓ – 6. Intestinal muscle ↓↓ - 7. Blood sugar ↑↑ –, ↑

18. Adrenaline action Heart
Cardiac stimulation (β1), ↑ rate, force and conduction velocity
Blood vessels
Both vasoconstriction (α) and vasodilatation (β2) can occur .
Constriction predominates in cutaneous, mucous membrane and renal arterioles.
Dilatation predominates in skeletal muscles, liver and coronaries arterioles.

19. Adrenaline action BP
Adr given by slow i.v. infusion or s.c. injection causes rise in systolic (α) but fall in diastolic (β2) BP. Mean BP generally rises.
Rapid i.v. injection of Adr produces:
1) a marked increase in both systolic
as well as diastolic BP.
2) The BP returns to normal within
a few minutes and a secondary fall
in mean BP follows.

20. Norepinephrine and BP It does not cause vasodilatation (no β2 action).
Peripheral resistance increases consistently due to α action.
NA causes only rise in systolic, diastolic and mean BP.

21. Adrenaline action
Respiration
Adr causes bronchodilatation (β2)(but not NA!)
Eye
Mydriasis due to contraction of radial muscles of iris (α1)
The intraocular tension tends to fall.
GIT
Relaxation (both α and β receptors)
CNS
Adr produces activation of brain →restlessness, apprehension and tremor may occur.
!Activation of α2 receptors in the brainstem results in decreased sympathetic outflow → fall in BP and bradycardia.

22. Inducations Hypotensive states (shock)/Anaphylaxis
Adr is the drug of choice in anaphylactic shock (raise BP + bronchodilation)
Along with local anaesthetics
Duration of anaesthesia is prolonged and systemic toxicity of local anaesthetic is reduced. Local bleeding is minimised.
Control of local bleeding
Cardiac arrest (Adr may be used to stimulate the heart)
Bronchial asthma
Mydriatic

23. Adverse effects Tachycardia Arrhythmia Anxiety Panic attack Headache
Tremor
Hypertension
Cerebral haemorrhage
Angina
Myocardial infarction

24. α1-adrenomimetics
Phenylephrine It is an effective mydriatic and decongestant and can be used to raise the blood pressure (in hypotensive states).
Methoxamine acts pharmacologically like phenylephrine.
Midodrine -the treatment of postural hypotension

25. α2-adrenomimetics Nasal decongestant: Naphazoline Xylometazoline
Oxymetazoline
CNS-activating:
Clonidine
Guanfacine (Estulic)
Tizanidine
produce local vasoconstriction
Regular use for long periods should be avoided because atrophic rhinitis and anosmia can occur due to persistent vasoconstriction.
to treat:
high blood pressure,
withdrawal (from alcohol, opioids or smoking)
spasms, cramping, and tightness of muscles

26. Mechanism of Clonidine action
Clonidine → stimulate presynaptic α2-receptors in the vasomotor center → inhibiting the release of NE →decrease in sympathetic tone → lowering blood pressure.
Clonidine → on the I1-receptor (imidazoline receptor), which mediates the sympatho-inhibitory actions of imidazolines to lower blood pressure.

28. Adverse effects of Clonidine
Orthostatic hypotension (Drops in blood pressure upon standing up)
Sedation
Sleepiness
Dizziness
Fatigue
Rebound effect (sudden discontinuation can cause rebound hypertension)

29. β1 STIMULANTS Dobutamine (in cardiogenic shock) Dopamine
Cardiac stimulation ↑ rate, force and conduction velocity
To treat:
acute heart failure
chronic heart failure in phase of cardiac decompensation
cardiogenic shock
ADR:
Hypertension
Angina
Arrhythmia, including fatal arrhythmias
Tachycardia
Atrial fibrillation

30. β2 STIMULANTS Short acting (4–6 hours) : Salbutamol Terbutaline
Ritodrine
Long lasting (12 hours):
Salmeterol
Formoterol
Clenbuterol
the relief of bronchospasm in asthma
to relax the uterine smooth muscle to delay premature labor.
for prevention of asthma symptoms
not for use in relieving an asthma attack (not be used to treat acute symptoms)
should be used with a corticosteroid

31. β2 STIMULANTS Side effects Dizziness Headaches Tachycardia Arrhythmia
Muscle cramps
Paradoxical bronchospasm!
Hypotension and collapse

32. β1β2-STIMULANTS Isoprenaline (isoproterenol) For the treatment of:
Bradycardia
heart block
For asthma (rarely)
ADR:
Tachycardia
Arrhythmia
Hypotension

33. Sympathomimetic drugs
- stimulant compounds (indirect-acting)which mimic the effects of epinephrine and norepinephrine
These drugs can act through several mechanisms:
Blocking breakdown of NA
Blocking reuptake of NA
stimulating production and release of NA.
Ephedrine (found in Ephedra)
Pseudoephedrine
Amphetamine (Benzedrine)
Phenylpropanolamine (norephedrine)

34. Ephedrine Ephedrine is a dangerous natural compound!
Repeated injections produce tachyphylaxis.
In traditional Chinese medicine, it is used as bronchodilators .
Ephedrine crosses to brain and causes stimulation.
Used as:
A stimulant (it increases performance in athletes)
Concentration aid,
Appetite suppressant
Weight loss (a popular supplement taken by body builders to cut down body fat before a competition).
For hypotension during spinal anaesthesia /postural hypotension
Bronchial asthma

35. Ephedrine Adverse drug reactions :
Cardiovascular: tachycardia, cardiac arrhythmias, angina pectoris, vasoconstriction with hypertension
Dermatological: flushing, sweating, acne vulgaris
Gastrointestinal: nausea
Genitourinary: decreased urination due to vasoconstriction of renal arteries
Nervous system: restlessness, confusion, insomnia, mania/hallucinations, paranoia, panic, agitation
Respiratory: dyspnea, pulmonary edema
Miscellaneous: dizziness, headache, tremor, hyperglycemic reactions, dry mouth

36. Pseudoephedrine Medical uses:
a stimulant (improvement in mental and physical functions )
a nasal/sinus decongestant (it reduces edema and nasal congestion/rhinitis)
a wakefulness-promoting agent (treatment of sleeping disorders, excessive daytime sleepiness and narcolepsy)

37. Pseudoephedrine Adverse effects
CNS stimulation- insomnia, nervousness, excitability, dizziness and anxiety.
Tachycardia
Arrhythmias
Hypertension
Hallucinations
Seizures
Systemic contact dermatitis
Paranoid psychosis
Stroke

38. Amphetamine(Adderall)
Amphetamine is used to treat:
Attention deficit hyperactivity disorder (ADHD)
Narcolepsy (a sleep disorder)
Obesity
Past medical indications:
Depression
Nasal congestion

39. Amphetamine(Adderall)
Hypertension
Tachycardia
Erectile dysfunction
Loss of appetite and weight loss
Seizure and tics
Irritability
Repetitive or obsessive behaviors
Amphetamine psychosis (paranoia)
Cardiogenic shock and circulatory collapse
Cerebral hemorrhage
Pulmonary edema and hypertension
Kidney failure
Addiction and Drug tolerance

40. Phenylpropanolamine is used as: A stimulant Decongestant
Anorectic agent
In Europe, PPA is still available in prescription and over-the-counter cough and cold medications.