PHARM-301 Dr.

MAZHAR-UL-HAQ

PHARMACOLOGY
SELECTIVE AND NON-SELECTIVE DRUGS
SELECTIVE NON-SELECTIVE
These drugs have selective effects and are: These could be:
(1) α1 and α2- selective (1) α1 and α2 non- selective
(2) β1 and β2- selective (2) β1 and β2 non-selective

α2-SELECTIVE
 Used as adjunct therapy as a pre-anesthetic medication to control the voluntary actions.
It is also used as sedative and analgesic.
 Present on neurons on CNS and related to control the perception of pain and level of
sedation. It also mediates the control neurons involved in blood pressure and heart rate.

β2-SELECTIVE
 The β2- bronchodilator located on bronchial smooth muscles. Used to treat obstructive
bronchitis, emphysema or Asthma.
 Administered orally and have long action e.g, Salbutanol, Isoproterenol,
Metaproterenol, Pirbuternol, Clenbuternol.
 Problem with their long use is that the patient becomes irresponsive or resistant or we
can say the desensitization of receptors.
 Loss of β2-type population agonist induced long term use refractory down regulation.
 Used with combination or comitent use of β2-bronchodilator like with Methylxanthine.
Aminophylline is used in COPD or Asthma.

SYMPATHOLYTIC DRUGS
They block the effects of sympathetic drugs by various mode of action either by receptor
blocking or neuron blocking mechanism.
RECEPTOR BLOCKING MECHANISM
 Adrenergic antagonist/ Competitive antagonist interact with adrenergic receptors.
 These bind to adrenergic receptors but do not trigger any type of series of reaction
which produce cellular responses that could be Reversible and Irreversible.
 They prevent catecholamines to produce effects.

BY: MUDASSIR ARSALAN

PHARM-301 Dr.MAZHAR-UL-HAQ

ADRENERGIC NEURON BLOCKING MECHANISM (Adrenolytics)

 These block adrenergic neuron stimulated physiological response. Act presynaptically at
nerve terminal and interfere with neuro-transmitter release so nor-epinephrine release
is affected.
 Vesicle is unable to burst to release neurotransmitter. Sometimes release but reuptake
back e.g, Cocaine, Reserpine, Guanithidine

ADRENERGIC ANTAGONIST
(1) α-adrenergic antagonist/ α-adrenergic blocking agents (α-blockers)
(2) β-adrenergic antagonist/ β-adrenergic blocking agents(β-blockers)

TYPES
Naturally Occurring Alkaloids
ERGOT ALKALOID
Mostly these are phenothiazene derivatives. Common are Acepromazine,
Phenoxybenzamine HCl, Phentolamin HCl, Prazosins(synthetic α–blocker) ,
Trazosin, Doxazosins, Tolazin HCl.

Synthetic
β-blockers
 These are β–receptor antagonist. They contain Dichloro-isoproterenol,
Proprenolol, Atenolol, Acebutolol.
α-blockers
 These are non-selective (both α1 and α2)
 α1-selective are Prazosins.
 α2-selective are Rauwolscine, Yohimbine(no clinical use only experimental use)
 Phenoxybenzamine(non-competitive) irreversible and reversible for
Phentolamine.
 Phenoxybenzamine covalently binds to α1-receptor post-synaptically and α2-
receptor pre-synaptically.
 Action longs for 24 hours for single dose but not rapid onset of action and take
some time.
 On blood vessels it acts pre-synaptically and prevents vasoconstriction, maintain
blood pressure by making catecholamin. Also provokes reflex of tachycardia to
decrease peripheral resistance.

BY: MUDASSIR ARSALAN

PHARM-301 Dr.MAZHAR-UL-HAQ

 Through α1-receptor increase cardiac output but in high blood pressure it does
not lower B.P
Vasoreversal phenomenon of Dales
 Epinephrine phenomenon of Dale (1st scientist who noted it)
 Non-selective α-blockers e,g Phentolamine they block α1-type receptors and
prevent vasoconstriction caused by epinephrine.
 Administer adrenaline (epinephrine) biphasic effect in which B.P once increases
then decreases. It acts through both α1 and α2- receptors.
 In high doses activates α1-receptors and vasoconstriction occurs.
 In low doses activates α2-receptors and vasodilation occurs.
 No biphasic effect of epinephrine when administered after non-selective drugs.
Only β2- mediated receptors effect will be there and fall in B.P could be seen
only.
β-blockers
 These are competitive antagonists and are non-selective acting on both β1 and
β2 receptors subtypes.
 Whereas selective one like cardioselective β-antagonists (β1-blockers) primarily
blocks β1-receptor subtype.
 β2- selective blockers has effect on respiratory system (bronchial tree).
 All β-blockers lower B.P in hypertension . Helpful in treatment of cardiac
erythema, Angina, Myocardial Infarction, prophylactically in migraine headache.
 But these are less used in vet. Practices and they are recommended to to use in
obstructive cardio-myopathy in dogs e.g, Dichloro-isoproterenol, properenolol.
Proprenolol
 It is non-selective β-antagonist.
 In case of cardiac erythema used in dogs at dose rate of 1mg/kg (I/V).
Particularly as pre-anesthetic medication like Halothane.
 In case of digitalis induce tachycardia and used at dose rate of 1-3 mg/kg body
weight slow I/V in dogs.
 Adrenergic antagonist administered slowly when given I/V induce cardiac
depression in the form of bolus.
 Other non-selective β-antagonist are Nodolol, Timolol, Pindolol. They affect β2-
receptors and also cause Insulin Dependent Diabetes.

BY: MUDASSIR ARSALAN

PHARM-301 Dr.MAZHAR-UL-HAQ

ADRENERGIC NEURON BLOCKING DRUGS (Atagonists)

 They affect uptake and release of neurotransmitter nor-epinephrine.
 These are catecholamin depleting agents and also called sympatho-pelagic
agents.
 Act pre-synaptically at adrenergic nerve terminal and prevent release of nor-
epinephrine.
 In vet. Medicine they are not clinically used e.g Reserpine, Cocaine,
Guanethidine, Bretyllium.
RESERPINE
 It is an alkaloid of plant Rauwolfia reserpina/serpentina).
 Used in human medicine in hypertension and physiological disorder.
 Used as pharmacological tool to deplete indigenous catecholamine in CNS and
PNS.
Mode of action
 This reserpine block Magnesium dependent ATPase transport of biogenic ions. It
blocks magnesium dependent ATPase transport from cytoplasm to storage
vesicles in adrenergic nerve terminal.
 It causes depletion of nor-epinephrine as mono-amine oxidase enzyme and also
degrade nor-epinephrine in cytoplasm.
 Reserpine has slow onset but prolong effects
 This reserpine is used in case of cardiac arrhythmia in case of dog at the dose
rate of 26µg/kg daily orally. It also crosses blood brain barrier and affect central
pathway as well.
 Reserpine is also used in hypertension when the drug fail to respond . Reserpine
can cause functional sympathectomy by depleting adrenergic neurons of their
storage of nor-epinephrine.
COCAINE
 It is a unique drug among local anesthetics and has the ability to block Na/k
ATPase transport system which is required for cellular uptake of nor-epinephrine
across cell membrane of adrenergic neurons. Consequently nor-epinephrine is
accumulated in synoptic space.

BY: MUDASSIR ARSALAN

PHARM-301 Dr.MAZHAR-UL-HAQ

GUANETHIDINE
 It also depletes catecholamines by blocking release of store nor-epinephrine. A
local anesthetic like effect is produced on adrenergic nerve terminal. So it
gradually reduce blood pressure in combination with proprenolol.
 Some miscellaneous agents are also use other than these specific drugs affecting
adrenergic nerves e.g, 6-hydroxy dopamine ( synthetic oxy-dopamine which is
taken up in adrenergic nerve and cause autonomic destruction of nerve
terminal). It produces chemical sympathectomy and several weeks are requires
regeneration of nerves.
α-methyldopa
 It is taken up into adrenergic nerve and biotransformed by catecholamine
synthesizing enzyme into α-methyl nor-epinephrine. Then this synthesized nor-
epinephrine is stored in granules.
 This attached α-methyl group protects this compound from oxidation by mono-
amine oxidase enzyme. This methylated nor-epinephrine remain present and
produce a potent α-2 agonist response.
 Sometimes some mono oxidase inhibitors are also used, they interfere with
oxidative deamination of catecholamines. So these catecholamines accumulate
in neurons e.g inhibitors are Slegeline, phenelzine. They inactivates the enzymes
both reversibly and irreversibly. They have high drug-drug and drug-food
interaction.
 In humans they are used as anti-depressants and mood elevators. They are also
present in Tyramine containing foods items like in cheese, wine, beer and
chicken liver and these food items are used with the use of these MAO inhibitor.
This may cause hypertension crisis and cerebral vascular accidents (level of
catecholamine is more)
 BRETYLLIUM for just research items.

AUTACOIDS
 These are anti-inflammatory drugs. These are peracrine secrections, local
hormones or neurotransmitters
 In inflammation many types of mediators are involved like Histamine, Serotonin
(5-hydroxy tryptamine), Bradykinins, interleukins, prostaglandins (PGE2), N2O
and substance P.

BY: MUDASSIR ARSALAN

PHARM-301 Dr.MAZHAR-UL-HAQ

ANTI-HISTAMINIC
 Inhibits the inflammatory reaction caused by histamine receptors (H-receptors).
 There are three main types of h-receptors: H1, H2 and H3. Here H1 and H2
receptors are dominant subtypes in skin and cause the inflammatory reactions.
 Anti-histamine is restricted to the agents that act on histamine receptors.
 H1 anti-histamine are classified as inverse agonist rather than histamine
antagonist. It reflects true mechanism of action which is to stabalize the H1
receptors in an inactivate state.
 H1 anti-histamine are divided into generations:
(1) 1st Generation Anti-histamine
(2) 2nd Generation Anti-histamine
 Examples of 1st generation Anti-histamine areChlorpheneramines, Diphen-
hydramine, Hydroxyzine.
 Examples of 2nd Generation anti-histamine are Cerizine, Loratidine, Desloratidine,
Fexofenadine.
 2nd Generation Anti-histamines are newer. They are non-sedative and introduced
after 1981.
 Where as 1st Generation are older one and have anti-histaminic properties and
easily cross blood brain barrier. So they produce CNS effects particularly sedation
are common. They are used clinically for treatment of Pruritus, atopic-dermatitis
and respiratory disorders like Asthma, COPD and other disorders.

BY: MUDASSIR ARSALAN