At the end of the last lecture we start talking about the sympathetic nervous system in which neurotransmitter are

epinephrine & nor-epinephrine also we have another catecholamine such as" isopronalen and dopamine" that are applicable to stimulate the sympathetic nervous system receptors

2 agonist use in the treatment of hypertension keep this in your mind by inhibiting the release of nor-epinephrine or in other ward inhibiting the sympathetic out flow. 1 increase the heart rate choronotropic effect & increase in contractility inotropic effect .

now lets begin with new lecture

sympathomimc drugs

Direct indirect (selective like 1, 2,1, 2 OR non selective like epinephrine ,nor-

epinephrine,dopamine,isoproline "
Amphetamine TCAs Cocaine -

Non-selective mean the drug act in more than one type of receptors the following table represent comparison between E and NE

Nor-epinephrine 1secreted from sympathetic nerve endings select 1,2,1 only Use to elevate blood pressure in case of shock used IV as Generalized vasoconstrictor Blood supply dont reach some tissues this might lead to tissue damage, it decrease renal blood flow

2- Epinephrine
secreted from adrenal medulla select 1,2,1,2 Use in the treatment of anaphylactic shock Its used mainly MI ,some times SC ,can be used also IV in the treatment of cardiac arrest

Anaphylactic shock is type of hypersensitivity reaction which lead to produce histamine now histamine is vasodilator to treat this situation we need epinephrine as "local vasoconstrictor"

3-Isoprinalne
" stimulant "doesn't have any effect on receptors it act only on 1 and 2 receptors as non-selective agonist it cant differentiate between 1 and 2 receptor and can act on both in similar ways . now this drug can relax the 1- bronchial smooth muscles ( bronchial dilatation 2) we cant use it in the treatment of bronchial asthma 2- stimulate the heart (tachycardia1 ) use in treat severe bradycardia this stimulation might produce fetal arrhythmia.

4- dopamine
Another catecholamine and an important neurotransmitter its action depends on its dose can Stimulate1- 1 receptor : by stimulation of 1 receptors its responsible to increase the cardiac output (increase heart rate and the force of contraction ) so dopamine can be used IV to treat congestive heart failure "acute severe heart failure " condition that characterized by decrease in cardiac out put , 2- dopamine receptors : which located in the blood vessel especially in renal blood vessel by the stimulation of these receptors renal vasodilatation will happen and this will maintain the renal blood flow also prevent renal shut down . Dopamine & nor-epinephrine are used in the treatment of shock but we prefer dopamine because dopamine will increase blood pressure(by working in 1 recepter)& maintain renal blood flow although nor-epinephrine increase blood pressure too , but it reduce renal blood flow .

Selective sympathomimc drugs (S-adrenergic drugs )

Selective :mean it can act only in one receptor "select one receptor " if they are used in therapeutic dose . Examples :

1-Phenylephrine :

(selective 1 agonist i.e. it select 1 only not 2,1,and2)

used locally as nasal decongestant by working only on 1 receptor and cause vasoconstriction of the blood vessel in the nasal mucosa to relief congestion .

2- Clonidine : (selective 2 agonist ) used in the treatment of hypertension by

reduce the sympathetic outflow : 1- No nor-epinephrine release this will lead to vasodilatation decreasing in total peripheral resistance reduce the BP . 2-reduce in myocardial contractility reduce the heart rate ,reduce in the cardiac output and decrease BP .

How the nervous system the control of blood pressure ??

1-autonomic feedback loop by baro-receptors which are located in

the arch of aorta or in the carotid sinus in which if there is an increase in the blood pressure this will activate those receptor discharge and activate parasympathetic system to increase the vagel tone and reduce the heart rate ,reduction in the heart rate will reduce the cardiac out put & reduce the blood pressure , in the same time there will be reduction in the sympathetic tone in which there will be reduction in the heart rate ,reduce the force of contraction reduce vasoconstriction this will reduce the blood pressure , now decrease in the blood pressure will inhibit the PSNS and activate SNS. Any drug increase TPR and cause vasoconstriction will cause reflex bradycardia also the drug that decrease TPR and cause vasodilatation will produce reflex tachycardia. Those are used Ca channels blockers (type of hypertensive drug) which block the enter of Ca either to the heart or to the smooth muscle in the blood vessel to reduce the contraction or it cause vasodilatation especially short acting some patient cant tolerate to this drug they returned back to the doctor and say that there heart rate is elevated because of the compensatory mechanism in which these drugs cause vasodilatation and the compensatory mechanism reflex tachycardia will occur.

2- hormonal feed back effect :

Blood pressure = heart rate *total peripheral resistance Cardiac output = heart rate * stroke volume Reduction in the blood pressure will reduce the renal blood flow and enhance renin secretion from juxtamedullary apparatus , Renin convert angiotensinogen to angiotensin 1 converting later on by( angiotensin converting enzyme)to angiotensin 2 now increase in angiotensin 2 will couse1- vasoconstriction increase TPR increase BP 2- increase production of aldesterone which inhance( Na,H2O) retention increase the volume of the blood increase preload also increase cardiac out put lead to increase BP. How to treat hypertension : // 1-drugs that reduce the blood volume 2- drugs can reduce the cardiac output. 3-drugs are reduce total peripheral resistance (TPR) Alpha and beta stimulation role in controlling BP ?? ------ 1 stimulation lead to vasoconstriction then increase in TPR this will lead to increase blood pressure .

------ 1 stimulation increase the heart rate and increase myocardial contractility this will increase cardiac output and increase blood pressure . also -1 stimulation produce renin NOTE : when we reduce the sympathetic action on 1 & 1 we can reduce BP.

3- Dobutamine (selective 1
used to C.O. in heart failure .

agonists )

4- Salbutamol its brand name "ventolin " (selective 2

agonists )

If we stimulate 2 in the bronchial tree this will lead to bronchodilator so it is given by inhalation to treat bronchial asthma , also 2 stimulation lead to uterine muscle relaxation we use it in the treatment of preterm laber (contraction of the uterine muscle).

Indirect Acting Sympathomimc Drugs

As we said sympathomimc drugs are direct (selective or non selective) or indirect now indirect drugs are either enhance the release of neurotransmitters e.g Amphetamine or inhibit the neurotransmitters reuptake e.g tri cyclen antidepressant .

MOA of amphetamine

Amphetamine is CNS stimulant , in picture B above amphetamine cause the NT release from the presynaptic neuron (triangles) & increase the response , but in picture A which is with no amphetamine few amount of NT release. Amphetamine may produce: 1-euphoria (extreme happiness) 2-increase mental activity . 3-reduce appetite but it shouldn't use in control the body weight due to high risk of dependence or addiction . ---- Amphetamine use only in tow situation : 1- narcolepsy : uncontrollable time of sleep the patient sleep at any time he/she may sleep during driving. 2-hyperreactivity in children : the child is hyperkinetic but his/her Attention is very low . ***** this drug is contraindicated in pregnancy .

Q:the following circle represent the papillary diameter in one eye before and after stimulation of drug X you will see this is the control sign and this is after application of drug X which of the following drug is responsible to cause this mydriasis :

1-Physostegmen (indirect acting cholinergic agonist & it cause meiosis ) 2-acytlcholin (parasympathomimic also cause meioses)

3- Phenylephrine ( 1agonist it cause mydriasis ) 4- Isoprenaline (non selective agonist ) 5-therpiamine (like sulbutamol 2 agonist ) Q : mioses can be induced by : 1- Phenylephrine 2- Isoprenaline 3- carbachol (activate ACH and induce meioses ), or pilocarpine (used in the management of glaucoma 4-non of the above.

Adrenergic blockers (adrenergic antagonist)

f rom the previous figure skip Irreversible (phenoxybenzamine) & beta2 selective (butoxamine ) yohimbine :used for sexual stimulant and in the treatment of postural hypotension .

non selective blockers : phentolamine because its responsible to block 1 receptor it can cause vasodilatation so it reduce BP and because of the vasodilatation effect this will lead to reflex tachycardia .

Side Effect of phentoamine : postural hypotension or orthostatic hypotension in which there is reduction in the blood pressure when there is change in the body position like going to the vertical position from setting to standing from lying down to setting or standing once the patient take phentolamine he change his position he will feel dizzy and fainting at the same time this is known as postural or orthostatic hypotension related to change in the body posture. Selective 1 blocker (end with the suffix" E.g (prazocin) , (terazocin ) There action by blocking 1recepter and by that induce vasodilatation , BP Uses : 1-treatment of hypertension 2-bengin Prostatic Hyperplasia or( benign prostatic hypertrophy) : those males are complain of prostate enlargement and one of there problem is urinary retention by using selective 1 blockers this relaxation of the bladder sphincter will happen & enhance the urine outflow . ***Side effect : Vasodilatation lead to vertigo , reflex tachycardia , postural hypotension (hypotension is severely seen in elderly PT by that the initial dose usually it reduce to 1/2 or 1/4 " and doctors advice the PT to take the drug at bed time to reduce the risk of postural hypotension ) blockers (end with the suffix olol) those drugs are only block receptor either they are selective or non selective its very important that any drug end with the suffix 'olol' is blocker with some exception (carvedilol , labetalol) Non selective blocker *** 1- Propranolol Non selective it can block both 1&2 Therapeutic uses: 1- hypertension : because it responsible to reduce cardiac out put.

cin")

2-glocuma : glaucoma is an increase in the intraocular pressure blocker reduce the secretion of aqueous humor by that it will decrease this pressure . 3-migrane: blocking of 2 receptor will prevent the vasodilatation of the cerebral artery and reduce the pain, Note here we dont use it in the treatment of migraine acute attack . 4- Angina pectoris, cardiac arrhythmias ,and myocardial infarction (MI) :those are ischemic heart disease there is imbalance between cardiac Oxygen demand and the Oxygen supply the action of blocker here by the C.O reduce the H.R ,and by that it will reduce the Oxygen requirement , in the treatment of MI as in people how have history of MI by enhances the recovery also it reduce the probability of have arrhythmia after MI . 5-Anxiety: control the symptoms of it ,,, some medical student take small amount of propanolol before there oral exams in order to reduce these symptoms like termer & palpitation . 6-Hyperthyroidism :excessive secretion of the thyroid gland hormone T3and T4 , --the symptoms (nervousness ,palpitation ,termer) propanolol will reduce this symptoms . -- propranolol reduce blood vessel sensitivity to the thyroid hormone -- propranolol also prevent the converge of T3 and T4 peripherally so it effective in the management of Thyrotoxicosis 7- Essential Tremor 2-timolol non selective block 1 and 2 and its used in the treatment of gluocoma ****selective blocker ** Mainly we concern in the cardiaoselective blocker which mean they block only 1 receptor if they are used in there therapeutic dose EXAMPLE :

atenolol
A- We can use it in which non selective blockers(Propranolol)are contraindicated >> this occur in the bronchial asthma Propranolol is contraindicated in the treatment of bronchial asthma because ; its non selective so it can block 2 receptor in the bronchial causing bronchoconstriction and this will

worse the bronchial attack also it may be fetal in asthmatic PT keep this in your mind. B- For hypertensive patients with impaired pulmonary function (but the patient should be carefully monitored by using it only on there therapeutic doses).

Q:

8 years child come to the emergency department , they measure

his BP in tow separate readings at relax situation & see that his BP 140/95 his mother told the doctor "my son is a Diabitec PT and he take insulin " which one of these 2 drugs (atenolol or propanolol) u prefer to control hypertension in this Diabetic PT & why ? the answer is cardioselective "atenolol " ; if we use non selective drug "propanolol " it will block beta 2 receptors and reduce gluconeogenesis (reduce glucose level in the blood ) and increase the risk of hypoglycemia also you notice the PT take insulin so the risk of hypoglycemia will be doubled

Labetolol
Is blocker (non selective ) and 1 blocker used in the treatment of emergency hypertension such as "pregnancy induced hypertension ".

endeolol
its a partial agonist . has lower intrinsic activity than the full agonist also know intrinsic sympathomimc agent and it act as blockers in the presence of catecholamine. Beta blockers S/E 1-brochoconstiction by blocking 2. 2-hypotension blocking 1 & reduce the cardiac output . 3- raynaud's : peripheral vascular disease due to decrease the blood flow to the extremities (especially digits ) by blocking 2 this will induce vasoconstriction also blocking 1 and reduce CO . 4- Nightmares : this is a CNS adverse effect mostly in propanolol users because it cross the BBB. 5- masking the symptoms of hypoglycemia

non selective beta blockers are mask the symptoms of hypoglycemia : (dizziness, fating, nervousness ,headache ,hunger ,palpitation, ,termer ) its very danger & can cause coma and death.
Other hypoglycemia symptom is sweating but NS-B cant masked it because sweet gland is controlled by SNS & ACH as NT and the receptors are MR

6-Sexual dysfunction in males : blockers also have this S/E . NOTE : beta antagonist (blocker ) shouldnt stopped suddenly that will worse the condition in which they are using for ; using of antagonist with time lead to receptor upregulation i.e.( increase the receptor number and there activity also increase the sensitivity of the drug) this high number of receptor will lead to what is known redound hypertension or it increase the risk of arrhythmia if its used in the treatment of cardiac arrhythmia ,, Q : 60 old ,hypertensive male ,asthmatic PT comes to check up and complain of having some difficulty when he starting to urinate physical examination is doing his BP is 160/100 (hypertensive ) ,,, which of the following medication will be used in the treatment of both (hypertension & urinary retention )of these conditions ? 1-lapetaolol : contraindicated because he is an asthmatic PT 2-phentoamine : non selective alpha blocker effective in the management of hypertension but we need treatment to both conditions 3-proponolol :contraindicated because he is an asthmatic PT

4- Terazocin

alpha 1 antagonist

5- isopropanol : Not used ,, beta agonist

Dental implications

Dryness of the mouth, or xerostomia, results from diminished secretions of Saliva , Drugs that produce xerostomia as a side effect include anticholinergics,antidepressants, antihistamines/decongestants, antipsychotics, diuretics, hypnotics, systemic bronchodilators, muscle relaxants,beta-blockers.

Fogive me if there is any mistake

3 important things to success : 1-work more than others 2-learn more than others 3-except less than others

Done by : zain mahdi Al.salameen