المحاضرة الثانية

Neurotransmitters

 Chemical Signaling Between Cells
-types of chemical signaling are Neurotransmitters , local mediators and the secretion of hormones .
-All  are too hydrophilic to penetrate the lipid bilayer of target-cell plasma membranes.
A. Local mediators
-Most cells in the body secrete chemicals that act locally.
-rapidly destroyed or removed
-do not enter the blood and are not distributed throughout the body ex:- Histamine and the prostaglandins.

B. Hormones
-secreted from Specialized indocrine cells
- enter the bloodstream where they travel throughout the body exerting effects on broadly distributed target cells in the body.

C. Neurotransmitters
-Communication between nerve cells and between nerve cells and effector organs occurs through the release of specific chemical signals, called neurotransmitters.
-Types of neurotransmitters
norepinephrine (and the closely related epinephrine), acetylcholine,
dopamine, serotonin, histamine, and GABA.

-The autonomic nerve fibers can be divided into two groups based on the chemical nature of the neurotransmitter released.
-If transmission is mediated by acetylcholine, the neuron is termed cholinergic
-if norepinephrine or epinephrine is the transmitter, the fiber is termed adrenergic (adrenaline being another name for epinephrine).
Acetylcholine mediates:
-the transmission of nerve impulses across preganglionic neuron  in both the sympathetic and parasympathetic
-Transmission from the autonomic postganglionic nerves to the effector organs in the parasympathetic system
and a few sympathetic system organs
- transmission In the somatic nervous system, transmission at the neuromuscular junction (that is,
between nerve fibers and voluntary muscles)
Norepinephrine and epinephrine mediate :
-the transmission of nerve impulses from  postganglionic neuron of sympathetic to effector organs .

Chemical Signaling Between Cells

local mediatorsمن أنواعها النواقل العصبية والهرمونات و

ِA-local mediators

ودى بتتفرز من بعض الخلايا وبتدى تأثيرها فى مكانها وبتتكسر فى مكانها 

عشان كده مش بتوصل للدم

   

B. Hormones

 بتتفرز من خلايا معينه زى الغدد وبتوصل لمكان التأثير بتاعها عن طريق دخولها فى الدم

C. Neurotransmitters

ودى هى اللى بتوصل الاشارات بين الخلايا العصبية وبعضها وبين الخلايا العصبية والاعضاء وأمثلة عليها

norepinephrine (and the closely related epinephrine), acetylcholine,
dopamine, serotonin, histamine, and GABA.

nerve fiber اسم ال

بيعتمد على الناقل العصبى اللى خارج من نهايته

acetylcholine لو المادة اللى خارجة

cholenergic  يبقى العصب اسمه

   

norepinephrine or epinephrine لو المادة اللى خارجة  
  adrenergic يبقى العصب اسمه
     Acetylcholine mediates:
-the transmission of nerve impulses across preganglionic neuron  in both the sympathetic and parasympathetic
-Transmission from the autonomic postganglionic nerves to the effector organs in the parasympathetic system
and a few sympathetic system organs
- transmission In the somatic nervous system, transmission at the neuromuscular junction (that is,
between nerve fibers and voluntary muscles)
Norepinephrine and epinephrine mediate :
-the transmission of nerve impulses from  postganglionic neuron of sympathetic to effector organs .

المحاضرة الأولى

Nervous System

 

Afferent neurons carries signals from tissues to brain

 Efferent neurons  carries signals from brain to tissues

 

there is Ganglia in sympathetic and parasympathetic  but not found in somatic

-one somatic fiber neuron is highly branched to skeletal muscles forming (a motor unit )

-Ganglia in sympathetic near CNS 

-preganglionic neuron is short

-postganglionic neuron is long and branched .

-Ganglia in parasympathetic is near the effector organ

-preganglionic neuron is long

-postganglionic neuron is short .

 

Sympathetic :- (Fight or Flight )

adjust responses to stressful situations (ex:- fear , exercises and hypoglycemia)

-increase    heart rate , blood pressure , blood flow to heart and skeletal muscles( while decrease it to skin & organs) , dilate pupil and bronchi

parasympathetic :-  (rest or digest )

oppose or balance action of sympathetic , maintains essential body functions(ex:- digestion and elimination) 

-it's required for life.

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الجهاز العصبى

الصورة اللى فوق بتوضحلنا تقسيمة الجهاز العصبى

Afferent هو اللى بيشيل الاشارة من الخلايا ويوصلها للمخ

يعنى مثلا فى دبوس شكنا يروح باعت اشارة للمخ يقولوا فى خطر 

Efferent هو اللى بيشيل الاشارات من المخ للخلايا

يعنى المخ يبعت اشارة عن طريقه يقول للخلايا اتحركى وابعدى عن الخطر

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Ganglia                            

sympathetic & parasympathetic ودى موجوده فى ال 

somatic لكن مش موجودة فى 

  ودى بتقسم العصب لجزئين 

1-  preganglionic

sympathetic ودى بتبقى قصيرة فى ال

 parasympathetic  وبتبقى طويلة  فى

2- postganglionic

 sympathetic
  بتبقى طويلة ومتفرعة (متفرعه لانه ممكن يحرك اكتر من عضو فى نفس اللحظة يعنى تجرى وتتنفس بسرعه وقلبك يدق بسرعه )

parasympathetic
بتبقى قصيرة جدا وغير متفرعه عشان احنا مش محتاجين انه يشتغل على اكتر من عضو فى لحظة واحده  يعنى الهضم الاول وبعدين الاخراج مش بيبقوا فى نفس الوقت يعنى 

     ---------------------------------

Sympathetic

وده مسؤول عن المواقف الحرجه او اللى بيبقى فيها حركة  زى التمارين مثلا

و بيزود معدل ضربات القلب وضغط الدم ومعدل سريان الدم للقلب والعضلات وبيقلله فى الاعضاء الداخلية عشان يخلى اكبر كمية دم تروح للقلب والعضلات لان الجسم محتاجها هناك فى الاماكن دى

وبيوسع حدقة العين والشعب الهوائية 

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 parasympathetic

وده هو اللى بيبقى فى اغلب الاحيان مسيطر على وضع الجسم 
 وهو عكس السيمباستيك او بيعادله

ومهم جدا لانه مسؤؤل عن عمليات حيوية مهمة زى الهضم والاخراج وهكذا

طبعا الصور شارحه وموضحه كل حاجه ، اى استفسار يا ريت نكتبه فى التعليقات

 

     

Desensitization of receptors

Desensitization of receptors

Repeated or continuous administration of an agonist (or an antagonist) may lead to changes in the responsiveness of the receptor

-repeated administration of a drug results in a diminished effect  وده تعريف  الtachyphylaxis

يعنى استمرار اعطاء الAgonist او ال Antagonist  بيقلل استجابة الreceptor  ليهم

وبالتالى التأثير بتاعهم هيقل.

                         

Dose Response Relationships

حجم تأثير الدواء بيعتمد على كمية او تركيز الدواء عند receptors  اللى بدورها بيتم تحديدها  بجرعة الدواء اللى داخلة الجسم  وpharmacokinetics الخاص  بالدواء.

فى الرسم البيانى  اللى جاى(اسم الرسم البيانى ده  ( graded dose response curves

 رسمنا  effect  على المحور ص مرة مع  ال dose  على المحور س.

ومرة مع ال log doseعلى المحور س وواضح ان العلاقة بينهم طردية.

Ec50 هى drug dose that shows fifty percent of maximal response

وكلما كانت ال Ec50  صغيرة كل مكان  ال drug more potent  .

وفى الرسم واضح ان drug A more potent than drug B))

ال curve  ده بنعرف منه حاجتين مهمين جدا

1-potency

a measure of the amount of drug necessary to produce an effect of a given  magnitude

2-efficacy

the ability of a drug to give a physiologic response when it interacts with a receptor.

the maximal response (Emax) or efficacy is more important than drug potency 

                          

Pharmacotherapeutics and drug interactions

Pharmacotherapeutics

it  is the use of drugs to treat disease.

types of drug therapies:-

• acute therapy, if the patient is critically ill and requires acute intensive therapy
• empiric therapy, based on practical experience rather than on pure scientific data
• maintenance therapy, for patients with chronic conditions that don’t resolve

• replacement therapy, to substitute for missing substances in the body
• supportive therapy, which doesn’t treat the cause of the disease but maintains other threatened body systems until the patient’s condition resolves
• palliative therapy, used for end-stage or terminal diseases to make the patient as comfortable as possible.
   
  -there are many Factors affecting a patient’s response to a drug Because no two people are alike physiologically or psychologically, such as
  ( age - gender - disease - drug interactions - infections -hepatic, renal and GIT functions - diet)
   
   drug dependence :-
    patient displays a physical or psychological need for the drug.
   Physical dependence produces withdrawal symptoms when the drug is stopped
  psychological dependence is based on a desire to continue taking the drug to relieve tension and avoid discomfort
  drug tolerance :-
    patient develops a decreased response to a drug over time. The patient then requires larger doses to produce the same response.
   

  Drug interactions

  Drug interactions can occur between drugs or between drugs and foods.The more drugs a patient receives, the greater the chances that a drug interaction will occur.

  1- additive action

   occur when two drugs with similar actions are administered to a patient .The effects are equivalent to the sum of the 2 drugs .

   advantages: lower doses of each drug, decreased probability of adverse reactions, and greater pain control than from one drug given alone 

   

   2- potentiation action
  also called synergistic effect occurs when two drugs that produce the same effect are given together and one drug enhances the effect of the other drug. This produces greater effects than when each drug is taken alone.

   

  3- antagonistic effect 
   occurs when the combined response of two drugs is less than the response produced by either drug alone.
   
  4- decreased or increased absorption
   two drugs are taken together can change the absorption of one or both of the drugs
  -  drugs can interact and form an insoluble compound that can’t be absorbed.
  -drugs that change the acidity of the stomach can affect the ability of another drug to dissolve in the stomach.
  it  can be avoided by administering the drugs at least 2 hours apart. 
  
  
   5-decreased or increased metabolism and excretion.
   When two drugs are given together, they can compete for protein-binding sites, leading to an increase in the effects of one drug as that drug is displaced from the protein and becomes a free, unbound drug.
   Toxic drug levels can occur when a drug’s metabolism and excretion are inhibited by another drug.
   

drug receptors

 drug receptors

receptor is target macromolecule present on the cell surface or intracellularly where the drug binds to.

After attachment to a receptor site, a drug may either initiate a response or prevent a response from occurring.

An agonist is a drug which produces a stimulation type response. The agonist is a very close mimic and "fits" with the receptor site and is thus able to initiate a response.

An antagonist drug interacts with the receptor site and blocks or depresses the normal response for that receptor because it only partially fits the receptor site and can not produce an effect.

Antagonists can be competitive or noncompetitive.

• A competitive antagonist competes with the agonist for receptor sites. Because this type of antagonist binds reversibly to the receptor site, administering larger doses of an agonist can overcome the antagonist’s effects.
  
  A noncompetitive antagonist
• binds to receptor sites and blocks the effects of the agonist. Administering larger doses of the agonist can’t reverse the antagonist’s action.
  
  

  -If a drug acts on a variety of receptors, it’s said to be non-selective and can cause multiple and widespread effects. In addition, some receptors are classified further by their specific effects. For example, beta receptors typically produce increased heart rate and bronchial relaxation as well as other systemic effects.

  Beta receptors, however, can be further divided into beta₁ receptors (which act primarily on the heart) and beta₂ receptors (which act primarily on smooth muscles and gland cells).

  -  Desensitization of receptors
  Repeated or continuous administration of an agonist (or an antagonist) may lead to changes in the responsiveness of  the receptor. To prevent potential damage to the cell (for example, high concentrations of calcium, initiating cell
  death), several mechanisms have evolved to protect a cell from excessive stimulation. When repeated
  administration of a drug results in a diminished effect, the phenomenon is called tachyphylaxis. 

  The receptor becomes desensitized to the action of the drug . In this phenomenon, the receptors are still present on the cell surface but are unresponsive to the ligand.

  - Dose Response Relationships 

  -The magnitude of the drug effect depends on the drug concentration at the receptor site.
  

   -Drug potency refers to the relative amount of a drug required to produce a desired response. Drug potency is also used to compare two drugs. If drug X produces the same response as drug Y but at a lower dose, then drug X is more potent than drug Y.

   -efficacy

   This is the ability of a drug to illicit a physiologic response when it interacts
  with a receptor.
  

  - a dose-response curve is used to graphically represent the relationship between the dose of a drug and the response it produces.

  

  
  

  Maximum effect

  On the dose-response curve, a low dose usually corresponds to a low response. At a low dose, a dosage increase produces only a slight increase in response. With further dosage increases, the drug response rises markedly. After a certain point, however, an increase in dose yields little or no increase in response. At this point, the drug is said to have reached maximum effectiveness.

  - therapeutic index

  it is The relationship between a drug’s desired therapeutic effects and its adverse effects . It’s also referred to its margin of safety.

  The therapeutic index usually measures the difference between:

  • an effective dose for 50% of the patients treated
  • the minimal dose at which adverse reactions occur.