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Physiology with pharmacology - L1 > Intro to pharm, endocrine, autonomic (& in pharm) > Flashcards

Intro to pharm, endocrine, autonomic (& in pharm) Flashcards

1
Q

What is a drug?

A

Chemical substance with a known structure, that when administered to a living organism produces a biological effect

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2
Q

What is pharmacology?

A

The study of mechanisms by which drugs affect the function of living systems.

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3
Q

What is bioassay?

A

Analytical method to determine the concentration or potency of a substance by its effect on living organism.

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4
Q

What is the importance of bioassay? (3 points)

A
  • measure pharmacological effect of chemically undefined substances.
  • investigate the function of endogenous mediators
  • measure drug toxicity & unwanted effects
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5
Q

What are 3 fundamental principles of pharmacology?

A
  • Drug action must be explicable in terms of chemical interactions between drugs & tissues.
  • Drug molecules must be BOUND to cells/tissues.
  • Drug molecules must EXERT chemical influence on cells
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6
Q

What 4 types of proteins are usually targeted for binding by drugs?

A
  • Enzymes
  • Transporters
  • Ion Channels
  • Receptors
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7
Q

What is an agonist?

A

A chemical mediator that produces a response when bound to a receptor.

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8
Q

What is an antagonist?

A

Chemical mediator that prevents the response of an agonist. These don’t elicit a response

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9
Q

What property of drugs can cause side effects?

A

Drugs that lack specificity

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10
Q

What drug binds to opioid receptors?

A

Morphine

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11
Q

How does CAR T immunotherapy kill cancer cells?

A

Through manipulation of contact-dependent signaling

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12
Q

What is a CAR receptor?

A

Chimeric antigen receptor that is inserted into the genome of patient T-cells, to create a ‘live’ drug.

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13
Q

What is an example of therapeutic manipulation of paracrine signaling in receptors?

A

Blocking of receptors for histamines

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14
Q

What is the role of mast cells & where are they found?

A

Located under the skin & detect allergens. Activated mast cells secrete mediators e.g. Histamine

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15
Q

What physiological changes can occur as a result of a release of histamines?

A
  • Vasodilation
  • activate neurones involed with itching
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16
Q

What is a way paracrine signaling can be affected by drugs?

A

Prostaglandins can cause inflammation. Paracetamol can target enzymes involved in the synthesis of mediators used to make up prostaglandins.

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17
Q

How can drugs target ion channels used to regulate neurotransmission?

A
  • block voltage-gated Na+ channels
  • prevent action generation
  • used as local anesthetics (lidocaine in Strepsils)
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18
Q

How can drugs target machinery involved in the release of neurotransmitters?

A

Cleaving of proteins involved in synaptic machinery (eg. Botulinum toxin - BoTox- produced by bacteria).

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19
Q

How can drugs target transporters involved in neurotransmission?

A

Drugs can target transporters found on the cell membrane. They can prevent the reuptake of neurotransmitters.

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20
Q

What is the purpose of targeting transporters for neurotransmission?

A
  • prevention of reuptake can alleviate symptoms through constant stimulation. Prozac is an antideppresant (blocks 5HT).
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21
Q

How can post-synaptic membranes by affected by drugs?

A

Through:
Activation (by agonists)
Inhibition (by antagonists)

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22
Q

What is an example of pharmacological manipulation of endocrine signaling?

A

Drugs increasing signaling to insulin receptor - Diabetes Type1 (no insulin produced)

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23
Q

What does the endocrine system regulate?

A
  • Development
  • Growth
  • Reproduction
  • Metabolism
  • Blood pressure
  • Concentration of ions in the blood
  • Behaviour
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24
Q

What are the signaling mediators used in the endocrine system?

A

Hormones

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25
Q

Describe the positioning of endocrine cells (think about function)

A
  • Close to capillary beds
  • Found in endocrine tissues or glands
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26
Q

Do endocrine glands have ducts?

A

No

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27
Q

What do endocrine glands release?

A

Hormones

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28
Q

Describe the distances, times & specificity involved in the endocrine system

A
  • long distances
  • slow
  • specific to receptors, not tissues/organs
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29
Q

What are the 3 types of hormones?

A
  • protein
  • amino acid derived
  • steroid
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30
Q

What is an example of a hormone as a protein?

A

Insulin

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31
Q

What is an example of a hormone as an amino acid derivative?

A

Adrenaline (epinephrine)

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32
Q

What is an example of a hormone as a steroid?

A

Estradiol

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33
Q

What is the main difference in the 3 different types of hormones?

A

Their cell permeability

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34
Q

Describe where different types of hormones are synthesized?

A

Peptide - from amino acids

Amino acid derived - derivatives of tyrosine

Steroids - metabolites of cholesterol

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35
Q

Describe where different types of hormones are released

A

Peptide - secretory granules (exocytosis)

Amino acid derivatives - vesicles (exocytosis) *except thyroid hormone.

Steroids - lipid soluble

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36
Q

Described the target receptors of different types of hormones

A

Peptide - cell membrane surface receptors

Amino acid derivatives - cell membrane surface receptors *except thyroid hormone

Steroids - diffuse into cell, binding to nuclear receptors

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37
Q

Describe the response times of different types of hormones

A

Peptide - secs to mins

Amino acid derivatives - secs to mins

Steroids - hours to days

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38
Q

What are the 7 endocrine glands?

A
  1. Pituitary (anterior & posterior)
  2. Thyroid
  3. Parathyroids
  4. Adrenals (cortex & medulla)
  5. Ovaries
  6. Testes
  7. Endocrine pancreas
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39
Q

What are the 6 endocrine tissues?

A
  1. Hypothalamus
  2. Kidneys
  3. GI tract
  4. Heart
  5. Liver
  6. Adipose tissues
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40
Q

What type of cells does the anterior pituitary have? (what do they do)

A

Troph cells - releasing hormones from small diameter neurons of the hypothalamus

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41
Q

What vein do hormones released from the troph cells travel through?

A

Portal vein

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42
Q

What is another name given to the anterior pituitary?

A

Adenohypophysis

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43
Q

What is another word for the posterior pituitary?

A

Neurohypophysis

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44
Q

What direction projection is seen in the adenohypophysis?

A

Upward projection

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45
Q

What direction projection is seen in the neurohypophysis?

A

Downward projection

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46
Q

What does the posterior pituitary release? (& into where?)

A

Hormones from the large diameter neurons directly into systemic circulation.

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47
Q

What are the 5 major pituitary hormones?

A
  • ADH (antidiuretic hormone)
  • oxytocin
  • growth hormone
  • tropic hormone
  • thyroid stimulating hormone
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48
Q

What are the hormones located in the thyroid gland?

A

T3 & T4

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49
Q

What is the necessary conditions (2 points) for the synthesis & release of T3 &T4 (thyroid hormones)?

A
  • iodine - an essential trace element
  • hypothalamic-pituitary hormones
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50
Q

How are T3 & T4 (thyroid hormones) transported across membranes?

A

Facilitated diffusion

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51
Q

What type of receptors do T3 & T4 (thyroid hormones) bind to?

A

Nuclear receptors (regulate transcription)

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52
Q

What 2 processes is the thyroid gland associated with?

A
  • Metabolism
  • Development & Growth
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53
Q

What hormone is produced by the parathyroid gland?

A

Parathyroid hormone (PTH)

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54
Q

What are the targets of parathyroid gland?

A
  • Bone
  • Intestine
  • Kidney
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55
Q

Describe the feedback loop involved in lowering plasma levels by using parathyroid hormone (PTH)

A
  1. Calcium levels sensed by chief cells
  2. increase in plasma
  3. decrease in PTH
  4. decrease in kidney tubule reabsorption
  5. decrease bone calcium (plasma) reabsorption
  6. decrease in intestinal calcium absorption.
  7. This results in lowering plasma (Calcium)
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56
Q

What cells sense plasma (calcium) levels?

A

Chief cells

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57
Q

What are the two parts of the adrenal gland?

A

Adrenal cortex & adrenal medulla

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58
Q

What is the role of the adrenal cortex?

A

Release steroid hormones:
- glucocorticoid - cortisol
- mineralocorticoid - aldosterone

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59
Q

What cells are found in the adrenal cortex?

A

Chromaffin cells

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60
Q

What is released from chromaffin cells?

A

Adrenaline & Noradrenaline

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61
Q

What complex is present in the endocrine pancreas?

A

Islets of langerhans

62
Q

What are the 2 types of cells present in the Islets of Langerhans?

A
  • B (beta) cells
  • a (alpha) cells
63
Q

What is the role of B (beta) cells in the Islets of Langerhans?

A

Release insulin

64
Q

What is the role of a (alpha) cells in the Islets of Langerhans?

A

Produce glucagon

65
Q

Where are insulin & glucagon released?

A

Into portal blood to influence the liver.

66
Q

What 4 processes occur when we sleep?

A
  • we breath
  • blood still reaches organs
  • food & drink still digested
  • we sweat
67
Q

What system ensures we survive when sleeping? (lack of consciousness)?

A

Autonomic nervous system

68
Q

Autonomic nervous system - voluntary or non-voluntary?

A

Non-voluntary

69
Q

What makes up the central nervous system?

A

Brain & Spinal Cord

70
Q

What type of neurons are found at the sensory part of the peripheral nervous system?

A

Afferent neurons

71
Q

What type of neurons are found at the motor (effector) part of the peripheral nervous system?

A

Efferent neurons

72
Q

What type of muscle is found in the somatic nervous system?

A

Skeletal muscle

73
Q

What types of muscles are found in the autonomic nervous system?

A

Smooth muscle, cardiac muscle & glands

74
Q

What set of nerves send information to the CNS, which will then require as response from the autonomic nervous system?

A

Visceral nerves

75
Q

When will the sympathetic response become activated?

A

FIGHT OR FLIGHT
- exercise
- excitement
- emergency
- embarrassment

76
Q

When will the parasympathetic response become activated?

A

REST & DIGEST:
- digestion
- defecation
- diuresis

77
Q

Describe the physiological changes during the sympathetic response

A
  • Eye - pupils dilate = more light
  • Heart - increase in heart rate
    -Blood vessels - constrict = more blood in muscles & less in digestive tract.
  • Lungs - brronchodilation
  • Liver - increase in level of glucose released

(reproductive system - relax bladder & constriction of sphincter)

78
Q

Describe the physiological changes during the parasympathetic responses

A

Eyes - constricts pupils = restricts light
Heart - slows heart rate
GI tract - increased levels of digestion.
Bladder - constriction of bladder & release of sphincter

(reproduction - supply muscular coats of the vagina & urethra, stimulate the erectile tissue)

79
Q

The sympathetic & parasympathetic pathways work synergistically. What does this mean?

A

Despite being antagonistic, they work together.

80
Q

What is the advantage of the sympathetic & parasympathetic working synergistically?

A

Allows for rapid, precise control of tissue function.

81
Q

What type of neuron is found in the central nervous system?

A

Preganglionic neuron

82
Q

What type of neuron is found in the peripheral neuron?

A

Postganglionic neuron

83
Q

Describe the general organization of the autonomic nervous system (ANS)

A

Central nervous system (preganglionic neuron)

Peripheral neuron (postganglionic neuron)

Target cell

84
Q

Describe the properties of preganglionic neuron

A
  • always CHOLINERGIC fibers.
  • Release ACh as primary neurotransmitter.
  • Ach activates nicotinic ACh receptors on the postsynaptic cell.
  • It is an example of a ligand-gated ion channel
85
Q

Describe the sympathetic pathway

A
  1. SHORT, cholinergic preganglionic neurons - from thoracic & lumbar spinal cord.
  2. LONG adrenergic (release noradrenaline) postganglionic neurons
  3. Target tissue - expresses a & b adrenergic receptors
86
Q

How is the adrenal medulla’s role in the sympathetic pathway differ to the normal pathway?

A

It is similar to postganglionic neurons, but releases mainly adrenaline.
- target tissues still express a & b adrenergic receptors.

THIS AMPLIFIES THE FLIGHT OR FLIGHT RESPONSE THROUGH THE RELEASE OF ADRENALINE.

87
Q

Describe the parasympathetic pathway

A
  • LONG cholinergic preganglionic neuron (brain stem & sacral spinal cord)
  • SHORT cholinergic postganglionic neurons.
  • Target tissue expresses muscarinic ACh receptors (g-protein receptor)
88
Q

What is another word for the vagus nerve?

A

Cranial nerve

89
Q

In which pathway is the vagus nerve important in?

A

Parasympathetic

90
Q

What % of total parasympathetic outflow is carried by the Vagus nerve?

A

80%

91
Q

Other than parasympathetic outflow, what else does the Vagus nerve carry?

A

Visceral afferents

92
Q

What are the 3 main components of the central components in the ANS?

A
  • Spinal cord
  • Brainstem nuclei
  • Hypothalamus
93
Q

What is the role of the spinal cord in the ANS?

A
  • mediates autonomic reflexes
  • receives sensory afferent & brainstem input
94
Q

What is the role of the brainstem nuclei in the ANS?

A
  • mediate autonomic reflexes
95
Q

What is the role of the hypothalamus in the ANS?

A
  • take in information from the limbic system
  • thermoregulation
  • circadian rhythms
  • water balance
  • sexual drive
  • reproduction
96
Q

Other than the main parts of the central components of the ANS, what other parts of the body regulate ANS output?

A

Forebrain - small level of cortical control e.g. anxiety leading to GI disturbances.

Visceral afferents - sensory input from visceral afferent neurons take priority over cortical (conscious) functions - e.g. can only hold a wee for a certain amount of time.

97
Q

What are the 2 principle transmitters in the ANS?

A
  • Acetylcholine
  • Noradrenaline
98
Q

What 2 types of receptors do Acetylecholine & Noradrenaline act upon?

A
  • nAChR (nicotinic acetylcholine receptors)
  • mAChR (musciarinic acetylcholine receptors)
99
Q

How may drugs indirectly target ANS receptors?

A

Through their synthesis or breakdown

100
Q

How may drugs directly target ANS receptors?

A

Through agonists & antagonists

101
Q

What is the physiological effect of nicotine?

A

Affect heart rate & brain

102
Q

What is the physiological effect of Curare?

A

Causes muscle paralysis, as blocks nicotine receptor - including neuro-muscular junction

103
Q

What are 2 agonists that effect cholinergic receptors?

A
  • Nicotine
  • Muscarine
104
Q

What are 2 antagonists that effect cholinergic receptors?

A
  • Curare
  • Atropine
105
Q

What are 2 examples of cholinergic receptors?

A
  • Nicotinic
  • Muscarinic
106
Q

How many types of muscarinic receptors are there?

A

5

107
Q

What type of G protein are the M1, M3 & M5 subtypes of mAChRs?

A

Gq

108
Q

Describe the pathway in which M1, M3 & M5 mAChRs cause an increase in intracellular calcium

A
  • Increase in PLC
  • Increase in IP3
  • Increase in intracellular Ca2+
109
Q

What type of G protein are the M2 & M4 subtypes of mAChRs?

A

Gi

110
Q

Where are muscarinic receptors found?

A
  • Postsynaptic in parasympathetic ganglion neurones
  • Sweat glands
111
Q

What is the effect of M2 & M4 G protein muscarinic receptors?

A

Inhibitor - decreases calcium channels

112
Q

Describe the pathway in which M2 & M4 G protein muscarinic receptors decrease voltage-gated Calcium channels

A

Gi - decrease adenylyl cyclase = decrease cAMP.
- increase in Potassium channel opening
- decrease in voltage gated Calcium channels

113
Q

What are the main location of the M2 Gi (G-protein) mAChR?

A

Heart, atria

114
Q

What is the functional response of the M2 mAChrR?

A

Cardiac inhibition

115
Q

What are the main locations of the M3 Gq G protein mAChR?

A
  • Exocrine gland
  • Smooth muscle
  • GI tract
  • Airways
  • Bladder
116
Q

What are the functional responses?

A
  • Gastric, salivary secretion
  • Gastrointestinal smooth muscle contraction
117
Q

Describe the effect of activated M2 receptors on heart rate

A
  1. M2 activation via ACh (acetylcholine)
  2. G(i) protein activation
  3. BY subunits open K+ channels.
  4. K+ move OUT of the nodal cells.
  5. More negative membrane potential
118
Q

What subunit causes a decrease in heart rate (M2)?

A

BY

119
Q

What physiological changes on muscle as a result of M1 & M3 muscarinic receptors?

A

CONTRACTION OF SMOOTH MUSCLE:
- bronchocontriction
- gastrointestinal motility
- bladder voiding

120
Q

What physiological changes on exocrine glands as a result of M1 & M3 muscarinic receptors?

A

STIMULATE EXOCRINE GLANDS:
- mucus in the lungs
- lacrimal glands
- salivary glands
- sweat glands

121
Q

Describe the effect of muscarine

A
  • decrease blood pressure (reduction in cardiac output)
  • increase saliva
  • increase in sweating
122
Q

What could an overdose of muscarine be due to?

A

A lack of cardiac action

123
Q

Why is the use of mAChR agonists limited in clinical settings?

A

Lack of specificity

124
Q

What physiological effects does the muscarinic antagonist - atropine - have?

A
  • Inhibition of salivation
  • Smooth muscle relaxant
  • Pupil dilation
  • Acid secretion
125
Q

What enzyme is used in the breakdown of acetylcholine?

A

Acetylcholinesterase

126
Q

What is an example of a long acting (irreversible) anticholinesterase?

A

Sarin - nerve gas

127
Q

What are the 2 types of adrenoreceptor?

A

B1 & B2

128
Q

Where is the B1 adrenoreceptor found?

A

Heart

129
Q

Where is the B2 adrenoreceptor found?

A

Bronchi

130
Q

What effect does stimulation of the B1 adrenoreceptor cause?

A

Tachycardia

131
Q

What effect does stimulation of the B2 adrenoreceptor cause?

A

Relaxation (in the bronchi)

132
Q

What is a clinical use of B2 selective agonists?

A

Treat asthma

133
Q

What do all beta adrenoreceptors couple with?

A

Gas

134
Q

What is the consequence of Beta adrenoreceptors & Gas coupling?

A

Increase cAMP levels

135
Q

What chemical mediators can increase heart rate?

A

Noradrenaline & adrenaline

136
Q

What neurons are noradrenaline released from?

A

Sympathetic neurons

137
Q

What cells release adrenaline (epinephrine)?

A

Chromaffin cells

138
Q

What are the receptor locations (2 types) involved in the increase in heart rate?

A
  • Nodal tissue
  • Ventricular myocytes
139
Q

What is the receptor type involved in an increase in heart rate?

A
  • B1 adrenergic receptors coupled to Gas G proteins.
140
Q

How do B1 receptors increase heart rate?

A

Exert a stimulant action which increases force of contraction. This leads to increased cardiac output.

141
Q

The effect of increased heart rate by activation of the B1 adrenoreceptor is regulated by what substance?

A

Calcium channel activity

142
Q

How does B1 adrenoreceptor cause an increase in calcium?

A

Through phosphorylation of calcium current:
1. B1 activation via noradrenaline/
2. Gas Protein activation
3. Increase in cAMP
4. Increase in PKA (protein kinase A)
6. Phosphorylation of calcium channels

143
Q

How does the activation of PKA lead to the phosphorylation of calcium channels?

A

Increased activated PKA = increased voltage-gated calcium channel open time = more calcium into myocytes = increased contraction.

144
Q

What is the chemical mediator that causes relaxation of smooth muscle in the bronchioles, as a result of activation of the B2 adrenoreceptor?

A

Adrenaline (released from Chromaffin)

145
Q

What is the receptor location for the B2 adrenoreceptor that causes muscle relaxation?

A

Bronchioles (in the lungs)

146
Q

What type of receptor type is used, when activated, to cause relaxation in smooth muscle located in the bronchioles?

A

B2 adrenoreceptor (adrenergic receptor), which is coupled to Gas G proteins

147
Q

What is the effect of agonist stimulation on the B2 adrenoreceptor?

A

Phosphorylation of smooth muscle machinery = relaxation of smooth muscle = bronchodilation

148
Q

What are the clinical uses of the adrenoreceptor agonist - Adrenaline?

A

Cardiac arrest - adrenaline
Anaphylaxis - adrenaline

149
Q

What are the clinical uses of the adrenoreceptor B2?

A

Bronchodilator (Salbutamol) - B2 selective

150
Q

What are clinical uses for adrenoceptors antagonists?

A
  • Treating hypertension
  • Heart failure
  • Anxiety (somatic symptoms)
151
Q

What are 2 unwanted effects of adrenoreceptors agonists?

A
  • Bronchoconstriction - beta blockers are avoided in asthma patients.
  • Cardiac depression - especially in the elderly

Physiology with pharmacology - L1 (17 decks)

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