Intro to pharm, endocrine, autonomic (& in pharm) Flashcards
(151 cards)
1
Q
What is a drug?
A
Chemical substance with a known structure, that when administered to a living organism produces a biological effect
2
Q
What is pharmacology?
A
The study of mechanisms by which drugs affect the function of living systems.
3
Q
What is bioassay?
A
Analytical method to determine the concentration or potency of a substance by its effect on living organism.
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
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
6
Q
What 4 types of proteins are usually targeted for binding by drugs?
A
- Enzymes
- Transporters
- Ion Channels
- Receptors
7
Q
What is an agonist?
A
A chemical mediator that produces a response when bound to a receptor.
8
Q
What is an antagonist?
A
Chemical mediator that prevents the response of an agonist. These don’t elicit a response
9
Q
What property of drugs can cause side effects?
A
Drugs that lack specificity
10
Q
What drug binds to opioid receptors?
A
Morphine
11
Q
How does CAR T immunotherapy kill cancer cells?
A
Through manipulation of contact-dependent signaling
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.
13
Q
What is an example of therapeutic manipulation of paracrine signaling in receptors?
A
Blocking of receptors for histamines
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
15
Q
What physiological changes can occur as a result of a release of histamines?
A
- Vasodilation
- activate neurones involed with itching
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.
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)
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).
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.
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).
21
Q
How can post-synaptic membranes by affected by drugs?
A
Through:
Activation (by agonists)
Inhibition (by antagonists)
22
Q
What is an example of pharmacological manipulation of endocrine signaling?
A
Drugs increasing signaling to insulin receptor - Diabetes Type1 (no insulin produced)
23
Q
What does the endocrine system regulate?
A
- Development
- Growth
- Reproduction
- Metabolism
- Blood pressure
- Concentration of ions in the blood
- Behaviour
24
Q
What are the signaling mediators used in the endocrine system?
A
Hormones
25
Describe the positioning of endocrine cells (think about function)
- Close to capillary beds
- Found in endocrine tissues or glands
26
Do endocrine glands have ducts?
No
27
What do endocrine glands release?
Hormones
28
Describe the distances, times & specificity involved in the endocrine system
- long distances
- slow
- specific to receptors, not tissues/organs
29
What are the 3 types of hormones?
- protein
- amino acid derived
- steroid
30
What is an example of a hormone as a protein?
Insulin
31
What is an example of a hormone as an amino acid derivative?
Adrenaline (epinephrine)
32
What is an example of a hormone as a steroid?
Estradiol
33
What is the main difference in the 3 different types of hormones?
Their cell permeability
34
Describe where different types of hormones are synthesized?
Peptide - from amino acids
Amino acid derived - derivatives of tyrosine
Steroids - metabolites of cholesterol
35
Describe where different types of hormones are released
Peptide - secretory granules (exocytosis)
Amino acid derivatives - vesicles (exocytosis) *except thyroid hormone.
Steroids - lipid soluble
36
Described the target receptors of different types of hormones
Peptide - cell membrane surface receptors
Amino acid derivatives - cell membrane surface receptors *except thyroid hormone
Steroids - diffuse into cell, binding to nuclear receptors
37
Describe the response times of different types of hormones
Peptide - secs to mins
Amino acid derivatives - secs to mins
Steroids - hours to days
38
What are the 7 endocrine glands?
1. Pituitary (anterior & posterior)
2. Thyroid
3. Parathyroids
4. Adrenals (cortex & medulla)
5. Ovaries
6. Testes
7. Endocrine pancreas
39
What are the 6 endocrine tissues?
1. Hypothalamus
2. Kidneys
3. GI tract
4. Heart
5. Liver
6. Adipose tissues
40
What type of cells does the anterior pituitary have? (what do they do)
Troph cells - releasing hormones from small diameter neurons of the hypothalamus
41
What vein do hormones released from the troph cells travel through?
Portal vein
42
What is another name given to the anterior pituitary?
Adenohypophysis
43
What is another word for the posterior pituitary?
Neurohypophysis
44
What direction projection is seen in the adenohypophysis?
Upward projection
45
What direction projection is seen in the neurohypophysis?
Downward projection
46
What does the posterior pituitary release? (& into where?)
Hormones from the large diameter neurons directly into systemic circulation.
47
What are the 5 major pituitary hormones?
- ADH (antidiuretic hormone)
- oxytocin
- growth hormone
- tropic hormone
- thyroid stimulating hormone
48
What are the hormones located in the thyroid gland?
T3 & T4
49
What is the necessary conditions (2 points) for the synthesis & release of T3 &T4 (thyroid hormones)?
- iodine - an essential trace element
- hypothalamic-pituitary hormones
50
How are T3 & T4 (thyroid hormones) transported across membranes?
Facilitated diffusion
51
What type of receptors do T3 & T4 (thyroid hormones) bind to?
Nuclear receptors (regulate transcription)
52
What 2 processes is the thyroid gland associated with?
- Metabolism
- Development & Growth
53
What hormone is produced by the parathyroid gland?
Parathyroid hormone (PTH)
54
What are the targets of parathyroid gland?
- Bone
- Intestine
- Kidney
55
Describe the feedback loop involved in lowering plasma levels by using parathyroid hormone (PTH)
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)
56
What cells sense plasma (calcium) levels?
Chief cells
57
What are the two parts of the adrenal gland?
Adrenal cortex & adrenal medulla
58
What is the role of the adrenal cortex?
Release steroid hormones:
- glucocorticoid - cortisol
- mineralocorticoid - aldosterone
59
What cells are found in the adrenal cortex?
Chromaffin cells
60
What is released from chromaffin cells?
Adrenaline & Noradrenaline
61
What complex is present in the endocrine pancreas?
Islets of langerhans
62
What are the 2 types of cells present in the Islets of Langerhans?
- B (beta) cells
- a (alpha) cells
63
What is the role of B (beta) cells in the Islets of Langerhans?
Release insulin
64
What is the role of a (alpha) cells in the Islets of Langerhans?
Produce glucagon
65
Where are insulin & glucagon released?
Into portal blood to influence the liver.
66
What 4 processes occur when we sleep?
- we breath
- blood still reaches organs
- food & drink still digested
- we sweat
67
What system ensures we survive when sleeping? (lack of consciousness)?
Autonomic nervous system
68
Autonomic nervous system - voluntary or non-voluntary?
Non-voluntary
69
What makes up the central nervous system?
Brain & Spinal Cord
70
What type of neurons are found at the sensory part of the peripheral nervous system?
Afferent neurons
71
What type of neurons are found at the motor (effector) part of the peripheral nervous system?
Efferent neurons
72
What type of muscle is found in the somatic nervous system?
Skeletal muscle
73
What types of muscles are found in the autonomic nervous system?
Smooth muscle, cardiac muscle & glands
74
What set of nerves send information to the CNS, which will then require as response from the autonomic nervous system?
Visceral nerves
75
When will the sympathetic response become activated?
FIGHT OR FLIGHT
- exercise
- excitement
- emergency
- embarrassment
76
When will the parasympathetic response become activated?
REST & DIGEST:
- digestion
- defecation
- diuresis
77
Describe the physiological changes during the sympathetic response
- 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
Describe the physiological changes during the parasympathetic responses
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
The sympathetic & parasympathetic pathways work synergistically. What does this mean?
Despite being antagonistic, they work together.
80
What is the advantage of the sympathetic & parasympathetic working synergistically?
Allows for rapid, precise control of tissue function.
81
What type of neuron is found in the central nervous system?
Preganglionic neuron
82
What type of neuron is found in the peripheral neuron?
Postganglionic neuron
83
Describe the general organization of the autonomic nervous system (ANS)
Central nervous system (preganglionic neuron)
Peripheral neuron (postganglionic neuron)
Target cell
84
Describe the properties of preganglionic neuron
- 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
Describe the sympathetic pathway
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
How is the adrenal medulla's role in the sympathetic pathway differ to the normal pathway?
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
Describe the parasympathetic pathway
- LONG cholinergic preganglionic neuron (brain stem & sacral spinal cord)
- SHORT cholinergic postganglionic neurons.
- Target tissue expresses muscarinic ACh receptors (g-protein receptor)
88
What is another word for the vagus nerve?
Cranial nerve
89
In which pathway is the vagus nerve important in?
Parasympathetic
90
What % of total parasympathetic outflow is carried by the Vagus nerve?
80%
91
Other than parasympathetic outflow, what else does the Vagus nerve carry?
Visceral afferents
92
What are the 3 main components of the central components in the ANS?
- Spinal cord
- Brainstem nuclei
- Hypothalamus
93
What is the role of the spinal cord in the ANS?
- mediates autonomic reflexes
- receives sensory afferent & brainstem input
94
What is the role of the brainstem nuclei in the ANS?
- mediate autonomic reflexes
95
What is the role of the hypothalamus in the ANS?
- take in information from the limbic system
- thermoregulation
- circadian rhythms
- water balance
- sexual drive
- reproduction
96
Other than the main parts of the central components of the ANS, what other parts of the body regulate ANS output?
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
What are the 2 principle transmitters in the ANS?
- Acetylcholine
- Noradrenaline
98
What 2 types of receptors do Acetylecholine & Noradrenaline act upon?
- nAChR (nicotinic acetylcholine receptors)
- mAChR (musciarinic acetylcholine receptors)
99
How may drugs indirectly target ANS receptors?
Through their synthesis or breakdown
100
How may drugs directly target ANS receptors?
Through agonists & antagonists
101
What is the physiological effect of nicotine?
Affect heart rate & brain
102
What is the physiological effect of Curare?
Causes muscle paralysis, as blocks nicotine receptor - including neuro-muscular junction
103
What are 2 agonists that effect cholinergic receptors?
- Nicotine
- Muscarine
104
What are 2 antagonists that effect cholinergic receptors?
- Curare
- Atropine
105
What are 2 examples of cholinergic receptors?
- Nicotinic
- Muscarinic
106
How many types of muscarinic receptors are there?
5
107
What type of G protein are the M1, M3 & M5 subtypes of mAChRs?
Gq
108
Describe the pathway in which M1, M3 & M5 mAChRs cause an increase in intracellular calcium
- Increase in PLC
- Increase in IP3
- Increase in intracellular Ca2+
109
What type of G protein are the M2 & M4 subtypes of mAChRs?
Gi
110
Where are muscarinic receptors found?
- Postsynaptic in parasympathetic ganglion neurones
- Sweat glands
111
What is the effect of M2 & M4 G protein muscarinic receptors?
Inhibitor - decreases calcium channels
112
Describe the pathway in which M2 & M4 G protein muscarinic receptors decrease voltage-gated Calcium channels
Gi - decrease adenylyl cyclase = decrease cAMP.
- increase in Potassium channel opening
- decrease in voltage gated Calcium channels
113
What are the main location of the M2 Gi (G-protein) mAChR?
Heart, atria
114
What is the functional response of the M2 mAChrR?
Cardiac inhibition
115
What are the main locations of the M3 Gq G protein mAChR?
- Exocrine gland
- Smooth muscle
- GI tract
- Airways
- Bladder
116
What are the functional responses?
- Gastric, salivary secretion
- Gastrointestinal smooth muscle contraction
117
Describe the effect of activated M2 receptors on heart rate
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
What subunit causes a decrease in heart rate (M2)?
BY
119
What physiological changes on muscle as a result of M1 & M3 muscarinic receptors?
CONTRACTION OF SMOOTH MUSCLE:
- bronchocontriction
- gastrointestinal motility
- bladder voiding
120
What physiological changes on exocrine glands as a result of M1 & M3 muscarinic receptors?
STIMULATE EXOCRINE GLANDS:
- mucus in the lungs
- lacrimal glands
- salivary glands
- sweat glands
121
Describe the effect of muscarine
- decrease blood pressure (reduction in cardiac output)
- increase saliva
- increase in sweating
122
What could an overdose of muscarine be due to?
A lack of cardiac action
123
Why is the use of mAChR agonists limited in clinical settings?
Lack of specificity
124
What physiological effects does the muscarinic antagonist - atropine - have?
- Inhibition of salivation
- Smooth muscle relaxant
- Pupil dilation
- Acid secretion
125
What enzyme is used in the breakdown of acetylcholine?
Acetylcholinesterase
126
What is an example of a long acting (irreversible) anticholinesterase?
Sarin - nerve gas
127
What are the 2 types of adrenoreceptor?
B1 & B2
128
Where is the B1 adrenoreceptor found?
Heart
129
Where is the B2 adrenoreceptor found?
Bronchi
130
What effect does stimulation of the B1 adrenoreceptor cause?
Tachycardia
131
What effect does stimulation of the B2 adrenoreceptor cause?
Relaxation (in the bronchi)
132
What is a clinical use of B2 selective agonists?
Treat asthma
133
What do all beta adrenoreceptors couple with?
Gas
134
What is the consequence of Beta adrenoreceptors & Gas coupling?
Increase cAMP levels
135
What chemical mediators can increase heart rate?
Noradrenaline & adrenaline
136
What neurons are noradrenaline released from?
Sympathetic neurons
137
What cells release adrenaline (epinephrine)?
Chromaffin cells
138
What are the receptor locations (2 types) involved in the increase in heart rate?
- Nodal tissue
- Ventricular myocytes
139
What is the receptor type involved in an increase in heart rate?
- B1 adrenergic receptors coupled to Gas G proteins.
140
How do B1 receptors increase heart rate?
Exert a stimulant action which increases force of contraction. This leads to increased cardiac output.
141
The effect of increased heart rate by activation of the B1 adrenoreceptor is regulated by what substance?
Calcium channel activity
142
How does B1 adrenoreceptor cause an increase in calcium?
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
How does the activation of PKA lead to the phosphorylation of calcium channels?
Increased activated PKA = increased voltage-gated calcium channel open time = more calcium into myocytes = increased contraction.
144
What is the chemical mediator that causes relaxation of smooth muscle in the bronchioles, as a result of activation of the B2 adrenoreceptor?
Adrenaline (released from Chromaffin)
145
What is the receptor location for the B2 adrenoreceptor that causes muscle relaxation?
Bronchioles (in the lungs)
146
What type of receptor type is used, when activated, to cause relaxation in smooth muscle located in the bronchioles?
B2 adrenoreceptor (adrenergic receptor), which is coupled to Gas G proteins
147
What is the effect of agonist stimulation on the B2 adrenoreceptor?
Phosphorylation of smooth muscle machinery = relaxation of smooth muscle = bronchodilation
148
What are the clinical uses of the adrenoreceptor agonist - Adrenaline?
Cardiac arrest - adrenaline
Anaphylaxis - adrenaline
149
What are the clinical uses of the adrenoreceptor B2?
Bronchodilator (Salbutamol) - B2 selective
150
What are clinical uses for adrenoceptors antagonists?
- Treating hypertension
- Heart failure
- Anxiety (somatic symptoms)
151
What are 2 unwanted effects of adrenoreceptors agonists?
- Bronchoconstriction - beta blockers are avoided in asthma patients.
- Cardiac depression - especially in the elderly
