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Week 2 Flashcards

1
Q

What is pharmacology

A

The study of the mechanism of drug action

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2
Q

What is a drug

A

The active ingredient of a medicine
Any substance which interacts with a biological system and changes it

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3
Q

Which drugs produce their effects not by binding to a receptor but due to their physicochemical properties

A

Antacids
Laxatives
Heavy metal antidotes
Osmotic diuretics
General anaesthetics
Alcohol
Effects are rather non-specific tend to need rather high concentrations

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4
Q

Characteristics of drugs

A

Occur at very low concentrations -high potency
Biological specificity (receptor wise)- molecule and receptor are same however receptors located on different tissues have different effects
Chemical specificity (drug wise)
Stereo selectivity - competition, certain isomer is the active form

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5
Q

How are drugs classified

A

Chemical nature or drug
Symptoms or disease in which they’re used
Organ system affected
Receptor
Duration of action
Generations
Route of administration

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6
Q

What is the receptor concept

A

drugs produce their effects by combining with specific receptor sites in cells
The response is a function of the number of occupied receptors

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7
Q

What is the lock and key hypothesis

A

the shape of the drug complements the shape of the receptor
Chemical specificity
Affinity - the binding ‘strength’ of the drug receptor interaction or the likelihood of binding

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8
Q

What is a drug receptor pharmacology

A

Anything that causes a physiological effect when interacting with a drug is a receptor

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9
Q

Relationship between drug concentration and response

A

Continuous
Saturating . Plateaus
Exhibits threshold
Emax= maximal response
EC50= concentration of agonist which produces half maximal effects
Threshold= required concentration of agonist needed for an initial response
On graph of response against [agonist] shape is HYPERBOLE
On graph of response against log[agonist] shape is SIGMOID
Assumption 1= “response” is ~ concentration of drug receptor complexes
Assumption 2=fixed number of receptors

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10
Q

What’s the difference between EC50 and Kd

A

EC50 is the model-free equivalent of a Kd value
Kd is not the same as EC50, as the point where half receptors are full does not always coincide with point where drugs affect is at 50%

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11
Q

What’s an agonist

A

It binds to a receptor and produce a response
Possess affinity (binding strength) and efficacy (causes effect)

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12
Q

What’s an antagonist

A

Binds to receptors but doesn’t produce a response
Prevent agonist binding and so prevent the response to an agonist
Possess affinity but not efficacy

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13
Q

What is potency

A

A measure of drug activity- a highly potent drug is only required in a very small dose. Hence potency is related to affinity

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14
Q

What is comparative endocrinology

A

Actions of hormones similar throughout evolution
Controlling molecules

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15
Q

What is clinical endocrinology

A

Action of hormones as related to pathology
Controlling molecules

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16
Q

What is the endocrine system

A

A system of ductless glands and cells that secrete hormones
Regulates metabolism, homeostasis and reproduction

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17
Q

What do the endocrine glands do

A

Release secretions into blood directly from cells- ductless glands

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18
Q

What do Exocrine glands do

A

Not part of endocrine system release their secretions outside the body and may be ducted e.g. gut secretions, sweat glands

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19
Q

Mixed glands

A

E.g. pancreas produces digestive juice and insulin, glucagon and somatostatin (growth hormone inhibiting hormone)

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20
Q

Differences between nervous and endocrine system

A

Endocrine has many hormones rather than few neurotransmitters
Endocrine is slower and more long lasting as nervous is generally short lived
Endocrine effect is widespread in blood whereas nervous is localised cell to cell

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21
Q

What is an intracrine signal

A

Generated by a chemical acting within the same cell

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22
Q

What is negative feedback

A

Process by which body senses change and activates mechanism to reduce it
the final product of an endocrine cascade acts to inhibit the release of hormones higher up the cascade

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23
Q

What take the 3 main groups of hormones

A

Protein/peptide
Steroid
Amine

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24
Q

Protein/peptide hormones

A

Made of chains of amino acids
Typically charged
Hydrophilic
Transported in blood without carrier
Preformed and stored in membrane bound vesicles ready for release by exocytosis because hydrophilic they can’t diffuse out

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25
Steroid hormones
Act by binding to nuclear receptors All made from cholesterol (lipid) so hydrophobic can’t travel in blood alone need carriers Cholesterol to pregnenolone converted to all other steroid hormones by different enzymes Not stored synthesised as required then diffuse out of cell Receptors typically in cell primary messengers
26
Amines/thyroid hormones
Tyrosine is an amino acid tyrosine derivatives bound together T4 contain 4 iodine atoms T3 contain 3 iodine atoms Small non polar molecules therefore hydrophobic Soluble in plasma membrane
27
The hypothalamus
Regulated by hormone-mediated signals and neural inputs The final common pathway by which signals from multiple systems reach anterior pituitary Involved in non-endocrine functions e.g. regulation of body temp, thirst, food intake Sends signals to other parts of nervous system
28
The pituitary gland
Pea sized Sits in bony cavity at base of brain Consist of two lobes Connected to hypothalamus by stalk Hypothalamus produces hormones directly affecting activity of pituitary
29
Hypothalamus-anterior pituitary hormones
GHRH —- GH Somatostatin inhibits GH GnRH (gonadotropin releasing hormone)——FSH (follicle stimulating hormone) LH (luteinising hormone ) CRH (Corticotropin releasing hormone) —— ACTH (adrenocorticotrophic hormone) Thyrotropin releasing hormone (TRH) —— thyroid stimulating hormone (TSH) Dopamine (inhibits) —— prolactin
30
Growth hormone GH
Released throughout life Stimulated by hypoglycaemia (low blood sugar) Suppressed by hyperglycaemia (high blood sugar) Effects mediated by IGF-I Linear growth in children Acquisition of bone mass Stimulates- protein synthesis, lipolysis (fat breakdown), glucose metabolism Regulation of body composition Psychological well being
31
Prolactin
Essential for lactation Levels increase dramatically in pregnancy and during breast feeding Inhibits gonadal activity through central suppression of GnRH (causing decreased LH/FSH) mainly causes disease when present in excess
32
What’s the function of ACTH
Main function is to regulate the glucocorticoid hormone cortisol
33
Function of cortisol
Regulates glucose levels Increases fat in the body Helps to defend the body against infection Helps the body respond to stress
34
What does ADH do
Polypeptide Synthesised in supraoptic and paraventricular nuclei of hypothalamus Secretory granules migrate down the axons of the supraopticohypophyseal tract into the posterior lobe Causes the kidneys to release less water decreasing the amount of urine produced
35
Oxytocin
Stimulates contraction of smooth muscle of breast and uterus Under positive feedback Roles in milk ejection reflex, parturition (birth)- synthetic oxytocin can be given to induce labour
36
Major causes of hypopituitarism
Pituitary/ parapituitary tumours Radiotherapy Pituitary infarction (apoplexy), sheehans syndrome Infiltration of the pituitary Trauma Isolated hypothalamic releasing hormone deficiency
37
GH deficiency
Children- poor growth Adults- increased abdominal fat, decreased lean body mass, impaired lipid profile, decreased muscle strength and exercise capacity, impaired cardiac function, decreased bone mineral density, impaired psychological well being
38
FSH/LH deficiency
Children-delayed puberty Men- decreased libido, impotence, infertility, decreased secondary sex. Decreased muscle mass and strength, mood and well being, osteoporosis, anaemia Women- decreased libido, menstrual disorders, infertility, dyspareunia, osteoporosis, premature atherosclerosis
39
ACTH deficiency
Manifestations- Fatigue, weakness, nausea/vomiting, anorexia, weight loss, hypoglycaemia, hypotension, anaemia
40
TSH deficiency
Manifestations- fatigue, weakness, cold intolerance, bradycardia, inability to lose weight, puffiness, pale and dry skin, constipation Diagnosis- TSH, fT4 and fT3 Treatment- hormone replacement
41
What is central diabetes insipidus
Deficient secretion of ADH Causes- idiopathic, familial, tumours, neurosurgery or trauma, infiltration disorders, infections, hypoxic encephalopathy or severe ischaemia
42
ADH deficiency
Manifestations- polyuria, polydipsia, nocturia Causes of polyuria- DM, renal failure, primary polydipsia, diabetes insipidus
43
What is insulin-like Growth factor 1 IGF-1
Hormone that manages the effects of growth hormone in your body Together IGF-1 and GH promote normal growth of bones of bones and tissues
44
What hormone increases prolactin secretion
Thyrotropin-releasing hormone (TRH) stimulates prolactin release
45
What hormone restrains release of prolactin
Dopamine inhibits prolactin secretion
46
Hormones secreted by the hypothalamus
GH Vasopressin (ADH) Adrenocorticotrophic hormone ACTH Oxytocin GH releasing hormone GHRH Gonadotropin releasing hormone GnRH Corticotropin releasing hormone CRH Thyrotropin releasing hormone TRH Follicle stimulating hormone FSH Thyroid stimulating hormone TSH Dopamine LH, somatostatin, insulin-like growth factor 1 IGF-1
47
What is somatostatin
Growth hormone inhibiting hormone Produces predominantly neuroendocrine inhibitory effects across multiple systems Known to inhibit GI, endocrine, exocrine, pancreatic and pituitary secretions
48
What are physicochemical properties
Intrinsic physical and chemical characteristics of a substance Include appearance, boiling point, density , volatility, water solubility and flammability Molecular weight, size, partition coefficient, acid dissociation constant and solubility have an impact on pharmacokinetics
49
What type of drug is sodium bicarbonate
Antacid- neutralises stomach acid Acid reflux Heartburn Indigestion
50
Examples of laxative drugs
Methylcellulose (bulk)- increases amount of water in your stools to help make them softer and easier to pass Magnesium sulfate (osmotic)- cause water to be retained in the intestinal lumen making stool easier to pass
51
Heavy metal antidotes example
EDTA (chelator) Remove heavy metals such as mercury and lead from blood to stop metal poisoning Metal poisoning
52
Example of osmotic diuretics
Mannitol- given by IV, used to decrease pressure in eyes, as in glaucoma, and to lower intracranial pressure Filtered in kidneys into the urine drawing water with it causing increased urine production
53
Example of general anaesthetic
Halothane
54
Affinity
The strength of the drug receptor interaction a potent drug has high affinity
55
Efficacy
Refers to ability of a drug-receptor complex to produce a maximum functional response
56
What is a receptor for a hormone endocrinology
A bio molecule they have to bind to exert their biological function
57
What is quantitative pharmacology
Based on assumption that drugs act by entering into a simple chemical reaction with certain receptors in cells -simple relation between the amount of drug bound to these receptors and action produced/ size of response
58
What is Kd
Dissociation constant Concentration of ligand which half the ligand binding sites on protein are occupied
59
The Langmuir isotherm
A+R<-> AR Kd= [A]. [R]/[AR] Rt=total conc receptors [Rt]= [R] +[AR] NB: p is the proportion of receptors with agonist bound P=[AR]/[Rt] P=[A]/Kd+[A] Units Kd=mol/litre or M With the Kd of the drug you can calculate the drugs action quantitatively, Kd only if real binding is according to model if not EC50
60
What are endogenous agonist
A compound naturally produced by the body which binds and activates receptor E.g. acetylcholine, histamine and TNF
61
Exogenous agonist
A synthesised drug which binds to a receptor and elicits a response External factors that bind to various receptors and induce biological a response For example: synthetic dopamine which binds to dopamine receptor and elicits a response analogous to endogenous dopamine signalling
62
What is meant by recombinant
A cell or organism whose genetic material is produced from segments of DNA from different sources joined together-recombinant DNA
63
What is meant by transgenic
Genes transferred from one species to another
64
Types of antagonists
Competitive Irreversible/ reversible Examples: Atropine -competitive antagonist of ACh, binds to muscarinic receptor to inhibit parasympathetic NS, reversible Mepyramine (antihistamine) Etanercept- a decoy receptor that binds to TNF agonist (usually antagonist is a ligand but this is a actual receptor which causes TNF agonist to bind to it and no response occurs)
65
What are beta blockers/ beta-adrenoceptor blocking agents)
Class of drugs that prevent stimulation of the adrenergic receptors responsible for increased cardiac action, used to control heart rhythm, treat angina, reduce high blood pressure
66
What’s the difference between an inverse agonist and an antagonist
An antagonist binds to receptors preventing agonists from binding and inducing their response An inverse agonist is a drug that binds to the same receptor as an agonist but induces a pharmacological response opposite to that of agonist A neutral antagonist has no activity in the absence of an agonist or inverse agonist but can block activity of either Both reduce activity of the receptor
67
Example of an inverse agonist
Benzodiazepines at GABA receptors
68
State which type of tissue the anterior pituitary is derived from and describe how the posterior pituitary differs from the anterior What factors are responsible for regulating anterior pituitary hormone production and release
Anterior pituitary is made up of glandular tissue. Rathke’s pouch, ectoderm Posterior pituitary differs in its neuronal origin: derived from the hypothalamus, not glandular but nervous tissue, its largely a collection of axonal projections from hypothalamus. and no hormones are actually made in posterior pituitary Anterior pituitary hormone production and release is controlled by hypothalamic releasing and inhibiting factors and negative feedback from peripheral hormones
69
Patch clamp technique
Used to measure responses generated at receptors Use a glass pipettes filled with fluid with an electrode in and suck up part of cell, usually one receptor Then apply electrode to rest of cell generate electric circuit which you can record electric current Measure electric current, response is now quantifiable current The binding of an agonist opens the channel Peaks show that channels open Partial agonists are less good because they decrease frequency of channel opening

CEP (10 decks)

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