Class Test 1 Flashcards by Emma Strang

How do you calculate Kd?

[H] x [R] / [HR]

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In what ways can drugs be classified by the components involved?

Receptors
Ion channels
Carrier molecule
Enzymes

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What are cells, tissues and organs controlled by?

Nervous system
Humoral agents
Local factors

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In what ways can a drug be classified?

By nature
By action
Which cell components are involved
Which of the body systems does the drug affect
How does the drug help in the disease state

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What is strength of signal replayed by the receptor dependent on?

Concentration of hormone-receptor complex

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Where can other drugs block signal transduction?

Inside the membrane

Intracellular signal reception points

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Common features of receptors?

Saturable

Activated by binding of an endogenous ligand

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What does the fraction of total membrane receptors occupied by Ligands determine?

Size of transmembrane signal transduction

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What is affinity of a drug?

Ability of a drug to bind to a receptor

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What do drugs participate in?

Intracellular communication via chemical signals

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What happens upon recognition of an appropriate chemical signalling molecule (ligand)?

Receptor proteins transmit the signal into a biochemical change in the target cell

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What are the important steps of hormone initiated signal transduction?

Biosynthesis of hormone
Storage and secretion of hormone
Transport of hormone to target cell
Recognition by the hormone receptor protein
Relay and amplification of the signal that leads to defined biochemical reactions within the target cell
Removal of hormone

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What properties do receptors have

Recognition

Transduction

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What does the signalling cascade allow?

Signal to be amplified to produce multiple responses

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Examples of responses produced by signal transduction?

Modulation of gene translation
Hormone secretion 
Energy production 
Cell division 
Cell motion

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Examples of intracellular second messenger signalling molecules

Cyclic nucleotides (cAMP, cGMP)
Calcium ions
IP3 and DAG

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What do second messengers regulate?

Function of specific cellular effectors

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Other examples of ligand-gated ion channels

GABA A receptor
Iontropic glutamate receptor
5-HT3 receptor

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What type of receptors are on ligand gated ion channels

Multimeric transmembrane receptors

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What does gaba a receptors do and used for?

Opens Cl- channel

Used as tranquillisers and anticonvulsant

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What’s the composition of GPCRs?

2 highly conserved cysteine residues in extracellular loops that form an intramolecular disulphide bond to stabilise the receptor structure

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What are the physiological roles of GPCRs

Sensation 
Immune system and inflammation 
Metabolism 
Behaviour 
Autonomic nervous system

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What do nuclear receptors affect

Gene transcription

Directly bind to DNA

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What kind of responses are consequence of this increase in membrane permeability?

Postsynaptic excitatory or inhibitory responses

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What is a second messenger?

Intracellular substance that mediates cell activity by relaying a signal from an extracellular molecule

Types of responses GPCRs allow?

Amplification | Diversity

What is efficacy?

Effect of a drug | More effect more efficacious the drug

What is potency?

Refers to the concentration of the drug | Less concentration required more potent the drug

What are nuclear receptors

Ligand activated transcription factors

What do GPCRs do?

Activate signal transduction inside the cell | E.g. cAMP

What does tyrosine receptor kinases do?

Act as an enzyme | Activated by hormones and growth factors

What is the structure and function of RTKs?

For cell growth differentiation Contain tyrosine (intracellular) Carry out messages through signal transduction

What is a kinase?

Something that has the ability to transfer phosphorus molecules, usually from a high energy substance like ATP

What are the types of heterotrimeric G-proteins

Gi- activated Cyclase to increase cAMP Gs- inhibits adenylate cyclase to decrease cAMP Gq- activates phospholipase C to produce IP3 and DAG

What do beta- adrenoceptors do?

Activate adenylate Cyclades

What are the effects of increased cAMP?

Heart (beta 1)- increased heart rate | Lungs- relaxes bronchial smooth muscle

Effects of agonists in the lung?

Dilates bronchial smooth muscle | Eases respiration

Effects of antagonists in the heart

Slows heart rate and reduces force of beat

What activates alpha alpha1-adrenoceptor?

Epinephrine | Expressed in smooth muscle

How does alpha-adrenoceptor increase intracellular Ca2+ concentration?

Release from SR (IP3) Through membrane channels (DAG) Ca2+ stimulates smooth muscle contraction

What is hypertension

High blood pressure

What is hypotension

Low blood pressure

What other cell responses are regulated by Gq inositol-phospholipid signalling

Liver- vasopressin- glycogen breakdown Pancreas- acetylcholine- amylase secretion Smooth muscle- acetylcholine- contraction Blood platelets- thrombin- aggregation

What is dimerisation?

Coupling by an agonist binding to 2 receptors

Examples of drugs that inhibit RTK signalling

Imatinib (Gleevec)- for leukaemia Lapatinib (Tykerb)- EGF receptor inhibitor for breast cancer Trastuzumab- antibody against EGF for breast cancer

What is thioureylene?

Converts T4 to T3

What do thyroid hormones promote the synthesis of?

Adrenoceptors

What is hypothyroidism for Hashimoto's thyroidtis?

Lack of hormone | Treated by giving T4

What does TSH act on?

Receptors on the membrane of the thyroid follicle cells through the mechanism that involves cAMP

What do thyroid hormones do?

Increase basal metabolic rate Increase heat production Increase glucose uptake

How can hyperthyroidism be treated

With beta adrenoceptors antagonists

Zones of adrenal cortex

Glomerulosa- aldosterone | Fasiculata and reticularis- adrenal androgens and cortisol

Adrenal medulla secretes

Catecholamines E.g. Epinephrine and norepinephrine Adrenaline in response to sympathetic nervous system

What are adrenocortical hormones?

Steroid hormones

What does failure of adrenal medulla cause? | What does tumour of adrenal medulla cause?

Failure- hypotension Tumour- hypertension E.g. Phrenocheomocytoma, neuroblastoma

What are glucocorticoids

``` Cortisol Actions Metabolic Negative feedback on AP and H Anti inflammatory and immunosuppressive effects ```

What are mineralcorticoids

Aldosterone

What are sex hormones

Testosterone

What are HREs?

Short segments of DNA able to bind a specific hormone receptor complex affecting transcription

What are oestrogen receptor antagonists for?

Prevention and treatment of breast cancer (tamoxifen)

What is the composition of a typical ligand

Lipophillic hormones with steroid hormones and dedicates of vitamin A and D

When is a mineralcorticoid receptor antagonist used?

Liver cirrhosis and heart failure

What are oestrogen receptor agonists used for?

Hormone replacement therapy in postmenopausal women

Adverse effects of glucocorticoids

``` Osteoporosis Cushing's syndrome Metabolic effects Suppression of infection Suppression endogenous glucocorticoid synthesis ```

What is glucocorticoid receptor agonist for?

Inflammation

What are the actions of adrenalin in tissues

Increase cyclic AMP

What do anti-inflammatory and immunosuppressive activity reduce?

Blood vessel dilation and leakage Glucocorticoids inhibit phospholipase A2- blocks production of arachidonic acid, pstoglanduns and leukotrienes from cell membrane phospholipid

What are androgen receptor antagonists used for?

Prostate cancer treatment

How do ADR and Na maintain blood pressure

Iontropic effects on heart and vasoconstrictor | I.e. Increases heart rate and contracts blood vessels

Dose vs concentration?

Dose- amount of drug (micro grams, nanomoles) | Concentration- amount of drug per unit volume (micromolar, nanomolar)

What are drug receptor controls?

Selectivity of drug effect Magnitude of response Mechanisms to prevent/mimic physiological function

What is magnitude of response?

Hyperbolic [AR] = [A] [RT] Kd + [A]

What is EC50?

Concentration required to get half the maximum response

How do allosteric Ligands produce effects

By increasing/decreasing potency | Causing an increase/decrease in efficacy

What is implied by receptors ability to spontaneously adopt an active site

Level of constitutive activity

What is an inverse agonist?

Ligand that binds to the receptor and limits constitutive activity