Learn the science of therapeutics: Pharmacology

At the end of this lecture, you will:

• Understand the pharmacodynamic response and signal transduction pathway

• Identify different receptor types (G-protein, Ligand-gated, Enzyme-linked, and Intracellular) and give examples for each

• Understand intrinsic activity at receptors

  • Define and distinguish full, partial, and inverse agonists

  • Define and distinguish competitive and non-competitive antagonists

  • Draw and identify different types of agonists and antagonists using dose-response curves

• Understand potency (EC50) and efficacy (Emax)

  • Compare potency and efficacy of drugs using dose-response curves

• Describe and explain amplification and spare receptors

At the end of this lecture, you will:

• Understand and describe different ways drugs can be absorbed

• Understand the different factors affecting the rate of drug absorption:

  • Lipophilicity

  • Surface area

  • Blood flow

  • Membrane permeability

  • pH

• Describe bioavailability and how it affects patient dosing and therapeutic outcomes

At the end of this lecture, you will:

• Understand how drugs distribute between different compartments in the body to achieve equilibrium

• Describe and understand the factors affecting the rate of drug distribution:

  • Lipophilicity

  • Blood flow

  • Capillary permeability

  • Protein binding

• Define and describe the volume of distribution and understand why it is used for dose estimation

• Explain the relationship between protein binding and volume of distribution

At the end of this lecture, you will:

• understand the two main mechanisms by which a drug is metabolised to inactive metabolites:

  • hepatic metabolism

  • enzymatic metabolism

• describe and explain hepatic first-pass metabolism and its effects on drug bioavailability

• distinguish between phase 1 and phase 2 hepatic metabolic reactions and list examples for each type

• understand the mechanism by which metabolism can produce active metabolites using the concept of prodrugs

  • describe a prodrug and its relevance using examples (Aspirin)

At the end of this lecture, you will:

• Understand and describe two modes of excretion:

  • Renal excretion

  • Hepatobiliary excretion

• Describe and calculate renal clearance

• Describe and explain the different types of drug excretion kinetics:

  • first-order kinetics

  • zero-order kinetics

• Distinguish between first- and zero-order kinetics using graphs

• Describe the relationship between the two types of kinetics and half-life

• Explain why, in zero-order kinetics, excretion is independent of the plasma drug concentration using:

  • concept of enzyme saturation

At the end of this lecture, you will:

• Understand the different branches of the Nervous System

  • Central Nervous System

  • Peripheral nervous system

• Distinguish between the two neuronal divisions of the peripheral nervous system:

  • Afferent Neurons

  • Efferent Neurons

• Compare and contrast between somatic and autonomic nervous system and their respective roles and responses that they govern in the body

• Describe the two divisions of the autonomic nervous system:

  • sympathetic nervous system

  • parasympathetic nervous system

• Compare and contrast the characteristics of sympathetic and parasympathetic nervous system in terms of the type of neurons and neurotransmitters involved

• Compare and contrast the effects of each neurotransmitter at the effector organs between the sympathetic and parasympathetic nervous system 

• Distinguish between cholinergic and adrenergic neurotransmission and the resultant effects on the body with each

At the end of this lecture, you will:

• Understand and describe the six steps in cholinergic neurotransmission:

  1. Synthesis of acetylcholine (Ach)

  2. Storage of Ach in vesicle and why

  3. Release of Ach from neuron

  4. Binding to muscarinic and nicotinic receptors and autoreceptors

     1. Discuss the location of these receptors in the body

     2. Explain the purpose of autoreceptors and their regulation of neurotransmitters in neurons

  5. Breakdown of Ach by Acetylcholinesterase (AchE)

  6. Recycling of choline into Ach

• Understand the link between parasympathetic activation and cholinergic neurotransmission

• Compare and contrast the mechanism of action of direct versus indirect cholinergic agonists

• List the direct and indirect cholinergic agonists and explain their therapeutic/clinical uses and side effects

• Describe the difference between reversible and irreversible AchE inhibitors (indirect agonists) and their effects

• Explain organophosphate poisoning and the mechanism of action of the antidotes used:

  • Pralidoxime (2-PAM)

  • Atropine

At the end of this lecture, you will:

• List antimuscarinic (muscarinic receptor antagonists) agents and explain their clinical or therapeutic uses and side effects associated with each pharmacological agent:

  • Describe and explain the utility of atropine as an antidote for organophosphate poising based on its mechanism of action

• Understand the differences between nicotinic neuronal and nicotinic muscular receptors

  • List nicotinic receptor antagonists, specifically neuromuscular blockers, and explain their clinical or therapeutic uses and side effects

    • Describe and differentiate between depolarising and non-depolarising neuromuscular blockers based on their respective mechanisms of action at the neuromuscular junction

    • Select the most appropriate neuromuscular blocker agent for a procedure based on the onset time and duration of action

• Describe the mechanism of action of ganglionic blockers and understand why they have no therapeutic use

At the end of this lecture, you will:

• • Understand and describe the six steps in adrenergic neurotransmission:

    1. Synthesis of norepinephrine (NE) (same as noradrenaline)

    2. Conversion of Dopamine to NE and the storage of NE in vesicles and why

    3. Release of NE from neuron

    4. Binding to adrenergic receptors and autoreceptors

       1. Identify the different adrenergic receptor subtypes

       2. Discuss the location of adrenoreceptors on various organs in the body and their role

       3. Explain the purpose of autoreceptors and their regulation of neurotransmitters in neurons

    5. Breakdown of NE by Catechol-O-Methyl Transferase (COMT) and monoamine oxidase inhibitor (MAO) enzymes

    6. Reuptake of NE into the neuron via the norepinephrine reuptake transporter (NET)

  • Understand the link between sympathetic activation and adrenergic neurotransmission

  • Compare and contrast the properties of catecholamines versus non-catecholamines based on their chemical structure

    • List direct-acting catecholamines and non-catecholamines (endogenous and synthetic)

    • List indirect-acting non-catecholamines

  • Explain the mechanism of action of direct adrenergic agonists:

    • Catecholamines and non-catecholamines

    • Understand the concept of receptor affinity and how that affects the selectivity of direct-acting agonists

      • Distinguish between non-selective and selective direct-acting agonists

        • Explain the therapeutic/clinical use of non-selective and selective direct-acting adrenergic agonists and their respective side effects

          • Explain the advantages of using selective agents over non-selective agents

At the end of this lecture, you will:

• Describe the mechanism of action of indirect agonists in relation to:

  • Blocking NE reuptake transporter

  • Blocking monoamine oxidase (MAO)

  • Stimulating the release of catecholamines from storage vesicles

• Understand why indirect adrenergic agonists are CNS stimulants

• Describe the therapeutic use of specific indirect agonists and associated side effects

  • Amphetamines use for ADHD

• List indirect agonists that are no longer used clinically and explain why

• Discuss tyramine and its significance in a clinical context

• Describe the mechanisms of action and side effects of mixed agonists

  • Explain their therapeutic use based on the mechanism

• Distinguish between CNS stimulant and opioid overdose using a key characteristic

At the end of this lecture, you will:

• Describe the mechanism of action of adrenergic antagonist

• Categorise antagonists according to their receptor affinity (selectivity):

  • Non-selective

  • Alpha-selective (alpha-blockers)

  • Beta-selective (beta blockers)

    • Explain why beta blockers are cardioselective based on receptor affinity

• Explain the therapeutic use for each category of antagonists and side effects related to the receptor selectivity

• Discuss and explain why propranolol is contraindicated in diabetics and asthmatics