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Fundamentals of Pharmacology - Coggle Diagram
Fundamentals of Pharmacology
Hypertension
(Increased Blood Pressure)
Regulation of Blood Pressure
Renin-Angiotensin-Aldosterone System (RAAS)
Increased Systemic Vascular Resistance
ACE induced inhibition of bradykinin (vasodilator)
Sympathetic activation of arterial vasculature
Angiotensin ll induced vasoconstriction
Increased Cardiac Output
Stimulation of sympathetic output: increased HR, increased contractility (increases stroke volume), and vasoconstriction (increased preload and therefore stroke volume)
Release of aldosterone and ADH, increasing plasma volume, venous return and stroke volume
Natriuretic Peptide System
(ANP and BNP)
Dilation of veins
Increased glomerular filtration
Dilation of arteries
Decreased renin secretion
Autonomic Nervous System
Parasympathetic Activation
Decreased HR (M2)
Sympathetic Activation
Increased contractility (B1)
Increased HR (B1)
Vasoconstriction (a1)
Increased renin secretion (B1)
Vascular Endothelium
Released vasodilators
Releases vasoconstrictors
Anti-Hypertensives
Inhibit Sympathetic Activity
a1 Antagonists
(vasodilation)
Prazosin
a2 Agonists
(decreases HR and contractility)
Methyldopa
Clonidine
Beta Blockers
(decrease HR and contractility)
Carvedilol
Propranolol
Atenolol (selective)
Direct Vasodilators
Calcium Channel Blockers
(decrease HR and contractility,
vasodilation)
Dihydropyridines
(Vasodilation only)
Lercanidipine
Amlodipine
Nifedipine
Non-Dihydropyridines
Verapamil
Diltiazem
Inhibit RAAS
ACE Inhibitors
(inhibit the production of angiotensin ll
and action of bradykinin)
Ramipril
Perindopril
AT1 Antagonists (ARBs/Sartans)
(inhibit angiotensin ll binding to AT1 receptors)
Candesartan
Olmesartan
Irbesartan
Telmisartan
Diuretics
(inhibit sodium reabsorption)
Potassium Sparing Diuretics (collecting duct)
Spironolactone (aldosterone antagonist)
Loop Diuretics (loop of henle)
Furosemide
Thiazide Diuretics (DCT)
Hydrochlorothiazide
Factors that Alter Blood Pressure
Cardiac Output
Stroke Volume
Contractility
Preload
Venous tone
Intravascular volume
Heart Rate
Systemic Peripheral Resistance
Direct innervation
Circulating regulators
Local regulators
Pharmacokinetics
Pharmacokinetic Process
Distribution
Metabolism
Absorption
Rate
Extent Absorbed / Bioavailability
Route
Excretion
Pharmacokinetic Parameters
Volume of Distribution (Vd)
Clearance (CL)
Bioavailability (F)
First Pass Effect/Metabolism
Secondary Parameters
Primary Parameters
Elimination Half-Life
Molecules and Receptors
Drug Characteristics
Relative Lipid Solubility
Molecular Size and Shape
Degree of Ionization (Polarity)
Drug Reactivity
Physical Nature
Selectivity
Drug Targets
Proteins
Enzymes
Adhesion Molecules
Receptors
GPCRs
Receptors with Linked Enzymatic Domains
Ion Channels
Intracellular Receptors
Nervous System
Cholinergic Drugs
Muscarinic Antagonists
Atropine
Reversible Acetylcholinesterase Inhibitors
Endrophonium
Pyridostigmine
Muscarinic Agonists
Bethanechol
Pilocarpine
Irreversible Acetylcholinesterase Inhibitors
Malathion
Sympathetic Nerve Stimulation
(Noradrenaline binds to adrenergic receptors)
Skeletal Muscle
Increased blood glucose (B2)
Increased contractility (B2)
Fat
Lipolysis (B1, B2, B3)
Liver
Increased blood glucose (B2)
GIT
Decreased GI motility (a1, a2, B2)
Blood Vessels
Arteries
Vasoconstriction (a1, a2)
Skeletal muscle arterioles dilate (B2)
Veins
Vasoconstriction (a1, a2)
Vasodilation (B2)
Kidney
Increased renin secretion (B1)
Lungs
Bronchodilation (B2)
Bladder
Relaxation of detrusor muscle
Constriction of sphincter muscle (a1)
Heart
Increased HR (
B1
, B2)
Increased contractility and conduction (
B1
, B2)
Eye
Radial muscle contracts (a1)
Ciliary muscle relaxes (B2)
Adrenergic Drugs
B1 Agonist
Dobutamine
B2 Agonist
Salbutamol
a2 Agonist
Methyldopa
a1 Antagonist
Prazosin
Tamsulosin
a1 Agonist
Phenylephrine
Oxymetazoline
B Antagonists
Beta Blockers
Propanolol
Atenolol
Inhibitors of Noradrenaline Storage
Pseudoephedrine
Parasympathetic Nerve Stimulation
(Acetylcholine binds to muscarinic receptors)
Blood Vessels
Arteries
Vasodilation in salivary tissue (M3)
GIT
Increased motility and secretion of digestive enzymes (M3)
Lungs
Bronchoconstriction (M3)
Bladder
Contraction of the detrusor muscle (M3)
Heart
Decreased HR (M2)
Decreased contractility (M2)
Eye
Pupil constriction
Sweat Glands
(Sympathetic Nerve Stimulation)
Increased sweating (sympathetic effect)
Asthma
(Narrowing of the Airways caused by Inflammation)
Anti-IGE Antibodies
(inhibits inflammatory mediator release)
Omalizumab
IL-4 and IL-13 Inhibitor
(inhibits eosinophil recruitment, IGE production, TH2 cell differentiation)
Dupilumab
Leukotriene Receptor Antagonists
(useful in AERD/NSAID-induced bronchospasm)
Monteleukast
Anti-IL-5 Therapy
(inhibit eosinophil production)
Mepolizumab (IL-5)
Benralizumab (IL-5 receptor)
Cromolyns/Cromones
(inhibit mast cell degeneration)
Cromoglycate
Inhaled Corticosteroids (ICS)
(decrease the number of inflammatory cells, damage to airways and swelling)
B2 Agonists
(bronchodilation)
Long Acting B2 Agonists
Salmeterol
Formoterol
Short Acting B2 Agonists
Terbutaline
Salbutamol
Xanthine Drugs (Methylxanthines)
(inhibit CAMP to AMP)
Theophylline
Muscarinic Receptor Agonists
Tiotropium
Chronic Obstructive Pulmonary Disease (COPD)
(Emphysema and Bronchitis)
Bronchodilators
Anti-muscarinics (Muscarinic Antagonists)
Short Acting Muscarinic Antagonists (SAMA)
Ipratropium
Long Acting Muscarinic Antagonists (LAMA)
Aclidinium
Glycopyrronium
Tiotropium
Umeclidinium
B2 Agonists
Inhaled Corticosteroids
Heart Failure
(Impaired Left Ventricular Filling or Pumping of Blood)
Heart Failure with Reduced Ejection Fraction (HFrEF)
Digoxin
(sodium/potassium exchange pump inhibitor (promoting less removal of calcium))
Ivabradine (Decreases HR)
Sacubitril and Valsartan
(angiotensin-receptor neprilyisin inhibitor (ANP/BNP))
Heart Failure with Preserved Ejection Fraction (HFpEF)
Dyslipidemia
(Abnormal Lipid Metabolism)
Fibrates
(PPARa activation)
Fenofibrate
Gemfibrozil (avoid use with statins)
Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Inhibitors (inhibits LDL receptor degradation)
Evolucumab
Ezetimibe (inhibit cholesterol absorption)
Bile Acid Binding Resins (Bile Acid Sequestrants)
(inhibits bile acid reabsorption)
Colestyramine
Statins (HMG-CoA Reductase Inhibitors)
(inhibit cholesterol production)
Rosuvastatin
Pravastatin (short half-life)
Atrovastatin (lipophilic)
Nicotinic Acid (Niacin)
(inhibits lipolysis)
Arrhythmias
(Abnormal Electrical Rhythm of the Heart)
Mechanisms of Arrhythmias
Altered Impulse Formation
Decreased Automaticity of the SA Node (B)
(PNS, escape beats)
Enhanced Automaticity
Increased Automaticity of Latent Pacemakers (T)
(ectopic beats)
Abnormal Automaticity (T)
(myocytes initiate impulses)
Increased Automaticity of the SA Node (T)
(SNS)
Triggered Activity (T)
(afterdepolarisations)
Altered Impulse Conduction
Unidirectional Block and Re-entry (T)
(circular stimulation)
Conduction Block (B)
(inexcitable tissue)
Types of Arrhythmias
Ventricular Tachycardia
(re-entry circuits)
Atrial Fibrillation
(erotic contractions, thrombus --> ischaemic stroke)
Ventricular Fibrillation
(erotic contractions, CO=0)
Paroxysmal Supraventricular Tachycardias (PSVT)
(due to exercise, AV nodal re-entry)
Bradycardias
(short-term treatment)
B1 Agonists
Isoprenaline
Anti-Muscarinics
Atropine
Tachycardias
(long-term treatment)
Class lll: Potassium Channel Blockers
(prolongs repolarization, treat re-entry circuits)
Amiodarone (also has class lA, ll and lV activity)
Class lV: Calcium Channel Blockers
(treat supraventricular arrhythmias)
Verapamil
Dilitazem
Class ll: Beta Blockers
(slow automaticity, contractility and conduction)
Metoprolol
Sotalol (prolongs AP)
Digoxin
(treatment of supraventricular tachycardias, reduces HR and conduction, increases contractility, many drug interactions)
Class l: Sodium Channel Blockers
(slow automaticity and conduction)
Lidocaine (rapid)
Flecainide (slow)
Disopyramide (K+ inhibition also)
Haemostasis
Regulation of Haemostasis
Protein C
(inactivates Va and Vlla)
Protein S
(inhibits Va-Xa complex)
Prostacyclin (PGI2)
(inhibits thromboxane A2)
Anithrombin
(inactivates lla, lXa, Xa, Xla, Xlla)
Tissue Factor Pathway Inhibitor
(inhibits the extrinsic pathway)
Phases of Haemostasis
Platelet Phase
(adhere to the SOI, thromboxane A2 released, GP expressed, activates more platelets, fibrinogen binds to GP)
Coagulation Phase
(irreversible fibrin clot, cascade of enzymatic reactions --> fibrin (end product))
Vascular Phase
(vasoconstriction, endothelians)
Fibrinolytic Phase
(plasminogen --> plasmin, fibrinolysis)
Thrombosis
Anti-Platelets
(prevent platelet activation and aggregation)
Adenosine Diphosphate Inhibitors (P2Y12 Antagonists)
Clopidogrel
COX Inhibitors
(inhibit prostaglandin --> thromboxane A2, irreversible)
Aspirin (low dose)
Anti-Coagulants
(prevent the formation of fibrin (fibrin clot inhibition))
Heparins
(binds to antithrombin lll, inactivates lla and Xa)
Heparin
Enoxaparin (low molecular weight heparin)
Direct Thrombin Inhibitors
(inhibit fibrinogen --> fibrin)
Dabigatran (reversible)
Vitamin K Epoxide Reductase Inhibitors
(vitamin K epoxide reductase activates vitamin K, active vitamin K produces ll, Vll, lX, X)
Warfarin (narrow therapeutic window)
Direct Xa Inhibitors (NOAC/DOAC)
(inhibit thrombin production)
Rivaroxaban
Apixaban
Inflammation
(Response to Perceived Harmful Stimuli, "itis")
Acute Inflammation
Cell Migration / Movement of WBCs
(attraction of WBCs to the SOI (chemotaxis), upregulation of adhesion molecules)
Phagocytosis
(recognition and adherence, engulfment, fusion with lysosome, destruction and digestion)
Vascular Changes
(vasodilation, increased permeability)
Repair / Healing
(release of anti-inflammatory mediators, collagen deposited (scar tissue))
Initiation
(release of inflammatory mediators (histamine, cytokines, leukotrienes))
Corticosteroids
(regulate gene transcription, anti-inflammatory and immunosuppressive properties, long-term risks, specific/specialised)
Prednisolone
Methylprednisolone
Fludrocortisone (sodium retaining potency)
Dexamethasone
Pain
Types of Pain
Neuropathic Pain
(pain sensation from nerve damage (primary afferent or CNS))
Nociplastic Pain
(pain sensation from altered nociception with no clear actual or potential tissue damage)
Nociceptive Pain
(pain sensation from actual or potential tissue damage)
Order of Management
Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)
(nociceptive, anti-inflammatory component, more adverse effects than paracetamol)
Opioids
(nociceptive, moderate/severe, significant harms)
Paracetamol
(nociceptive)
Adjuvants
(neuropathic, reduces central sensitisation)
Non-Pharmacological Management
(> analgesics for chronic non-cancer pain)
Analgesics
Opioids (Mu Opioid Receptor Agonists)
analgesic: inhibit neurotransmitter release from primary afferent terminals (inhibits calcium influx) and activate descending inhibitory controls
mu opioid receptors: highly concentrated in the brain, decrease cellular excitability
ADRs: sedation, N/V, constipation, respiratory depression, endocrine effects, osteoporosis
Agonists
Weak
Codeine
(effect depends on conversion to morphine in the liver)
Tramadol
(inhibits re-uptake of noradrenaline and serotonin (toxicity))
Partial Agonist
Buprenorphine
(highly potent, long-acting, opioid addiction treatment)
Strong
Methadone
(lipophilic, CYP450 metabolism, opioid addiction treatment)
Fentanyl
(short-acting, highly potent (lipophilic), patch administration)
Oxycodone
(CYP450 metabolism, combined with naloxone (constipation))
Tapentadol
(inhibits noradrenaline re-uptake)
Morphine
(metabolised in the liver, no CYP450 metabolism)
Peripheral Action
(anti-diarrhoeal)
Diphenoxylate
(decrease bowel motility, used with atropine (discourage misuse))
Loperamide
(decrease bowel motility, used with atropine (discourage misuse))
Antagonists
Long Acting
Naltrexone
(long-acting, maintenance of opioid abstinence)
Peripheral Action
Methylnaltrexone
(does not cross BBB, prevents constipation)
Short Acting
Naloxone
(competitive antagonist, short-acting, used for opioid overdose or opioid sedation reversal)
Adjuvants
secondary analgesic effects: inhibit pain transmission and modulate/reduce central sensitisation
ADRs: sedation, respiratory depression
Gabapentinoids
(inhibit voltage gated calcium channels)
Gabapentin
Pregablin
Antidepressants
(inhibit synaptic noradrenaline and serotonin re-uptake)
Tricyclic Antidepressants (TCAs)
Amitriptyline
Nortriptyline
Serotonin Noradrenaline Re-uptake Inhibitors (SNRIs)
(sedation less common)
Duloxentine
Venlafaxine
Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) (COX Inhibitors)
inhibit the production of eicosanoids (
prostaglandins
, thromboxane, prostacyclin)
prostaglandins: cause inflammation (vasodilation), pain, fever + many more effects
effects: anti-inflammatory (SOI), analgesic (tissues/CNS), antipyretic (hypothalamus)
adverse effects: AERD/bronchospasm, gastropathy, nephrotoxicity, decreased renal function, prolonged bleeding
COX-2 Inhibitors
Celecoxib
Aspirin
Mixed COX-1/COX-2 Inhibitors
(more side effects)
Ibuprofen
Diclofenac
Cannabinoids
Medical Cannabis
(inhibit cannabinoid receptors (CB1 and CB2))
Tetrahydrocannabinol (THC)
("high", partial agonist)
Cannabidiol (CBD)
(antagonist, fewer ADRs)
Paracetamol
(analgesic and antipyretic effects, side effects uncommon)
Insomnia
(Changes to Sleep Pattern)
Sedation Scale
normal --> relief from anxiety (benzodiazepines) --> Sedation (benzodiazepines, z-drugs, antihistamines) --> Hyponosis (benzodiazepines, z-drugs, antihistamines) --> .......... death
Medications
Z-Drugs
MOA: same as benzodiazepines (reduced sedation and tolerance)
bind to alpha-1 subunit on GABA-A receptors
Zolpidem
(can cause parasomnias)
Zopiclone
Sedative Antihistamines
(inverse agonists at histamine type 1 receptors (promote wakefulness))
Diphenhydramine
Doxylamine
Benzodiazepines
potentiate/increase the inhibitory effects of GABA (inhibitory neurotransmitter) --> decreasing neuronal excitability
GABA: membrane hyperpolarization (K+ efflux, Cl- influx)
bind to allosteric site on GABA-A receptors
Temazepam (short-acting)
Diazepam (long-acting)
Oxazepam (short-acting)
other uses of benzodiazepines: Panic Attacks
Alprazolam
Oxazepam
Lorazepam
Melatonin
controls circadian rhythms and sleep regulation
binds to MT1 and MT2 receptors
Arthritis
Osteoarthritis
(degenerative joint disorder)
Paracetamol
(symptom/pain relief)
Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)
(symptom/pain relief)
Gout
(chronic, inflammatory arthritis, too much urate in the blood resulting in the formation of crystals)
Gout Flare Treatment
(treat acute flares, short-term)
Colchicine
(affects immune cell division and movement --> reducing inflammation, can be toxic)
Corticosteroids
Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)
(avoid aspirin (competes with uric acid for excretion))
Gout Flare Prophylaxis
(reduce frequency of flares when starting ULT)
Low Dose NSAIDs
Low Dose Corticosteroids
Low Dose Colchicine
Urate Lowering Therapy
(crystals dissolve, prevents formation of new crystals)
Allopurinol
(xanthine oxidase inhibitor, converted to oxypurinol --> inhibiting the production of urate)
Probenecid
(inhibits renal transporters --> inhibits urate reabsorption (filtrate))
Rheumatoid Arthritis
(chronic, systemic autoimmune disease, targets synovial tissue)
Disease-Modifying Anti-Rheumatoid Drugs (DMARDs)
(disease control, acts on the immune system)
Conventional (Synthetics) DMARDs (csDMARDs)
(immunosuppressants and/or immunomodulators)
Sulfasalazine
(broken down into 5-ASA, inhibits COX enzymes and other inflammatory mediators)
Hydroxychloroquine
(increases pH of lysosomes --> inhibits the function of WBCs)
Methotrexate
(inhibits DHFR --> inhibiting the production of purines/pyrimidines (WBCs))
Leflunomide
(inhibits DHODH --> inhibiting the production of pyrimidines)
Biological DMARDs (bDMARDs)
(pro-inflammatory cytokines: TNFa and IL-1)
Adalimumab
(TNFa antagonists, production of other cytokines also decreases)
Abatacept
(binds to antigen presenting cells --> inhibiting the activation of T cells --> reducing cytokine production)
Glucocorticoids
Prednisolone
Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)
(symptom relief)
Spasticity
(Stiffness or Involuntary Muscle Spasms)
Muscle Relaxants
Baclofen
(GABA-B Receptor Agonist, inhibits neurotransmission at the spinal level and depresses the CNS)
Diazepam
Dantrolene
(interferes with calcium release from the sarcoplasmic reticulum)
Depression
(Lack of Serotonin and Noradrenaline)
Antidepressants
Serotonin and Noradrenaline Reuptake Inhibitors (SNRIs)
(inhibit presynaptic reuptake)
Desvenlafaxine
Duloxetine (neuropathic pain)
Venlafaxine
Tricyclic Antidepressants (TCAs)
(inhibit presynaptic reuptake, block cholinergic, histaminergic, a1 and serotonergic receptors)
Amitriptyline
(larger effects in sedation, anticholinergic and orthostatic hypotension)
Nortriptyline
Selective Serotonin Reuptake Inhibitors (SSRIs)
(inhibit presynaptic reuptake)
Fluoxetine
(increases QT interval)
Fluvoxamine
Escitalopram
(increases QT interval)
Paroxetine (constipation)
Citalopram
(increases QT interval)
Sertraline (diarrhoea)
Mono-Amine Oxidase Inhibitors (MAOIs)
Non-Selective MAOIs
irreversible
MOA-A: DA, NA, 5-HT
MOA-B: DA
ADRs: unable to breakdown tyramine
Phenelzine
Tranylcypromine
Selective MAOIs
reversible
MOA-A: DA, NA, 5-HT
no diet restrictions
Moclobemide
Tetracyclic Antidepressants
Mirtazapine
blocks 5HT2 and 5HT3 --> increasing serotonin neurotransmission
blocks a2 receptors --> increasing NA and 5-HT reuptake
H1 antagonist
Epilepsy
(Potential for Recurrent Seizures)
Antiepileptics
Modification of Ion Conductance
(act on sodium channels --> slow recovery from inactive state)
Carbamazepine
(simple partial, complex partial, generalised tonic-clonic)
Lamotrigine
focal, generalised tonic-clonic
also inhibits glutamate release
Phenytoin
(focal, generalised tonic-clonic)
Increase Inhibitory Transmission (GABAergic)
Benzodiazepines
absence or myoclonic
potentiate effects of GABA binding, inhibit enzymes that degrade GABA, inhibit action potential, increase surround inhibition
Clonazepam
Clobazam
Multiple Mechanisms
Topiramate
focal, generalised tonic-clonic
blocks sodium channels, enhances GABA effects
Levetiracetam
(focal, generalised)
Valproate
absense, tonic-clonic, myoclonic, focal
prolongs sodium channel activation, inhibits calcium channels, enhances GABA effects
Cannabidiol
(antagonise GPCR 55 --> inhibiting calcium release)
Diabetes
(Chronic Hyperglycaemia)
Type 1: auto-immune beta-cell destruction
Type 2: insulin resistance
Secretion of Insulin (Beta Cells)
Membrane hyperpolarised (resting state) --> Glucose enters via GLUT2 transporters --> ATP synthesis --> K+/ATP channel inhibition --> Membrane depolarisation --> Calcium channel activation --> Vesicle fusion with membrane --> Insulin secretion
Insulin Receptor Activation
Insulin binds to receptor --> Signal cascade --> Exocytosis --> GLUT-4 expressed --> Glucose entry
Chronic Complications of Diabetes
Macrovascular
Atherosclerosis
(pro-coagulation effects, build up of plaque)
Microvascular
Nephropathy
(hyperglycaemia --> glomerular hyperfiltration --> glomerular damage --> proteinuria)
Retinopathy
(damage to blood vessels of the retina --> blindness)
Neuropathy
(nerve damage, sensorimotor or autonomic, diabetic foot infection)
Medication
Parentral
GLP-1 Analogues (incretin hormone)
released from the small intestine
enhances insulin secretion
inhibits glucagon secretion
Dulaglutide
Semaglutide
Exenatide
Insulins
(increase glucose uptake, storage and metabolism)
Short-Acting Analogues
Insulin Aspart
Insulin Lispro
Insulin Glulisine
Long-Acting Analogues
Insulin Glargine
Insulin Detemir
Oral
DPP-4 Inhibitors (incretin hormone)
(inhibits the breakdown of GLP-1)
Linagliptin
Sitagliptin
(renal impairment)
SGLT2 Inhibitors (Flozins)
(inhibits glucose reabsorption in the filtrate)
Dapagliflozin
Empagliflozin
Sulfonylureas
(inhibits the K+/ATP channel --> increasing insulin secretion)
Glimepiride
Gliclazide
Thiazolidinediones (Glitazones)
(PPARa agonist, increases sensitivity of tissue to insulin and increased fatty acid storage)
Pioglitazone
Metformin (first choice)
increases sensitivity of insulin to tissues
decreases gluconeogenesis
increases peripheral glucose uptake
ADRs: delayed gastric emptying, decreased appetite
Acarbose
(delays intestinal absorption of carbs)
Glucagon
(increases release of glucose from the liver, decreases GI motility)
Endocrine Pharmacology
(Reproduction, Growth, Lactation, Thyroid Function, Adrenal Function, Water Homeostasis)
Thyroid Imbalances
Hyperthyroidism
causes: grave's disease, thyroiditis, thyroid nodules
primary hyperthyroidism: decreased TSH, increased T3/T4
secondary hyperthyroidism: increased TSH and T3/T4
Thyroid Synthesis Inhibitors
(oral, decrease TH levels)
Carbimazole (longer half-life)
Propylthiouracil
Thyroidectomy
(surgery, decrease TH levels)
Hypothyroidism
causes: hashimoto's thyroidectomy
primary hypothyroidism: increased TSH, decreased T3/T4
secondary hypothyroidism: decreased TSH and T3/T4
Liothyronine (T3, absorbed form)
(increase TH levels, rapid onset, short duration, severe cases)
Levothyroxine (T4, metabolised to T3)
(increase TH levels, long half-life, long duration, drug of choice for PH and SH)
Common Problems and Conditions of the Adrenal Gland
Adrenal Crisis
(adrenal insufficiency accompanied by severe stress, medical emergency)
Injectable Hydrocortisone
Cushing's Disease
(pituitary gland tumour --> overproduction of cortisol)
Caberogoline
(block the release of ACTH)
Mifepristone
(block the effect of cortisol on the body)
Ketoconazole
(block the release of cortisol)
Adrenal Insufficiency
insufficient cortisol and aldosterone production
primary insufficiency (addison's disease): autoimmune destruction of the cortex
secondary insufficiency: insufficient ACTH production
Glucocorticoids
Hydrocortisone (endocrine)
Prednisolone
Cortisone
Mineralocorticoids
Fludrocortisone
(treatment of PI e.g. low aldosterone levels, fluid retaining properties)
Infectious Disease
Viruses (unicellular, not living)
usually dormant (not contagious), activated when it hijacks a host cell
virus life cycle: attachment --> penetration --> uncoating --> biosynthesis --> assemble --> release
Antivirals
Inhibits Replication (biosynthesis)
Nucleoside Inhibitor
(binds to DNA --> resulting in chain termination)
Acyclovir
(ADRs: nausea, headache)
Inhibits Assembly (assembly)
Protease Inhibitor
(degrades the enzyme protease --> inhibiting the packaging and assembling of virions)
Fosamprenavir
(ADRs: liver toxicity)
Inhibits Integration (uncoating)
Integrase Inhibitor
(binds to the viral genome --> inhibiting integration into human DNA)
Raltegravir
(ADRs: liver toxicity)
Inhibits Release (release)
Neuraminidase Inhibitor
(degrades neuraminidase --> inhibiting the release of the virus)
Oseltamivir
(ADRs: nausea, headache)
Inhibits Fusion/Entry (attachment)
Entry Inhibitor
(binds to the receptor (cell membrane) --> inhibiting virus from binding)
Maraviroc
(ADRs: neutropenia)
Fusion Inhibitor
(binds to spikes (virus) --> inhibiting spikes binding to receptors (cell membrane))
Enfuvirtide
Fungi (multicellular, living)
(mould, mushroom, dermatophytes (require keratin to grow (skin, nails)), yeasts (skin, mucous membrane))
Antifungals
Cell Membrane Synthesis Inhibitors
(inhibit the cell membrane synthesis pathway (squalene --> lanosterol --> ergosterol), favourable)
14a-Demthyase Inhibitors
(inhibit the conversion of lanosterol to ergosterol)
Imidazole
Clotrimazole
Triazole (more potent)
Fluconazole
Squalene Epoxidase Inhibitors
(inhibit the conversion of squalene to lanosterol)
Allylamines
Terbinafine
Microtubule Inhibitor
Cell Wall Synthesis Inhibitors
DNA/RNA Synthesis Inhibitor
Bacteria (unicellular, living)
gram negative: no cell wall, two membranes, lipopolysaccharide
gram positive: cell wall (peptidoglycan), one membrane
Antibiotics / Antimicrobials
Cell Wall Synthesis Inhibitors (gram-positive)
(inhibits peptidoglycan synthesis --> cell death/lysis, favourable)
B-Lactams
Penicillins
Amoxycillin
Glucopeptide
Vancomycin
Cell Membrane Synthesis Inhibitors
(inhibits lipopolysaccharide and phospholipid bilayer synthesis --> cell death/lysis, unfavourable)
Polymyxins
Colistin
Lipopeptides
Daptomycin
Protein Synthesis Inhibitors
(inhibit ribosome function --> cell death/lysis, favourable)
Targeting 50S Subunit
Macrolides
(ADRs: CYP 3A4 inhibition)
Roxithromycin
Targeting 30S Subunit
(bacteriostatic)
Tetracyclins
(ADRs: absorption)
Doxycycline
Aminoglycoside
(gram-negative)
Gentamicin
Metabolite Synthesis Inhibitor
(inhibits the production of thymidylate --> inhibiting metabolism and the production of DNA/RNA)
Sulfamethoxazole
(dihydropteroate synthase inhibitor)
Trimethoprim
(dihydrofolate reductase inhibitor)
DNA/RNA Synthesis Inhibitor
(inhibits the production of DNA/RNA)
Ciprofloxacin
(DNA gyros or topoisomerase inhibitor)
Osteoporosis
(Compromise of Spongy/Trabecular Bone, Loss of BMD)
Hormonal Replacement Therapy (HRT)
(reduces osteoclast activity, menopause)
Oestrogen
Tibolone
Selective Estrogen Receptor Modulator (SERM)
(SER agonist at bone and on lipids (reduces osteoclast activity))
Raloxifene
Bisphosponates
binds to calcium in the bone
inhibits osteoclast binding/activity (reduces resorption)
inhibits osteoblast apoptosis (increases BMD not quality)
side effect: osteonecrosis
Alendronate
Risedronate
Monoclonal Antibody / RANK Ligand Inhibitor
inhibits osteoclast synthesis/production
RANK-L: differentiation and activation of osteoclasts
most significant BMD elevator
Denosumab
Calcium and Vitamin D Supplementation
Calcium
(increases blood calcium levels --> increasing mineralisation into bone)
Vitamin D
(maintains blood calcium levels: increases absorption from the GIT, decreases excretion within the kidneys and increases mineralisation into bone)
Anti-Sclerostin Antibody
inhibits the synthesis on sclerostin --> promoting bone formation
sclerostin: inhibits osteoblast activity
Romosozumab
Drug-Induced Osteoporosis
Thyroid Hormones
increase osteoblast and osteoclast activity (net decrease in BMD)
Anti-Epileptics
inactive vitamin D
Glucocorticoids
decrease bone formation
increase bone resorption
Proton Pump Inhibitors
decrease calcium absorption
increase bone resorption
Schizophrenia
(Recurrent Episodes of Psychosis, Imbalance of Neurotransmitters (Dopamine) in the Brain)
Antipsychotics
(decrease positive symptoms)
Atypical (2nd Generation)
Low Affinity Dopamine 2 Receptor Antagonists
(also useful for negative symptoms (agonists at 5-HT1a))
Clozapine
binds to D1-5, 5-HT, M2/M3, a1 and H1 receptors
ADRs: decreased neutrophil production
Adverse Effects of D2 Blockage
Increased prolactin secretion (hypothalamus)
Hyperprolactinemia (hypothalamus)
Tardive Dyskinesia (basal ganglia)
Neuroleptic Malignant Syndrome
Extrapyramidal effects (basal ganglia)
Typical (1st Generation)
High Affinity Dopamine 2 Receptor Antagonists
(greater risk of extrapyramidal side effects)
Bipolar Disorder
(Mood Dysregulation Disorder (Mania/Depression))
Bipolar l: at least one manic episode + depressive
Bipolar ll: hypomanic + depressive
Antipsychotics
(treat acute mania)
Risperidone
Quetiapine
Olanzapine
Antidepressants
(treat depressive episodes)
Mood Stabilisers
(maintenance)
Valproate
Lithium
enters cells via sodium channels --> increasing serotonin synthesis/release and decreasing dopamine synthesis/storage/release/reuptake
narrow therapeutic range excreted by the kidneys
ADRs: hypothyroidism (lowers thyroid function)
Cancer
(Abnormal/Uncontrolled Cell Division)
Benign: localised, less aggressive, functional cells, removable
Malignant: uncontrolled proliferation, loss of function, invasiveness and metastasis, fast growing
Hallmarks of Cancer
Evasion of Apoptosis
Limitless Replicative Potential
Insensitivity to Antigrowth Signals
Angiogenesis
Self-Sufficiency in Growth Signals
Invasion and Metastasis
Treatments
can be used in combination
curative or non-curative
Radiation
(remove localised growths, induces DNA damage, highly effective)
Pharmacotherapy
(systemic)
Traditional Cytotoxics (Chemotherapy)
exploit uncontrolled and higher rate of proliferation of cells
inhibit division of rapidly dividing cells
Cell-Cycle Specific
Antimetabolites
inhibit DNA production/replication (s-phase specific)
analogues of DNA bases (purines and pyrimidines)
Methotrexate
inhibits dihydrofolate reductase (DHFR) --> blocking the synthesis of both purines and pyrimidines
ADRs: myelosuppression, pneumonitis, nephrotoxicity
5-Fluorouracil (5-FU)
targets thymine (pyrimidine) --> causing apoptosis through lack of thymine
ADRs: myelosuppression, severe diarrhoea, cardiotoxicity
Antimitotic Agents
inhibit mitosis (m-phase specific)
Vinca Alkaloids
bind to beta-tubulin --> preventing polymerisation into microtubules --> preventing microtubule formation --> cell is stuck in m-phase --> initiating apoptosis
ADRs: mild myelosuppression
Vincristine
Vinblastine
Taxanes
stabilise microtubules --> preventing microtubules disassembly --> chromosomes can't be pulled apart properly --> preventing mitosis
ADRs: myelosuppression, cumulative neurotoxicity, hypersensitivity
Paclitaxel
Docetaxel
Cell-Cycle Non-Specific
Anthracyclines
intercalation: inhibit DNA and RNA synthesis, inhibit DNA repair
inhibit topoisomerase ll
generates free radicals --> damaging DNA
ADRs: hair loss, cardiac failure
Epirubicin
Idarubicin
Daunorubicin
Mitoxantrone
Doxorubicin
Platinum Agents
forms covalent bonds with DNA --> stopping replication of cells --> leading to apoptosis
bi-functional
ADRs: mild myelosuppression, severe nephrotoxicity, severe nausea/vomiting
Oxaliplatin
Carboplatin
Cisplatin
Alkylating Agents
forms covalent bonds with DNA --> stopping replication of cells --> leading to apoptosis
mono-functional or bi-functional
toxic to normal cells
ADRs: myelosuppression, hair loss, infertility, hemorrhagic cystitis
Cyclophosphamide
Targeted Therapies
(target differences between cancer cells and normal cells)
Monoclonal Antibodies
very specific, work extracellularly, "-mab"
inhibition of signal transduction via; ligand sequestration, receptor inhibition, blockage of receptor dimerisation and/or downregulation of cell surface receptors
Trastuzumab
used within anti-HER2 therapy (decreases proliferation and increases apoptosis of cancer cells)
binds to HER2 receptor --> downregulating HER2 receptor expression --> preventing HER2 receptor dimerisation --> inhibiting HER2 signal transduction cascade
Use: HER2+ breast cancer
ADRs: mild infusion reactions, cardiac toxicity
Protein/Tyrosine Kinase Inhibitors
less specific, work via antagonism, "-nib"
small molecule inhibitors of enzyme activity
Lapatinib
used within anti-HER2 therapy (decreases proliferation and increases apoptosis of cancer cells)
binds to intracellular portion of HER2 --> stopping phosphorylation and activation of HER2 receptors --> inhibiting signal transduction
Use: HER2+ breast cancer
ADRs: fatigue, rash, diarrhoea, QT prolongation, hepatotoxicity
Hormonal Therapy
(stops the growth of cancer)
Anti-Oestrogens
Tamoxifen
(selective (o)estrogen receptor modulator (SERM) (antagonist effect on oestrogen receptors in breast tissue))
Aromatase Inhibitors
Anti-Androgens
Analogues of Hormones
Surgery
(remove localised growths, highly effective)
Cell Cycle
Synthesis (S)
(chromosome replication)
Gap-2 (G2)
(readying for mitosis)
Gap-1 (G1)
(readying itself for division, upregulation of proteins)
Mitosis (M)
(segregation of chromosomes, cytokinesis)
Gap-0 (G0)
(resting phase)
Cell Cycle Checkpoints
G2 Checkpoint
(DNA replication)
M Checkpoint
(spindle assembly)
G1 Checkpoint
(growth factors, DNA damage, nutrients, cell size)
Parkinson's Disease
(Dopaminergic Deficiency)
Idiopathic: destruction of dopaminergic neurons (substantia nigra)
Familial: mutations --> lewy bodies --> neurodegeneration
Medications
Anticholinergics
(centrally acting, block muscarinic actions of acetylcholine)
Benzatropine
Amantadine
(block NMDA receptors, increase dopamine release, block cholinergic receptors)
Inhibition of Dopamine Metabolism
MAO-B Inhibitors
(reduce the breakdown of dopamine --> reduce motor symptoms)
Rasagiline
Selegiline
COMT Inhibitors
(reduces the breakdown of levodopa and dopamine (off periods))
Entacapone
Anti-Emetics
(treat nausea/vomiting)
Dopamine Antagonists
Prochlorperazine
(avoid, crosses the BBB)
Metoclopramide
(avoid, crosses the BBB)
Domperidone
(use, doesn't cross the BBB)
Dopaminergic Agents
Dopamine Agonists
(stimulate dopamine receptors --> improves motor symptoms)
Pramipexole
Rotigotine
Levodopa
most common
precursor for dopamine (crosses the BBB --> converted to dopamine)
given with a PDI (carbidopa or benserazide (do not cross the BBB)) to minimise conversion in peripheries, tolerance and sensitisation
Differential Diagnosis: Parkinsonism
Vascular Parkinsonism
(infarcts in basal ganglia)
Dementia with Lewy Bodies
(no/slight tremor)
Drug-Induced Parkinsonism
(antipsychotics)
Dementia
(Cognitive and Functional Decline)
Subtypes
Frontotemporal Dementias
Dementia with Lewy Bodies
Vascular Dementia
Parkinson Disease Dementia
Alzheimer's Disease
(degeneration/destruction of neurons --> decreasing acetylcholine concentration, increases tumour necrosis factor alpha (pro-inflammatory cytokine))
Neurotransmitters Involved
Acetylcholine
Treatment: increase acetylcholine availability
Cholinergic neurons are lost in AD
Glutamate
Excessive/Eradicate glutamate stimulation in AD --> impaired learning
Treatment: normalise glutamate neurotransmission
Medications
Acetylcholinesterase Inhibitors
begin with
decrease the breakdown of acetylcholine --> reducing the apparent deficiency of neurotransmitter activity
avoid the use of anticholinergic drugs
Rivastigmine
Galantamine
Donepezil
NMDA Receptor Antagonists
if condition worsens
reduce glutamate-induced neuronal degradation
Memantine