Pharmacology2

• Benzodiazepine
• Anxiolytic/muscle relaxant/anticonvulsant
• Bind to the alpha subunit of the GABA_A receptor in the CNS
• - alpha-1: sedation and amnesia
• - alpha-2: anxiolytic
• Enhance activation of GABA_A mediated chloride channels
• Long acting
• Lipid soluble
• Well absorbed orally
• Side effects: drowsiness, confusion, amnesia, impaired coordination, potentiate depressant effects of other drugs, tolerance and dependence

Can be used i.v. as an anticonvulsant

• Anxiolytic
• Partial 5-HT1A receptor agonist - reduce 5HT synthesis/release
• Non-sedative, non-drowsy
• Takes several weeks to work - alteration in receptor number?
• Ineffective at treating acute attacks
• Side effects: nausea, dizziness, headache (doesnt cause sedation or drowsiness

• SSRI
• Antidepressant/depression associated with anxiety/OCD/panic disorders
• Leads to receptor downregulation due to increased 5HT in synapse

• SSRI
• Antidepressant/depression associated with anxiety/OCD/panic disorders
• Leads to receptor downregulation due to increased 5HT in synpase

• SSRI
• Antidepressant/depression associated with anxiety/OCD/panic disorders
• Leads to receptor downregulation due to increased 5HT in synpase

• SSRI
• Antidepressant/depression associated with anxiety/OCD/panic disorders
• Leads to receptor downregulation due to increased 5HT in synpase

• Barbiturate
• Sleeping tablet
• Popular in 60's
• Enhance action of GABA
• Side effects: repiratory and CV depression on OD, induce CYP450, high degree of tolerance and dependence

• Barbiturate
• Anticonvulsant
• Control of seizure by i.v. administration, ineffective in absence seizures
• Enhance activation of GABA_A mediated chloride channels
• Plasma t1/2 = 50 - 140 h
• Side effects: repiratory and CV depression on OD, induce CYP450, high degree of tolerance and dependence, sedation, megaloblastic anaemia, osteomalacia

• Barbiturate CNS depressant
• I.v. anaesthetic
• Enhance action of GABA

• Advantages:
• Very lipid soluble - rapid induction
• Rapid redistribution into tissues - blood concentrationd declines rapidly
• Recovery within 5 minutes

• Disadvantages:
• Slowly distributes into fat - long lasting hangover
• No analgesic effect
• Profound cardiac and repiratory depression
• Negative ionotrope - inc HR, coronary blood flow and cardiac demand, pooling of blood in peripheral veins, hypotension in hypovolaemic patients
• Tissue necrosis or arterial spasm - gangrene

C/I in: low circulating blood vol, cardiac disease, asthma (bronchospasm)

• Benzodiazepine (Xanax)
• Anxiolytic
• Antidepressant
• Bind to the alpha subunit of the GABAA receptor in the CNS
• - alpha-1: sedation and amnesia
• - alpha-2: anxiolytic
• Medium acting
• Lipid soluble
• Well absorbed orally

• Benzodiazepine
• Anxiolytic/muscle relaxant/anticonvulsant
• Bind to the alpha subunit of the GABAA receptor in the CNS
• - alpha-1: sedation and amnesia
• - alpha-2: anxiolytic
• Side effects: drowsiness, confusion, amnesia, impaired coordination, potentiate depressant effects of other drugs, tolerance and dependence
• Well absorbed orally
• Lipid soluble, accumulate in fat
• Long acting

• Benzodiazepine
• Hypnotic/anxiolytic
• Bind to the alpha subunit of the GABAA receptor in the CNS
• - alpha-1: sedation and amnesia
• - alpha-2: anxiolytic
• Short acting

Side effects: drowsiness, confusion, amnesia, impaired coordination, potentiate depressant effects of other drugs, tolerance and dependence

• Benzodiazepine
• Anxiolytic/hypnotic
• Bind to the alpha subunit of the GABAA receptor in the CNS
• - alpha-1: sedation and amnesia
• - alpha-2: anxiolytic
• Short acting
• Side effects: drowsiness, confusion, amnesia, impaired coordination, potentiate depressant effects of other drugs, tolerance and dependence

• Anticonvulsant
• Na channel blocker: use dependent block (block inactivated state)
• Preferentially block cells firing repeatedly (as in seizure) normal activity not compromised
• Good for partial/generalised siezures, not absence seizures
• Good oral absorption
• 80%-90% plasma protein bound (albumin)
• Side effects: vertigo, ataxia, headache, nystagmus
• (high dose) confusion, intelluctual effects, gum hyperplasia, hirsutism, acne, megaloblastic anaemia
• Don't give to adolescents

• Anticonvulsant
• Na channel blocker: use dependent block (block inactivated state)
• Preferentially block cells firing repeatedly (as in seizure) normal activity not compromised
• Effective in most types except absence seizures, also can be used for manic depressive illness
• Hepatic inducer
• Side effects: dizziness, drowsiness, ataxia, nausea, vominting,
• Severe: mental and motor disturbances

• Anticonvulsant
• Na channel blocker: use dependent block (block inactivated state)
• Preferentially block cells firing repeatedly (as in seizure) normal activity not compromised

• Anticonvulsant
• Mildly inhibits GABA activation enzymes (GABA transaminase, SSA dehydrogenase)
• Some Na channel inhibition: use dependent block (block inactivated state)
• Enhances post synaptic action of GABA
• Preferentially block cells firing repeatedly (as in seizure) normal activity not compromised
• Drug of choice for primary generalised seizures, absence seizures, myoclonic seizures, patients with "grand mal" and "petit mal", infantile epilepsy
• Side effects: thinning and curling of hair, hepatotoxicity, teratogenic

• Anticonvulsant
• Ca channel blocker -T type
• Treats absence seizures
• Plasma t_1/2 = 50h
• Side effects: nausea, anorexia, lethargy, dizziness, may precipitate tonic clonic seizures in susceptible patients, rare hypersensitivity reactions

Dopamine antagonist

Can be used to treat Huntington's disease (readdress balance)

Treats schizophrenia - typical antipsychotic

Side effects: sedation, atropinic side effects, motor side effects

• GABA antagonist
• CNS stimulant/convulsant
• Lab tool to model epilepsy, no clinical use

• Anticonvulsant
• Mechanism not entirely clear
• May block calcium channel - L type contriubuting factor, not main drug action
• May bind to amino acid transporter
• Treats seizures - adjunctive therapy
• Plasma t1/2 = 6h
• Relatively free from side effects

Antagonist at glycine receptors on motorneurones

Cause skeletal mucle spasm

Blocks post synaptic ACh receptors

• Treats Alzheimers disease
• Block NMDA glutamate receptor

MAO-B inhibitor

Prevents dopamine metabolism and so increases the half life of dopamine derived from L-dopa in the CNS

No peripheral inhibition of MAO-A - no cheese reaction

• Antipyretic analgesic
• Irreversible COX inhibitor
• Reduced PG production, "thermostat" back to normal
• Side effects: GIT upset, bronchoconstriction, bleeding problems, Reyes syndrome
• High dose side effects: CNS stimulation -> hyperventilation -> decreased PCO2 -> respiratory alkalosis, disturbance of cellular metabolism -> increased lactic/ketoacids -> metabolic acidosis

• Antipyretic analgesic
• Reversible, non-competitive COX-3 (CNS isoenzyme) inhibitor
• Not anti-inflammatory
• Reduced PG production, "thermostat" back to normal
• Analgesic and antipyretic effect equivalent to aspirin
• Regarded as safer, no gastric damage, haemorrhage, or bronchospasm

• Antipyretic analgesic
• Reversible, competitive COX inhibitor
• Reduced PG production, "thermostat" back to normal

Inhaled anaesthetic

• Advantages:
• Excellent analgesia
• Non flammable
• Rapid onset and recovery
• Little or no toxicity
• Use as adjunct to other inhalation agents to reduce their dose

• Disadvantages:
• No skeletal muscle relaxation
• Weak anaesthetic - not suitable as sole agent
• Air pockets in closed spaces expand - "bends"
• Post-anaesthetic hypoxia - dilutes o2 in lungs for a few minutes - flush out with o2 at end of anaesthesia
• Methionine synthase inactivation (prolonged/repeat exposure) - inhibits DNA and protein synthesis, megaloblastic anaemia and leucopoenia
• Foetal abnormalities/spontaneous abortion - theatre staff

Inhaled anaesthetic

Widely used in paediatrics

• Advantages:
• Non flammable
• Potent and high oil:gas partition coefficient
• Rapid induction
• Rapid recovery
• Controlled hypotension to limit bleeding
• Non-irritant
• Few post-op effects

• Disadvantages:
• Doesn't provide adequate analgesia
• May not provide adequate muscle relaxation
• Vasodilator and cardiac depressant -> myocardial depression
• Highly potent so easy to over anaesthetise
• Sensitises heart to adrenaline - cardiac dysrhythmias (avoid beta blockers and adrenaline)
• Respiratory depression
• Hepatotoxic if repeated exposure (3 months between exposures)
• Malignant hyperthermia

Inhaled anaesthetic

• Advantages:
• Low solubility in blood
• Minimal systemic effects
• Minimal metabolism
• Few side effects

• Disadvantages:
• Expensive
• Some respiratory tract irritation

I.v. anaesthetic

• Advantages:
• Rapid metabolism, rapid recovery, no hangover
• Can be continuously infused to maintain anaesthesia
• None of the effects of epotomidate

• Disadvantages:
• Rapid metabolism, short duration of action
• Not water soluble, painful injection

Muscarinic antagonist (competative)

• Muscarinic antagonist
• Used for treatment/prevention of motion sickness
• Less effective after onset
• Ineffective against substances acting directly on CTZ
• Side effects: dizziness, dry mouth, blurred vision

• Opioid analgesic
• Mixture

• Beta blocker
• Can be used to treat hyperthyroidism
• Decreases symptoms, but patient still hyperthyroid biochemically
• Used prior to surgery, in treatment with thyrotoxic crisis, initially with carbimazole, following radiation

• Benzodiazepine antagonist
• Competitive inhibition at the benzodiazepine binding site on the GABAA receptor

• Typical antipsychotic
• Thioxanthine
• Antagonist at various dopamine (D1-D5), serotonin (5-HT2), adrenaline (α1), and histamine (H1) receptors, without affecting the muscarinic acetylcholine receptors
• Side effects: slight sedation, slight atropinic side effects, pronounced motor effects

• Typical antipsychotic
• Piperazine

Methylxanthine

Effects: stimulate cardiac and skeletal muscle, relax smooth muscle, induce diuresis, offset fatigue, reduce reaction time

Least potent

• Antagonism at adenosine (A2) receptors
• Inhibition of phosphodiesterase
• Mobilization of intracellular calcium

Methylxanthine

Effects: stimulate cardiac and skeletal muscle, relax smooth muscle, induce diuresis, offset fatigue, reduce reaction time

Middle potent

• Antagonism at adenosine (A2) receptors
• Inhibition of phosphodiesterase
• Mobilization of intracellular calcium

DNA nucleoside

• Can be used in depression
• Pre-cursor for 5HT
• Potentiates effect of MAOI's
• Limited use: adjunct in mild/moderate depression

• Monoamine
• Responsible for Cheese reaction with MAOI's

Amino acid

• Antidepressant
• Controls both depression and mania, so drug of choice for bi-polar
• Displaces Na ions
• Affects inositol phosphate inhibits conversion from IP1 to inositol
• Has other effects
• Side effects: tremor, mental confusion, sinus node toxicity, polydipsia, polyuria
• Narrow TI - levels need monitoring

• Treats type II diabetes
• Inhibits alpha glucosidase enzymes which turn complex carbohydrates into glucose
• Reduces glucose available for absorption
• No hypoglycaemia
• No weight gain

• Treats type II diabetes
• Activates nuclear receptor - PPARy
• Receptor binds to DNA - increases gene transcription
• Increase plasmalemmal glucose transporters - increase muscle glucose uptake
• Reduce liver glucose output
• Increases lipogenesis, uptake of fatty acids
• Overall effect increases sensitivity to insulin
• Slow onset - 1-2 months
• No increased risk of hypoglycaemia
• Almost unique metabolic pathway - CYP2C8
• Rare reports of liver toxicity - monitor

• Treats type II diabetes
• Activates nuclear receptor - PPARy
• Receptor binds to DNA - increases gene transcription
• Increase plasmalemmal glucose transporters - increase muscle glucose uptake
• Reduce liver glucose output
• Increases lipogenesis, uptake of fatty acids
• Overall effect increases sensitivity to insulin
• Slow onset - 1-2 months
• No increased risk of hypoglycaemia
• Almost unique metabolic pathway - CYP2C8
• Rare reports of liver toxicity - monitor

• Treats type II diabetes
• Mechanism unclear
• - receptor sensitivity?
• - peripheral glucose uptake?
• - liver glucose production
• Requires insulin presence
• Does not promote insulin release - no risk of hypoglycaemia

• Treats type II diabetes as adjunct
• Inhibits dipeptidyl peptidase-4
• - increased levels of incretin
• - increase insulin release
• - inhibit glucagon release
• -slow gastric emptying

• Sulphonylurea
• Used to treat type II diabetes
• Stimulates insulin secretion by blocking K+ATP channels in B cells
• Require functioning B cells
• Also block other K+ATP channels e.g. vascular smooth muscle
• T1/2 = 12
• Side effects: hypoglycaemia, stimulate appetite, drug interactions (NSAIDs, warfarin, antifungals)

• Antabuse
• Blocks the enzyme acetaldehyde dehydrogenase

Treatment of Parkinson's Disease

Used because dopamine cannot cross BBB

Metabolised to dopamine in CNS

Also in periphery - side effects and reduction in LDOPA in brain

• D2 receptor antagonist
• Does cross BBB
• Reduced side effects
• Side effects: migraine

• Cannabinoid antiemetic
• Treats vomiting caused by cytotoxic anticancer drugs (also as adjuvant for neuropathic pain)
• Effective against substances which stimulate the CTZ
• Thought to act via opioid receptors in the CTZ
• Sometimes effective where other treatment has failed
• Side effects: drowsiness, dizziness, dry mouth, modd changes, postural hypotension, hallucinations, psychotic reactions

• 5HT3 receptor antagonist
• Used for nausea and vomiting caused by cytotoxic anticancer drugs, post-op vominting and radiation induced vomiting
• Primary site of action is on the CTZ
• Side effects: headache, GI upset

H1 receptor antagonist

• Oral non-steroidal
• Treats women having difficulty conceiving
• Binds oestrogen receptors
• - hypothalamus unable to recognise endogenous oestrogen
• - alters pulsility of GnRH
• - pituitary gonadotrophin secretion increased
• - may also affect gonadotrophin secretion directly
• Side effects: increased risk of multiple pregnancy, visual disturbances, hot flushes, breast tenderness, headache, ovarian cancer?

• Morning after pill
• Mechanism unclear
• - delays ovulation?
• - prevents implantation?
• - inhibition of sperm transport?

• Estrogen combined oral contraceptive
• Need high dose if used alone

• Termination of pregnancy
• Progesterone antagonist
• - progesterone receptor/antagonist complex binds DNA and recruit corepressors
• Used for medical terminations in 1st trimester

• SERM
• Binds Estrogen receptor - partial agonist
• Treats breast cancer

• Treats hyperthyroidism
• Rapid effect, not sustained
• Inhibits peroxide generation?
• Inhibits iodination?
• Decreases size and vascularity of gland
• Used prior to surgery, treatment of thyrotoxic crisis
• Allergic responses possible

• Thioureylene
• Competitive inhibition of thyroperoxidase enzymes
• - reduce iodination of tyrosine
• - reduce T3 and T4 output
• Treats hyperthyroidism
• Slow reponse - relapse common
• Side effects; hypothyroidism, skin rash (less common than carbimazole), granulocytopenia

Reversible inhibitor of acetylcholinesterase

Used to treat dementia

Inhibitory CNS transmitter

Found mostly in spinal cord

Derived from serine by action of SMHT

Inactivated by uptake and metabolism

ACh released by a collateral of the alpha motor neurone which acts on nicotinic receptors of the Renshaw cell to cause glycine release

Modulates contraction of skeletal muscle by providing a negative feedback loop by acting on receptor at alpha motor neurone causing hyperpolarisation

Main inhibitory transmitter in the brain

Widespread distribution

Synthesised from glutamate by GAD

Inactivated by active uptake

GABA transaminase converts GABA to succinic semialdehyde (glutamate formed in process)

Facilitates entry of chloride ions into neurones, resulting in hyperpolarisation (neurone depression)

Main excitatory transmitter in CNS

Widely and uniformly located in CNS

Formed from alpha-oxoglutarate (Krebs cycle) by GABA-aminotransferase

Inactivated by active uptake

Actions exerted via receptors

Dopamine antagonist

Can be used to treat Huntington's disease (readdress balance between dopamine and GABA)

Treats schizoprenia - typical antipsychotic

• SERM
• Binds Estrogen receptor
• Treats breast cancer

Inhibits glycine release

Causes uncontrollable muscle spasm

Ligand gated ion channel

Pentamer structure with alpha, beta and gamma subunits

Located post-synaptically

Activation opens Cl- channels which reduced membrane excitability

Several binding sites (barbiturates, benzodiazepines, GABA)

G protein coupled receptor

Linked to adenylyl cyclase

Inhibit cAMP formation

Located pre and post synaptically (results in pre and post synaptic inhibition)

Prevents Ca2+ channel opening

Increases K+ permeability

ligand gated cation channels

Named after specific agonists (NMDA, AMPA and kainate)

Pentameric structure

NMDA and AMPA are post-synaptic

Kainate is pre and post synaptic

NMDA and possibly AMPA have modulatory sites (glycine binds to NMDA)

Cause slow (NMDA) or fast (AMPA) EPSP

Highly permeable to Ca2+

Blocked by Mg2+

Blocked by some anaesthetics (ketamine)

Blocked by some psychomimetics (phencyclidine)

G protein coupled receptor

No homology with other GPCR

linked to intracellular second messenger systems (phospholipase C) which result in IP3 production and release of Ca2+

Widely distributed in CNS - cortex, basal ganglia, brainstem, spinal cord

Main excitatory action

Inactivated by acetylcholinesterases

Ligand gated ion channels

Pentameric

alpha and beta subunits

pre-synaptic

facilitate release of other transmitters (glutamate and dopamine)

activated by acetylcholine

GPCR

M1 class

activate phospholipase C

Reversible inhibitor of acetylcholinesterase

Used in treatment of dementia

Reversible inhibitor of acetylcholinesterase

Used in treatment of dementia

Synthesis, storage, release, inactivation as in PNS

Mainly inhibitory via beta, but some excitatory via alpha and beta

Involved in blood pressure regulation

Important in mood, arousal and reward pathways

Derived from tryptophan (diet)

Similar pathway to NA - tryptophan dehydroxylase, NH2 acid decarboxylase

Inactivated by uptake and metabolism by MAO, aldehyde dehydrogenase

Roles in: hallucinations, behaviour, sleep, wakefulness, body temperature, sensory pathways, vomiting (5HT3), mood, emotion

7 subtypes

All GPCR except 5HT3 which is a ligand gated ion channel

• 5HT1,2,3 appear to be the most important in CNS
• 1. linked to cAMP (inhibitorys)
• 2. linked to IP3/DAG (excitatory)
• 3. excitatory

Synthesis via dopamine beta-hydroxylase

Tyrosine to dopa is controlled by tyrosine hydroxylase (rate limiting step)

Inactivated by selective active re-uptake, metabolism by MAO-B and COMT to DOPAC and HVA

Found in nigrostrital pathway (motor control), mesolimbic/mesocortical (behavioural effects) pathway, tubero-hypophyseal (endocrine) pathway

Two types:

• D1 type (D1 and D5)
• GPCR linked to adenylyl cyclase
• increase cAMP
• Mainly post-synaptic inhibition

• D2 type (D2, D3, D4)
• GPCR linked to adenylyl cyclase
• Decrease cAMP
• pre and post synaptic inhibition
• Mediate most known CNS functions of DA

COMT inhibitor

Co administered with L-DOPA to reduce peripheral DOPA metabolism to treat Parkinsons

Peripheral dopa decarboxylase inhibitor

Prevents conversion of L-dopa to dopamine in peripheral tissues

Do not cross BBB

Reduces peripheral side effects and increases L-dopa dose getting into the brain

Peripheral dopa decarboxylase inhibitor

Prevents conversion of L-dopa to dopamine in peripheral tissues

Do not cross BBB

Reduces peripheral side effects and increases L-dopa dose getting into the brain

Ergot derivative dopamine agonist

Act directly at D2 receptors

Can be used in the treatment of Parkinson's

Cause nausea (action at CTZ) - reduce by administration of domperidone

Ergot derivative dopamine agonist

Act directly at D2 receptors

Can be used in the treatment of Parkinson's

Cause nausea (action at CTZ) - reduce by administration of domperidone

Ergot derivative dopamine agonist

Act directly at D2 receptors

Can be used in the treatment of Parkinson's

Cause nausea (action at CTZ) - reduce by administration of domperidone

Ergot derivative dopamine agonist

Act directly at D2 receptors

Can be used in the treatment of Parkinson's

Cause nausea (action at CTZ) - reduce by administration of domperidone

Dopamine agonist

Non-ergot derivative

Act directly at D2 receptors

Treats Parkinson's

Cause nausea (action at CTZ) - reduce by administration of domperidone

Dopamine agonist

Non-ergot derivative

Act directly at D2 receptors

Treats Parkinson's

Cause nausea (action at CTZ) - reduce by administration of domperidone

Dopamine agonist

Non-ergot derivative

Act directly at D2 receptors

Cause nausea (action at CTZ) - reduce by administration of domperidone

Treats Parkinson's

Anti-viral drug

However also has weak anti-Parkinson's action

• Mechanism unclear;
• Increase dopamine release?
• Inhibit dopamine uptake?
• Agonis activity at D2 receptors?

Muscarinic antagonist

Treats Parkinson's

More effective against tremor than hypokinesia

Antimuscarinic side effects due to peripherally blocked muscarinic receptors

Worsen signs of dementia - C/I

Muscarinic antagonist

Treats Parkinson's

More effective against tremor than hypokinesia

Antimuscarinic side effects due to peripherally blocked muscarinic receptors

Worsen signs of dementia - C/I

Treats Huntington's

Mechanism unclear - depletes dopamine to readdress balance?

GABA B agonist

Treats Huntington's

Inhaled anaesthetic

• Advantages:
• Stable
• Non flammable
• Potency/induction similar to halothane

• Disadvantages:
• Dose related depression of myocardial contractility
• Produces fluoride ions - renal toxicity
• Lowers threshold for seizures
• Known to cause malignant hypothermia

Inhaled anaesthetic

Widely used

• Advantages:
• No metabolism - little toxicity
• Not pro-convulsive
• Excellent muscle relaxant

• Disadvantages:
• Expensive
• Hypotension
• Coronary vasodilator

Inhaled anaesthetic

• Advantages:
• More potent then desflurane
• Less respiratory irritation

• Disadvantages:
• Expensive
• Partially metabolised

• I.v. anaesthetic
• GABA receptor agonist - CNS depressant
• Induction agent only

• Disadvantages:
• No analgesic activity
• Mild dose related respiratory depression
• Decreased cerebral metabolism
• Pain on injection (propylene glycol)
• Myoclonic activity
• Cortisol suppression
• Post-op nausea and vomiting

Favoured over thiopental - large margin between anaesthetic dose and resp/CV depression also faster metabolism, less hungover

• Benzodiazepine
• Anxiolytic
• Bind to the alpha subunit of the GABAA receptor in the CNS
• - alpha-1: sedation and amnesia
• - alpha-2: anxiolytic
• Ultra short acting
• Lipid soluble
• Well absorbed orally
• Side effects: drowsiness, confusion, amnesia, impaired coordination,
• potentiate depressant effects of other drugs, tolerance and dependence

• Benzodiazepine
• Anxiolytic
• Bind to the alpha subunit of the GABAA receptor in the CNS
• - alpha-1: sedation and amnesia
• - alpha-2: anxiolytic
• Ultra short acting
• Lipid soluble
• Well absorbed orally
• Side effects: drowsiness, confusion, amnesia, impaired coordination,
• potentiate depressant effects of other drugs, tolerance and dependence

Can be used i.v. in anaesthesia

• Benzodiazepine
• Hypnotic
• Bind to the alpha subunit of the GABAA receptor in the CNS
• - alpha-1: sedation and amnesia
• - alpha-2: anxiolytic
• Ultra short acting
• Lipid soluble
• Well absorbed orally
• Side effects: drowsiness, confusion, amnesia, impaired coordination,potentiate depressant effects of other drugs, tolerance and dependence

• Benzodiazepine
• Anxiolytic/hypnotic
• Bind to the alpha subunit of the GABAA receptor in the CNS
• - alpha-1: sedation and amnesia
• - alpha-2: anxiolytic
• Short acting
• Lipid soluble
• Well absorbed orally
• Side effects: drowsiness, confusion, amnesia, impaired coordination,potentiate depressant effects of other drugs, tolerance and dependence

• Benzodiazepine
• Anxiolytic/hypnotic
• Bind to the alpha subunit of the GABAA receptor in the CNS
• - alpha-1: sedation and amnesia
• - alpha-2: anxiolytic
• Short acting
• Lipid soluble
• Well absorbed orally
• Side effects: drowsiness, confusion, amnesia, impaired coordination,potentiate depressant effects of other drugs, tolerance and dependence

• Benzodiazepine
• Anxiolytic/hypnotic
• Bind to the alpha subunit of the GABAA receptor in the CNS
• - alpha-1: sedation and amnesia
• - alpha-2: anxiolytic
• Medium acting
• Lipid soluble
• Well absorbed orally
• Side effects: drowsiness, confusion, amnesia, impaired coordination,potentiate depressant effects of other drugs, tolerance and dependence

• Benzodiazepine
• Anxiolytic
• Bind to the alpha subunit of the GABAA receptor in the CNS
• - alpha-1: sedation and amnesia
• - alpha-2: anxiolytic
• Long acting
• Lipid soluble
• Well absorbed orally
• Side effects: drowsiness, confusion, amnesia, impaired coordination,potentiate depressant effects of other drugs, tolerance and dependence

• Benzodiazepine
• Anxiolytic/anticonvulsant
• Bind to the alpha subunit of the GABAA receptor in the CNS
• - alpha-1: sedation and amnesia
• - alpha-2: anxiolytic
• Long acting
• Lipid soluble
• Well absorbed orally
• Side effects: drowsiness, confusion, amnesia, impaired coordination,potentiate depressant effects of other drugs, tolerance and dependence

• Anticonvulsant
• Enhances GABA action by inhibiting uptake - GABA analogue
• Adjunctive therapy for partial seizures
• Effective in patients resistant to established drugs
• Side effects: drowsiness, confusion

• Anticonvulsant
• Enhances GABA action by irreversibly inhibiting GABA transaminase (breakdown to succinic semialdehyde)
• Increases GABA and inhibitory transmission
• Treats simple complex generalised, tonic clonic seizures
• 1st "designer" epilepsy drug
• Short plasma t1/2 but long lasting effect
• Side effects: rare - depression and psychotic disturbances

• Pro-drug
• Similar to gabapentin but less side effects
• Mechanism not clear
• May block Ca channel
• May bind to amino acid transporter

• Pro-drug
• Anticonvulsant
• Metabolised to a compound sinilar to carbamazepine
• Na channel blocker

• Stimulant
• Displaces vesicular monoamine while inhibiting MAO and monoamine reuptake
• Indirect receptor activation
• Effects: vasoconstriction, mydriasis, inhibition of GIT and urinary bladder, alertness, increased motor activity, anorexia, anxiety (due to overstimulation of brain)

• Weight loss drug
• Amphetamine
• Did not produce CNS side effects
• Withdrawn due to cardiac effects

• Amphetamine
• Treats hyperkinesia and narcolepsy

• Ritalin
• Amphetamine
• Treats hyperkinesis and narcolepsy

• GABA antagonist
• CNS stimulant/convulsant
• Lab to model epilepsy
• No clinical use

• Analeptic
• Previously used to treat drug induced repiratory depression
• CNS mechanism unknown
• Peripheral mechanism, only one still used

• Analeptic
• Previously used to treat drug induced repiratory depression
• CNS mechanism unknown
• No longer used

• Analeptic
• Previously used to treat drug induced repiratory depression
• CNS mechanism unknown
• No longer used

Methylxanthine

Effects: stimulate cardiac and skeletal muscle, relax smooth muscle, induce diuresis, offset fatigue, reduce reaction time

Most potent

• Antagonism at adenosine (A2) receptors
• Inhibition of phosphodiesterase
• Mobilization of intracellular calcium

• Typical antipsychotic
• Butyrophenone
• Antagonism at dopamine receptors, 5HT and histamine receptors
• Pronounced motor effects

• Atypical antipsychotic
• Diphenylbutylpiperidine

• Atypical antipsychotic
• Phenothiazines piperidines

Atypical antipsychotic

• Lower chance of extrapyridamol side effects
• Mechanism uncertain
• D1 D2 5HT2 H1 ACh alpha-2 receptors blocked

Potentially fatal haematological side effects

Atypical antipsychotic

• Lower chance of extrapyridamol side effects
• Mechanism uncertain
• D1 D2 5HT2 H1 ACh alpha-2 receptors blocked

Atypical antipsychotic

• Lower chance of extrapyridamol side effects
• Mechanism uncertain
• D1 D2 5HT2 H1 ACh alpha-2 receptors blocked

Atypical antipsychotic

• Lower chance of extrapyridamol side effects
• Mechanism uncertain
• D1 D2 5HT2 H1 ACh alpha-2 receptors blocked

Atypical antipsychotic

• Lower chance of extrapyridamol side effects
• Mechanism uncertain
• D1 D2 5HT2 H1 ACh alpha-2 receptors blocked

• MAOI
• Irreversible inhibitor
• Indicated in psychotic and neurotic depression
• Take over 3 weeks to work
• Limited use

Side effects: convulsions, excitement (related to amphetamine), hepatoxiicity, pyrexia, hypertensive crisis i.e. cheese reaction

• MAOI
• Slowly reversible inhibitor
• Indicated in psychotic and neurotic depression
• Take over 3 weeks to work
• Limited use

Side effects: convulsions, excitement (related to amphetamine), hepatoxiicity, pyrexia, hypertensive crisis i.e. cheese reaction

• MAOI
• Reversible inhibitor
• Indicated in psychotic and neurotic depression
• Take over 3 weeks to work
• Limited use

Side effects: convulsions, excitement (related to amphetamine), hepatoxiicity, pyrexia, hypertensive crisis i.e. cheese reaction

• Monoamine uptake inhibitor
• Tricyclic antidepressant
• Antidepressant drug of choice
• 2-4 weeks to work
• Inhibits NA and 5HT uptake
• Antagonist at muscarininc receptors - dry mouth, blurred vision, urinary retention, arrhythmias, tachycardia, syncope

• Monoamine receptor agonist
• A 5HT agonist?
• Relieve both psychotic and neurotic depression

• Opioid analgesic
• Agonist at opioid receptors
• More convulsions (metabolite norpethidine)
• Not dependent on glucuronide conjugation metabolism

• Opioid analgesic
• Long duration of effect

• Opioid analgesic
• Opioid receptor agonist
• Short duration of action
• Side effects: cough suppression

• Opioid analgesic
• Opioid receptor agonist
• Weaker activity than morphine
• More nausea

• Opioid analgesic
• Opioid receptor agonist
• More analgesic activity than morphine and faster onset of action
• Short duration

• Competitive antagonist at all 3 opioid receptors
• Used to treat drug induced respiratory depression
• Short action
• Precipitate withdrawal

• Opioid analgesic
• Reduced abuse potential
• Partial agonist at Mu
• Kappa antagonism
• Withdrawal less intense than morphine
• Respiratory depression not fully reversed by naloxone
• Analgesic and in management of dependence
• Side effects: sedative, marked nausea and vomiting

• Opioid analgestic with reduced abuse potential
• Limited respiratory depression
• Mu antagonist
• Kappa agonist
• Sigma agonist
• Prolonged use gives dependence

• Cough suppressant
• Structurally related to opioids - large substituent added at 3 position
• Little analgesic effect
• Action at CNS cough centre, via mu and delta receptors?

• Cough suppressant
• Structurally related to opioids - large substituent added at 3 position
• No analgesic effect
• Not blocked by opioid antagonists
• Action at CNS cough centre, via mu and delta receptors?
• Has non opioid binding sites

• Opioid analgesic
• Mu1 selective agonist
• Less respiratory depression than other opioids

• Dopamine agonist
• Structurally similar to morphine, causes emesis without other opioid actions
• Used in Parkinson's

• Opioid analgesic with lower abuse potential
• Not used clinically - dysphoria
• Mu antagonist
• Delta kappa partial agonist
• Sigma agonist

• Histamine H1 receptor antagonist
• Used in prevention/treatment of motion sickness
• Ineffective against substances acting directly on CTZ
• Side efffects: drowsiness and sedation

• Histamine H1 receptor antagonist
• Used in prevention/treatment of motion sicknes and treatment of vestibular disorders (Menier's)
• Ineffective against substances acting directly on CTZ
• Side effects: drowsiness and sedation

• D2 receptor antagonist
• Treats nausea and vomiting associated with cancer treatment, radiation therapy, cytotoxics, opioids, post-op nausea, severe morning sickness
• Pass BBB
• Also block histamine and mACh receptors
• Effective after vomiting onset
• Side effects: sedation, hypotension, dystonia, dyskinesia

• D2 receptor antagonist
• Treats nausea and vomiting associated with cancer treatment, radiation
• therapy, cytotoxics, opioids, post-op nausea, severe morning sickness
• Pass BBB
• Also block histamine and mACh receptors
• Effective after vomiting onset
• Side effects: sedation, hypotension, dystonia, dyskinesia

• D2 receptor antagonist
• Treats nausea and vomiting associated with cancer treatment, radiation
• therapy, cytotoxics, opioids, post-op nausea, severe morning sickness
• Typical antipsychotic
• Phenothiazine piperidine
• Pass BBB
• Also block histamine and mACh receptors
• Effective after vomiting onset
• Side effects: sedation, hypotension, dystonia, dyskinesia

• D2 receptor antagonist
• Passes BBB
• Acts on DA receptors throughout CNS
• Also peripheral prokinetics
• 2nd line treatment for severe morning sickness
• Side effects: movement disorder, fatigue, motor restlessness, spasmodic torticolis, occulogyric crisis, menstruation disorder, diarrhoea

• Steroid
• Glucocorticoid
• Long acting
• Treats vomiting caused by cytotoxics
• Unknown mechanism
• Used in combo with D2 or 5HT3 receptor antagonists

• Substance P antagonist
• Treats vomiting caused by cytotoxics/post-op NV
• Side effects: hiccuping, fatigue, listlessness, constipation/diarrhoea, loss of appetite, dizziness, ringing in ears

• Natural steroid
• Synthesised from cholesterol
• Control of synthesis and release via hypothalamus, anterior pituitary and negative feedback
• Shows both glucocorticoid and mineralocorticoid action
• Enzyme in kidneys etc converts these to mineralo-inactive compounds
• Short acting
• Used for replacement therapy in adrenal failure - few side effects as natural situation mimicked, and for anti-inflammatory/immunosuppressant actions
• Side effects: drug induced Cushing's syndrome (buffalo hump, moon face, inc abdo fat, poor wound healing, osteoporosis, muscle wasting, hypertension, thinning of skin), increased risk of infection, suppression of normal steroid synthesis (abrupt withdrawal can lead to acute adrenal failure)

• Synthetic steroid
• Mixed gluco-/mineralocorticoid action
• Medium acting
• Used for asthma
• Side effects: drug induced Cushing's syndrome (buffalo hump, moon face,
• inc abdo fat, poor wound healing, osteoporosis, muscle wasting,
• hypertension, thinning of skin), increased risk of infection,
• suppression of normal steroid synthesis (abrupt withdrawal can lead to
• acute adrenal failure)

• Synthetic steroid
• Glucocorticoid
• Long acting
• Side effects: drug induced Cushing's syndrome (buffalo hump, moon face,
• inc abdo fat, poor wound healing, osteoporosis, muscle wasting,
• hypertension, thinning of skin), increased risk of infection,
• suppression of normal steroid synthesis (abrupt withdrawal can lead to
• acute adrenal failure)

• Synthetic steroid
• Glucocorticoid
• Long acting
• Used for asthma
• Side effects: drug induced Cushing's syndrome (buffalo hump, moon face,
• inc abdo fat, poor wound healing, osteoporosis, muscle wasting,
• hypertension, thinning of skin), increased risk of infection,
• suppression of normal steroid synthesis (abrupt withdrawal can lead to
• acute adrenal failure)

• Synthetic steroid
• Glucocorticoid
• Used for asthma
• Side effects: drug induced Cushing's syndrome (buffalo hump, moon face,
• inc abdo fat, poor wound healing, osteoporosis, muscle wasting,
• hypertension, thinning of skin), increased risk of infection,
• suppression of normal steroid synthesis (abrupt withdrawal can lead to
• acute adrenal failure)

• Steroid
• Mainly mineralocorticoid
• Short acting
• Side effects: drug induced Cushing's syndrome (buffalo hump, moon face,
• inc abdo fat, poor wound healing, osteoporosis, muscle wasting,
• hypertension, thinning of skin), increased risk of infection,
• suppression of normal steroid synthesis (abrupt withdrawal can lead to
• acute adrenal failure)

• Cancer drug
• Inhibits conversion of cholesterol to pregnenolone
• Reduces adrenal output of androgens/oestrogens
• Used for post-menopausal breast cancer and prostate cancer
• Require corticosteroid replacement as they are also inhibited
• Rarely used now

• Inhibits conversion of pregnenalone to progesterone
• Reduces output of adrenal steroids
• Treats Cushings syndrome, hyperaldosterism, postmenopausal breast cancer

• Inhibits beta hydroxylation at C11
• Reduces output of hydrocortisone and CS
• Treats Cushings syndrome
• Also reduces -ve feedback so increases ACTH - used to test anterior pituitary function

• First 24 aa's of ACTH
• Stimulates synthesis and release of adrenal hormones
• Used to diagnose adrenal insufficiency

• Sulphonylurea
• Used to treat type II diabetes
• Stimulates insulin secretion by blocking K+ATP channels in B cells
• Require functioning B cells
• Also block other K+ATP channels e.g. vascular smooth muscle
• T1/2 = 7h
• Side effects: hypoglycaemia, stimulate appetite, drug interactions (NSAIDs, warfarin, antifungals)

• Sulphonylurea
• Used to treat type II diabetes
• Stimulates insulin secretion by blocking K+ATP channels in B cells
• Require functioning B cells
• Also block other K+ATP channels e.g. vascular smooth muscle
• T1/2 = 4h - favoured
• Side effects: hypoglycaemia, stimulate appetite, drug interactions (NSAIDs, warfarin, antifungals)

• Sulphonylurea
• Used to treat type II diabetes
• Stimulates insulin secretion by blocking K+ATP channels in B cells
• Require functioning B cells
• Also block other K+ATP channels e.g. vascular smooth muscle
• T1/2 = 36h
• Side effects: hypoglycaemia, stimulate appetite, drug interactions (NSAIDs, warfarin, antifungals)
• Inhibits alcohol metabolism

• Non-sulphonyl structures
• Treats type II diabetes
• Stimulate insulin secretion by blocking K+ATP channels in B cells
• Require functioning B cells
• Unknown if this is the same site as sulphonylureas
• Relatively selective for B cells - reduced side effects?

• Non-sulphonyl structures
• Treats type II diabetes
• Stimulate insulin secretion by blocking K+ATP channels in B cells
• Require functioning B cells
• Unknown if this is the same site as sulphonylureas
• Relatively selective for B cells - reduced side effects?

• Cannabinoid receptor antagonist
• Developed to treat obesity
• Causes increased insulin senstivity?
• Recently withdrawn

• Treats type II diabetes as adjunct
• Mimics incretin: acts through GLP-1 receptor
• - increases insulin release
• - inhibits glucagon release
• - reduces blood glucose
• Little risk of hypoglycaemia
• Given only by s/c injection

• Treats chronic hypoglycaemia
• Non-diuretic thiazide structure
• Promotes K+ATP channel opening
• - blocks insulin release
• Side effects: hypotension, reflex tachycardia

• Thioureylene
• Competitive inhibition of thyroperoxidase enzymes
• - reduce iodination of tyrosine
• - reduce T3 and T4 output
• Treats hyperthyroidism
• Slow reponse - relapse common
• Side effects; hypothyroidism, skin rash (less common than carbimazole), granulocytopenia