Pharmacology2

Diazepam

BenzodiazepineAnxiolytic/muscle relaxant/anticonvulsantBind to the alpha subunit of the GABAA receptor in the CNS - alpha-1: sedation and amnesia - alpha-2: anxiolyticEnhance activation of GABAA mediated chloride channelsLong actingLipid solubleWell absorbed orallySide effects: drowsiness, confusion, amnesia, impaired coordination, potentiate depressant effects of other drugs, tolerance and dependenceCan be used i.v. as an anticonvulsant

Buspirone

AnxiolyticPartial 5-HT1A receptor agonist - reduce 5HT synthesis/releaseNon-sedative, non-drowsyTakes several weeks to work - alteration in receptor number?Ineffective at treating acute attacksSide effects: nausea, dizziness, headache (doesnt cause sedation or drowsiness

Fluoxetine

SSRIAntidepressant/depression associated with anxiety/OCD/panic disordersLeads to receptor downregulation due to increased 5HT in synapse

Paroxetine

SSRIAntidepressant/depression associated with anxiety/OCD/panic disordersLeads to receptor downregulation due to increased 5HT in synpase

Citalopram

SSRIAntidepressant/depression associated with anxiety/OCD/panic disordersLeads to receptor downregulation due to increased 5HT in synpase

Sertaline

SSRIAntidepressant/depression associated with anxiety/OCD/panic disordersLeads to receptor downregulation due to increased 5HT in synpase

Pentobarbital

BarbiturateSleeping tabletPopular in 60'sEnhance action of GABASide effects: repiratory and CV depression on OD, induce CYP450, high degree of tolerance and dependence

Phenobarbital

BarbiturateAnticonvulsantControl of seizure by i.v. administration, ineffective in absence seizuresEnhance activation of GABAA mediated chloride channelsPlasma t1/2 = 50 - 140 hSide effects: repiratory and CV depression on OD, induce CYP450, high degree of tolerance and dependence, sedation, megaloblastic anaemia, osteomalacia

Thiopental

Barbiturate CNS depressantI.v. anaestheticEnhance action of GABAAdvantages:Very lipid soluble - rapid inductionRapid redistribution into tissues - blood concentrationd declines rapidlyRecovery within 5 minutesDisadvantages:Slowly distributes into fat - long lasting hangoverNo analgesic effectProfound cardiac and repiratory depressionNegative ionotrope - inc HR, coronary blood flow and cardiac demand, pooling of blood in peripheral veins, hypotension in hypovolaemic patientsTissue necrosis or arterial spasm - gangreneC/I in: low circulating blood vol, cardiac disease, asthma (bronchospasm)

Alprazolam

Benzodiazepine (Xanax)AnxiolyticAntidepressantBind to the alpha subunit of the GABAA receptor in the CNS - alpha-1: sedation and amnesia - alpha-2: anxiolyticMedium actingLipid solubleWell absorbed orally

Chlordiazepoxide

BenzodiazepineAnxiolytic/muscle relaxant/anticonvulsantBind to the alpha subunit of the GABAA receptor in the CNS - alpha-1: sedation and amnesia - alpha-2: anxiolyticSide effects: drowsiness, confusion, amnesia, impaired coordination, potentiate depressant effects of other drugs, tolerance and dependenceWell absorbed orallyLipid soluble, accumulate in fatLong acting

Lorazepam

BenzodiazepineHypnotic/anxiolyticBind to the alpha subunit of the GABAA receptor in the CNS - alpha-1: sedation and amnesia - alpha-2: anxiolyticShort actingSide effects: drowsiness, confusion, amnesia, impaired coordination, potentiate depressant effects of other drugs, tolerance and dependence

Oxazepam

BenzodiazepineAnxiolytic/hypnoticBind to the alpha subunit of the GABAA receptor in the CNS - alpha-1: sedation and amnesia - alpha-2: anxiolyticShort actingSide effects: drowsiness, confusion, amnesia, impaired coordination, potentiate depressant effects of other drugs, tolerance and dependence

Phenytoin

AnticonvulsantNa channel blocker: use dependent block (block inactivated state)Preferentially block cells firing repeatedly (as in seizure) normal activity not compromisedGood for partial/generalised siezures, not absence seizuresGood oral absorption80%-90% plasma protein bound (albumin)Side effects: vertigo, ataxia, headache, nystagmus(high dose) confusion, intelluctual effects, gum hyperplasia, hirsutism, acne, megaloblastic anaemiaDon't give to adolescents

Carbamazepine

AnticonvulsantNa channel blocker: use dependent block (block inactivated state)Preferentially block cells firing repeatedly (as in seizure) normal activity not compromisedEffective in most types except absence seizures, also can be used for manic depressive illnessHepatic inducerSide effects: dizziness, drowsiness, ataxia, nausea, vominting, Severe: mental and motor disturbances

Lamotrigne

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

Valproate

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

Ethosuxamide

AnticonvulsantCa channel blocker -T typeTreats absence seizures Plasma t1/2 = 50hSide effects: nausea, anorexia, lethargy, dizziness, may precipitate tonic clonic seizures in susceptible patients, rare hypersensitivity reactions

Chlorpromazine

Dopamine antagonistCan be used to treat Huntington's disease (readdress balance)Treats schizophrenia - typical antipsychoticSide effects: sedation, atropinic side effects, motor side effects

Bicuculline

GABA antagonistCNS stimulant/convulsantLab tool to model epilepsy, no clinical use

Gabapentin

AnticonvulsantMechanism not entirely clearMay block calcium channel - L type contriubuting factor, not main drug actionMay bind to amino acid transporterTreats seizures - adjunctive therapyPlasma t1/2 = 6hRelatively free from side effects

Strychnine

Antagonist at glycine receptors on motorneuronesCause skeletal mucle spasm

Tubocurarine

Blocks post synaptic ACh receptors

Memantine

Treats Alzheimers diseaseBlock NMDA glutamate receptor

Selegiline

MAO-B inhibitorPrevents dopamine metabolism and so increases the half life of dopamine derived from L-dopa in the CNSNo peripheral inhibition of MAO-A - no cheese reaction

Aspirin

Antipyretic analgesicIrreversible COX inhibitorReduced PG production, "thermostat" back to normalSide effects: GIT upset, bronchoconstriction, bleeding problems, Reyes syndromeHigh dose side effects: CNS stimulation -> hyperventilation -> decreased PCO2 -> respiratory alkalosis, disturbance of cellular metabolism -> increased lactic/ketoacids -> metabolic acidosis

Paracetamol

Antipyretic analgesicReversible, non-competitive COX-3 (CNS isoenzyme) inhibitorNot anti-inflammatoryReduced PG production, "thermostat" back to normalAnalgesic and antipyretic effect equivalent to aspirinRegarded as safer, no gastric damage, haemorrhage, or bronchospasm

Ibuprofen

Antipyretic analgesicReversible, competitive COX inhibitorReduced PG production, "thermostat" back to normal

Nitrous Oxide

Inhaled anaestheticAdvantages:Excellent analgesiaNon flammableRapid onset and recoveryLittle or no toxicityUse as adjunct to other inhalation agents to reduce their doseDisadvantages:No skeletal muscle relaxationWeak anaesthetic - not suitable as sole agentAir pockets in closed spaces expand - "bends"Post-anaesthetic hypoxia - dilutes o2 in lungs for a few minutes - flush out with o2 at end of anaesthesiaMethionine synthase inactivation (prolonged/repeat exposure) - inhibits DNA and protein synthesis, megaloblastic anaemia and leucopoeniaFoetal abnormalities/spontaneous abortion - theatre staff

Halothane

Inhaled anaestheticWidely used in paediatricsAdvantages:Non flammablePotent and high oil:gas partition coefficientRapid inductionRapid recoveryControlled hypotension to limit bleedingNon-irritantFew post-op effectsDisadvantages:Doesn't provide adequate analgesiaMay not provide adequate muscle relaxationVasodilator and cardiac depressant -> myocardial depressionHighly potent so easy to over anaesthetiseSensitises heart to adrenaline - cardiac dysrhythmias (avoid beta blockers and adrenaline)Respiratory depressionHepatotoxic if repeated exposure (3 months between exposures)Malignant hyperthermia

Desflurane

Inhaled anaestheticAdvantages:Low solubility in bloodMinimal systemic effectsMinimal metabolismFew side effectsDisadvantages:ExpensiveSome respiratory tract irritation

Propofol

I.v. anaestheticAdvantages: Rapid metabolism, rapid recovery, no hangover Can be continuously infused to maintain anaesthesiaNone of the effects of epotomidateDisadvantages:Rapid metabolism, short duration of actionNot water soluble, painful injection

Atropine

Muscarinic antagonist (competative)

Hyosine

Muscarinic antagonistUsed for treatment/prevention of motion sicknessLess effective after onsetIneffective against substances acting directly on CTZSide effects: dizziness, dry mouth, blurred vision

Papaveretum

Opioid analgesicMixture

Propranolol

Beta blockerCan be used to treat hyperthyroidismDecreases symptoms, but patient still hyperthyroid biochemicallyUsed prior to surgery, in treatment with thyrotoxic crisis, initially with carbimazole, following radiation

Flumazenil

Benzodiazepine antagonistCompetitive inhibition at the benzodiazepine binding site on the GABAA receptor

Flupentixol

Typical antipsychoticThioxanthineAntagonist at various dopamine (D1-D5), serotonin (5-HT2), adrenaline (?1), and histamine (H1) receptors, without affecting the muscarinic acetylcholine receptorsSide effects: slight sedation, slight atropinic side effects, pronounced motor effects

Fluphenazine

Typical antipsychoticPiperazine

Theobromine

MethylxanthineEffects: stimulate cardiac and skeletal muscle, relax smooth muscle, induce diuresis, offset fatigue, reduce reaction timeLeast potentAntagonism at adenosine (A2) receptorsInhibition of phosphodiesteraseMobilization of intracellular calcium

Theophylline

MethylxanthineEffects: stimulate cardiac and skeletal muscle, relax smooth muscle, induce diuresis, offset fatigue, reduce reaction timeMiddle potentAntagonism at adenosine (A2) receptorsInhibition of phosphodiesteraseMobilization of intracellular calcium

Thymidine

DNA nucleoside

Tryptophan

Can be used in depressionPre-cursor for 5HTPotentiates effect of MAOI's Limited use: adjunct in mild/moderate depression

Tyramine

MonoamineResponsible for Cheese reaction with MAOI's

Tyrosine

Amino acid

Lithium carbonate

AntidepressantControls both depression and mania, so drug of choice for bi-polarDisplaces Na ionsAffects inositol phosphate inhibits conversion from IP1 to inositolHas other effectsSide effects: tremor, mental confusion, sinus node toxicity, polydipsia, polyuriaNarrow TI - levels need monitoring

Acarbose

Treats type II diabetesInhibits alpha glucosidase enzymes which turn complex carbohydrates into glucoseReduces glucose available for absorptionNo hypoglycaemiaNo weight gain

Pioglitazone

Treats type II diabetesActivates nuclear receptor - PPARyReceptor binds to DNA - increases gene transcriptionIncrease plasmalemmal glucose transporters - increase muscle glucose uptakeReduce liver glucose outputIncreases lipogenesis, uptake of fatty acids Overall effect increases sensitivity to insulinSlow onset - 1-2 monthsNo increased risk of hypoglycaemiaAlmost unique metabolic pathway - CYP2C8Rare reports of liver toxicity - monitor

Rosiglitazone

Treats type II diabetesActivates nuclear receptor - PPARyReceptor binds to DNA - increases gene transcriptionIncrease plasmalemmal glucose transporters - increase muscle glucose uptakeReduce liver glucose outputIncreases lipogenesis, uptake of fatty acids Overall effect increases sensitivity to insulinSlow onset - 1-2 monthsNo increased risk of hypoglycaemiaAlmost unique metabolic pathway - CYP2C8Rare reports of liver toxicity - monitor

Metformin

Treats type II diabetesMechanism unclear- receptor sensitivity?- peripheral glucose uptake?- liver glucose productionRequires insulin presenceDoes not promote insulin release - no risk of hypoglycaemia

Sitagliptin

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

Glibenclamide

SulphonylureaUsed to treat type II diabetesStimulates insulin secretion by blocking K+ATP channels in B cellsRequire functioning B cellsAlso block other K+ATP channels e.g. vascular smooth muscleT1/2 = 12Side effects: hypoglycaemia, stimulate appetite, drug interactions (NSAIDs, warfarin, antifungals)

Disulfiram

AntabuseBlocks the enzyme acetaldehyde dehydrogenase

Levodopa

Treatment of Parkinson's DiseaseUsed because dopamine cannot cross BBBMetabolised to dopamine in CNSAlso in periphery - side effects and reduction in LDOPA in brain

Domperidone

D2 receptor antagonistDoes cross BBBReduced side effectsSide effects: migraine

Nabilone

Cannabinoid antiemeticTreats vomiting caused by cytotoxic anticancer drugs (also as adjuvant for neuropathic pain)Effective against substances which stimulate the CTZThought to act via opioid receptors in the CTZSometimes effective where other treatment has failedSide effects: drowsiness, dizziness, dry mouth, modd changes, postural hypotension, hallucinations, psychotic reactions

Ondansetron

5HT3 receptor antagonistUsed for nausea and vomiting caused by cytotoxic anticancer drugs, post-op vominting and radiation induced vomitingPrimary site of action is on the CTZSide effects: headache, GI upset

Promethazine

H1 receptor antagonist

Clomiphene

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

Levonorgestrel

Morning after pillMechanism unclear- delays ovulation?- prevents implantation?- inhibition of sperm transport?

Mestranol

Estrogen combined oral contraceptiveNeed high dose if used alone

Mifepristone

Termination of pregnancyProgesterone antagonist- progesterone receptor/antagonist complex binds DNA and recruit corepressorsUsed for medical terminations in 1st trimester

Tamoxifen

SERMBinds Estrogen receptor - partial agonistTreats breast cancer

Iodine

Treats hyperthyroidismRapid effect, not sustainedInhibits peroxide generation?Inhibits iodination?Decreases size and vascularity of glandUsed prior to surgery, treatment of thyrotoxic crisisAllergic responses possible

Propylthiouracil

ThioureyleneCompetitive inhibition of thyroperoxidase enzymes- reduce iodination of tyrosine- reduce T3 and T4 outputTreats hyperthyroidismSlow reponse - relapse commonSide effects; hypothyroidism, skin rash (less common than carbimazole), granulocytopenia

Galantamine

Reversible inhibitor of acetylcholinesteraseUsed to treat dementia

Glycine

Inhibitory CNS transmitterFound mostly in spinal cordDerived from serine by action of SMHTInactivated by uptake and metabolismACh released by a collateral of the alpha motor neurone which acts on nicotinic receptors of the Renshaw cell to cause glycine releaseModulates contraction of skeletal muscle by providing a negative feedback loop by acting on receptor at alpha motor neurone causing hyperpolarisation

GABA

Main inhibitory transmitter in the brainWidespread distributionSynthesised from glutamate by GADInactivated by active uptakeGABA transaminase converts GABA to succinic semialdehyde (glutamate formed in process)Facilitates entry of chloride ions into neurones, resulting in hyperpolarisation (neurone depression)

Glutamate

Main excitatory transmitter in CNSWidely and uniformly located in CNSFormed from alpha-oxoglutarate (Krebs cycle) by GABA-aminotransferaseInactivated by active uptakeActions exerted via receptors

Haloperidol

Dopamine antagonistCan be used to treat Huntington's disease (readdress balance between dopamine and GABA)Treats schizoprenia - typical antipsychotic

Raloxifene

SERMBinds Estrogen receptorTreats breast cancer

Tetanus toxin

Inhibits glycine releaseCauses uncontrollable muscle spasm

GABA A receptors

Ligand gated ion channelPentamer structure with alpha, beta and gamma subunitsLocated post-synapticallyActivation opens Cl- channels which reduced membrane excitabilitySeveral binding sites (barbiturates, benzodiazepines, GABA)

GABA B receptors

G protein coupled receptorLinked to adenylyl cyclaseInhibit cAMP formationLocated pre and post synaptically (results in pre and post synaptic inhibition)Prevents Ca2+ channel openingIncreases K+ permeability

Ionotropic Glutamate receptors

ligand gated cation channelsNamed after specific agonists (NMDA, AMPA and kainate)Pentameric structureNMDA and AMPA are post-synapticKainate is pre and post synapticNMDA and possibly AMPA have modulatory sites (glycine binds to NMDA)Cause slow (NMDA) or fast (AMPA) EPSP

NMDA receptor

Highly permeable to Ca2+Blocked by Mg2+Blocked by some anaesthetics (ketamine)Blocked by some psychomimetics (phencyclidine)

Metabotropic receptors

G protein coupled receptorNo homology with other GPCRlinked to intracellular second messenger systems (phospholipase C) which result in IP3 production and release of Ca2+

Acetylcholine

Widely distributed in CNS - cortex, basal ganglia, brainstem, spinal cordMain excitatory actionInactivated by acetylcholinesterases

Nicotinic receptors

Ligand gated ion channelsPentamericalpha and beta subunitspre-synapticfacilitate release of other transmitters (glutamate and dopamine)activated by acetylcholine

Muscarinic receptors

GPCRM1 classactivate phospholipase C

Donepezil

Reversible inhibitor of acetylcholinesteraseUsed in treatment of dementia

Rivastigmine

Reversible inhibitor of acetylcholinesteraseUsed in treatment of dementia

Noradrenaline in CNS

Synthesis, storage, release, inactivation as in PNSMainly inhibitory via beta, but some excitatory via alpha and betaInvolved in blood pressure regulationImportant in mood, arousal and reward pathways

Serotonin in the CNS

Derived from tryptophan (diet)Similar pathway to NA - tryptophan dehydroxylase, NH2 acid decarboxylaseInactivated by uptake and metabolism by MAO, aldehyde dehydrogenaseRoles in: hallucinations, behaviour, sleep, wakefulness, body temperature, sensory pathways, vomiting (5HT3), mood, emotion

Serotonin receptors

7 subtypesAll GPCR except 5HT3 which is a ligand gated ion channel5HT1,2,3 appear to be the most important in CNS1. linked to cAMP (inhibitorys)2. linked to IP3/DAG (excitatory)3. excitatory

Dopamine

Synthesis via dopamine beta-hydroxylaseTyrosine 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 HVAFound in nigrostrital pathway (motor control), mesolimbic/mesocortical (behavioural effects) pathway, tubero-hypophyseal (endocrine) pathway

Dopamine receptors

Two types:D1 type (D1 and D5)GPCR linked to adenylyl cyclaseincrease cAMPMainly post-synaptic inhibitionD2 type (D2, D3, D4)GPCR linked to adenylyl cyclaseDecrease cAMPpre and post synaptic inhibitionMediate most known CNS functions of DA

Entacapone

COMT inhibitorCo administered with L-DOPA to reduce peripheral DOPA metabolism to treat Parkinsons

Carbidopa

Peripheral dopa decarboxylase inhibitorPrevents conversion of L-dopa to dopamine in peripheral tissuesDo not cross BBBReduces peripheral side effects and increases L-dopa dose getting into the brain

Benserazide

Peripheral dopa decarboxylase inhibitorPrevents conversion of L-dopa to dopamine in peripheral tissuesDo not cross BBBReduces peripheral side effects and increases L-dopa dose getting into the brain

Pergolide

Ergot derivative dopamine agonistAct directly at D2 receptorsCan be used in the treatment of Parkinson'sCause nausea (action at CTZ) - reduce by administration of domperidone

Bromocriptine

Ergot derivative dopamine agonistAct directly at D2 receptorsCan be used in the treatment of Parkinson'sCause nausea (action at CTZ) - reduce by administration of domperidone

Cabergolide

Ergot derivative dopamine agonistAct directly at D2 receptorsCan be used in the treatment of Parkinson'sCause nausea (action at CTZ) - reduce by administration of domperidone

Lisuride

Ergot derivative dopamine agonistAct directly at D2 receptorsCan be used in the treatment of Parkinson'sCause nausea (action at CTZ) - reduce by administration of domperidone

Pramipexol

Dopamine agonistNon-ergot derivativeAct directly at D2 receptorsTreats Parkinson'sCause nausea (action at CTZ) - reduce by administration of domperidone

Ropinirole

Dopamine agonistNon-ergot derivativeAct directly at D2 receptorsTreats Parkinson'sCause nausea (action at CTZ) - reduce by administration of domperidone

Apomorphine

Dopamine agonistNon-ergot derivativeAct directly at D2 receptorsCause nausea (action at CTZ) - reduce by administration of domperidoneTreats Parkinson's

Amantadine

Anti-viral drugHowever also has weak anti-Parkinson's actionMechanism unclear;Increase dopamine release?Inhibit dopamine uptake?Agonis activity at D2 receptors?

Benzatropine

Muscarinic antagonistTreats Parkinson'sMore effective against tremor than hypokinesiaAntimuscarinic side effects due to peripherally blocked muscarinic receptorsWorsen signs of dementia - C/I

Orphenadrine

Muscarinic antagonistTreats Parkinson'sMore effective against tremor than hypokinesiaAntimuscarinic side effects due to peripherally blocked muscarinic receptorsWorsen signs of dementia - C/I

Tetrabenazine

Treats Huntington'sMechanism unclear - depletes dopamine to readdress balance?

Baclofen

GABA B agonistTreats Huntington's

Enflurane

Inhaled anaestheticAdvantages:StableNon flammablePotency/induction similar to halothaneDisadvantages:Dose related depression of myocardial contractilityProduces fluoride ions - renal toxicityLowers threshold for seizuresKnown to cause malignant hypothermia

Isoflurane

Inhaled anaestheticWidely usedAdvantages:No metabolism - little toxicityNot pro-convulsiveExcellent muscle relaxantDisadvantages:Expensive HypotensionCoronary vasodilator

Sevoflurane

Inhaled anaestheticAdvantages:More potent then desfluraneLess respiratory irritationDisadvantages:ExpensivePartially metabolised

Etomidate

I.v. anaestheticGABA receptor agonist - CNS depressantInduction agent onlyDisadvantages:No analgesic activityMild dose related respiratory depressionDecreased cerebral metabolismPain on injection (propylene glycol)Myoclonic activityCortisol suppressionPost-op nausea and vomitingFavoured over thiopental - large margin between anaesthetic dose and resp/CV depression also faster metabolism, less hungover

Triazolam

BenzodiazepineAnxiolyticBind to the alpha subunit of the GABAA receptor in the CNS - alpha-1: sedation and amnesia - alpha-2: anxiolyticUltra short actingLipid solubleWell absorbed orallySide effects: drowsiness, confusion, amnesia, impaired coordination,potentiate depressant effects of other drugs, tolerance and dependence

Midazolam

BenzodiazepineAnxiolyticBind to the alpha subunit of the GABAA receptor in the CNS - alpha-1: sedation and amnesia - alpha-2: anxiolyticUltra short actingLipid solubleWell absorbed orallySide effects: drowsiness, confusion, amnesia, impaired coordination,potentiate depressant effects of other drugs, tolerance and dependenceCan be used i.v. in anaesthesia

Zolpidem

BenzodiazepineHypnoticBind to the alpha subunit of the GABAA receptor in the CNS - alpha-1: sedation and amnesia - alpha-2: anxiolyticUltra short actingLipid solubleWell absorbed orallySide effects: drowsiness, confusion, amnesia, impaired coordination,potentiate depressant effects of other drugs, tolerance and dependence

Temazepam

BenzodiazepineAnxiolytic/hypnoticBind to the alpha subunit of the GABAA receptor in the CNS - alpha-1: sedation and amnesia - alpha-2: anxiolyticShort actingLipid solubleWell absorbed orallySide effects: drowsiness, confusion, amnesia, impaired coordination,potentiate depressant effects of other drugs, tolerance and dependence

Lometazepam

BenzodiazepineAnxiolytic/hypnoticBind to the alpha subunit of the GABAA receptor in the CNS - alpha-1: sedation and amnesia - alpha-2: anxiolyticShort actingLipid solubleWell absorbed orallySide effects: drowsiness, confusion, amnesia, impaired coordination,potentiate depressant effects of other drugs, tolerance and dependence

Nitrazepam

BenzodiazepineAnxiolytic/hypnoticBind to the alpha subunit of the GABAA receptor in the CNS - alpha-1: sedation and amnesia - alpha-2: anxiolyticMedium actingLipid solubleWell absorbed orallySide effects: drowsiness, confusion, amnesia, impaired coordination,potentiate depressant effects of other drugs, tolerance and dependence

Flurazepam

BenzodiazepineAnxiolyticBind to the alpha subunit of the GABAA receptor in the CNS - alpha-1: sedation and amnesia - alpha-2: anxiolyticLong actingLipid solubleWell absorbed orallySide effects: drowsiness, confusion, amnesia, impaired coordination,potentiate depressant effects of other drugs, tolerance and dependence

Clonazepam

BenzodiazepineAnxiolytic/anticonvulsantBind to the alpha subunit of the GABAA receptor in the CNS - alpha-1: sedation and amnesia - alpha-2: anxiolyticLong actingLipid solubleWell absorbed orallySide effects: drowsiness, confusion, amnesia, impaired coordination,potentiate depressant effects of other drugs, tolerance and dependence

Tiagabine

AnticonvulsantEnhances GABA action by inhibiting uptake - GABA analogueAdjunctive therapy for partial seizuresEffective in patients resistant to established drugsSide effects: drowsiness, confusion

Vigabatrin

AnticonvulsantEnhances GABA action by irreversibly inhibiting GABA transaminase (breakdown to succinic semialdehyde)Increases GABA and inhibitory transmissionTreats simple complex generalised, tonic clonic seizures1st "designer" epilepsy drugShort plasma t1/2 but long lasting effectSide effects: rare - depression and psychotic disturbances

Pregabalin

Pro-drugSimilar to gabapentin but less side effectsMechanism not clearMay block Ca channelMay bind to amino acid transporter

Ozcarbamazepine

Pro-drugAnticonvulsantMetabolised to a compound sinilar to carbamazepineNa channel blocker

Amphetamine

StimulantDisplaces vesicular monoamine while inhibiting MAO and monoamine reuptakeIndirect receptor activationEffects: vasoconstriction, mydriasis, inhibition of GIT and urinary bladder, alertness, increased motor activity, anorexia, anxiety (due to overstimulation of brain)

Fenfluramine

Weight loss drugAmphetamineDid not produce CNS side effectsWithdrawn due to cardiac effects

Dexamphetamine

AmphetamineTreats hyperkinesia and narcolepsy

Methylphenidate

RitalinAmphetamineTreats hyperkinesis and narcolepsy

Picrotoxin

GABA antagonistCNS stimulant/convulsantLab to model epilepsyNo clinical use

Doxapram

AnalepticPreviously used to treat drug induced repiratory depressionCNS mechanism unknownPeripheral mechanism, only one still used

Bemeglide

AnalepticPreviously used to treat drug induced repiratory depressionCNS mechanism unknownNo longer used

Nikethamide

AnalepticPreviously used to treat drug induced repiratory depressionCNS mechanism unknownNo longer used

Caffeine

MethylxanthineEffects: stimulate cardiac and skeletal muscle, relax smooth muscle, induce diuresis, offset fatigue, reduce reaction timeMost potentAntagonism at adenosine (A2) receptorsInhibition of phosphodiesteraseMobilization of intracellular calcium

Haloperidol

Typical antipsychoticButyrophenoneAntagonism at dopamine receptors, 5HT and histamine receptorsPronounced motor effects

Pimozide

Atypical antipsychoticDiphenylbutylpiperidine

Thioridazine

Atypical antipsychoticPhenothiazines piperidines

Clozapine

Atypical antipsychoticLower chance of extrapyridamol side effectsMechanism uncertainD1 D2 5HT2 H1 ACh alpha-2 receptors blockedPotentially fatal haematological side effects

Risperidone

Atypical antipsychoticLower chance of extrapyridamol side effectsMechanism uncertainD1 D2 5HT2 H1 ACh alpha-2 receptors blocked

Olanzapine

Atypical antipsychoticLower chance of extrapyridamol side effectsMechanism uncertainD1 D2 5HT2 H1 ACh alpha-2 receptors blocked

Sertindole

Atypical antipsychoticLower chance of extrapyridamol side effectsMechanism uncertainD1 D2 5HT2 H1 ACh alpha-2 receptors blocked

Zotepine

Atypical antipsychoticLower chance of extrapyridamol side effectsMechanism uncertainD1 D2 5HT2 H1 ACh alpha-2 receptors blocked

Phenelzine

MAOIIrreversible inhibitorIndicated in psychotic and neurotic depressionTake over 3 weeks to workLimited useSide effects: convulsions, excitement (related to amphetamine), hepatoxiicity, pyrexia, hypertensive crisis i.e. cheese reaction

Tranylcypromine

MAOISlowly reversible inhibitorIndicated in psychotic and neurotic depressionTake over 3 weeks to workLimited useSide effects: convulsions, excitement (related to amphetamine), hepatoxiicity, pyrexia, hypertensive crisis i.e. cheese reaction

Moclobemide

MAOIReversible inhibitorIndicated in psychotic and neurotic depressionTake over 3 weeks to workLimited useSide effects: convulsions, excitement (related to amphetamine), hepatoxiicity, pyrexia, hypertensive crisis i.e. cheese reaction

Amitrypyline

Monoamine uptake inhibitorTricyclic antidepressantAntidepressant drug of choice2-4 weeks to workInhibits NA and 5HT uptakeAntagonist at muscarininc receptors - dry mouth, blurred vision, urinary retention, arrhythmias, tachycardia, syncope

Iprindole

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

Pethidine

Opioid analgesicAgonist at opioid receptorsMore convulsions (metabolite norpethidine)Not dependent on glucuronide conjugation metabolism

Morphine

Opioid analgesicLong duration of effect

Fentanyl

Opioid analgesicOpioid receptor agonistShort duration of actionSide effects: cough suppression

Codeine

Opioid analgesicOpioid receptor agonistWeaker activity than morphineMore nausea

Heroin

Opioid analgesicOpioid receptor agonistMore analgesic activity than morphine and faster onset of actionShort duration

Naloxone

Competitive antagonist at all 3 opioid receptorsUsed to treat drug induced respiratory depressionShort actionPrecipitate withdrawal

Buprenorphone

Opioid analgesicReduced abuse potentialPartial agonist at MuKappa antagonismWithdrawal less intense than morphineRespiratory depression not fully reversed by naloxoneAnalgesic and in management of dependenceSide effects: sedative, marked nausea and vomiting

Pentazocine

Opioid analgestic with reduced abuse potentialLimited respiratory depressionMu antagonistKappa agonistSigma agonistProlonged use gives dependence

Pholcodine

Cough suppressantStructurally related to opioids - large substituent added at 3 positionLittle analgesic effectAction at CNS cough centre, via mu and delta receptors?

Dextromethorphan

Cough suppressantStructurally related to opioids - large substituent added at 3 positionNo analgesic effectNot blocked by opioid antagonistsAction at CNS cough centre, via mu and delta receptors?Has non opioid binding sites

Meptazinol

Opioid analgesicMu1 selective agonistLess respiratory depression than other opioids

Apomorphine

Dopamine agonistStructurally similar to morphine, causes emesis without other opioid actionsUsed in Parkinson's

Nalorphine

Opioid analgesic with lower abuse potentialNot used clinically - dysphoriaMu antagonistDelta kappa partial agonistSigma agonist

Cyclizine

Histamine H1 receptor antagonistUsed in prevention/treatment of motion sicknessIneffective against substances acting directly on CTZSide efffects: drowsiness and sedation

Cinnarizine

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

Chloropromazine

D2 receptor antagonistTreats nausea and vomiting associated with cancer treatment, radiation therapy, cytotoxics, opioids, post-op nausea, severe morning sicknessPass BBBAlso block histamine and mACh receptorsEffective after vomiting onsetSide effects: sedation, hypotension, dystonia, dyskinesia

Perphenazine

D2 receptor antagonistTreats nausea and vomiting associated with cancer treatment, radiationtherapy, cytotoxics, opioids, post-op nausea, severe morning sicknessPass BBBAlso block histamine and mACh receptorsEffective after vomiting onsetSide effects: sedation, hypotension, dystonia, dyskinesia

Trifluoroperazine

D2 receptor antagonistTreats nausea and vomiting associated with cancer treatment, radiationtherapy, cytotoxics, opioids, post-op nausea, severe morning sicknessTypical antipsychoticPhenothiazine piperidinePass BBBAlso block histamine and mACh receptorsEffective after vomiting onsetSide effects: sedation, hypotension, dystonia, dyskinesia

Metoclopramide

D2 receptor antagonistPasses BBBActs on DA receptors throughout CNSAlso peripheral prokinetics2nd line treatment for severe morning sicknessSide effects: movement disorder, fatigue, motor restlessness, spasmodic torticolis, occulogyric crisis, menstruation disorder, diarrhoea

Dexamethasone

SteroidGlucocorticoidLong actingTreats vomiting caused by cytotoxicsUnknown mechanismUsed in combo with D2 or 5HT3 receptor antagonists

Neuronkinin-1-antagonist

Substance P antagonistTreats vomiting caused by cytotoxics/post-op NVSide effects: hiccuping, fatigue, listlessness, constipation/diarrhoea, loss of appetite, dizziness, ringing in ears

Hydrocortisone

Natural steroidSynthesised from cholesterolControl of synthesis and release via hypothalamus, anterior pituitary and negative feedbackShows both glucocorticoid and mineralocorticoid actionEnzyme in kidneys etc converts these to mineralo-inactive compoundsShort actingUsed for replacement therapy in adrenal failure - few side effects as natural situation mimicked, and for anti-inflammatory/immunosuppressant actionsSide 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)

Prednisolone

Synthetic steroidMixed gluco-/mineralocorticoid actionMedium actingUsed for asthmaSide 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 toacute adrenal failure)

Betamethasone

Synthetic steroidGlucocorticoidLong actingSide 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 toacute adrenal failure)

Beclomethasone

Synthetic steroidGlucocorticoidLong actingUsed for asthmaSide 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 toacute adrenal failure)

Budesonide

Synthetic steroidGlucocorticoidUsed for asthmaSide 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 toacute adrenal failure)

Fludrocortisone

SteroidMainly mineralocorticoidShort actingSide 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 toacute adrenal failure)

Aminoglutethimide

Cancer drugInhibits conversion of cholesterol to pregnenoloneReduces adrenal output of androgens/oestrogensUsed for post-menopausal breast cancer and prostate cancerRequire corticosteroid replacement as they are also inhibitedRarely used now

Trilostane

Inhibits conversion of pregnenalone to progesteroneReduces output of adrenal steroidsTreats Cushings syndrome, hyperaldosterism, postmenopausal breast cancer

Metyrapone

Inhibits beta hydroxylation at C11Reduces output of hydrocortisone and CSTreats Cushings syndromeAlso reduces -ve feedback so increases ACTH - used to test anterior pituitary function

Tetracosatrin/tetracosatride

First 24 aa's of ACTHStimulates synthesis and release of adrenal hormonesUsed to diagnose adrenal insufficiency

Gliclazide

SulphonylureaUsed to treat type II diabetesStimulates insulin secretion by blocking K+ATP channels in B cellsRequire functioning B cellsAlso block other K+ATP channels e.g. vascular smooth muscleT1/2 = 7hSide effects: hypoglycaemia, stimulate appetite, drug interactions (NSAIDs, warfarin, antifungals)

Tolbutamide

SulphonylureaUsed to treat type II diabetesStimulates insulin secretion by blocking K+ATP channels in B cellsRequire functioning B cellsAlso block other K+ATP channels e.g. vascular smooth muscleT1/2 = 4h - favouredSide effects: hypoglycaemia, stimulate appetite, drug interactions (NSAIDs, warfarin, antifungals)

Chlorpropamide

SulphonylureaUsed to treat type II diabetesStimulates insulin secretion by blocking K+ATP channels in B cellsRequire functioning B cellsAlso block other K+ATP channels e.g. vascular smooth muscleT1/2 = 36hSide effects: hypoglycaemia, stimulate appetite, drug interactions (NSAIDs, warfarin, antifungals)Inhibits alcohol metabolism

Repaglinide

Non-sulphonyl structuresTreats type II diabetesStimulate insulin secretion by blocking K+ATP channels in B cellsRequire functioning B cellsUnknown if this is the same site as sulphonylureasRelatively selective for B cells - reduced side effects?

Nateglinide

Non-sulphonyl structuresTreats type II diabetesStimulate insulin secretion by blocking K+ATP channels in B cellsRequire functioning B cellsUnknown if this is the same site as sulphonylureasRelatively selective for B cells - reduced side effects?

Rimonobant

Cannabinoid receptor antagonistDeveloped to treat obesityCauses increased insulin senstivity?Recently withdrawn

Exenatide

Treats type II diabetes as adjunctMimics incretin: acts through GLP-1 receptor- increases insulin release- inhibits glucagon release- reduces blood glucoseLittle risk of hypoglycaemiaGiven only by s/c injection

Diazoxide

Treats chronic hypoglycaemiaNon-diuretic thiazide structurePromotes K+ATP channel opening- blocks insulin releaseSide effects: hypotension, reflex tachycardia

Carbimazole

ThioureyleneCompetitive inhibition of thyroperoxidase enzymes- reduce iodination of tyrosine- reduce T3 and T4 outputTreats hyperthyroidismSlow reponse - relapse commonSide effects; hypothyroidism, skin rash (less common than carbimazole), granulocytopenia