Drug Class

Drug Name
Enalapril, Captopril

MOA
- block conversion of angiotensin I to angiotensin II - block degradation of bradykinin - blockage of ATII reduction in vasoconstriction, Na+ retention and aldosterone release - AT1 receptors constriction - AT2 receptors vasodilation - blocks AT1 block vasoconstriction, block aldosterone release and Na+ reabsorption, bradykinin breakdown not inhibited - mech 1: diuretic that decrease blood vol and TPR - mech 2: decrease TPR by modulating activity of K+ channels in arterioles

Uses

Side Effects
- first dose effect steep fall in BP (susceptible to volume depleted patients - hyperkalaemia - dry cough - oedema - taste disturbance - dizziness - headache - hyperkalaemia - first dose hypotension - Li+ toxicity - hypokalaemia - metabolic alkalosis - dizziness, weakness, muscle cramps, hypotension, hypercalcaemia - hypercalcaemia - hyperuricaemia - adverse lipid profile effect -erectile dysfunction

Miscellaneous info
- need to stop K+ supplements - temp stop of diuretics - start therapy on low dose - check renal function C/I pregnancy and renal artery stenosis - interact with diuretics, NSAIDs, Li+ toxicity risks - K+ sparing diuretics may increase risk of hyperkalaemia - thiazides plateau in BP treatment i.e. increasing thiazide dose beyond threshold will not change BP but side effects will continue to increase - thiazide and ACEI have additive effects

Anti-hypertensives
- anti-hypertension - recomm. For patients with heart failure and for diabetics with proteinuria

ACEI (-pril)

ATII receptor antags (sartan)

Losartan, Irbesartan, Candesartan, Telmisartan Bendrofluazide, Hydrochlorthiazid e

- anti hypertensives - better than ACEI due to selectivity for AT1 as ACEI stops AT production hence not ATII action - anti-hypertensive

Thiazides

K+ sparing diuretics

Amiloride Triamterene (both avail in combo with hydrochlorothiazi de) Spironolactone

- block Na+ channels in distal tubules no Na+/K+ exchange K+ excretion reduced

- anti-hypertensive

Aldosterone antag Propranolol and Metopolol both lipid soluble Atenolol less lipid soluble Carvedilol mixed 1 blocking ability Dihydropyridines : nifedipine, amlodipine, Benzothiazepines : diltiazem Phenylalkylamine s: verapamil

- aldosterone antagonist - competes with aldosterone for receptors in distal tubule

- anti-hypertensive

-blockers (olol)

- acts on 1 - -ve inotropic and chronotropic effects decrease CO and HR - acts in CNS to decrease sym outflow - reduce renin production in kidney - blocks pre-synaptic which would facilitate NA release to decrease BP - block Ca2+ channel relax vascular SMM decrease peripheral vascular resistance decrease BP - dihydropyridines: most vascular selective - benzothiazepines: acts on cardiac + vascular SMM - phenylalkylamines: greater cardiac effects

- anti-hypertensive vasodilation

- endocrine adverse effect gynecomastia, menstural abnormalities - due to aldosterone being secreted from adrenal cortex - heart failure - bradycardia - bronchospasm - peripheral vascular disease - CNS effects (lipid soluble) i.e. dizziness, nightmares, depression

Ca2+ blocker (dipine)

- for cardiac decompensation - cardiac decompensation: inability of heart to maintain adequate circulation

- headache - flushing - postural hypotension - chest pain due to HR increase to compensate for sudden drop in BP - bleeding gums - oedema

- no reflex increase in peripheral vascular resistance - C/I in asthmatics, heart block, peripheral vascular disease, hyperlipidaemia, diabetes - effective for Caucasians, myocardial infarct, ischaemia, angina, phaechromocytoma - can be sued in combo with blocker to prevent reflex tachycardia - not good for Africans - patients with diabetes or hyperlipidaemia no metabolic effects

Drug Class

Drug Name

MOA

Uses

Side Effects

Miscellaneous info

1 selective blockers

Doxazosin, Prazosin, Terazosin

- block 1 post synaptic in arteries and veins vasodilation decrease peripheral vascular resistance - does not block 2 feedback inhibition of NA can still occur reflex tachycardia unlikely to occur - H1 receptors contraction of gut and airways; vasodilation

- asthmatics - patients with peripheral vascular disease, hyperlipidaemia, prostate symptoms, impotence

dizziness postural hypotension nasal congestion headaches weakness, fatigue, drowsiness stress incontinence in women

- first dose hypotension - withhold diuretic before starting blocker

Autacoids
H1 antag Mepyramine, terfenidine, fexofenadine, loratadine, promethazine Cimetidine, Ranitidine, famotidine, nizatidine Buspirone (5HT1A) Sumatriptan (5HT1B/D) - sedative: from histaminergic neurones from hypothalamus - atropinic effects - anti-emetic effect through vomiting centre - peptic ulcer - non-sedating anti-his have potentially fatal tachycardia - terf, fexo and lora nonsedating anti-histamine dont pass BBB

H2 antag

- competitive antag - inhibit ACh, gastrin and histamine induced acid secretion - decreases 5-HT from tryptaminergic nerves by action on auto-receptor - abnormal discharge from brainstem causes 5HT release transgeminal nerve activation SP release vasodilation and oedema of blood vessels - sumatriptan acts directly on blood vessels to cause constriction

- reduce anxiety - decrease aggression - migraine - cerebral vasoconstrictor

5-HT agonist

- dizziness, flushing, weakness, fatigue - maybe nausea and vomiting - pain or sensations may be caused by vasospasms

- non-sedating - no addictive effects

Ketanserin (5HT2A) Mianserin (5HT2C) Ondansetron (5HT3) Cisapride/ metoclopramide (5-HT4) Alprosadil (PGE1) Prostin E2 (PGE2) Prostin F2 (PGF2 salt) Prostin VR (PGE1) Misoprostol (PGE1) - cytoprotective action protect gut lining - decrease acid secretion

- anti-hypertensive -research only - anti-hypertensive - passes BBB - anti-emetic - adjunct to chemo

5-HT antag

- GI stimulant (transit); Metoclopramide (5-HT agonist) gastrointestinal motility Antiemetic (5-HT antagonist) - general vasodilator for SMM - erectile dysfunction - ripen cervix and induce labour - therapeutic abortion - dilation of ductus arteriosus in neonates (heart problems) - protection against NSAID gastric damage/peptic ulcer

PGs

- diarrhoea

Drug Class

Drug Name

MOA

Uses

Side Effects

Miscellaneous info

SAIDs

NSAIDs

Aspirin, indomethacin, ibuprofen

- induce formation of lipocortin decrease phospholipase A - phospholipase A required to make arachidonic acid - arachidonic acid acted on by COX makes PGH2 - reacts with serine on COX inactivates enzyme no PG - indomethacin: reversible non-competitive - ibuprofen: rapid, reversible, competitive

- anti-inflammatory

- withdrawal due to adrenal suppression - chronic use: hypertension, osteoporosis, growth retardation, increase infections - dizziness, tinnitus, headache (toxicity related) - increase in resp - gastric and renal damage, delays labour -decrease GFR

- analgesic - found to have protective action against colon cancer

Leukotrienes? ?

Nitric Oxide
Glyceryl trinitrate, amyl nitrate, sodium nitroprusside, Isosorbide dinitrate, Monnitrate - dont act to increase production of NO, act as if NO would i.e. directly diffusing into SMM to cause relaxation - vasodilator - relax SMM of lungs in resp distress syndrome - hypertrophic pyloric stenosis - impotence headache skin reactions postural hypotension dizziness reflex tachycardia nausea vomiting - cross tolerance between nitrates can occur - CI in hypotension, cardiomyopathy and hypersensitivity to nitrates - interacts with antihypertensives, sildenafil, alcohol, TCAs

Increase NO

NOS inhibitors Castor oil, bisacodyl, senna NO-NSAID Other NO drugs Sildenafil

- competitive inhibitors - prevents conversion of L-Arg NO - increase NOS activity in GIT increase fluid secretion and relaxation - same effect as aspirin but causes release of NO instead - increase mucosal secretion to counter stomach SE - inhibit COX-I and COX-II - potentiation of NO-stim cGMP pathway - inhibit phosphodiesterase relaxation of cavernosal SMM - KATP channel activator - causes vasodilation - D antag acts in chemoreceptor trigger zone - D2 antag - D2 antag

migraine neurodegenerative disorders hypotensive crisis laxative

- pain relief??

Nicorandil

- vasodilator

Central Nervous System

Domperidone Prochlorperazine Anti-emetics Chlropromazine - anti-emetic - anti-emetic - Schizophrenia D antag in mesocortical/limbic sys - Parkinsons D antag in nigrostriatal path - extrapyramidal side effects i.e. loss of fine motor control - doesnt cross BBB hence wont cause Parkinsons like SE

Drug Class

Drug Name

MOA

Uses

Side Effects

Miscellaneous info

Emetics

Ipecachuanha, heavy metal salts Apomorphine Pentelenetetrazol e, Bemegride strychnine

- act as irritants to the stomach to causing vomiting - D2 agonist - acts on chemoreceptor trigger zone

- emesis - emesis

- glycine antag - GABA antag (competitive) - GABA antag (non-competitive - Benzodiazepine antag

Resp stimulants

Bicuculline Picrotoxin Flumazenil

Anti-psychotics
Typical Phenothiazine s and butyronpheno nes (-zines) Chlorpromazine (CPZ) Haloperidol (Promethazine, Prochloroperazin e, thioridazine little antipsychotic action) Clozapine, Risperidone, Olanzapine, Quetiapine Atypical (-pines) Aripiprazole anti-psychotic D2 antag anti-N catalepsy cataplexy (muscle relaxation local anaesthetic decrease aggression/agitation decrease epileptic fits - anti-psychotic - CPZ best binding to H1 and 5-HT2 - anti-emetic H1 antag (Prochloroperazine) - anti-histamine (sedation through H1) (Promethazine) - anti-psychotic - convulsions, drowsiness - extrapyramidal effects i.e. Parkinsons, dyskinesia - weight gain - endocrine problems block DA increases prolactin - anti-M i.e. anti-SLUD - jaundice, clouding of lens - skin rash - increase risk to diabetes from Cloz and Olan but not Risper cells of pancreas blocked decrease insulin - weight gain from Cloz and Olan - headache - agitation - insomnia - takes several weeks to take effect - not very effective - low compliance due to SE - not effective for control of ve symptoms for schizo

Amisulpride

- initiate response from mesocortical D system - increase DA in prefrontal cortex (reverse of typicals) - 5-HT2A antag - 5-HT1A agonist - weak D2 antag - partial agonist: D2, D3 and 5-HT1A - antag: 5-HT2A - D2 stabilise dopaminergic neurotransmission - 5-HT1A effective for ve symptoms - 5-HT2A decrease chance of EPS - D2 and D3 antag limbic system - if antag in striatum SE much worse block neuronal uptake of NA and 5-HT block H1, M, 5-HT, 1/2 1 block decrease feedback increase NA improves mood and decreases aggression decrease 1, 2, 5-HT2 receptors

- no extrapyramidal effects - better for treating ve symptoms - higher affinity for 5-HT2A than D2 - less risk of suicide

- D system stabiliser

- good for ve symptoms

- Insomnia - EPS but much less than typicals - initial: sedation, confusion, motor unco-ordination - chronic: atropinic effects, postural hypotension (thru medullary vasomotor centre), hyperpyrexia, arrhythmia

- no catalepsy, fewer EPS

Anti-depressants
Amitriptyline (AMI), Clomipramine (CMI), Doxepin, Dothiepin - depression - enuresis through M block - sedation/hypnotic - takes a few weeks to notice changes - interacts with sedatives (increase effect of OH), MAOIs and Phenothiazines potentially lethal, Clonidine

Tri-cyclics

Drug Class
SSRI

Drug Name
Fluoxetine, Citalopram, Sertraline,

MOA
- 5-HT brake - 5-HT1A pre +post synaptic on cell bodies; involved in neuronal firing (more important)

Uses
- anti-depressant - Cit., Fluoxetine, Ser. Have active metabolites

Side Effects
- low SE profile due to decrease affinity for D (not anti-psy), M (less atropinic effects), H (decrease

Miscellaneous info
- 2o changes down regulate (reduce receptors) of 5-HT1A on Raphe nucleus increase 5-HT

Paroxetine, Fluvoxamine

- 5-HT1B pre-synaptic nerve terminals; involved in decreasing 5-HT release - acts to increase 5-HT release - meaning non-selective for either isoenzyme - blocks conversion of catecholamines to aldehyde derivatives - since NT breakdown blocked NT spill out of neurone increasing transmission - can displace NA from presynaptic nerves - more A than B in intestine - found predominantly in NA neurones, gut, liver - substrates: tyramine, D, 5-HT, NA - more B than A in brain - found predominantly in 5-HT and H neurones - substrates: tyramine, D, phenyl amines - 2 antag - blocks uptake of NA - 2 antag - 5-HT2/3 antag

- Paro., Fluvox., do not have active metabolites

sedation) and (less drop in BP) - nausea, vomiting, insomnia, sweating, diarrhoea, decrease libido

release - interact with MAOI serotonin syndrome - no potentiation of alcohol effects but still not advised

Non-selective: Iproniazid, Isocarboxazid, Phenelzine, Pragyline, Tranyclopromine MAOI MAO-A selective: Clorgyline, Moclobemide (reversible) MOA-B selective: Selegiline Mianserin

- anti-depressant - jaundice - hypotension reflex bradycardia - CNS stim excitement, agitation, insomnia - nausea - possible hypertensive crisis due to tyramine displacing NA NA leaks out increase BP - need to avoid cheeses

- moclobemide: depression, Parkinsons <ONLY NEED TO KNOW MOCLOBEMIDE FOR EXAM> - anti-depressant

- 2o adaptive changes down regulate 1, 2, 5-HT2 receptors

- anti-depressant

Tetracyclic (Atypical)

Mirtazapine (NA and specific serotonergic NSSA) Venlafaxine (SNRI) Bupropion

- anti-depressant

- block reuptake of 5-HT and NA - weak DA uptake inhibitor - no affinity for M, H1, or - NA and D uptake inhibitor - increases D in reward centres of brain - monoamine uptake inhibitor more action on 5-HT and NA than D

- anti-depressant

- increase appetite and weight gain 5-HT2 block - drowsiness H1 block - CNS excitation - seizures, tremor, mania - fatigue, nausea, dizziness, drowsiness, nervousness, headache, constipation, impotence

- well absorbed - interacts with CNS depressants i.e. alcohol, benzos or MAOIs

- no anti-M, sedation or BP effects - has active metabolite - no interaction with alcohol

Other antidepressants

- only used for nicotine dependence - many interactions with metabolising enzymes

St. Johns Wort

Pain
Naloxone Naltrexone Opioids Buprenorphine, Meptazinol - agonis, antag - opioid antagonist - antag - for reversing opioid OD - alcohol dependence decreases voluntary intake - opioid dependence - relief of moderate/severe pain - used in opioid dependency - nausea - hepatotoxicities - resp depression - hypotension - bradycardia - short half life - CI for opioid analgesics, reduced hepatic function - long half-life - CI for resp compromised, hepatic insufficiency, alcohol and CNS depressants

Drug Class
Opioids

Drug Name
Morphine, Codeine

MOA
- natural opioid agonist ( ) - behavioural: lethargy, drowsiness - analgesic: mimics enkephalins in dorsal horn - nausea and vomiting: acts on chemoreceptor trigger zone

Uses
- mild to moderate pain treatment - cough suppressant - diarrhoea - sedation -

Side Effects
resp depression light headed nausea vomiting sweating

Miscellaneous info

Nalorphine, nalbuphine, butorphanol Pethidine

- miosis: pin-point pupils - thermoregulation: decrease body T - resp system: decrease rate and response to CO2 and H+; bronchoconstriction - CV: postural hypotension - GI: decrease coordination, increase tone, sphincter spasm - bile duct: causes biliary colic - genitor-urinary: increase detrusor and sphincter tone, increase ADH - antag, agonist

sedation -dyspnoea/pulmonary oedema

- constipation - dry mouth - opioid dependence

- agonist

- colic less SMM effects as morphine - for moderate/severe pain - moderate/severe pain greater analgesic potential than morphine - not used for opioid dependence - less abuse potential - moderate/severe pain - adjunct to general anaesthetics

- toxicities causing convulsions and excitement prevent its use for chronic pain treatment - similar profile to other opioid agonists

Hydromorphone

- agonist

Tramadol

- agonist - inhibits NA and 5-HT re-uptake stops SP release - agonist (similar to pethidine)

- nausea, vomiting, dizziness, constipation, asthenia (tingling), fatigue, allergic reactions, headache, sedation

Fentanyl

- shorter onset than morphine - shorter duration than morphine - not as active as morphine - DI for MAOI - shorter half life than morphine - rapid absorption orally - DI for MAOI and CNS depressants - metabolite has greater affinity for receptor than tramadol itself - hypersensitivities - CI for MAOIs and CNS depressants - only for short term analgesic - DI for MAOI and CNS depressants - tumescent: swollen or become swollen - blocks small diameter fibres more readily than large fibres

Local anaesthetics
Local Anaesthetics Esters: Cocaine, Procaine, Benzocaine Amides: Ligno., Dibucaine, Prilocaine etc. Alcohol - blocks Na+ channels from inside nerve(charged form) - enters nerve through Na+ channel or through membrane - used under occlusive dressing - infiltrating tissue hypersensitivity double vision tinnitus light-headedness anxiety, tremor, resp depression arrhythmia, hypotension

Social drugs
Social Drugs - chronic effects: anaemia, increase in GI ulcers - foetal effects: retardation, hyperactivity, decrease in social skills

Drug Class

Drug Name
Nicotine

MOA
- induces CYP1A2 isoenzyme - accumulate in tissues extends half life

Uses
- increase HR, BP and vasoconstriction, increase ADH, increase resp rate - increase alertness, calms ppl in stressful situations - temazepam increase opioid effect - flunitrazepam hypnotic

Side Effects
- cancer, peripheral vascular disease, coronary heart disease, COPD, pregnant women

Miscellaneous info

Benzodiazepin es

Temazepam, flunitrazepam

- facilitates action of opioids

drink spiking Cannabis Ecstasy - acts on CB1 neuronal or CB2 spleen, immune system - increase 5-HT release - increase HR and appetite, decrease BP, muscle strength, body T and intraocular P - boosts self confidence, emotional and sensual effects - causes dementia, mental confusion, ataxia, decrease learning and memory, oedema, hepatotoxicities - increased sweating, blurred vision, ataxia, insomnia, muscle tension - OD: tachycardia, hypertension, hyperthermia, renal failure

- residual effects: flashbacks, anxiety, rage, psychosis