AUTACOID & ANTI-INFLAM DRUGS

Autacoids : subs that initiate & sustain inflam &

immune response activate the repair process localy acting hormones

examples : amino acids derivatives

- histamine - 5-ht

vasoactive peptides - angiotensin - kinin- endothelins

Fatty acid derivatives - eicosanoids

Family of cytokines - Interleukins- TNF- Interferones- Growth fc

Histamine

Formed from amino acid histidine. Stored mainly in mast cells Non-mast cell histamine found in several

tissue – brain : neurotransmitter Synthesis/metab : not affected by any

clinically useful drug Certain drugs cause the release from

mast cell

Pharmacological Actions of HistamineActs on at least 4 ,types of receptors

H1 ReceptorsDistribution: neuronal tissue, bl vs, sm msEffects:

Intense VD e increased cap. Permeability, flare & swelling

Pain & itching Constriction of airway & GIT sm ms Inc bronchial/intestinal secr. Dec of systolic/diastolic bl pressureHistamine Releasers

- Morphine- Tubocurarine- Certain radiocontrast media- Trimetaphan- Deferoxamine

H2 Receptors

Distribution: gastric mucosa, cardiac msEffect: Inc gastric HCl & Pepsin secr Inc cardiac contractility & HR

H3 ReceptorsDistributon: CNSAction: wakefulness, modulation of other transmitter release

H4 ReceptrosDistribution: various inflam cellsAction: regulation of inflam response

Histamine Antagonist

Physiological antagonist: Adrenaline Sm ms actions opposite to histamine Act at diff rec

Histamine rec. antagonist:- H1-blockers - Diphenhydramine

- Loratidine- H2-blockers - Cimetidine

- Ranitidine- Famotidine

- H3 & H4-blockers (not available)

Histamine Release Inhibitors: Inhibit Ca2+ influx into mast cell –

prevent degranulation- Ketotifen- Cromoglycate

Immunotherapy Process – allergic patient can become

desensitized to pollens/inhalants that trigger allergic patient response

H1-Rec Antagonist (AntiHistamine)

1st Generations Ethanolamines

- Clemastine- Diphenhydramine- Dimenhydrinate

Ethylenediamines- antazoline

Piperazines- Cyclizine- meclizine

Alkylamines- Chlorpheniramine

Phenothiazines- Promethazine

Others- Cyproheptadine

2nd-Generations Loratidine Azelastine Fexofenadine Cetirizine

Pharmacokinetics

Absorption: rapidly after oral admin.

Distribution: widely throughout the body1st-Gen. drugs enter CNS readily

Metabolism: most by hepatic microsomal enzymeseveral 2nd-Gen by CYP3A4 syst. [important interactions when given with other drugs (ketoconazole) that inhibit this subtype of P450 enzymes]

Pharmacological Effects

Related to H1-rec Blockage (antiallergic react)

Alleviation of itching, pain & allergic resp.

Dec cap permeability & inflam. edema Dec bronchoconstriction & bronchial

secr.

Not Related to H1-rec Blockage (1 st -Gen. only)

Sedation (marked excitation, convulsions in some cases)

Antiemetic Action: prevent motion sickness

Antiparkinsonian Action: ability to block central muscarinic rec. in extrapyramidal syst.[Diphenhydramine]

Anticholinergic Action: most – can block peripheral muscarinic rec urine retention & blurred vision

Alpha-rec Blocking Action: cause orthostatic hypotension [Promethazine]

5-HT rec Blocking Action: useful drug to treat Carnicoid syndrome & as appetite stimulant

Local Anesthetic Action: block sodium channels in excitable membranes

Clinical Uses of H1-Blockers

Allergic condition:- In which histamine is 1° mediator

[allergic rhinitis/urticaria] effective- In bronchial asthma largely

ineffectiveMotion Sickness & Vestibular Disturbance:

- Scopolamine & 1st-Gen : efficacy I Menier’s syndrome is not established

Carcinoid Syndrome:- Caused by serotonin-secreting

neoplasm of enterochromaffin cells- When tumor not operable, use of

cyproheptadine & other 5-HT blockers is useful.

Side Effect of H1 Blockers

1st-Gen: Sedation Anticholinergic Act Orthostatis Hypotention Drug Allergy (common aftr topical

use)2nd-Gen:

Dangerous arrhythmia (torsade de pointes) – due to prolongation of QT-interval

Drug Interactions:

1. Several 1st-Gen: potentiate Central Depressant Action sedatives, hypnotics, alcohol

2. Several 2nd-Gen: metabolized by CYP3A4 syst. Dangerous Arrhythmia when given e other drugs that inhibit this subtypes of P450 enz.

H2-rec Antagonist- Dec HCl in acid-peptic disease

Serotonin (5-hydroxytrypyamine; 5-HT)

Formed from amino acid tryptophane Stored mainly in chromaffin tissue Synthesis/metab : not affected by any

clinically useful drug Many drugs act on 5-HT as agonist/antag.

Pharmacological Action: Act on at least 7 types of receptors During inflam, 5-HT can affect bl vs

tone via activation of 5-HT receptors

5-HT Agonists:

Buspirone

Activate central 5-HT(1A) rec. Selective & non-addictive anxiolytic ttt: anxiety (esp-in elderly patients)

Triptan- sumatriptan- zolmitriptan- naratriptan

activate 5-HT(1B/1D) rec. cause VC of dilated cerebral vs inhibit release of VD peptides

alleviation of acute attacks of migraine headache

Side Effect : coronary VC C/I = ischemic Heart Disease

5-HT Antagonist

Cyproheptadine

Block 5-HT, H1 & muscarinic rec. ttt: symtoms of carcinoid tumor

allergic Side Effect: Atropine-like action (dry

mouth/ urine retention)

Ketanserin Block 5-HT(2) rec in platelet Inhibit 5-HT promoted platelet

aggregation

Block vascular alpha-1 adrenoceptor -> VD

ttt: hypertension, vasospastic conition Side Effect: mild dizziness, fatigue

RitanserineSimilar to Ketanserin – but has little/no alpha-1 blocking action

Ondansetron Selectively block central/peripheral 5-

HT(3) rec (CTZ/GIT) ttt: nausea, vomiting associated e

surgery, cancer chemotherapy

Alosetron block 5-HT(3) ttt: severe irritable bowel syndrome e

diarrheaRenin-Angiotensin-Aldosterone System

plays an important role in regulating bl volume & systemic vascular resistance influence cardiac output & arterial pressure

Pharmacological Effect of Angiotensin IIActs on at least 2 subtypes of rec.:

AT1 rec;Distribution: vascular/renal tissue, cardiac

ms, CNSEffects: VC

Inc aldosterone/vasopressin secrInc peripheral noradrenergic actModulation of central symp actvty

Central osmocontrolCardiac hypertrophyVascular sm ms cells proliferationExtracellular matrix formation

AT1 rec;Distribution: fetus/ neonateEffects: Inhibition of cell growth

Fetal tissue developmentModulation of extracellular matrixApoptosisCellular differentiationVD (maybe)

DRUGS ACTING ON R-ANGIOTENSIN SYST.Inhibitors:

Drugs which inhibit Renin release- Beta blockers- Clonidine- Alpha methyl dopa- Prostaglandin inhibitors (indomethacin)

Drugs which inhibit Renin- enalakrine- pepstatin

Drugs which inhibit conversion of Ang I Ang II- Angiotensin Converting Enz Inhibitors

(ACEIs)> Sulph-hydryl containing ACEIs> ACEIs without sulph-hydryl group> ACEIs inhibitor which contain phosphinate group - Fosinopril

Angiotensin II rec blockers- Saralasin- Losartan- Valsartan

KININ

Potent VD peptides Formed from Kininogen by effect of

kallikrein enz

Pharmacological Action of Kinins:Acts on at least 2 subtypes of rec.: B1, B2

VD of arterioles & VC of venules inc cap permeability & breaf fall of bl pressure

Contraction of sm ms (BC, GIT colic) Stimulation on sensory nerves pain

Kinin rec Antaginist:

Kinin B2 rec blockers – under trials ttt inflam. & neurogenic pain

Synthesis of kinins – inhibited by kallikrein inhibitor : aprotinin

ENDHOTHELINS

VC peptide Produced by endothelium 3 isoforms Endothelin 1 = strongest VC

Pharmacological EffectAct at least 2 subtypes of rec: ET(A), ET(B)

ET(A) recDistribution: sm ms of vascular/other tissueEffects: Potent VC

Vascular sm ms proliferationCardiac hypertrophySodium retentionProlong elevation of bl pressure

ET(B) recDistribution: vascular endothelial cellsEffects: Diuresis

NatriuresisTransient dec of bl pressure

Endothelin rec Antagonist:

Non-selective: BosentanSelective [ET(A)]: Sitaxentan

Uses: ttt – essential/pulm. Hypertension

Ischemic Heart DiseaseCardiac hypertrophyHeart Failure

PROSTAGLANDINS

Derived from arachidonic acid [by action of cyclooxygenase enz-has 3 isoforms]

1. COX-1 (physiological/constitutive) - Synth. of protective PGs: PGE2, PGI2

> protection of stomach fr HCl> reg of RBF> inhibition of platelet aggregation

2. COX-2 (pathological/inducible) - Synth. of undesirable PGs: PGF2α, PGD2

> inflam reaction> BC

3. COX-3 (central) - Only found in brain- Synthesis PGs responsible for fever &

pain sensation- Selectively inhibited by analgesic/

antipyretic drugs : acetaminophena & dipyrone

Therapeutic Uses of PGs

PGE1o ttt: erectile dysfunction (men) –

Alprostadilpeptic ulcer [dec HCl, inc gastric mucus secr] – Mesoprostol

o during surgery of cong great vs transposition in infants (i.v) – Alprostadil :

maintain VDpatency of ductus arteriosuspulmonary vascular bedprevent hypoxia

PGE2o Induction of Abortion/facilitation of labor

[stimulate uterine contr] – Dinoprostone

o ttt:peripheral vascular disease

PGI2o Prevent platelet aggregation –

Prostacycline :Thrombotic disordersCardiopulmonary bypass surgery

HemodialysisRetinal artery occlusion

o ttt:pulm.hypertensionperipheral vascular disease

PGF2αo Induction of Abortion/facilitation of labor –

Enzaprost

o ttt:open-angle glaucoma [enhance uveoscleral outflow of aqueous humor] – Latanoprost

THROMBOXANES (TXs)

Products of cyclooxygenase enz Synthetized in high concentration in

platelets 2 forms : TXA2 (active),

TXB2 (inactive) TXA2 – most potent endogenous

stimulator of platelet aggregation

LEUKOTRIENES (LTs)

Derived from arachidonic acid by the action of lipooxygenase enz

4 main types : LTB4, LTC4, LTD4, LTE4

Mixture of LTC4, LTD4, LTE4 = released during inflam response [termed –> SRS-A (slow-reacting subs of anaphylaxis)]

LTB4 – powerful BC & chemotactic for leucocytes

:TXs & LTs – no clinical uses:

Leucotriene Inhibitor:

Zafirlukast & Montelukast

Block leukotriene rec Absorbed orally Zafirlukast : twice daily Montelukast : once daily

Uses: ttt - bronchial asthma & other inflam cond.

Zileuton

Inhibit 5-lipooxygenase enz dec LTs synth.

Uses: ttt - bronchial asthma & other inflam cond.

Inhibitors Of Eicosanoid Synthesis

Corticosteroid Inhibit phospholipase A2 enz &

consequently all eicosanoids family

Non-Steroidal anti-inflam drugs (NSAIDs)

Inhibit cyclooxygenase enz

- Classical NSAIDs : inhibit both COX-1 & COX-2 non selectivelyi. Aspirinii. Ibuprofen

- Newer NSAIDs : inhibit COX-2 selectively (induced during inflam)i. Celecoxib

Leukotriene Inhibitor : see B4

Pharmacological Action of Eicosanoids Act on cell surface seven-

transmembrane rec (G-protein coupled rec)

NSAIDs

1. Non selective COX inhibitors

Salicylic acid derivatives- Aspirin- Aloxiprine- Aminosalicylic acid- Diflunisal- Methyl salicyliate

Acetic acid derivatives- Carboxylic acetic acid

i. Indomethacinii. Sulindaciii. Etodolac

- Phenyl acetic acidi. Diclofenac

Propionic acid derivatives- Iboprufen- Ketoprufen- Fenoprufen- Naproxen

Fenamic acid derivatives- Mefenamic acid- Fulfenamic acid

Pyrazolone derivatives- Phenylbutazone- Azapropazone

Oxicams- Piroxicam- Tinoxicam

2. Selective COX-2 inhibitors- Celecoxib- Valdecoxib- Meloxicam

Aspirin/acetylcsalicylic acid

Chemistry: White crystalline subs Stable in dry air Hydrolyses in moist air -> salicylic &

acetic acidPharmacokinetics:Absorption

Oral absorption – complete & rapid (peak level after 2 hrs

Most absorption – stomach & upper GIT

Rectal absorption – slow & regularDistribution

Widely to all tissue including CNS Plasma prot binding – high

Metabolism/Excretion Metabolism by hepatic microsomal enz Elimination : Low doses - 1st order

process Elimination : High doses – Zero order

pro. Excretion inc by alkalinization of urine

(pH8)

Mech of ActionNon selective COX inhibitor inh. of PGs/TXs

Pharcological EffectsAnalgesic effect:

- Mild/med intensity pain (not severe)- Mech – dec PGS synth

i. Peripheral – in peripheral inflamed tisii. Central – in thalamus/hypothalamus

Antipyretic effect:- Not hypothermic agent (can lower

elevated body temp, not normal temp)- Mech –

i. Dec PGE2 synth in hypothalamusii. Dec hypothalamic response to IL-1iii. Cutaneous VD/inc sweating

Anti-inflam, anti-immunological, anti-rheumaticMech –

i. Dec PGs synth & other inflam med.ii. Decreased Leucocytes Margination,

Emigration, Migration (fr blood -> site of inflam)

iii. Stabilize lysosomal membraneiv. Dec cap permeabilityv. Dec synth of mucopolysaccharides

(form ground subs)vi. Dec hyaluronidase enz & spread of

inflamvii. Analgesic/Antipyretic effects

Therapeutic Uses – Salicylates

a. Anelgesic- Headache- Arthritis- Rheumatic pain

b. Antipyretic- Not used routinely

c. Anti-inflam/anti-rheumatic- Rheumatic fever- Rheumatoid arthritis- Osteoarthritis

d. Antithrombotic- Ischemis heart dis- Deep vein thrombosis- AF

e. Cancer colon & Alzheimer’s dis- Thru COX inhibition

f. Keratolytic- ttt – warts (salicylic acid)- counter irritant – local rheumatic

pain (metylsalicylic acid)Side Effect

Hypersensitivity- Bronchospasm, urticaria, skin rash,

shock- More in bronchial asthma

GIT- Epigastric pain, nausea, vomiting- Acute/Chr gastric ulcers

Hepatic- Mild hepatic injury- Severe hepatic injury (child) –

Reye’s syndromeKidney

- Analgesic nephropathy- Salt/Water retention- Dec diuretic effect of loop diuretic- Dec anti-hypertensive effect of β

blocker- Precipitation of acute gout (low D)

– in hyperuricemic patient

Blood- Inc bleeding tendency- Displacement of other drugs fr

plasma prot

Male/Female reprod. Fc- Prolonge pregnancy – delay labor- Reversible infertility – male

Drug interactions

1. Antagonizes uricosuric effect of probenecid

2. Antagonizes diuretic effect of loop diuretic

3. Antagonizes anti-hypertensive effect of β blocker/ACEIs

4. Inc plasma conc of anticoagulants (heparin/warfarin), phenytoin, thyroxin & others inc effect/toxicity

5. Antacids dec aspirin absorption

Salicylate toxicity

Acute toxicityCause: ingestion of large D of salicylates

Manifestatons:i. Nausea, vomiting, hematemesisii. Acidosis, dehydrationiii. Pulm. Edema, CVS collapseiv. Hyperpyrexia, hyperventilation,

coma

Treatment:i. Repeated gastric lavage e

activated charcoalii. Cold fomentations – hyperpyrexiaiii. Vit K -> control heiv. i.v fluid -> dehydrationv. i.v sodium bicar. -> acidosisvi. Alkalinization of urine -> enhance

salicylate excretionvii. Hemodialysis (severe case)

Chr. ToxicityCause: prolonged admin.

Manifestations:i. Headacheii. Tinnitusiii. Tachypneaiv. Resp. alkalosis

Treatment:i. Stop salicylates (cond. is

reversible)

Precautions & C/I

1. GIT : peptic ulcer, gastritis2. He : Hemophilia, thrombocytopenia3. Ch. Renal dis : Renal Art stenosis, RF4. Ch. Liver dis : Bleeding tendency5. CVS dis : CHF, sev. HTN6. Gout7. Pregnancy8. B4 surgery9. Child (< 12 yrs) -> Reye’s Syndrome

Selective COX-2 inhibitors

- Reduces risk of peptic ulcer- Inc risk of CVS accidents (inc in TXA2

& platelet aggr.)i. Myocardial infarct.ii. Thrombosisiii. Stroke

Acute Rheumatic FeverGoal of therapy

1. Suppression of the acute inflam. response

2. Prevention of complication3. Eradication of streptococcal inf.4. Prevention of recurrence

Non Drug-therapyAbsolute bed restAim : avoid cardiac complicationDuration :

- 2 weeks : in absence of carditis- 4 weeks : in presence of carditis- 8 weeks : in presence of Heart

Failure/cardiomegallySalt & Fluid restriction

- In presence of carditis/HF – avoid volume overload & cardiac strain

Drug Therapy

1. Eradication of streptococcal inf - 1st choice : penicillin-G- 2nd choice : Co-trimoxazole

Erythromycin

2. Suppression of acute inflam

- Salicylates (aspirin/Na salicylamide)Indication: acute rheumatic fever

wo carditisMech : Analgesic action

Antipyretic actionAnti-inflam/rheumatic

- CorticosteroidIndication: acute rheumatic fever e

carditisMech : Anti-inflam/rheumatic

3. Prevention of recurrence (prophylaxis) - Long-acting penicillin : Benzathine

penicillin

- When stop?Severe carditis/recurrent ARF : lifeMod. Carditis: till 21 yrsMild/No Carditis: 3 yrs fr last episode

Rheumatoid Arthritis

1 st -line Drugs (background therapy)

1. NSAIDs Symptomatic relief Not prevent joint destruction Large D required

2. Corticosteroid Bridging therapy (during DMARDs not

take effect yet) By direct injection in affected joint

2 nd -line Drugs (dis-modifying antirheumatic drugs-DMARDs)

- Prevent progressing of dis- Slow down joint destruction- Effect takes 6w – 6m to be evident- Combination 2/more – more

effective

Methotrexate 1st choice – used >60% of RA cases Used in much lower D – needed in

cancer chemo. Mech: inh multiple intracellular enz

(for activation of PMLs, T cells & macrophage)

Hydroxychloroquine (AntiMalarial Drug) Dec synth of DNA & RNA in inflam cell Dec response of T cells to antigen Stabilizes lysosomal membranes

Sulfasalazine Metab sulfapyridine & 5-

aminosalicylic acid Leads to inh IgA & IgM rheumatoid fc

production Causes suppression of T cells & B cells

response & proliferation

Immunosuppressant Drugs Cyclophosphamide : cause DNA

alkylation prevent cell replication, suppresses T/B cells func.

Cyclosporine-A : inh IL-1&2 rec prod.

Inh T cells func.

Gold Salt i.m/orally alter morphology/func human

macrophage inh release many inflam. cytokines

& GF fr inflam. cells

TNF- α -Blocking Drugs Have central role in patho of RA Mabs :

i. Adalimumabii. Infliximabiii. Rituximab- Monoclonal ab – complex e suitable

TNF-α- Inh its interaction e T cells &

macrop.

Etanercept :- Recombinant prot- Interferes e soluble TNF-α- Prevent it fr binding to its cell sf

rec.

Leflunamide Suppresses pyrimidine synth arrest

stimulated cell growth Suppresses T/B cells func. Inh bone damage, radiographic

change

Anti-Gout Drugs

Hyperuricemic Drugs (for chr) - Inc uric acid excretion

i. Probenecidii. Sulfinpyrazoneiii. Benzobromarone

- Inc uric acid metabi. Uricase enz

- Dec uric acid synthi. Allopurinolii. Thiopurinol

Anti-Inflam Drugs (for acute) i. Colchicineii. Corticosteroidiii. NSAIDs

Probenecid

Chemistry : organic acid

Pharmacokinetics Absorption : good – oral Metabolism : hepatic active

metabolite Excretion : via kidney

Mech of Action Low D : dec tubular secr of uric.A by

Renal PCT Ther D: inc uric.A excr by 50% (inh

reabs. Fr Renal PCT)

Therapeutic Uses1. Uricosuric agent – chr gout2. Prolong half-life of some acidic drugs

by inh renal tubular secr. : i. Penicillins ii. Rifampicin

Side Effect1. GIT disturbance2. Skin Rash3. Fever4. Nephritic syndrome (rare)5. Aplastic anemia (rare)

Sulfinpyrazone Similar to Probenecid Has antithrombotic action (dec TXA2)

Benzobromarone Potent uricosuric Low D : No hyperuricemic effect

Allopurinol

Chemistry : structural analogue of Purine

Pharmakinetics Absorption : good oral admin Long duration of action (converted to

active metabolite) Excretion : kidney

Mech of action Inh xanthine oxidase enz inh uric.A

synth- Allopurinol : competitive inhibitor- Its Metabolite : non-compet. Inh.

Therapeutic Uses Chr gout Adjuvant therapy – ttt of hematologic

mg (prevent massive uricosuria & renal calculi)

Side Effect1. GIT disturbance2. Hypersensitivity react. (skin rash)3. Precipitation of acute attack of gout

Precaution1. Do not give during acute attack2. Give NSAIDs/Colchicine e Allop. –

prevent initial hyperuricemic & acute gout

Uricase Enz

Enz of bact origin Convert uric.A allantoin Parentally admin Indicated in: Gout e renal failure

ttt of hematologic mg (prevent massive uricosuria & renal calculi)

Colchicine

Chemistry : natural plant alkaloid

Pharmacokinetics Absorption : good after oral admin Excretion : thru bile

Mech of Action1. Inh intracellular microtubular syst.

inh leucocyte motility & phagocytosis2. Inh mitotic spindle & cell division3. Inh release of LTB4 by leucocytes

Therapeutic Uses1. Accute attack of gout (fatal D: 8mg-

24h)

2. Familial Mediterranean fever

Side Effect1. Nausea, vomiting, diarrhea (most

common)2. Allopecia, myopathy (most rare)3. Aplastic anemia, agranulocytosis

(serious)NSAIDs

Indomethacin & Naproxen Provide symptomatic relief D must be reduced if taken e

precenebid (precenebid inh their renal excr)

Corticosteroid As anti-inflam agent (when other 2 not

sufficient or C/I)

HYPERTENSION

Non-Drug Therapy Dec Na intake Weight reduce (obese) Stop smoking, coffee, alcohol Exercise program Control DM & hyperlipideamia

Drug Therapy (antihypertensives)

Common :1. ACEIs/ARBs2. β-Blockers3. Calcium-channel Blockers4. Diuretics

Other :1. Agent interfering adrenergic func

(centrally acting)a. α-methyl dopab. clonidinec. guanfacine

2. Ganglion blockers - trimetaphan3. Adrenergic neuron blockers

a. reserpineb. α-methyl dopa

4. α-adrenergic blockers - prazocin5. Concurrent α & β blockers - labetalol6. Serotonin antagonist - ketanserine7. Direct VD - hydralazine8. Dopamine rec agonist – fenoldopam

DIURETICS

Thiazides Initial therapy – most cases Part of most combined

antihypertensive regimenLoop Diuretics

Hypertensive crises Ch renal failure Resistant htn (marked Na retention)

Spironolactone 1ry hyperaldosteronism Correct hypokalemia (caused by T &

LD)

β -BLOCKERS

1. e stable angina, supraventricular/ventri. arrhythmia

2. e Inc adrenergic activity3. Hyperrenenimic htn4. Part of combine therapy

CALCIUM CHANNEL BLOCKERs (CCBs)

Block slow ca2+ influx (during terminal phase – depolarization / plateau phase – act potential)

Classification:1. More selective on heart

- Verapamil- Diltiazem

2. More selective on bl vs- Nifedipine- Nimodipine- Almodipine

3. e tissue protection- Flunarizine- Nifedipine

Pharmacokineticso Absorption: nearly complete after oral

admino 1st past hepatic metabolism – dec

bioavailabilityo Effects evident within 30-60min (oral)o Peak effect verapamil – 15min (i.v)o Some have metabolite [verapamil,

diltiazem– VD]o In patient e hepatic cirrhosis –

bioavailability & half-life – inc [D should be dec]

oHalf-lfe longer in older patient

Pharmacological Effecto Relaxation of vascular sm ms,

bronchiolar, GIT, uterineo Dec cardiac contractility (in D-dependent)o Protect against damaging effect of Ca2+o Block tachy in Ca dependent cellso Dec platelet aggregabilityo Inhibit insulin release (verapamil)o Inh Ca influx across CNS – limit seizure

activity

Therapeutic Indication

Cardio-selective

1. Ischemic heart dis (angina/myocardial infarction)MoA :- Dec art bl pressure, contractility,

HR dec myocardial O2 demand- Dec coronary vascular resistance- Dilation of epicardial coronary

artery

- Dec Ca load improve myocardial relaxation & dec myocardial cell necrosis

2. Cardiac arrhythmias- Prolong intranodal conduction time- Slow AV conduction- Lengthen ERP of AV node

3. Hypertrophic obstructive cardiomegally- Dec contr force during systole

dec O2 consumption & inc exercise tolerance

- Inc relax during diastole improve coronary flow

4. Arterial htn- d2 VD of bl vs, dec of HR & contr.

Vascular-selective

1. Arterial htn2. Cerebral vasospasm3. Peripheral vascular dis4. Ch renal failure5. Re-perfusin injury in myocardium6. Migraine

Side Effect

i. Aggravation of CHFii. AV block-in-patient e pre-existing

dis or when combined e β-blockersiii. Nausea, vomiting, constipation,

hepatotoxicity (reversible)iv. Worsen diabetes

v. Hypotension, flushing, tinnitus, nasal congestion, occasional aggravation of angina

vi. Ankle edema

C/I & precaution

1. Verapamil – HF, unstable AV block, sick sinus symdrome, low bl pressure states

2. Verapamil & Diltiazem – C/I in Wolf-Parkinson-White symdrome complicated e AF & A flutter

3. Nifedipine – C/I in Idiopathic hypertrophic subaortic stenosis & unstable angina

4. Verapamil – C/I in non-insulin dependent DM

Drug Interaction

1. Verapamil – e digitalis/β-blocker AV block (d2 additional effect on conducting syst) – Nifedipine : DoC

2. CCBs & Direct VD profound hypotnsion

ACEIs

Mech of Action Interrurt R-A-A pathway thru inh of

peptidyl dipeptidase enz (convert ang I -> ang II) [prevent ang-II form]

Prevent inactivation of kinins inc conc of bradykinins (potent VD)

Pharmacological Effects Dec peripheral resistance Not modify cardiovascular response to

autonomic reflex. Not cause tachy despite of

hypotension Inc RBF Maintain cerebral/coronary BF

(systemic bl pressure is reduced) In CHF – inc COP, cardiac index

Dec HR Dec Lt ventricular mass/wall thickness

(prevent ventri. enlargement after myocardial infarction)

Clinical Uses1. HTN2. HF3. Postinfarction ventricular remodeling4. Renal dis (microalbuminuria, ch renal

dis)5. Insulin resistance6. Arteriosclerosis7. RA

Side Effect1. 1st D hypotension2. Cough & bronchospasm3. Angiedema resp arrest & death4. Proteinuria (patient e compromised

renal func)5. Skin rashes6. Temporary lost of taste7. Headache, dizziness, fatigue8. Teratogenic9. Hyperkalemia10.Neutropenia

C/I Hypotension Severe renal failure Hyperkalemia Severe anemia Immune problem Neutropenia/thrombocytopenia Pregnancy/breast-feeding Bilateral renal artery stenosis/stenosis

in solitary kidney

Precaution Initial low D Diuretic use e caution Electrolyte assay (potassium) Measure bl urea/creatine (b4, 1w after,

every 3 months)

ARBs

Pharmacological Action/Effects

Block ang-II type 1 rec

No effect on bradykinin metabolism (more selective blockers of ang)

More complete inh of ang action

Side Effect

1. Similar as ACEIs2. Havard during pregnancy3. Cough/angioedema less common

VASODILATORS

- include oral agent- used for long-termed outpatient

therapy- used to treat HTN emergencies

Arterio-dilators- Hydralazine- Nifedipine- Minoxidil

Venodilators- Nitrates

Mixed arterio-venodilaters- Na nitroprusside- Prazocin- ACEIs- Trimetaphan

HYDRALAZINE Absorbed from GIT Acetylated in liver Directly relaxes small

arteries/arterioles Dec art bl pressure

Uses1. Ocombination therapy – HTN2. 1ry pulm. HTN

Side Effect1. Systemic Lupus-like syndrome2. Nasal congestion3. Flushing

4. Drug fever5. Skin rash6. Headache7. Palpitation8. Tachycardia9. Angina pain10.Anorexia, nausea, dizziness

MINOXIDIL Absorbed from GIT Metab by conjugation e glucorinic A in

liver Excrete in urine Arteriolar VD activation of K channel

hyperpolarization of cell memb relax of vasc sm ms

Uses1. Severe HTN in comb. Therapy2. Azotemic hypertensive patient3. Topical Minoxidil : ind hair growth

Side Effect1. Palpitation2. Tachycardia3. Angina pain4. Headache5. Edema6. Hypertrichosis

DIAZOXIDE Related to chlorothiazide Produce Na retntion rather than

dieresis 90% bound to plasma albumin Direct VD action on arterioles (activate

K channel)

Uses1. HTN emergency (HTN encephalopathy,

toxaemia of pregnancy)2. Hypoglycemia (d2 hyperinsulinism –

dec insulin secr from pancreatic β cells

Side Effect1. Tachycardia precipitate angina2. Hyperglycemia 3. Na/Water retention4. Hyperuricaemia5. Nausia, vomiting, constipation

SODIUM NITROPRUSSIDE

VD effect on sm ms of venoarteriolar beds (activate guanylate cyclase inc cGMP)

Rapidly metab in red cells cyanide metab thiocyanate prior to renal excr.

Uses1. HTN encephalopathy2. Refractory cases of CHF

Side Effect1. Nausea, vomiting, restlessness2. Headache3. Palpitation4. Substernal pain5. Prolonged therapy metabolic

acidosis, arrhythmias & death (accumulaton of cyanide) / delirium & psychosis (acc. of thiocyanate)

Precaution1. Infusion must not stop abruptly – avoid

rebound HTN2. In liver dis : cyanide not thiocyanate &

hence more toxic3. Higher rates of infusion acc of

cyanide4. Avoid exposure to light

CENTRALLY ACTING ANTIHYPERTENSIVES

CLONIDINEPharmacological Action/Effects

Suppressing symp outflow & dec bl pres. (agonist to central postsynaptic α2 adrenoceptors & imidazoline rec)

Dec synth of NE (dec dopamine β-hydroxylase & N-methyl tranferase enz)

Act on peripheral postsynaptic α2 adrenoceptors inh NE release

Dec plasma rennin activity, dec renal vascular resistance, maintain RBF

Dec HR Dec COP

Uses1. Mod. & severe HTN2. Prophylaxis in Migraine3. In opiate withdrawal (dec signs of

symp. overactivity)4. Sedation/Dec anxiety (preanaesthetic

medication)

Side Effect1. Dry mouth2. Sedation3. Salt/Water retention4. Withdrawal syndrome HTN crisis5. Pressor effect of clonidine not

observed6. Overdose – induce severe HTN

Drug Interaction1. Tricyclic antidepressant (TCA) – may

block antiHTN effect of clonidine2. β-blockers – may aggravate HTN crises

following sudden clonidine withdrawal3. CNS depressant – cause excessive

drowsiness e clonidine

GUANFACINE MoA similar to clonidine HypoTN effect – associated e reduction

in peripheral resistance, HR & COP Side Effect – Dry Mouth - Dizziness

Somnolence - AstheniaCONCURRENT α & β ADRENOCEPTOR BLOCKER

LABETALOL Block both αβ (selective α,non

selective β) Stimulate β2 rec Dec periph resistance lower bl

press. (not affect COP) Dec plasma rennin activity Has rapid onset as antiHTN Used for emerg. control of sev HTN e

pheochromocytoma

KETANSERIN

Lower the BP e’out postural hypotention / reflex tachy

Not affect gromerular filteratn rate/RBF

Uses1. Orally : HTN, periph vasc dis2. i.v : asthmatic attack,

thrombophlebitis, pulm emboli

DOPAMINE (D1) REC AGONIST

Pharmacokinetics cont. i.v admin metab in liver by conjugation

Pharmacological Effects stimulate D1 rec (periph art)

arteriodilatation & natriuresis

Uses1. ttt – HTN emengency2. ttt – post operative HTN

Side Effect1. Reflex Tachy2. Headache3. Flushing4. Inc Intraocular Pressure (avoid in

glaucoma)

HYPERTENSIVE EMERGENCIES- HTN encephalopathy- Cerebral stroke- Acute Lt ventricular failure- Aortic dissection- Epistaxis- Severe renal failure

Management Hospitalized Reduction of BP (in hours) Sublingual therapy :

nifedipine/captopril Parenteral therapy :

- Diuretics – frusemide/bumetanide (i.v)

- Diazoxid (i.v)- Na Nitroprusside (infusion)- Hydralazine (i.v)- Propanolol (i.v)- Methyl Dopa (i.v diluted)

- Nifedipine (i.v diluted)- Nitroglycerin (i.v)

THERAPY OF ANGINA PECTORIS

General Measures1. Alteration of life style

- Avoid stress, heavy meal, smoking- Daily dynamic exercise

2. Correct obesity & reduce fat intake3. ttt predisposing fc : hyperlipidaemia,

HF, HTN, DM

DrugsA. Acute Attack

1. Short acting nitrites & nitrates2. Sedative, analgesics

B. Between Attack1. Long acting nitrates2. β-Blockers3. CCBs4. Cytoprotective drugs5. Antiplatelet drugs: Aspirin

Dipyridamol

Surgical : Myocardial RevascularizationNITRITES & NITRATES

Chemistryi. Nitrates : nitric acid (ester)ii. Nitrites : nitrous acid (ester)

Pharmacokinetics Absorption : readily by buccal mucous

memb, GIT, skin, tracheobronchial tree (inhalation)

Sublingual admin – rapid onset, short duration

Oral – more prolonged prophylaxis Metabolism : rapidly by liver (1st pass

metab) Excretion : kidney

Mech of Actiono Involve formation of nitric oxide (NO)

o NO stimulate guanylate cyclase inh Ca entry / promote Ca exit produce cGMP coronary VD

o cGMP dephosphorylation of myosin light

chain prevent interaction – myosin e actin prod. PGE, PGI2

Pharmacological Effects (Side Effect*)

Blood Vessels- dec RV/LV end diastolic pressure- inc coronary BF- arteriolar dilatation (face ->

flushing)- VD (meningeal art throbbing

headache)Heart

- Dec VR dec cardiac work

Blood Pressure- Rapid admin high D – dec systolic &

diastolic BP & COP palpitation, weakness, dizziness & tachy

- Inc systemic venous capacitySmooth Ms

- Relax biliary, GIT, bronchial, uterine

Respiration- Inc RR- Sm ms relax in bronchospastic

disorder

Therapeutic Uses

Angina Pectoris CHF Acute myocardial infarction Biliary colic Constriction ring of uterus ttt of cyanide poisoning

How nitrates relief angina pain

[a] Reduction myocardial O2 demando Venodilatation dec VR/ R&L ventri

end diastolic volume dec systolic ejection time

o Arteriodilatation dec periph resistance

[b] Enhancement myocardial perfusiono Dilatation large epicodial vs

redistribution coronary flow to ischaemic subendocardium

o Coronary collateral VD inc BF to ischaemic area

Precaution1. Start e smallest possible D (minimize

SE)2. Nitrate – shouldn’t abruptly stopped –

avoid withdrawal symptoms3. > 3 tablets sublingually over 15 min

e,out improvement doctor – fear MI4. Nitroglycerine – not in sunlight/ e

cotton5. Burning taste – check expired date

β -BLOCKERs-ANGINA

o Useful in stable/unstable angina

o May worsen variant angina (coronary spasm

o Sudden cessation – may worsen angina (up-regulation)

o Beneficial effect :- Slow HR

i. Red myocardial O2 consumpt.

ii. Inc diastolic perfusion time- Redistribution of coronary BF to

ischaemic area- Exert cytoprotective effect- ttt typical angina (combine e

nitrates)

CYTOPROTECTIVE AGENTS

o provide emough energy to maintain efficient myocardial contraction during ischaemia

o trimetazidine :

- prod metabolic switch (inh fatty acid oxidation toward activation of glucose oxidation during ischaemia

- limits intracellular acidosis & Na/Ca accumulation

- preserves contractile func & limi cytolysis

- limits membrane damage induced by O2 free radical

THERAPY of ACUTE MYOCARDIAL INFARCT.

1. Admitted to coronary care unit2. Take Vital Sign freq.

- RR, BP, pulse3. Daily recording of ECG4. Oxygen : inc PO2, inc diffusion of O2

to ischemic myocardial5. Morphine Sulfate : relief pain6. Mepridine : relief pain (e inferior MI,

bradycardia, Av conduction delay)7. Diazepam : sedation8. β-blockers, NG, CCBs : limit size infarct9. Fibrinolytic therapy10.Anticaogulant : patient – obese,

history of prev MI/transient ischemic attack

11.ttt of arrhythmias,HF, cardiogenic shock

12.Control of risk factor : smoking, physical activity, obesity, HTN, DM

HEART FAILURE

1. General measures : rest, sedatives, freq small meals e salt restriction

2. ttt of cause : hyperthyroidism, cong H dis

3. Diuretics4. +ve inotropic agents

- Cardiac glycosides- Dopamine- Dobutamine- Prenalterol- PDE inhibitors

5. ACEIs6. VDs

7. Nitrates8. β-Blockers : Carvedilol

POSITIVE INOTROPIC DRUGS

CARDIAC GLYCOSIDES (DIGITALIS)

Chemistry : combination of aglycone & genin

Pharmacodynamics

I) +ve inotropic actiono Inc free Ca concentration during

systole inc contractile force of cardic cells :- Inh membr bound Na/K ATPase

inc intracellular Na inc in free intracellular Cai. Diminution of exchangeii. Displacement of Ca fr its

binding site- Directly facilitates entry of Ca to

cardiac cells- Inc release of Ca from sarcoplasmic

reticulum

II) Autonomic action of digitalis

o Vagal action :- Sensitization of barorec in aortic

arch/carotid sinus- Stim. Of central vagal nuclei &

nodose gang.- Sensitization of cholinergic rec in

heart

o Symp action :- Dec sensitivity of SAN & AVN to β-

stim.- Toxic D : inc cardiac symp activity

Therapeutic Uses

1. Ch congestive HF (asso. e atr fibrillation)

2. HF failing to response to other drugs3. AF :

- Red ventr rate- Elimination of pulse deficit- Improve ventr func

4. Atrial flutter5. Paroxysmal atrial tachy

C/I1. Heart block2. Hypertrophic obstructive

cardiomyopathy3. Wolf-Parkinsonism-White Syndrome4. Paroxysmal ventr. Tachy VF5. Cardiopulm dis : ch lung dis e hypoxia6. Renal/hepatic insufficiency7. Hypertensive HF8. Sick sinus syndrome

Side Effect1. Coronary constriction (toxic D)2. Nausea, vomiting3. Diarrhea, anorexia4. Excitability, convulsion5. Yellow vision6. VF & ventr tachy7. Skin rash

Precaution1. Patient in other drugs w inh AV

conduction (β-blockers)2. Patient likely to require cardioversion3. Patient e hypersensitive carotid sinus4. Never give i.v b4 sure patient not

received digoxin during prev 14 days – avoid digitalis toxicity

5. Make sure K level normal6. In elderly patient – changes in kinetics

in elderly

Fc Modifying Response to Digitalis1. Renal failure – red excr of digoxin2. Lean person – red binding digoxin to

sk ms3. Ch pulm dis, hyspoxia, acid base

imbalance: arrhythmia (inc occurance)4. Myxedema – heart more sensitive to

digit.

5. Hepatic dis – inc bl conc of digit6. Acute mMI – inc sensitivity of cardiac

ms to arrhythmogenic effect of digit.

DIGITALIS TOXICITY

1. Stop digit admin2. Stop drugs cause hypoK3. Slow i.v K – correct hypoK4. Antiarrhythmic drugs

- Lignocaine- Phenytoin- β-Blockers- Atropine

5. Fab fragment of digit

DOPAMINEo Small D : Useful in starting dieresis in

resistant HFo Mod D : enhance myocardial contr

Stim β1o Large D : adverse α-adrenergic VC

Useso Correct haemodynamic imbalance in

shock syndrome d2 AMI, trauma, open-heart surg & chr cardiac decomposition (CHF)

DOBUTAMINEo Cause D-related inc in COP (β1 stim)o Used in short-term myocardial support

CHF & MI)

PRENALTEROLo Similar to Dobutamineo Longer duration & can given orally

PHOSPHODIESTERASE INHIBITORSCARDIOACTIVE BIPYRIDINES[Inamrinone, Milrinone – more potent]

o +ve inotropic e VD propertieso Inc myocar contr & dec periph

resistanceo No effect on HR / BPo Orally/parenterally

MoA

- PDE-3 inhibitors inc cAMP (cardiac tissue & sm ms)

- Inc inward Ca (act potential)Uses

- Acute Heart Failure- Acute exacerbation of Ch HF

Side Effect1. Thrombocytopenia2. Nausea, vomiting3. Hepatotoxic4. Cardiac arrhythmias (less than digit)

CARDIAD ASTHMA & PULM EDEMA[Acute Lt Ventr Failure]

1. Hospitalization2. Semisitting/sitting position – dec VR3. ttt of causes (AF, rapid rise BP)4. Morphine

- Pain relief- Arteriolar dilatation- Venodilatation- Sedation dec anxiety

5. Oxygen (mask/tent)- Inc intra-alveolar press- Dec transudation & pulm cap pressure

6. Diuretics - Relief pulm edema7. VD

- Na nitroprusside/Nitroglucerin (i.v)- Nifedipine/Captopril (subling)

8. Rapid digitalization9. Aminophylline -

- diminish bronchospasm- Inc renal plasma flow- Inc Na excr & has diuretic effect- Inc myocardial contr

ARRHYTHMIA

Non-Pharmacological tech1. Ablation tech2. Implantable cardiovector defibrillator3. Artificial pacemaker4. Electric shock therapy

ANTIARRHYTHMIC DRUGS

Class I (Sodium Channel Blockers) Red max rate of depolarization Depress excitability Dec cond velocity Block fast Na & K channels Ia : Quinidine

DisopyramideProcainamide

Ib : Lidocaine

MexiliteneAprinidineTocainide

Ic :- Flecainide- Lorcainide- Encainide

Class II (β-Blockers)o Depression of phase-4 depolarizationo Slow conducton thru AVNo Esmolol, Metoprolol, Propanolol

Class III (K Channel Blockers)o Homogenous prolongation of act

potential duration (delay repolarization)

o Amiodarone, Bretylium, Ibulilide, Sotalol

Class IV o Ca Channel Blockers: Verapamil,

Diltiazemo K Channel Openers :

- Adenosine- Cromakalim - Pinacidil

Therapeutic classification

1. Supraventricular arrhythmias- Adenosine- Verapamil- Digoxin- β-blockers

2. Ventricular arrhythmias- Lidocaine- Mexiletine- Disopyramide- Sotalol

3. Supraventricular & Ventricular arrhythm.- Amiodarone- Quinidine- β-blockers

QUINIDINE

Chemistry : alkaloid of Cinchona bark

Phamacokinetics Absorption : 70% fr gut Peak plasma conc. : 1-3hrs Half-life : 7-9hrs (inc in renal/liver dis) Protein binding : 80-90% Metabolism : liver Plasma level – arrhythmic affect : 2-

5ug/ml

Pharmacodynamics Block Na channel antiarrhythmic action Atropine-like action α blocking properties VD, activate

symp efferent Antimalarial Antipyretic Analgesic Oxytoxic Sk ms relaxantTherapeutic Indication

1. AF (less than 6 month duration)2. Atrial flutter3. Paroxysmal atrial tachy4. Atrial/Ventricular extrasystoles5. Ventricular tachy6. Maintenance of sinus rhythm (after

successful direct current cardioversion)

Side Effect1. Cinchonism : ear ring, blurred vision2. Embolism : d2 dislodgment mural

thrmbus3. Quinidine syncope : recurrent light

headedness, episode of painting, Torsade de pointes

4. Paradoxical tachy : (atropine-like effect)

5. Idiosyncrasy : fever, skin rash, diarrhea

6. Hypotension : (if i.v)

C/I1. Complete AV block

2. Old standing AF3. Prolongation QT interval4. Congestive HF5. Hypotension6. Hypersensitivity7. Myasthenia gravis

PROCAINAMIDE Differ fr procaine (contain amide str)

Pharmacological Action/Effects Cardiac effect : as Quinidine Autonomic : weaker anticholinergic,

not cause α blockage, has ganglion blocking ef.

Therapeutic Uses1. Ventr Arrhythm. (2nd line after

Lidocaine)2. Supraventr Arrhythm. (as effective as

Quinidine – higher D)

DISOPYRAMIDE

Pharmacokinetics Absorption : well after oral admin Excretion : 50% in the urine –

unchanged

Pharmacological Action/Effects Marked anticholinergic & –ve inotropic

Therapeutic Uses1. Ventr Arrhythm. 2. Supravent Arrhythm in WPWS e’out

CHF3. Hypertrophic cardiomyopathy

Side Effect 1. Anticholinergic sympt.: dry mouth,

consti.2. Nausea, vomit, abd pain3. Congestive HF

C/I : HF, hypoT, glaucoma, bg hypertrophy prostate

LIDOCAINE

KineticsAmide local anaestheticOral admin – very low plasma conc (1st pass metb)

Pharmacological Action/Effects Dec slope of phase 4 depolarization &

pacemaker activity of Purkinjie fibers No effect on SAN Dec memb excitability of Purkinjie

fibers Inc threshold for ventr fibrillation Red APD in PF & vent ms (K chan

Opener)

Therapeutic Uses1. Ventr arrhythmias (during/after

cardiac surg, e AMI)2. Digitalis induced arrhythmias

Side Effects1. Least cardiotoxic of antiarrhythmias2. Perioral parasthsia, tremors, dizziness

PHENYTOIN (Diphenylhydantoin,DPH)

Pharmacokinetics Absorption : slow after oral admin Inactivated by microsomal enz in liver 90% bound to plasma protein

Pharmacological Action/Effects Heart : as Lidocaine ANS : depressant effect

Therapeutic Uses1. Digitalis induced cardiac arrhythmias2. Ventr arrhythmias (after surg - cong

heart dis/cong prolonged QT syndrome)

3. Epileptic seizures (antiepileptic drug)

Side Effect1. Nystagmus, vertigo, dysarthria,

confusion2. Hepatotoxicity, hirsutism, megalob

anemia, hypoT, gingival hyperplasia

PROPAFENONE Some β blocking Class III & IV activity Uses :

- Vent/supravent arrhythmias & WPWS

Side Effect :- AV block- Visual disturbance

- Metallic taste

β -BLOCKERs Substantial inc in effective refractory

period of AVN & SAN Dec conduction velocity thru AVN Propanolol : class I & IV Sotalol : class III

Therapeutic Uses1. Supravent arrhythm. (exercise-

induced)2. Digitalis induced vent arrhythm.3. Chest pain & arrhythmias of mitral

valve prolapsed (DoC)

AMIODARONE

Pharmacokinetics Absorption : well orally Extensively bound to tissue Metabolism : slowly in liver

Pharmacological effects Prod prolongation act potential ( block

K chan) Block Na chan. (class I) Block α & β rec (class II) Weak Ca chan. blocker (class III) Potent sm ms relaxant Prod marked coronary/periph VD

Therapeutic Uses1. Supravent/vent arrhythmias2. Arrhythmias e WPWS3. Control – recurrent vent

tachy/fibrllation

Side Effect1. Corneal micro-deposits2. Alteration of thyroid func3. Photosensitivity4. Pulm infiltration5. Myopathy6. Periph neuropathy7. Hepatotoxicity8. Sleeplessness9. AV block

10.Sinus bradycardia

VERAPAMIL – prevent supravent tachy, red ventr rate in AF & A flutter

MoA : delay impulse transmission thru AVNADENOSINE

K chan. opener Uses : AV tachy in WPWS

Prod controlled hypoT (in surg & diag. coronary art dis)

DIGOXIN Shorten refractory period in artial cells Prolong effective refractory period &

diminish conducting velocity in AVN & PF

Uses : control ventr response rate in AF & A fluter

MG SULFATE Admin i.v Suppress drug-induced torsade d

pointes Treat digitalis-induced ventr

arrhythmias ttt : supravent arrhythm e mg

deficiency

NEUROGENIC SHOCK (1ry)

resting a recumbent / head down position

Narcotic analgesic (morphine) Sympathomimetics – elevate BP

HYPOVOLAEMIC/OLIGAEMIC SHOCK (2ry)

Blood transfusion (in blood loss) Transfusion human plasma / plasma

substitute (blood compatible not available)

Plasma transfusion (plasma loss) Saline (severe vomit) Saline & Na lactate (severe

diarrhea) Phenoxybenzamine (only after full

replacement of iv fluid volume e blood or other appropriate fluids

Dopamine Cortisone

CARDIOGENIC SHOCK Dopamine/Dobutamine iv fluid – correct hypovolaemia VD ( Na nitroprusside) / VC

(noradren)

SEPTIC SHOCK Antibiotics Corticosteroid (high D) Dopamine/Dobutamine (CVS

support) Initial fluid – balanced salt solution Maintain ventilation

ANAPHYLACTIC SHOCK Recumbent position Adrenaline (DoC) Glucocorticoid Antihistamine (H1 antagonist) Aminophylline (iv slowly) – severe

bronchospasm Plasma transfusion (severe case)

ATRIAL FIBRILLATIONEmergency

Digitalis iv (DoC) – dec AVN conduction

Cardioversion (cause : hyperthyroidism)

Non-emergency Digitalis orally Quinidine (convert

AF sinus rhythm[SR])

ATRIAL FLUTTEREmergency

Digitalis iv Cardioversion

Non-emergency Digitalis orally convert rhythm to AF

& slow vent rate. stop digitalis SR not reappear within 48hrs :

maintain digitalis & oral Quinidine

WPWS Amiodarone Sotalol/Propanolol +

procainamide/quinid Cadioversion (show sign of CHF /

angina)

JUNCTIONAL TACHYCARDIAS Vagotonic maneuvers – inc vagal

tone Verapamil, Esmolol, Adenosine – iv

(DoC) Class Ia/Ic Class Ia/III/IV – avoid recurrence

VENTRICULAR TACHYCARDIAS

Emergency Lidocaine (1st choice –

haemodynamically stable) Amiodarone iv Cardioversion (VT persist after

lidocaine)

Propholyxis Lidocaine iv – cont at least 2-3days

after return of SR Quinidine oral – cont at least 3

months (AMI)

TORSADE DE POINTES

Mg sulfate, cardiac pacing, isoproterenol (iv) – patient e arrhythmia shorten QT

VENTRICULAR FIBRILLATION

Adjunct ttt – admin b4 & () attempts at electricaldefibrillation :- Lidocaine- Procainamide- Bretylium- Amiodarone

Implantable cardioverter-defibrillator long-termed preventive therapy

BRADYARRHYTHMIAS & HEART BLOCK

Cardiac pacemaker (ttt of choice) Atropine iv/isoprenaline Hydrocortisone iv acute case HB

DIURETICS

WATER DIURESIS Water – dilute irritant subs in urine

dec crystalluria & renal lithiasis

Mech of Action- Inc plasma volume stim vol rec (Lt

atrium) dec ADH secr

- Dec plasma osmotic pressure dec ADH secr

Inh ADH secr dec water reabs (coll ducts) inc volume voided urine (by):

LOOP DIURETICS (high ceiling) Furosemide Bumetanide Torsemide Ethacrynic Acid Indacrinone

Pharmacokinetics Absorption : rapidly fr GIT & can be given

iv Strongly bound to plasma prot. Reach site of action : actively secreted by

prox convulated tubules by orgnc acid transport syst.

Genaral CharecteristicSite of Action : thick part ascend limb of Loop

of HenleEfficacy : high (at the segment), effective at

low GFROnset : rapid (oral = ½-1hr, iv = 5-10min)Duration : short (4 hrs)

Mech of Action [A] Renal :- inh Na/K/2cl co-trnsport dec Na & Cl reabs- inh NaCl reabs in PCT- stim cyclooxygenase activity inc synth of PGE2, PGI2 inc glom filtration, promote water & Na excr

[B] Extra-renal:- venodilator action RBF & dec LV filling pres.

Uses1. Acute pulm edema2. Na & water retention (all types)3. Hypertensive emergengies (iv)4. HyperCalcemia5. Oliguria d2 acute renal failure6. HyperKalemia7. Anion overdose8. Drug poisoning9. Uricosuric agent – hyperuricaemic

Side Effect1. HypoK metabolic alkalosis2. HypoMagnesaemia3. HypoVolaemia & HypoNatraemia4. Hyperuricaemic (dec uric A excr)5. Ototoxicity (D related hearing loss)6. Glucose intolerance (inh insulin

release)7. Hypersensitivity & idiosyncrasy8. Hyperlipidemia (inc LDL & TG, dec

HDL)9.

Interaction Diuretic-induced K defi inc sens of

myocardium to digitalis Furosemide/Ethacrynic A – high plasma

prot binding capacity – compete e other (warfarin)

Ethacrynic potentiate ototoxicity of aminoglycoside

Furosemide potentiate ephrotoxicity of cephalosporins

NSAIDs potent inh of PG synth – dec furosemide diuretic effect

THIAZIDES Chlorothiazide Hydrochlorothiazide Bendroflumethazide Indapamide

PharmacokineticsAbsorption : well fr GITDistribution : widely – can cross placentaExcretion : renal orgnc acid secr syst (PCT)

General CharacteristicSite of Action : prox part of DCTEfficacy : moderate

(avoid in renal impairment)

Onset : 1hr after oral admin

Duration : vary (chloroT/hydroCT: 8-12hrs bendroflumeT : 24hrs)

Mech of ActionInh NaCl co-transport (prox part of DCT) Na & Cl reabs

Uses1. Essential HTN (initial monotherapy-

alone, combined antiHTN regimen) 2. Idiopathic hypercalcuria e recurrent

urinary calculi (dec Ca excr dec tubular fluid Ca conc dec renal Ca stone form)

3. DI (nephrogenic type)4. HyperK5. Edema & ascites (all types Na/water

ret) –d2 mild/mod congestive HF & hepatic dis

6. Toxemia of pregnancy7. Premenstrual tension d2 pelvi

congestion

METOLAZONE Thiazide-like analogue More potent Cause Na excr in advanced renal

failureSide Effect

1. HypoK metabolic alkalosis2. HypoVolaemia & HypoNatraemia3. Hypotension4. Hyperuricaemia5. Hyperglycemia6. Hyperlipidemia-d2 dec insulin

act/release7. Hypersensitivity8. Deterioration (patient e hepatic/renal

F)9. Parathesia (D related)10.Drowsiness (D related)11.Fatigability (D related)12.Impotence (D related)

INDAPAMIDE Not thiazide (qualitatively similar) Sulfonamide diuretic Useful in patient e renal insufficiency

Alter Ca flux in vasc wall dec BP 1ry use – HTN, not edema Less side effect than thiazide

K-SPARING DIURETICS Aldosterone antagonist :

- Spironolactone- Eplerenone

Direct Na-chan inhibitors :- Triamterene- Amiloride

PhamacokineticsMetabolism : largely in liverExcretion : Kidney (Triamterene, Amiloride)

General CharacteristicSite :Distal part of DCT/cortical - CDEfficacy : weakOnset : slow (Spironolactone)Duration : Amiloride < Triamterene

Mech of Action Block aldosterone rec dec Na reabs

& inc K & H secr Inh Na transport thru spec epith Na

chan

Uses1. Balance excess K loss (e

Loop/Thiazide)2. Hyperaldosteronism (1ry – Conn’s

Synd, 2ry – CHF, hepatic cirrhosis, nephritic synd)

3. Refractory edema4. Hirsutism in female (spironolactone)

– antiandrogenic effect

Side Effect1. HyperK (dec K secr)2. Hyperchloraemic metabolic acidosis

(dec H secr)3. Nausea, abd pain, drowsiness,

confusion4. Gynecomastia, impotence, menstrual

disorder

C/I1. HyperK2. Combination e other K sparing drug/ K

supplement3. Chr renal insufficiency4. Liver dis – red D (metabolized in liver)

Interaction1. Admin e ACEIs, other agent causing

hyperK & K supplement hyperK2. Spironolactone – not e

carbenoxolone (antagonist to each other)

- Spironolactone – dec ulcer healing effect

- Carbenoxolone – aldosterone-like action

OSMOTIC DIURETICS Mannitol Concenterated glucose Glycerol

- Relatively inert & largely excreted e’out metabolic changes

- Filtered freely thru glom- Undergo limited reabs by renal tubules

Mech of Action Inc osmolarity of plasma inc

osmolarity of glom filtrate & tubular fluid dec water reabs. marked inc urine volume & smaller inc Na secr

Uses1. Maintain high urine vol

- Acute renal failure (prophylaxis/ttt)- Drug intoxication (ttt)

2. Acute congetive glaucoma- dec intraoccular pressure

3. Inc intracranial tension

Side Effect1. Headache, nausea, vomiting2. Dehydration/hypernatraemia3. Hypersensitivity (mannitol)4. Hyperglycemia/glucosuria (glycerol)

C/I1. Severely impaired renal function2. Marked pulm edema3. Congestive HF4. Active intracranial bleeding

PEPTIC ULCER

Genaral lines1. Rest & sedation2. Stop smoking3. Diet ; small freq reg meals4. Avoid ulcerogenic agent: caffeine,

alcohol

Drug Treatment

1. Medication – dec acid secr- proton pump (H/K ATPase)

inhibitors- H2 rec antagonist- Anticholinergic drug

2. Drug – enhance mucosal defense mech- Antacids- Sucralfate- Colloidal Bismuth compounds- PGs analogues

3. Antimicrobials- Amoxicillin- Tetracycline- Bismuth subsalicylate - Metronidazole- Clarithromycin

PROTON PUMP INHIBITORS (PPIs) Omeprazole Lansoprazole Pantoprazole

Rabeprazole

Mech of Action Diffuse across gastric paretal cell

convert into active metabolite bind (irrev) to parietal cell in H/K ATPase enz D-dependent inh gastric acid secr (basal/stimulated)

Pharmacokinetics Unstable in acid – formulated in

gelatin capsule Metabolism : liver Excretion : bile & urine

Uses1. Gastric/Duod ulcer2. Stress ulcer3. Severe gastro-esophageal reflux dis

(GERD)4. Patho. Hypersecretory synd. ‘Zollinger

Ellison Syndrome’

Side Effect1. Diarrhea, abd colic, headache,

dizziness, skin rash (low incidence)2. D-dependent dec in Vit-B12 absorption3. Alter bioavailability – oral admin drugs4. Inh hepatic P450 isoenz (dec

elimination of phenytoin, diazepam, warfarin.

5. Gastric carcinoid tumor (rat)

H2-RECEPTOR ANTAGONISTS Cimetidine Ranitidine Famotidine

Pharmacokineticso Absorption : rapidly fr GITo Metabolism : livero Excretion : kidney

Pharmacological Actiono Competitive block of H2 reco Endocrine action (Cimetidine)o Enz inhibition (Cimetidine)

Uses1. Gastric/Duod ulcers2. Zollinger Ellison Syndrome3. Reflux oesophagitis

4. Gastritis5. Prophylaxis – injury of gastric mucosa6. Prophylaxis – gastric ulcer/bleeding in

stressSide Effect

1. Nausea, vomiting, diarrhea, constipation

2. Antiandrogenic side effect (high D)3. Hyperprolactinaemia gynecomastia

(male) & galactorrhea (female)4. Metabolic enz inhibition5. Myalgia, arthralgia & fatigue6. Headache, slurred speech, delirium,

confusion, occasionally coma7. Granulocytopenia, aplastic anemia8. Rev. hepatitis, cholestasis

Precaution Cross placenta/pass e milk – avoid

during pregnancy & lactation Rebound ulcer d2 sudden withdrawal

Interaction Cimetidine inh cytochrome oxidase

P450 dec metab/inc effect many drugs (β-blockers, CCBs, warfarin)

Cimetidine/Ranitidine– dec glucouronation of acetaminophen(paracetamol) inc its effect

RANITIDINE More potent than cimetidine Doesn’t affect cutochrome oxidase

P450 Minimal risk of untoward

antiandrogenic effects & hyperprolactinaemia

FAMOTIDINE Most potent Longer half-life No antiandrogenic / enz inhibitory

effect

ANTICHOLINERGIC DRUGS Pirenzepine (gastrozepin) Telenzepine

Mech of Action Selective blocker of periph M1

muscarinic rec (intramural ganglia/ECL cell) suppress basal gastric acid secr

Less effect on secr stimulated by food

Uses Adjuvant to H2 rec antagonist

Side Effect Untoward effect of cholinergic

blockage- Dry mouth- Mydriasis- Glaucoma- Constipation- Tachy- Urine retention

ANTACIDS

Mech of Action Weak bases – neutralize gastric acidity

(inc pH) dec total acid delivery to duod & inh pepsin act dec pain (ulcer), promote healing

Uses1. Symptomatic ttt – gastric/duod ulcer &

oesophagitis2. Duod ulcer (high D)

Classification1. Na bicarbonate (NaHCO3)2. Ca carbonate3. Mg salts- Mg hydroxide- Mg oxide & mg trisilicate4. Aluminium hydroxide5. Antacid combination

NaHCO3 Absorbable antacid Rapid onset Inc pH 5-7 Short duration

Induce systemic alkalosis, Na retention, release of CO2 rebound hyperacidity & perforation

Can combine e alginic acid (as in gaviscon)

Ca carbonate Non absorbable Relative rapid onset Ca stim secr & release gastrin acid

rebound e Na intake milk-alkali-syndrome

(hypercalcemia, constipation, alkalosis, renal failure)

Mg hydroxide Non-absorbable Rapid onset Inc pH 8-9

Mg oxide/Mg trisilicate Slow onset Long duration Coats base of ulcer by Sico2

(physically) Inc gut motility & prod diarrhea

Aluminium hydroxide Non-systemic Binds bile, pepsin & phosphate Dec hyperphosphatemia in Ch RF Has direct cytoprotective action (bind

bile, pepsin) Induces constipation

Antacid combination Gaviscon

Side Effect1. Change bowel habits

- Constipation- Diarrhea

2. Cation absorption- Ca hypercalcmia e calculi

formation & milk-alkali-synd (in renal impairment)

- Mg ms weakness & fatigue- Na systemic alkalosis

3. Hypophosphatemia e ms weakness & bone resorption

4. Rebound hypersecretion of HCl5. Dec absorption of tetracycline

(Ca,Al,Mg)6. Dec absorption of digoxin, isoniazid,

warfarin, anticholinergic drug & iron (Al)

7. Inc excr of quinidine

SUCRALFATE

Mech of Action Protect gastric/duod mucosa fr acid

pepsin :- Formation complex e prot at ulcer

site form protective layer Dec back diffusion of H Inc secr of endogenous PGs

PharmacokineticsAbsorption : slightly fr GITExcretion : stool & urine

Uses Duod/gastric ulcer heal & dec recur.

Side Effects1. Constipation2. Dec bioavailability of tetracycline,

digoxin & phenytoinCOLLOIDAL BISMUTH COMPOUNDS

Tripotassium Dicitrato Bismuthate (TDB)

Bismuth Subcitrate

Mech of Action Act locally Selective binding e exudates, mucus &

prot (in base of ulcer) Coat & protect fr acid & pepsin Inhibit pepsin activity Inc mucus & PGs synth Antimicrobial activity (gastric H.pylori)

Uses Duod/gastric ulcer

Side Effects1. Stool & teeth discoloration

2. Encephalopathy (in renal failure)

CARBENOXOLONE (biogastrone)

Mech of ActionInc prod, secr & viscosity of mucus inc mucosal resistance & dec back diffusion of H into mucosaSlow down gastric epith turn overAffect metab of PGE, PGF Dec pepsin activity

Uses1. Gastric ulcer2. Oesophagitis3. Duod ulcer

Side Effect1. Na retention2. HypoK (aldosterone-like effect)3. Edema4. HTN5. HF

PGs ANALOGUES Synthetic PGE1 analogue

(misoprostol)

Mech of Action Inh histamine stimulated cAMP production

inh gastric acid secr Cytoprotective effect e inc mucus &

biocarbonate secr Maintain gastric mucosal bl flow & stim

mucosal cellular reg

PharmacokineticsAbsorption : rapid Excretion : urine

Uses1. Peptic ulcer2. Prevention/ttt mucosal damage by NSAIDs

Side Effect1. Diarrhea2. Uterine contraction (delivery/pregnancy)

bleeding/abortion

BLEEDING PEPTIC ULCER

Hospitalization & keep in bed Blood transfusion Gastric lavage (after suction of blood) Cimetidine/Ranitidine/Omeprazole (iv –

high D) Antacids (best – Mg hydroxide, avoid –

Al hydroxide) Human thrombin, fibrin, vit K /

coagulin After bleeding stop oral regimen as

‘peptic ulcer’ Surgical (if fails)

Prophylactic therapy1. Maintain pH in neutral range (aim)2. PPIs (DoC) – sucralfate/H2 rec antag

Prokinetic Drugs & Stimulant of GI Contractility

Cholinomimetics 5-HT4 agonist Chloride chan. activator

(lubiprostone) Cholecystokinin 1 eceptor antagonist

(dexloxiglumide) Octreotide (somatostatin analogue) GABA agonists (baclofen) Nitric oxide synth inhibitors Prokinetic drugs ;

- Metoclopramide- Domperidone- Erythromycin

METOCLOPRAMIDE (primperan)

Mech of Action Cholinergic effect – release ACh fr GIT

cholinergic neurons Sensitizes intestine sm ms cells to

action of ACh

Block inhibitory action of dopamine on GIT tone & motility

Act as an agonist on 5-HT4 recUses

1. GIT investigation2. Gastro-esophageal reflux & peptic

oesophagitis3. Patient e gastric motor failure

(diebetic gastro paresis)4. Disorder of gastric emptying (post-

operative & idiopathic gastric emptying)

5. Rapid emptying of stomach into intestine (b4 emegency surg/labor)

6. Improve analgesics absorption (migraine)

7. Vomiting d2 anaesthesia, uremia, drugs

Side effect1. Sedation2. Diarrhea3. Extrapyramidal effect4. Hyperprolactinemia

Drug interactions Give e dopamine antag precipitate

acute dystonic reaction (ms contr) Corticosteroid – synergetic effect in its

antiemetic activity

DOMPERIDONE (motilium)

Mech of Action Dopamine antag (D2 rec) Less antiemetic effect than

metoclopramide Inc GI motility (block α adrenoceptor)

Pharmacokineticso Absorption : rapidly after oral admino Excretion : feceso Half-time : 7-8hrso Cross BBB

Uses1. Disorder of gastric emptying

(accelerate)2. Gastroparetic condition

3. Long-termed therapy – ch & debilitating nausea & gastric retention

4. Counteract GIT effect of levadopa & bromocriptine in Parkinson’s dis

5. Chr gastric reflux (inc low esoph spinc pres)

6. Vomiting d2 cancer chemo.

Side Effect1. Headaches2. Hyperprolactinemia (d2 antag of D2

rec)

ERYTHROMYCIN Macrolide antibiotic Prokinetic activity in stomach Used for diabetic gastroparesis

Other agents that suppress GIT motility- Organic nitrates- CC antagonists- Botulinum toxin

GASTRO-ESOPHAGEAL REFLUX DIS (GERD)

Non-Drug measure1. Sleeping in high pillow2. Avoid :- Large meal & eat b4 sleep- Alcohol, smoking, spicy & coffe- Aspirin, NSAIDs- Tight clothes aroung abd.3. Weight reduction

Drug Therapy1. Prokinetic drugs2. Antacids & Antacid Anginic Acid

Products- Neutralize gastric fluid- Inc lower esoph spinc pressure- Gaviscon :

i. Alginic acid + Mg trisilicate + Al hydroxide gel + NaHCO3

ii. Form highly viscous foamy solution of Na-alginate

iii. Prevent gastric reflux3. H2 antagonist4. PPIs- Provide symptomatic relief- Provide esoph. Healing in severe GERD

& severe erosive esophagitis

5. Surgical

Drug inc LESP – antacids, cholinergic, prokineticsDrug dec LESP – anticholinergic, nitrates

PORTAL SYSTEMIC (HEPATIC) ENCEPHALOPATHY

A) Treat precipitating fc- e.g : drug, infection, GI bleeding

B) Treat hyperammonemia- Dietary restriction of prot- Lactulose- Metronidazole- Neomycin- Flumazenil- Branched chain amino acids

(BCAA)

C) Treat metablic complication- Hypoglycemia – by 10% glucose

solution- Hypokalemia – by K chloride (iv)

LACTULOSE Non-absorbable disaccharide Metabolized in colon by intest.

Bacteria Have osmotic laxative action Used for long-termed therapy for PSE Improve prot tolerance in patient e

advanced hepatic cirrhosis Admin as retention enema for patient

in impending coma, or coma stage of encephalopathy (slow onset)

Side effect : abd distention, flatulence, nausea, vomiting, diarrhea

METRONIDAZOLE Dec ammonia prod fr GI bact Side Effect :

i. renal impairment ii. ototoxicity

NEOMYCIN Non absorbable aminoglycoside

antibiotic Dec elevated blood ammonia level in

patient e PSE by destroy some intest. bact

In acute exacerbation : rapid > lactulose, toxic > lactulose

Side effect : diarrhea, rev malabsorption, super infection, inflammatory bowel dis, ototoxicity, nephrotoxicity

FLUMAZENIL Alternative – conventional ttt failed Antagonizes benzodiazepines-like

mediators produced during PSE Parenteral route Short duration

BCAA Dec false transmitter form (GABA-like) Improve some measure in ch PSE –

liver function test & nutritional measure

ACUTE VARICEAL BLEEDING (d2 portal HTN)

A) Fresh blood transfusion/fresh frozen plasma

B) Drugs – dec intravariceal bleeding (constriction of splanchnic BF & hence dec portal pressure)

- Somatostatin & octreotide- Glypressin

i. Analogue of vasopressinii. Long durationiii. Inc pulm & mean BP dec

systemic VC effect (combined e nitroglycerine)

- Vasopressini. Act as glypressinii. Side effect : cardiac VC, skin art VCiii. Used as combined e nitroglycerine

C) Sclerotherapy- By injection of varices by spec

sclerosant liquid (ethamolin, Na morrhuate)

D) Drugs – prevent re-bleeding fr varices- Propanolol- Venodilators : isosorbide dinitrate- H2 blockers : ranitidine / famotidine- Surgical

VOMITING TTT (ANTIEMETIC DRUGS)

H1 rec antagonist- Meclizine- Promethazine

Muscarinic rec antagonist- Hyoscine/scopolamine

Dopamine antagonist (D2)- Phenothiazine- Butyrophenones- Metoclopramide- Domperodone

5-HT3 antagonist- Granisetron- Ondansetron

Miscellaneous agents- Benzodiazepines- High D – steroids- Vit B6- Nabilone

H1 REC ANTAGONISTS

Mech of Action Inh cholinergic pathway of vestibular

apparatus

Uses

Nausea, vomiting (ass e motion sickness)

True vertigo Vomiting d2 drugs

Side Effect (atropine-like action) Dry mouth Blurred vision

CHOLINERGIC ANTAGONISTS

Mech of Action Block muscarinic receptor

Uses Prevention & ttt of motion sickness

Side Effect Drowsiness Dry mouth Blurred vision

DOPAMINE ANTAGONISTS(Phenothiazines, butyrophenones)

Mech of Action Block D2 in CTZ Inh periph transmission to vomit

center

Uses Vomiting d2 : Cancer chemo

Radiation therapyPost operativeMigraine

Side Effect Anticholinergic effect- Drowsiness, dry mouth, blurred vision Extrapyramidal effect – dystonia

5-HT3 ANTAGONISTS

Mech of Action Block 5-HT3 rec in CTZ

Uses Prevent chemo-induced vomiting Post-operative nausea & vomiting

Side Effect : Constipatin & headache

NABILONE

Mech of Action Block opiate rec

Uses Control chemo-induced vomiting

Side Effect Sedation Psychoactive effect Dry mouth

VIT B6

Mech of Action Related to GABA & glutamate balance

Uses Vomiting of pregnancy

EMETICS

1. SYRUP IPECAC MoA : stim CTZ & induce GI irritation Use : remove unabsorbed toxin fr

stomch

2. APOMORPHINE MoA : dopaminergic agonist – stim

CTZ Parenterally admin (SC) Not toxic Can cause CNS, RC depression

ANTISPASMODICS

Anticholinergic drugs- Propantheline- Dicyclomine- Oxphencyclimine- Oxyphenonium- Buscopan

Direct Sm Ms relexants- Papaverine- Mebeverine

- Alverine- Camylofin (avafortan)- Pinaverium- Drotaverine

Mixtures- Librax (clinidium +

chlordiazipoxide)- Donnatal (hyoscyamine +

atropine + scopolamine + phenobarbital)

ALVERINE CITRATE, MEBEVERINE & DROTAVERINE

MoA : Direct sm ms relaxant

Uses 1. GIT spasm2. Irritable bowel syndrome3. Relief of period pain

PAPAVERINE

MoA : inh phosphodiesterase enz elevation of cAMPAlter mitochondrial resp.

Uses1. Spasm – GIT, Bile duct, Ureter2. VD (cerebral, coronary) in

subarachnoid he & coronary art bypass surg

3. Sm ms relexant – microsurgery4. Erectile dysfunction (male)

Side Effect1. Polymorphic ventri tachy2. Constipation3. Inc transaminase level4. Inc alkaline phosphatase level5. Somnolence6. Vertigo

LIBRAX

MoA : 1. Relax digestive syst2. Reduce stomach acid3. CNS depressant

Uses

1. Stomach/intestinal prob – ulcer, colitis2. Abd/stomach spasm/cramps

Side Effect1. Constipation2. Eye pain3. Mental depression4. Skin rash5. Confusion6. Drowsiness7. Dry mouth, nose, throat8. Tachycardia9. Skin flushing

CONSTIPATION

Drugs cause constipation

1. Antacid

2. CCBs

3. Ms relaxant - Baclofen- Dantrolene

4. Opioids- Codeine- Dextropropoxyphene- Fentanyl- Loperamide- Morphine

5. Anticholinergic (atropine)

Non-drug treatment

1. Fluid intake2. Reduce strong/excess tea/coffee3. Fiber intake (fruit, vegetable)4. Exercise

Drug treatment (LAXATIVES)

1. Bulk laxatives- Agar- Psyllium seeds- Dietary fiber

2. Osmotic laxatives- Lactulose- Mg sulphate

- Na sulphate- Na-K tartrate

3. Stimulant/irritant laxatives- Castor oil- Anthraquinone derivatives- Diphenylmethane derivatives –

Phenolphthalein & bisacodyl

4. Surfactant laxatives (stool softeners)- Docusate salt – Na, K, Ca of dioctyl

sulfosuccinate- Liquid paraffin- Glycerin suppositories

5. 5-HT4 rec antagonist

Uses 1. Constipation2. Hepatocellular failure3. Prepare & clean bowel – xray,

proctoscopic, colonoscopic4. Hasten excretion of poisonous subs5. Postoperative – after hemorrhoids

BULK LAXATIVES

MoAretain water in gut lumen gels distending LI & stim peristalsis

Useconstipation e diverticulosis, irritable BS & ulcerative colitis

Side Effects1. Flatulence2. Bind digoxin, salicylate3. Form masses in gut int obstruction

OSMOTIC LAXATIVES

1. Saline LaxativesMoA

- Retain water in lumen (osmosis) distention & reflex in in peristalsis

Side Effects- Congestive HF- Precipitate dehydration- hypoK- RF

2. Polyethylene GlycolMoA- Retain in lumen by its osmotic

nature effective laxative effect

Side Effect- Electrolyte imbalance- Bowel dependent

3. LactuloseMoA- Transformed by bact lactic A +

acetic A (have osmotic laxative activity) inc fluid accumulation in colon

Other Use- Hepatic encephalopathy

Side effect- Abd discomfort- Bad taste

IRRITANT/STIMULANT LAXATIVES

MoA- Induce inflam in SI & LI

accumulation of water/electrolytes & stim int motility

1. CASTOR OILUse- Not for common constipation- Prepare radiological exam

Side Effect

- Bad taste- Morphologic change alter

mucosal permeability, colic, dehydration

2. ANTHRAQUINONE GLYCOSIDE Cascara Senna Danthron Aloes

Side Effect- Red discoloration - urine- Cathartic effect in babies (milk)- Bg pigmentation of colon- Cathartic colon- Inc menstrual blood flow

3. PHENOLPHTHALEIN

MoA- Stim sensory nerves reflex stim

– peristalsis alter active electrolyte transport

Side Effect- Cumulation- Mucosal & liver damage- Dermatitis- Itching- Colored urine

4. BISACODYL

MoA : as Phenolphthalein

Side Effect- Atonic colon (used > 10 days)- Mucosal damage- Fluid/electrolyte disturbance

STOOL SOFTENER

1. DIOCTYL

MoA- Facilitate incorporation of water into

fatty intestinal material

Uses- Replace mineral oil – reduce strain of

defecation

2. LIQUID PARAFFIN

MoA- Coats intestine dec water

absorption soften stool

Uses- Ch constipation

Side Effect- Malabsorption of fat soluble- Infiltration in liver- Granulomatous reaction mg

3. GLYCERIN SUPPOSITORIES

MoA- Promoting stool evacuation tissue

dehydration soften inspissated faecal material

Use- Re-establish proper bowel habit

(temporary use)

Side Effect- Local discomfort- Burning- Hyperaemia- Irritation

DIARRHEA

A) Maintenance - Fluid/Electrolytes Balance

B) Non-Specific Antidiarrheal Therapy1. Adsorbents

- Kaolin- Pectin- Dietary fibers- Active charcoal

2. Bismuth Subsalicylate3. Anti-cholinergic agents (atropine)4. Opiates/opioid containing

preparation- Diphenoxylate- Loperamide (Imodium)

5. Cholestyramine

C) Specific Anti-Infective AgentsD) Anti-Inflam Drugs

1. Glucocorticoid2. Sulfasalazine3. Immunosuppressive agents

ADSORBENTS

MoAAdsorption of microorga./toxic compoundsCoat mucosaProtectants

BISMUTH SUBSALICYLATE

MoA Provide protective coat for mucosa Subsalicylate hydrolyzed by

coliform salicylic A inh synth of PG (int inflam, hypermotility, secr)

Usesttt & prophylaxis of traveler’s diarrhea

ANTICHOLINERGIC AGENTS

MoABlock response of int sm ms to cholinergic stim inh colonic peristalsis

UsesDiarrhea e cramps

OPIATES/OPIOID CONT. PREPARATION

MoA Act on opiate Mu rec in submucous

plexus inc int segmenting contraction & inc resistance to flow thru lumen

Dec fluid/electrolyte secr into lumen Inc viscosity of luminal content & stool

form. Act on presynaptic opioid rec dec

ACh release

DIPHENOXYLATE Synth morphine derivative Cross BBB poorly Therapeutic D no CNS effect Give e atropine dec motility more

LOPERAMIDE (IMODIUM) Synth morphine derivative Can’t cross BBB Inactivation calmodium dec int secr Uses : irritable bowel synd Side Effect

- Anti-cholinergic- Narcotic effect- Precipitate toxic megacolon in

ulcerative colitis

CHOLESTYRAMINE Uses :

- diarrhea caused by bile salt malabs- pseudomembranous colitis (e

vancomycin)

SPECIFIC ANTI-INFECTIVE AGENTS

E coli : TetracyclineSalmonellosis :

ChloramphenicolCo-timoxazole

Campylabacter : ErythromycinShigella : AmpicillinMost cases bact diarrhea :

CiproflaxacineNorfloxacinCo-trimoxazole

Amoebic dysentery : Diloxanide furoate +

MetronidazoleGiardiasis :

Metronidazole

GLUCOCORTICOID

MoA : stim. Na-absorption fr intestine

Uses1. refractory diarr. unresponsible to other2. control acute episode

SULFASALAZINE

MoA Inh of PG & Leukotreines prod Alter cytokine func Free radical scavenger Prod cytoprotective &

immunosuppressive act

Uses1. Active ulcerative clitis2. Rheumatoid arthritis

Side Effect1. Allergy2. Nause3. Vomiting4. Headache5. Fever6. Bone marrow depression7. Megaloblastic anaemia8. Serum sickness

IMMUNOSUPRESSIVE AGENTS ACTH Hydrocortisone Prednisone Cytotoxic drug- Azathioprine- Mercaptopurine- Effective to patient e ulcerative colitis,

crohn’s dis- More effective as prophylaxis in

crohn’s dis Cyclosporine : limited use – toxicity on

ch use

DRUG THERAPY – TRAVELER’S DIARRHEAProphylaxis : ciprofloxacinTreatment : replace fluid/electrolytes

CiprofloxacinCo-trimoxazoleBismuth subsalicylate

BILE FLOW & CHOLELITHIASIS

Choleretics : inc bile prod Bile acids Bile salt

Hydrocholeretics : inc bile volume Dehydrocholic acid

Cholagogue : stim GB evacuation

Mg sulphate Cholecystokinin Fat/olive oil

CHENODEOXYCHOLIC ACID (CDCA)

MoA Dec hepatic cholesterol synth/secr Dec cholesterol saturation of bile Inc bile acid pool & phospholipid

output

URSODEOXYCHOLIC ACID (UDCA) Metabolite of CDCA More potent in dec hepatic cholesterol

synth UDCA & CDCA – interconvertible

during enterohepatic cycling in man Given orally Side effect : diarrhea (CDCA -

common, UDCA – unusual)

PARASYMPATHOMIMETICS(cholinomimetics)

Classification1. Directly acting Choline esters- Acetylcholine- Bethanechol- Methacholine

- Carbachol- Cavimilline

Alkaloids- Pilocarpine- Muscarine- Nicotine- Lobeline

2. Indirectly acting (choline esterase inh) Reversible- Physostigmine- Neostigmine & substitutes- Tacrine- Donepezil

Irreversible- Organophosphorous compound

3. Augment ACh action- Sildenefil

ACETYLCHOLINE (ACh)

Pharmacokinetics Inactive orally Poorly absorbed iv – short duration (d2 rapid

metabolized) resynth – pseudocholinesterase (few

weeks), true cholinesterase (months)

Pharmacological Action stim muscarinic rec stim nicotinic rec

Therapeutic uses limited (d2 short dur & non-selectivity)

Side Effect

all except thoese needed therapeutically

Phamacalogical Effect

CVSo Dec all cardiac properties exc

conduction in atriao VDo Dec BP (small D)

GITo Inc peristalsis (gastric/intestinal)o Relax sphinctero Stim salivary/gastric sect

Lungo BCo Inc bronchial secr

Urinary To Contract detruser mso Relax sphinctero Inc peristaltic waves – ureters

Eyeo Miosiso Dilate central retinal artery

Sk Mso Stim motor end plate

METHACHOLINE

Pharmacokinetics not effective orally subcutaneous – best iv/im – abolish selectivity & inc toxicity not hydralized by psuedoCE &

destroyed less rapidly by true CE longer duration

Pharcological Action stim muscarinic rec (CVS)

Uses paroxysmal atrial tachycardia

Side Effect Heart block Hypotension Bronchoconstriction

BETHANECHOL

Pharmacokinetics Long duration – not hydrolyzed by CE Effective orally

Pharmacological Action Stim muscarinic rec (alimentary tract

& urinary bladder)

Pharmacological Effect Inc motility Relaxes sphincters Inc secr

Uses Post-operative retention of urine Paralytic ileus Acute dilatation of stomach

CARBACHOL

Pharmacokinetics Effective orally Long duration

Pharcological Action

Stim musc/nicotinic rec

Uses Miotic – glaucoma

Side Effect : as ACh

CEVIMILLINE Direct muscarinic agonist Not hydrolyzed by CE Taken orally Uses : xerostomia

PILOCARPINE

Pharmacokinetocs Not inactivated by CE Longer duration

Phamacological action Stim M rec

Pharmacological Effect : as ACh

Uses Glaucoma Counteract mydratic effect of

homatropine & eucatropine Xerostomia

PHYSOSTIGMINE (eserine)

Phamacokinetics Diffuse readily thru mucous memb Caross BBB

Pharmacological Action Bind to esteratic & anionic site of CE enz

accumulation of ACh in effector organ

Phamacological Effects Muscarinic/nicotinic effect CNS : headache, restlessness, insomnia,

nightmares, tremors & convulsions

Uses Glaucoma

Counteract mydriatic effect & cycloplegia by atropine

Alternatively e mydriatics Atropine poisoning & tricyclic

antidepressant toxicity Alzheimer dis

Side Effects All muscarinic/nicotinic/CNS effect

NEOSTIGMINE

Pharmacokinetics Irreg absorbed fr GIT Can’t sross BBB

Phamacological Action Rev inh of CE Direct stimulant action on NMJ

Pharmacological Effect Muscarinic – more on alimentary T Nicotinic – more on NMJ No CNS effect

Uses Myasthenia gravis Antidote to D-tubocurarine Post-operative retention of urine Paralytic ileus

Side Effect All muscarinic & nicotinic effect (exc

needed therapeutically)

NEOSTIGMINE SUBSTITUTES

1. PYRIDOSTIGMINE More selective on NMJ than

neostigmine Longer duration Uses : Myasthenia gravis

2. AMBENONIUM : as pyridostigmine

3. EDROPHONIUM

More selective on NMJ than neostigmine

very short acting Uses :

i. Myasthenia gravis (diag)ii. Myasthenic crisisiii. Diff () myasthenic crisis &

cholinergic crisisiv. Antidote for D-tubocurarinev. Paroxysmal atrial tachy

4. BENZYPYRINIUM More selective on GIT & urinary T Weak action on NMJ Uses :

i. post-operative urine retentionii. paralytic ileus

DONEPEZIL – TACRINE & RIVASTIGMINE centrally acting rev CE inhibitors readily cross BBB act – inc conc of ACh at central

cholinergic synapses uses : Alzheimer’s Dis

MYASTHENIA GRAVIS

Diagnosis :1. Edrophonium- Improve sk ms contr.

2. Neostigmine + atropine- Atropine given b4 – produce initial

brady followed by tachy- Initial brady by atropine – potentiate

brady by neostigmine cardia arrest

Treatment :1. CE inhibitors

i. Ambenonium/pyridostigmineii. Neostigmine + atropine

2. Ephedrine3. Immunosuppressives4. Corticosteroids5. ACTH

6. Cyclosporine7. Thymectomy8. KCl & spironolactone

ORGANOPHOSPHOROUS COMPUNDS Nerve gases : Sarin & Soman Insect killer : Malathion, Parathion

& TEPP Drug used clinically : DFP

MoA Bind covalently to CE ACh

accumulate at effector site parasymp. Effect

Takes about 1-12hrs looses alkyl & alkoxyl group (aging of enz)

Phamacological Effect Muscarinic, Nicotinic & CNS effect

Side Effect Resp – bronchospasm, resp distress CVS – brady, hypoT, excessive cold

sweat GIT – excessive secr, abd colic,

diarrhea CNS – severe miosis, headache, sk ms

fasciculation, convultion & coma

Treatment of Side Effects

Protection1. Wear gloves & masks2. Thorough washing of vegetables3. Kept away fr children

Treatment1. Stomach wash2. Skin wash e Na bicarb. / ethyl alcohol3. Maintain air passage4. Atropine – high D5. Cholinesterase re-activator

6. Anticonvulsant (dialpezam) – convulsion

SILDENAFIL

Pharmacokinetics Rapidly absorbed after oral admin Oral bioavail. – 40% Widely distrib. Metab. By cytochrome P450 enz Excreted 1rily in feces

Uses Male erectile dysfunction

Side Effect Headache (mild, transient) Blurred vision Nasal congestion

C/I Don’t take e organic nitrate

profound hypoT, reflex tachy, worsen angina pectoris, death

PARASYMPATHOLYTICSA) Naturral Alkaloids- Atropine- ScopolamineB) Synthetic Esters

1. Use 4 ttt – parkinson’s disi. Benzatropineii. Trihexyphenidyliii. Cycrimineiv. Biperiden

2. Use to prod mydriasis/cycloplegiai. Atropineii. Homatropineiii. Eucatropineiv. Cyclopentolatev. Tropicamide

3. Use to prod BDi. Ipratropium

ii. Tiotropium

4. Use as antisecretory/antispasmodici. Buscopanii. Novatropineiii. Propantheliniv. Pipenzolatev. Pirenzepinevi. Glucopyrrolatevii. Dicyclomineviii. Methscopolamine

5. Used for genitourinary systi. Oxybutyninii. Glucopyrrolateiii. Dicyclomineiv. Emepronium

ATROPINE

Pharmacokinetics Readily cross membrane barrier Well distrib. Metabolism in liver Renal excretion Half-life : 2 hrs Duration : 4-8hrs

MoA Competitive pharmacologic antagonist Blocking effect can be overcome by

inc conc of muscarinic agonist

Uses

CVS1. Bradycardias (by excessive β blocker,

by α stimulant-noradrenaline)2. Heart block

CNS1. Motion sickness

2. Parkinson’s dis

Eye1. Fundus exam2. Iritis & iridocyclitis3. Counteract effect of miotics4. Alternative e miotics

Bronchi BC in asthma & c hobs. pulm dis

GIT GIT spasm Acid peptic dis

Bladder Cystitis Nocturnal enuresis Ureteric spasm in renal colics

Side Effect Dry mouth Skin flushing Urine retention Acute attack of glaucoma

Toxicity1. Hyperthermia/atropine fever –child2. Dryness of secr3. Acute angle-closure glaucoma4. Urinary retention5. Constipation6. Blurred vision7. Lost light reflex8. CNS : sedation, amnesia, delirium,

halluci.9. CVS : block intraventri. conduction

Toxicity ttt1. Control env. temp2. Catheterization3. Avoid over ttt of convulsion

(barbiturate)4. Physostigmine – counteract CNS effect

C/I & Precaution1. Used cautionly in infant -

hyperthermia2. Glaucoma esp closed angle form3. Prostatic hypertrophy

NEUROMUSCULAR BLOCKING AGENTS

A) Competitive (non-depolarizing)- D tubocurarine- Gallamine

B) Depolarizing- Decamethonium- Succinylcholine

Competitive (non-depolarizing)

Pharmacokinetics Long half-live Given parenterally Prolonged action in patient e impaired

renal function

MoA Surmountable blockers Compete e ACh CE reverse their effect Act directly to plug ion channel

operated by ACh rec (some)

Depolarizing

Pharmacokinetics Metabolized by plasma CE Duration : few minutes (single D) Given by continuous infusion (prolong

paralysis) Not rapidly hydrolyzed by true CE

MoA Like nicotinic aginist Depolarize NM end plate Twitching & fasciculation – accompany

the initial depolarization Plug end plate channel

Uses

1. Induce muscular relaxation (during general anesthesia & to facilitate endotracheal intubation

2. Control convulsions – during ECTToxicity

1. Resp paralysis2. Aiutonomic effect & histamine release3. Mg hyperthermia4. Post-operative pain & acute hyperK

(d2 severe ms contr)

Interactions1. Inhaled anesthetics – strongly

potentiate & prolong NM blockage2. Aminoglycoside antibiotics &

antiarrhythmic – prolong & potentiate relaxant action of NMB to lesser degree

C/I & Precaution1. General anesthetic – reduce D of

curare2. Antibiotics – curare-like action3. Quinidine & lidocaine – curare-like

action4. Glaucoma – prevent by prior

tubocurarine5. Myasthenia gravis – sensitive to

compet. Agents & resistant to depolarizing agents

6. Tetracyclines & CCBs – inc NM blockage

GANGLION BLOCKER AGENTS Trimetaphan Pentolinium Mecamilamine

Pharmacological Action Competitive blockade of autonomic

ganglia

GANGLION STIMULANT Nicotine Lobeline

Phamacological Action Stim of ganglia Large D – initial stim of ganglia

followed by block Stim chemoreceptive & neuroeffector CNS stim

Uses Neonatal asphyxia (lobeline – as

analeptic - intraumbilical)

Side Effect1. VC2. Tachy3. Elevated BP4. Nausea, vomiting, diarrhea5. Dryness of exocrine gland6. Tremors, convulsion7. Depression

COUGHANTITUSSIVES

Reduce freq/intensy of coughing

Classification1. Peripheral

i. Demulcent - linctuseii. Steam inhalation – menthol

2. Central- Narcotic

i. Codeineii. Pholcodein

- Non-narcotici. Dextromethorphanii. Noscapineiii. Levopropoxyphen

3. Central/Peripherali. Benzonatateii. Carbetapentane

CODEINE Weak analgesic effect Respiratory depressant Drug of abuse

Uses Acute/ch cough

Side Effect Nausea, vomit, constipation, dizziness Dryness of mucosa, thickening-sputum Dependence Resp depression/excitement

PHOLCODEINE Little/no analgesic effect Less addictive property than codeine

DEXTROMETHORPHAN Act centrally Selective depressant action on cough

center No analgesic, resp depressant,

dependence liability Not prod constipation Used as over the counter Overdose antagonist by naloxone

NOSCAPINE Selective central antitussive No CNS effect Papaverine-like action Relax. Of bronchial ms

LEVOPROPOXYPHEN Selective central antitussive No opioid effect

BENZONATATE/CARBETAPENTANE Depress pulm stretch rec Cough rec Inh transmission of afferent impulse to

cough center Have central antitussive effect

EXPECTORANTS

1. Sedativei. Alkalineii. Nauseantiii. Iodidesiv. Guaifenesin

2. Stimulant/aromatic

i. Creosoteii. Guaiacol

ALKALINE Na/K citrate & acetate – inc alkali

reserve of blood Na/K stim bronchial gl secr

protective mucus Dissolve mucus/sputum less sticky

easily expectorated Uses – early dry stage of acute

bronchitis

NAUSEANT Stim sensory nerve ending (stomach)

reflex copious bronchial secr Uses - early dry stage of acute

bronchitis e.g :

i. tincture ipecacuanha, ii. tincture senega, iii. ammonium chloride

IODIDES Rapidly reach bronchial mucus gland

stim mucus secr (low viscosity watery)

Have mucolytic action Uses – cough e ch resp dis & ch BA Side effect :

- Metallic taste- Inc secr of lanchrymala, nasal, saliv

glands painful swelling of gland- Gastric irritation (long used)- Thyroid dysfunc- Allergic manifestations

C/I :- Acute bronchitis- Tuberculosis

GUAIFENESIN Inc rept tract secr Dec adhesiveness & surface tension of

viscid sputum expectoration

CREOSOTE/GUAIACOL Dec sputum amount Deodorant action Mild antiseptic action Stim healing/repair of ch. Inflam. resp

mucosa Uses : lung abscess, ch bronchitis,

bronchiectasis

MUCOLYTICS Reduce viscocity of resp tract secr

liquefaction of viscid sputum Not inc secr amount

a) Bromhexine (bisolvon)b) Ambroxol (mucopect)c) Acetyl cysteine & carbocysteined) Iodidese) Enzymesf) Water vapourg) Cough mixture

BROMHEXINE Reduce viscocity by fragmenting its

glycoprot.

Uses : 1. Ch bronchitis2. Ch obstractive pulm dis3. Ch sinusitis4. Otitis media

AMBROXOL Metabolite of bromhexine As bromhexine but less gastric irritant

ACETYL CYSTEINE/CARBOCYSTEINE Have free sulphydryl groups that open

disulfide bond in mucus reduce viscocity

Used to dissolve inspissated mucus plug

Uses :1. Ch resp dis- Bronchitis- Emphysema- Bronchiectasis- Cystic fibrosis

2. Acute resp dis- Bronchitis- Pneumonia- Asthma

3. Post-operative/post traumatic pulm complication

4. Care of tracheostomies

IODIDES By potentiate effect of proteolytic enz

ENZYMES Trypsin, chymotrypsin & streptokinase

WATER VAPOUR Excellent expectorant/mucolytic Dilute/liquefies resp sect Act rapidly

COUGH MIXTURE Symptomatic ttt Contain : expectorant,

sympathomimetics, antihistamine Criteria :

i. No more than 3 active ingredientsii. Each – present in effective safe

conc & contribute to ttt for w the product is used

iii. Used only – multiple symptoms present concurrently

BRONCHIAL ASTHMA

BRONCHODILATORS1. β-adrenergic agonist2. Methyl Xanthines3. Muscarinic rec antagonist

β -ADRENERGIC AGONIST

a) Non-selective- Adrenaline- Isoprenaline- Ephedrine

b) Selective

- Salbutamol [short acting]- Terbutaline [short acting]- Fenoterol [short acting]- Salmeterol [long acting]- Formeterol [long acting]

MoA Adrenergic β-agonist bind e β rec

activate adenyl cyclase convert ATP to cAMP i. Relax. of airways msii. Inh of release of BC subs fr mast

celliii. Enhance mucociliary funciv. Dec microvascular permeability

ADRENALINE Stim α rec VC of submucus vs

mucus memb decongestion (addition to BD)

SELECTIVE β2 AGONIST Least systemic effect – can given to

hypertensive patients Uses : - acute episode BA, - prophylactically – prevent airway

obstruc.

Side Effect :- Tremor sk ms, nervousness, weakness- Tachy (2ry to hypoT by sk VD)- hypoK- tolerance- loses its selectivity – given large freq

D

XANTHINES CNS stimulants

1. Natural Caffeine Theophylline Theobromine

2. Synthetic Aminophylline

Pharmacokinetics Well absorbed fr GIT Eliminated mainly by hepatic

metabolism Clearance reduce in

- Infant < 6 months- Cirrhosis, HF, corpulmonale- Erythromycin, quinolones,

cimetidine Clearance inc in

- Smoking- Rifampin, phenobarbitol,

carbamazepin

MoA Block cell surface rec for adenosine Inh phosphodiestrase enz (PDE) inc

intracellular cAMP relax of airway ms & inh BC subs fr mast cell

Stim release of catecholamines fr adrenal medulla & inh COMT enz BD

Improve diaphragmatic contr & reduce resp ms fatigue (theophylline)

Exert anti-inflam & immunomodulating effect (theophylline)

Uses Symptomatic relief – acute attack of

BA CNS depressant overdose Physical fatigue, Headache & Migraine Paroxysmal dyspnea ass e Lt HF &

acute Lt side HF (acute pulm edema) Refractory case of congestive HF Neonatal apnea syndrome Acute biliary colic

Side Effect Nausea, vomit, anorexia, react PU Palpitations, tachy, precordial pain,

arrhythmias

hypoT, syncope, cardiac arrest (rapid iv)

irritability, insomnia, nervousness, conv.

Tachypnea, resp arrest (large D)

PrecautionReduced D to following :

Severe cardia dis, severe hypoxemia [inc sensitivity arrhythmias]

Renal & hepatic dis (elder/neonate) [dec clearance]

Not to patient e PU

MUSCARINIC ANTAGONIST Atropine – block M rec unoppse β2

action BD Side effect – excessive dryness of

sputum diff to expectorate asthma attack & episode of cough

IPRATROPIUM BROMIDE Quaternary amine derivative of

atropine Poorly absorbed fr mucosal surface Not enter CNS – fewer side effect More selective BD effect Less effect on sputum viscocity Less effective than β2 agonist Given in combination e β2 agonist

more effective, longer duration

ADRENOCORTICAL STEROIDES Glucocorticoid By inhalation – dec side effects

MoA Inc stability of endoth. Cells, sm ms

cells & lysosomes Reduce cap permeability Suppress immune mech & reduce ab

synth

Potentiate effect endogenous cathecolamine by prevent their non-neuronal uptake & inc no of β2 rec

Modify inlfam response in airway Reduce bronchial hypersensitivity Corticosteroids – inh phospholipase A2

enz prevent form. Oh BC PGs, LTs, platelet activating fc

Uses Acute BA Ch asthmatic patient – severe

disabling asthma

Side Effect (high D-long duration) Adrenal suppression Cushing syndrome Weight gain Salt/water retention Depression Psychosis Growth retardation (child) Peptic Ulcer Cataract Oropharyngeal candidiasis

Precaution Withdrawal gradually – avoid

Addison’s Diet – rich in K & low in NaCl, CHO Continues check–weight, edema,

sugar, BP Acute inf – ttt by antibiotic, dec steroid

LEUKOTRIENES INHIBITORS Mediators in inflam events

contribute to bronchospasm in patient e asthma

e.g : Zafirlukast, montelukast, Zileuton

PROPHYLACTIC TTT

MAST CELL STABILIZERS1. DISODIUM CROMOGLYCATE (cromolyn)

MoA Stabilizes mast cell inh Ca influx

across mast cell prev mediator release

Suppress inflam cell influx Chemotactic activity

Antigen induced reactivity

Uses Mild/moderate asthma (prophylaxis) Allergic rhinitis/hay fever Allergic conjunctivitis Ulceratice colitis & crohn’s dis

2. NEDOCROMIL Similar as cromolyn Greater antiasthmatic potency

3. KITOTIFEN Similar as cromolyn Has antihistaminic effect Uses : - BA (prophylaxis)- Allergic rhinitis- Allergic skin dis

Side effect :- Sedation- Dry mouth- dizziness

OTHER DRUGS1. Mucolytics/Expectorants2. Mixture of O2 & Helium – severe case

of acute BA & status asthmaticus

OXYGEN Mixteures : e CO2 & helium Humidified : under water sealing Hyperbaric

Uses Correction of hypoxia- Inadequate O2 delivery- Cyanide poisoning During ansthesia Hyperbaric O2 :

- Decompression sickness- e air embolism- Ch refractory osteomyelitis- Anaerobic infection : gas gangrene- Generalized hypoxia – CO

poisoning

Side Effect & Precaution Fire & explosion can occur Irritation of nose, pharynx & trachea

(exposure to high conc) Inh mucociliary transport mech inh

tracheal out flow of mucus Hypoxemia (rapid admin) Retrolental fibroplasias : pre-mature

infant exposed to high conc O2 under pressure greater than 2

atmos twitching, visual symp, mood change, nausea & vomit, loss of consciousness, generalized convultions (all-high pressure nervous syndrome)

CARBON DIOXIDE Carbogen :

i. CO poisoningii. Anesthesia – stim resp center inc

resp minute volume inc induction & recovery speed

Dry Ice