Drug Book

DRUG BOOK
(All the details were taken from lecture notes)

Last modified 16/10/2020
Made by
MFSU - Peradeniya Chandula (15/16 batch)
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PAIN CONTROL 3 GENERAL ANASTHETICS 45

ANS 5 LOCAL ANASTHETICS 47
SPECIAL POPULATIONS 7 HYPNOTICS/SEDATIVES 48
ANTINEOPLASTIC 8 MOVEMENT DISORDERS 49
Y2S2 ANTIBIOTICS - CELL WALL, PROTEIN, NA
ANTIVIRAL
9
14 NEURO
DEMENTIA
EPILEPSY
50
51
ANTIMICROBIALS ANTI FUNGAL 15 MIGRAINE 53
ANTIMALARIAL 17 MOOD DISORDERS 54
ANTIHELMINTHEC 18 NMJ 56
Y3S2 ANTIPSYCHOTICS 57
SMALL AIRWAY DISEASE 19
RESPI ANTI TB 21 ALIMENTATION 58
GI ULCER DISEASE 60
VASCULAR TONE 23 IBD 62
LIPID REGULATING 25
CVS ANTIARRHYTHMIC 26 FEMALE REPRODUCTIVE SYSTEM 64
MYOCARDIAL CONTRACTILITY 28 ANDROGEN RECEPTORS 67
COAGULATION 29
GENITOURINARY BLADDER 68
MYOMETRIUM 69
DIURETICS
Y3S1 32
IV FLUIDS 34
ENDOCRINE THYROID DISEASES 35
HOMEOSTASIS GLUCOCORTICOIDS & MINERALOCORTICOIDS 36
ANTI DIABETIC 38
IMMUNOMODULATORS 40
JOINT DISEASES 41
LOCOMOTION
METABOLIC BONE DISEASES 43
BACK TO HEADINGS SHEET
PAIN CONTROL
Methods of pain control Types of pain Types of pain
•Pharamcological •Acute - protective mechanism •Nocieceptive
•Non pharmacological •Chronic - at least 6 months - Somatic
- Lifestyle interventions - Visceral
- Healthcare interventions •Neuropathic - Tx see below
- Distraction
Drug classfication Drug name Mode of action Pharmacokinetics Uses Adv ADR Special notes
Opioid peptides •In 1ry afferent neurons : Bind to GPCR → •Well absorbed •Respiratory depression Tolerance for -
Inhibit AC → ↓ CAMP →Block voltage gated Ca •SC, IM, Oral, nasal insuffalation, - in neonate when given to the mother in labour •Analgesia
Act on channels → inhibit substance P & glutamate trans dermal patches •Nausea / vomiting •Emesis
•peripheral nerve endings release •↑first pass metabolism •Constipation •Euphoria
•CNS •In nociresponsive neruons : Opening of K+ •Bind to plasma protein with varying - Reduce GI motility •Respiratory depression
•Descending inhibitory pathway channels → hyperpolarization→ ↓ excitability affinity - Delay in gastric emptying Less tolerance for
•Concentrate in brain, lungs, liver, •Increase pressure in biliary tract •constipation,
Agonists - Etorphine, Methadone, Morphine PHARMACOLOGICAL EFFECTS kidneys, spleen •Euphoria •pupillary constriction
Weak agonist - Codeine, Tramadol •Analgesia- •Metabolism by cytochrome P450 •dysphoria & hallucinations Dependance
Mixed agonist antagonists - Pentazocine - supraspinal,spinal, peripheral •Conjugate with glucuronides •Urticaria, bronchospasm, hypotension •Irritability , runny nose
Antagonists- Naloxone, Naltrexone - tissue injury/ inflammation (Neonates relatively less) •Pupilary constriction •Weight loss , diarrhoea
- Tumour growth •Excrete via kidneys •Shakes
Opiod receptors - mu, delta, kappa, sigma •Suppress immune function •T½- 3-6 hrs •Sweating
•Suppression of cough reflex •Piloerection
•Other - look ADE
Morphine
Codeine •Less potent (20%) •for mild pain , antitussive, •No euphoric effect Constipation People who lacks
•Demethylate to morphine combined analgesia •Rarely addiction demethylating enzyme resist to
analgesic effect
Fentanyl Rapid action •Intrathecal administration Used for anaesthesia No Urticaria,
•Analgesic patches bronchospasm,
hypotension
Pethidine Similar to morphine Prefer in labour pain - Does No Urticaria, Anti muscarinic effect-
not reduce uterine bronchospasm, •Pupil dilate →blurred vision
contractions hypotension •dry mouth
Tramadol Oral, IM, IV Effective analgesia for Post
operative pain
Naloxone Pure opiod antagonist Short T ½- 2-4 hr - need repeated respiratory depression by
•Affect all 3 receptors doses opioid overdose
•Blocks endogenous opioid as well as (Naltrexone has ↑ T ½)
exogenous morphine
Inhibiters of NSAID Non selective Ibuprofen •Almost complete absorption •Gastric irritation •↑ effect of Warfarin- by
COX •No first pass metabolism •Na & water retention → Odema and hypertension displacing from plasma protein
PG synthesis
inhibitors •Highly protein bound •papillary necrosis and interstitial nephritis •Antogonises effect of
Diclofenac
•Small volume of distribution •Rashes uricosuric drugs
•Majority are weak organic acids → •Worsening of asthma Probenecid, sulfinpyrazone
Indomethacin localize preferentially in synovial •Bronchoconstriction, urticarial, flushing,
tissue of inflamed joints hypotension, shock
Naproxen •Salicylism- with large doses of aspirin
•Reye syndrome
Aspirin irreversible inhibitor in plateles
Selective Celecoxib Less GI irritation •↓ synthesis of PGI2 - Vascular thrombosis

COX-2 Etoricoxib •others similar to NSAIDs
inhibitors Meloxicam
Drug classfication Drug name Mode of action Pharmacokinetics Uses Adv ADR Special notes
Acetaminophen (PCM) Proposed mechanism is inhibition of COX-2 •Well absorbed from GI tract no significant anti- •Liver toxicity at high doses - by excess NAPQI
•Inactivated in the liver inflammatory effect, but •Usually well tolerated.
•Conjugated as glucuronides and used for its mild analgesic •Allergic reaction and rashes some times
sulphate effect •Chronic renal disease- with long term daily dosing
•Minor metabolite formed- NAPQ1 -
Conjugated with glucuronides
Adjuvant Antidepressants
pain Anticonvulsants
Corticsteroids Block conversion of phospholipids to AA
medications
Anesthetics Block the voltage gated Na channels → AP
cannot be generated → Nerve block
Neuropathic pain Tx…….
Respond poorly to conventional analgesics
•Antidepressants- amitryptalline
•Gabapentin
•Carbamazepine- for trigeminal neuralgia
•Lidocaine- topically
AUTONOMIC NERVOUS SYSTEM

Drug classfication Mode of action Uses ADR
Parasympathetic ACh receptor agonists Choline esters Carbachol topical miotic

(on Cholinergic (parasympathomimetics) Bethanechol promotes urinary tract motility
system) Alkaloids Pilocarpine (eye drops) topical miotic
ACh receptor antagonists Atropine Tx of bradycardia, anticholinesterase poisoning,
(parasympatholytics) to ↓ secretions
Hyoscine As antispasmodic, Tx of motion sickness
Ipratropium/Tiotropium Bronchodilator in asthma, COPD
Tropicamide To produce mydriasis
Oxybutinin Tx of overactive urinary bladder
AChE inhibitors Short acting Edrophonium Dx of MG
(anticholinesterases) Medium acting Neostigmine Reverese NM block Tx of MG
Pyridostigmine Tx of MG
Irrevesible Organophosphate compounds
AChE reactivators Pralidoxime In anticholinesterase poisoning
Drugs inhibit ACh release Aminoglycoside Gentamycin inhibit Ca entry into cell
Botulinum toxin inhibits binding of ACh
vesicles to the presynaptic
membrane
Sympathetic Adrenoceptor agonists α1 Phenylephrine, Oxymetazoline Nasal decongestion
(on Adrenergic α2 Clonidine, Methyldopa Antihypertensive
system) β1 Dobutamine cardiogenic shock
β2 Salbutamol, Terbutaline Asthma/COPD
β1, β2 Isoprenaline heart block, bradycardia
α1/β1 Adrenaline (epinephrine) cardiac arrest, anaphylactic shock
Adrenoceptor antagonists α Non Phenoxybenzamine Tx of phaeochromocytoma prior to surgery Hypotension, flushing, reflex tachycardia
selective Phentolamine
α1 Prazosin, Doxazosin Hypertension Postural hypotension. (Adv-Less reflex
tachycardia)
Tamsulosin α1A urinary symptoms of BPH
β (beta blockers) Non Propranolol anxiety, thyrotoxicosis, essential tremor Bronchoconstriction
selective Bradycardia and heart block
β1 Atenolol, Metoprolol, Pure antagonist Hypertension, cardiac failure Fatigue
Bisoprolol
Acebutolol Partial antagonist Intrinsic sympathomimetic activity (ISA)

α1, β1, β2 Labetalol, Carvedilol
MAO inhibitors MAO-A Phenelzine
MAO-B Selegiline
MA transporter inhibitors Amphetamines
Cocaine
Cholinergic transmission
Adrenergic transmission
Phaeochromocytoma
•Neuroendocrine tumor secreting catecholamines
•Secrete epinephrine , norepinephrine , or dopamine
•Preoperative blood pressure management:
non-selective alpha blocker → beta blocker
DRUGS IN SPECIAL POPULATIONS

Pregnant - Pre embryonic
Embryonic
Fetal phase
Lactating
Peadiatrics
Geriatric
Renal diseases
Liver diseases
Heart failure
Obesity
ANTI NEOPLASTIC DRUGS

Treatment Drug classification Mode of action Pharmacokinetics Uses ADR Special notes
Surgery
Radiotherapy
Cytotoxic •Proportional to total drug exposure (AUC) •Nausea and vomiting
•Kill constant fraction of cells - log kill hypothesis •Suppression of BM and LR system
chemotherapy
•Not selectively toxic towards cancer cells •Diarrhoea and mouth ulcers
•Resistence - de novo, acquired •Alopecia
•Cell cycle specific •Opportunistic infection
•Non specific •Combined chemotherapy - maximum cell kill, prevent resistence •Urate nephropathy
•Specific organ damage
•Local extravasation, Hypersensitivity
•Late - gonadal dysfunction
Alkylating agents Busulphan Transfer alkyl groups to N7 position of guanine •↓↓ T ½ - except cyclophosphamide
Cyclophosphamide in the DNA during cell division →lead to DNA •Clearance is rapid
Chlorambucil strand breakage/ cross linking •Unaffected by even significant impairment
Ifosfamide of hepatic & renal function
Melphalan
Antimetabolites Methotreaxate Competitively inhibit DHFR → Prevent •Myelosuppresion & mucositis FA rescue – to allow
synthesis of THF •CNS damage the normal cells to
(synthetic •Chemical hepatitis recover
analogues of •Cirrhosis and portal vein fibrosis
normal metabolites) 5 fluro uracil Converted to active metabolites intracellularly
Arabinosides → inhibit DNA synthesis
Purine Azathioprine
antagonists Mercaptopurine
Antibiotics Anthracyclines Daunorubicin Produced by
Doxo rubicin microorganisms
Other Bleomycin
Dactinomycin
Mitomycin
Streptozotocin
Topoisomerase Non specific Doxo rubicin
inhibitors T 1 inhibitor Topotecan
Irinotectan
T 11 inhibitor Epipodophyllotoxins Etoposide
Teniposide
Spindle poisons Plant alkaloids Vincristine Inhibit microtubule assembly → Cell cycle myelosuppression, alopecia, neuropathy
Vinblastine arrest in mitosis
Vindesine
Platinum drugs Cisplatin Crosslinking DNA similar to alkylating agents emesis, nephrotoxicity ototoxicity
Carboplatin
Oxaliplatin
Asparaginase Starves tumour cells of asparagine AA ALL
Hormonal therapy Hormones Breast
Hormone antagonists cancer
Inhibitors of hormone synthesis
Immuno therapy Natural Cytokines
Synthesised IL-2 by recombinat DNA
Interferon-α tech.
Immune Calcineurin Tacrolimus Calcineurin activates NFATc by
inhibitors dephosphorylating → translocated into the
suppression
nucleus → upregulates expression of IL-2
(activate T cells)
Targeted biological Monoclonal AB Ex- Rituximab (anti CD 20) Against tumour associated antigens on cell •↑ cancer
surface specificity
therapy
•↓ host toxicity
ANTIBIOTICS (ANTI BACTERIALS)

Cell wall synthesis inhibitors Protein synthesis inhibitors Nucleic acid synthesis inhibitors
BACK TO HEADINGS SHEET BACK TO ANTIBIOTICS
ANTIBIOTICS - Cell wall synthesis inhibitors

Drug classfication Mode of action Pharmacokinetics Spectrum Uses ADR Special notes
β lactams Penicillins Standard G (Benzylpenicillin) Bind to active site •Inactivated by acid – variable absorption IV Drug of choice - •Allergic reactions
Penicillins of transpeptidase •Wide distribution, crosses BBB in •mainly GP - B.anthracis C.perfringens (gas gangrene) and tetani, •Rarely anaphylactic shock
•Bactericidal (PBP) covalently → meningitis & placenta C.diphtheriae, Actinomyces, •GN - N.meningitides, •cross-allergy - btw all forms of penicillin
•Time-dependent Inhibit formation of •rapid clearance - secretion- anion •Spiro - T.palidum, Leptospira spp., B.burgdorferi •Partial cross-allergy btw penicillins and
•Eliminated cross links between transport cephalosporins
unchanged by V (Phenoxymethylpenicillin) peptidoglycan •excretion delayed by probenecid- Oral •Diarrhoea
kidney Procaine penicillin polymers competition Depot 24 h •Neutropenia
•↑ TI Benzathine penicillin •↓Dose - impaired renal function (IM) 3-4 •Rarely anaemia & thrombocytopenia
•Main ADE - wks •Interstitial nephritis
hyper sensitivity β-lactamase- Meticillin Oral
•Inactivated by resistant Cloxacillin IV T ½ 0.5 h
bacterial β penicillins Flucloxacillin T½1h may cause cholestatic jaundice - > 2 w or pt >55 y
lactamases better absorbed - ↑ conc than cloxacillin
Temocillin
β lactamase Clavulanate •Covalently bind to βL Available in fixed-dose Amoxicillin + clavulanate = (Co-amoxiclav) oral tx for BL-
inhibitors •No intrinsic antibacterial activity combinations with penicillins Ticarcillin + clavulanate = (Timentin) producing
Sulbactam Ampicillin + sulbactam organisms
Tazobactam Piperacillin + tazobactam = (Tazocin)
Broad Aminopenicillins Ampicillin Acid-stable, absorption ↓ by food many GNB (do not resist b lactamases), semi-synthetic
spectrum (IV) ↓ active than benzylpenicillin against GPC, but ↑ active than BL resistant penicillins
Amoxicillin absorbed from gut (especially after food) penicillins Diarrhoea
E.faecalis, H.influenzae
Extended- Carboxypenicillins Ticarcillin T½1h •same as ampicillin (susceptible to BL)
spectrum IM, slow IV injection, rapid IV infusion •additional - P.aeruginosa, indole-+ve Proteus spp
penicillins •Timentin - ↑ activity against BL organisms
Ureidopenicillins Piperacillin zero-order kinetics, T ½ 1 h Additional - GNB such as Pseudomonas aeruginosa ampicilin + urea
Mecillinam Pivmecillinam Oral GN including many (ESBL) Enterobacteriaceae,
T ½ 1h but inactive against P.aeruginosa
Cephalosporins 1st gen Cephalexin •Orally, parenterally (IM, IV) Down the generations: •penicillin like ADE •structure is close
Cephradine •widely distributed in the body •↑ activity vs.aerobic GNB •If continued > 2 wks to penicillin
2nd gen Cefuroxime •some cross the BBB (cefotaxime, cefuroxime and •↓ antistaphylococcal activity - reversible thro.cytopenia •many semi
Cefaclor ceftriaxone) - Haemolytic anaemia synthetic forms
3rd gen Cefotaxime •water-soluble & relatively acid stable. resist attack by some b-lactamases - neutropenia •low toxicity
Ceftriaxone •Excreted unchanged in the urine, - interstitial nephritis •10% cross-
Ceftazidime •actively secreted - can blocked with probenecid - Abnormal liver FT hypersensitivity
4th gen Cefepime •Dose ↓ in poor renal function. - opportunist infection (resistant bac or C.albicans) with penicillins
5th gen Ceftaroline •ceftriaxone 40% is eliminated in the bile - C.difficile diarrhoea
Ceftobiprole
Cephamycins
Carbapenems Imipenem inactivated by dehydropeptidase-1 in kidneys (co- •Broad spectrum
administered with cilastatin) •most GP & GN aerobic and anaerobic bacteria
Meropenem •resistant to most BL, including ESBLs
Doripenem Only some pseudomonas are naturally resistant
Ertapenem
Monobactems Aztreonam IV •resistant to most BL •similar to other β-lactams
•GN (aerobic) - pseudomonas spp, N.meningitidis, H.influenzae •No cross reaction with penicillin-sensitive
•no action against GP organisms or anaerobes individuals.
Glycopeptides Vancomycin bind to D-Ala – D- Poorly absorbed from GIT GP - MRSA, •Ab associated pseudomembranous colitis •Nephrotoxicity
Ala of murein IV infusion C.difficile •streptococcal endocarditis + with aminoglycosids •Ototoxicity
monomer → Elimination renal •stap infection if allergic to penicillins •Flushing of upper body (red-man syndrome)
Inhibit
Teicoplanin polymerisation
Mycobacterial Pyrazinmide inhibits bacterial FA synthesis Go to Anti-TB drugs
Ethambutol Inhibits arabinosyl transferase in arabinogalactan synthesis for more details
Isoniazid a prodrug - activated by bacterial enzymes

Cell membrane Polymixin Cationic peptide antibiotics
Selective on bacterial cell membranes
Contain both hydrophilic and lipophilic groups → Act as detergents → disrupt phospholipid components of membrane
Daptomycin Lipopeptide T½ 9 h GP - Penicillin-resistant S.pneumoniae & MRSA
antibiotic Unable to cross the GN outer membrane
ANTIBIOTICS - Protein synthesis inhibitors

Drug classfication Pharmacokinetics Spectrum Uses Resistance ADR Special notes
Tetracyclins Tetracyclines •Orall Bacteriostatic Drug resistance - limited use Increasing resistance •GI adverse effects should not give to
•Partially absorbed Wide spectrum of activity •Rickettsial and chlamydial infections, brucellosis, •transmitted by plasmids •chelat with Ca phosphate → Deposit in growing bones & children, pregnant
Demeclocyclines •Remains alter gut flora- diarrhoea GP, GN anthrax, lyme disease •produce an efflux pump teeth → staining women and nursing
•chelate metal ions - Ca, Mg, Fe, Al → absorption ↓ with milk, •Mycoplasma, rickettsia, chlamydia, Acne → not accumulate the ab •Dental enamel hypoplasia mothers
Doxycyclines antacids, Fe preparations spirochaetes, protozoa (amoeboa), •2nd choice - mycoplasma, leptospira, minor SSTI •Alteration of ribosomes •hepatotoxicity during pregnancy
•Excreted mainly unchanged in urine – avoid in renal impairment bartonella, borreliae •RTI – chronic bronchitis, CAP •Phototoxicity - sp with demeclocyclines
•Doxycycline and minocycline excreted in non renal routes. •Minocycline- N.Memngitidis •SIADH - demeclocycline (Distinct action) •Vestibular disturbances- minocyclines
Minocyclines
•Disturbances to BM - with long term tx
Macrolides Erythromycin •Oral, i.V. •T ½ 90 m •Similar to penicillin (Except •Atypical pneumonia (Mycoplasma) Plasmid controlled •GI disturbances, nausea, Vomiting Many membered
(E) •Well absorbed •Incactivated in Mycoplasma pneumoniae and •Diptheria, pertussis, some chlamydial infections alteration of binding site - less common with A & C lactone ring - one
•Do not cross BBB liver Legionnaires' disease •C.jejuni gastroenteritis •Fever, rashes or more deoxy
•Poor penetration to synovial tissues Chlamydia) •for penicillin allergic patients - s.aureus, •>2 weeks : cholestatic jaundice , Opurtunistic infection of GI/ sugars attached
Clarythromycin •T ½ E X 3
•Concentrated in phagocytes → enhance •GP - streptococci, staphylococci, s.pneumonia, s.pyogenes, T.Pallidum Vagina
(C) •Converted to
intracellular killing of bacteria by phagocytes pneumococci and clostridia •Acne •IV → can cause local thrombophlebitis
active
•Inhibit CYP 450 → drug interaction •not sensitive for GN (Except N. •A & C – also effective for H.Influenza, Legionella
metabolites
Eg: with theophylline gonorrhea, H.Influenzae) •C - leprosy, H. Pylori, MAC
Azithromycin •T ½ E X 8-16
(A) •Resistant to
inactivation
Chloramphenicol •I.V. Oral •Wide spectrum •Systemic use only for serious infections •by chloramphenicol •depression of BM → Pancytopenia (Type A & B) Isolated from
•Rapid, complete absorption •GP GN, rickettsia •H.influenzae resistant to other drugs acytyl transferase •Neonates → grey baby symdrome - due to failure of culture of
•Wide distribution, Including CSF •Bacteriostatic •Meningitis if penicillin can't be used •plasmid mediated conjugation & renal excretion. Streptomyces
•T ½ - 2 h •Yet bactericidal for H.influenzae, •Typhoid fever •Hypersensitivity reactions, GI disturbances
•10% excreted unchanged in urine N.meningitidis, S.pneumoniae •Topical use: Eye drops for bacterial conjunctivitis
•Rest inactivated by liver with conjugation with glucuronides
Aminoglycosides Gentamicin •Not absorbed from GIT •Aerobic GP & GN •GN septiceamia , Renal, pelvic, abdominal sepsis Several mechanisms. •Ototoxicity commonly used
(G) •Given IM IV •enterobacteriaceae •Bacterial endocarditis transmitted via plasmids - dose related
Streptomycin •Polycations → Water soluble – not readily cross cell membrane •Bactericidal Effect is enhanced by •TB, brucellosis, tularaemia, plague •produce enzymes → - Vertigo, ataxia, loss of balance, Deafness for M.Tb
(S) •Cross placenta agents that interfere with cell wall inactivate the drug by - S & G- more effects on vestibular function
Amikacin •Don't cross BBB, even meninges are inflamed synthesis (with penicilins for – acetylation, - N & A- more effects on hearing •widest spectrum
(A) •↑ concentrations in bone and joint fluids streptococcal infectons, listeria & phosphorylation or - ↑ with other ototoxic drugs- loop diureitcs •For infections
•T ½ - 2-3 h P.aeruginosa) adenylation. •Nephrotoxicity resistant to G & T
•Excretion- entirely renal •alterations of envelope - More likely to occur in pre-existing renal disease, oliguric
•Concentraton dependant killing to prevent access conditions, concomitant use of nephrotoxic drugs-
•Narrow TI •alteration of binding vancomycin,
Tobramycin for p.aeuriginosa
•Single daily dose - gives immediate high plasma conc site on 30S subunit •NM blockage
(T)
•Dose according to weight and renal function - inhibition of Ca uptake → ↓ release of ACh
Neomycin •infections of
•poorly diffuses to adipose tissue → LBW should be used - ↑ (or ↓) MG or transient myasthenic syndrome in normal
(N) conjunctiva and
•Need plasma concentration monitoring - Dose adjustment patients
external ear
•Rashes: haematological abnormalities
•orally to sterilize
bowel prior to sx
Oxazolidinones Linezolid •Oral and IV •Bacteriostatic for GP Useful for MRSA, penicillin resistant S.Pneumoniae, •Thrombocytopenia, diarrhea, nausea New class of
•Elimination: via renal and hepatic routes •Bacteriocidal for pneumococi vancomycin resistant enterococci, anaerobes: •Rashes, dizzinus, peripheral neuropathy, optic neuropathy antibiotic
C.difficile •Non selective inhibitor of MAO
Lincosamide Clindamycin •GPC - penicillin resistant •staph infections of bones and joints •GI effects. Action similar to
staphylococci, •Eye drops for staph conjunctivitis •Pseudomembranous colitis- caused by a toxin forming macrolides &
•Anerobes: bacteroides c.difficile chloramphe...
Fusidic acid •iv, oral, ointment, gel, eye drops •Narrow spectrum Staphylococcal infections: skin, eye use with another Usually Well tolerated •Steroid
•Readily absorbed. Destributes widely to tissues including bones •Effective for BL producing Osteomyelitis antistaphylococci agent Mild GI effects antimicrobial. •Act
staphylococci (flucloxacillin) to avoid High doses- may cause jaundice → monitor LF by inhibition of
resistance translocation.
ANTIBIOTICS - Nucleic Acid synthesis inhibitors

Drug classfication Mode of action Pharmacokinetics Spectrum Uses ADR Special notes
Quinolones •Inhibit bacterial DNA gyrase (topoisomerase II) •Good oral bioavailability (except norfloxacin) •GI disturbances – •Synthetic
→ Inhibits relaxation of positively supercoiled - Impaired by antacids, divalent cations dyspepsia, vomiting, •Derived from quinine
DNA •Distributed widely in body tissues, fluids – kidney, ,bone, irritative diarrhoea •Fluoroquinolones -
- Primarily in GN prostate, lung & phagocytes •Skin rashes – Addition of F molecule
•Inhibit bacterial topoisomerase IV → Prevents •CSF penetration poor photosensitivity → modified properties
cutting and seperating of daughter DNA strands •↑ T ½ in newer quinolones (levofloxacin, moxifloxacin) – •Tendinitis & tendon - ↑ potency
- Primarily in GP once daily rupture - expanded spectrum
•Hepatic metabolism – acetylation, glucoronidation •Headaches, Dizziness, - ↑ tissue penetration
•Renal excretion- GF and TS Seizures,
Polyneuropathy
1st gen Nalidixic acid GN (except pseudomonas spp.) •Arthropathy
Cinoxacin •Contraindicated in
2nd gen norfloxacin •potency < ciprofloxacin GN (including •UTI and genital tract infections pregnancy
•↓Lower concentration in tissues pseudomonas) •Mainly for GN. ↓ effects on pseudomonas and GP
+ some GP & some •Bacterial diarrhoeas – high conc. in gut
atypicals •Not recommended for RTI
Ciprofloxacin Interactions •Bactericidal
•Inhibit hepatic enzymes – ↑ conc. of theophylline, warfarin •Broad spectrum
•Antacids, sucralfate, Fe - ↓ absorption •↑ susceptibility – Enterobacteriaceae
•H.influenzae, N.gonorrhoea, Campylobacter spp.
Also give as topical - eye drops •Pseudomonas
•M. tuberculosis – 2nd line drug
•Weak inhibition of streptococci and pneumococci – should
not used as primary drug in RTI
Enoxacin
Ofloxacin •↓ active against GN compared to cipro
•Good activity against chlamydia and mycoplasma
•Atypical pneumonias
•GP and some anaerobes
3rd gen Levofloxacin Oral bioavailability almost 100% same as 2nd gen + •strep. pneumoniae and GP
entended coverage •For CAP and chronic bronchitis
of GP & atypicals •Anaerobes - moderately susceptible
•UTIs and SSTI
Sparfloxacin
Moxifloxacin
Gemifloxacin
4th gen Trovafloxacin Same as 3rd gen + broad anaerobic coverage
Sulfonamides •Structural analogues of PABA •competitively •Good oral bioavailability •bacteriostatic - S.pyogenes, H.influenzae, H. ducreyi, V.cholerae, Chlamydia
Short acting
inhibit dihydropteroate synthase → Impaired •Widely distributed – crosses BBB and placenta •Staph, gonococci, pneumococci, e. coli largely resistant
Interme. Acting
bacterial folate synthesis → Metabolic injury •Variable plasma protein binding (10%-95%) •Anaerobes not susceptible
Long acting
•Acetylation / glucoronidation in liver
Sp. Purpose
•Renal excretion - GF
Co-trimoxazole •combination of sulfamethoxazole + •P.jirovecii, S.typhi, Klebsiella, Enterobacter •N&V
trimethoprim •Sulfonamide resistant strains - S.aureus, S.pyogenes, E.coli •Stomatitis
•Trimethoprim inhibits DHFR •Folate deficiency
•Blood dyscrasias
•Hypersensitivity
•Uremia in renal
disease
Rifamycins Rifampicin •Inhibits bacterial DNA dependent RNA Bacteriostatic or bactericidal
polymerase → RNA synthesis inhibited
Nitroimidazoles Metronidazole •Enters cell by diffusion → nitro group reduced •Selectively toxic to anaerobes
to highly reactive nitro radical → toxic to •Protozoa
bacterial DNA •Moderate - H.pylori
ANTIVIRAL DRUGS
•Mainly acts on viral replication •Target viral DNA polymerases & enzymes
•Accumulate in virus infected cells •Activated by virus encoded enzymes
•Dose related toxicity seen
Drug classfication Mode of action Pharmacokinetics Uses ADR Special notes
Anti viral Compunds Neuraminidase Zanamivir •Inhibits neuraminidase Influenza A N - connect viral haemaglutinin &
agents that Interfere (N) Inhibitors Oseltamivir •Prevents release of virus progenies host cell
with Nucleoside Acyclovir used systemically HSV - 1 & 2 resistance due to mutations in
replication analogues VZV •viral thymidine kinase → unable
to phosphorylate acyclovir
•viral DNA polymerase → unable
to recognize
Ganciclovir •6-9% oral bioavailability CMV •BM suppression

•penetrates CSF •CNS problems (headaches,
convulsion, psychosis)
•seen in ~40% of pts
Ribavirin •Phososphorylated to triphosphate in vivo Hepatitis C serious side effects in some
•Inhibits viral RNA polymerase → inhibit
RNA / DNA synthesis
Interfere with Foscarnet Inhibits DNA polymerase •No oral forms available HIV Neurotoxicity seen in some No in vivo activation required
protein synthesis
Interferon / interferon inducers •Binds to surface of other cells → inhibit Host specific Chronic Hep B in certain individuals / Small GP produced in virus
mRNA → inhibit transcription & translation Chronic Hep C - Ribavirin + populations infected cells
Interferon
Specific Reverse Nucleoside Zidovudine No longer used due to AVR - 1st treatment for HIV/AIDS
retroviral transcriptase analogues (RTIs) Abacavir introduced for tx of chronic
(HIV/AIDS) inhibitors Lamivudine hepatitis B
drugs Tenofovir •Tenofovir and/or Favourable safety profile Truvada®
disoproxil nevirapine - in cases with (Tenofovir + Emtricitabine) Once
fumarate ↑ cholesterol, TAG daily tablets
•Prevention of mother to
child HIV transmission
•Chronic hep B
Non-nucleoside Nevirapin Binds directly to RT
RTIs (NNRTIs) Efavirenz /
Sustiva
Protease Indinavir •interfere with production of HIV combination with other HIV-1 protease - cleaves
inhibitors Lopinavir protease → ↓ of virus (sometimes HIV/AIDS drugs - due to polyproteins in process of
undetectable levels) rapid development of producing mature virus particles
Saquinavir
resistance
ANTI FUNGAL DRUGS

Drug classfication Mode of action Pharmacokinetics Uses Interactions ADR Special notes
Cell Azole Imidazoles Ketoconazole Interfere with fungal •Variable oral absorption •Spectrum: yeasts & moulds •Potent inhibitor of CYP 450 3A4 •N&V, worse with higher doses
membrane oxidative enzymes → lethal •dependent on pH •Poor absorption limits its for severe infections •Rifampicin and phenytoin ↓ •Hepatoxicity (2-8%), ↑
accumulation of H2O2 → •T ½ 7-10 hours •Used in mucosal infections only ketoconazole levels transaminases, hepatitis
•Ergosterol formation of ergosterol ↓ •Protein binding > 99% •Drugs that ↑ gastric pH will ↓ •Inhibition of CYP 450 →
•Hepatic & kidney elimination blood levels of ketoconazole ↓ testosterone synthesis →
(Antacids, omeprazole, H2 blockers) (Gynecomastia, oligosperma,
•Often given with fruit juice decreased libido)
•↓ adrenal cortisol synthesis
Miconazole topical agent for dermatophyte, yeast and other
Clotrimazole fungal infections
Econazole
Sulconazole
Tioconazole fungal nail infections
Isoconazole vaginal candidiasis
Fenticonazole
Triazoles Fluconazole Inhibit lanosterol 14-a- •Oral and IV •C. albicans & C.neoformans •↑ phenytoin, cyclosporin, •Headaches •have greater
demethylase enzyme → •Oral bioavailability > 90% •C.non-albicans exhibit primary resistance rifampacin, warfarin, and zidovudine •Reversible alopecia selectivity against
Damage cell membrane •Excreted largely unchanged by kidney (T ½ 30 •Oral - oropharyngeal & oesophageal candidiasis concentrations •↑ levels of liver enzymes fungi
h) •IV - systemic candidiasis and cryptococcosis •Allergic rash •Better penetration of
•penetrates CSF well - Protein binding < 12% •No Aspergillus •Terotogenicity the CNS, resistance to
degradation
•↓ endocrine
disturbance than
Itraconazole •Oral and IV Similar Candida coverage as fluconazole, + •(rifampicin) induction of CYP 3A - Uncommon imidazoles
•T½ 25 h Aspergillus ↓plasma conc. of itraconazole. •Transient hepatitis
•Absorption from gut (55%) •Inhibit oxidation of - phenytoin, •Hypokalaemia
- ↑ by ingestion with food warfarin, ciclosporin, tacrolimus, •Prolonged use → CF (especially with
- ↓ by fatty meals & therapies that ↓ gastric midazolam,triazolam, cisapride, pre-existing cardiac disease)
acidity terfenadine – ↑ intensity and/or
•Heavily protein bound - not found in CSF duration
•completely oxidised in liver (CYP 3A) •excreted
in the bile
Voriconazole •Oral and IV. Oral absorption - •Broad •Visual disturbances (~ 30%)
- reliably & rapidly than itraconazole •More active in vitro than itraconazole against - ↓ vision, photophobia, altered color
- is not significantly ↓ by gastric hypoacidity Aspergillus perception, ocular discomfort
•CSF & brain tissue conc - at least 50% of •More avid binding of the sterol synthetic
plasma enzymes of filamentous fungi
Posaconazole
Polyene Amphotericin B •Bind to sterols in fungal •IV The drug of choice for: ↑ Nephrotoxicity with other Fermentation product of
antifungals cell membrane → trans- •not absorbed from GI tract •Cryptococcal meningitis •Nephrotoxic drugs Streptomyces spp
membrane channels → •Oral solution - sometimes used to •Mucormycosis •Antineoplastic agents
electrolyte leakage decontaminate gut; few side effects •Invasive fungal infection, not responding to
other tx
Nystatin similar in structure & •Too toxic for systemic use
mechanism to •Used only topically - creams, ointment and
amphotericin B suppositories
•Not significantly absorbed from skin, MM, GIT
Allylamine Terbinafine Interferes with ergosterol •absorbed from GIT •Topically - dermatophyte infections of the skin nausea , diarrhoea, dyspepsia,
biosynthesis •extensive metabolism in the liver •orally - infections of hair and nails when abdominal pain, headaches and
•T ½ 14 h severity or extent of the infection increases cutaneous reactions
DNA/RNA Griseofulvin •interfering with •oral •Fungistatic, has a narrow spectrum Induces cytochrome P450 enzymes •Gastrointestinal upset
synthesis microtubule function •Absorption ↑ with fatty meal •dermatophyte infections •rashes
→Inhibits mitosis •Not effective topicaly •Ineffective in pityriasis versicolor, superficial •Photosensitivity
•Bind to keratin - formed •T ½ 24 hours candidiasis, all systemic mycoses •headache
in cells of nail bed, hair •Metabolised in liver •CNS disturbances
follicles & skin •↑ alcohol intoxication
Flucytosine •Metabolised in the fungal •well absorbed from gut •Restricted spectrum
cell to 5-fluorouracil → •penetrates effectively into tissues •Acquired Resistance - Not used as
inhibits NA synthesis •excreted unchanged in urine monotherapy
•combination with amphotericin B or
fluconazole.
- Candidiasis
- Cryptococcosis
Cell wall Caspofungin acetate (Cancidas) inhibit β-glucan synthesis •IV only •Invasive candidiasis infusion related:
(essential to cell wall •Widely distributed in body tissues •Invasive aspergillosis refractory to other tx •IV site irritation (15-20%)
intergrity) •Highly protein bound - Penetrates CSF poorly •Mild - moderate - fever, headache,
flushing, erythema, rash (5-20%)
•Asymptomatic ↑ of serum
transaminases (10-15%)
Echinocandins
ANTI MALARIAL DRUGS

Drug name Mode of action Pharmacokinetics Uses ADE Sp. Notes
Chloroquine Prevent detoxification of •Well absorbed from GIT •Blood Schizonticide for P. vivax •Nausea, vomiting •Safe in pregnancy
haem •Concentrated in liver, •Pruritus •Most P.falciparum strains are
kidneys •Hypertension resistant
•Plasma half life – 50 h •ECG changes – high doses
Quinine •Well absorbed from GIT IV - Severe Falciparum Malaria in 1st Trimester of •Cinchonism - Tinnitus, headache, nausea,
•Metabolism – 80% liver, Pregnancy visual disturbances
20% kidneys •Hypoglycaemia - Monitor Blood Glucose
•Infusion – each dose should •Hypotension
give over 4 h in 5% dextrose •Arrhythmias – High doses - ECG Monitoring
Artemisinins •rapidly hydrolyzed to short half lives, rapid action •Blood schizontizide - P.vivax & P.falciparum Well tolerated. Mild GI & CNS side effects P.falciparum resistence to
dihydroartemisnin (active •Gametocytocide Artemisinin
Artemether ingredient)
•Generate free radicals in Contraindications Tx = Quinine
Artesunate
parasitized RBC ? •Pregnant women in 1st trimester
•Exclusively breastfeeding
ACT - Coartem® •Artemisinin - ↓ main Absorption is ↑ by fat →
•Children weighing < 5 kg
= Artemether & parasite load in first 3 days Take with a glass of milk
Lumefantrine •partner drug -eliminate
remaining parasites
Primaquine •Orally absorbed – almost •P. vivax - prevent relapses contraindications
100% - Tissue schizonticide •Infants
•Hepatic elimination •Px Transmission of P. vivax & P. falciparum •Pregnancy & Lactation
•T ½ 6h - Gametocytocidal •G6PD deficiency (in P.vivax anti
relapsing tx - 14 d)
Blood Chloroquine 5 groups - AMC Tx guidelines Treatment

schizonticides Quinine
Artemisinins P. vivax Chloroquine blood schizonticide
Mefloquine Primaquine Kills hypnozoites & gametocytes
Sulfadoxine and Pyrimethamine (Fansidar) P. falciparum uncomplicated CO-ARTEM®
Tissue Primaquine Primaquine – single dose destroy gametocytes
schizonticides Proguanil Uncomplicated P.falciparum - in Pregnancy
Gametocytocides Primaquine Severe P. falciparum Intravenous Artesunate
Chloroquine Quinine (in T1 of pregnancy)
Quinine Mixed infections
Artemisinins
ANTIHELMINTHICS
Drug name Mode of action Dose
Benzimdazoles Mebendazole ingested by worm → Binds to worm’s gut Not absorbed in to human 100mg bd for 3 days or
microtubules → affects glucose absorption & circulation 500mg single dose
digestion by worm
Albendazole Prevents polymerization of parasite tubulin in Absorbed in to human Single dose
microtubules → Inhibits glucose uptake by adult & circulation → adjust dose/ •400mg
larval worms kg body weight - Adults & older children
•200mg
- Children <2yrs
- < 25kg body weight
Pyrantel paramoate Acts rapidly and selectively on ACh receptors of syrup - Children > 1 year old
nematode muscle → spastic paralysis of worm → Single dose
Worms passed with faeces 10mg/kg/ body weight
Disease Drug Dose Special notes
Enterobius Mebendazole 100 mg Why 2 doses ?
vermicularis 2 doses - 2 weeks apart •Eggs and young worms resistant
•Re infection is common
Ascariasis Mebendazole Single dose Don’t give if child is ill or •Mild side effects
starving ! - Mild abdominal pain
- N & V, diarrhoea
- fatigue
Worm migration
Albendazole Single dose
Trichiuriasis Mebendazole 100mg bd – 3 days
Hook worms Albendazole
Mebendazole 500mg single dose – once a year Routine deworming ONLY for children (18 m – 10 y) in High
Risk Areas
CLM Albendazole 1 week course
VLM
Strongyloidiasis
Hydatid disease Albendazole Long intermittent course To ↓ size of cyst before sx
Tape worms Praziquantel Single dose
T.solium
SMALL AIRWAY DISEASE (ASTHAMA, COPD)

Asthma - revesible Mechanism of action Clinical use
COPD - not full revesible - Bronchodilators - Quick relief (“relievers”)
- Anti-inflammatory drugs - Long-term control (“preventers”)
Drug classfication Drug name Mode of action Pharmacokinetics Uses ADR Special notes
Bronchodilators β2 agonists Short acting Salbutamol •Modes of administration - MDI, DPI, via for quick relief of symptoms Tremors
nebuliser, IV, IM, SC, oral Palpitations
•Rapid onset (5 min) Muscle cramps
Terbutaline •Peak effect: 30-60 min hypokalaemia
•Duration of action 4-6 h
•Metabolized in liver (sulfation)
Long acting Salmeterol Lipophilic side chains that •MDI, DPI Slower onset of •Maintenance therapy of asthma
(partial agonist) resist degradation •12 - 24 h action action & COPD
•Not used as monotherapy
Formoterol Quicker onset of : combination with glucocorticoids
(full agonist) action - Salmeterol + fluticasone
- Formoterol + budesonide
Muscarinic rec Short acting Ipratropium •Mainly M3 MDI, DPI, nebuliser Quick relief of symptoms in Dry mouth
antagonist •Less lipid soluble than asthma & COPD Throat irritation
atropine
Long acting Tiotropium •Systemic absorption ↓ DPI Maintenance therapy of COPD
Methyxanthines Theophylline •PDE 3 & 4 inhibition in •Well absorbed from Short half-life → Maintenance therapy of asthma & •Dyspepsia, tremor, cardiac Drug
airway smooth muscle GIT sustained-release COPD arrhythmias, convulsions interactions
•PDE 4 inhibition in •Hepatic elimination formulations •Low therapeutic index •Plasma conc.
T-lymphocytes & - ↑ by
Aminophylline eosinophils: has IV Acute asthma Erythromycin
immunomodulatory & anti- Cimetidine
inflammatory effects - ↓ by
Rifampicin
Phenytoin
MgSO4
Anti Glucocorticoids Inhaled Beclomethasone •MDI, DPI, via nebuliser •Maintenance therapy of asthma •Low doses Most effective
inflammatory & COPD - Dysphonia anti
drugs •Fixed-dose combinations with - Oropharyngeal candidiasis inflammatory
Budesonide
long-acting β2 agonists •High doses drug
Fluticasone + salmeterol - HPA suppression
Fluticasone Budesonide + formoterol - ↓Bone mineral density
- Cataract
- Growth retardation in children
Oral Prednisolone
IV Hydrocortisone
Drug classfication Drug name Mode of action Pharmacokinetics Uses ADR Special notes
Leukotriene Cysteinyl LT Montelukast •Administered orally - (children) Maintenance therapy of asthma •Abdominal pain, diarrhoea,
modifiers rec •Hepatic elimination headache
antagonists Zafirlukast •Hepatitis with zileuton → periodic
LFTs
5- Zileuton
•Churg-Strauss syndrome (rare)
lipoxygenase
inhibitor
Monoclonal Anti-IgE Omalizumab •Binds to portion of IgE SC •Moderate/severe persistent recombinant
antibodies that recognizes its receptor asthma when → humanized IgG1
(FcεR1) on mast cells & inhaled corticosteroids, long- antibody
basophils acting β2 agonists & LT modifiers
•↓ circulating IgE, down- →
regulation of FcεR1 not effective or have intolerable
ADE
Anti- Mepolizumab Bind to circulating IL-5 monthly SC In severe eosinophilic asthma
interleukin-5 Reslizumab monthly IV
ANTI TUBERCULOSIS DRUGS

•Kill actively multiplying bacteria - bactericidal •Intensive phase - 4 drugs
•Treat persisting dormant - sterilizing - kill actively multiplying bacteria
•Prevent emergence of drug resistance - multiple therapy - prevent drug resistance
•Continuation phase - 2 drugs, longer period
- treat persisters
Drug name Mode of action Pharmacokinetics Interactions ADR Special notes
Isoniazid Bacteriostatic •Readily absorbed through GIT •↓ metabolism of AED → ↑ Occurs in 5% . Dose dependant Cross resistance with other tb drugs
(H/INAH) Bacteriocidal •Widely distributed - tissues, body fluids, CSF, caseous tb plasma conc. & toxicity •Commonest- allergic skin eruptions, systemic and cutaneous hypersensitivity doesn't occur
•Inhibit synthesis of mycolic acid lesions. → can treat TB Meningitis. •Fever
•Hepatotoxicity
•Combine with an enzyme (found in isoniazid •Metabolism (Acetylation)
- risks: age & underlying liver disease
sensitive strains) → disorganize cellular - by acetyl transferease enz.
- Caused by acytylated metabolite/s.
metabolism. - Depend on genetic factors. Best response with slow - Commoner in fast acetylators
acetylators (T ½ - 3 hr) - Monitor transaminases & bilirubin
•Excreted in urine. •Perepheral neuropathy
- Due to pyridoxine deficiency
- specially in malnourished, chronic alcoholics, pregnancy, lactating
mothers, diabetes, HIV
- commoner in slow acetylators
- Tx: Pyridoxine supplement - Give at least 12 hours apart from anti-TB drugs
•Neurological disturbances- optic neuritis, generalized convulsions
• Haemolytic anaemia- in G6PD deficiency
- Haematological changes, arthritic symptoms and vasculitis.
Rifampicin •Against most gram +ve & -ve •Absorbed - GIT Induction of hepatic metabolizing Relatively infrequent Resistance - Due to chemical modification
(R) •Kill intracellular organisms •Widely distributed in tissues and body fluids enzymes- ↓ concentration of •Skin eruptions, and GI disturbances of DNA dependant RNA polymerase
•Bind and inhibit DNA dependant RNA •Reaches CSF - 10-40 % of serum concentration. drugs metabolized by liver •Hepatotoxicity
polymerase in prokaryotes •Red discoloration of sputum, tears and urine. - ↑ risk - chronic alcoholics, pre existing liver disease
•Orange disloloration of soft contact lenses. •Flu like syndrome- fever, chills, myalgia
•Excreted - urine, bile •Acute tubular necrosis
•Thrombocytopenia, haemolytic anaemia
Pyrazinamide (Z) •Pro drug •Well absorbed orally •Gout- due to hyperuricaemia Synthetic analog of nicotinamide
•Converted by pyrazinamidase to pyrazinoic acid •Widely distributed. •Hepatotoxicity- dose dependant
•Acts against intracellular organisms. •Penetrate into meninges •Fever, malaise, GI disturbances
•Effective for MTB •Excreted through kidneys.
Ethambutol Bacteriostatic against MTB •Effective for several •Never used alone Uncommon
(E) mycobacteria. •Orally absorbed •Optic neuritis-
•Unclear mechanism •Therapeutic conc. in CSF - dose and time dependant and more if renal function ↓
•Inhibit RNA synthesis •Partly metabolized •Excreted in kidneys - C/F : red green blindness → ↓ visual acuity
- Baseline and serial visual acuity & colour perception tests
Streptomycin Bactericidal Deep IM injection •Nephrotoxicity - dose related •Aminoglycoside
•Autotoxicity •Caution :-Elderly & renal insufficiency pts
•Skin rashes •If facilities are available plasma conc.
should measured
VASCULAR TONE
Local Endothelial Sympathetic Hormonal mediators

Regulation of activity
Vascular tone H+, K+, lactate, adenosine NO, Prostacyclin, Endothelin-I Circulating catecholamines, Angiotensin-II, Vasopressin
Bradykinin, Natriuretic peptides
Vasodilators Drugs ↑ cGMP NO donors Organic nitrates GTN (nitroglycerin) •Metabolised to NO (enzyme-dependent) •Rapidly absorbed •Rapid onset & short DOA acute attacks of angina, •Headache Nitrate tolerance
•NO-mediated dilatation of veins > arteries from GIT, skin, MM •T ½ 1-4 m LVF •Hypotension •↓ biotransformation to NO
•Minimal arteriolar dilatation •Sublingual tablets Esp. with PDE-5 inhibitors •Endothelial dysfunction
•↓↓ Preload ; ↓ Afterload •GTN & ISDN - - inactivated by light, plastic •Free radical formation
•↑ subendocardial perfusion extensive first-pass •Sublingual spray •Neurohormonal activation
•Dilate epicardial coronary arteries metabolism •Transdermal patches
including collaterals •ISMN no first-pass •i.v. infusion ↓ by nitrate free intervals
ISDN •No intracoronary steal metabolism •Long acting For prophylaxis of angina
•Oral tablets
•sublingually
ISMN
Sodium nitroprusside •Spontaneously degrades to NO •IV In hypertensive •CN accumulation (sweating,
•Arterial & venous dilatation •T ½ 2 m emergencies hyperventilation, arrhythmias,
metabolic acidosis, pink colour of
skin, dilated pupils)
•SCN accumulation (confusion,
tinnitus, blurred vision, ataxia)
PDE-5 inhibitors Sildenafil •↓ hydrolysis of cGMP •Good oral bioavailability In erectile dysfunction, •Flushing
•Vasodilatory effect in corpus cavernosum •Hepatic metabolism pulmonary arterial •Hypotension (esp. with nitrates)
Tadalafil & pulmonary arterial circulation hypertension •Headache
Sympatholytic Centrally acting α2-adrenoceptor Methydopa Converted to α- •Oral bioavailability 50% Hypertesion during •Sedation, depression, sleep
drugs agonists methylnoradrenaline •Hepatic metabolism pregnancy disturbances
↓ sympathetic
•Haemolytic anaemia, hepatitis
outflow from
medulla
Imidazoline-1 rec Moxonidine In rostral •Oral bioavailability 90% Dry mouth, faintness
agonists ventrolateral •Elimination renal > hepatic
medulla
α1-adrenoceptor Non-selective α Phenoxybenzamine In phaeochromocytoma •First-dose hypotension
antagonists antagonists Phentolamine •Orthostatic hypotension
Selective α1 Prazosin •Elimination hepatic
antagonists Terazosin •Prazosin relatively short T ½
Doxazosin
Ca2+ channel Phenylalkylamines Verapamil •Vasodilatation cardiac >> vascular •Metabolised by CYP •Bradycardia, AV conduction block L type in vascular smooth
blockers (arteries, arterioles) •First-pass metabolism in intestinal wall & liver •Constipation muscle & myocardium
Benzothiazepines Diltiazem •↓ myocardial cardiac > vascular •Elimination hepatic
contractility •Felodipine, Amlodipine relatively long T ½
Dihydropyridines Nifedipine •↓ SAN rate & AVN vascular >> cardiac •Hypotension, reflex tachycardia
conduction velocity •Ankle oedema
Felodipine
•Gingival hyperplasia
Amlodipine
Drugs inhibit RAA ACE inhibitors Short acting Captopril Elimination hepatic, renal •Dry cough •Renoprotective effect in
•Angioedema CKD
Long acting Enalapril •First dose hypotension (diabetic nephropathy)
•Renal failure in b/l renal artery •Inhibit myocardial
Ramipril stenosis remodelling in post-MI
•Hyperkalaemia patients
Lisinopril
Angiotensin receptor Losartan •No effect on bradykinin →

antagonists cough & angioedema
Candesartan
Telmisartan
Renin inhibitors Aliskiren
K+ channel Minoxidil •Open ATP-sensitive K+ channels in •Well absorbed from GIT In refractory hypertension Excessive hair growth With β-adrenoceptor
openers vascular smooth muscle → •T ½ 4 h antagonists & diuretics to
hyperpolarisation → Ca channel block •Metabolised in liver prevent reflex tachycardia &
Na+ & water retention
Nicorandil •Well absorbed from GIT In angina Headache Also NO donor

•Metabolised by denitration
Endothelin-I Bosentan •Good oral bioavailability In pulmonary arterial Hepatotoxicity
antagonists Sitaxsentan •metabolised in liver hypertension
Ambrisentan
Hydralazine Inhibits release of Ca2+ from ER •Oral bioavailability 30-50% Used in hypertensive SLE-like syndorme
•Hepatic metabolism (acetylation) emergencies; (PIH)
Vasopressor α1 adrenoceptor agonists Sympathomimetics •Short T ½ hypotension endogenous & synthetic
drugs •IV infusion catecholamines
Vasopressin Vasopressin •Vasoconstriction via in splanchnic, renal •Metabolised in liver & kidney •Hyponatraemia
receptor agonists V1 receptors in & cutaneous •T ½ <10 min •Ischaemia in coronary, mesenteric,
vascular smooth circulations •IV infusion peripheral circulation
muscle
Telipressin •↑ vascular •Converted to lysine T ½ 40 m Bleeding: oesophageal Vasoconstriction-related ADE
sensitivity to α1 vasopressin (active) varices
adrenoceptor •in splanchnic and
agonists portal circulation
Ca channel blockers
LIPID REGULATING DRUGS

Dyslipidaemias : •Hypercholesterolaemia •Hypertriglyceridaemia •Mixed dyslipidaemia
Drug classfication Drug name Mode of action Pharmacokinetics ADR Special notes
Statins Natural Pravastatin •Reversibly inhibits HMG-CoA reductase in liver •Given orally •Mostly well tolerated Pleiotropic effects
•Activation of SREBP2 → ↑ hepatic LDL receptors •Well absorbed - GIT •Mild: Dyspepsia, abdominal pain, diarrhoea •Reversal of endothelial dysfunction
Simvastatin •↓ bioavailability •Hepatotoxicity •↓ coagulation
•↓ LDL: 25-55% •↑ protein bounded except pravastatin - Asymptomatic •↓ vascular inflammation
Lovastatin •↑ HDL: 5% •Metabolism by CYP (esp 3A4) - ↑ ALT, AST •Improved stability of atherosclerotic plaques
•↓ TAG: 10-35% •Active and inactive metabolites •Myotoxicity
Synthetic Atorvastatin •Mainly fecal excretion - Pain / tenderness, weakness Contraindications
- ↑ CK > 10 X •In pregnancy
Fluvastatin - Reversible •Discontinued if ALT / AST > 3 times
- ↑ risk with concurrent fibrate therapy, hypothyroidism,
Rosuvastatin renal insufficiency •Effective in 1ry & 2ry prevention
•Angioedema
Fibrates Gemfibrozil Activate PPARα → heterodimerizes with RXR → binds to PPREs in promoter •Rapidly absorbed with meals •GI symptoms
regions of genes related to lipid metabolism → regulation •↑ albumin binding •Myositis – ↑ risk with statins
•↑ lipoprotein lipase activity → ↑ VLDL degradation •T½: gemfibrozil – 1 h, fenofibrate – 20 h •↑ liver transaminases
•Inhibit Apo-CIII •Wide distribution
Fenofibrate
•↑ Beta oxidation of FA → ↓ Hepatic TG synthesis •90% renal elimination •Gallstone formation (Gemfibrozil)
•↑ LDL rec in liver & ↑LDL clearance •Displace warfarin from albumin
•↑ Apo AI, AII → ↑HDL •Inhibit glucuronidation of statins
Clofibrate •↓ TAG: 20-50%

•↓ LDL: 5-20%
•↑ HDL: 10-35%
Bile acid Cholestyramine •Cationic polymer resins → bind non covalently to bile acids (-ve) in SI → Powder form taken with liquid •Bloating & dyspepsia •As addition to statin
binding resins Prevent bile acid reabsorption •↓ absorption of digoxin, warfarin, fat-soluble vitamins – •When statin contraindicated
•Compensatory ↑ in HMG-CoA reductase activity and LDL receptor take 1 hour before or 4 hours after resin •Other
expression - Pruritis in biliary obstruction
Colestipol - Bile acid diarrhoea
•↓ LDL: 15-30%
•↑ HDL: 3-5%
•TAG: no effect or ↑
Niacin/Nicotinic acid/Vit B3 •Inhibits lipolysis in Adipose T → ↓ FFA formation → ↓TGA (VLDL) Flushing
synthesis in Liver: 20-50% Pruritus
•↓ LDL 5-25% Dyspepsia
•↑ HDL 20-35% Hyperuricaemia
Hepatotoxicty
Impaired insulin sensitivity
Myopathy
Inhibitors of Ezetimibe •Inhibit brush border protein NPC1L1 → ↓ cholesterol transport from Combined with statin for maximum Headache
cholesterol micelles into enterocytes effect Diarrhoea
absorption •↓ cholesterol absorption ~ 50% Myalgia
•↓ LDLc ~ 20% Raised AST/ALT
•↓ cholesterol incorporation into VLDL in liver
Omega-3 fatty Eicosapentaenoic acid (EPA) ↓ TAG
acids Docosahexaenoic acid (DHA) ↑ cholesterol
PCSK9 Monoclonal Ab Alirocumab ↑ availability of LDL receptors PCSK9 enzyme: Binds to LDL rec & ↓ LDL clearance
inhibitors Evolocumab
ANTIARRHYTHMIC DRUGS
ANS effects Mechanism of arrhythmias
•Sympathetic (β1) •Abnormal impulse initiation
↑ Pacemaker current - Abnormal automaticity
↑ Ca2+ current - Triggered activity (prolonged QT interval, Ca2+ overload)
•Parasympathetic (M2) •Abnormal impulse conduction
↓ Pacemaker current - Conduction block
↓ Ca2+ current - Re-entry
↑ K+ current
Drug classfication Mode of action Pharmacokinetics Uses ADR Contraindications Special notes
Vaughan Class 1 1a Procainamide Blocks Na+ channels (open & inactivated) & Elimination renal & For SVT, VT •Agranulocytosis
Williams Na+ channel Intermediate K+ channels hepatic (acetylation) •Drug-induced LE
classification blockers binding/unbinding Slowing phase 0 depolarization
(moderate block) APD prolonged
Quinidine
Disopyramide
1b Lignocaine •Blocks Na+ channels (inactivated & open) •Extensive first-pass Ventricular arrhythmias •Seizures
Fast in late phase 2 metabolism VT, VF •Heart failure
binding/unbinding •Little action on atrial myocardium (brief •DOA 10-20 m
(mild block) inactivated state of Na+ channels) •Elimination T ½ 100 –
•Antagonizes after-depolarizations 120 m
•↓ automaticity in ectopic foci •IV bolus → infusion
•APD unaffected or ↓
Phenytoin
Mexiletine
1c Flecainide •Slows upstroke of AP, ↓ excitability VTs, SVTs, A flutter, A structural heart
Slow •Most effect on His-Purkinje system, fibrillation disease, previous
binding/unbinding ventricular myocardium MI
(marked block) •APD not changed
Encainide
Propafenone
Class 2 Propranolol •Act on SAN and AVN Sinus tachycardia
β receptor •Block sympathetic tone (phaeochromocytoma)
antagonists Atenolol •Prolong phase 4
Metoprolol
Esmolol
Drug classfication Mode of action Pharmacokinetics Uses ADR Contraindications Special notes
Class 3 Amiodarone •Blocks phase 3 of AP Additional Na+, Ca2+ •Highly lipophilic , SVT, AF, VT •Thyroid disorders Prolongs QT, bradycardia, heart block
K+ channel •Prolong APD channel blockade & •PO / IV (Hypo/Hyper)
blockers •Prolong QT interval α, β antagonist •↑ T ½ (up to 5 •Pulmonary toxicity
months) •Photosensitivity :
•Hepatic metabolism bluish skin
discolouration
•Corneal
microdeposits
•Hepatotoxicity
Sotalol also β blocker

Dofetilide
Class 4 Verapamil •Slow rise prolonged APD PSVT, rate control in AF bradycardia, heart Heart block,
Ca2+ •Prolong phase 4 in SAN,AVN block advanced cardiac
channel •↓ rate, conduction failure
blockers
Diltiazem
Non classified Digoxin •↑ vagal activity (vagomimetic) → Blocks A- •Slow onset of action long-term tx of AF (rate Nausea, diarrhoea,
V conduction → ↓ rate •Narrow therapeutic control) yellow vision
•Membrane effects – blocks Na/K exchange index
→ ↑ intracellular Ca → ↑ contractility
Adenosine •A1 rec agonist (SAN, AVN, atria) •Rapid onset SVT Facial flushing,
•K+ channel opening → Membrane •short DOA hypotension,
hyperpolarization → Transient A-V block •IV bolus bronchospasm
Ivabradine Newer drug
DRUGS INFLUENCING MYOCARDIAL CONTRACTILITY

Drug classfication Drug name Mode of action Pharmacokinetics Uses ADR Sp. notes
Digoxin •Inhibit Na+/K+-ATPase •Oral bioavailability 75% •Nausea, vomiting, anorexia Found in
•Contractile myocardium •Metabolised to dihydrodigoxin by gut flora •Gynaecomastia leaves of
- ↑ force of contraction •Slow distribution to cardiac tissue → Onset of action - 30 m (after IV) •xanthopsia foxglove
•Small proportion metabolized in liver, non-CYP-450 dependent
•Conduction system •Cardiac arrhythmias
•Elimination 70% renal; 30% hepatic
↑ - ↓ SAN automaticity - AV conduction block
Cardiac •T ½ 36 h
Intracellular - ↓ conduction velocity through AVN •Hypokalaemia: ↑ binding to Na+/K+-ATPase - Ventricular ectopics
glycosides
Ca - ↑ automaticity of His-Purkinje system •Verapamil, quinidine, amiodarone: ↓ renal clearance - Junctional rhythm
•Autonomic •Low therapeutic index
- ↑ vagal tone
Digitoxin - ↑ baroreceptor sensitivity
Ouabain
Noradrenaline Positive inotropic & lusitropic action •Oral bioavailability poor tx of acute heart may cause arrhythmia
Adrenaline •Metabolised by MAO & COMT failure & circulatory
β1 agonists
Dopamine •Short T ½ shock
↑
Dobutamine •IV infusion
Intracellular
cAMP Milrinone •↓ breakdown of cAMP •IV infusion Short-term tx of •Ventricular arrhythmias - Long-
PDE-3 •Positive inotropic & lusitropic action •T ½ 2-3 h severe CHF term tx a/w with ↑ mortality
inhibitors •Vasodilatation (ino-dilators) •Elimination renal •Hypotension
COAGULATION
•Prevent thrombosis Vascular Phase
Platelet Phase Antiplatelet drugs Platelet function
Coagulation Phase Anticoagulants Affect fibrin formation
•Dissolve thrombus Fibrinolytic Phase Fibrinolytic drugs Fibrinolysis
•Promote haemostasis Antifibrinolytic
Vit K
Drug classfication Mode of action Pharmacokinetics Uses Advantages Disadvantages ADR Contraindications Special notes
Anticoagulants Indirect Parenteral - Unfractionated Bind to anti thrombin •SC, IV •Venous Gives immediate effect •dose Antagonism- by protamine •CNS- stroke within 3 w •muco polysachcharide
thrombin Heparin III → change it's •↓ T ½ thromboembolism - adjustments sulphate •GI - active peptic ulcer, Active •Found in mast cells.
inhibitors conformation → •Saturation kinetics prevention & tx •Monitoring •Haemorrhage IBD, oesophageal varices, •commercial preparations- extracted
(Antithrombin •Thrombosis
activate it •APTT (Intrinsic •Acute myocardial required uncompensated hepatic cirrhosis from beef lungs, hog intestine.
activators) •Thrombocytopenia (2-14 d tx)
•Inhibit thrombin & pathway) disease routinely •CVS- severe uncontrolled HPT •preparations differ in potency
•Osteoporosis (long term use)
other serine proteases •Renal excretion •Perepheral arterial •Hypoaldosteronism •Severe renal impairement •Doses in units
•Inhibit factor x occlusion •Hypersensitivity reactions •Haematological- bleeding
disorder
LMWH Dalteparin •Inhibit factor xa, but •SC •effects are more predictable & •thrombocytopenia &
not thrombin. •↑T ½ dosing is less frequent thrombosis
•1st order kinetic •Monitoring is not required •Less inhibition of PLT
Enoxaparin
•Safe and effective as
(Independent of dose) function
unfractionated heparin
•Do not prolong APTT
Tinzaparin •Convenient to use ,Pts can be
•Renal excretion taught to inject.
Synthetic pentasaccharide
analogues (newer)
Direct thrombin Ximelagatran Oral •No dosing problems
inhibitors •No monitoring needed.
Hirudin • i.v. , s.c. •Elimination
renal
•T ½ 1-2 h
Bivalirudin • i.v.
•Elimination renal &
hepatic ,
•T ½ 25 min
Argatroban
Oppose action Oral - Warfarin •Inhibit the vitamin K •Given orally Effect takes •Haemorrhage Factors that potentiate
of Vitamin K reductase •Complete absorption several days to - withhold warfarin •liver disease
- Vit K reductace: from GIT develop - Use IV Vit K, FFP, CF •hepatic CYP inhibitors
•Drugs that inhibit PLT function (NSAID)
reduce vit K to it’s •strongly bound to concentrate
•Drugs that displace warfarin from
active form- albumin •hepatotoxicity
albumin (chloral hydrate)
(hydroquinone) •Peak conc. within 1 •inhibition of protein c → Drugs that inhibit reduction of vit K
hour necrosis of soft tissues (cephalosporins)
•Peak effect- 48 h - use heparin tx before •Drugs that ↓ availability of vit K (broad
•Effect last 4-5 d warfarin spectrum ab)
•T ½- variable- 40 h •Teratogenicity- CNS
•Metabolism- hepatic abnormalities, bleeding Factors that ↓ effect
P450 •Physiological (affect CF): pregnancy,
•Monitoring of the hypothyroidism
•Drugs
effect- INR (Extrinsic &
- Affect action: Vit K
common pathway) - Affect metabolism: Hepatic P450
inducers
- ↓absorption: cholestyramine
Direct Factor Xa Apixaban Oral bioavailability 60%

inhibitors Half life 12 h
Elimination hepatic >
Rivaroxaban renal
Oral bioavailability 80%
Half life 7-11 h
Elimination renal >
Acivated Protein C (newer) hepatic
TFPI (newer)
Antiplatelet drugs ADP antagonists Ticlopidine slow action, 3-7 days related to arterial neutropenias
(Thienopyridine thrombosis
derivatives)
Clopidogrel less likely to cause
•Acute MI neutropenia
Prasuqrel •pts with ↑ risk of MI,
COX inhibitors Aspirin Irreversibly inhibit Daily dose 75-150 mg - angina, TIA, intermittent •(dose related) upper GI
acetylation of cox-1 in long term px of serious claudication toxicity: nausea, epigastric
PLT → ↓ synthesis of vascular events in high •1ry & 2ry prevention of pain,
TXA2 risk pts vascular events •Gastric erosions- bleeding
•After coronary artery \Enteric coated aspirin can
bypass grafting be used
•Unstable coronary
•↑ intracellular cAMP → syndromes Less potent than
PDE inhibitors Dipyridamole •modified-release No excess risk of bleeding headache With aspirin (or clopidogrel) has a
inhibit PLT function: •After coronary artery aspirin &
formulation additive beneficial effect.
adhesion, aggregation & angioplasty/ stenting thienopyridines
release of active •Transient cerebral
substanses ischaemic attacks
•↓ Adenosine uptake •Atrial fibrillation- if oral
anticoagulation is CI
GP IIb/IIIa Tirofiban Blocks final common IV Thrombocytopenia

inhibitors pathway for platelet
Eptifibatide
aggregation.
Abciximab
Fibrinolytic drugs Streptokinase (SK) •Binds to plasminogen Action blocked by antistreptococcal ab
→ activates it → - 1 year must elapse before it give
Dissolve existing again
thrombi
Tissue-type Alteplase •tPA More active on •↓ T ½ •Acute MI – within 12 h •Bleeding- GI haemorrhage •Active internal bleeding •Produced by recombinant DNA
plasminogen fibrin bound •I.V. infusion •Ischaemic stroke (tPA) & stroke •Haemorrhagic cerebrovascular technology
activator (tPA) plasminogen than •Reteplase- ↑ T ½ •Acute arterial •Allergic reactions & low disease
Dutrplase plasma plasminogen •Bleeding diathesis
•Not immunogenic thromboembolism grade fever.
→ clot selective •Pregnancy
•Clearing thrombosed •Streptokinase → bursts of
•Uncontrolled HPT
Reteplase shunts and canulae plasmin formation releasing •Invasive procedures where
kinins → hypotension haemostasis is important
•Recent trauma- vigorous CPR
Antifibrinolytic Tranexemic acid inhibit plasminogen Orally or IV •Life threatening bleeding
drugs activation following thrombolytic drugs
→ prevent fibrinolysis •Haemorrhage following
prostatectomy , dental
extraction
•Menorrhagia
Aprotinin inhibit proteolytic •Hereditory angioedema
enzymes
Vitamin K Vit K act as cofactor in •Natural •Tx & px of bleeding

•Naturally in plants:Fat soluble (Phytomenadione) post translational γ Oral – absorbed in - due to oral anticoagulants
•Synthetic: Water soluble - menadiol sodium phosphate carboxylation of upper intestine, in (IV)
- Haemorrhagic disease of
glutamic acid residues presence of bile salts
newborn (IM, oral)
in CF - ii vii, ix, x •Synthetic - oral IV
•Vit K deficiencies
- Coeliac disease,
steatorrhoea
- Obstructive jaundice (Lack
of bile)
DIURETICS
•Inhibit Na+ reabsorption from tubular fluid → ↑ urinary Na+ & water elimination
•Used to treat conditions with excessive Na+ & water retention
Drug classfication Mode of action Efficacy Pharmacokinetics Uses ADR Special notes
CA Acetazolamide •Reversibly inhibit proximal-tubule cytoplasmic CA II Efficacy too low Glaucoma to ↓ IOP
inhibitors & luminal CA IV (Loss of Na 5%)
•↓ H+ available to exchanged with luminal Na+
Osmotic Mannitol •Crystalline solid •pharmacologically inert •IV infusion •Cerebral oedema: move water from •Contraindicated in
diuretics •↑ osmolality in tubular fluid •Filtered by glomerulus & not reabsorbed brain, CSF Established ARF:
•Passive H20 reabsorption ↓ •To prevent ARF in oliguria: maintains expansion of
•↓ Na+ reabsorption in PCT GFR plasma volume will
•Expands ECF volume, draws water from ICF occur
compartment
Loop Furosemide •Inhibit Na+-K+-2Cl- cotransporter in apical High efficacy •Oral bioavailability 60% Bumetanide - severe CHF •Hypokalaemia
diuretics membrane of thick ascending limb •↓ lipid solubility •Hyponatraemia
•↓ paracellular reabsorption of Ca2+, Mg2+ •↑ plasma protein binding In rapid venodilation •Hypovolaemia
•↑ blood uric acid levels •T ½ 1-2 h •Acute pulmonary oedema •Hypocalcaemia
•Rapid venodilatation (IV) •Secreted in to PT by organic anion transport •Chronic eodematous states: •Hyperuricaemia –
•Excreted unchanged Nephrotic syndrome, cirrhosis, CHF lesser than thiazides
•Unsecreted fraction metabolised in liver •Hypertension (with low GFR) •Ototoxicity – with
Bumetanide • x40 potent than furosemide aminoglycosides
•Oral bioavailability 80-100% •Alkalosis
•Partly metabolized, partly excreted in urine
Ethacrynic acid
Thiazide Hydrochlorothiazide •Inhibit Na+-Cl- cotransporter in early DCT Moderate •Good oral absorption •Hypertension •Hypokalaemia Ineffective when
diuretics •↓ Ca2+ excretion efficacy •Variable lipid & protein binding •Nephrotic syndrome, cirrhosis, CHF •Hypercalcaemia GFR < 30 - 40 ml /
Metolazone
•↑ blood sugar (Na excretion •Secreted into PT, also filtered at glomerulus •Hypercalciuria •Hypovolaemia min / 1.73 m2
Indapamide •Metalozone has additive action with furosemide 5%) •Excreted unchanged (except Indapamide) •Hyperuricaemia (except
Bendrofluazide •Hyperglycaemia metolazone)
•Metabolic Alkalosis
K+ sparing Aldosterone Spironolactone inhibits formation of aldosterone induced proteins Weak diuretics •Oral bioavailability 75% •Hypertension •Hyperkalaemia
diuretics rec •High protein binding •with K+ loosing diuretics to prevent •Gynaecomastia - ↑
antagonists •Completely metabolized in liver to canrenone hypokalaemia Testos. clearence
(active) •CHF: Inhibit myocardial interstitial •Erectile dysfunction
fibrosis, improves survival •Menstrual disorders
•Ascitis, nephrotic syndrome •Acidosis
Eplerenone •Counteracts hyperaldosteronism Advantage - less
hormonal
disturbance
E Na+ c Amiloride
blockers Triamterene
IV FLUIDS
For Dehydration, electrolyte abnormalities, hypotension Osmolarity vs Tonicity
Classfication Uses ADR/Disadvantages
Oral rehydration salts (ORS) •Powder to be dissolved in drinking water Diarrheal disease
•Total osmolarity 245 mOsm / l
IV fluids Colloids Albumin Suspension of a substance that does not easily cross the capillary membrane oedema a/w Expensive
•Reference colloid solution hypoalbuminaemia
•Prepared from donated blood
Hydroxyethyl starch Solution of ions / molecules that easily cross the capillary membrane Risk of acute kidney injury in critically ill
•Hydroxyethyl groups added to amylopectin (obtained from sorghum, maize, potatoes) patients
to reduce hydrolysis by nonspecific amylases in blood
Gelatin
Dextran Long-chain glucose polysaccharide Hypersensitivity, platelet dysfunction
Crystalloids NaCl 0.9% (normal saline) Distributed in ECF
0.45% + 5% glucose
0.18% + 4% glucose
Dextrose 5% •Water without electrolytes
•Distributed in whole body water
•Glucose metabolised by cells
Compound sodium lactate •Electrolyte concentrations approximately similar to plasma replace plasma,in GI
(Hartmann's solution) fluid loss
K replacement KCl tablets May cause gastric irritation

KCl IV solution To be diluted before i.v. infusion
Ca replacement Ca gluconate 10% Elemental calcium 93 mg / 10 ml
CaCl 10% Elemental calcium 272 mg / 10 ml
Mg replacement MgSO4 50% To be diluted before i.v. infusion
THYROID DISEASES
Hypothyroidism - Thyroxine replaxement
Hyperthyroidism - Antithyroid drugs, Sx
Thryxonine Levothyroxine •Given daily on empty stomach •Replacement therapy ↓Absorption

replacement (mane) - TSH normal range •Drug interactions
•Oral bioavailability of tablets: 65 - 50-150 μg daily - FeSO4, CaCO3, Al(OH)3, sucralfate, bile acid
– 85% •Suppressive therapy sequestrants, and raloxifene
•Absorption better in fasting - TSH <0.01 mU/l •Comorbidities
state - Thyroid cancer, I - Disorders of malabsorption
•Metabolised by deiodination & deficiency goitre - Previous SI sx
conjugation (glucuronides & - 150-200 μg daily
sulfates) in liver ↑ Clearance
•Eliminated in urine & bile •Drug interactions
•Deconjugation → enterohepatic - Phenytoin, Carbamazepine, Phenobarbitone,
recycling Rifampicin, Tyrosine kinase inhibitors
•T ½ 7 days •Coexisting conditions
- Pregnancy
- Nephrotic syndrome
Antithyroid Thionamides Carbimazole (C) → •Interfere with thyroid peroxidase- •Rapidly •↑DOA; once- Minor Pregnancy & Lactation
drugs methimazole (M) mediated iodination of absorbed from daily •Skin reactions •cross the placenta
thyroglobulin GIT •Not bound to - urticaria, macular rashes •Risk of neonatal hypothyroidism
- Tx: antihistamines
•Immunomodulating effects •Actively plasma proteins •No significant differences in neonatal thyroid function
- Cross reactivity 50%
- ↓antithyrotropin-rec ab concentrated by between drugs
- Severe→discontinuation
- apoptosis of intrathyroidal L thyroid gland → •Arthralgia •Congenital anomalies with C & M
•Propylthiouracil blocks T4 → T3 Plasma conc. •Dyspepsia - Aplasia cutis
not correlate Major - Choanal or oesophageal atresia
with antithyroid •Polyarthritis - Umbilical abnormalities
activity •Agranulocytosis •P preferred in 1st trimester
- 0.1–0.5% •Safe during breast feeding
- within first 3 months
Propylthiouracil (P) •↓DOA; b.d. or
- Autoimmune basis
t.d.s. - fever, sore throat, mouth ulcers
•Bound to - Routine blood counts not necessary
albumin: cross - G-CSF enhances recovery
placenta ↓ •Hepatitis
- C & M : Intrahepatic cholestasis, Resolves after discontinuation
- P : Allergic hepatitis with HC necrosis, Recovery variable
•Vasculitis
- Mainly by P
- ANCA-positive
- Acute renal dysfunction, arthritis, skin ulceration, vasculitic rash,
respiratory symptoms
- immunosuppressive tx
Supersaturated KI •Excess intrathyroidal I inhibits Effect lasts 1-2 weeks •For rapid control of Same effect with iodinated contrast agents, amiodarone,
thyroid peroxidase hyperthyroidism topical povidone–iodine
•Known as Wolff–Chaikoff effect - thyroid storm
•↓ vascularity - preparation for sx
- severe cardiac disease
Radioactive iodine Taken up by thyroid cells → β •NaI (Na131) •Radiation thyroiditis CI in pregnancy & lactation
emission → tissue necrosis •Lq or capsule •Hypothyroidism
•Efeect over 6-18 w
Beta adrenoceptor antagonists Control symptoms
GLUCOCORTICOIDS & MINERALOCORTICOIDS

Drug classfication Effects Pharmacokinetics Adv Uses Disadv / ADR
Glucocorticoids Anti inflammatory & immunosuppresive •Rapid oral absorption Treating unwanted inflammation & •Replacement therapy- •Suppress useful
•Genomic •T ½ - 1 - 3 h in most drugs hypersensitivity reactions physiological effect defence reactions →
- Bind to IC receptors → nucleus translocation → interact with DNA → modify gene •Max effect in 2-8 h - Addisons disease opportunistic infection
transcription → induce anti inflammatory proteins •Given 2-3 times a day •Pharmacotherapy- higher •Impaired wound
- protein interference mechnism (at ↓ cortisol conc.) •Even topical application allows doses - Inflammation/ immuno healing
↓ DNA transcription of pro inflammatory proteins absorption, → systemic effects suppression •Cushing's syndrome
- longer time to act •Metabolism- by liver - Asthma,inflammatory
•Non genomic •Excretion- renal conditions of skin •Suppression of HPA
- Through signaling systems in the cytosol triggered by a liganded glu- receptor → •Hepatic and renal disease- ↑ T ½ - Hypersensitivity states axis
effect on anti inflammatory proteins •Enzyme induction – ↓ T ½ - Autoimmune diseases
- Rapid action •Transport in the blood - Neoplastic diseases
•On inflammatory cells - Bound form(95 %): CBG, albumin •Diagnostic use
↓ N,MAC, Mast cells, T –helper cells, fibroblast function- GAG- healing and repair, - Free - biologically active (5%) - Dexamethasone suppression
osteoblast action •Changes in free cortisol conc. test
↑ osteoclast action - circadian rythem
•On inflammatory cells - ↑ CBG in pregnancy, use oestrogens,
↓ cytokine II,Lk,TNF-α, cell adhesion factors,GM-CSF, prostanoids (COX-2 ), OCP
complement, NO, IgG, histamine release-mast cells - Liver disease- ↓ albumin, metabolism
↑ IL-10,IL-1, annexin-1
Metabolic
•CHO & proteins
- ↓ uptake and utilization of glucose
- ↑ gluconeogenesis → hyperglycaemia
- ↑ glycogen storage
- ↓ protein synthesis
- ↑ protein break down → wasting
Hydrocortisone - cAMP dependant
Principally naturally lypolytic
occurringresponse
steroid Oral, IV IM Inra articular
Prednisolone •Predominantly anti inflammatory - standard choice Orally
•little mineralocorticoid activity
Dexamethasone Powerful predominantly anti inflammatory steroids Long acting than prednisolone Used for therapeutic
Betamethasone suppression of adrenocortical
function
Methyl prednisolone •IV
•Mega dose pulse therapy
Beclomethasone Potent soluble steroids •By Inhalation, intranasally •Suppression of the HPA axis is for hay fever ,asthma
Budesonide •90% of the inhaled dose is swallowed minimal.
Fluticasone → largely inactivated by the first pass •Newer drugs: ↑ first pass
Mometasone metabolism metabolism, protein binding,
Ciclesonide •Absorption through gut, lungs, mouth lipophilicity → ↑ pulmonary
↓ residence time & ↓ systemic effects
Fluorinated Triamcinolone No Na retaining effect •muscle wasting can

corticosteroids be severe
•↑ dose- anorexia,
mental depression
Drug classfication Effects Pharmacokinetics Adv Uses Disadv / ADR
Mineralocorticoids Aldesterone •↑ Na reabsorption by the distal tubule of kidney

(main endogenous) •↑ excretion of K & H
Regulation of aldosterone synthesis and release
•↓ Na & ↑ K in plasma → RAA
•Genomic effect
- Transcription and translation of specific genes
- ↑ Na channels in apical membrane, Na,K ATPase in BL membrane
- ↑ K excretion
•Non genomic effect
- Action on Na,H exchange in apical membrane
Fluorinated Fludrocortisone •Strong mineralocorticoid activity Oral •Replacement therapy
corticosteroids •Can replace aldosterone effect •Addisons disease, autonomic
neuropathy- for volume
expansion
Glucocorticoid excess Tx Glucocorticoid Metyrapone •Prevents beta hydroxylation at C11

synthesis - ↑ 11 deoxy corticosterone- mineralocorticoid activity
inhibitors - ↑ 17 hydroxy progesterone- adrenal androgen formation, hirsutism
Ketoconazole •Inhibit multiple sites in steroidogenesis Inhibit CYP 450 hypogonadism in men.
Aminoglutethimide •Inhibit sex steroid precursors also
Mitotane •Inhibit steroidogenesis in ACTH regulatory step adrenal cancer
•Cause atrophy of adrenal cortex
Glucocorticoid rec Mifepristone (not effective)
antagonist
ANTI DIABETIC
Insulin indications
DM Tx of DM •T1 D: for survival •T2 D: for control
•T2(deficient)/T1 (absent) insulin production •OHA •Insulin •GD : optimize outcomes •Acute illness: sx or infection
•Insulin resistance •Insulin + OHA •Inject - GLP-1 RA •Hyperglycemic emergencies: rapid-acting
- Hyperosmolar state
- Diabetic ketoacidosis
Drug classfication Drug name Mode of action Pharmacokinetics Advantages Disadvantages ADR Special notes
Biguanides Metformin •Inhibit mitochondrial respiratory chain •Monotherapy Low risk of Accumulates in renal •Anorexia, abdominal discomfort •1st line drug in
complex-1 → ↑ AMP/ATP → Activate AMPK → •Immediate & slow release formulations hypoglycaemia failure. Discontinued •Diarrhoea T2DM
↑ catabolism & ↓ anabolism •Combine with other OHAs/ insulin/ both if Creatinine >1.6. •Metallic taste •Also used in
↑Insuling sensitivity •Oral bioavailability 50-60% •Weight loss - PCOS
↑Glucose uptake •Very low plasma protein binding •Lactic acidosis (rare) occur in : - Gestational
↑Glucose absorption •Not metabolized - Renal insufficiency diabetes
↑FA oxidation •DOA 6-8 h - Liver disease
↓Glycogen synthesis •Renal elimination through tubular secretion - Severe infection
↓FA synthesis
↓Protein synthesis
↓LDL ↑HDL
↓Gluconeogenesis
Sulphonylureas Glibenclamide Bind to SUR1 subunit → Block ATP sensitive K+ •Monotherapy/ combine •DOA 24 h •Can cause •Hypoglycaemia – ↑ risk in elderly , renal •Displaced from
channel → K+ efflux restricted → Partial with other OHA/insulin •50% to active metabolite, renal hypoglycemia disease protein binding (↑
depolarisation → •Taken before meals excretion •Down regulation of - Tolbutamide, Glipizide preferred action) –
Open Ca channels → Ca influx + release •Good oral absorption •50% excreted unchanged in SUR1s with time - ↑ - ↑ risk with glibenclamide salicylates,
intracellular Ca →fuse insulin containing •90% bound to plasma faeces dose •Weight gain – appetite sulfonamides
Glimepiride granules with cell membrane protein •DOA 24 h stimulation •Metabolism
→ release insulin (glu independant) •Varying DOA •Inactive metabolite, renal •Hypersensitivity reactions induced (↓ action)
•Variable metabolism and excretion – rashes, photosensitivity •Opposite actions
Extrapancreatic excretion – corticosteroids,
Tolbutamide •DOA 6-8 h
•↑ insulin receptors in target cells •Risk of hypoglycaemia ↑ thiazides increase
•Inactive metabolite, renal
•Inhibit liver gluconeogenesis with longer DOA glucose
excretion
•Stimulate appetite
Gliclazide •DOA 12 h
Glipizide •Inactive metabolite, renal

excretion, 10% excreted in
faeces
Thiazolidinediones Pioglitazone •Agonist of nuclear PPARγ (mainly in adipose •Good oral absorption No risk of Blood glucose •Weight gain – new adipocyte formation
(Glitazones) tissue. Also muscle , liver •99% bound to plasma proteins hypoglycemia reduction over 1-2 •Fluid retention – more with insulin
•Insulin sensitizer •Slow onset of action months therapy, may worsen HF
- ↑ transcription of insulin responsive genes •T ½ 3-4 h. active metabolite 24 h •Peripheral oedema – spironolactone may
- ↑ glucose uptake into fat, muscle. •Hepatic CYP metabolism be effective
- Activates genes regulating FA metabolism •Biliary (70%) & urinary elimination •↑ risk of fractures
- ↓ hepatic gluconeogenesis •Pioglitazone – a/w bladder cancer risk
- ↓ TGLs, ↑HDL
Drug classfication Drug name Mode of action Pharmacokinetics Advantages Disadvantages ADR Special notes
Incretin based drugs DPP4 Sitagliptin •prevent degredation of incretins by DPP-4 •Monotherapy •DOA 24 h No risk of •Nausea, vomiting, abdominal pain •Incretins - GLP-1
inhibitors enzyme •with metformin/ insulin •Excreted unchanged in urine hypoglycaemia •Anorexia & GIP secreted
•Look sp. Notes for MOA •With Metformin + SU •↓Dose in renal impairment with monotherapy •Weight loss from SI after meals
•Slows gastric emptying → With/without •URTI, nasopharyngitis •GLP-1 & GIP
•Suppresses appetite food •Severe allergy – Angioedema, promote insulin
Vildagliptin •DOA 12-24 h anaphylaxis, Steven-Johnson syndrome secretion from β
•Hepatic metabolism 75% •↑ incidence of pancreatitis cells (glucose
•↓Dose in liver, renal disease dependant)
•GLP-1 ↓
glucagon secretion
Saxagliptin CYP metabolism to active
metabolite from α cells & ↓
hepatic glucose
Linagliptin
production
GLP-1 rec Exenetide •Stable analogues of GLP-1 •S/C injection short acting (twice daily) •Nausea & vomiting
agonists •Look sp. Notes for MOA •With metformin and/or •Pancreatitis
Liraglutide •Delays gastric emptying SU long acting (once daily) •Headache
•Nasopharyngitis
Semaglutide first oral – recently approved
SGLT2 inhibitors Canagliflozin •Inhibits reabsorption of glucose from PCT •Monotherapy / combinations No risk of Efficacy reduced in •↑ GU infections
Dapagliflozin •↑ glycosuria •Once daily dosing hypoglycaemia renal failure •Hypotension
Empagliflozin Modest weight loss •Modest ↑ LDL-c (Canagliflozin)
α Glucosidase Inhibitors Acarbose •α-glucosidase in SI converts polysaccharides •Monotherapy/combinations Beneficial on both •Flatulence
→ monosaccharides •Taken with first bite of food T1 & T2 DM •Abdominal discomfort
Miglitol •Delays glucose absorption & ↓ post prandial •Diarrhoea
glucose rise •Rise in liver transaminases
Meglitinides Repaglinide •Quick short acting stimulation of insulin Taken with meals. No meal no tablet •hypoglycaemia (↓ risk compared to SU)
release •headaches, arthraligia
Nateglinide •Blocks K channels
•↓ post-prandial hyperglycaemia
INSULIN
Sources
•Bovine, porcine
- antigenic. Rare
•Human
•Insulin analogs
- less antigenic
ADE
Hypoglycaemia
Weight gain
Lipohypertrophy
Lipoatrophy
Allergic reaction
Hexamer → Dimer → Monomer - ↑ diffusion

IMMUNOMODULATORS
Immunosuppressants Immunostimulants
Immunosuppressants - Drug classfication
Inhibitors of Glucocorticoids
Lymphocyte
Gene Expression
Inhibitors of Inhibition of IL-2 Calcineurin Tacrolimus Use

Lymphocyte expression Inhibitors •Prophylaxis of solid-organ allograft rejection
Signaling •Topical - for use in atopic dermatitis and psoriasis
Cyclosporine
Inhibition of IL-2 mTOR Sirolimus
rec signaling Inhibitors Rapamycin
Cytotoxic Agents Antimetabolites Inhibition of de Methotrexate Inhibit DHF reductase
novo purine Azathioprine nonenzymatically cleaved to mercaptopurine
synthesis: That acts as a purine analogue and an inhibitor of DNA
synthesis.
Mycophenolate Prodrug - Mycophenolic acid
mofetil Inhibits IMPDH – enzyme in guanine synthesis
Inhibition of de Leflunomide Block Dihydroorotate → orotate reaction
novo
pyrimidine Methotrexate
synthesis:
Alkylating agents Cyclophosphamide form covalent with DNA or RNA → Introduce alkyl groups
→cross links in between strands of DNA → prevent cell
division & protein synthesis
Cytokine TNF-α Inhibitors Etanercept To treat rheumatoid arthritis, and psoriatic arthritis
Inhibitors Infliximab In Cronh’s disease and rheumatoid arthritis
(Anticytokine- Adalimumab in rheumatoid arthritis
Antibodies) IL-1 Inhibitors
IL-2 Inhibtors
Antibodies Polyclonal Ab Antithymocyte Globulin (ATG) •↓ circulating L by direct cytotoxicity
Against Specific •In Acute renal transplant rejection, recovery from
Immune Cell ischemic reperfusion injury
Molecules Monoclonal Ab Muromunab
Inhibitors of Efalizumab
Immune Cell
Adhesion
Janus kinase (JAK) inhibitors Bind to intracellular domains of Type I/II cytokine
receptors
Immune checkpoint inhibitors
JOINT DISEASES
DISEASE Drug Classification Mode of action Pharmacokinetics Uses ADR Special notes
Rheumatoid NSAID Non- Ibuprofen •Don't slow the progression of

selective disease
arthritis
COX Diclofenac sodium •Provide partial relief of pain &
inhibitors stiffness
TNF-α
COX–2 celecoxib •Adv - ↓ GI toxicity
IL - 1,6,17
inhibitors •Dis - ↑ risk of CV events
Goal: control the DMARD Synthetic Conventional methotrexate •DHF reductase inhibitor •7.5 – 30 mg weekly •↓FA -GI & BM effects •Gold standard for DMARD therapy
disease early •↓ thymidine & purine •Absorption variable - BM suppression •Monitoring - FBC, ALT, Creatinine
•↓swelling & nucleotide synthesis •Elimination mainly - Dyspepsia, oral ulcers
inflammation renal - Pneumonitis
•Improve pain - Teratogenicity
•Improve function •Hepatotoxicity
•↓radiographic sulfasalazine •Remove toxic free radicals Elimination hepatic •Dyspepsia, rashes, BM suppression Sulphapyridine + 5- ASA
progression •Remission in 3-6 m •Liver toxicity, haemolytic anemia
(erosions) leflunomide •Competitive inhibitor of •Oral •Hepatotoxicity Avoid pregnancy for 2 years
dihydroorotate dehydrogenase •T ½ - 4 – 28 days due to •Hypertention
(rate-limiting enzyme in de novo EHC •Pneumonitis
synthesis of pyrimidines) •Elimination hepatic •Peripheral neuropathy
•↓L proliferation •Action in one month •BM suppression
•Diarrhoea
•rashes
Chloroquine •Mechanism ? For mild disease •Irreversible retinal toxicity, corneal deposits •Take a month to see the effect
•Interference with Ag processing •Photosensitivity •Ophthalmologic evaluation every 6 months
? •Haemolytic anaemia
•Anti- inflammatory & •Blue–grey skin discolouration
immunomodulatory
hydroxychloroquine
corticosteroids
Targeted JAK inhibitors Bind to intracellular domains of
Tofacitinib Type I/II cytokine receptors
Biologic Tumour necrosis Adalimumab SC •Infection

factor Golimumab - Common (Bacterial)
If 2 of above antagonists Certolizumab pegol - Opportunistic (Tb)
is not •Demyelinating Disorders
Infliximab Kills cells that express TNFα •IV
working •Malignancy
•Every 2 month
properly •Worsening CHF
Etanercept •SC
•Twice / week
IL-1 receptor Anakinra Recombinant human IL-1 •SC •skin irritation at the injection site
antagonist receptor antagonist •Elimination renal •infections
IL-6 receptor Tocilizumab
antagonist
Anti-CD20 Rituximab •killing of CD20+ cells via
monoclonal - complement-mediated
antibody cytotoxicity
- ab-dependent cell-mediated
cytotoxicity
T cell co- Abatacept
stimulatory
blockers
Glucocorticoids Potent anti-inflammatory drugs Oral •To control the diaseas Serious ADE with long-term use
Intra articular - As bridge to DMARD tx
IM-depot - Systemic complications (e.g.
vasculitis)
DISEASE Drug Classification Mode of action Pharmacokinetics Uses ADR Special notes
Osteoarthritis NSAID Topical Diclofenac (1% gel or patch) •Effect not apparent till Indomethacin should avoid for long term use (a/w ↑
3-4w joint destruction
Goals •Topical inferior to,
•Control pain & safer than oral
swelling Coritcosteroid Intra articular injections
•↓ disability
•Improve the Glucosamine sulfate pain relief, ↓ tenderness, and Oral •Glycoprotein derived from marine exoskeletons or
quality of life improve mobility IV produced synthetically
•Prevent IM •Found - tendons, ligaments, cartilage, synovial fluid
progression Intra articular •Effectiveness not yet proven
Hyaluronic acids ↓ friction & improves Intra articular injections

articulation (act as synovial fluid)
Emerging therapies SNRI Duloxetine Improve pain

Strontium ranelate •↑ in overall arthritis score &
joint space narrowing
•Inhibits subchondral bone
resorption by regulating OPG,
RANKL, & MMPs produced by
osteoblasts
IL-1 rec antagonists ↑ level of IL – 1 a/w the severity of radiographic

changes
Abs to nerve Tanezumab •↑ levels of NGF found in synovial fluid with
growth osteoarthritis
factor •NGF modulates expression of peripheral & central
pain-related substances & sensitizes adjacent
nociceptive neurons in response to inflammation
Regenerative therapy •MSC - BM, adipose tissue, & synovium

Gouts Acute flare NSAIDS
Colchicine •Prevent migration of N to joints •pain subsides within 12 •Nausea
•Monosodium urate •↓ pain, swelling, & h & relief occurs after 48 •Vomiting
crystals in joints inflammation h •Diarrhea
•↑ production or ↓ •Rahes
excretion of uric Corticosteroids mod-high doses
acid Future flare Uricosuric Probenecid ↑secretion of urate into urine by
agents ↓ reuptake
Xanthine Allopurinol •Effective in overproducers
oxidase •May be effective in
inhibitor underexcretors
•Can work in pt.s with renal
insufficiency
Febuxostat If allergic to allopurinol
Rasburicase Recombinant uricase – If resistant to others
metabolize urate
DMARDs continued…
•Excep sulfasalazine & hydroxychloroquine, all other Combinations
are unsafe or of uncertain safety during pregnancy •Triple Therapy
- Methotrexate, Sulfasalazine, Hydroxychloroquine
•Monitor for •Double Therapy
- Myelosuppression - Methotrexate & Leflunomide
- Hepatotoxicity - Methotrexate & Sulfasalazine
- Malignancy - Methotrexate & Hydroxychloroquine
- Infection
METABOLIC BONE DISEASES

DISEASE Drug Classification Mode of action Pharmacokinetics Uses Advantages Disadvantages ADR Special notes
Vit D deficiency Vit D Vitamin D2 (Ergocalciferol) Physiological role of Vit D Toxicity 30% effective as vitamin
•↑ efficiency of intestinal •Hypercalcaemia D3 in maintaining serum
•Poor mineralisation of absorption of Ca & phosphate •Hyperphosphataemia 25-hydroxyvit D
bone matrix •↑ efficiency of renal absorption of
•Rickets in children, Vitamin D3 (Cholecalciferol) Ca
osteomalacia in adults 1α -hydroxyvitamin D3 (Alfacalcidol) •↑ expression of RANKL in
•Bone pain, proximal osteoblasts
myopathy 1,25-dihydroxyvitamin D3 (Calcitriol) •↓ secretion of PTH
•Serum 25-hydroxyvit D <
20 ng / ml 19-nor-1,25-dihydroxyvitamin D2 ↓ cause
(Paricalcitol) hypercalcaemia in
•Causes CKD
- Dietary deficiency
Ca supplements CaCO3 •Dyspepsia
- Malabsorption
•Constipation
- ↑ catabolism Ca acetate
•Hypercalcaemia
- CLD
Ca citrate •Interfere with absorption of digoxin,
- CKD
isoniazid, quinolones, tetracycline
- Hereditary Ca lactate
Posphate binders CaCO3 ↓ intestinal absorption of To control hyper

Vit D + Ca supplements
Ca acetate phosphate when given with meals phosphataemia in
Al(OH)3 CKD risk of aluminum toxicity
Ion-exchange resins
Osteoporosis Vit D + Ca
Antiresorptive Bisphosphonates Alendronate •Nonhydrolysable pyrophosphate •Poorly absorbed from GIT In both txt & •Upper GI irritation
agents (weekly) analogues •Taken on empty stomach prevention of •Contact stomatitis, oesophagitis
•Loss of bone mass & Risedronate •Incorporated into bone mineral •Shouldn't lie flat or eat osteoporosis •Osteonecrosis of the jaw (rare)
microarchitectural (block bone (weekly, •Suppress resorption by within 30 min •Atypical femoral fractures (rare)
deterioration of skeleton resorption by monthly) - Inhibiting the attachment of •Eliminated by glomerular IV; may cause flulike symptoms within the
→ ↑ risk of fracture inhibiting Ibandronate osteoclasts to bone matrix filtration - Contraindicated if first 3 days (usually with the first infusion)
•Bone resorption osteoclasts) (monthly) - Enhancing programmed cell eGFR < 35 ml/min - Fever, myalgia, bone pain
(osteoclatic) exceeds bone
Zoledronic acid death - Transient renal toxicity
formation (osteoblastic)
(yearly i.v.
infusion)
•Dx
PMHT E slows bone resorption by risk of breast cancer, CVD
- Bone mineral density
suppressing transcription of genes
measurement by DEXA
encoding RANKL, IL-6
- Lumbar spine, hip
SERM Raloxifene E receptor agonist in bone, •No effect on non-
- As T score
antagonist in endometrium & vertebral fractures
breast •↑risk of
thromboembolic events
Calcitonin Partially inhibits osteoclast activity SC or nasal No effect on non Endogenous peptide
vertebral fractures
RANKL antagonists Denosumab Inhibits differentiation of SC twice a year Atypical femoral fractures & osteonecrosis of Humanised monoclonal
osteoclasts the jaw (rarely) antibody
Anabolic agents Teriparatide •PTH analogue (PTH 1-34) •SC injection daily upto 2 May cause hypercalcemia PTH & PTHrP ↑
•Should be followed by an years osteoclastic activity with
(stimulate bone antiresorptive agent since the •Effect ↓ with time as bone continuous exposure
formation by anabolic effect is not sustained resorption catches up with (endogenous) but ↑
acting on after discontinuation bone formation (anabolic osteoblastic activity with
osteoblasts) window) intermittent (exogenous)
Abaloparatide PTHrP analogue Anabolic window exposure
wider than for
teriparatide
DISEASE Drug Classification Mode of action Pharmacokinetics Uses Advantages Disadvantages ADR Special notes
CKD
Hyperparathyroidism
Hypoparathyroidism
Hypercalcemia Isotonic saline + frusemide i.v
•Occur in
Hyperparathyroidism
Malignancy
Vitamin D toxicity
Calcitonin •Rapid action

•SC IM
Bisphosphonates Pamidronate IV infusion
Zoledronic acid
Glucocorticoids Oral IV
Calcimimetics Cinacalcet •↑ Ca-mediated inhibition of PTH •Oral bioavailability 20-25%; In secondary

(Allosteric modulator) release from parathyroid cells ↑ when taken with a high-fat hyperparathyroidism
•Modulate the Ca-sensing receptor meal in patients with CKD
(CaR) •Half life 30-40 hours
•Metabolized by hepatic CYP
3A4,1A2
Inhibitor of CYP2D6
GENERAL ANASTHETICS
•Absence of sensation Triad - Unconsciousness
•With revesible loss of consciousness Analgesia
Alter GABA & Glutamate receptors
Muscle relaxation
Drug classfication Drug name Mode of action Pharmacokinetics Uses Advantages Disadvantages ADR Contraindications Special notes
Inhalational NO Entonox (50:50 •light anasthesia- without •maintain surgical anasthesia- •Induction rapid •expensive- used in •nausea & vomiting •air in pleural, pericardial, •diffusion hypoxia - must always mixed with O2LL
NO:O2) demonstrably depressing the combination with other •Pleasant to breathe conjunction with other •prolonged repeated exposure a/w peritoneal spaces
respiratory & VMC anaesthetics •Recovery rapid. Rarely potent anasthetics megaloblastic changes in bone marrow •intestinal obstruction
Soulubility in blood
•strong analgesic effect •Entonox - in obstetric exceed 4 mins •bone marrow depression •arterial air embolism
↑ - slow induction
practice, tx of injuries •teratogenic risk •decompression sickness
↓ - diffusion hypoxia
•severe COAD
•emphysema
Halogenated Halothane •Highest blood/gas coefficient of •inexpensive •Slow recovery •Reduce CO Malignant hyperthermia
the volatile •pleasant to breathe •Sensities heart to arrythmatic effect of •Pharmacogenetic syndrome (AD)
catecholamines and hypercapnia •Inherited mutation of RyR in SR
•Induce hepatic enzymes (pt & OT staff) •Abnormally increased release of Ca
•Hepatic damage (2-3 days) •During or immediately after anaesthesia
•Severe hepatitis in repeated •Precipitated by potent inhalational agents
administration
•Malignant hyperthermia Signs/symptoms
•Muscle contraction, Rhabdomyolysis, Hypermetabolic
state, Hyperkalaemia, Acidosis
•Cardiac arrhythmia
medical emergency
Tx- Dantrolene, non specific

Isoflurane •Relatively low blood gas •Minimally metabolised - •Does not sensitise heart to •Pungent odor - •Peripheral vasodilation - ↓BP
coefficient breakdown products non catecholamines unpleasent, bronchial •Coronary vasodilator - coronary steal in
•Relaxes volantary muscels toxic •Does not induce convulsions irritation coronary artery stenosis
- ↓cortical electrical activity
Sevoflurane •Less chemically stable •2.5% metabolised in •In children •Pleasant to breathe •Respiratory & CVS effects similar to
•Less soluble than Isoflurane body Isoflurane - not cause coronary steal
Enflurane •Respiratory depression
•CVS depression, arrhythmias
•Poly uric renal failure, jaundice,
hepatotoxicity - but lower than Halothane
Intravenous Propofol •Dose dependent cortical •Continous infusion - targeted •Rapid induction (30 sec) •↓BP (70-80%) - HR unchanged, small
depression controlled infusion •Smooth & pleasant reduction in CO
•Anti convulsant induction •Rapid induction - transient apnoea
•Rapid induction
•Depress laryngeal reflexes •Nausea & Vomitting •Resumption of respiration - transient
•Rapid recovery after
extremly low tachypnea
single dose
Thiopental •No analgesic effect •Metabolism - liver •Potent anticonvulsant •Smooth rapid induction •Repeated doses •Nausea & vomiting •Short acting barbiturate
•Rapid redistribution - swift accumulate in fat - •Extravasation - local damage
recovery after a single dose prolong recovery •Accidental intra arterial - serious injury
•CNS - cerabral vasoconstriction -
↓cerebral blood flow & ICP
•CVS - hypotension -
Compensatory ↑ HR
Augment the effect by antihypertensives,
diuretics
•Respi - ↓RR, TV
Methohexitone •Anasthesia for ECT •Barbiturate similar to Thiopental

Etomidate •In emergency anasthesia •Less CVS suppression & •Pain on induction •Nausea & vomiting (20-50%) •Carboxylated imidazole
hypotension than Propofol or •Excitatory muscle •Adrenocortical suppression
Thiopental movements
Drug classfication Drug name Mode of action Pharmacokinetics Uses Advantages Disadvantages ADR Contraindications Special notes
Ketamine •Antagonist of NMDA receptor •Induction - IV IM •Subanasthetic doses - •Persist upto 15 min after •No muscular •Hypertnesion •Phencyclidine deravative (hallucinogen)
•Dissociative anaesthesia •Maintanence - repeated analgesia for painful single IV injection relaxation •Congestive cardiac failure •Tonic clonic movements resembling seizures
(sedation, amnesia, dissociation, doses procedures •Profound analgesia - can be •↑ICP & IOP •Hx of stroke
analgesia) •Anaesthesia for short used as the sole analgesic for •Hallucinations with •Alcohol intoxication
duration diagnostic and minor surgical interventions delirium during •Cerebral trauma
surgical interventions that •Tachycardia, ↑BP & CO - in recovery - ↓ by •Intracerebral haemorrhage,
don't require muscle shoked pts Benzodiazepine mass, ↑ICP
relaxation specially for •Pharyngeal & laryngeal •Salivary secretions - •Eye injury
children reflexes are only slightly ↓ with Atropine •↑IOP
impaired. Potent •Schitzophrenia, acute psychosis
bronchodilator - for
asthmatics requiring medical In pregnancy
ventilation •Caesarian section - less fetal &
neonatal depression
•Before term - oxytocic activity
•Eclampsia, pre eclampsia
PRE MEDICATION → INDUCTION → MAINTENANCE → POST OP CARE

Propofol NO
Thiopental Sevoflurane
Etomidate Desflurance/Isoflurane
Ketamine Propofol
Sevoflurane Ketamine
LOCAL ANASTHETICS
Prevent pain perception
Without loss of consciousness
Mode of action PPharmacokinetics Anaesthetic potency AE

Absorption at local site Infalmmed tissues Duration of action Metabolism
Penetrate to interior of axons as lipid soluble free base→inside •Effect within few minutes •Systemic toxicity, •Acidic pH→ Dissociation is 1-1.5 hrs. •ESTERS: via plasma Potency α lipid solubility Anaphylactoid reactions – Ester > Amide
–ionized→block the voltage gated Na channels→no AP→Nerve •Dissociate in the tissues to •Distribution, delayed Duration = protein esterases & hepatic ↑ solubility → can use a lower
block liberate free base (biologically •Washout •Risk of spreading infection binding enzymes concentration → ↓potential Systemic toxicity
active) related to local blood flow -Bupivacaine 95% •AMIDES: via hepatic for toxicity Affects action potential propagation throughout the body
↓ So undesirable to use LA -Lidocaine 65% enzymes
↓ -Procaine 6% CNS - excitation
Vasoconstrictors Impaired liver functions •Paresthesia, anxiety , tremors, euphoria, agitation, convulsions
•Slows the absorption → delay elimination →
•Prolong the action toxicity CVS
• ↓ systemic distribution (Specially in repeated Direct action on
• ↓ systemic toxicity in large doses. doses & infusions) - myocardium: myocardial depression
- peripheral vasculature: vasodilation (except cocaine)
Use dependent Contraindications
In extremities
Differential block Blood supply lost→area may be damaged.
Small fibers are more sensitive than large fibers
•Small: pain and autonomic blocked first
•Large: touch and movement later
Methods of administration
Surface/Topical anesthesia Infiltration anesthesia Regional anesthesia
Nerve block IV Epidural Spinal
Mucous membranes Topical paralyse the sensory nerve endings, small Inject a drug around nerve, plexus •Injected into an exsanguinated limb. Direct action on nerve roots •Into lumbar subarachnoid space
-Nose •EMLA -Eutectic mixture of local anaesthetics cutaneous nerves Both motor and sensory block •Tourniquet - prevents reaching systemic Diffusion across the dura •Following local anesthetic injection
-Mouth -Bases of prilocaine or lidocaine circulation Thoracic, lumbar, sacral •Sympathetic nerve block
-Esophagus -Absorption is very slow •Effect- in 6-8 min. lasts 40 min. regions •Cause Hypotension
-Tracheobronchial tree -Cream applied under an occlusive dressing for at least 1 hr. - 0.5-1% lidocaine without adrenaline No hypotension •Headache due to CSF leakage (use pencil point needles)
-Genitourinary tract -Used as a dermal anaesthetic Can give continuous
•Ametop – Tetracaine gel 4%
AMIDE ESTERS
Lignocaine •T ½- 1.5 hr. Cocaine •More toxicity
•First choice for Surface use, injections. •Only local anaesthetic having built- in vasoconstrictor action
•Used in cardiac arrythmias •Use is limited as a surface anaesthetic- for nose
Prilocaine •Similar to lidocaine, yet less toxic Tetracaine •Drops are used in ophthalmology –anaesthetize cornea
•Surface, dermal, regional anaesthesia •Less toxic drugs are available( proxymetacaine)
Bupivacaine •Slow onset: 30 min Benzocaine •Low potency
•Long duration of action- 8 hr •Surface anaesthesia (mouth/ pharynx)
Ropivacaine •Regional anaesthesia Procaine
HYPNOTICS SEDATIVES
Sedatives Cause diminished cognitive function Slow onset , longer duration
Hypnotics Drugs that induce & maintain sleep Quick onset, shorter duration
Drug classfication Drug name Mode of action Pharmacokinetics Uses Advantages Disadvantages ADR Special notes
Hyonotics Diazepam GABA A Cl- complex Variability in Eldery are more susceptible Interactions -
Nitrazepam •Oral absorption (>50 fold)
Alprazolam •Lipid solubility •Drowsiness •Alcohol
Temazepam •Plasma protein binding •Amnesia, confusion •CYP3A4 enzyme inhibitors
•Half life •Ataxia -Ketoconazole
Anti anxiety drugs Diazepam •Rapid redistribution (IV diazepam) •Impaired manual skills, driving -Erythromicin
Chlordiazepoxide •Hepatic metabolism •Tolerance -Isoniazid
Lorazepam •Active metabolites. Drugs with active metabolites may •Dependence - physical
Anti convulsants cumulate withdrawal. Anxiety, insomnia,
Diazepam •Renal elimination depression
Lorazepam Bind to BDZ receptor site →Allosteric Flurazepam For frequent nocturnal •Respiratory depression with
Clonazepam modulation (agonist) → ↑affinity to GABA to Slow elimination waking alcohol
receptor → ↑Cl- channel opening → •Active metabolite •Hypotension
Benzodiazepines Hyperpolarization •Long t1/2
↓ •Cumulation. To reverse symptoms of BZD
Enhance GABA mediated inhibition of CNS Diazepam Hypnotic, anxiolytic, muscle overdoses - BDZ receptor
Slow elimination/marked redistribution relaxant, premedicant, status antagonist (flumazenil)
•Active metabolite. epilepticus
•Accumulation & prolonged anxiolytic effect
Alprazolam Hypnotic, anxiolytic, panic
Rapid elimination/marked redistribution disorder
•Short acting.
•Marked withdrawal after regular use.
Midazolam Premedicant (endoscopic,
Ultrarapid elimination dental procedures)
•Rapid action:
Non benzodiazepine Zopiclone •Structurally different to BDZ •Shorter duration of action compared to BDZ •Mainly hypnotic •Less daytime sedation •Weal anti anxiety, muscle
hypnotics Zolpidem •Agonist at α1 subunit (Zaloplon - shortest acting, rapidly cleared) short term (>2 weeks) tx of •Less chance of developing relaxant, anticonvulsant
Zalepion •Elimination - hepatic, renal insomnia tolerance effect
Melatonin receptor Ramelteon MT1 Mt2 receptor agonist •Short half life •No BDZ like ADE Melatonin (secreted by
agonists •High first pass metabolism pineal gland in night)
Important for circadian
rhythm of brain
Thiopentone Not commonly used apart
Barbiturates from thiopentone in
ansthesia
Long term effects of Hypnotics/BDZ
•Tolerance
•Dependence
- Withdrawal syndrome
- Anxiety, tremor, dizziness, nervousness, convulsions, hallucinations
- Withdrawal symptoms quicker with short acting drugs
•Cognitive impairment
MOVEMENT DISORDERS
Disorder Introduction Drug classfication Drug name Mode of action Pharmacokinetics Uses Advantages ADR Special notes
•Degenration of Dopamine Levodopa •Most efficacious mode of •Anorexia, nausea, vomiting •Dopamine does not cross BBB
dopaminergic precursor symptom relief •Postural hypotension •Oral - 95% coverted to dopamine by
neurons •Psychosis dopa decarboxylase in extracerebral
•In substantia nigra •Motor complications tussues
pars compacta -Wearing off •Given with an extracerebral dopa
•Relative -Dyskinesia (peak dose) decarboxylase inhibitor
overactivity of Ach -On off effect -L dopa + Carbidopa
-L dopa + benserazide
•Motor Dopamine Ergot Bromocriptine •Used alone or as an •Motor complications lower •Anorexia, nausea, vomiting
-Tremor receptor derivatives adjunct to Levodopa than Levodopa •Postural hypotension
Pergolide
-Rigidity agonists •Ankle oedema
Non ergot Ropinirole
-Bradykinesia/ •Hallucinations
derivatives Pramipexole
hypokinesia •Ergot deravatives
-Postural instability SC -Fibrotic reactions (retroperitoneal,
PARKINSONISM Apomorphine pulmonary, cardiac valves)
•Non motor Inhibitors of MAO-B Selegiline •As an adjunct to Levodopa •Anorexia, Nausea
-Cognitive MAO-B & inhibitors •Insomnia
Rasagiline
-Autonomic COMT •Hallucinations
COMT Entacapone •↓O-methylation of Levodopa •Hepatotoxicity
inhibitors in gut - ↑ absorption & half
life
•↑On time ↓off time
Amantadine Amantadine •Dopamine release •Insomnia Disadvantage - Some loss of efficacy
(anti viral) •NMDA antagonist •Hallucinations after 3-6 months
•Livedo reticularis
•Ankle oedema
Muscarinic Benzhexol Mainly reduce tremor In drug induced •Dry mouth, constipation, urine retention
receptor Benztropine parkinsonism •Psychosis, cognitive disturbances
•Dopamine antagonists
Dopamine Haloperidol D2 receptor antogonist •Good oral Less sedation
overactivity in basal receptor bioavailability
ganglia antogonist •Metabolized in liver
•Jerky involuntary
Chorea movements
VMAT-2 Tetrabenazine Reversible inhibitor Metabolised in liver •Drowsiness
-Rhematic fever inhibitor •Depression
-Huntington disease •Suicidal thoughts
Benzhexol High dose

Botulinum toxin •Cleaved by trypsin or •Dystonia •Synthesized as single chain
bacterial enzymes into •Hemifacial spasm polypeptide
heavy chain & a light chain •Spasticity •Little potency until cleaved
Dystonia •Light chain (Zn)
dependent protease act on
NMJ
DEMENTIA
Chronic progressive deterioration in brain function with loss of memory, reasoning, language skills, personality etc.Multiple causes
Alcheimer's dementia ◘β amyloid plaque deposition

◘Neurofibrially tangles
(commonest cause)
◘Inflammation
◘Synaptic degenration
•↓ Cholinergic (nicotinic) transmission • Glutametergic excitotoxicity
Ach a/w memory, learning, attention, wakefulness/sleep Glu involve in cognition, neuroprotection
- ↓Cholinergic neurons - Pathological activation of NMDA receptors by glutamate → Ca influx ↑ → neuronal
- ↓Choline uptake damage and cell death
- ↓ACh release
- ↓Choline acetyl transferase
- ↓Nicotinic receptors
◘Neuronal loss
Drug classfication - AD Drug name Mode of action Pharmacokinetics Uses Advantages Disadvantages ADR Special notes
AchE inhibitors •Prevent degradation of ACh •Mild to moderate dementia. So •Progressive Relate to Ach excess •Currently the most
•Maintain & delay synaptic ACh best started early presynaptic neuron •Nausea & vomiting effective tx
levels •Symptomatic improvement only. loss → progressive •Diarrhoea •Modest clinical benefits
Don’t delay disease progression diminishing •Dizziness for a limited time period
production of Ach •Weight loss •Dose titration over
Rivastigmine •Inhibits AChE + BuChE •Highly lipid soluble •Transderaml patch \ can't cure •Myalgia months
•Inhibits AChE for ≈ 10 hrs •Extra hepatic metabolism •Fatigue
(pseudo irrevesible inhibitor) •Bradycardia, arrhythmia Contraindication
Donepezil •Highly selective revesible •Long half life •Once a day •Severe asthma
inhibitor •100% oral bioavailability dosing For 2-3 days. Can temporally •Severe COPD
•Liver metabolism lower dose •GI ulcers
Galantamine •Revesible AChE inhibitors •Liver metabolism •Cardiac conduction
•Some nicotinic receptor defects
agonist •Significant bradycardia
NMDA Memantine •Noncompetitive blocking of •Good oral bioavailability •If AChE inhibitors intolerant or •Confusion
antagonists NMDA receptor & inhibit •Hepatic metabolism contraindicated •Dizziness
prolonged influx of Ca •T 1/2 60-80 hrs •May be added on to AChE inhibitor •Drowsiness
•Also antagonist at 5-HT3 rec & •Renal elimination therapy •Anxiety
nACh rec •Mod-severe dementia •Hallucinations
•Insomnia
Novel agents Anti-amyloid Zolanezumab
immunotherapy Crenezumab
(monoclonal AB) Gantenerumab
Inhibitors of beta-
amyloid
production
ANTI EPILEPTIC DRUGS

Mechanisms of epilepsy Mechanisms of AED
•↑ excitation •↓ inhibition • ↑GABA activity •Ion channel block
- ↑Na influx - ↓ GABA activity -↑ post synaptic activity (use dependence)
- ↑ Ca influx (T type) •Abnormal neuronal circuits - Inhibit GABA transaminases
- ↓ K efflux •Channelopathies - Inhibit GABA uptake
Drug name Mode of action Pharmacokinetics Interactions Uses Advantages ADR Special notes
Phenytoin Na channel blockade (use dependent) •Slow absorption from GIT (bioavailability 85%) •Inducer of CYP 450 •Status epilepticus •Cosmetic - gum hyperplasia, acne, hirsutism, facial coarsening •Regular monitoring is
•Unpredictable after IM •Inhibit albumin binding competitively → phenytoin level ↑ •Trigeminal neuralgia •Cognitive impairement needed
•80-90% albumin bound (Salycylates, phenylbutazone, Na valporate) •Myotonic dystrophy •Osteomalacia
•Metabolized by liver •Competitively inhibit metabolism by CYP 450 •Megaloblastic anaemia
•Saturation kinetics. ↑dose - ↑ [plasma] (Phenobarbitone) •Teratogenicity - cleft palate
•T 1/2 at low doses 12-36 h •↓ metabolism •Toxicity - drowsiness, diplopia, dysarthria, ataxia, vertigo
(Valporate, isoniazid) •Overdose
- ↑seuzure activity
- Prolonged unconscious state due to saturation kinetics
•IV - cardiac depression
•Extravasation - severe ulceration
•Distal ischaemia - purple glove syndrome
Carbamazepine Na channel blockade (use dependent) •Oral bioavailability 80% •Inducer of CYP 450 •Partial seizures •Rash - 5-10%, maculopapular, rarely SJS Relatively safe in
•Metabolized by liver to an epoxide Autoinduction \ start with low dose and ↑ dose •Generalized tonic clonic •Osteomalacia pregnancy (if
•T 1/2 with repeated doses 15-30 h No loading dose - toxicity can occur as enzyme induction does •Neuropathic pain - trigeminal •Folic acid deficiency appropriate)
not occur with initial doses neuralgia •Drowsiness, imbalance, diplopia, ataxia,
•interacions with Phenytoin, OCP, Warfarin, Corticosteroids •Manic depressive illness •Agranulocytosis rarely, SIADH, hyponatraemia
Oxcarbazepine Prodrug - similar to Carbamazepine Metabolism doesn't produce epoxide Less tendency to induce enzymes •Dizziness
•Headache
•Hyponatremia
Lamotrigine •Na channel, Ca channel (T type) blockade •Well absorbed from GIT •↑ metabolism Monotherapy/ adjunctive in •Headache, nausea, vomiting, insomnia
•↓ Glutamate release •Metabolized by liver (Phenytoin, CBZ, Phenobarb) -Patial •Rash (with high doses & valporate)
•T 1/2 25 h •↓ metabolism -Generalised tonic clonic, abscence
(Na valporate)
Na valporate •Na channel, Ca channel (T type) blockade •Oral bioavailability 95-100% •Inhibitor of CYP 450 •Partial •Dyspepsia
•GABA rec activation •Metabolized by liver So inhibit own metabolism & of Phenytoin, CBZ, Lamotrigine •Tonic-clonic seizures •Tremor
•Inhibit GABA transaminases •T 1/2 7-17 h •Absence seizures •Weight gain, impaired glucose tolerance
•Myoclonic •Hair loss - curly regrowth
•Bipolar depressive illness •Hepatotoxicity - ↑ liver enz
-Idiosyncratic
-Children < 2 yrs on multiple AEDs
•Teratogenicity - neural tube defects (↓ by folic acid)
Phenobarbitone •GABA rec activation •Oral bioavailability 95% •Inducer of CYP 450 •Sedation with therapeutic levels
•Metabolized by liver (75%), excreted unchanged (25%) •Changes in cognition, mood & behaviour, megaloblastic changes, osteomalacia
•T 1/2 72-144 h •Hypersensitive reactions
•Addiction - withdrawal should be done slowly
•Overdose
- Depress brain stem function
- Coma, respiratory failure, cardiac arrest
•Teratogenecity - cardiac malformations
Clonazepam •GABA rec activation •Oral bioavailability 80% •Sedation

•Ca channel (T type) blockade •Metabolized by liver •Tolerance with prolonged use
•T 1/2 30 h
Vigabatrin Inhibit GABA transaminases (irrevesible) Effect longer - Peripheral visual field defect - tunnel vision (need visual field monitoring)
once daily
Gabapentin Inhibit glutamate release by blocking high voltage •Well absorbed from GIT No effect on metabolizing enzymes Adjunctive therapy for partial Less severe
activated Ca channels •Saturablre system seizures
•Eliminate unchanged in urine •Sedation
•T 1/2 6 h - needs tds dosing •Fatigue
•Weight gain
Drug name Mode of action Pharmacokinetics Interactions Uses Advantages ADR Special notes
Topiramate •Na & Ca channel blockade •Well absorbed from GIT •Partial Less severe
•GABA potentiation •70% eliminate unchanged in urine •Generalised - tonic clonic,
•Glutamate receptor block •T 1/2 21 h myoclonic •Sedation
•Carbonic anhydrase inhibition •Fatigue
•Weght loss
•Renal calculi
•↑ IOP
Levetiracetam Bind to synaptic vesicle protein SV2A (inhibit •Oral bioavailability 96% •Partial seizures •Drowsiness
synaptic vesicle fusion & NT release) •Elimination mainly renal (unchanged) •Migrain prevention •Dizziness
•T 1/2 6-8 h
Ethosuximide •Ca channels (T type) blockade in thalamic neurons •Oral bioavailbility 95% •Absence seizures - rhythmic •Dyspepsia
•Metabolized by liver 25%, excreted unchanged discharges of thalamic neurons •Ataxia, imbalance
•T 1/2 20-60 h
Clobazam
Felbamate
Tiagabine
Zonisamide
Drugs in Status Epilepticus Pnemonics

CYP 450 Inducers - CRAP GPS / PC BRAS
•Benzodiazepines CYP 450 Inhibitors - SICK FACES.COM Group
- Lorazepam (iv)
- Diazepam (iv, rectal)
- Midazolam (iv, buccal, intranasal)
may cause respiratory deprssion, hypotention, impaired consciousness
•Phenytoin (iv)
•Phenobarbitone (iv)
•General anasthesia (iv)
- Thiopentone
- Propofol
- Midazolam
MIGRAIN
Pathophysiology- Trigemino vascular theory Treatment options
•Neurogenic inflammation of vessels •Non pharmacological
•5-HT key role •Pharmacological - Acute attack (abortive therapies)
•Release of mediators → pulsatile dialation of - Prophylaxis
-CGRP large cranial vessels
-Neurokinin
-Substance P
Pharma. Tx Drug classfication Drug name Mode of action Pharmacokinetics Uses Adv ADR Contraindi Special notes
Acute attack Simple analgesics Paracetamol

NSAIDs
Antiemtics Metochlorpramide
Domperidone
Specific Triptans (5-HT 1B/1D Sumatriptan -Trigeminal nerve : presynaptic autoreceptors 5-HT •Complete absorption after SC injection Usually mild •IHD
drugs agonists) 1B/1D •Poor oral bioavailability 15% (>ergots) •Hypertension
-Cranial vessels : 5-HT 1B •Short half life 1.5 h •Tightness in head, chest •Epilepsy
•Metabolized by MAO-A enz, CYP-450 •Parasthesia
•↓ Trigeminal nerve transmission & neurogenic •Excreted in urine •Dizziness
Zolmitriptan inflammation Newer triptans -Greater oral bioavailability •Bradycardia, coronary vasospasm (rare)
↓ Release of vasoactive peptides (substance p, CGRP)
Rizatriptan
CGRP Monoclonal Erenumab •SC injections CGRP

inhibitors AB to CGRP & •Eptinezumab - 3 monthly IV •Produced in central, peripheral
Fremanezumab
receptors injection neurons
Galcanezumab •Prophylaxis - monthly or less •Potent vasodialator
frequently •Transmission of nociception
Eptinezumab
•Produced in cell bodies of
CGRP Rimegepant Rapid brain
trigeminal ganglion & released
antagonists penetrartion
Urbrogenpant during migrain attacks
(gepants)
Ergot alkaloids Ergotamine -Partial agonism of 5-HT 1 receptors αadrenoceptor •Poor GI absorption - low oral bioavailability •Administer Oral, sublingual, •Nausea, vomiting •CAD
•Constrict blood vessels agonist •Caffeine ↑ absorption early in attack, rectal •Parasthesia, tingling •PVD
•Blocks trigeminal nerve •Liver metabolism repeated if •Coronary vascular spasm, pheripheral •Pregnancy
Dihydroergotamine transmission αadrenoceptor •Excreted in urine necessary (semisynthetic): vasoconstriction
•↓ Neurogenic inflammation antagonist nasal spray, SC,
IM \ Going out of use
Prophylaxis β blockers Propranolol Unclear •Fatigue Effects seen in about 4 weeks
Metaprolol •Bronchoconstriction
(In mod-severe Tricyclic antidepressents Amitriptylline NA/5-HT reuptake inhibition Sedetaion, dry mouth, constipation,
migraine) Imipramine arrhythmias
Ca channel blockers Flunarizine Unclear Useful in children Sedetion, weight gain, parkinsonism
Topiramate Topiramate •Antiepileptic drug •Sedetion
•Na channel blockade •Weight loss
•GABA enhancement •Renal stones
•Teratogenic - not used in females of
child bearign age
5-HT2 receptor antagonists Pizotifen •Antimuscarinic effect
Methysergide •Weight gain
MOOD DISORDERS
Major depressive disorder
Bipolar disorder
Pathology Drug classification Drug name Mode of action Pharmacokinetics Interactions Advantages ADR Special notes
Depression Antidepressants Monoamine Tricyclic (non Imipramine Also have antagonist action of •Well absorbed after oral •Sedation Other uses
reuptake selective) - muscarinic administration •Constipation, dry mouth, urinary retention •Panic disorder
inhibitors Amitriptyline - α1 •Highly protein bound •Orthostatic hypotension •Neuropathic pain
•Lowered mood state
- H1 •Hepatic metabolism •Cardiac arrhythmias (Na channel blockade) - Post herpatic neuralgia
Doxepin
•Monoamine →ADE •Weight gain - Painful diabetic neuropathy
hypothesis •Lowered seizure threshold •Migraine
Dothiepin
- ↓NE, 5 HT & •Nocturnal enuresis
dopamine activity in
brain Selective serotonin Fluoxetine •Well absorbed after oral Seretonin syndrome •Safer than TCA in overdose •Anorexia, nausea, vomiting •Disadvantage - Clinical response
reuptake inhibitors administraion •When co-administered with •Sexual dysfunction delayed by about 2 weeks
•Neuroplasticity (SSRI) Sertraline •Hepatic metabolism TCA, triptans, tramadol, MOI •Suicidal thoughts (esp adolescents)
-Functional/structural •Causes hyperthermia, rigidity, •Other uses
changes in brain Citalopram tremors, myoclonus, altered -Obsessive compulsive disorder
response to mental state, autonomic -Panic disorder
environment & instability
experience Serotonin and Venlafaxine •Oral bioavailability 45% Nausea, insomnia, HPT, agitation, sexual
norepinephrine •Metabolised by CYP2D6 & others dysfunction
reuptake inhibitors •Immediate & extended release
(SNRI) formulations
Duloxetine •Good oral bioavailability Other uses - Neuropathic pain
•Metabolised by CYP2D6 & CYP1A2
•T 1/2 12 h
Atypical Mirtazapine •5HT 2, 5 HT 3, presynaptic α2, H1 •Good oral bioavailability ↑appetite - weight gain Sedation
antidepressants antagonist •Metabolised by CYP2D6, CYP1A2 &
•Minimum effects on monoamine reuptake CYP3A4
•T 1/2 20-40 h
Bupropion •Inhibit NE& Dopamine reuptake Metabolised in liver Less sedation, sexual •Insomnia
•No direct action on serotonin system dysfunction, & GI •Agitation
disturbances than with SSRI •Seizures
Bipolar disorder Mood stabilizer Lithium •Enters cell via Na channels •Oral bioavailability > 95% Plasma lithium concentration •Metallic taste, nausea, diarrhea
•Mechanism not clear •No metabolism increased by NSAIDs, ACE •Polyuria, polydipsia (↓ ADH action); may
Neuroplasticity leading •Proposed mechanisms •Eliminated by kidneys inhibitors, diuretics (esp. progress to nephrogenic DI
to alterations in - Down regulation of 2nd messenger •T 1/2 20 h thiazides) •↓ SA node function
systems (phosphotidylinositol cycle) •Therapeutic conc 0.4 – 1.0 mmol/l •Hypothyroidism, goitre (↓ TSH action)
•Intracellular signaling - Inhibition of GSK-3 (12 h after last dose) •Neurotoxicity
cascades - Inhibition of glutamatergic •Low therapeutic index - tremor, ataxia, dysarthria, myoclonus,
- Phosphotidylinositol neurotransmisson hyperrefexia, impaired consciousness
pathway - 5-HT 1B antagonist
- GSK-3 pathway Carbamazepine Na+ channel blockade (use-dependent) •Oral bioavailability 80% •Rash (5-10%); maculopapular; rarely SJS
•Metabolized by liver •Drowsiness, imbalance, diplopia
•Glutametargic •T 1/2 8-24 h •Rarely agranulocytosis, hyponatraemia
neurotransmission •CYP-450 inducer→
Autoinduction (pharmacokinetic
tolerance)
Na valporate •Blocks Na+, T-type Ca++ channels •Oral bioavailability 95-100% •Dyspepsia
•Potentiats GABA receptor activation •Metabolized by liver •Tremor
•Inhibits glutamate activity •T 1/2 7-17 h •Weight gain
•CYP-450 inhibitor •Hair loss
•Hepatotoxicity
•Teratogenicity
-Neural tube defects (↓ by folic acid)
Lamotrigine •Blocks Na+, T-type Ca++ channels •Well absorbed from GIT •Headache, nausea, vomiting
•Inhibits glutamate release •Metabolized by liver •Rash (more likely with high doses &
•T 1/2 25 h valproate)
DRUGS ACTING ON NMJ

Drug classification Drug name Mode of action Pharmacokinetics Uses Advantages ADR Special notes
Pre synaptic Botulinum toxin Inhibit ACh release Local injection •Spasticity Botulinum Poisoning
•Urinary incontinence associated with
bladder overactivity •Progressive parasympathetic and motor paralysis
•Squint •Dry mouth
•Hyperhidrosis •Blurred vision
•Sialorrhoea •Difficulty in swallowing -progressive respiratory paralysis.
•Headache prophylaxis •Mortality is high, and recovery takes several weeks.
•Anticholinesterases and drugs that increase transmitter release are
Cosmetic uses - ineffective in restoring transmission.
•Blepharospasm
•Forehead wrinkles
Synaptic cleft AChE inhibitors Short acting Edrophonium •Binds anionic site of enzyme - •Diagnostic - in myasthenia gravis: Effects in Peripheral and central cholinergic synapses
readily reversible improvement of muscle strength is
•Action - very brief characteristic (doesn't occur when muscle ◘NMJ
weakness is due to other causes) Twitch tension of muscle is stimulated
•Myasthenia gravis (↓ Ach receptors) – ChE inhibition ↑ transmission
Medium acting Neostigmine •Quaternary ammonium •Works in 4 min •Treat - myasthenia gravis Too much - act as depolarizing blocker •Curarised muscle (nondepolarising blocking ) – to reverse
compounds •Act for 30 min
Pyridostigmine •Accumulation of Ach in motor ◘Parasympathetic cholinergic synapse
end plate ↑ Ach activity
Physostigmine Calabar bean
•In parasympathetic synapse ◘CNS
Irrevesible Organophosphate •Pentavalent phosphorus Highly lipid soluble War gases, pesticides, clinical use Tertiary compounds (physostigmine), and non-polar organophosphates
compounds penetrate BBB → affect brain
•No appreciable hydrolysis occurs (convulsions → depression → unconsciousness & respiratory failure)
•Recovery - depends on the Antagonised by atropine
synthesis of new enzymes – may
take weeks ◘Neurotoxicity of organophosphates
•In parasympathetic synapse Chronic low level exposure of agricultural and other workers to
organophosphorous pesticides a/w neurobehavioural disorders
AChE reactivators Pralidoxime Bind to organophosphate bound

AChE
Post synaptic NM blockers Non Atracurium •Flaccid paralysis – block Ach T1/2 – 15- 30 min •During surgical procedure •Spontaneously inactive Histamine release – bronchospasm and
Depolarizing receptors •Not abosorbed- give IV •During electroconvulsive therapy - no need to of reversal hypotension
(antagonist) •Acts as competitive antagonist •Do not cross the placenta – can use - In renal and hepatic
•Reversed by AChE inhibitors- in pregancey impairment
increase Ach at end plate •Most - metabolised by liver/
excreted unchanged in urine.
Vecuronium (Exceptions No histamine release Sugammadex for recovery
- Atracurium: hydrolyses •Ring like structures
spontaneously in plasma •Gama cyclodextrin:
Rocuronium - Mivacurium - hydrolysed by plasma •Rapid onset of action - encapsulate & take away
ChE tracheal intubation to •No SE of AChE Inhibitors
be achieved after 60 s.
•Negligible
•Similar duration of action to
cardiovascular effects
vecuronium
Depolarizing Suxamethonium •Muscle contraction – •Rapid onset – 1 min •Bradycardia ( tx with atropine) For intubation
(agonist) fasciculation- paralysis •Short action – 4 min •Muscle pain
•Not destroyed by AChE •Destroyed by plasma ChE •Hyperkelamia
•↑IOP
•Phase 1 block - Persistent
activation of nAChR → keeps the •Malignant hyperthermia (rare) -
membrane depolarized → mutation of the Ca2+ release channel of
prevent further AP the SR → muscle spasm → ↑ T (tx -
•Phase 2 block - Prolonged dantrolene)
exposure → repolarization but
the receptor remains •Prolonged paralysis.
unresponsive to Ach. - Genetic: ↓ activity of plasma ChE
- Anticholinesterase drugs
- Neonates: ↓ plasma ChE
ANTIPSYCHOTICS
Treatment of Schizophrenia - Non pharmalogical
- Pharmalogical - Antipsychotics - ↓ dopaminergic transmission
Drug classification Mode of action Pha.kinetics Advantages Disadvantages ADR Special notes
First Potent dopamine D2 rec Phenothiazines Chlopromazine D2 blocking in •Variable •Antispyschotic Have more neurological ADR •Also block D1,
generation antagonist •Mesolimbic areas → Antipsychotic effect → bioavailability effect developes •Movement disorders D3, D4
(typical) ↓ Positive symptoms (10-70%) over weeks - Dystonias (Phenothiazines,
Thiorizadine - hallucinations •Highly lipophilic •Sedative effect - Tardive dyskinesia thioxanthenes)
- delusions •High plasma quicker - Akathasia •Also block H1,
- irrational behaviour protein binding - Pseudoparkinsonism M1, α1
Trifluoperazine - hyperactivity (75-99%) •Neuroleptic malignant syndrome receptors
- agitation & aggression •Large volume of
- Thought & behaviour normalized distribution Other
•Long half-lives •Sedation, weight gain (H1, 5HT2C block)
Butyrophenones Haloperidol
•Mesocortical areas → ↑ negative symptoms •Hepatic •Orthostatic hypotension (α1 block)
metabolism •Dry mouth (M1 block)
•Basal ganglia → Extrapyramidal ADE •Prolonged QT interval
•Hyperprolactinaemia (dopamine inhibits prolactin
Thioxanthenes Flupenthixol
release)
•↑ of blood glucose, triglycerides: i.e. CPZ (5HT2c
block)
Second Potent serotonin (5-HT2A) antagonists Risperidone Recommended as •Less extrapyramidal More expensive Have more metabolic ADR •Also block M1,
generation Olanazapine first line drugs ADE •Weight gain, glucose intolerance (Clozapine, H1, α1, 5HT2c
(Atypical) Amisulpiride Release dopamine in prefrontal cortex → improve negative •Negative symptoms olanzapine)
Aripripazole sym. (5-HT2A inhibit DA release) respond better to •Hyperlipidaemia
Loose binding to D2 receptors → •Compared with FGAs, affinity 5-HT2 > D2 •Specificity: newer agents •Prolonged QT interval
Moderate/weak antagonists mesolimbic > striatal •↑ efficacy & •Anticholinergic effects
compliance (e.g., •↑ mortality among older patients with dementia
decreased due to stroke (Risperidone, olanzapine)
5-HT1A agonists Ziprasidone •↑ DA release from prefrontal cortex rehospitalization rates •Agranulocytosis (Clozapine)
Quetiapine •↓ glutamate release & bed days of care)
Clozapine First SGA
First Generation ADE continued…….

Mechanism Tx
Dystonias Appears in first days of therpy Nigrostriatal D2 blockade - ↑ cholinergic output •Acute Tx. IM Benzatropine (Anticholinergic/Antihistamine)
•Stop/reduce offending drug
Tardive dyskinesia •Develop slowly month - years D2 receptor supersensitivity •Stopping offending drug can worsens symptoms
Movement •50% irrevesible •Clozapine least likely to cause TD
disorders •Reversible VMAT2 (Valbenazine, Tetrabenazine)
Akathasia Common with FGA (haloperidol) •Benzodiazepines
•β blockers – i.e. propranolol
Pseudoparkinsonism •Benzhexol (Trihexiphenidyl) - Antimuscarinic
•Idiosyncratic reactions •D2 receptor blockade in NS pathway, hypothalamus •Bromocriptine (Dopamine agonist)
•Within weeks of starting neuroleptic •Glutamate release •Dantrolene – reduces muscle rigidity
Neuroleptic malignant syndrome
•Cause by Butyrophenones (haloperidol), phenothiazines (Chlorpromazine) •Removal of tonic inhibition of sympathetic NS sympathetic
•May occur with atypicals- less frequently hyperactivity
DRUGS IN ALEMENTATION
Drug classification Mode of action Pharmacokinetics Uses ADR Special notes
ANTIEMETICS H1 rec Cinnarazine For vestibular diseases - acute Sedation

antagonists Promethazine labrynthitis
Cyclizine Cinnarazine also in motion
Dimenhydrinate sickness
Betahistine Meniers disease (H1, H3)
Muscarinic rec Hyoscine hydrobromide (Scopolamine) •Well absorbed from GIT, In motion sickness Dry mouth, blurred vision,
antagonists skin drowsiness
•Oral, dermal patch
D2 rec Domperidone Gastric prokinetic action (DA inhibit upper GI Oral, rectal, IM, IV Drug-induced vomiting,
antagonists Metoclopramide motility) autonomic gastroparesis, Acute dystonic reactions possible
Prochlorperazine Also H1 & M1 migraine For neurotransmitters and
5HT3 rec Granisetron IV, oral, transdermal patch, High efficacy in •Headache receptors involve in vomiting
antagonists submucosal patch - Chemotherapy / radiation- •Transient elevation of hepatic see below
induced vomiting aminotransferases
Ondansetron - Post-operative vomiting •Constipation
Lack ADEs of dop. antagonists

Neurokinin 1 rec Aprepitant Oral, IV •Chemotherapy induced vomiting •Drowsiness, nausea, loss of
antagonists Rolapitant •Also anxiolytic action apetite
Casopitant •Stevens- Johnson syndrome
Cannabinoid rec Nabilone Chemotherapy-induced vomiting •Postural hypotension
agonists Dronabinol •Mood changes
LAXATIVES Bulk forming la. ↑ fiber Diet - indigestible

intake polysaccharides
Fibre Psyllium
supplements Methylcellulose
Polycarbophil
↑ vol of colon contents → peristalsis
Stimulant Bisacodyl •Stimulates secretion & motility of small Tablets, suppositories Abdominal cramps Contraindicated in intestinal
laxatives intestine & colon obstruction
Senna •Act on nerve plexus
Osmotic Lactulose •Synthetic disaccharide
laxatives (galactose & fructose) linked by
Water
a bond resistant to
retention →
disaccharidases
↑ bowel
•Undergoes bacterial
bulk
fermentation in colon
Mg salts MgSO4
Stool softners & Softner Docusate •Malabsorption of fat-soluble
lubricants Lubricant Arachis oil vitamins
Paraffin Lq •Anal seepage
ANTIDIARRHOEAL Opioids Loperamide µ opioid receptor agonist (↓ activity in In motility disorders Should not be used in
myenteric plexus) - Irritable bowel syndrome infective diarrhoeas
DRUGS
Muscarinic rec Atropine - Autonomic neuropathy
antagonists Diphenoxylate (co-phenotrope)
PROKINETC D2 antagonists Metoclopramide Accelerate Also has 5HT3 antagonist & •Diabetic gastroparesis
gastric 5HT4 agonist effect •Irritable bowel syndrome
DRUGS
5HT4 agonists Mosapride emptying,
Cisapride small bowel
Motilin agonists Erythromycin & colonic Cause antral contraction •Abdominal pain, vomiting Motilin secreted from
transit •Cardiac arrhythmias duodenum, jejunum
Clarithromycin
Controls inter-digestive
Azitromycin contractions
Neurotransmitters and receptors involved in vomiting
NT REC
Ach M
Dopamine D2
5HT 5HT3
Histamine H1
Substance P NK1
Endocannabinoids CB1
PEPTIC ULCER DISEASE

Basis of action
- ↓ HCl acid production - ↑ mucosal protection
Drug classification Drug name Mode of action Pharmacokinetics Advantages ADR Special notes
Inhibitors of Proton pump Omeprazole •React with a cysteine residue on the H+/K+-ATPase → form a •Enteric coated - to prevent pre mature activation •Well tolerated May cause Omeprazole & esomeprazole
acid production inhibitors Esomeprazole covalent disulphide bond → irreversible inhibition •Absorbed from duodenum •More effective •Nausea inhibit CYP-450
•Inactive at neutral pH (pro drug) → reactive in acidic •Should be taken 1 hour before meal than H2 rec. •Abdominal pain
Lansoprazole environment of the parietal cell canaliculi •Inhibition of HCL secretion within 1 hr. antagonists •Headache
Rabeprazole •Maximum action in 3-4 days – 95% suppression •Dizziness
Pantoprazole •Metabolized by CYP2C19 , CYP3A4. •Hypergastrinaemia
•Excreted in urine
H2 rec Cimetidine •Reversible competitive antagonists for histamine on parietal •Absorbed rapidly from the small intestine •Well tolerated •May cause confusion (esp. in •Cimetidine inhibits CYP-450
antagonists Ranitidine cell •Not affected by food •Relieve pain, ↑ elderly) •↓ metabolism of phenytoin,
Famotidine •Indirectly ↓ gastrin & ACh-induced HCl secretion •Peak plasma conc. 1-3 hours ulcer healing •Cimetidine - antiandrogenic effects quinidine, theophylline,
Nizatidine •Elimination renal & hepatic – 2/3rd unchanged (gynaecomastia) warfarin
Mucosal Sucralfate May interact with food. Given on empty stomach May cause constipation •Complex salt of sucrose
•Polymerizes at pH<4
protectants sulphate and aluminum
•Forms sticky gel →
hydroxide
adheres to ulcer base →
•May bind to quinolones,
coats ulcer crater with
phenytoin, warfarin
polymer-glycoprotein
Bismuth chelate •May stimulate mucosal bicarbonate Colloidal compound
complex
& PGE2 secretion precipitates at pH<5.
•Impedes growth of H. pylori
Antacids Al(OH)3 •Basic substances •Acid rebound : gastrin ↑ → acid production ↑ Constipation Al+3 may bind to drugs i.e.
• ↑ luminal pH of stomach increased amount of antacid needed @ begining tetracyclines
Mg(OH)2 •Symptomatic relief of dyspepsia •Tablets, liquids Diarrhoea due to laxative effect
NaHCO3
Combinations Al + Mg OH
H. pylori Triple therapy (7-14 d) PPI + amoxicillin + clarithromycin
treatment PPI + metronidazole + clarithromycin
PPI + amoxicillin + metronidazole
Quadruple (10-14 d) PPI + tripotassium dicitratobismuthate + tetracycline + metronidazole
therapy
Sequential (1- 5 d) PPI + amoxicillin
therapy (6 -10 d) PPI + clarithromycin + tinidazole
Prostaglandins PGE2 •Inhibit acid secretion
PGI2 •Promote mucus and HCO3- secretion
Misiprotosol •Long acting synthetic prostaglandin E1 analogue Often causes abdominal discomfort Contraindicated in pregnancy
•Used to prevent NSAID-induced peptic ulcers & diarrhoea
INFLAMMATORY BOWEL DISEASES

Aims of therapy
•Suppress inflammatory response •Suppress the immune reaction
Drug classification Mode of action Pharmacokinetics Uses Advantages Contraindications ADR Special notes
Aminosalicylates •Induction & maintenance of Azo compunds

remission of mild to moderate IBD 5-ASA ---diazo bond--- other molucule
•Especially in UC
•Act on epithelial cells → release 5-ASA : active component
-Lipid mediators ex- Mesalazine
-Cytokines
-ROS
→ ↓ inflammation
Sulfasalazine •Spliting by bacterial flora into •Oral tablets •Sulfasalazine - patients with •Dose-related
(5-ASA + sulfapyridine) -5-ASA→ act on mucosa •Sachets or suspension sulfa allergy. -Folate deficiency
-Sulfapyridine→ absorb→ADE •Liquid -Nausea
•5-ASA -Vomiting
- Salicylate hypersensitivity -Diarrhoea
-Headache
•Sulfapyridine -Arthralgia
- G6PD deficiency •Idiosyncratic
(haemolysis) -Hepatotoxicity
- Slow acetylator status (↑ -Haemolytic anaemia
risk of hepatic and blood -Pancreatitis
disorders) -Pneumonitis
-Interstitial nephritis
-↓ sperm count
Olsalazine
(5-ASA + 5-ASA)
Balsalazide
(5-ASA + inert mol)
Glucocorticoids Prednisolone Induction of remission of both UC & CD Alone or in
•(Mild - moderate) that has failed combination with
aminosalicylate therapy other therapies
Hydrocortisone
•(Moderate - severe) necessitates rapid
symptom Mx
Methylprednisolone •(Severe - fulminant) with potential for
surgical intervention
Budesonide •orally •Effects confined

•Significant first pass to the GI tract and
metabolism limited systemic
Low systemic bioavailability toxicity
Drug classification Mode of action Pharmacokinetics Uses Advantages Contraindications ADR Special notes
Immunosuppressives Azathioprine /6- •Effects - delayed •Failed treatment with mesalazine Not useful for
mercaptopurine •6 months to achieve •For corticosteroid-sparing effect (whose induction of
results disease is dependent on chronic remission
Ciclosporine
corticosteroids)
Methotrexate
Cytokine modulators/ TNF Infliximab •Monoclonal AB •UC - moderate to severe
biologics blockers Adalimumab •Bind cytokine and TNF-α → Inhibit its •CD - refractory to anti-inflammatory &
Certolizumab inflammatory effects immune-modulating therapies
Golimumab
Leucocyte Natalizumab •Humanized monoclonal AB Brain -Progressive Multifocal
adhesion •Inhibits the adhesion of α-4-β-7 integrin Leukoencephalopathy (PML)
inhibitors to receptors on the endothelial cells of
the gut → prevent inflammation
•Also binds α-4-β-1 integrin: expressed in
the skin, bone marrow, brain
Vedolizumab •Humanised monoclonal AB More specific to

•Inhibits leucocyte adhesion (more the GI tract than
selective for α-4-β-7 integrin natalizumab
Antibiotics Ciprofloxacin ↓ peri anal fistula
Metronidazole drainage
Probiotics Living microorganisms Able to survive
•Antimicrobial activity stomach acid and
•↓ bacterial growth bile
•Immunomodulation
•Initiation of an immune response
•↑ of barrier activity
•↓T-cell proliferation
Prebiotics Indigestible carbohydrates
•Stimulate growth of particular species
of microflora → ameliorated enteric
function
Synbiotics Pro + Pre
DRUGS ACTING ON FEMALE REPRODUCTIVE SYSTEM

ESTROGEN RECEPTORS PROGESTERONE RECEPTORS HORMONAL CONTRACEPTIVES POST MENOPAUSAL HORMONE THERAPY GNRH ANALOGUES GONADOTROPINS
Drug classification Mode of action Pharmacokinetics Uses Advantages Disadvantages Contraindications ADR Special notes
Estrogen Estrogen Natural Estradiol •Development of 2ry sexual characteristics •Preparations - Oral, Topical, Patches, •Primary hypogonadism •Breast tenderness Endogenous Es
receptors •Mineralocorticoid action Implants, Rings •Primary amenorrhea- cyclically with •Nausea, vomiting, anorexia Estradiol
•Mild anabolic •Oral/topical – well absorbed progestogen •Retention of water •Most patent
Estriol
•↑ HDL •Metabolized in liver – natural Es •Contraception •↑ risk of thromboembolism •Principle Es in
•↑ coagulation quick •Post menopausal hormone •Endometrial hyperplasia premenopausal
Synthetic Mestranol •First-pass metabolism by CYP450 to replacement Estrone
estrone, estrone sulfate and estrone •Metabolite of Estradiol
Ethinylestradiol glucuronide •After menopause
•Enterohepatic circulation present •From conversion of
•Natural E – circulate binding to SHBG androsteredione in
Diethystilbestrol or albumin peripheral tissues
•Excrete in urine as sulphates and Estriol
glucuronides •Metabolite of Estradiol
•During pregnancy: placenta
SERMS Tamoxifen •Lack steroid structure of estrogens but •Tx or prevent Breast cancer Provide benefits of Es
possess a tertiary structure → allows bind •Es action on lipids while avoiding
to Es receptor •Endometrium drawbacks
•Agonist in some tissues & antagonist in •Bone
Toremifene others •Tx advanced breast cancer
Raloxifene •Tx or prevention postmenopausal

osteoporosis
•Breast and endometrium
Clomiphene •Es Rec antagonist at anterior pituitary and Rx infertility
hypothalamus → no negative feed back →
↑GnRH, gonadotrophins
Aromatase 1st generation Aminoglutethemide •Suppress Es synthesis in ovaries & in •Breast cancer Aromatase
inhibitors peripheral tissues •Endometrial cancer •Sources- ovarian granulosa
2nd generation Formestane •Endometriosis cells in premenopausal
Fadrazole •Ovulation induction women & adipose cells in
3rd generation Exemestane
postmenopausal women
Anastrazole
Letrozole
Vorozole
Progesterone Progestogens Pro derivatives Hydroxyprogesterone •Make the secretory phase of the •Pro derivatives - Oral ,IM, vaginal, •Contraception •Weak androgenic effect
receptors endometrium rectal •Post menopausal Tx (hirsutism, acne)
Medroxyprogesterone •Make the endometrium suitable for •Tes derivatives - oral •Treat endometriosis •Fluid retention
Dyhydrogesterone implantation •Natural pro – orally inactive (high •Endometrial cancer •Weight changes
•Cervical mucus – hostile to sperm first pass metabolism) •Depression
Testosterone 1st gen Northisterone •Thermogenic effects •Bound to albumin •Breast tenderness
derivatives
•Metabolized in liver •Breakthrough bleeding
2nd gen Levenogestrel
•Stored in fatty tissues •↑ incidence of
•Metabolites excreted in urine thromboembolism
Norgestrel
3rd gen Desogestrel Less androgenic Greater risk of Less change in lipoprotein
action thromboembolic metabolism
events
Anti Mifepristone •Partial agonist at progesterone receptors •Given orally Medical termination of pregnancy -
progestogens •Sensitizes uterus to prostaglandins •T 1/2- 21 hr. combination with prostaglandin
(Geme prost)
Hormonal Both Estrogen & Combined oral Es •Es & Pro: Feedback inhibition of FSH and LH → •Metabolized by cytochrome P450 •Improves dysmenorrhea, PICTURES •Nausea , vomiting, breast tenderness Hx
Progesterone contraceptive Ethinylestradiol Inhibit ovulation (main mechanism) •Enzyme inducing drugs ↓ the drug levels intermenstrual bleeding, •Pigmentation, acne •First COCP - higher
contraceptives
pills Mestranol •Pro: thicken the cervical mucous → prevent entry •Broad spectrum antibiotics → disturb the irregular menstruation •Weight gain concentrations of Es & Pro
Pro of sperm EHC → contraceptive failure •↓ Fe deficiency anemia •Depression & irritability →intolerable side effects
Norethesterone •Effects on uterine tubes & endometrium → ↓ •↓ premenstrual tension •Thromboembolic events (risk = to
Levonorgrestrel fertilization and implantation •↓ benign breast normal pregnancy) •Monophasic → biphasic &
Desogestrel tumours, functional •↑ BP triphasic introduced to
Gestodone ovarian cysts, uterine •Amenorrhea after cessation of the pill - ↓ total dose of steroids in each
fibroids •Cancer risk cycle
•↓ endometrial, ovarian - To mimic physiological
and colorectal cancers fluctuations
•EE has gradually been reduced

over the years and pills are now
available containing 35, 30, 20, 15
and 10 µg.
Transdermal Ethinyl estradiol

patch (20 μg)
Norelgestromin
(150 μg)
Vaginal rings Ethinyl estradiol

(15 μg)
Etonogestrel
(120 μg)
Progestogen only Mini pil •Place the endometrium prematurely to the Indications •Break through bleeding
preparations secretory phase •Thromboembolism •Less reliable
•↑ viscocity of cervical mucus •IHD
•High doses inhibit the ovulation (injectable, •Smoking
implants) • > 35 years of age
•Breast feeding
• ↑ BP due to COCP
Implants/ depot Levonorgestrel

Medroxyprogesterone
IUCD Levonorgrestrel last for 35 years
Subdermal Levonogrestrel •Avoid first pass metabolism

implant •Release for 5 years
Emergency Levenogestrel Depend - time in a women's cycle it is taken •Take within 72 h & repeat in 12 h If None •Headache Postcoital contraception
contraceptives •Prevent ovulation •95% effective if taken within first 24 hrs •Birth control was not used •Dysmenorrhea
•Alter tubal transport •Condom breaks •Nausea
Ulipristal acetate •Make the endometrium unfavorable •Sexual assault/ rape Selective progesterone receptor
•Forgot to take birth control pill modulator
Post menopausal Estrogen Orally •Don't ↓ IHD & •Breast cancer pts Related to duration & age of Symptoms at menopause
hormone therapy Transdermal patches cognitive •Endometrial cancer patient •Vasomotor
Topical gels or creams impairment pts •Endometrial cancer (if given •Genitourinary: sexual
Vaginal cream or pills •Cyclical bleeding •Thromboembolic hx without Pro) dysfunction
Subcutaneous implants (DVT, PE) •Ovarian cancer •Psychological: affective &
Progesterone Orally •Hypercoagulability •Breast cancer cognitive disorders
Topical disorders •Venous thromboembolism •Osteoporosis
Vaginal cream •Liver disease •Stroke •Dyslipidemia
Injectable •Undiagnosed genital •Coronary heart disease
bleeding •Pro related AE Candidates
Tibolone Selective Es Pro & weak androgenic activity Short term treatment of Es deficiency For No effect on ↑Risk of stroke •Symptomatic pts at the
•Vasomotor symptoms endometrium and time of menopause
•Improve mood breast •Premature ovarian failure
•Libido pts
•Vaginal atrophy •Surgically menopausal pts
•Osteoporosis •Tx - osteoporosis
Combination of SERM/ Bazedoxifene (20 mg) •Tx of vasomotor symptoms
CEE (0.45 mg) •Prevent osteoporosis
GnRH analogues Synthetic GnRH Gonadorelin Mode of action
Agonist Buserelin SC pulses •Induce ovulation 200 x potent than endogenous GnRH
Leuprorelin •Stimulate gonadotropin release
Goserelin
Nafarelin Nasal spray
Depot injections Initialy stimulate gonadotrophin release → •Prostate(male) •Flushing

then inhibition •Breast cancers •Vaginal dryness
•Endometriosis •Bone loss
•Large uterine fibroids
Antagonist
Analogue Nafarelin
Danazol Synthetic anabolic steroid – modified Pro •Active orally •Endometriosis •GI disturbances
•Negative feedback → Inhibit release of •Metabolized in liver •Breast dysplasia •Weight gain
GnRH and Gonadotrophins •Gynecomastia •Fluid retention
•Inhibit estrogen synthesis & •Hereditary angioedema •Dizziness
spermatogenesis •Menopausal symptoms
•Androgenic activity •Muscles cramps
•Headache
•Virilization in females
Gonadotropins LH •Preparations- natural, synthetic •Infertility due to hypopituitarism Glycoproteins produced By
FSH •I.M. •To harvest ovum to in-vitro anterior pituitary, placenta
HCG fertilization
•Hypogonadotropic hypogonadism in
males
•Delayed puberty
DRUGS ACTING ON ANDROGEN RECEPTORS

Testosterone/ Anabolic Steroids Anabolic effects •Extensive first- •Replacement •Supraphysiologic doses → •Anabolic activity ↑ by
•Protein synthesis → skeletal pass metabolism therapy in male effects on other steroid Structural modification
muscle hypertrophy • i.m. injection, hypogonadism receptors of testosterone
•↑ muscle size & strength transdermal •Performance •Testicular atrophy, •Anabolic : androgenic
•Disproportionately large upper- patches enhancing agent by gynaecomastia in males ratio
body mass athletes. (Banned by •Virilisation in females -Testosterone (1)
•↑ collagen synthesis in WADA) (hirsutism, amenorrhoea, -Nandrolone (10)
connective tissue hoarse voice, clitoral -Stanozolol (30)
•Suppression of osteoclast hypertrophy)
activity → •Acne, male pattern
↑ bone density baldness, striae
•↑ erythropoietin production •Peliosis hepatis
(hemorrhagic liver cysts)
Androgen Steroidal Cyproterone Used in androgen- Other actions
antagonists acetate dependent conditions Progesterone agonist
Drospirenone •Acne Progesterone agonist &
•Hirsutism mineralocorticoid
•Androgenetic antagonist
Spironolactone alopecia Mineralocorticoid
antagonist
Non steroidal Flutamide In prostate cancer
Bicalutamide
Nilutamide
Enzalutamide
DRUGS ACTING ON THE BLADDER

Drug classification Mode of action Pha.kinetics Uses ADR Special notes
Muscarinic Selective (M3) Darifenacin Overactive bladder

receptor antagonist Solifenacin
Non selective Trospium M2 also present in salivary glands, CVS, brain, GIT
Oxybutynin
Tolterodine
Festosterodine
Phosphodiesterase Tadalafil •Smooth muscle relaxation
5 inhibitors •Antiproliferative effects in prostatic &
bladder smooth muscle
α1 adrenoceptor Non-selective Prazosin For Benign prostatic
•First-dose Intraoperative floppy iris syndrome
antagonists Terazosin hyperplasia/Bladder
hypotension (esp. •Intraoperative miosis, flaccid iris, prolapse of the iris
outlet obstructionprazosin) during cataract surgery in patients taking α1 adrenoceptor
Doxazosin
•Intraoperative antagonits
Selective Tamsulosin
Dynamic component floppy iris syndrome •Discontinuation of medication doesn't ↓ incidence
(α1A) Silodosin (esp. tamsolusin) •Should not initiate treatment until after the surgery
5α reductase Finasteride Inhibit type II Tx for several Static component •↓ libido Present in prostate, hair follicles
inhibitors Dutasteride Inhibit type I & II months needed •Breast tenderness
DRUGS ACTING ON MYOMETRIUM

Drug classification Mode of action Pharmacokinetics Uses Advantages Disadvantages ADR Special notes
Drugs cause Oxytocin Coordinated synchronous •T ½ 6 min Induction of labour Heat-sensitive: •Nausea, vomiting
uterine myometrial contractions •IV infusion needs cold •Water retention
contraction •Dose needed to be adjusted closely storage
with uterine contractions.
Carbetocin Synthetic analogue of oxytocin Heat-stable: Cold-chain
transport & cold storage
not needed
Ergometrine •Ergot alkaloid •Given IV, IM In PPH •Nausea •Sustained contraction
•Binds with α adrenergic •Rapidly & completely absorbed •Vomiting •Occur immediately after IV
receptors → ↑ intracellular Ca → after IM injection •Hypertension administration & last up to 45
myometrial contractions •Eliminated by liver min
Prostaglandins Dinoprost (PGF2 α) Vaginal gel, pessary, IV •Induction of labour •Vomiting
•Terminate pregnancy •Diarrhea
Dinoprostone (PGE2) •Headache
•Pyrexia
Carboprost (PGF2) Deep IM injection PPH unresponsive to •Hypertension

ergometrine & oxytocin •Asthma
•Pulmonary oedema
Gemeprost (PGE1) Vaginal gel, pessaries Induction of late
therapeutic abortions
Uterine Oxytocin antagonists Atosiban IV infusion To inhibit premature No major ADE
relaxants β2 agonists Salbutamol IV infusion labour •Tachycardia,
Terbutaline hypokalaemia,
hypotension
Ritodrine •LVF (due to fluid)
Ca channel blockers Nifedipine oral
COX inhibitors Indomethacin oral POG < 32 weeks
Magnesium sulphate Maternal NM blockade Crosses placenta
Drug causes uterine contraction Uterine relaxants

Drug Book

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DRUG BOOK

(All the details were taken from lecture notes)

PAIN CONTROL 3 GENERAL ANASTHETICS 45

Selective Celecoxib Less GI irritation •↓ synthesis of PGI2 - Vascular thrombosis

Neuropathic pain Tx…….

Respond poorly to conventional analgesics

AUTONOMIC NERVOUS SYSTEM

Parasympathetic ACh receptor agonists Choline esters Carbachol topical miotic

Acebutolol Partial antagonist Intrinsic sympathomimetic activity (ISA)

DRUGS IN SPECIAL POPULATIONS

ANTI NEOPLASTIC DRUGS

ANTIBIOTICS (ANTI BACTERIALS)

ANTIBIOTICS - Cell wall synthesis inhibitors

Isoniazid a prodrug - activated by bacterial enzymes

ANTIBIOTICS - Protein synthesis inhibitors

ANTIBIOTICS - Nucleic Acid synthesis inhibitors

Drug classfication Mode of action Pharmacokinetics Uses ADR Special notes

Ganciclovir •6-9% oral bioavailability CMV •BM suppression

ANTI FUNGAL DRUGS

ANTI MALARIAL DRUGS

Blood Chloroquine 5 groups - AMC Tx guidelines Treatment

SMALL AIRWAY DISEASE (ASTHAMA, COPD)

ANTI TUBERCULOSIS DRUGS

Drug name Mode of action Pharmacokinetics Interactions ADR Special notes

Local Endothelial Sympathetic Hormonal mediators

Drug classfication Mode of action Pharmacokinetics Uses ADR Special notes

Angiotensin receptor Losartan •No effect on bradykinin →

Nicorandil •Well absorbed from GIT In angina Headache Also NO donor

LIPID REGULATING DRUGS

Clofibrate •↓ TAG: 20-50%

Sotalol also β blocker

DRUGS INFLUENCING MYOCARDIAL CONTRACTILITY

Direct Factor Xa Apixaban Oral bioavailability 60%

GP IIb/IIIa Tirofiban Blocks final common IV Thrombocytopenia

Vitamin K Vit K act as cofactor in •Natural •Tx & px of bleeding

Classfication Uses ADR/Disadvantages

K replacement KCl tablets May cause gastric irritation

Drug classfication Mode of action Pharmacokinetics Uses ADR Special notes

Thryxonine Levothyroxine •Given daily on empty stomach •Replacement therapy ↓Absorption

GLUCOCORTICOIDS & MINERALOCORTICOIDS

Fluorinated Triamcinolone No Na retaining effect •muscle wasting can

Mineralocorticoids Aldesterone •↑ Na reabsorption by the distal tubule of kidney

Glucocorticoid excess Tx Glucocorticoid Metyrapone •Prevents beta hydroxylation at C11

Glipizide •Inactive metabolite, renal

Hexamer → Dimer → Monomer - ↑ diffusion

Immunosuppressants - Drug classfication

Inhibitors of Inhibition of IL-2 Calcineurin Tacrolimus Use

Rheumatoid NSAID Non- Ibuprofen •Don't slow the progression of

Biologic Tumour necrosis Adalimumab SC •Infection

Hyaluronic acids ↓ friction & improves Intra articular injections

Emerging therapies SNRI Duloxetine Improve pain

IL-1 rec antagonists ↑ level of IL – 1 a/w the severity of radiographic

Regenerative therapy •MSC - BM, adipose tissue, & synovium

METABOLIC BONE DISEASES

Posphate binders CaCO3 ↓ intestinal absorption of To control hyper

Hypercalcemia Isotonic saline + frusemide i.v

Calcitonin •Rapid action

Bisphosphonates Pamidronate IV infusion

Calcimimetics Cinacalcet •↑ Ca-mediated inhibition of PTH •Oral bioavailability 20-25%; In secondary

Tx- Dantrolene, non specific

Methohexitone •Anasthesia for ECT •Barbiturate similar to Thiopental

PRE MEDICATION → INDUCTION → MAINTENANCE → POST OP CARE

Mode of action PPharmacokinetics Anaesthetic potency AE